Rsna 2009 Research Education Foundation Awards

2009 Grants and Awards RSNA RESEARCH & EDUCATION FOUNDATION FUNDING RADIOLOGY’S FUTURE®

Improving patient care by supporting research and education in radiology and related scientific disciplines through funding grants and awards to individuals and institutions that will advance radiologic research, education, and practice.    

Dear Colleague, Our commitment to radiology research and education is stronger than ever. This year, the Foundation is celebrating its 25th anniversary and the successful completion of a $15 million campaign. Through the generous support of our corporate, private practice, and individual donors, we will be able to continue funding grant programs for the next 25 years. We know that getting the first grant can be the hardest, and we are proud of our 25-year history of providing these critical grants to launch successful academic careers. To date, the Foundation has awarded over $29 million for radiologic research and education. The results are impressive—grant recipients have planted our seed money and turned it into over $900 million in additional funding and countless improvements in patient care. On behalf of the RSNA Research & Education Foundation, I would like to congratulate this year’s grant recipients. We look forward to your discoveries in the years ahead. I would also like to give special thanks to our Vanguard companies for their support. With the backing of the entire community we will keep radiology at the forefront of medicine. Sincerely,

Jack E. Price Chair, Board of Trustees RSNA Research & Education Foundation

Agfa HealthCare

Canon U.S.A.

Bayer HealthCare Pharmaceuticals Bracco Diagnostics

Carestream Health

GE Healthcare

Covidien Cook Medical

Hitachi Medical Systems

Philips Healthcare

Toshiba America Medical Systems

Siemens Healthcare USA

Varian Medical Systems

RSNA R&E Foundation

Vanguard Companies  

Fujifilm Medical Systems

Research Grant Programs Research Scholar Grant ............................................................................................................. 3–6 To provide protected research time to junior faculty members who have completed the conventional resident/fellowship training program(s). The grant prepares research-oriented faculty to obtain larger grants from other sources, such as the National Institutes of Health (NIH), and to be able to establish their own fully funded research program. $75,000 annually for 2 years ($150,000 total) to be used as salary support for the scholar.

Research Seed Grant .................................................................................................................. 6–7

“Survey data reveal the extraordinary success—measured in subsequent dollars—of investigators with RSNA R&E Foundation-funded research early in their careers. Many of the topics these creative and inquisitive investigators soon translate into clinical application and dissemination. There is no better investment in the future of radiologic practice anywhere in the world.” Gary J. Becker, MD 2009 President, RSNA; Executive Director, American Board of Radiology

To enable investigators to gain experience in defining objectives and testing hypotheses in preparation for major grant applications to corporations, foundations, and governmental agencies. The grant is intended to support the preliminary or pilot phase of scientific projects, not to supplement major funding already secured. Up to $40,000 for a 1-year project.

Research Resident/Fellow Grant ......................................................................................... 8–14 To support trainees who are pursuing careers in academic medicine by allowing recipients to devote 50% of their time to an approved research project under the guidance of a scientific advisor/sponsor. The grant provides investigators an opportunity to gain further insight into scientific investigation and to develop competence in research techniques and methods. $30,000 for a 1-year resident project or $50,000 for a 1-year fellow project to be used for salary and/or non-personnel research expenses.

Research Medical Student Grant ........................................................................................14–27 To make radiology research opportunities possible for medical students and to encourage them early in their medical careers to consider academic radiology as an option for their future. Students are expected to complete a 3-month, full-time research project under the guidance of a scientific advisor. $3,000 for a 3-month research project to be matched by the sponsoring department ($6,000 total) as a stipend for the medical student.

Education Grant Programs Education Scholar Grant ........................................................................................................28–32 To provide funding opportunities for individuals with an active interest in radiologic education. Any area of education related to the radiologic sciences is eligible for Education Scholar Grant support. Up to $75,000 annually for up to 2 years ($150,000 maximum) for salary support and/or other project costs.

RSNA/AUR/APDR/SCARD Radiology Education Research Development Grant ........................................................................................................................ 33

“We have to continue working on advancing radiology science and research to sustain our specialty and compete with others. RSNA R&E Foundation grants played a critical role in my career, acting as a springboard to get NIH funding. The work I have done with my grants has advanced contrast medium delivery technology and improved diagnostic quality of the images we interpret in our daily clinical practice.” Kyongtae Ty Bae, MD, PhD 1996 Research Resident Grant Recipient; 1999 Research Seed Grant Recipient; Member of Research Study Section

To encourage innovation and improvement in health sciences education by providing research opportunities to individuals in pursuit of advancing the science of radiology education. This program will help build a critical mass of radiology education researchers and promote the careers of persons advancing the science of radiology education. Up to $10,000 for a 1-year project to help cover the costs of research materials, research assistant support, and limited primary investigator salary support.

Recognition Awards Roentgen Resident/Fellow Research Award ..................................................... 34–36 To recognize and encourage residents and fellows who have played an active role in radiologic research during the past year. Participating North American residency programs receive an award plaque with room for the name of each year’s recipient. The Foundation provides a personalized award for the department to present to the selected resident or fellow.

Outstanding Researcher/Educator Awards ....................................................... 37–38 To annually recognize and honor one senior individual in each category who has made original and significant contributions to the field of radiology or radiologic sciences throughout a career of research or teaching and education. Awardees are honored at the opening session of the RSNA Scientific Assembly and Annual Meeting.

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Grant

Research Scholar Prostate Specific Membrane Antigen (PSMA) PET Imaging for Detection of Metastatic Prostate Cancer and Solid Tumor Neovasculature Metastatic prostate cancer diagnostic imaging using traditional anatomic modalities including CT, MRI, and ultrasound, as well as [18F]-FDG PET metabolic imaging, is limited. PSMA is a protein highly restricted to prostate cancer. PSMA is also found to be specifically expressed on the neovasculature of many solid tumors but, interestingly, not in prostate tumor neovasculature. ProstaScint®, a radiolabeled monoclonal antibody binding to the intracellular domain of PSMA, was developed to detect prostate cancer lymph node metastases but has limited accuracy due to antibody targeting characteristics. Tumor vascular imaging in a number of solid tumors with another PSMA monoclonal antibody, J591, has been recently demonstrated.

Steve Y. Cho, MD Radiology Division of Nuclear Medicine/PET The Johns Hopkins University School of Medicine Bracco Diagnostics/RSNA Research Scholar Grant

Intact monoclonal antibodies-based tumor detection is limited because of their low permeability in solid tumors and slow clearance from the circulating blood pool. Smaller molecular weight-based radiotracers are more optimal for tumor detection because of their higher permeability into solid tumors and improved blood clearance in comparison to intact antibodies. [18F]-DCFBC is a novel, low-molecular-weight radiotracer targeting the more accessible extracellular domain of PSMA. Preclinical mouse prostate cancer tumor model imaging studies of [18F]-DCFBC demonstrate that this new ligand has high uptake in PSMA-expressing prostate cancer cells. [18F]-DCFBC is a clinically practical PET imaging agent with superior pharmacodynamic and pharmacokinetic characteristics that warrants further evaluation in clinical trials. [18F]-DCFBC PET images will be compared to conventional imaging methods and bone scan to localize tumors in patients with advanced metastatic prostate cancer. Radiation dosimetry and biodistribution of [18F]-DCFBC will be determined by PET imaging in patients with metastatic prostate cancer to calculate whole-body and organ-specific radiation dosimetry. We will also evaluate the potential of [18F]-DCFBC PET to specifically target neovasculature in solid tumors, excluding prostate cancer. Tumor neovasculature PSMA expression will be obtained by tissue immunohistochemistry and compared to [18F]-DCFBC PET findings.

Direct Imaging and Quantification of Cortical Bone on a Clinical 3 T MR Scanner Imaging of bone has been of fundamental importance to the practice of radiology. Plain radiographs and CT provide images of high spatial resolution, and bone density is readily measurable with DEXA and CT. However, the images and measurements very largely reflect the mineral content of bone, not the organic matrix or bone water that occupy a larger volume and have important mechanical and biological properties.

Jiang Du, PhD Radiology University of California, San Diego Agfa HealthCare/RSNA Research Scholar Grant

There has been considerable interest in assessing the organic matrix and water in bone with magnetic resonance (MR) imaging. But bone has a very short T2, producing no signal with all clinical pulse sequences. Ultrashort echo time (UTE) sequences with TEs 100-1000 times shorter than these available on clinical scanners allow direct visualization of cortical bone. The objective of this proposal is to develop qualitative and quantitative techniques to image and quantify cortical bone on a 3 T clinical scanner. The research plan includes three parts: 1) Developing UTE imaging sequences. Technical issues including eddy currents, gradient non-linearity, and long T2 suppression will be addressed. 2) Developing quantitative techniques. A saturation recovery technique will be used for T1 measurement and multiecho techniques for T2* measurement. Reference standards will allow bone water to be estimated. Bone bulk susceptibility will be estimated using a novel UTE spectroscopic imaging (UTESI) technique. 3) Applying UTE imaging and quantitative techniques to normal volunteers and two groups of patients (osteoporosis and osteomalacia). Volunteer data will be correlated with age, sex, and weight and will serve as a control group. Patient population data will be compared to the control group. After the proposed project period, we will have developed UTE sequences for the first quantitative evaluation of cortical bone in normal volunteers and patients. The noninvasive characterization of cortical bone could be revolutionary if it proves to have a specific MR signature.

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Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia A third of men aged 50 years and over will develop bladder outlet obstruction/irritation from benign prostatic hyperplasia (BPH), and a quarter will require surgical intervention. The surgical standard, transurethral resection of the prostate, requires a 5-day hospital stay and has >50% incidence of complications (eg, urethral stricture, urinary incontinence, impotence) leading many to search for alternative, minimally invasive options. Selective embolization of the prostatic artery has been reported as a safe and effective treatment for prostate bleeding after TURP or biopsy. Along these lines, we generated preliminary results in six dogs with BPH and demonstrated a 40% reduction in prostate volume at 1 month following embolization with microspheres, with subjectively better results, but greater initial urinary retention, using a bilateral embolization technique. Specific aims: 1. To determine 6-month safety of prostate embolization in a canine model; 2. To assess short/mid-term effects of prostate embolization for BPH on gland volume and perfusion, urethral obstruction, and histology; 3. To refine the technique by optimizing embolization particle size and assessing the need for bilateral versus unilateral embolization. Dogs with BPH will undergo selective bilateral embolization of the prostatic arteries with 100-300µm, 300-500µm or 500-700µm (n=6, each) microspheres. Animals will be monitored clinically for 1 month after embolization for infectious, ischemic, or other complications. Retrograde urethrocystography and dynamic contrast-enhanced MRI will be obtained prior to embolization and after 1 month for quantitative and qualitative analysis of urethral stenosis, prostate volume, and enhancement. After 1 month, prostates will be excised for radiologic-pathologic correlation and microscopic analysis (particle distribution, necrosis, inflammation). Unilateral versus bilateral embolization with the ideal particle size will be compared (n=6, each), with a 6-month follow-up (results of Phase I).

Salomao Faintuch, MD Radiology Beth Israel Deaconess Medical Center Harvard Medical School GE Healthcare/RSNA Research Scholar Grant

This is a potential revolutionary treatment analogous to uterine artery embolization that has the ability to evolve into treatment for prostate cancer (radioembolization-Y90, chemo/hormonal embolization).

Evaluation of Magnetic Nanoparticle Enhanced Magnetic Resonance Imaging in Clinical Autoimmune Diabetes Type I diabetes mellitus (DM) is an irreversible, chronic disease causing disproportionately high percapita healthcare expense (~5 fold greater than non-diabetics), secondary to both long-term glycemic management and occasional devastating acute and chronic complications. Although it is well established that DM results from autoimmune destruction of the insulin producing beta cells of the pancreatic islets, a true understanding of its immunopathogenesis in humans has remained elusive. Previous techniques used to quantify insulitis (to measure the degree of inflammation and islet destruction) and beta cell mass (BCM—a measure to gauge the amount of residual beta cells) are invasive and impractical for most human studies. Imaging may therefore play an important role in quantifying insulitis and BCM. Radionuclide attempts have shown initial promising results in animal models of diabetes, without successful translation into human clinical trials. As novel immunomodulatory therapies evolve in order to prevent beta cell destruction, a noninvasive, accurate means of visualizing and quantifying BCM and insulitis becomes critical. Recently, we developed a technique based on the properties of magnetic resonance imaging (MRI) enhanced with magnetic nanoparticles (MNP) to allow indirect quantification and visualization of insulitis in animal models of DM. We validated this MNP-MRI technique by correlating our findings with the standard invasive techniques used to study diabetes, including histology and flow cytometry of the pancreas and pancreatic inflammatory infiltrate samples. Initial translation of this technique has resulted in a trial to study insulitis in humans, funded by the NIAID (PI Mathis/Weissleder). Twelve patients with early onset diabetes have been enrolled with encouraging results. We are now poised to translate and optimize this technology and apply it to an extended human clinical trial.

Alexander R. Guimaraes, MD, PhD Radiology Massachusetts General Hospital Bayer HealthCare Pharmaceuticals/RSNA Research Scholar Grant

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Chronological Analysis of Tumor Size, Volume, and CT Attenuation Coefficient in Women with Adenocarcinoma of the Lung Treated with Erlotinib Lung cancer is a leading cause of cancer death in the United States and worldwide. One of the recent breakthroughs in lung cancer treatment was the discovery of the somatic activating mutations of the EGFR tyrosine kinase domain in non-small cell lung cancer, which is associated with a dramatic clinical response to EGFR inhibitors such as gefitinib and erlotinib. Erlotinib is particularly effective in women with adenocarcinoma. However, most patients with initial responses to erlotinib treatment eventually relapse due to acquired resistance to erlotinib.

Mizuki Nishino, MD Radiology Brigham and Women's Hospital Dana-Farber Cancer Institute Agfa HealthCare/RSNA Research Scholar Grant

The purpose of this proposal is to analyze chronological changes in tumor size and volume in women with adenocarcinoma of the lung treated with erlotinib, and to determine if the tumor size change rate and the tumor volume change rate precede the actual increase in tumor size and volume due to relapse. If a perceptible tumor size change rate and tumor volume change rate precede the increase in tumor size and volume, oncologists can switch to another therapeutic agent before relapse in order to prolong disease-free survival. The study will be performed using data collected in a Phase II prospective clinical trial of erlotinib in women with previously untreated advanced adenocarcinoma of the lung at Dana-Farber/Harvard Cancer Center, which has enrolled 84 subjects. Data include chest CTs performed every 8 weeks and EGFR mutation analysis. Size, volume, and CT attenuation will be measured using a semiautomatic image-processing program. Rate of tumor size and volume changes will be calculated and will be correlated with clinical outcome and genetic analysis results. The long-term goal is to determine the imaging parameters that most efficiently predict acquired resistance to erlotinib by correlating the imaging parameters with the genomic characterization of the tumor, in order to optimize the therapeutic benefit of erlotinib and contribute to the prolongation of survival in lung cancer patients.

Hyposmia, Septohippocampal Cholinergic Denervation, and Amyloidopathy in Mild Cognitive Impairment Alzheimer’s disease (AD) is the most common form of dementia, accounting for over 50% of cases of age-related dementia in the over 65 population. Amyloid misprocessing/deposition and cholinergic neuron degeneration are key aspects of AD pathogenesis. In addition, substantial reductions in neuronal nicotinic Acetyl Choline receptors (nAChRs) in the cortex of AD patients have been documented on post mortem specimens.

Myria Petrou, MA, MBChB Radiology University of Michigan Health System Covidien/RSNA Research Scholar Grant

Given the recent emergence of potential disease modifying anti-amyloid treatments there is a compelling need for biomarkers that can identify subclinical/very early disease. Identification of amyloidopathy is possible using PET imaging, however, the cost of this technology is prohibitive for screening large populations. Olfactory disturbances commonly precede clinical manifestations in a number of neurodegenerative disorders including AD. There are reports of selective olfactory abnormalities in subjects with mild cognitive impairment (MCI) who convert to fulminant AD; pathophysiological mechanisms underlying the hyposmia do however remain unclear. We propose evaluating the potential of an AD-selective smell identification test as an early screening test for AD. For this purpose, we intend to study well-characterized subjects with mild cognitive impairment (MCI) with a clinical olfactory test and amyloid PET imaging assessment. We will also go on to explore mechanisms underlying the hyposmia in MCI subjects, specifically that degeneration of septo-hippocampal cholinergic projections occurs early in AD and may provide an explanation for the selective deficits in odor identification. We will use well established methodology for imaging of cholinergic pathways using Acetylcholinesterase (AChE) PET with [11C]PMP. We also propose to investigate the specific role of synaptic nicotinic cholinergic receptors in amyloidopathy-related hyposmia using [18F]XTRA, a novel Acetylcholine Receptor (nAChR) PET radioligand. Improved insights in pathobiological mechanisms of hyposmia in AD will not only allow early screening of at risk subjects but may also provide novel therapeutical targets in patients with very early disease.

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Creation of a Model for Predicting Response to Chemoradiation in Head and Neck Squamous Cell Carcinoma Chemoradiation of head and neck squamous cell carcinoma (HNSCC) is challenging due to frequent local or regional failures. Our objective is to develop a prediction model using pre-therapy demographic, pathologic, and MRI parameters to identify HNSCC patients who respond poorly to chemoradiation. Our long-term goal is application of the model prospectively in a multicenter clinical trial to identify poor responders who may benefit from escalated radiation doses, which are now feasible and safer due to advances in targeted radiation delivery, and can improve disease-free survival. Among the factors influencing tumor response, we will study tumor cellularity as a key predictor. Diffusion weighted MR imaging (DWI) is a molecular imaging technique measuring apparent diffusion coefficient (ADC), which is considered a surrogate marker for tumor cellularity. The proposed study is part of an ongoing trial at the University of Michigan involving serial MRIs in HNSCC patients (baseline, during third week of therapy and at 3 months) to study the utility of serial ADC values in assessing tumor response. Patients undergo standard-of-care chemoradiation and therapeutic response is assessed after 3 months. As an additional step to this trial, we propose to use only the baseline MRI data to construct a prediction model that will provide information on the utility of pretherapy scans alone in predicting response.

Ashok Srinivasan, MD Radiology University of Michigan Health System Carestream Health/RSNA Research Scholar Grant    

 

Our specific aims are (1) building a prediction model using age, pathological grade, tumor volume, nodal status, whole tumor mean ADC, and fractional tumor volume below an ADC threshold as parameters influencing tumor response to chemoradiation, and (2) assessing the value of adding “fractional tumor volume below an ADC threshold” to “whole tumor mean ADC” in predicting therapeutic response. Developing noninvasive imaging parameters that identify poor responders to chemoradiation is important since therapy can then be individualized to increase chances of treatment response.

Grant

Research Seed Quantification of Tumor Angiogenesis Using Diffusion and Perfusion Weighted MR Derived Parameters Correlated with Vascular Endothelial Growth Factor (VEGF) Expression and Microvessel Density in Renal Cell Carcinoma There is up-regulation of vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) and this VEGF expression has been shown to be an important prognostic marker. Furthermore, new experimental drugs which target angiogenic tumor pathways in the treatment of metastatic RCC are being designed, tested and have been recently introduced in the clinical practice. The aim of this project is to correlate quantitative MR markers of tumor angiogenesis with VEGF expression and microvessel density (MVD) in RCC. We hypothesize that VEGF expression and MVD measured with pathology is strongly associated with imaging parameters of angiogenesis measured with diffusion (using intravoxel incoherent motion [IVIM] model) and perfusion-weighted MRI (PWI). We will prospectively enroll 30 patients with RCC prior to undergoing surgical treatment (total or partial nephrectomy). Imaging will be performed within 60 days of the surgery at 1.5 or 3.0 T utilizing diffusion weighted imaging (DWI) with multiple b values, and PWI with high temporal resolution. DWI data will be processed to extract the IVIM parameters (perfusion fraction fp and pseudodiffusivity Dp). A twocompartment adiabatic tissue homogeneity (ATHs) model will be used to analyze the PWI data and to generate perfusion parameters (including tumor blood volume and tumor blood flow). Quantitative MR parameters will be correlated with lesion size and differentiation, MVD, and VEGF expression obtained at histopathology. If validated, MRI could be used as a non invasive biomarker of angiogenesis, and could be used for predicting and monitoring response to targeted anti-VEGF and tyrosine kinase inhibitor drugs which are currently under investigation in RCC. Future work will be oriented towards the prospective use of MRI biomarkers of angiogenesis in prediction and monitoring of RCC response to anti-VEGF treatments.

Hersh Chandarana, MD Radiology New York University School of Medicine Toshiba America Medical Systems/RSNA Research Seed Grant

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Exploiting Angiogenic Rebound with Ionizing Radiation Vascular endothelial growth factor receptor (VEGFR) inhibitors represent a promising class of antineoplastic agents and early investigations of combined VEGFR blockade and ionizing radiation suggest impressive clinical activity. However, several critical questions remain. VEGFR inhibitors may lead to compensatory increases in circulating pro-angiogenic and decreases in circulating antiangiogenic molecules. We hypothesize that these “rebound” phenomena may drive brisk angiogenesis and tumor cell proliferation with inhibitor discontinuation. We further hypothesize that ionizing radiation may be uniquely efficacious during this rebound phase.

Kevin Kozak, MD, PhD Human Oncology University of Wisconsin School of Medicine and Public Health Philips Healthcare/RSNA Research Seed Grant

To rigorously test these hypotheses, we will use a human pancreatic cancer xenograft model. We will quantify changes in the plasma angiogenic proteome with continuous and discontinuous VEGFR inhibition. Combined regimens of VEGFR inhibitors and ionizing radiation will be examined to test for potential deleterious effects of cyclic VEGFR inhibitor monotherapy and for enhanced tumor radiosensitivity during angiogenic rebound. These studies will meaningfully address three central clinical questions. First, they will assess the consequences of VEGFR discontinuation and clarify the merits of continuous versus cyclic antiangiogenic therapy. Second, these studies will provide insights into the potential value of VEGFR inhibitor continuation even in the face of apparent clinical resistance. Finally, through the identification of a novel interaction between anti-angiogenic and radiation therapies, these studies will quantitatively examine the potential for exploitation of angiogenic rebound with ionizing radiation. Answers to these questions will provide the foundation for hypothesis-testing in humans in the setting of translational and Phase I clinical trials. Moreover, continued refinement of our model of angiogenic rebound will permit follow-on preclinical evaluation of potentially useful technologies including, for example, [18F]-fluorothymidine positron emission tomography to track rebound endothelial and tumor cell proliferation. The proposed project will be the first step in an integrated “bench-to-bedside-andback” effort to optimize anti-angiogenic therapy.

Real-Time MRI Evaluation of the Upper Airway in Patients with Obstructive Sleep Apnea with EEG Correlation Obstructive sleep apnea (OSA) is a common and frequently undiagnosed condition where there is recurrent upper airway collapse during sleep. Patients experience repetitive, brief awakenings resulting in fragmented sleep which causes fatigue and excessive daytime sleepiness. Consequences of OSA are numerous but include serious cardiovascular and neurovascular diseases. OSA treatments are poorly tolerated, ineffective and/or invasive. Patients who can not tolerate conventional positive airway pressure therapy can undergo “Phase 1” oral-maxillofacial surgeries to enlarge the upper airway and reduce collapsibility.

Lewis Shin, MD Diagnostic Radiology Stanford University Hitachi Medical Systems/RSNA Research Seed Grant

Failure rates are as high as 60% and poor surgical outcomes have been attributed to inaccurate preoperative localization and characterization of airway collapse. Most pre-surgical evaluation is performed while the patient is awake or under a pharmacologically induced sleep. As a result, airway collapse that occurs during natural sleep is not always reflected in these exams. We hypothesize that pre-surgical MR imaging with EEG correlation under natural sleep will more accurately identify site(s) of airway collapse, thereby improving surgical planning and clinical outcomes. We will scan 20 subjects who will undergo “Phase 1” OSA surgery. Before and after review of MRI/EEG data, we will evaluate the OSA surgeon for changes in: 1) assessment of characterization of airway collapse; 2) surgical plan; and 3) prediction of successful correction. Surgeon's impression of MRI/EEG usefulness will be investigated. To evaluate for improved clinical outcomes, we will compare polysomnography and sleepiness scale questionnaire results with data from matched controls. Appropriate statistical analysis will be performed to determine significance. Dramatic improvements in clinical efficacy may result in a new paradigm for pre-OSA surgical evaluation. Long-term goals would include: optimizing (shortening) scan protocol for clinical practice; evaluating other existing therapies (dental appliances, radiofrequency ablation, Phase 2 surgery) and emerging treatments to advance improvement strategies; and computational modeling with this data to lay groundwork for developing innovative, minimally invasive treatments.

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Grant

Research Resident/Fellow

Molecular and Bioinformatic Identification of Epithelial Ovarian Cancer Stem Cells Stem cells organize and populate the body through a hierarchy of proliferation and differentiation, while retaining the capacity to continuously self-renew. The insight that this physiologic order mirrors the deranged orderliness of a developing malignancy led to the cancer stem cell (CSC) hypothesis, which proposes that each tumor consists of a heterogeneous population of cells at various stages of differentiation, but all derived from the same small CSC pool; that purging tumors of this CSC pool will be sufficient to undermine their accumulated bulk and recurrence risk. Originally conclusively demonstrated for AML, this elemental population has since begun to be described in solid tumors, most prominently in breast cancer. Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers, with 14,000 deaths annually. While EOC is thought to arise from the ovarian surface epithelium, pathogenesis is poorly understood. Therapy options are similarly limited, especially with radiotherapy hobbled by toxicity. This study proposes to build on our previous monoclonal antibody library work, in which we identified a potential negative marker for EOC stem cells. Aim 1 seeks to exploit this foothold by use of genetic array, single cell expression array, and bioinformatics to rapidly expand the list of potential markers. These markers will then be screened against published datasets linked to clinical outcomes data to screen for clinical significance. Aim 2 seeks to validate the efficacy of these markers both in vivo by their ability to fractionate ever purer populations of CSCs and in vitro by induction of either differentiation or killing of tumorigenic spheroids. Potentially therapeutic antibodies will be evaluated in murine xenograft models.

Robert Chin, MD, PhD Radiation Oncology Stanford University Medical Center Philips Healthcare/RSNA Research Resident Grant

The CSC hypothesis has far reaching implications for both scientific understanding and therapy. An identified CSC population permits more specific screening for vulnerable molecular pathways and immunologic targets amenable to radioimmunologic therapy.

Increasing Spatial Resolution and Depth of Optical Fluorescent Imaging Using Microbubble Ultrasound Contrast Agents Optical imaging is the most sensitive molecular imaging tool that can capture molecular and cellular processes in real time. Its major limitations are poor spatial resolution (~1cm3) and limited penetration (2–3cm) due to extremely high scattering and absorption by tissues. The high scattering results in poor spatial resolution because of the inability to accurately localize the exact origin or path of the detected photon. It is well known that ultrasound (US) modulates photons passing through its focal zone because the US wave moves optical scatterers/absorbers to affect the light differently during the US compression and rarefaction phases. This technique, called acousto-optic imaging (AOI), can accurately localize the detected US-modulated photons since the location of the US focal zone is known in the 2D space. AOI can potentially improve optical imaging resolution to nearly that of US resolution (few mm3). Since the detected optical signal is dominated by near field photons, modulated photons detected from greater depth improve imaging of deeper tissues. The major challenge in AOI is the recognition of the few modulated photons leading to poor signal-to-noise ratio (SNR) that decreases further with depth. We showed in preliminary studies that microbubbles not only increase photon modulation amplitude because of their greater oscillation in an US field, but also generate harmonic modulation that improves sensitivity and specificity of the detected modulation. Since it is known that US can also modulate fluorescent signal, we plan to test whether microbubbles will also improve fluorescent SNR to improve spatial resolution and depth of optical fluorescent imaging.

Mohammad Eghtedari, MD, PhD Diagnostic Radiology University of California, San Diego Bracco Diagnostics/RSNA Research Resident Grant

We propose to engineer a custom AOI system to image fluorescent-labeled targets within turbid media, produce and optimize fluorescent-labeled microbubbles to be employed as contrast agents for AOI, and determine the improvement in maximum depth of imaging and spatial resolution when fluorophores are used without, with and when attached to microbubbles.

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Molecular Imaging of the Inflammatory Enzyme Myeloperoxidase in Murine Cerebral Ischemia Inflammation has been shown to correlate with adverse stroke outcome but the specific underlying molecular mechanisms and their impact on stroke outcome remain poorly understood. Myeloperoxidase (MPO) activity has been widely used as a pathological marker for inflammation in animal models of stroke in biochemical and histopathological analyses. However, traditional methods of investigation that require sacrificing the animals limit serial and longitudinal investigations that would greatly facilitate pathobiological and pharmacological investigations, and often require excessively large numbers of animals to achieve sufficient statistical power to confirm a therapeutic benefit. The emergence of molecular imaging methods can largely overcome these obstacles.

Reza Forghani, MD, PhD Radiology Center for Molecular Imaging Center for Systems Biology Massachusetts General Hospital RSNA Research Fellow Grant

We propose to use Gd-bis-5-HT-DTPA (MPO-Gd), a highly sensitive and specific molecular imaging reporter of MPO activity developed in our laboratory, to study the role of inflammation in mouse models of cerebral ischemia. We will evaluate the role of MPO in infarct propagation by serially examining MPO activity and infarct volume on MPO-Gd enhanced MRIs with and without treatment with the specific MPO inhibitor 4-aminobenzoic acid hydrazide. In addition, we will perform a similar evaluation on MPO knock-out mice for comparison. We will then correlate the findings with biochemical and histopathological analyses to confirm our imaging observations and validate MPO molecular imaging as a tool for noninvasive in vivo investigation of inflammation. These investigations could provide the basis for novel therapies to improve stroke outcome in conjunction with an imaging paradigm for assessing the effectiveness of such interventions in diseases with an inflammatory component in animals and potentially in human diagnostic imaging.

Using Micro-CT to Define the Role of Endothelial Cells in the Response of Primary Lung Cancers to Radiation Therapy Despite aggressive treatment with radiation therapy, lung cancer remains the leading cause of cancer death in the United States. Efforts to improve the efficacy of radiation therapy are hindered by uncertainties in its mechanism of cell death and in identifying its precise cellular targets. The role of the vasculature in the response of carcinomas to radiation therapy is controversial. Furthermore, the mechanism of cell death in the vasculature after radiation therapy is unclear, and the role of p53 in mediating these processes is debated.

A. Paiman Ghafoori, MD Radiation Oncology Duke University Medical Center Fujifilm Medical Systems/RSNA Research Resident Grant

We aim to resolve this important controversy using sophisticated genetically engineered mouse models of lung cancer combined with state-of-the-art small animal imaging techniques. Using Cre-lox technology we will delete Bax specifically in endothelial cells and determine whether endothelial cell apoptosis regulates the response of primary lung tumors to radiation therapy. We will also clarify the role of the p53 gene in mediating apoptosis in endothelial cells and in the response of primary lung tumors to radiation therapy by deleting p53 specifically in endothelial cells. Microcomputed tomography will be used to follow primary lung tumors in mice and assess the effect of these genetic alterations on the response of tumors to radiation therapy. We postulate that lung cancers with endothelial cells that lack p53 will be more sensitive to radiation therapy and that lung cancers with endothelial cells unable to undergo apoptosis will be more resistant. These studies will enhance our understanding of lung tumor biology and will lay the foundation for new treatment approaches to cure patients with lung cancer.

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Adenosine Induced Stress Myocardial Perfusion Imaging Using Dual Source Cardiac Computed Tomography The current workup of symptomatic coronary artery disease (CAD) usually includes noninvasive imaging. Nuclear myocardial perfusion imaging (MPI) provides reliable information on the functional significance of coronary stenosis, yielding important management and prognostic information. However, it cannot assess coronary anatomy, thereby necessitating invasive coronary angiography (ICA) in many patients. Advances in cardiac CT have enabled noninvasive assessment of coronary stenosis with excellent diagnostic accuracy. Recent studies have demonstrated that cardiac CT can assess myocardial function including perfusion and regional wall motion. In a preliminary study of 27 patients, we demonstrated that dual-source CT can identify adenosine stress-induced myocardial perfusion defects in patients with suspected CAD with a diagnostic accuracy at least equal to MPI, with similar radiation dose, while simultaneously assessing coronary anatomy. In this observational study, we will investigate 50 patients who have undergone recent MPI and are scheduled for ICA. Using a DSCT, we will perform adenosine stress retrospective CT (QCT) followed by rest prospective CT (CTA). Images will be analyzed to assess myocardial perfusion reserve and angiographic evidence of stenosis. We will determine the sensitivity and specificity of QCT on a perpatient and per-vessel basis for the diagnosis of significant CAD, compared to MPI, using ICA as a reference.

Brian Ghoshhajra, MD Radiology Cardiac CT/MR/PET Program Massachusetts General Hospital Siemens Healthcare/RSNA Research Fellow Grant

Aim 1: Determine the feasibility and accuracy of QCT to detect myocardial perfusion defects in a symptomatic population as compared to MPI. Hypothesis: The accuracy of QCT for the detection of hemodynamically significant coronary stenosis is equivalent or better than MPI, using ICA as the reference standard. Aim 2: Determine the incremental value of CTA in conjunction with QCT for the detection of significant coronary stenosis as compared to MPI. Hypothesis: Incorporation of CTA data with QCT data allows significantly greater accuracy for the detection of hemodynamically significant coronary stenosis than MPI, using ICA as the reference standard.

Targeted Radioiodinated Nanoparticles for the Treatment of High Grade Glioma Utilizing biopanning techniques with bacteriophage, we have recently demonstrated that among screened phage-displayed peptides, the HVGGSSV peptide binds with high sensitivity and specificity to irradiated xenograft glioma tumors. When bound to near infrared imaging agents, this peptide selectively binds to responding irradiated tumors differentiating responding from non-responding tumors. We propose that radioiodination of the HVGGSSV peptide/phage, an HVGGSSV-decorated liposome, labeled nanoalbumin or other biocompatible and biodegradable vector systems could be used to deliver targeted radioactive iodine NP vectors for the treatment of high grade glioma. We will study the biodistribution and pharmacokinetics of these systems to determine the optimal NP vector system for the treatment of high grade glioma. Aim 1: To determine the mechanism by which the HVGGSSV binds to irradiated tumor microvasculature. We hypothesize that the HVGGSSV peptide binds to a radiation-inducible antigen on tumor vascular endothelium. Utilizing affinity purification techniques and PDZ domain arrays, we will identify proteins bound by our peptide. Aim 2: To conjugate radioactive iodine directly to the HVGGSSV peptide and bacteriophage. We hypothesize that radioactive iodine bound to our polyvalent peptide will retain its tumor specificity. We will directly conjugate the HVGGSSV peptide and phage to radioactive iodine and optimize conditions to achieve tumor-specific targeting. We will also evaluate pharmacokinetics of the radioiodinated peptide and phage to determine the best candidate for studies of therapeutic response in xenograft models of glioma.

Jerry Jaboin MD, PhD Radiation Oncology Vanderbilt University Medical Center Philips Healthcare/RSNA Research Resident Grant

Aim 3: To conjugate radioactive iodine to nanoalbumin and liposome vectors. We hypothesize that radioactive iodine bound to HVGGSSV-decorated liposomal and nanoalbumin vectors can retain tumor specificity and deliver the nanoparticles to irradiated tumors. To form targeted radioiodinated nanovectors, we will conjugate radioactive iodine to HVGGSSV-decorated liposome and nanoalbumin vectors. We will determine the ability of these nanoparticles to bind to irradiated tumors and alter tumor growth kinetics in vivo.

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An Investigation of EphB1 as a Mediator of the AT Phenotype Ataxia telangiectasia (AT) syndrome is a rare, autosomal dominant condition characterized by ionizing radiation sensitivity, lymphoid abnormalities, and ataxia with cerebellar degeneration. The molecular response to ionizing radiation via ATM (the gene that is mutated in AT) is mediated by a variety of receptor tyrosine kinases. The mechanism of cerebellar degeneration is not completely established, although it has been hypothesized to include defective DNA damage repair. Our work with candidate gene analysis in AT cell lines has suggested that the receptor tyrosine kinase EphB1 is regulated by ATM. EphB1 is a member of the Eph/Ephrin family of ligands and cell membrane receptor tyrosine kinases, which play an important role in regulating neural development, cell sorting and synapse formation.

Christopher Lominska, MD Radiation Medicine Georgetown University Medical Center

We propose to further characterize the ATM/EphB1 interaction with regard to the response to radiation and the neurological phenotype. Cell culture studies will be performed to confirm regulation of EphB1 by ATM. The effect of EphB1 inhibition on the response to radiation in human cell lines will be evaluated. We will further characterize the anatomy of the cerebellum in transgenic EphB1 mice. Additionally, we will study EphB1 expression and cerebellar anatomy in AT human brain tissue.

RSNA Presidents Circle Research Resident Grant

The project will increase our understanding of downstream signaling in the ATM pathway, as well as investigating the role of EphB1 in radiation response and development of the cerebellum.

Mechanism of Anti-tumor Immunity Induced by Radiotherapy and Irradiated Autologous Tumor Vaccination Emerging evidence suggests that radiotherapy, although traditionally considered immunosuppressive, may boost anti-tumor immunity. We therefore hypothesize that radiotherapy can be combined with immunotherapy for therapeutic advantage. Our preliminary data indicate that mice vaccinated with irradiated autologous tumor cells become resistant to future challenge with that tumor. Similar results are not seen in mice receiving heat-inactivated or lysed tumor cell vaccines.

Arta Monjazeb, MD, PhD Radiation Oncology Wake Forest University Health Sciences Philips Healthcare/RSNA Research Resident Grant

We propose to examine the interaction between radiotherapy (XRT) and irradiated autologous tumor vaccines (IATV). Mice with established tumors will be split into five treatment groups: placebo vs IATV vs XRT vs IATVĺXRT vs XRTĺIATV. Isobolographic interpretation of tumor growth will determine synergy or antagonism of modalities. We will also investigate the underlying immune mechanisms of these therapies. Naïve mice will receive adoptive transfer of immunocytes from vaccinated mice. Transference of tumor resistance would confirm an immune mediated mechanism. Mice vaccinated against S-180 will be challenged with CT-26 and vice versa. Lack of cross resistance would indicate a tumor specific immune response. Tumor infiltrating immunocytes from mice in the aforementioned treatment groups will be analyzed by flow cytometry to determine the types of immune cells involved in tumor resistance. To determine which are obligatory for tumor resistance, treated mice will be depleted of individual cell types and then challenged with tumor. Antigen and cytokine expression changes of irradiated tumor cells will be examined in vivo and in vitro. In light of the growing importance of immunotherapy in cancer treatment, understanding the effects of radiotherapy on the immune system and how to combine these modalities has significant therapeutic implications.

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High-Resolution RNA-Based Targeted PET Imaging Agents for Prostate Cancer Despite advances in screening approaches for prostate cancer (PC), it is anticipated that 28,000 men will die of the disease this year in the United States alone. This highlights a need for safer and more effective imaging technologies for staging and monitoring of PC in these patients. ProstaScint® is the only FDA-approved targeted-imaging agent for PC. However, its clinical utility is limited by low specificity and sensitivity. Therefore, we propose the development of a novel imaging tool for PC that overcomes these limitations. This imaging agent will comprise a biological targeting moiety (an RNA aptamer) and an imaging moiety (a chelator) that is conjugated to the aptamer via a molecular linker. The RNA aptamer binds with high affinity and specificity to an antigen (PSMA) expressed on the surface of PC cells. The aptamer will be conjugated to a chelator housing a positron emitting radionuclide for use in highresolution positron emission tomography (PET). We hypothesize that by optimizing the imaging and targeting moieties of the imaging agent we will enhance binding to its target and improve the overall stability of the radionuclide complex. In specific aim 1, we will test various chelators and linkers used to conjugate the chelator to the RNA aptamer. In specific aim 2, we propose the development of structural homologs and multimers of existing PSMAspecific aptamers to increase the aptamers’ stability and functionality. Finally, in specific aim 3, we test the binding affinity and specificity of the resulting optimized agents in PSMA-positive PC cell lines. In summary, we predict that this work will lead to a highly specific PET-based imaging agent that may substantially improve the management of PC. The work proposed herein will also contribute to the advancement of methodologies that can be applied to engineer targeted imaging agents for other human diseases.

William Rockey, MD, PhD Radiation Oncology University of Iowa Hospitals and Clinics Bracco Diagnostics/RSNA Research Resident Grant

A Novel CT-based Biomarker for Predicting Therapy Response in Hepatocellular Carcinoma by Selective Quantification of Non-necrotic Tumor Components Rapid developments in imaging techniques and advent of newer chemotherapeutic agents for treatment of hepatocellular carcinoma (HCC) have highlighted the limitations of Response Evaluation Criteria in Solid Tumors (RECIST). Estimation of total tumor volume has shown to be more effective than RECIST but proves tedious for manual segmentations and poses problems for incorporation in workflow. Moreover, some targeted chemotherapeutic agents may cause more tumor necrosis compared to another. This may lead to false positive enlargement of the total tumor size on imaging, which results in overestimation of an otherwise regressed or stable disease, as progressive according to existing RECIST or total tumor volumetry criteria. Revisions in tumor response assessment criteria on imaging are therefore needed. Our hypothesis is that estimation of interval change in soft tissue volumes in a treated HCC by segmenting and excluding necrotic portions on baseline and post-treatment MDCT datasets is possible through automation and can be a better predictor of therapy response than RECIST. This project will involve retrospective collection of baseline and post-treatment MDCT datasets of patients with advanced HCC who were treated with the same drug protocol.

Anand Singh, MD Radiology (3-D Imaging) Massachusetts General Hospital Siemens Healthcare/RSNA Research Fellow Grant

Interval change in non-necrotic volume between CTs obtained at different time point by manual and automated method will be estimated, followed by maximum one-dimensional tumor measurements (RECIST). RECIST measurements and interval change in non-necrotic volume will be obtained by manual and proposed automated method and correlated with patient’s overall and progression-free disease survival. The inter-method and intra-method agreements will also be evaluated by manual and the proposed automated method. After successful testing of our hypothesis, this method may have significant impact in clinical oncology for therapy response assessment on wider latitude where similar principles for automations can be applied to other organ tumors.

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In Vivo MRI Assessment of Erythropoietin Treatment on the Migration of Iron Oxide-labeled Neuronal Stem Cells in a Rat Stroke Model Stroke-related mortality in the Western world is second only to that related to heart disease. Current treatment options are of limited benefit. Imaging can play a pivotal role in providing the means for delineating in vivo molecular mechanisms of the reparative process and site-directed therapy and by offering early prognostic information. Partial success has been achieved in reversing stroke-induced deficits with stem cell administration in experimental animals. The conditions required by stem cells to migrate to peri-infarct tissue and to differentiate into neuronal cells is not yet understood.

M. Reza Taheri, MD, PhD Radiology University of Washington GE Healthcare/RSNA Research Fellow Grant

Erythropoietin (EPO) promotes angiogenesis in the ischemic boundary region and facilitates migration of neuroblasts to this area. We hypothesize that co-administration of neural stem cells (NSC) and EPO will result in improved migration of NSC (primary endpoint), decreased size of infarcted tissue, and better functional outcome in a rat stroke model (secondary endpoints). NSC labeled with iron oxide particles with/without the co-administration of EPO will be transplanted into the corpus callosum after temporary middle cerebral artery occlusion (MCAO) in a rat. The size of the area of infarct/ischemia as well as the in vivo rate of migration of NSC will be measured multiple times with MRI during the 3 weeks after MCAO. Evolution of the imaging findings will be correlated to changes in neurologic deficits. This project will provide new information about the in vivo role of EPO on migration of NSC to periinfarct tissue and about the importance of this process in post-stroke recovery. This project will allow me to hone my understanding of the pathophysiology of stroke as well as the role of stem cells and imaging in this process. I intend to build on this project and systematically explore the in vivo mechanism of migration and differentiation of stem cells.

Identification of Anti-Neoplastic FADD Kinase Inhibitors Utilizing a Molecular Imaging-Based High Throughput Screen

Terence Williams, MD, PhD Radiation Oncology University of Michigan Toshiba America Medical Systems/RSNA Research Resident Grant

Despite advances in our understanding of the derangements in genes and signal transduction pathways associated with neoplastic initiation and progression, there has been minimal impact on survival for many types of cancer. For instance, the 5-year overall survival for lung cancer over the past 15 years remains poor, with mortality in the range of 70–90% for locally advanced disease. Previous work has identified that Fas-associated death domain (FADD) overexpression and phosphorylated FADD (p-FADD) serve as prognostic biomarkers in a number of human malignancies including lung cancer, where they are associated with higher proliferation and poor survival. Furthermore, increased p-FADD expression correlated with elevated NF-kB activation. These results suggest a relationship between FADD phosphorylation and NF-kB activation, a hallmark of therapyresistant cancers. I hypothesize that inhibiting FADD phosphorylation may sensitize cancer cells to chemotherapeutic agents. To aid in identification of FADD kinase inhibitors, I will utilize a previously generated pan-FADD kinase reporter (FKR), which non-invasively senses FADD-kinase activity in real-time through bioluminescent imaging. In aim 1, the sensitivity and specificity of FKR will be characterized. In aim 2, a high-throughput screen will be performed to identify compounds that target FADD phosphorylation from a diverse set of compound libraries. Utilizing secondary screens, the toxic and less sensitive lead molecules will be eliminated. Their relative efficacy will be evaluated by quantifying IC50 of the top lead compounds. Finally, the specificity of candidate molecules in inhibiting FADD kinases will be investigated using western blotting and protein kinase arrays. The long-term goals are to identify compounds which inhibit FADD kinase activity and which can be tested in pre-clinical models, perhaps in combination with other chemotherapies to determine whether inhibition of FADD phosphorylation sensitizes cells to chemotherapeutics. Ultimately, these compounds may benefit the treatment of tumors that are resistant to conventional therapies.

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Ultra-High Resolution Clinical Imaging of the Human Medial Temporal Lobe with 7 T MRI My research goal for neuroradiology fellowship is to investigate the medial temporal lobe at ultra-high resolution with high-field magnetic resonance imaging. I will develop a novel methodology for in vivo imaging of human hippocampal microanatomy using 7 Tesla MRI, employing both structural imaging and diffusion tensor imaging with tractography for microanatomic functional correlation. In order to obtain maximum resolution under controlled conditions, this protocol will be applied to postmortem specimens of normal brains as well as brains from Alzheimer patients. We then plan to apply this imaging procedure to patients with clinically defined Alzheimer disease and mild cognitive impairment to facilitate the diagnosis of Alzheimer pathology before dementia ensues. Additionally, we will scan epilepsy patients with possible medial temporal sclerosis to identify with greater accuracy earlier signs of hippocampal derangement.

Michael Zeineh, MD, PhD Radiology Stanford University RSNA Research Fellow Grant

Grant

Research Medical Student Investigating the Role of the Gradient Index in Predicting Side Effects from Gamma Knife Radiosurgery in the Treatment of Meningiomas During the development of radiosurgery treatment plans, clinicians use several different approaches to choose the best plan, clinical expertise being the most important factor. Several measures are in use clinically, such as the conformality index, to help clinicians objectively assess the merits of different treatment plans. Recently, Paddick and Lippitz suggested that the gradient index, a measure of the dose falloff outside the tumor volume, might be an effective approach for choosing among plans with similar conformity. The goal of this project is to investigate whether clinicians can use the gradient index (GI) in addition to other dosing parameters to develop treatment plans that will lead to fewer side effects post-gamma knife radiosurgery (GKRS) for the treatment of meningiomas, one of the most common brain tumors. Specifically, we are interested in studying whether the gradient index is correlated with the frequency and occurrence of side effects post-GKRS treatment in these patients. We are also interested in studying whether treatment plans with lower isodose volumes have the same effect on tumor volume reduction but lead to fewer side effects. These studies are novel as they will use patient follow-up data to study the efficacy of the gradient index and will close the gap between the theoretical benefit of the gradient index and its clinical benefit. Our study has the potential of having tremendous impact in the treatment planning process. If the GI is found to be correlated with the occurrence of fewer side effects, clinicians can supplement their expertise by using this simple and objective calculation to assess the quality of treatment plans leading to significantly fewer side effects and better overall outcomes.

Ehsan Balagamwala, BA Radiation Oncology Cleveland Clinic Foundation RSNA Research Medical Student Grant

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Evaluation of MR-Visible ThermaSphere® Microspheres for Simultaneous Chemoembolization and Thermal Ablation Evaluate the efficacy of transarterial chemoembolization with different MR-visible ThermaSphere® formulations that simultaneously provide thermal ablation and doxorubicin release when exposed to an external alternating magnetic field on tumor kill in vitro and in the rabbit Vx-2 liver tumor model. Tumor kill efficacy will be compared to four optimized microsphere formulations including 1) Bland ChemoSpheres®, 2) Doxorubicin Loaded ChemoSpheres®, 3) Bland ThermaSpheres® and 4) Doxorubicin Loaded ThermaSpheres®.

Brad Barnett, BS Radiology The Johns Hopkins University School of Medicine RSNA Research Medical Student Grant

It is our hypothesis for this study that control and efficacy can be achieved by localizing, combining, and synchronizing the heat delivery and doxorubicin release. We further hypothesize that such a delivery can be achieved using the appropriate combination of micron- and nano-scale materials and energy-based remote activation of these materials. The rationale for this approach is three-fold: First, localizing heat and chemotherapeutic delivery provides tissue-sparing control of both agents. Further, synchronizing the delivery of the two agents can potentially enhance the tumoricidal effects of each agent, increasing the therapeutic benefits through potentiation or synergy. Finally, potential benefit arises from the remote activation and control of dose and rate by adjusting the heat level with AMF power. In this proposal it is only the initial hypothesis that will be tested. An understanding of the mechanism will be the subject of future efforts.

Improving Specificity and Sensitivity of a ComputerAided Detection Algorithm for Intracranial Aneurysms Early detection of intracranial aneurysms is important for prevention of the morbidity and mortality that result from aneurysm rupture. Detection rates of small intracranial aneurysms (3 mm–7 mm) with MRA are low, with sensitivities for trained neuroradiologists of 60%–70%. We have designed a computer-aided-detection (CAD) algorithm designed to detect small intracranial aneurysms on MRA images. The goal of this project is to enhance the sensitivity and specificity of this algorithm through detailed analysis of output data and identification of “typical” false-negative and false-positive results.

Waleed Brinjikji, BS Radiology Mayo Clinic RSNA Research Medical Student Grant

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Using available clinical reports and consultation with the scientific advisor, I will analyze 200 MRA patient datasets with angiographically confirmed aneurysms and 500 MRA patient datasets with angiographically confirmed absence of aneurysms establishing “ground truth” for presence or absence of aneurysms. I will then manually delineate a region of interest (ROI) containing each aneurysm. Each segment of the intracranial vasculature will be assigned a unique number to allow for automated analysis of vessel location. The ROI will be compared to the results of the CAD algorithm to identify false-negative and false-positive CAD outcomes on a location-by-location basis. We will assess the characteristics of false-negative and false-positive cases, including: 1) aneurysm location; 2) aneurysm neck and dome size; 3) diameter of branch vessels near “false-positive” aneurysm neck; and 4) degree of imaging artifact in parent artery. The dataset generated will then be used by the computer scientist group to identify specific, reproducible, and problematic arterial locations or aneurysm types that lead to erroneous CAD outputs. This enhanced understanding of the CAD algorithm will lead to improvements in the algorithm itself, with the long-term goal of optimizing accuracy.

Evaluation of the Coagulation State in Relation to Transarterial Chemoembolization for Hepatocellular Carcinoma Transarterial chemoembolization (TACE) is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC). Incidences of both hypercoagulability and bleeding disorders have been reported following TACE for HCC, though these findings are complicated by the baseline hypercoagulable state of malignancy and the transient prothrombotic state observed following other embolization procedures. Therefore, it is unclear what net effect TACE has on coagulability in the setting of HCC and whether certain patients may be more at risk of complications due to bleeding or clotting. We propose to obtain serial longitudinal peri- and intra-procedural measurements of coagulation and hyperfibrinolysis markers for this investigation including: thrombin-antithrombin (TAT) complex, prothrombin fragment 1 and 2 (F1.2), platelet factor 4 (PF4), plasmin-2-antiplasmin (PAP) complex, and D-dimer. Samples will be obtained at intervals before and within the first 24 hours after transarterial chemobolization. We hope to determine if clotting and/or bleeding risk is high enough to warrant special precautions for some patients undergoing this procedure.

Jacob Brown, BA Radiology Georgetown University & National Institutes of Health MD/PhD Partnership Program RSNA Research Medical Student Grant

Detecting Complicated Plaque in the Coronary Arteries using Magnetic Resonance Intraplaque Hemorrhage (MRIPH) Technique in a Porcine Model of Diabetes-Induced Accelerated Atherosclerosis Atherosclerosis is a complicated disease process that is implicated in a number of conditions including coronary artery disease (CAD). Despite much research, its pathogenesis is not yet fully elucidated; therefore, good animal models are required in order to learn more about the disease process. Using magnetic resonance intraplaque hemorrhage (MRIPH), we propose to visualize the progression of coronary artery atherosclerosis in a previously established porcine model of diabetes-induced accelerated atherosclerosis. Six pigs (8–12 weeks of age) will be randomly allocated to one of two groups: diabetic-hyperlipidemic (D-HL) (n=4) and nondiabetic-normolipidemic (N-NL)(n=2). In the DHL group, the diabetic pigs will receive an intravenous injection of streptozotocin (a b-cell cytotoxin) to induce diabetes and a high-cholesterol (15%), high-fat (15% lard) diet to induce hyperlipidemia. The N-HL group will not receive streptozotocin and will be on a regular diet. Both groups will receive an MRIPH scan every 5 weeks for 20 weeks and blood work (cholesterol, lipids, fasting blood glucose) every week for 20 weeks. The animals will be sacrificed at 20 weeks and the left anterior descending and right coronary arteries will be dissected. The tissue will be analyzed for histological characteristics (evidence of complicated plaque) and the lumen stenosis will be measured. A trained, blinded observer will interpret the MRIPH images. Imaging results will be correlated with blood work and histological data.

Helen Cheung, BSc Radiology University of Toronto RSNA Research Medical Student Grant

We hypothesize that diabetic, fat-fed pigs will be more likely to have a positive MRIPH than the nondiabetic, normolipemic group and that there will be an increase in the prevalence and the size of the MRIPH signal with increased progression of the disease. The goal of this project is to develop the use of imaging to follow disease progression in animal models and to determine the usefulness of the MRIPH technique in detecting complicated plaque in the coronary arteries.

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Correlation Between Tumor Perfusion Measurements and Tumor Growth Delay with Radiation Therapy in an Autochthonous Prostate Cancer Murine Model

Michael Connolly, BMSc Radiation Oncology Schulich School of Medicine & Dentistry, The University of Western Ontario RSNA Research Medical Student Grant

Today’s radiation therapy treatments offer unprecedented radiation delivery flexibilities and if oncologists knew which tumor sub-volumes are radioresistant and which sub-volumes are radiosensitive, dose could be prescribed on the basis of biologic target volumes. Prior to implementing this tumor or normal tissue functional imaging for radiotherapy, we have to overcome two hurdles. First, we need to find an imaging modality that yields information relevant to radiation sensitivity. Second, such information needs to be translated quantitatively into an increase or decrease in radiation dose for the intended response (enhanced tumor kill or reduced normal tissue damage). CT-perfusion (CTP) and power doppler ultrasound (PDUS) imaging of tumors are two promising techniques for imaging biologic responses to radiation. The use of image-guided animal irradiation experiments can be an effective pre-clinical assay for novel radiotherapy targeting. Our study represents the first known attempt at radiotherapy delivered to intact prostate in an autochthonous prostate cancer animal model with image guidance. Using a murine model of prostate cancer, the tumor growth delays (time to reach 5x pre-radiation volume) will be derived from the weekly micro-CT scans following radiation, and we seek growth delays’ correlation with the level of tumor perfusion from pre-treatment micro-CT and micro-US scans. The changes in tumor blood flow and volume will be monitored weekly after irradiation by micro-CT and every other day by micro-US. The micro-PDUS data will be cross-correlated with the micro-CTP data (that we considered to be the gold standard) to see how well measurements with one modality can be predicted based on measurements with the other modality. I will be responsible for the micro-US scans as well as the cross-correlation of data between microCTP and micro-USPD scans. The supervisor will be responsible for overseeing the entire project, including micro-CT perfusion scans and the radiation therapy.

Retrospective Review of Extra Hippocampal White Matter Abnormality in Patients with Hippocampal Sclerosis, Using Diffusion Tensor Imaging: Three Automated Post Processing Methods Detection of white matter abnormality by visual inspection has played an instrumental role in identification and diagnosis of brain pathology. High resolution scanning and increased computational power provide an overwhelming quantity of data for analysis. Minute anatomical abnormalities detected are at a level not visually apparent. Therein lies the motivation for an algorithm that can detect these changes and distinguish the pathological change. To this end, the diffusion tensor magnetic resonance imaging (DT-MRI or DTI) technique has arisen, to characterize white matter connectivity as a means of inferring pathological change at the neural tract level.

Cristian Coroian, BS Radiology University of California, Los Angeles David Geffen School of Medicine Fujifilm Medical Systems/RSNA Research Medical Student Grant

MRI has been particularly successful in demonstrating hippocampal pathology in patients with MTLE. Approximately 1% of the world’s population suffers from epilepsy and current surgical treatments leaves 10%–30% of patients with persistent disease. Studies have shown putative extra-hippocampal changes may be of importance. Currently, DTI has improved detection of hippocampal pathology with significant diffusivity and fractional anisotropy parameter changes. Furthermore, detected whole brain parameter changes suggest that in conjunction with a detection algorithm, DTI can yield a more effective diagnostic study. There are multiple methods that can be employed to programmatically detect anatomical changes. We propose to perform a blind retrospective study to analyze pre-surgical DTI imaging of patients who became seizure-free or not seizure-free post-surgically. Three methods will be utilized to research optimal detection of minute abnormal anatomical change. Correlation will be made between identified regions of white matter and neuropsychological testing, electro-encephalographic data, and postsurgical seizure frequency. Consequently false positive and negative rates can be quantified to optimize the choice of method with corresponding threshold values. Automatically detecting minute white matter abnormalities will supplement visual diagnosis and improve pre-surgical planning and patient's post-surgical outcome.

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Comparison of Quantification Techniques for Long T2 Components in Patellar Articular Cartilage at 3 T: Multi-Echo Spin Echo (ME-SE), 2D Spiral Chopped Magnetization Preparation (2D-SCMP) and T2 Preparation with Ultrashort Echo Time (UTE) Acquisition Osteoarthritis (OA) is the most common type of arthritis, affecting an estimated 20.7 million adults and costing nearly $60 billion per year in the United States alone (Buckwalter JA, et al. ADDR 58 [2006] 150-67). Conventional imaging modalities capture later stages of OA in the form of tissue loss, which is too late for preventative treatment. In contrast, noninvasive MR evaluation has proven effective in characterizing both morphologic change in articular cartilage as well as biochemical change reflecting infrastructural degradation. Specifically, T2 values (an intrinsic MR tissue characteristic) have been shown to reflect collagen integrity within articular cartilage, offering a noninvasive means of detecting the earliest structural changes in the degenerative cascade (Gray ML, et al. J MSK Neuron Interact 2004; 4(4):365-68, Dijkgraaf LC, et al., J Oral MF Surg 1995;53(10):1182-92). Articular cartilage has a known zonal variation in T2 relaxation times that ranges from 1 msec in the deepest layers to 40 msec in the more superficial layers, the former definitely representing a technical challenge for conventional MR evaluation.

Eric Diaz, BS Radiology University of California School of Medicine, San Diego RSNA Research Medical Student Grant

We propose to test the feasibility of two novel pulse sequences for T2 quantification, the 2D-SCMP and T2 Preparation UTE acquisition, against the standard clinical reference (ME-SE). All pulse sequences will be tested first in phantoms and subsequently in cadaveric patellar specimens. Cadaveric patellae will be sectioned into 3 mm axial slices using a high-precision saw. MR imaging data will be collected with a home grown finger coil on a GE Signa Hdx 3.0T clinical scanner. For the phantoms, calculated T2 values from each technique will be compared with known T2 phantom values. For the patellar slices, T2 relaxation times will be processed off-line using a Matlab subroutine. In addition, to determine if the novel sequences are sensitive to articular cartilage degeneration, the cadaveric patellae will be subsequently analyzed by biochemical assay and immuno-histochemical evaluation. Sequence efficiency will be assessed by duration of scan time.

Development of a Decision-Analytic Model to Estimate Long-Term Outcomes of Cryoablation and Radiofrequency Ablation for Renal Cancer A rise in the incidental detection of renal tumors by diagnostic imaging has contributed to an increase in the incidence of renal cell carcinoma (RCC). Despite improved detection rates, mortality rates from RCC have not improved, suggesting that current RCC surgical treatment paradigms require reexamination. Determining conditions under which ablative therapies are effective will improve the quality of patient care significantly and prevent the unnecessary use of invasive and costly surgical procedures. The use of ablative therapies in RCC treatment is of considerable interest as they are less invasive and expensive than the standard surgical treatment, nephron-sparing surgery (NSS). However, they may be associated with higher local recurrence rates. Our group's preliminary work suggests that radiofrequency ablation (RFA) is preferred to surgery under most assumptions. Now, building upon the group’s current decision model, we will assess and compare the long-term outcomes of percutaneous imaging-guided radiofrequency ablation, cryoablation, laparoscopic, and open NSS for the treatment of small RCC in a refined, updated decision-analytic model. To accomplish this, we will first collect data by performing a systematic review of the literature on RFA, cryoablation, and laparoscopic and open nephron-sparing surgery (NSS) for renal tumors. We also will perform a systematic review on renal tumor growth/behavior and recurrence, and use the SEER cancer registry to obtain relevant outcomes data. The cumulative data elicited will provide insight into the current performance status of radiofrequency ablation, cryoablation, and laparoscopic and open NSS for treating renal tumors, and will be used to build an updated decision-analytic model that will estimate the life expectancy and lifetime costs consequent to each strategy.

Rebecca Hartman, BA Institute of Technology Assessment Massachussetts General Hospital Rebecca is enrolled at the University of Pennsylvania School of Medicine RSNA Research Medical Student Grant

The long-term effectiveness, cost, and cost-effectiveness of each strategy will be compared.

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64Cu-ATSM Uptake In Vitro and Ex Vivo in Cervical Cancer The objective of this research is to evaluate 64Cu-ATSM uptake in cervical cancer cell lines and in tumor explants from biopsy specimens of patients with newly diagnosed cervical cancer. This is an exploratory study to demonstrate the feasibility of this technique in anticipation of developing further translational research. This is especially important in light of the soon to be activated American College of Radiology Imaging Network study (ACRIN 6682), (Phase II Trial of 64Cu-ATSM PET/CT in Cervical Cancer). Cervical cancer ranks among the top three cancer diagnoses in women worldwide.

Wesley Haynes, BS Radiation Oncology Washington University School of Medicine RSNA Research Medical Student Grant

In the United States, the SEER Cancer Statistics Review identified cervical cancer as the third leading cause of average years of life lost per person dying of cancer for all races and both sexes. About onethird of cervical cancer patients develop recurrent disease, with the majority of these recurrences detected within the first 2 years after completion of therapy. Proven predictors of disease recurrence include tumor stage, lymph node status, and tumor hypoxia. Copper (II)-diacetyl-bis (N4methylthiosemicarbazone), Cu-ATSM, labeled with a positron emitting isotope of copper has been shown, in vitro and in vivo, to be selective for hypoxic tissue. In silico studies have explored the mechanism of its hypoxia selectivity, and clinical studies with this agent have shown noninvasive imaging data that are predictive of cervical cancer patients’ response to conventional therapy. Tumor hypoxia is an important prognostic factor in cervical cancer and predicts for decreased overall and disease-free survival. In part, this is because hypoxic tumors are resistant to radiation and chemotherapy.

Efficacy of Targeted Molecular Therapies Combined with Irradiation on Skin Squamous Cell Carcinomas

Kristina Hoot, PhD Radiation Oncology Oregon Health & Science University Canon U.S.A./RSNA Research Medical Student Grant

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Skin cancers are the most common cancer in the United States, of which squamous cell carcinomas (SCCs) are the second most common type. Loss of transforming growth factor beta (TGFb) signaling mediators, Smad2 and Smad4, are among the most common alterations seen in skin SCCs. Keratinocyte-specific Smad2 knockout mice were more susceptible to skin carcinogenesis via transcriptional upregulation of Snail subsequently downregulating Ecadherin leading to epithelial-tomesenchymal transition. Keratinocyte-specific Smad4 knockout mice developed spontaneous SCCs mediated by increased TGFb and Smad3 resulting in increased inflammation and genomic instability. Further, both Smad2 and Smad4 knockouts developed increased angiogenesis compared to chemically induced tumors in wildtype mice mediated by hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), respectively. Radiation therapy is commonly used in the treatment of skin SCCs of the head and neck or as adjuvant treatment with a salvage rate of <50% for patients with positive lymph nodes. Our preliminary data indicate that molecular targeting of the HGF receptor, c-met, reduces angiogenesis in Smad2-deficient skin to that of wildtype skin. However, the effects of molecular targets on Smad2- and Smad4-knockout tumor growth and metastasis have not been assessed. Further, the radiosensitivity of Smad2- and Smad4-deficient cells and tumors have not been fully characterized. We aim to address whether irradiation with molecular targeted therapy to the HGF receptor, cMet, or to VEGF is capable of increasing the therapeutic efficacy of irradiation alone.

Development of Magnetic Resonance Imaging-Visible Embolic Agents Transcatheter arterial chemoembolization (TACE) is a minimially invasive procedure and the current standard treatment for unresectable hepatocellular carcinoma. Chemotherapeutics and embolic materials such as polyvinal alcohol (PVA) particles are injected locally to produce a combination of cytotoxic and ischemic effects to induce tumor necrosis. However, difficulty in assessing embolization endpoint sometimes leads to incomplete treatment, liver damage, or non-target embolization, which can decrease treatment response rate or increase mortality and morbidity. To overcome this limitation, we aim to devise and validate MR contrast agent-modified PVA particles (CA-PVA) that can be visualized intra- and post-procedurally. Commercially available PVA particles 300–700 µm in size used clinically will be modified with Gd(III) complexes. Building on previous work in PVA modification done at Northwestern, a new chemical modification strategy will be used to improve the loading of Gd(III) per particle and maximize MR signal. The synthesized CA-PVA will be validated and the imaging parameters optimized using in vitro and ex vivo model systems on a clinical MR scanner. Specifically, CA-PVA will be imaged in capillary tubes, agarose phantoms, rabbit liver tissues, and a dynamic flow model mimicking human arteries. The long-term goals of this work include validation of CA-PVA using in vivo rabbit tumor models to monitor real-time delivery and in vivo fate of the embolic material, and eventual clinical translation of CA-PVA to help optimize TACE protocols to improve success rate.

Hsiang-Hua Hung, BASc, MASc Radiology Northwestern University Feinberg School of Medicine RSNA Research Medical Student Grant

Comparison of CT Perfusion and MR Perfusion Derived Cortical Grey Matter CBF in Cognitively Impaired and Unimpaired Multiple Sclerosis Patients Quantitative MRP derived CBF correlates with CTP derived values in MS patients. A similar reduction of cortical grey matter CBF is expected for each modality in patients with and without cognitive impairment. Our primary objective is to compare measured CTP and MRP derived cortical CBF. Secondarily, we will analyze whether the correlation is maintained in the presence of cognitive impairment. The single center pilot study will evaluate 44 MS patients; 22 with cognitive impairment and 22 without. Patients will be matched for disease duration, age, sex, and their EDSS scores. I will use my learned expertise to assist with image analysis and compiling research data. MRP will be performed on a Philips 3 T with a quadrature coil to ensure compatibility with our current in-house software applications. To allow for direct comparison of the different image sequences, the volumetric T1 and T2/PD weighted images will be coregistered with the DSC images. These images will then be analyzed in a stepwise sequence. CTP will be performed on a 64-slice VCT (GE, Lightspeed VCT). The calculation of CBF, CBV, BBB PS maps from the acquired CT perfusion data will be performed on a GE advantage workstation (ADW4.2) with the CT perfusion software. No prior study has evaluated the correlation between CTP and quantitative MRP-derived cortical CBF. Validating this association provides an opportunity for MS patient follow-up using either modality. It is secondarily anticipated that perfusion parameters may provide an important correlation with impaired neurocognition and that this may be used as a surrogate marker of disease activity.

Marcus Jansen, BSC Radiology University of Ottawa Philips Healthcare/RSNA Research Medical Student Grant

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The Correlation of Tumor Perfusion with Clinical Outcomes during Chemoembolization of Hepatocellular Carcinoma Transcatheter arterial chemoembolization (TACE) is an established treatment for non-resectable hepatocellular carcinoma. However, optimal angiographic endpoints of the procedure have not been established. Transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging offers an objective method to quantify intraprocedural tumor perfusion change. This study will test the hypothesis that intraprocedural tumor perfusion change, as detected and quantified by TRIP-MR imaging, correlates with clinical outcomes of TACE on non-resectable hepatocellular carcinomas.

Brian Jin, BA Radiology Northwestern University Brian is enrolled at Albert Einstein College of Medicine RSNA Research Medical Student Grant

We will recruit 100 consecutive patients with non-resectable hepatocellular carcinoma patients who are scheduled for TACE using MR monitoring. TACE will be performed in a combined MR/interventional radiology (MR-IR) suite that allows intra-procedural monitoring. Using TRIP-MR, we will measure the immediate pre-procedural and post-procedural perfusion by calculating the forward volume transfer constant (Ktrans). Pre-procedural, post-procedural, and interval change in Ktrans will be separately correlated with clinical outcomes immediately after the procedure, and at 1, 3, and 6 months follow-up. Clinical outcomes will consist of a) MR response b) functional MR response as indicated by diffusion weighted MR c) toxicity levels , and d) survival. We expect that baseline and interval reductions in TRIP-MR detected perfusion levels during TACE can predict future clinical outcomes. If so, then TRIP-MR could be used as a prognostic biomarker during therapy and be used to establish an endpoint for TACE. It could also potentially help stratify which patients should receive TACE or another therapy.

Anatomopathological Correlation of Diffusion Tensor Imaging in Epilepsy Patients with Focal Cortical Dysplasia Focal cortical dysplasia (FCD) is the most common cause of pediatric intractable epilepsy. For the 30% of epilepsy patients who cannot be treated with medication, surgical resection is an effective therapy. However, subtle forms of cortical dysplasia may be difficult to define on MRI. Pilot studies have suggested that diffusion tensor imaging (DTI) may improve recognition of FCD in epilepsy surgery patients, but the correspondence between imaging anatomy and pathology remains unclear. The purpose of this study is to relate changes in imaging parameters apparent diffusion coefficent (ADC) and fractional anisotropy (FA) with histopathological changes in patients with focal cortical dysplasia. Further insight into this relationship should enhance the utility of DTI in directing the management of epilepsy patients.

Jennifer Kung, BA Radiology University of California, Los Angeles David Geffen School of Medicine RSNA Research Medical Student Grant

ADC and FA measurements will be made in 25 cases of surgically proven FCD between 2003 and 2008 in whom DTI was a component of presurgical evaluation. Values will be obtained in the region of FCD as well as in the surrounding tissue and in the contralateral equivalent region. Histopathological studies of the resected tissue will be performed using Kluber Barrera myelin stain, GFAP, MAP2, NeuN, Vimentin, Ki67, CD68 and HE stains. Statistical analysis will be performed to explore relationships between DTI values and pathology results. The presence of dyslamination, balloon cells, dysmorphic neurons, degree of gliosis, ectopic neurons, and polymicrogyria will be assessed and compared to the clinical features including seizure frequency, EEG pattern, and post surgical outcome. We hypothesize that increased ADC will be associated the decreased myelin protein. In DTI, FA reflects the density and orientation of dendrites, neurons, and axons, and we expect to see this correspondence on a histopathological level.

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Radiologic and Microarray (Radiogenomic) Analysis of Gastric Adenocarcinoma: A Novel Classification of Tumor Subtypes and Prognosis Carcinogenesis is marked by a progression through a series of accumulated genetic aberrations and mutations. With the development of microarray, the simultaneous evaluation of thousands of genes and their individual expression patterns is now possible. Nonetheless, the clinical utility of such genetic profiling is currently limited due to cost and limited availability. Therefore, a method of translating some of these molecular insights into a clinically useful framework is needed. In this project, we hope to correlate genetic profiles of gastric cancer with phenotypic features on CT and then use this information to generate gastric cancer subtypes and identify novel prognostic factors using radiogenomic data. Gastric adenocarcinoma tissue from deceased patients who also have accessible imaging studies at UCLA will be collected from the UCLA Pathology Department. Medical records will be examined for pertinent patient data, including demographics, oncologic history, pathologic examination of gastric lesion, disease interventions (eg, chemotherapy, radiation therapy, gastric resection), and length of survival after initial diagnosis of gastric adenocarcinoma. The tissue samples will undergo microarray gene expression analysis after extraction of RNA using RNAeasy Mini Kit (Qiagen, Valencia, Calif, USA) according to manufacturer’s protocol. T-test will be used to identify differences in mean gene expression levels between comparing groups. Diagnostic CT scans will be reviewed by two board-certified radiologists and several traits will be closely examined and scored, including tumor diameter, distribution, presence of enhancement after intravenous contrast, tumor margins, and presence or absence of lymph node involvement or distant metastases. Finally, radiogenomic analysis correlating gene expression data and phenotypic CT image data will be performed.

Valentin Lance, BS Radiology University of California, Los Angeles RSNA Research Medical Student Grant

Improved Isotropic 3D FSE Methods for Imaging the Knee Conventional MR imaging of the knee utilizes two-dimensional fast spin-echo (FSE) acquisitions that require imaging at anisotropic resolutions and gaps between excitation slices. These highly anisotropic methods introduce the risk of partial volume artifacts and prevent reformatting of image data in different planes. Three-dimensional volumetric acquisitions at isotropic resolutions overcome these problems, and may increase detection accuracy of pathology in joints imperceptible using 2D methods. A newly developed 3D FSE sequence with extended echo train (3D-FSE-Cube) is currently under investigation for use in diagnostic joint evaluation at 3 T. However, optimal pulse sequence parameters for producing the highest quality images have yet to be determined. To ascertain these values for a particular joint, 10 healthy subjects will receive knee MRIs at 3 T. The imaging parameters repetition time (TR), receiver bandwidth, echo train length and parallel imaging factor will be systematically altered for each subject while maintaining a constant scan time of 5 minutes and isotropic spatial resolution of 0.6 mm. Qualitative measures for blurring and detail and quantitative measures for signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for different tissues will be calculated. Parameter combinations maximizing SNR, CNR, and detail while minimizing blurring will be considered optimal. The optimized 3D acquisition can then be further evaluated with respect to traditional 2D FSE sequences, pre-optimized 3D-FSE-Cube sequences or arthroscopy for detection sensitivity of joint pathology.

Charles Li, BS Radiology Lucas Center for MR Spectroscopy and Imaging Stanford University Charles is enrolled at the University of California, San Diego School of Medicine RSNA Research Medical Student Grant

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Evaluation of the Effect of Spleen Irradiation on the Extent of Ischemic Stroke in a Rat Model Stroke is the leading cause of long-term neurological disability in adults and the third leading cause of death in the United States. Currently, the only FDA-approved treatment for stroke is tissue plasminogen activator (tPA), which has a narrow therapeutic window (~3 hours) and limited success. The goal of our research is to reduce the impact of this devastating disease by applying a novel approach: temporary radiation-induced splenectomy (radiologic splenectomy).

Ted Ling, MS, BS Radiation Oncology James M. Slater MD Proton Treatment and Research Center Loma Linda University Ted is enrolled at Saint Louis University School of Medicine RSNA Research Medical Student Grant

The spleen is an organ with multiple functions; aside from storing red blood cells, it is also a part of the immune system and contributes to the inflammatory response seen in stroke. Our hypothesis states that temporary radiation-induced suppression of the spleen may promote neuroprotection by interrupting the splenic inflammatory responses after an ischemic or hemorrhagic stroke. The translation of radiologic splenectomy into clinical application will be straightforward as spleen irradiation with relatively low doses is already often used in the palliative treatment of hematological malignancies. This experiment will explore the response of the spleen to radiation as it pertains to stroke progression. Twenty aged Sprague–Dawley male rats will be divided into one control and three experimental groups testing different times of splenic radiation after the initiation of focal cerebral ischemia using the intraluminal thread occlusion of the middle cerebral artery (MCAO). Each animal will be followed for a period of 7 days after which it will be euthanized for histological analysis. The following data will be collected and analyzed at 1, 2, and 7 days after MCAO: (1) venous blood cell counts (2) infarct size (DWI) (3) brain cell morphology and lesion size (hematoxylin-eosin [H&E] staining) (4) standardized neurological score. If this study is successful, the benefit would be enormous for the millions of people newly affected by ischemic stroke each year in our aging society.

Evaluation of 18F-FDG PET/CT in Monitoring Tumor Ablation Efficacy of Irreversible Electroporation (IRE) in Rabbit VX2 Liver Tumor Primary liver cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Recently, irreversible electroporation (IRE) has emerged as a promising minimally invasive method to ablate liver cancer. Our preliminary studies have demonstrated that IRE can be used to cause cell death of aggressive rabbit VX2 tumor of the liver. However, the effectiveness of different imaging modalities in monitoring tumor response to irreversible electroporation has not been investigated. Therefore, in this study, we will evaluate 18F-FDG PET/CT and CT alone in monitoring tumor ablation efficacy of irreversible electroporation.

Christina Ma, BS Radiology University of Southern California Keck School of Medicine RSNA Research Medical Student Grant

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Previous studies have shown that 18F-FDG PET/CT performed after treatment provides additional, earlier, and more accurate information about treatment efficacy compared to CT alone. This technique has been accepted in the diagnosis, staging, and follow-up of non-small cell lung cancer, lymphoma, colorectal and esophageal cancer, melanoma, head and neck cancers, and breast cancer. In this proposal, we hypothesize that 18-FDG PET/CT is an effective method in monitoring tumor response to irreversible electroporation. Given the appropriate results, we propose to translate our findings into a practical treatment and follow-up method for liver cancer patients. Ten rabbits will have VX2 tumors implanted into the left lobe of the liver and will be subjected to ultrasound-guided IRE of the implanted tumors. Pre-procedure, immediately post-procedure (within 24 hours), and post-op (in 14 days) follow-up CT alone and PET/CT imaging will be performed using Siemens microPET scanner to evaluate radiologic changes. PET/CT data will be compared to CT alone data to assess which modality is more effective in monitoring the IRE-ablation of VX2 tumor. Ablated tissues will be collected and investigated for immunohistological evaluation using H&E and TUNEL assay.

Post-Thrombotic Syndrome: Outcomes of ImagingGuided Endovascular Intervention Established Post-Thrombotic Syndrome (PTS) is considered a debilitating, lifelong condition that impairs quality of life and has no consistently effective treatments. To date, there is no study that systematically evaluates the effectiveness of novel imaging-guided endovascular interventions for PTS. The purpose of our study will be to 1) describe the effectiveness of imaging-guided endovascular interventions for the management of established PTS in patients with deep vein thrombosis (DVT); and 2) identify patient factors that predict favorable outcomes. A retrospective analysis of clinic records and imaging studies of patients diagnosed with PTS who have received an endovascular intervention (stent placement in the iliac vein or endovenous thermal ablation) at our institution between 2003 and 2008 will be performed. Patients will be retrospectively categorized as having exhibited complete response, partial response, or no response to therapy based upon their physicians’ overall assessments at follow-up visits. The presence of symptoms (pain, cramps, heaviness, pruritus, paresthesia) and signs (edema, skin induration, hyperpigmentation, venous ectasia, redness, pain during calf compression) of PTS at presentation and at interval follow-up will also be recorded and used to retrospectively to estimate a Villalta score (a standardized assessment for PTS). The proportion of patients exhibiting complete, partial, and no response will be described. The mean Villalta score and severity category will be calculated and compared for the pre-treatment and posttreatment data. The following baseline patient factors will be noted: presence or absence of venous thrombosis of the common femoral or iliac vein, presence or absence of femoropoliteal vein patency, and presence or absence of previous ipsilateral venous thrombosis, body mass index, age, and sex. Analysis will be performed to determine if there is a statistically significant improvement in PTS severity after intervention and if any patient factors correlate with a statistically significant improvement in PTS severity.

Lina Nayak, BA Radiology Washington University Medical School Mallinckrodt Institute of Radiology RSNA Research Medical Student Grant

Impact of Radiation Dose on Tumor Downstaging, Pathological Complete Response Rate, and Overall Survival Rates in Advanced Stage Rectal Cancer In 2008, colorectal cancer was the third most lethal cancer in both men and women in the United States. Several studies have demonstrated the efficacy of pre-operative 5FU-based radiochemotherapy in rectal cancer. The main advantages of pre-operative compared to postoperative radiotherapy include the possibility of reduction in tumor size, increased chances of surgical resection with negative margins, and reduced toxicity. However, the impact of radiation dose fractionation on pathologic outcomes in rectal cancer remains unclear. To begin answering these questions, we propose to evaluate the impact of long-course (five-week duration) pre-operative radiochemotherapy on tumor downstaging, pathologic complete response rate (pCR), and overall survival rates in advanced stage rectal cancer. The proposed project will retrospectively analyze pre- and post-operative rectal cancer pathology slides from two cohorts of patients receiving pre-operative radiochemotherapy. One cohort received capecitabine + 45 Gy (in five weeks, 1.8 Gy/morning) while the other cohort received capecitabine + 52.5 Gy (in five weeks, 1.8 Gy/morning with additional 1.5 Gy/afternoon in the last pre-operative week). We will quantify tumor downstaging, pCR, and overall survival rates. We hope to determine whether concomitant boost radiotherapy is superior to traditional fractionation methods for preoperative radiochemotherapy in advanced stage rectal carcinoma.

Chirag Patel, MSE Radiation Oncology The University of Texas MD Anderson Cancer Center RSNA Research Medical Student Grant

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Dissecting the Role of p53 in the Response of Primary Lung Cancers to Radiation Therapy Efforts to improve radiation therapy are hindered by uncertainties in its cellular target and mechanisms of cell death. Moreover, how specific gene mutations affect the response of lung cancers to radiation therapy is unknown. For example, the p53 tumor-suppressor gene is frequently mutated in lung cancers. Following ionizing radiation the p53 protein causes both a G1 cell cycle arrest and apoptosis, which have opposite effects on cell survival. The consequences of p53 gene mutations on the response of lung cancers to radiation therapy remain unclear.

Bradford Perez, BS Radiation Oncology Duke University School of Medicine RSNA Research Medical Student Grant

We aim to clarify the role of p53 in radiation response using mouse models of primary lung cancers which are now available in our laboratory. Using Cre-lox technology, we will generate primary lung adenocarcinomas in the lungs of mice with either wild-type (WT) or no expression of p53. We will use micro-computed tomography (micro-CT) to follow the response of lung tumors from each genotype (Kras mutation vs. K-ras mutation and p53 deletion) to radiation therapy. Tumor growth delay will be measured using three dimensional volume assessments from serial CT scans at time points before and after radiation treatment. We will also assess the degree of apoptosis and cell cycle arrest after radiation treatment in lung tumors from each genotype. These studies will test our hypothesis that lung cancers without p53 expression are less likely to undergo apoptosis and therefore are more resistant to radiation therapy. These findings will provide us with important insights into the critical role of p53 and its downstream pathways in determining the response of lung adenocarcinomas to radiation therapy.

Surveillance with FDG PET/CT vs Conventional Follow-up Algorithm and CT: Impact on Management and Survival

Srikar Rao, BA Radiology Mount Sinai School of Medicine RSNA Research Medical Student Grant

The 5-year survival rate for head and neck cancer remains less than 60%. Despite adoption of aggressive therapy, at least 30% of patients will relapse within 2 years of therapy. Accurate and timely detection of recurrence may be critical for attempting surgical salvage and may offer a survival benefit. There is no standard approach integrating diagnostic modalities into routine clinical work-up for detecting recurrence and imaging decisions are at the discretion of the treating physician. PET/CT may be a superior modality in this setting. However, previous studies lacked high statistical power and lacked comparative data with NCCN guidelines and HRCT. At our institution, there is an established surveillance program incorporating PET/CT which we will compare to the NCCN guidelines and HRCT. We also aim to evaluate the impact of PET/CT on clinical management and survival as well as its cost-effectiveness. The findings of this work may drastically alter management of patients with head and neck squamous cell carcinoma (HNSCC). We will conduct a retrospective analysis of patient data from 2005–2008. We believe results will show surveillance with FDG-PET/CT is superior to the NCCN follow-up algorithm as well as high resolution CT (HRCT) in the early detection of recurrent HNSCC.

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Evaluation of Hippocampal Damage and Episodic Memory Loss in Multiple Sclerosis Using DTI Until recently, little emphasis has been placed on cognitive deficits in multiple sclerosis (MS). Although direct-effect gray matter pathology in MS brains is unknown, it is clear that greater than 50% of MS patients become cognitively impaired with 30%–40% of patients demonstrating specific episodic memory dysfunction. A portion of MS patients that present with memory deficits demonstrate relatively few physical disabilities or white matter lesions. These findings suggest that hippocampal pathology, unrelated to white matter lesion load, may cause memory impairment in MS patients. Diffusion tensor imaging (DTI) is likely the best possible tool for in vivo study of the hippocampus. Specifically, transverse diffusivity offers the most promising imaging measure available to detect the hippocampal demyelination and axonal pathology in MS. The overall goal of the present study is to determine the relationship between hippocampal damage, as determined by DTI measurements, and loss of episodic memory in patients with MS. This work will contribute to a larger, ongoing, funded project of my advisor’s, to develop imaging markers for cognitive changes in MS, specifically, those relating to the loss of episodic memory. The long-term goal is to develop a sensitive biomarker for evaluation of episodic memory that will be instrumental in the development and assessment of therapies to halt or slow memory loss in MS. I will be participating in research-related clinical procedures, such as cognitive evaluations and MRI examinations, and my major role will involve the image processing and statistical analysis. My advisor will be involved with many of the clinical aspects of the study, including selecting patients and performing procedures. After initially training me, he will review my analyses of the imaging data at both intermediate and final stages.

Chintan Shah, BS Radiology Cleveland Clinic Foundation Canon U.S.A./RSNA Research Medical Student Grant

Enhanced Radiosensitization of Prostate Cancer Cells Using Combined Treatments of Genistein and Vitamin D Prostate cancer (PCa) affects millions of men worldwide and although advances have been achieved, numerous limitations still exist with current treatment options. Experimental evidence suggests that genistein plus vitamin D is superior to genistein alone in treating PCa. Genistein is a soybean-derived isoflavone which we have previously shown potentiates radiotherapy effects on PCa cells in vitro and in animal models. The active form of vitamin D, 1 alpha-25-dihydroxyvitamin D3 [1,25(OH)2D3], is a multifunctional hormone which in addition to regulating calcium and bone homeostasis also exerts antiproliferative and pro-differentiation effects on PCa cells. 1,25(OH)2D3 induces apoptosis, inhibits metastasis, and like genistein potentiates radiotherapy effects on PCa cells. In the absence of radiation, genistein enhances the antiproliferative effects of 1,25(OH)2D3 by inhibiting CYP24, the catabolic enzyme that initiates 1,25(OH)2D3 breakdown. Other downstream targets such as the vitamin D receptor (VDR), cell proliferation proteins (p21, cyclin D, IGFBP3), and antiapoptotic proteins (bcl2, bax) are also modulated by combined genistein and 1,25(OH)2D3 treatments. Based on the findings that genistein or 1,25(OH)2D3 potentiates radiation-induced cell killing in PCa cells, we will investigate whether the combination enhances the radiosensitization of PCa cells, beyond the effect seen with each one independently combined with radiation. Time- and dose-dependent treatments and clonogenic survival assays will be used to determine whether the combined treatment increases the cytotoxicity effects in PC-3 PCa cells. Northern blot, western blot, and invasion assays will be used to elucidate the treatment-induced changes that occur in downstream signaling pathways which are involved in cell survival/death. Statistical analysis of the data will be performed to determine the significance in three or more independent experiments.

Alvin Thompson, PhD Radiation Oncology Wayne State University School of Medicine RSNA Research Medical Student Grant

We hope to validate our in vitro findings in an animal model and use the study to lead to strategies for using safe compounds to enhance the effect of radiotherapy.

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Transcranial Sound Field Characterization Using High-Focused Ultrasound (for the Purpose of Mechanical Sonothrombolysis in Stroke) Recently, Hoelscher, et al., demonstrated in vitro that transcranial high-focused ultrasound (HiFU) enables clot liquification within 30 seconds of insonation in absence of further lytic agents (ie, tissue plasminogen activator). Moreover, they demonstrated in a small series of cadaveric skulls that phase aberration correction might be negligible to focus the ultrasound (US) beam after transskull insonation.

Christian Welch, BS Radiology University of California School of Medicine, San Diego RSNA Research Medical Student Grant

   

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We believe that, once a preferred US parameter setting (ie, duty cycle, pulse length, duration) has been evaluated, acoustic intensity might remain the only parameter which has to be adapted interindividually to achieve efficient transcranial sonothrombolysis independent from the individual skull bone density and/or thickness. The goal of this project is to compare bone density and bone thickness with acoustic signal absorption in a series of human cadaveric skulls and to test whether this three parameters correlate with each other. We aim to acquire 50 volumetric computed tomography (CT) datasets of cadaveric skulls to generate bone density and bone thickness maps. In parallel, we will characterize the transcranial sound fields of these 50 skulls to assess the amount of the individual signal absorption and defocusing. The data acquired will be used to compare bone density, bone thickness, and signal absorption for each skull and to test whether they correlate using statistical methods. If correlation can be shown a coefficient might be generated to compensate for inter-individual differences in bone density and/or bone thickness to achieve comparable acoustic intensity exposure at the target site. This correlation coefficient might contribute to provide optimal US exposure for each individual stroke patient by compensating for individual bone characteristics. We strongly believe that this approach could be a future landmark in stroke treatment using HiFU for non-invasive, mechanical clot lysis.

Grant

Education Scholar

Includes recipients of the Education Seed Grant and Fellowship Training Grant (not available in 2010)

Developing a “Best Practice” National Registry for CT Scans in Children Five years after the Institute of Medicine (IOM) issued its pivotal report, “To Err is Human: Building a Safer Health System,” JAMA 2005;19:2384-2390, Lucian Leape, MD, a leader in safety in medicine, wrote, “improvement of the magnitude … [of change] …envisioned by the IOM requires a national commitment to strict, ambitious, quantitative, and well-tracked national goals.” He explains that “no comprehensive nationwide monitoring system exists for patient safety. ...The most important single step … would be to set and adhere to strict, ambitious, quantitative and well-tracked national goals.” This project, “Best Practice Registry for CT Scans in Children,” would identify patient safety/best practice benchmarks, create a consortium to work on this issue and collect data as to how CT scans are performed in children compared to these benchmarks. Goals are to: 1. Improve my knowledge by learning the “science” of quality and safety. This will be done through graduate-level classes and partnering with national experts in quality at my institution. 2. Create a team of national pediatric radiology experts to develop a consensus for best practice for CT scans in children based on this science. 3. Develop a consortium of five hospitals to collect pilot data on CT scanning practice for pediatric patients. 4. Work with the American College of Radiology (ACR) Quality and Safety team to pilot collection of these measures of CT performance through the National Radiology Data Registry (NRDR). Agreement to work on this database has already been obtained from ACR.

Marilyn Goske, MD Radiology Cincinnati Children's Hospital Medical Center Derek Harwood-Nash Education Scholar Grant

Once the pilot phase is completed and evaluated, expansion into a nationwide CT registry may be indicated. The goal is to establish benchmarks in best practice in CT for children by creating a small community of thought leaders to evaluate five hospitals in this pilot with the ultimate goal to improve patient safety through the creation of a national registry.

The influence of Evidence-Based Teaching Methodology on Appropriate Imaging Utilization in a Large Academic Radiology Department Diagnostic imaging has become widely available and plays an increasing role in clinical diagnosis and therapy. Inappropriate imaging utilization is also increasing at a high rate as referring clinicians are often unsure what test to order and when. Such use is costly and can delay diagnosis and therapy (thus decreasing patient throughput) and exposes patients to unnecessary ionizing radiation. Appropriateness criteria for imaging tests are available but are not widely known or easily applied. The long-term objectives of this research (or work) are to increase appropriate utilization of cardiothoracic imaging studies in hospital settings. The short-term objectives of the study described herein are to increase appropriate utilization of cardiothoracic imaging in our tertiary care academic center, by disseminating appropriateness information and imaging pathways, via formal and informal teaching. The first specific aim of this proposal will be to devise clinical imaging pathways for cardiothoracic imaging modalities, using evidence-based guidelines. We will develop explicit guidelines (similar to the ones that exist for pulmonary embolism) for patient work-up for cardiothoracic diagnostic imaging in the clinical scenarios of cough, shortness of breath, and chest pain (cardiac, atypical, and noncardiac).

Aine Kelly, MD Radiology (Cardiothoracic) University of Michigan GE Healthcare/RSNA Education Scholar Grant

The second specific aim is to educate clinical and radiology colleagues, using formal and informal teaching methods such as short didactic presentations, handouts on important points, the use of flow charts, and small group case based interactive sessions. The outcome measure is increased clinicians’ and radiologists’ use of appropriateness criteria for cardiothoracic imaging studies in their practice. This is expected to improve healthcare by improving diagnosis and therapy in patient care, increasing reimbursements, decreasing costs, increasing efficiency in the imaging department, increase patient throughput in clinical departments, and decrease radiation burden.

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Developing a Curriculum for Teaching the Business of Radiology Organized academic radiology has largely ignored the needs of radiology trainees with respect to teaching them the essentials of radiology practice management and business principles. Residents and fellows enter their new careers vulnerable to and ignorant of pitfalls in establishing a radiology office, purchasing equipment, negotiating contracts, ensuring accurate billing and collection, and avoiding potential medicolegal entanglements. The proposed educational program is designed to provide an electronic curriculum of 1 year's duration (24 lessons) for teaching these principles.

David Yousem, MD, MBA Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins Medical Institutions

I will use the Education Scholar Grant to develop the skills needed to design Web-based electronic interactive learning modules that incorporate video and static teaching material, to create the most effective multiple-choice questions and answers for determining the knowledge gained by the viewer, to input spread sheets that can be downloadable for offline use, and develop tools for assessing the relevancy of the modules to clinical and academic practice. The value of the program will be tested serially as well as via electronic surveys as trainees enter their careers. I will spend time taking lessons on educational techniques and Web design while using the textbook I co-edited, Radiology Business Practice: How to Succeed (2007) as a starting point for developing the curriculum.

Philips Healthcare/RSNA Education Scholar Grant The main benefit to the radiology community would be the development of a practical user-friendly

interactive online program that teaches business principles for a successful radiology practice whether in academia or private practice.

Creating a Blended Introductory Radiology Course for Geographic Dispersed Campuses The aim of this proposal is to create open digital educational resources for introductory radiology instruction in the preclinical medical school curriculum. This will include: 1) a standardized series of introductory radiology modules with self-paced online instruction to augment live lectures; and 2) a computer-based case application laboratory session. The two medical colleges at Michigan State University are expanding their campuses and enrollment. Currently the introductory radiology course is taught to over 350 students at one location, but by 2011 it will be taught to over 500 students at four geographically dispersed locations. We want to ensure that consistency and quality are maintained.

Gerald Aben, MD Radiology Michigan State University RSNA Education Seed Grant

We are looking at this expansion as an opportunity to redesign, pilot, and evaluate various educational methods. We will identify best practices in radiology instruction and build on them to enhance delivery of radiology curricular material in second year courses, the fourth year radiology elective clerkship and radiology concepts in other clerkships. We propose to redesign the 10 introductory radiology lectures into blended instruction, with the live lectures presented remotely via videoconferencing technology, as well as available by streaming video. Each lecture will be accompanied by two online modules, one for preparation for the lecture, and the second for practice after the lecture. The modules will contain images, examples, and case studies. Online office hours and a live lab at each site will allow students access to instructors. We will make the modules and recorded lectures freely available online and will present the project at national meetings. We hope to use this course redesign as a template for other courses. As the primary care physician shortage worsens and medical schools expand their enrollments, the lessons we learn from this project may help them.

 

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Teaching Systems-Based Analysis: Operational Engineering and Management Concepts for Radiology Residents The goal of this preliminary study is to develop and test educational materials for teaching radiology residents and fellows concepts of operational engineering and management to provide an intellectual framework for management decisions, as well as to provide “hands-on” experience with the radiology department’s LEAN improvement projects. This study will use a multidisciplinary approach integrating the campus-wide resources available, especially those from the Department of Industrial and Operational Engineering, Center for Research on Learning and Teaching, and the University of Michigan Health Systems LEAN Program “Michigan Quality System” with concepts of managing for innovation. One of the goals is to develop a series of radiology case-based teaching examples; compelling stories that illustrate real-life management issues and have the residents make decisions about these complex situations based on their readings and experience. Their analysis and proposed solutions would then be compared with the actual results. By involving faculty specialized in teaching techniques, these stories and their analysis and teaching points could be presented as an instructional package. Two additional goals would evaluate by interview and survey residents’ participation in ongoing departmental improvement projects to discover the optimal period in their training for such hands-on involvement and to determine the project characteristics most advantageous to resident participation.

Catherine Brandon, MD Radiology University of Michigan GE Healthcare/RSNA Education Seed Grant

The main benefit to the radiology community would derive from the use of these case-based examples by other radiology departments to supplement their residency education programs on systems-based problems. These preliminary examples could be used as a basis for securing additional funding to support a full 4-year program of case-based learning. Information gained on the timing and characteristics of resident participation in hands-on systems improvement would also benefit other residency training programs.

Training Tool For Colonic Insufflation and Scanning in Virtual Colonoscopy The goal of the study is to create a training module that can be used by radiologists and technologists to learn how to perform CT colonography exams. Extensive training and experience is needed to learn how to properly insufflate the colon using either a mechanical pressure-sensitive carbon dioxide pump or manual insufflation of room air. While lectures and written material can provide a guide, actual experience dealing with difficult cases is needed to obtain excellent scans necessary to properly interpret CTC. However a visit to an institution or training program where technologists can view or practice performing CTC has several drawbacks. First, information will not be retained unless a sufficient volume of cases are performed in an ongoing basis. Second, many scenarios dealing with different grades of patient pain, colonic spasm, retained fluid, and other pitfalls are difficult to teach. This project will develop a prototype software-based training tool using an upgradable modular graphics and text interface. Modules will simulate the patient, insufflator, CT scanner, and CT images produced. A sophisticated hierarchy of possible patient, insufflator, and scanning conditions will be simulated providing an interactive training environment that can be used to train and test students. The modules will be made using an existing graphics interface (National Instruments, LabView) that can be updated and used by any CT vendor or insufflator vendor to accommodate the unique features of their equipment. This design will potentially enable national and even international use of the training tool. The final product will be tested by training technologists who have not had CTC experience and testing their proficiency and time needed to acquire the necessary skills.

Abraham Dachman, MD Radiology The University of Chicago RSNA Education Seed Grant

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Integration of Radiation Oncology into the Undergraduate Medical Curriculum Radiation oncology is a subject that is not widely taught in the mainstream undergraduate medical curriculum, nor is it well understood by medical students and physicians outside of the field; yet it is an integral component of multidisciplinary cancer care. Integrating radiation oncology into the undergraduate medical curriculum would serve to provide broad teaching opportunities for all medical students including detailed review of anatomy and imaging, as well as an opportunity to teach multidisciplinary cancer screening, diagnosis, and management. I propose a multifaceted approach to the integration of radiation oncology education into the undergraduate medical curriculum:

Ariel Hirsch, MD Radiation Oncology Boston University Medical Center Varian Medical Systems/RSNA Education Seed Grant

First, as a component of the Oncology Education Initiative, in which we have begun incorporating formal didactic radiation oncology teaching into the 4th year of medical school during the radiology core clerkship. Beginning with the class of 2009, the radiology core clerkship is being moved into the 3rd year alongside core medicine and surgery rotations, which allows exposure to radiation oncology earlier in the curriculum. Second, a structured oncology block is being added to the 2nd year pre-clinical curriculum. As Oncology Block Leader, this past year I have worked to design the curriculum for the oncology course, which is planned for the final block of the academic year. Over the next year, we plan to meet in periodic focus groups to discuss student feedback and obtain perceptions and critiques of the effort from both pre-clinical and clinical faculty. Third, PI-led educational programming has emerged as an excellent avenue to share what I have learned as a medical educator with others and advance collaborative educational efforts on an institutional level. These three facets combine to support a basic understanding of the field and role of radiation oncology as well as to promote a clinical mindset that seeks to explore and leverage the advantages of interdisciplinary collaboration.

Development and Implementation of a National WebBased Examination System for Medical Students in Radiology Radiology clerkships and electives remain highly variable among medical schools, and there is no standardized examination. Evaluations at institutions differ significantly in scope, detail, and presentation method and many clerkship/elective directors are limited in time and academic resources. Developing fair and comprehensive tests is time consuming and difficult. There is significant variation in the level of expertise in writing questions; most are not validated and thus are not necessarily testing students effectively and fairly.

Petra Lewis, MD Radiology Dartmouth-Hitchcock Medical Center, Dartmouth Medical School RSNA Education Seed Grant

We have collected over 600 questions from 11 medical schools. We plan to develop a centralized, Web-based quiz database and exam-taking system. This would allow clerkship directors to contribute questions to a central bank, use this bank of questions to create exams, or use pre-existing exams from the database. Students would then take these exams online. By eventually developing several standardized exams similar to shelf exams, we have the opportunity to develop and apply standards for medical student education in radiology. ExamWebTM will develop the database software and exam-taking system according to our specifications and will provide server support. Questions will be collected and edited by a team of radiology educators. Questions will be based on the AMSER National Radiology Curriculum for Medical Students and test across the standard competencies. Course directors at individual medical schools will be provided with secure access to construct their own exams, use or edit pre-existing exams, and will be allocated PIN-type access for students to take examinations online. Eventually a series of “shelf-type” AMSER-certified exams will be developed. Question and exam performance analysis will be assessed on national pooled and individual institutional data, allowing questions to be refined and pass marks set, as well as allow a comparison among institutions.

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Radiologic Informatics Fellowship Program at Brigham and Women's Hospital   The specific aim of the RSNA Research & Education Foundation Institutional Fellowship in Radiologic Informatics at the Center for Evidence-Based Imaging at Brigham and Women's Hospital, Harvard Medical School, is to provide a formally designed training program in radiologic informatics consisting of educational, research, and experiential components. The fellowship was created in response to a present and future need for the training of radiologists in the specific area of information technology as it relates to the radiologic sciences. The main purposes of the program are as follows:   x x x

To promote and enhance the understanding and utilization of information technologies within radiology departments, to improve the quality, safety, and efficiency of care.   To increase the integration of systems and electronic access to image and relevant nonimage information within radiology and throughout the healthcare enterprise.   To assist in collaboration with industry in the establishment and implementation of clinical requirements for medical imaging informatics technologies and tools.  

As part of the research activities for the 2009–2010 fellowship, we will investigate various user interface devices currently unavailable in radiology. The idea is to have an in-depth understanding of the adequacy/inefficiencies of the standard keyboard and mouse as interface devices in the setting of radiology. Once these aspects are recognized, we will then create/design prototypes of various alternative input devices interfaced to a commercially available PACS system. We expect that results from this project will help shape the future of radiologist-computer interaction in the modern digital image environment that would maximize performance, comfort, and operation.

Ivan K. Ip, MD, MPH Brigham and Women's Hospital Harvard Medical School RSNA Fellowship Training Grant

Combined Fellowship Training in Musculoskeletal Radiology and Imaging Informatics The proposed fellowship program provides broad-based training in musculoskeletal radiology and imaging informatics. The program consists of three components: 1) Clinical training in musculoskeletal radiology, 2) a didactic informatics curriculum, and 3) research projects at the intersection thereof. Forty percent of the program will be spent as a clinical imaging fellow at The Johns Hopkins Hospital in the musculoskeletal radiology section. This work will have a strong focus on MRI, and will also include radiography, CT, image-guided procedures, and participation in interdisciplinary conferences. This work will be supervised by seven attending musculoskeletal radiologists. Another 30% of the program will be spent as an informatics fellow in the Department of Diagnostic Radiology and Nuclear Medicine at the University of Maryland Medical Center. The trainee will participate in a year-long didactic curriculum, covering core technologies, imaging information systems, and leadership issues in radiology informatics. A series of projects and literature reviews will complement lectures in topics such as decision support, enterprise imaging systems, and radiology reporting standards. Three faculty-level informaticists will supervise this work. The remaining 30% of the program will be devoted to original research at the intersection of musculoskeletal radiology and imaging informatics, with direct mentorship from the scientific advisors and with specific goals of promoting quality in radiology interpretation, communication, and education through informatics. Decision support will be a primary area of research during the program, and a modular application framework for radiology decision support will be developed. An initial application of this framework to problems in musculoskeletal imaging will also be implemented.

Kenneth Wang, MD, PhD Radiology Johns Hopkins Medical Institutions RSNA Fellowship Training Grant

Upon completion of this program, the trainee will have gained a broad range of expertise in musculoskeletal radiology and imaging informatics, and demonstrated original work in these areas. The program will promote leadership in technology as a clinical radiologist and the ability to perform ongoing research.

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Grant

RSNA/AUR/APDR/SCARD Radiology Education Research Development Using Six Sigma Techniques to Reduce Radiation Dose Radiologists and technologists must work as a team in order to optimize the risk/benefit ratio of fluoroscopic procedures.

In this project, a technologist with a strong quality and safety background will enroll in Six Sigma Green Belt Training. As part of that course, she will develop the project charter for capturing dose metrics from pediatric fluoroscopy procedures. Through a combination of classroom instruction, Webbased training and collaborative learning with other Green Belt trainees, the applicant will learn the Design, Measure, Analyze, Improve, and Control (DMAIC) steps.

Mandie Street, RT(R)(MR) Radiology Washington University RSNA/AUR/APDR/SCARD Radiology Education Research Development Grant

   

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The second project aim is to inspire technologists and other team members to actively seek process improvement opportunities. The applicant’s experience as a technologist will provide valuable insight into technologist workflow. The applicant has already demonstrated strong leadership and educator skills through her role in the department’s Quality and Safety Office. As a result, she is uniquely qualified to lead this process improvement project.

Award

Roentgen Resident/Fellow Research Nishard Abdeen, MD Diagnostic Radiology University of Ottawa Sunil Advani, MD Radiation and Cellular Oncology University of Chicago Rajan Agarwal, MD, MBA Radiology University of Pennsylvania Health System Demetrios Agriantonis, MD Radiology Texas Tech University Health Sciences Center Jeff Alpert, MD Radiology Lenox Hill Hospital Morgan C. Althoen, MD Radiology Mercy Catholic Medical Center Wilson B. Altmeyer, MD Radiology Ochsner Clinic Foundation New Orleans Christopher J. Anker, MD Radiation Oncology Huntsman Cancer Hospital, University of Utah Ryan W. Arnold, MD Radiology Aultman Hospital Mary Elizabeth Atherton, MD Radiology University of Arkansas for Medical Sciences

Alan Best, MD Radiology University of Colorado, Denver School of Medicine James A. Betler, DO Radiation Oncology Allegheny General Hospital Joseph J. Blake, MD Radiology and Radiological Sciences Vanderbilt University Medical Center Rachel Blitzblau, MD, PhD Therapeutic Radiology Yale University School of Medicine SoHyun Boo, MD Radiology West Virginia University Charles Douglas Brooks, MD Radiology Texas A&M HSC–College of Medicine/Scott & White Hospital Richard Bruce, MD Radiology University of Wisconsin Hospital and Clinics John Chi-Hung Chang, MD, PhD Radiology Stanford University Govind Chavhan, MBBS, MD, DNB Diagnostic Imaging The Hospital for Sick Children

Kevin Auerbach, MD Radiology Albany Medical Center

Sheema Chawla, MBBS, MD Radiation Oncology University of Rochester Medical Center

W. C hris topher B aughman, MD Department of Radiology MetroHealth Medical Center

Jonathan C. Cheng, MD, PhD Radiation Oncology University of California, Irvine

Anne-Marie Beaudet, MD Radiology Memorial University

Bhishamjit Chera, MD Radiation Oncology University of Florida

Luis S. Beltran, MD Radiology Thomas Jefferson University Hospital

Alison Chetlen, DO Radiology Penn State Milton S. Hershey Medical Center

Junzo P. Chino, MD Radiation Oncology Duke University Medical Center

Devang J. Doshi, MD Radiology Baystate Medical Center

Asim F. Choudhri, MD Radiology University of Virginia

Neal E. Dunlap, MD Radiation Oncology University of Virginia Health System

Jonathan Chung, MD Radiology University of Washington Paul Clark, DO Radiology Tripler Army Medical Center Kevin J. Croce, MD Radiology University of Kentucky Medical Center Andrew R. Deibler, MD Radiology Wake Forest University School of Medicine Carlo Demandante, MD Radiation Oncology The University of Texas Health Science Center at San Antonio

Carolyn S. Dupuis, MD Radiology University of Massachusetts Medical School Kirsten Emery, MD Radiology SUNY Downstate Medical Center Brenda Farnquist, MD Diagnostic Radiology Queen's University Myra Kay Feldman, MD Diagnostic Radiology Allegheny General Hospital Steven Eric Finkelstein, MD Radiation Oncology Moffitt Cancer Center University of South Florida

Paul B. DiDomenico, MD Radiology David Grant USAF Medical Center

Aaron Fischman, MD Radiology Mount Sinai School of Medicine

Jonathan Dillman, MD Radiology University of Michigan Health System

Angelique C. Floerke, MD, PharmD Radiology George Washington University

Federico Discepola, MD Radiology McGill University

Richard J. Gessman, MD Department of Radiology St. Vincent's Medical Center

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Wende N. Gibbs, MD Radiology Baylor University Medical Center at Dallas Daniel Ginat, MD, MS Imaging Sciences University of Rochester Medical Center

Bradley Huth, MD Radiation Oncology Drexel University College of Medicine, Hahnemann University Hospital Puneeth Iyengar, MD, PhD Radiation Oncology The University of Texas MD Anderson Cancer Center

Daniel R. Gomez, MD Radiation Oncology Memorial Sloan-Kettering Cancer Center

Bharathi Jagadeesan, MBBS Radiology University of Minnesota

Brandon Gunn, MD Radiation Oncology The University of Texas Medical Branch at Galveston

Adam J uyoung J ung, MD, P hD Radiology The University of Texas Health Science Center at San Antonio

Shivani Gupta, MD Radiology St. Vincent's Catholic Medical Center

Yasha Kadkhodayan, MD Radiology Washington University

Soterios Gyftopoulos, MD Radiology Beth Israel Medical Center Marsha Lee Haley, MD Radiation Oncology University of Pittsburgh Medical Center Medical Education Program Ethan Hansen, MD Radiology North Shore University Hospital

Joshua Kallen, MD Radiology Hartford Hospital Daniel R. Karolyi, MD, PhD Radiology Emory University Nicole M. K elleher-Linkonis , MD Diagnostic Radiology Medical College of Virginia James Martin Kessler, MD Radiology Jacobi Medical Center

Samantha Lynn Heller, PhD, MD Radiology NYU School of Medicine

Charles Y. Kim, MD Radiology Duke University

Heidi B. Henslee, MD Radiology University of South Alabama

Hee Kyung Kim, MD Radiology Cincinnati Children's Hospital Medical Center

Christine Hill-Kayser, MD Radiation Oncology University of Pennsylvania

Young W. Kim, MD Radiology Brooke Army Medical Center

Andrew Hines-Peralta, MD Radiology Beth Israel Deaconess Medical Center

Randall Kimple, MD, PhD Radiation Oncology University of North Carolina Hospitals

Charles Wesley Hodge, MD Radiation Oncology University of Wisconsin

Seth Klein, MD Radiology SUNY–Stony Brook University

Steve C. Hong, MD Diagnostic Radiology William Beaumont Hospital

Angelos A. Konstas, MD Radiology Massachusetts General Hospital

Ryan Hung, MD, PhD Radiology and Diagnostic Imaging University of Alberta

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Timothy Korytko, MD Radiation Medicine Arthur G. James Cancer Hospital, Ohio State University Medical Center

Matthew Koshy, MD Radiation Oncology University of Maryland Mark Landis, MD Medical Imaging The University of Western Ontario Kenneth Le, MD Radiology Tulane University Hospital Thu Trong Le, MD Radiology Santa Barbara Cottage Hospital David Lee, MD Radiology Albert Einstein Medical Center Justin Steven Lee, MD Radiology Georgetown University Hospital Jeffrey Levsky, MD, PhD Radiology Montefiore Medical Center Amanda Demetri Lewis, DO Diagnostic Radiology Hahnemann University Hospital Brett E. Lewis, MD, PhD Radiation Oncology UMDNJ-Robert Wood Johnson Medical School Jie Li, MD Radiology Memorial Sloan-Kettering Cancer Center, New York Daniel Mandell, MD Medical Imaging University of Toronto Susan A. McCloskey, MD Radiation Oncology Roswell Park Cancer Institute Mark W. McDonald, MD Radiation Oncology Emory University Tasha L. McDonald, MD Radiation Medicine Oregon Health & Science University

Joshua E. Meyer, MD Radiation Oncology New York Hospital of Queens/ Weill Cornell Medical College Asif Moinuddin, MD Radiology/Nuclear Medicine Saint Louis University Matt T. Moore, MD Radiology St. Joseph's Hospital & Medical Center Andrew Mullins, DO Radiology National Capital Consortium Akira Murakami, MD Diagnostic Radiology Boston University Medical Center Amy Musk, MD Diagnostic Radiology University of Maryland Medical Center Jeremy Neuman, MD Radiology Staten Island University Hospital Joshua Nickerson, MD Radiology University of Vermont/Fletcher Allen Health Care Refky Nicola, DO Diagnostic Radiology Cooper University Hospital/ UMDNJ-Robert Wood Johnson Medical School Mehul K. Patel, MD Radiation Oncology Henry Ford Health System Ashish B. Patel, MD Radiation Oncology University of Maryland Medical Center Stephanie M. Perkins, MD Radiation Oncology Washington University School of Medicine

Samuel McGrath, MD Radiation Oncology William Beaumont Hospital

Kiley D. Perrich, MD Diagnostic Radiology Dartmouth-Hitchcock Medical Center

Sonali Mehandru, MD Radiology University Hospitals Case Medical Center

Joseph Platnick, MD Radiology Staten Island University Hospital

Kenneth Meng, MD Radiological Sciences University of California, Irvine

Sanjay P. Prabhu, MBBS Pediatric Radiology Children's Hospital Boston

Ario Rezaei, MD Radiology University of Cincinnati Andrew L. Rivard, MD, MS Radiology University of Florida Clifford Grant Robinson, MD Radiation Oncology Cleveland Clinic Foundation Dave Roy, MD Radiology The University of Texas Southwestern Medical Center Ramin R. Saket, MD Radiology UCSD Medical Center Luke Scalcione, MD Radiology Winthrop-University Hospital

Yuji Seo, MD Radiation Oncology University Hospitals Case Medical Center Curt Settlemoir, MD Diagnostic Radiology Southern Illinois University School of Medicine Naishadh Shah, DO Radiology Temple University Hospital Navesh K. Sharma, DO, PhD Radiation Oncology Fox Chase Cancer Center John J. Sheehan, MD Radiology NorthShore University HealthSystem Feinberg School of Medicine

Todd C. Schirmang, MD Diagnostic Imaging Rhode Island Hospital/Brown Medical School

Timothy Norman Showalter, MD Radiation Oncology Thomas Jefferson University Hospital

Brian J. Schiro, MD Radiology UPMC Presbyterian

Ravi Shridhar, MD, PhD Radiation Oncology Wayne State University

David A. Schomas, MD Radiation Oncology Mayo Clinic

Dorothy Sippo, MD Radiology St. Luke's–Roosevelt Hospital

Adam Sciuk, MD Radiology Louisiana State University Health Sciences Center– Shreveport

Dee Dee K. Smart, MD, PhD Radiation Oncology Branch National Cancer Institute

Andrew D. Smith, MD, PhD Radiology Cleveland Clinic

Jennifer Tynan, MD Medical Imaging University of Saskatchewan

Joshua P. Smith, MD Radiology University of Alabama at Birmingham

Venu Vadlamudi, MD Diagnostic Radiology Michigan State University Flint Area Medical Education

Salil Soman, MD Radiology UMDNJ-Robert Wood Johnson Medical School

Waseet Z. Vance, MD Radiation Oncology Columbia University Medical Center New York Presbyterian Hospital

Susanna Spence, MD Diagnostic & Interventional Imaging The University of Texas Medical School at Houston Michael Spiotto, MD, PhD Radiation Oncology Stanford University

Robert N. Walker, MD, MPH Radiology Geisinger Medical Center

Ashmitha Srinivasan, MD Radiology Upstate Medical University

Jessica Leigh Walls, BSc, MD Radiology Residency Program University of British Columbia

Nicholas J. Statkus, MD Diagnostic Radiology Oregon Health & Science University

Nylah F. Wasti, MD Radiology Eastern Virginia Medical School

Jan Stauss, MD Radiology Brigham and Women's Hospital

John M. Watkins, MD Radiation Oncology Medical University of South Carolina

Aaron Stevenson, MD Radiology University of Tennessee Medical Center, Knoxville

Adam J. Weisbrod, MD Radiology Mayo Clinic

Pal Suranyi, MD, PhD Radiology Medical University of South Carolina

David Wilson, MD, PhD Radiology University of California, San Francisco

Krishna Surapaneni, MD Radiology Long Island College Hospital

J oel Aaron Y alowitz, MD, P hD Diagnostic Radiology Indiana University School of Medicine

Uma Swamy, MD Radiation Oncology New York Methodist Hospital Ronald Scott Swanger, MD Radiology New York Medical College Katharine Tansavatdi, MD Radiology University of California at Davis Stuart Yukio Tsuji, MD Radiation Oncology University of California, San Francisco

Jonathan Dillman, MD (center), radiology fellow at the University of Michigan with N. Reed Dunnick, MD (left), department chair, and Isaac R. Francis, MD (right), associate chair for research

Vikram Venkatesh, MD Diagnostic Imaging McMaster University

Eddy S. Yang, MD, PhD Radiation Oncology Vanderbilt University Medical Center Nam Chul Yu, MD Radiological Sciences UCLA Medical Center Hadi Zahra, MD Section of Radiation Oncology Baylor College of Medicine Katherine A. Zukotynski, MD Joint Program in Nuclear Medicine Harvard Medical School

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Award  

Outstanding Researcher

Sanjiv Sam Gambhir, MD, PhD

is the Virginia and D.K. Ludwig Professor of Radiology and Bioengineering at Stanford University. He received his bachelor of science degree in physics from Arizona State University in 1983. He subsequently received both his medical degree and doctorate in biomathematics in 1993 while in the Medical Scientist Training Program (MSTP) at the University of California at Los Angeles (UCLA). He completed an internship in internal medicine followed by a residency in nuclear medicine and a fellowship in PET/CT, at the Center for Health Sciences at UCLA. He rose up the ranks at UCLA to become director of the Crump Institute for Molecular Imaging and professor/vice chair of molecular and medical pharmacology. Dr Gambhir moved to Stanford in 2003 to direct the Molecular Imaging program and to lead nuclear medicine. He brought over 35 scientists with him from UCLA and has grown the program at Stanford to more than 150 scientists including 30 students, post-doctoral fellows, and scientists in his own multimodality molecular imaging laboratory. He was recently appointed head of the new Canary Center for Cancer Early Detection at Stanford and was appointed the Virginia and D.K. Ludwig Endowed Professorship in Cancer Research in 2009. Professor Gambhir is internationally recognized as a leader in the field of molecular imaging. His laboratory has developed fundamental new ways to image living subjects including methods to image gene expression and cell trafficking. He has developed methods to image signal transduction pathways including protein-protein interactions and other fundamental cellular events. Dr Gambhir has recently pioneered novel Raman nanomolecular imaging strategies that are being clinically translated for endoscopic imaging. He has translated novel molecular imaging strategies using reporter genes with PET/CT for pilot trials in gene and cell therapies. He played a major role in obtaining reimbursement for FDG PET from the Centers for Medicare and Medical Services including the development of several cancer cost-effectiveness models “Dr Gambhir brings an extraordinary blend of focus, intensity, and creativity for lung, colorectal, and other cancers. He is currently working to advance the merger of in to his work on imaging cellular and vitro and in vivo diagnostics using novel nanotechnology for earlier disease detection and molecular events in vivo. A team builder individualized patient management. and gifted scientist, he is renowned for his work on imaging gene expression and for the development of many clinical algorithms for cost-effective cancer care involving PET imaging.” –Gary J. Becker, MD 2009 President, RSNA; Executive Director, American Board of Radiology “Sanjiv Sam Gambhir is an innovative thinker, prolific writer, much sought-after speaker, mentor, and thought leader. He is an excellent example of a physician scientist and has become a model for what young research-oriented radiologists can aspire.” –Peter L. Choyke, MD Chief, Molecular Imaging Program, NCI “Dr Gambhir is instrumental in educating clinicians and scientists alike in the application of PET in solving fundamental problems in biomedicine. His biggest contribution is moving gene expression imaging from the bench to the bedside.” –King C. P. Li, MD, MBA Chair, Department of Radiology, The Methodist Hospital/Weill Medical College

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Dr Gambhir has more than 20 patents pending or granted and is the author of over 325 peerreviewed journal articles, including publication in Nature Medicine, Nature Biotechnology, Nature Methods, Science, PLOS Medicine, PNAS, Journal of Nuclear Medicine, Radiology, and many other journals. His work has been featured on the cover of over 20 journals including Science, Journal of Nuclear Medicine, Circulation, JACC, Journal of Urology, Gastroenterology, FASEB, Cancer Cell, Nano Letters, and Nature Reviews Drug Discovery. He is the co-editor of one of the best-selling books in the field of nuclear medicine, Nuclear Medicine in Clinical Diagnosis and Treatment. He is also co-editor of a new book, Molecular Imaging: Principles & Practice. He has received over $50 million in federal grant funding and currently is the principal investigator for several National Institutes of Health (NIH) R01s and program projects from the National Cancer Institute (NCI), including a Center for Cancer Nanotechnology Excellence and the In Vivo Cellular and Molecular Imaging Centers. Dr Gambhir has trained more than 150 residents, fellows, post-doctoral scholars, graduate students, undergraduates, and high school students in his laboratories and clinic, and is head of a NCI-funded R25T post-doctoral training grant. Always in demand, Dr Gambhir has given over 250 invited talks including more than 50 Keynotes at major international meetings. He has served as President of the Academy of Molecular Imaging (AMI) and in numerous advisory capacities to professional societies including RSNA and SNM. He is active in both AMI and Society for Molecular Imaging (SMI), serves on the NCI Scientific Advisory Board, and is an associate editor for several journals including Journal of Nuclear Medicine, Radiology, and Nature Clinical Practice Oncology. Dr Gambhir has received numerous awards including the Hounsfield Medal from Imperial College, Tesla Medal from the UK Royal College of Radiologists, Holst Medal, Doris Duke Distinguished Clinical Scientist Award, Paul C. Aebersold Award from the SNM, Achievement Award from the SMI, and the Distinguished Basic Scientist Award from the AMI. He co-hosted the 2007 Nobel Symposium on Imaging in Stockholm and was elected in 2008 as one of the youngest members to the Institute of Medicine of the National Academies.

Award

Outstanding Educator Elliot K. Fishman, MD is professor of radiology and oncology at The Johns Hopkins University School of Medicine and director of Diagnostic Imaging and Body CT at The Johns Hopkins Hospital. He began his medical career with a medical degree from the University of Maryland Medical School and his radiology career with a diagnostic radiology residency at Sinai Hospital of Baltimore and a computed body tomography fellowship from Johns Hopkins.

From the start, Dr Fishman approached radiology from the standpoint of an educator–from his earliest manuscripts focused on educating the practicing radiologist about body CT and the value of 3D imaging to his later articles on the science of radiology education. He has now produced more than 1000 journal publications, the majority of which include students or trainees as first author or co-author, a testament to his ongoing role as mentor to generations of residents, fellows, and junior faculty. His unique and engaging teaching style, highly innovative and inspirational, has proven to be an effective tool for career development for everyone he encounters. In addition to journal publications, Dr Fishman has co-authored 10 books and monographs including PocketRADIOLOGIST® Abdominal Top 100 Diagnoses and Multidetector Row CT: Principles, Techniques and Applications, now in its third edition, and 50 book chapters. He has developed 25 audiovisual and Web-based programs in his pursuit of widespread dissemination of radiologic educational materials through computer-based methods, including CTisus.com, a Web site used by more than 60,000 radiologists and technologists in over 120 countries worldwide. The site won the gold medal at the American Roentgen Ray Society (ARRS) annual meeting and the Magna Cum Laude at the RSNA scientific assembly and annual meeting. Other awards and honors include election in 2002 to Alpha Omega Alpha—The Honors Medical Society and Aunt Minnie Awards in Radiology—“Best Educator” in 2001 and 2007 and “Best Researcher” in 2004. Additional honors include America’s Top Doctors, Castle Connolly Medical Ltd’s “America’s Top Doctors for Cancer” 2005–2009, “America’s Top Doctors” 2001–2009, and Medical Imaging Magazine’s “Top Radiologist in the Nation” in 2007. His contributions continue with 75 visiting professorships, numerous industrial consultations, service to 40 advisory committees, and as reviewer, consultant, and member of editorial boards for more than 35 journals. He is an active member of at least 16 professional radiology organizations and has contributed to them all with thousands of lectures and principal presentations, and countless abstracts presented at national and international meetings. Each year, Dr Fishman brings to the RSNA scientific assembly and annual meeting at least 20 education exhibits, scientific posters, scientific papers, plenary sessions, and refresher courses.

“Elliot has demonstrated a commitment to and effectiveness in educating radiologists, technologists, and referring physicians through innovation, communication, and inspiration that is second to none. He has also mentored generations of residents, fellows, and junior faculty who have gone on to achieve success in their academic pursuits.” –Jonathan S. Lewin, MD Professor and Chair, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions

“Elliot Fishman has been at the forefront of every new technical development in the field of body CT and has surely educated more radiologists around the world about CT than anyone. I am proud to know him as a careerlong colleague and friend.” –Michael P. Federle, MD Professor and Associate Chair for Education Department of Radiology, Stanford University Medical Center

In the last 20 years, Dr Fishman has coordinated more than 100 continuing medical education (CME) courses for the Johns Hopkins School of Medicine. His CME courses focus on state-of-the-art body CT and include hot topics such as CT angiography and cardiac imaging. He currently organizes 8–10 CME courses annually across the country and recently added an international CME meeting.

“Elliot has been tirelessly innovative in harnessing unexpected benefits of rapidly evolving technology for the purpose of effectively communicating clinical and educational information. He envisioned how 3D imaging would expand the usefulness of imaging beyond diagnosis to therapeutic planning; and CTisus.org has harnessed the power of the Internet to allow any radiologist anywhere in the world to bring these benefits to their patients.”

Elliot Fishman has demonstrated a long-standing commitment to education directed toward the improvement of the art and science of radiology and, ultimately, the benefit of patient care.

–Alec J Megibow, MD, MPH Professor, New York University Medical Center

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2009 RSNA Research & Education Foundation Board of Trustees

Back Row: E. Russell Ritenour, PhD G. Scott Gazelle, MD, PhD James P. Borgstede, MD Hedvig Hricak, MD, PhD, Dr(hc) Burton P. Drayer, MD Gary J. Becker, MD R. Gilbert Jost, MD, Treasurer

Front Row: William T. Thorwarth, Jr, MD Beverly B. Huckman, Secretary Theresa C. McLoud, MD Jack E. Price, Chair Not Available for Group Photo: Vijay M. Rao, MD

RSNA Research & Education Foundation

820 Jorie Blvd Oak Brook, IL 60523-2251 1-800-381-6660 [email protected] RSNA.org/Foundation