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D I A LO G U E O F E X P E R T S

A PIECE OF EDITOR’S LEXIS

PANEL OF ISA

President : Dr. Dheeraj KhuranaImmediate Past President : Dr. D. NagarajaPresident Elect : Dr. Ashok UppalSecretary : Dr. V. G. Pradeep KumarTreasurer : Dr. Vinit Suri

Executive Committee Members : Dr. Anand Alurkar Dr. Sunil Narayan Dr. Jeyaraj Pandian Dr. P. N. Sylaja

Dear Friends,

We welcome you to this new issue of Stroke talk entitled ‘Stroke Brain Imaging. The

Pandora’s Box’. This issue will be equally engaging and informative for you with some

interesting articles by experts in neurology and neuroimaging.

We bring to you an exclusive case study addressing significance of diffusion reversal in

predicting clinical outcomes in stroke patients. In acute ischemic stroke, the diffusion-

weighted imaging (DWI) lesion is commonly considered a surrogate marker of irreversible

core, and this underpins all MR methods currently in use to screen candidates for

reperfusion therapy. A number of clinical trials suggest a strong association between

diffusion reversal on imaging and clinical improvement among stroke patients which will

be dealt in detail in this issue. Also recent advances in brain imaging with special emphasis

on CT perfusion and its status as a ‘Pandora’s Box’ will be discussed by experts for better

management of patients for reperfusion therapies.

We hope you find this issue as compelling as the earlier one. We sincerely thank our

readers for supporting us in this endeavour and hope to achieve our goals in improving

outcomes in stroke management with your trust and support.

Regards,

Dr. S.M. Hastak

Stroke Brain ImagingThe Pandora’s Box IS

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Mr. M.J , 45 year old male , a jeweler by occupation presented to the emergency department of this hospital with acute onset of left Hemiplegia, dysarthria and left Upper motor neuron facial palsy just 15 minutes prior. He was a known case of coronary artery disease - single vessel on anti platelet agents. His admission NIHSS was 10. He was rushed in to the MRI and as he was uncooperative his Diffusion weighted images (DWI) alone were obtained. His initial MRI Brain showed restricted diffusion involving the fronto-parieto -temporal cortex and sub cortical white matter and the insular cortex on the right side with associated hypo intensity on ADC images. As he was not cooperative for an angio he was shifted out and after obtaining consent for thrombolysis he was started on IV alteplase with a door to needle time of 45 minutes and an onset to needle time of 1 hour. Post thrombolysis no change was noted in his NIHSS. His repeat MRI at 24 hours showed reduction in the Diffusion restriction of about 50% to 60%. A thrombus in the M2 segment of the right middle cerebral artery was seen. No improvement in clinical condition was seen in the initial 24 hours.

As per mainstream thought DWI lesions in acute ischemic stroke is often considered as an indicator of the infarcted core tissue and is often considered irreversibly infarcted. Based on this concept much work has been done to estimate the penumbra based on perfusion imaging so as to rescue the salvageable brain from a developing infarct.

Diffusion reversal post stroke is a lesser known and even less frequently documented factor. However multiple case reports and analysis have shed light on a very interesting phenomenon. In the hyper acute phase of stroke if the patient is Thrombolysed very early on (~ Onset to needle time of 1-2 hours) the probability of diffusion reversal on imaging is better in such patients. In one case series by Labeyrie et al1, out of 176 patients, eighty nine patients (which is 50%) showed visually detectable diffusion reversal. They also observed that patients who were treated within 3 hours showed greater evidence of diffusion reversal. Evidence of this diffusion reversal translates into predicting clinical improvement which may either be an early neurological improvement or a gradual improvement over several days. In this case series it was also shown that patients who had diffusion reversal had better clinical outcomes.

Earlier the prospective multicenter study - Diffusion and Perfusion Imaging for Understanding Stroke Evolution (DEFUSE) trial was suggestive of the fact that DWI reversal on imaging translated in to favorable outcomes. However in a pooled analysis of the DEFUSE study with the Echo Planar Imaging Thrombolytic Evaluation Trial (EPITHET) the diffusion reversal was small and hence considered clinically irrelevant2. Though it was a minor setback, more and more isolated case reports and case series are being published which point towards an independent association between diffusion reversal on imaging and clinical improvement.

Even in the posterior circulation, there has been isolated case reports where they have documented complete diffusion reversal

THE MIRAGE IN THE BRAIN - DWI REVERSAL POST THROMBOLYSIS

Dr. Philip Anemon, Dr. Shirish M Hastak

Department of Neurology, Adam - Wylie Unit - Wockhardt Hospital, Mumbai Central.

of the pontine infarct. Interesting to note here is that both the patients in this case report received IV thrombolysis within 3.5 hours of the stroke onset. Clinical improvement with an NIHSS of 0 was also noted in both the patients3.

In our patient though we had demonstrated diffusion reversal on imaging, no clinical improvement was noted up to 1 week. Later he showed gradual improvement with NIHSS & MRS of 0 at the end of one month.

Learning Points:

1) Diffusion reversal may or may not mean Early Neurological Improvement but it definitely will lead to improved clinical outcomes.

2) Shorter onset to needle time will help translate stroke care to not only imaging improvement but also clinical improvement.

3) Diffusion is not a sine qua non of brain infarction as thought in the past.

A B C

D EPRETHROMBOLYSIS IMAGES (A - F ) SHOWING LARGE AREA OF RESTRICTED DIFFUSION INVOLVING THE FRONTO PARIETO TEMPORAL CORTEX AND SUBCORTICAL WHITE MATTER AND INSULAR CORTEX ON RIGHT SIDE

1 2POST THROMBOLYSIS IMAGES AT 24 HOURS (1& 2) SHOWING RIGHT MIDDLE CEREBRAL ARTERY TERRITORY INFARCT .THERE IS 50-60% REDUCTION IN THE REVERSAL OF RESTRICTED DIFFUSION.

References:1) Labeyrie et al. Diffusion lesion reversal after thrombolysis. A MR correlate of early

neurological improvement. Stroke.2012;43:2986-2991.2) Campbell BC, Purushottam A, Christensen S, Desmond PM, Nagakane Y, Parsons MW, et

al . The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent . J Cereb Blood Flow Metab.2012;32:50-56.

3) Gory B, et al. DWI lesions reversal in posterior circulation stroke after reperfusion: Two i l l u s t r a t i v e c a s e s a n d r e v i e w o f l i t e r a t u r e . J N e u r o r a d i o l ( 2 0 1 5 ) , http://dx.doi.org/10.1016/j.neurad.2015.02.007

F

Despite advancements in acute stroke imaging and treatment, stroke remains a leading cause of morbidity and disability in developed countries. It is estimated that 60 to 80% of patients presenting with a proximal vessel occlusion in the anterior circulation will die within 90 days of stroke onset or will not regain functional independence despite alteplase treatment.1 Intra-arterial therapy (IAT) uses mechanical devices delivered via catheter angiography to recanalize intracranial arteries blocked by thrombi. Recent clinical trials MR CLEAN, ESCAPE, EXTEND IA, and SWIFT PRIME have shown efficacy of adding IAT to standard care in treating patients with acute ischemic stroke.1, 2, 3, 4 There is now level 1 evidence for the administration of IAT in patients with proximal occlusions. Nevertheless, no matter how we recanalize vessels (tPA or IAT), the decision to open or not is based on the same imaging defined constructs i.e. 1) presence of a target occlusion 2) small core 3) salvageable brain tissue

Currently, NCCT acquisition is considered the most common imaging modality used when making tPA administration decisions. NCCT offers the ability to simultaneously rule out hemorrhage, while getting a sense of the extent of early ischemic change using the 1/3 MCA rule to decide on recanalization. However, inter-observer agreement for the criterion of 1/3 MCA territory involvement is rather poor.5 The Alberta Stroke Program Early CT Score (ASPECTS) is a systematic scoring technique based on a ten point rating system for assessing the extent of early ischemic changes on NCCT.6 It is easy to implement and provides valuable information for predicting patient outcome after thrombolysis. However, ASPECTS has moderate inter-rater reliability even amongst experts.7-10 Reliability is reduced by acute presentation (within 90 minutes from stroke symptom onset)11 and is affected by patient motion and advancing age.6 In addition, NCCT alone increases uncertainty around treatment decisions.12

Multi-phase CT angiography (mCTA) is a reliable, safe, quick, and widely available tool which generates multiple time-resolved images of backfilling arteries beyond a blocked artery filled by collaterals.12 mCTA can be used to a) to determine presence of occlusion, and b) to determine presence of salvageable brain via collateral scoring. The latter is done by assessing extent of pial arterial filling within the presumed ischemic territory in comparison to the contralateral brain hemisphere, a construct used for patient inclusion in the ESCAPE trial.1,13 Presence of moderate to good pial arterial filling in symptomatic brain can be considered as a surrogate for presence of salvageable tissue.13,14 Image acquisition and interpretation is rapid (less than 5 minutes), potentially saving valuable time when compared to techniques like MRI and CT Perfusion (CTP). mCTA provides whole brain coverage, good temporal resolution, does not require additional resources or CT contrast (compared to conventional CTA), and is minimally affected by patient motion.

CT Perfusion (CTP) can be used to identify: a) infarct core b) salvageable tissue volume c) clot permeation (anterograde flow) d) hemorrhagic risk for large proximal occlusions and e) lacunar

STROKE BRAIN IMAGING. WHAT’S NEW?Connor Batchelor, Christopher D. d’Esterre,

Bijoy K. Menon, Mayank Goyal

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lesions (which encompass 25% of all ischemic strokes).15-19 CTP was used in the EXTEND-IA and SWIFT PRIME trials. A CTP-defined infarct core volume of 70 mL is considered to be the critical upper limit above which poor outcome is experienced, despite high recanalization rates.20-22 Significant drawbacks of using CTP are susceptibility to patient motion and significant variability across vendors and perfusion algorithms.23, 24

Figure. Example of multi-modal CT imaging in acute stroke. A patient with an NIHSS of 18 obtained < 90mins mins post stroke onset. ASPECTS of 8 are observed on the NCCT (A). A proximal right M1 occlusion is shown (B-i). mCTA (3 phases) maximum intensity projection images are shown in B-ii, iii & iv. mCTA collateral score of 4 is indicative of intermediate collaterals, presence of salvageable brain tissue (small core and large penumbra), and positive treatment response. CTP Tmax and CBF maps are depicted in C-i & ii respectively. Tissue with a Tmax > 10 seconds is superimposed onto the CTP-average maps in pink for both gray and white matter (C-iii & iv, respectively). CBF < 8 ml•min-1•(100g)-1 for white matter and CBF < 7 ml•min-1•(100g)-1 for gray matter are flooded in blue on the CTP-average maps (C-iii & iv). D-i shows the pre-treatment angiogram. IV+IA tPA was administered, and TICI 3 reperfusion was achieved in 62 mins post- CT imaging (D-ii). MR-diffusion imaging taken 24 hrs post admission imaging denotes the final infarct as a hyperintense region (E).

The Calgary Stroke Program adopts a pragmatic decision-making approach.25,26 Briefly, we aim to get by with information that is relevant to decision-making and to put the rest of the information accrued to scientific use later. In the acute stroke setting, the decision to pursue thrombectomy (versus IV tPA or no treatment) is an evolving decision with some factors pushing us towards intervening and some arguing against. We have found that analysis of basic imaging consisting of NCCT and CTA allows for a rapid and clear decision in most cases.24, 27-29 Use of an algorithm helps establish the level of confidence in available information and the need for further tests (‘no further test threshold’).30 Speed and efficiency are paramount when dealing with acute stroke patients and must be taken seriously if imaging and treatment is to be of any benefit.30-32 Therefore, time required to diagnose and treat acute stroke patients must be considered if proficiency and productivity are to improve in the clinical setting. Consistent efforts have been made to improve workflow by ensuring emergency staff are present to stabilize patients, imaging is accessible with established protocols for

stroke, and clinical assessment can be quickly and easily overseen.30 In our center, advanced imaging and research studies are performed in parallel with routine investigations and treatment, interfering minimally with efficiency of clinical decision-making and care. This process helps us to recognize the importance of additional information while never being biased by an ‘information heuristic’.26

In summary, clinical stroke severity at presentation provides a general estimate of dysfunctional brain tissue, while tissue defined as non-salvageable core can be discerned on a good quality NCCT. On its own, this paradigm may help identify the patients at risk of harm from thrombolytic treatment. Further information can be gained by examining the state of collateral circulation on mCTA. The collateral score can predict which patients will benefit from thrombolysis or endovascular intervention, and confirms what is seen on NCCT. The small core-proximal occlusion paradigm with clinical-imaging mismatch is a very good surrogate for information that can be obtained by the penumbra-core mismatch paradigm using perfusion imaging, and takes much less imaging time especially when further correlated with collateral imaging on multiphase CTA. Although no one disputes the value of the concept of penumbra and mismatch in acute ischemic stroke treatment, current perfusion techniques lack robust evidence validating their use in reliably identifying the penumbra. In addition, perfusion is affected by non-standardized nomenclature, conceptual issues, and measurement errors have also limited more widespread use of CTP. Therefore, routine use of perfusion imaging in clinical practice could be premature when seen in the context of other imaging paradigms currently available. The utility of CTP in stroke has yet to be fully explored, making it the ‘Pandora’s box’ of stroke imaging at this present time.

References:1. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized

assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 20152. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, et al. A

randomized trial of intraarterial treatment for acute ischemic stroke. The New England journal of medicine. 2015;372:11-20

3. J S. Swift prime results. International Stroke Conference. 20154. Campbell BC, Mitchell PJ, Yan B, Parsons MW, Christensen S, Churilov L, et al. A

multicenter, randomized, controlled study to investigate extending the time for thrombolysis in emergency neurological deficits with intra-arterial therapy (extend-ia). International journal of stroke : official journal of the International Stroke Society. 2014;9:126-132

5. Kalafut MA, Schriger DL, Saver JL, Starkman S. Detection of early ct signs of >1/3 middle cerebral artery infarctions : Interrater reliability and sensitivity of ct interpretation by physicians involved in acute stroke care. Stroke. 2000;31:1667-1671

6. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. Aspects study group. Alberta stroke programme early ct score. Lancet. 2000;355:1670-1674

7. Gupta AC, Schaefer PW, Chaudhry ZA, Leslie-Mazwi TM, Chandra RV, Gonzalez RG, et al. Interobserver reliability of baseline noncontrast ct alberta stroke program early ct score for intra-arterial stroke treatment selection. AJNR. American journal of neuroradiology. 2012;33:1046-1049

8. Wardlaw JM, Mielke O. Early signs of brain infarction at ct: Observer reliability and outcome after thrombolytic treatment--systematic review. Radiology. 2005;235:444-453

9. Patel SC, Levine SR, Tilley BC, Grotta JC, Lu M, Frankel M, et al. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. JAMA : the journal of the American Medical Association. 2001;286:2830-2838

10. Coutts SB, Hill MD, Demchuk AM, Barber PA, Pexman JH, Buchan AM. Aspects reading requires training and experience. Stroke. 2003;34:e179; author reply e179

11. Bal S, Bhatia R, Menon BK, Shobha N, Puetz V, Dzialowski I, et al. Time dependence of reliability of noncontrast computed tomography in comparison to computed tomography angiography source image in acute ischemic stroke. International journal of stroke : official journal of the International Stroke Society. 2012

12. Menon BK, d'Esterre CD, Qazi EM, Almekhlafi M, Hahn L, Demchuk AM, et al. Multiphase ct angiography: A new tool for the imaging triage of patients with acute ischemic stroke. Radiology. 2015:142256

13. Nambiar V, Sohn SI, Almekhlafi MA, Chang HW, Mishra S, Qazi E, et al. Cta collateral status and response to recanalization in patients with acute ischemic stroke. AJNR Am J Neuroradiol. 2014;35:884-890

14. Menon BK, Smith EE, Modi J, Patel SK, Bhatia R, Watson TW, et al. Regional leptomeningeal score on ct angiography predicts clinical and imaging outcomes in patients with acute anterior circulation occlusions. AJNR. American journal of neuroradiology. 2011;32:1640-1645

15. Das T, Settecase F, Boulos M, Huynh T, d'Esterre CD, Symons SP, et al. Multimodal ct

provides improved performance for lacunar infarct detection. AJNR. American journal of neuroradiology. 2015

16. Aviv RI, d'Esterre CD, Murphy BD, Hopyan JJ, Buck B, Mallia G, et al. Hemorrhagic transformation of ischemic stroke: Prediction with ct perfusion. Radiology. 2009;250:867-877

17. Ahn SH, d'Esterre CD, Qazi EM, Najm M, Rubiera M, Fainardi E, et al. Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator. Stroke. 2015

18. d'esterre CD, Aviv RI, Fainardi E, Lee TY. . Comparing multiple neuroimaging techniques and histology in a porcine model of endothelin-1 induced cerebral ischemia. Accepted with revisions Translational stroke research. 2015:Accepted with revisions

19. d'Esterre CD, Aviv RI, Lee TY. The evolution of the cerebral blood volume abnormality in patients with ischemic stroke: A ct perfusion study. Acta Radiol. 2012;53:461-467

20. Campbell BCV, Mitchell PJ, Yan B, Parsons MW, Christensen S, Churilov L, et al. A multicenter, randomized, controlled study to investigate extending the time for thrombolysis in emergency neurological deficits with intra-arterial therapy (extend-ia). International Journal of Stroke. 2014;9:126-132

21. Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, et al. Mri profile and response to endovascular reperfusion after stroke (defuse 2): A prospective cohort study. The Lancet Neurology. 2012;11:860-867

22. Yoo AJ, Verduzco LA, Schaefer PW, Hirsch JA, Rabinov JD, González RG. Mri-based selection for intra-arterial stroke therapy: Value of pretreatment diffusion-weighted imaging lesion volume in selecting patients with acute stroke who will benefit from early recanalization. Stroke. 2009;40:2046-2054

23. Goyal M, Menon BK, Derdeyn CP. Perfusion imaging in acute ischemic stroke: Let us improve the science before changing clinical practice. Radiology. 2013;266:16-21

24. Menon BK dEC, Qazi E, Almekhlafi MA, Hahn L, Demchuk AM, Goyal M. Multi-phase cta: A new tool for the imaging triage of patients with acute ischemic stroke. Radiology. 2015

25. Goyal M, Fargen KM, Menon BK. Acute stroke, bayes' theorem and the art and science of emergency decision-making. Journal of neurointerventional surgery. 2013

26. Menon BK, Goyal M. A systems approach towards intra-arterial management of acute ischemic stroke: Need for novel outcome measures and a focus on sequence rather than steps. Interv Neuroradiol. 2011;17:296-298

27. Demchuk AM, Menon B, Goyal M. Imaging-based selection in acute ischemic stroke trials - a quest for imaging sweet spots. Ann N Y Acad Sci. 2012;1268:63-71

28. Menon BK DA. Computed tomography angiography in the assessment of patients with stroke/tia. Neurohospitalist. 2011;1:187-199

29. Menon BK, Puetz V, Kochar P, Demchuk AM. Aspects and other neuroimaging scores in the triage and prediction of outcome in acute stroke patients. Neuroimaging clinics of North America. 2011;21:407-423, xii

30. Goyal M, Menon BK, Hill MD, Demchuk A. Consistently achieving computed tomography to endovascular recanalization <90 minutes: Solutions and innovations. Stroke. 2014;45:e252-256

31. Menon BK, Almekhlafi MA, Pereira VM, Gralla J, Bonafe A, Davalos A, et al. Optimal workflow and process-based performance measures for endovascular therapy in acute ischemic stroke: Analysis of the solitaire fr thrombectomy for acute revascularization study. Stroke. 2014;45:2024-2029

32. Goyal M, Almekhlafi MA, Fan L, Menon BK, Demchuk AM, Yeatts SD, et al. Evaluation of interval times from onset to reperfusion in patients undergoing endovascular therapy in the interventional management of stroke iii trial. Circulation. 2014;130:265-272

ACUTE ISCHEMIC STROKE BRAIN IMAGING – RECENT ADVANCES

Sinchu Maniangatt, Post doctoral fellow; Sylaja PN, Additional Professor Comprehensive stroke care program, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram

The purpose of thrombolytic and endovascular therapy in stroke is to restore perfusion in the ischemic tissue. Brain imaging plays a crucial role in early diagnosis of stroke and yields essential information regarding tissue integrity, a factor that is determinant in identifying patients likely to benefit from thrombolytic therapy. The efficacy of these modes of treatment depends on the clot burden and the leptomeningeal collaterals. The current multimodal stroke imaging CT protocol includes non-enhanced CT (NECT), CT angiography (CTA) and perfusion CT. In this review, we will be dealing with the advances in stroke imaging with emphasis on clot burden, leptomeningeal collaterals and CT perfusion (CTP).

Clot burden

The assessment of clot burden is an important aspect of acute stroke imaging. This can be assessed by measurement of the clot length and analyzing the clot burden score in the CTA. In a study by Riedel et al, a clot length of more than 8 mm in CTA failed to recanalize with intravenous thrombolysis (IVT). [1] The location of the vessel occlusion also predicts the clot length. In a study by Kamalian S, a clot length of more than 8 mm was seen in 94%, 73% and 22% of the internal carotid terminus, M1 and M2 occlusions respectively suggesting that more proximal the occlusion, less

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likely are the chances of recanalizaton with IVT. [2] The hyperdense middle cerebral artery sign in the non-contrast CT was used previously as an important prognostic marker in acute stroke. But in this era of CTA, it is not only the presence of the hyperdense MCA, but the length of the clot and clot burden which is more important in the prognosis.

A novel clot burden score was developed by the Calgary group for quantification of the intracranial thrombus extent. [3] This score allots 10 points for the presence of contrast opacification in CTA. Two points were subtracted for absence of contrast opacification in any part (ICA) of proximal M1 segment, distal M1 segment and supraclinoid internal carotid artery and one point each for M2 branches, A1 segment and infraclinoid ICA. A score of 10 indicates absence of visible occlusion on CTA and 0 indicates occlusion of all major intracranial anterior circuation arteries. They have shown that the quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The intra-arterial thrombus burden also had an impact on intra-arterial treatment (IAT) and clinical outcome, and a high thrombus grade contributed to poor clinical outcome. [4]

4D CT angiography has been developed in recent years as a technique that combines the non-invasive nature of CTA with the dynamic acquisition of DSA. This technique enables the non-invasive evaluation of flow dynamics of the intracranial vasculature by multiple subsequent CT acquisitions or a continuous volume CT acquisition for a period of time. The cumulative dose of 4D-CTA is usually substantially higher than that in conventional CTA. Recent studies have shown that 4D CTA demarcates clot burden and collateral supply better than conventional CTA.[5,6] Evaluation of the clot length using 4D-CTA in middle cerebral artery occlusion showed cutoff value of 11 mm predicted recanalization with IVT and favourable outcome.[7]

In MRI, direct imaging of intra-arterial thrombus can be assessed with the susceptibility vessel sign (SVS) on T2*-MRI. Legrand et al proposed a T2*-MR adaptation of the computed tomography angiography-clot burden score and found out that T2*-CBS >6 was significantly associated with 24-hour recanalization or with favorable outcome.[8] Though studies have shown that the thrombus length predicts reperfusion success of IVT, thrombus length of the MCA occlusion assessed by susceptibility-weighed imaging did not have an impact on reperfusion success of endovascular therapy.[9]

Figure 1. CT angiography shows left middle cerebral artery M1 occlusion with a thrombus measuring 12.6 mm.

Figure 2. CT angiography shows left middle cerebral artery M1 o c c l u s i o n w i t h g o o d , i n t e r m e d i a t e a n d p o o r collaterals.

Collateral status

The ischemic penumbra is described as the cerebral parenchyma adjacent to the area of dense ischemic infarction. Irrespective of the mechanism of ischemia, various collateral pathways are recruited to limit ischemic injury to the brain. The wide variations in the clinical manifestations and the rates and extent of neurologic recovery in patients with acute stroke may be attributable to these collateral pathways. In proximal artery occlusion, collateral vessels provide blood flow to preserve viable tissue and can potentially extend the time window for recanalization. The pial collateral circulation thus limits core infarct size by supporting penumbral tissue during acute ischemia.

Various methods like Mass scoring system, Miteff scoring system and Modified Tan Scale have been described for the assessment of intracranial collaterals on CTA in patients with acute stroke. A comparison of the different scoring system showed that only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke, but poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.

In patients with proximal vessel occlusion in the anterior circulation, CT angiographic pretreatment collateral grade determines the final infarct volume and the functional outcome after endovascular reperfusion and hence the assessment of the collaterals helps in treatment decision of patients with acute ischemic stroke.[10,11,12,13] The collateral scoring has also been shown to predict recanalization after reperfusion therapy and infarct growth. In a study by Bang et al , complete revascularization occurred in 14.1% patients with poor pretreatment collateral grades, whereas it was observed in 25.2% patients with good collaterals and 41.5% patients with excellent collaterals (P=0.001). When revascularization was achieved, greater infarct growth occurred in patients with poor collaterals than in those with good collaterals.

The collaterals in the CTA correlates with admission DWI infarct size and malignant collateral profile was highly specific for large admission DWI lesion size and poor functional outcome in patients with acute ischaemic stroke with proximal arterial occlusions.[14] This malignant CTA collateral profile was highly specific for patients with large baseline infarcts and poor long-term outcome. Their CTA collateral score of 0 (absent collaterals in >50% of an M2 territory) had 95% specificity for an admission DWI lesion volume of 100 mL and a 90% rate of 3-month death or dependency. The Calgary group described a novel 20 point

leptomeningeal scoring system and good score strongly correlated with final infarct and functional outcome. [15] So a combination of higher Clot burden score (CBS) and collateral score predicted better clinical outcome and final infarct volume. Hence the assessment of the clot length, clot burden and the collaterals helps in the decision of thrombolysis and predicting the outcome.

CT perfusion

Advanced imaging techniques like CT and MR perfusion will help to identify a larger proportion of patients who will benefit from thrombolytic therapy by imaging the salvageable brain tissue in patients beyond 3 and 4.5 hours of stroke onset. Perfusion CT imaging enables rapid, non-invasive evaluation of cerebral perfusion, ischemia and infarction. A recent systematic review and meta-analysis of outcomes of patients selected for IVT by perfusion CT showed that the mortality, morbidity and symptomatic intracerebral bleed rates for those treated more than 3 hours after symptom onset was favourable.[16] CTP can also predict the chances of haemorrhagic transformation. In a study of acute ischemic stroke, a lower rCBV was found to be significantly associated with a relatively higher chance of haemorrhagic transformation. [17] The disadvantage of CTP is that the Contrast to Noise ratio (CNR) of infarct cores on CTP-derived CBF images is very low in comparison to DWI. Hence the outline of the core is easily identified on the DWI, the boundaries are unclear on the CBF images.

Campbell et al examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND-IA trial which is randomized trial of endovascular thrombectomy after standard dose tPA in patients within 4.5 hours of onset of acute ischemic stroke. [18] CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no ‘mismatch’ classification that determined eligibility for trial therapies. They concluded that automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. In conclusion, the rapid advances in stroke imaging helps us to select patients better and faster for reperfusion therapies.

References1. Riedel CH, Zimmermann P, Jensen-Kondering U, et al. The importance of size:

successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke 2011; 42:1775–77.

2. Kamalian S, Morais LT, Pomerantz SR, Aceves M, Sit SP, Bose A, et al. Clot length distribution and predictors in anterior circulation stroke. Implications for intra-arterial therapy Stroke. 2013; 44:3553-56.

3. Puetz V, Dzialowski I, Hill MD, Subramaniam S, Sylaja PN, Krol A, et al. Intracranial thrombus extent predicts clinical outcome, final infarct size and haemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke 2008; 3:230–36.

4. Barreto AD, Albright KC, Hallevi H, Grotta JC, Nosern EA, Khaja AM, et al. Thrombus burden is associated with clinical outcome after intra-arterial therapy for acute ischemic stroke. Stroke. 2008; 39:3231-35.

5. Frölich AMJ, Schrader D, Klotz E, Schramm R, Wasser K, Knauth M, et al. 4D CT angiography more closely defines intracranial thrombus burden than single-phase CT angiography. AJNR Am J Neuroradiol. 2013; 34:1908-13.

6. Kaschka IN, Kloska SP, Struffert T, Engelhorn T, Gölitz P,Kurka N et al. Clot Burden and Collaterals in Anterior Circulation Stroke: Differences Between Single-Phase CTA and Multi-phase 4D-CTA. Clin Neuroradiol 2014 ;(epub ahead of print).

7. Rohan V, Baxa J, Tupy R, Cerna L, Sevcik P, Friesl M, et al. Length of Occlusion predicts recanalization and outcome after intravenous thrombolysis in middle cerebral artery stroke. Stroke. 2014; 45:2010-17.

8. Legrand L, Naggara O, Turc G, Mellerio C, Roca P, Calvet D, et al. Clot burden score on admission T2*-MRI predicts recanalization in acute stroke. 2013; 44:1878-84.

9. Weisstanner C, Gratz PP, Schroth G, Verma RK, Köchl A,Jung S et al.Thrombus imaging in acute stroke: correlation of thrombus length on susceptibility-weighted imaging with endovascular reperfusion success. Eur Radiol 2014; 24:1735–41.

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