Imaging Of Acute Stroke-ct And-or Mri.pdf

Journal of Neuroradiology (2015) 42, 55—64

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ScienceDirect www.sciencedirect.com

REVIEW

Imaging of acute stroke: CT and/or MRI Karl-Olof Lövblad a,∗,b, Stephen Altrichter a,b, Vitor Mendes Pereira a,b, Maria Vargas a,b, Ana Marcos Gonzalez a,b, Sven Haller a,b, Roman Sztajzel a,b a

Service neuro-diagnostique et neuro-interventionnel, DISIM, 4, rue Gabrielle-Perret-Gentil, 1211 Genève, Switzerland b Service de neurologie, Genève, Switzerland Available online 25 November 2014

KEYWORDS Stroke; Imaging; Magnetic resonance imaging; Computed tomography

Summary Acute ischemic stroke is now clearly recognized as a medical emergency. As such diagnosis has to be done quickly and in a precise way during the therapeutic window. Both computed tomography and magnetic resonance imaging are tools that can adequately demonstrate ischemia really very early on. MRI using diffusion techniques has a much higher sensitivity for acute lesions but its implementation has not been unproblematic due to initial resistance and some technical problems. Thus, very often CT is still preferred with MR used for situations where the answer given is not sufficient as well as for follow-up of lesions. However, the parallel development of new therapeutic strategies have rendered the precision of the tools more and more sophisticated and their combined use can help to improve patient outcomes in ways never imagined previously. No matter which technique is used, be it alone or in combination, the idea is to speed up and optimize management in order to provide early revascularization and reperfusion. © 2014 Published by Elsevier Masson SAS.

Introduction Since cerebral ischemia has been declared to be at least partially treatable within the therapeutic window, stroke has now become a clearly defined medical emergency [1—3]. Indeed, the trend started by the NINDS trials was followed by an increasing interest in both pharmacological and interventional therapies for acute ischemia. While almost all

∗

Corresponding author. E-mail address: [email protected] (K.-O. Lövblad).

http://dx.doi.org/10.1016/j.neurad.2014.10.005 0150-9861/© 2014 Published by Elsevier Masson SAS.

neuroprotective agents have unfortunately proven to be only successful in the laboratory setting [4], thrombolysis and thrombectomy have proven to have their benefits in patients treated within a clearly defined therapeutic window [5]. Initially, brain imaging has been done on an exclusion basis only, meaning that unenhanced CT was used mainly to determine if there was hemorrhage or some other kind of easily visible brain pathology (e.g. tumour) that caused the acute neurological deficit [5—10]. While this was an initial success and worked for the first trial it is also true that this did not per se determine that all these patients really had ischemia; indeed, the exclusion of hemorrhage is per se not equivalent with the presence of a stroke; thus, most new imaging

56 techniques also revolve around determining if there is some kind of stroke mimic. One major issue is that since there is very little time available (4.5 hours currently for MCA ischemia using rTPA), the patient needs to be acutely treated within this therapeutic window. Since any given stroke protocol is very complicated and imaging only represents a portion of any kind of acute management, it is imperative that imaging provides both a quick and precise answer, thus not prolonging the time needed to make a decision on treatment. A majority of patients with acute stroke still arrive outside the therapeutic window but those who do still need a full work-up with a neurological examination, full laboratory tests etc. Indeed, and much to the distress of many traditional neurologists and even neuroradiologists, imaging has become an inherent part of the early work-up and as such represents a little part, but a part that is technology intensive and personnel intensive. The main aims of primary neuroimaging are manifold: first of all the overall aim even before imaging is to exclude another pathology: the main pathology to be excluded is of course hemorrhage (since thrombolysis is the treatment being proposed) but it also encompasses diseases such as multiple sclerosis, epilepsy, functional states. Thus, after having simply looked at the parenchyma it is necessary to look at some more parameters that can be obtained with either CT or MRI. The next logical step is to see if there really is cerebral ischemia: indeed, treatment should not be done only when nothing is seen but offered to patients who actually are harboring an acute cerebrovascular event: this can be done by looking for further signs of ischemia on DWI with MR or for the acute signs of ischemia on CT; then when that is done the level of occlusion can be looked for: here CT can sometimes often demonstrate an acute hyperdense artery and T2* will show a thrombus as well. When this is done one will also look at the proximal vessels in order to provide almost a one stop shopping approach: one is also to look at the level of the carotids and possibly of the aortic arch in order to see if there is any plaque or calcification that may be the cause of embolism. Also, adding perfusion imaging will allow assessing the perfusion status of the tissue. While this was only initially possible with nuclear medicine techniques such as PET and SPECT, and PET with O still remains the gold standard, techniques using CT and MRI have progressed greatly over the last decades. These techniques have allowed determining a model of the penumbra based on either the diffusion-perfusion mismatch and on a match or mismatch of the perfusion maps. Imaging will also be used to detect any kind of complication due directly or indirectly to the treatment or procedure: CT will demonstrate an early bleeding well but may be more problematic when it comes to demonstrating the presence of small ischemic changes. Here, MRI with diffusion has a major role. Final outcome is of course based on measures such as clinical status and clinical scores but also by imaging: here CT can demonstrate final lesions but less well that T2 images done at 3 months. While FLAIR after a few weeks will often provide a lesion definition that approximates the final size, imaging at 3 months with T2 MRI is mandatory. MRI can also be done in order to assess the possibility and success of any preadaptation measures. This review mainly aims to look at the differences between CT and MRI for the acute detection of ischemia and looks at some current novel methods such as arterial

K.-O. Lövblad et al. spin labeling or dual source CT that can be added to current protocols.

Computed tomography Computed tomography has been the cornerstone of brain imaging since its introduction in the early 1970s [11,12]. Besides its use for the diagnosis of any brain pathology, in stroke it was primarily used for lesion exclusion then became a strong diagnostic tool once the NINDS studies proved that therapy was feasible. It was also the main neuroradiological tool until the emergence of MR and it was marred by questions of low resolution especially in the posterior fossa until recently. However, the technique that set things in motion was the development of spiral CT [13], then volumetric CT and also of scanners with more and more rows of detectors. CT in our opinion has the easiest capacity to detect hemorrhage, be it intraparenchymal or subarachnoid. It can also in well-trained hands demonstrate rather well the presence of ischemic changes [14] (Figs. 1—3). The acute signs on CT [15,16], when read by experienced readers are quite accurate: one can see the dense artery which corresponds to the clot, as well as signs of early swelling and edema: this will lead to smaller sulci on the affected side; also as soon as there is slight water accumulation one will have a loss of the capacity of CT to differentiate between white and grey matter. This is especially well seen in the basal ganglia and in the insula but can be seen everywhere. Additionally, where CT has proven to be of prime importance is the capacity to demonstrate the presence of early hypo density: indeed, this was shown at least for tap to be an early sign of potential malignant hemorrhagic transformation, especially if the hypo density was more than 30% of the affected territory. Where CT played an important role was in showing that when one third or more of the affected territory was hypo dense there is an acute danger of increasing fatal hemorrhage by initiating treatment with rTPA [17]. This may create the need for other drugs or approaches such as other thrombolytic or even other mechanical practices. While very useful, the one-third approach has not been without limitations or criticisms. Thus, scoring systems have been developed that try to address this. One of the more known ones is the ASPECTS score [18] where a number of points is allocated to the MCA territory and points subtracted for each hypodense area. The aspects score is used more and more and has even been applied to DWI [19—21]. Brain hemodynamics are at the core of the cerebral ischemic event: indeed, initially the drop in cerebral blood flow (CBF) will be compensated by an increase in collateral blood flow and in the local cerebral blood volume (CBV); this will maintain some kind of penumbra or tissue at risk. While the hemodynamic models do not reflect the electrophysiological model initially postulated in the penumbra, they have proven to be perfectly usable working models for daily clinical practice. Then, when both CBF and SBV drop, tissue will be considered lost. Thus, adding perfusion techniques can help identify the hypoperfused territory (Fig. 4) as well as an infarcted core (Fig. 5). This can be done by looking for a match or a mismatch visually between the perfusion maps of CBF and CBV; when both are decreased and there is a match, there will often be massive infarction whereas in

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Figure 1 Patient with left-sided symptoms and right cerebral ischemia. Right hyperdense MCA (a), with occlusion seen on CTA (b: arrow, c), there is loss of white grey differentiation: the right-sided striatum is no longer visible (d: arrow, e), as well as loss of sulcal effacement (f, g).

Figure 2 Predictive effect of CT; this is the same case as figure 1. One can see that the area affected by the sulcal effacement and slight hypodensity on the early CT (A) corresponds to the final infarction almost perfectly on follow-up CT (B).

a mismatch when only CBF is decreased, a lesser infarct is to be expected (Figs. 4 and 5). However due to its very high increase in usage, CT has become an important factor in the irradiation of the population so that care must be taken when using it in order not to do unnecessary studies. Dual source CT is a technique that has been available for some time but which has known recent resurgence. Initially used for bone density measurement, it has recently

Figure 3 Predictive effect of CT: patient with infarction in the basal ganglia on the left: the area where there is acute loss of differentiation of white and grey matter with disappearance of the striatum (A) becomes hypodense on the late CT (B).

been introduced in clinical practice to subtract calcifications (Fig. 6) or provide more objective measures of insular density. It has been used to differentiate hemorrhage from contrast extravasation inpatients after interventional stroke therapy [22]. Indeed, very often after interventional therapies, contrast extravasation has been problematic in that it will either mimic blood or even obscure an underlying pathology such as an ischemic region.

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Figure 4 Patient with a right hemispheric stroke and a mismatch on perfusion CT: there is a decrease in CBF (c) in the right MCA territory but the CBV is normal (b). MTT is increased (d). The final CT on the right show very little lesion (e).

Figure 5 Patient with a left hemispheric stroke and matching hypoperfusion: there is a match in the surfaces of decreased CBV (b) and CBF (c). MTT is increased (d). There is a large final lesion (e).

The combined use of techniques such as PET and CT or PET and MRI has known a great increase over the last few years but while not really usable in the emergency situation we describe here, PET CT will be of use on the work-up of patients with carotid disease. Indeed, it may well demonstrate the presence of activity in plaques that are sometimes morphologically not suspicious and may thus help to provide treatment to some patients [23]. These techniques are gaining in acceptance quickly since sometimes plaques that are

not significant may be found to be inflammatory and thus the cause of embolism.

Magnetic resonance imaging Magnetic resonance imaging has proven itself to be a revolutionary and evolutionary tool, maybe even more so than CT. While the advantages of its non-ionising nature are evident,

Imaging of acute stroke: CT and/or MRI

Figure 6 Dual source energy CT of a patient after intraarterial thrombolysis for a left MCA stroke: on the left one can see some blood (A) but on the right there is more contrast extravasation visible (B) thus allowing differentiation between acute blood and contrast on the same examination.

the examinations were initially extremely time consuming and ill suited to acutely ill patients. It would be the advent of echo-planar imaging that was the revolution not just for stroke but for many areas that required an increase in imaging speed and a reduction in overall acquisition time [24,25]. Indeed, echo-planar meant that diffusion and perfusion MRI would be finally clinically feasible [26]. Conventional MR has been in use from the start but more to demonstrate the presence of established ischemic lesions that will be hypo-intense on T1 and hyper on T2 due to water accumulation these conventional techniques are still used for the follow-up of patients where they remain the standard. Diffusion techniques are MR techniques that image water movement [27—30]. These techniques are now more than 20 years old. Le Bihan et al. developed them; his team made a Stejskal-Tanner modification of a spin echo technique. Thus, the protons were given an impulsion and if they moved more or less would transmit more or less signal back. The technique was initially very sensitive to motion and it was only with the development of clinically available echo-planar

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Figure 8 Patient with acute posterior fossa infarction: on the acute CT (A) there is no visible lesion while on the DWI one has clearly a lesion of the left pons (B).

scanners that this technique could translate from the lab to the clinical site. Once it was clinically applied to patients with acute stroke, it showed itself to have a high sensitivity and specificity [31—34]. As in animal models the capacity for detection of acute ischemic changes starts minutes after stroke onset only [35]. Comparison studies have shown DWI to be far superior to CT [36—42] (Figs. 7 and 8). Of interest also is the capacity of DWI volumes to correlate with clinical status and outcome [43]; this implies that at least for studies implicating drugs it can be used as a surrogate marker of ischemia. It is also known that diffusion lesions tend to grow with time and this can be used more when using the so-called diffusion-perfusion mismatch [44]. The diffusion-perfusion mismatch is a rather simplistic model but which clinically works at times: one supposes that at an early time point the diffusion lesion is the core and around that the hypoperfused area represents the penumbra [45]. The problem is that from a historical perspective at least the penumbra is a physiological definition of an area between thresholds of dysfunction and definitive damage, Thresholds of ischemia are also present in the diffusion image and most certainly on the ADC maps: while this has not been as well reproduced in humans as in the animal models it seems that there is a definable threshold [46,47]. Also, another area where diffusion imaging has helped to do a lot of progress is its capacity

Figure 7 Acute CT in a patient with a right hemisyndrome and aphasia: slight hypodensity in left hemisphere visible on CT (A), but there is a large DWI lesion (B) on the MRI performed afterwards on the same day.

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Figure 9 Patient with proximal origin of embolic lesions of cardiac origin: there are bilateral lesions on the diffusion images.

to locate more precisely the lesions: this can even allow differentiating between lesions that are due to a more distal (Fig. 9) or a more proximal (Figs. 10 and 11) cause [48]. Those that have a more proximal origin will be more distributed widely with at times a starry sky appearance of the emboli on the DWI images (Fig. 9). For patients who sometimes wake-up with a stroke, a mismatch between FLAIR and diffusion can be sought: if the lesions are of same size, it is highly probably that the lesion is more than the allowed therapeutic window (Fig. 12). Perfusion techniques have been available for a long time using MR scanners [49—51]. These techniques can be performed in a multitude of ways. The most frequent way is to use T2* imaging techniques: images are repeated quickly using echo-planar technology and images covering the whole brain are done: a gadolinium based chelate is then injected and when this enters into the blood there is a decrease in

K.-O. Lövblad et al. contrast that is due to the induction of local changes in magnetic susceptibility: this will allow to calculate maps of mean transit time as well as of relative cerebral blood flow and volume [52]. Additionally, T1-weighted techniques can be used but are far less common but could be advantageous. Another technique that has been available for a number of years but has been underutilized is the so-called arterial spin labeling technique [53—60]; this relies on the tagging of blood flow at the cervical level with creation of maps of cerebral blood flow at the distal cerebral level. This allows obtaining perfusion maps without any contrast agent, which could cause toxic allergic or nephrologic problems. Also with advances in MR technology, it has been possible to obtain multi-slice data sets covering the whole brain. The disadvantage is fewer signals but there are many advantages of ASL besides the non-utilization of contrast such the possible demonstration of collaterals and selective demonstration of vascular territories. Thus, contradictory series have shown data that is slightly contradictory with either concurrence or overestimation of hypoperfusion; this may be due in part to the lower signal but also due to a lack in consensus on the use of technical parameters used for ASL in clinical practice across vendor platforms [61—67]. While conventional T2* imaging has been playing a major role in imaging of hemorrhage and calcifications, the advent of so-called susceptibility-weighted imaging has changed this even further: indeed, these SWI images now allow to obtain high-resolution images of e.g. the brain. While good for the detection of hemorrhage these sequences could also improve our knowledge about the presence of trans cerebral veins in acute stroke [68,69]. MR Angiography techniques: these techniques have evolved greatly over the last decade. At first images based on either time-of-flight or phase contrast techniques were used. These did not involve any contrast agent but used

Figure 10 Patient a left-sided carotid stenosis on contrast-enhanced MRA (A) embolic lesions are only present in the ipsilateral left hemisphere (B).

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Figure 11 Patient with carotid occlusion and stroke: there is a typical flame-like tapering of the carotid (A), compatible with a dissection and there are internal watershed lesions due to occlusion (B).

Figure 12 Patient presenting in the morning with a wake-up stroke: there is a match in the size between the diffusion (A) and the FLAIR image (B). Thus this patient is not eligible for thrombolysis.

inherent movement of intravascular fluids. One may also look for a matching between the occlusion seen as with the diffusion lesion: this is called the MRA-diffusion mismatch [70,71].

Discussion Since therapeutic options have emerged for acute ischemic stroke there has been an increased pressure to develop tools for an early diagnosis. Indeed, the era when stroke was synonymous with death or lengthy stays in recovery are now far gone. The main diagnostic tool over the first decades when treatment was initiated was computed tomography. Indeed, the early thrombolysis trials were done base don the use of

unenhanced CT alone. This was in a way sufficient to exclude a hematoma or a mass as well as to demonstrate early severe ischemia but was unfortunately insufficient for a more accurate work-up. Nuclear medicine tools such as PET and SPECT while they were able to demonstrate hypoperfusion and even the penumbra were not usable due to the difficulty of use in the clinical setting. PET and SPECT had initially been used to establish the clinical data we have about brain perfusion and has established the baseline blood flow and volume values that we use today but the techniques, while very precise were difficult to implement clinically and they have been partially abandoned; this is unfortunate because as validation tools especially using PET with oxygen, they are still irreplaceable and could be used to validate new techniques more seriously. Also, the use of MRI was restricted in

62 the early phase due to the fact that it could only detect T2 changes in the late phase and also due to the fact that early scanners were closed and that patients could not take the long examination times. Thus, there was a first technological revolution when MR saw the development of early clinical echo-planar scanners; this allowed implementing sequences such as diffusion and perfusion that allowed modeling the first human penumbra. Indeed, these techniques, which had been in development for a while had been almost impossible to use clinically due to time constraints and duet o sensibility to motion. The two techniques that got a boost from echo-planar technology were diffusion and perfusion MR techniques. Diffusion-weighted MRI, which was indeed a revolution, was initially met by much resistance due to a multitude of factors: on the one hand radiologists were not enthusiastic about performing emergency MRI and on the other hand neurologists doubted its capacity to adequately represent the neuronal damage and thus be an equivalent if not replacement of an accurate clinical examination. This led to a delay in the adequate utilization of these tools. Then the development of computed tomography techniques such as CT perfusion made the acceptance of multimodality imaging much more widespread. With treatment modalities becoming more and more sophisticated with intravenous and intra-arterial thrombolysis as well as mechanical techniques being proposed such as the MERCI device or the current modern stentrievers, it has become possible to open vessels that could not be before. Thus, in more and more situations, the practical issue initially posed by MRI techniques has been overcome and more and more centers tend to propose the technique in first intention. In other places, MRI will still be done but either in cases where it is unclear or as a followup method. The main problem may be sometimes blood: even though in theory MR techniques are known to have a much higher sensitivity to the detection of hemosiderin and blood degradation products, it is sometimes a question of experience with the appearance of acute hemorrhage that is an issue when using the method. Much data points to the fact that both techniques can be used almost equally but may also be used together: in some instances CT will be used primarily to exclude hemorrhage and perfusion and angiographic techniques will demonstrate hemodynamics and occlusion with an MR done as follow-up; MR can also be used when there is a clinically very strong suspicion of stroke but with no real CT parameters; on the other hand when using MR in first intention, very often CT can be used to detect early hemorrhage or pooling of contrast in case an intra-arterial intervention has been done. Thus, both techniques tend now to become complementary and not so much exclusive [72,73].

Conclusions Neuroradiological tools such as CT or MRI have become an indispensable part of the examination and work-up of patients with acute cerebrovascular insults. The patient who comes into the emergency department must be examined as quickly as possible since factors as time to needle play a more and more important role. What type of imaging is used is very often dependent on local organizational factors. Overall, MRI is more sensitive to ischemic changes and thus

K.-O. Lövblad et al. a more powerful tool especially when looking for smaller lesions that may not even be seen on CT.

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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