Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 50, Num. s1, 2002, pp. S30-S36

Neurology India, Vol. 50, (Suppl. 1), Dec, 2002, pp. S30-S36

Imaging in Acute Ischemic Stroke : Relevance to Management

M. Moonis

Department of Neurology, University of Massachusetts Medical School, Worcester MA 01655, USA.
Correspondence to : Dr. M. Moonis, Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA E-mail : MoonisM@UMMHC.ORG

Code Number: ni02160

Summary

With the advent of thrombolytic therapy in the treatment of acute ischemic stroke, it has become increasingly important to identify the suitable patients for whom such therapy may be useful. The success of reperfusion therapy depends on salvaging ischemic tissue at risk (penumbra). Imaging techniques continue to evolve. MRI with diffusion weighted and perfusion imaging can identify the penumbra (diffusion-perfusion mismatch). MR Angiography provides additional information about large and medium size vessel occlusion. However, MRI is limited by its lesser availability and slower acquisition times. Ultrafast perfusion CT scans are more widely available and seem capable of identifying the ischemic tissue at risk. Newer techniques of perfusion CT and triphasic perfusion CT are becoming more refined and along with CT Angiography provide information not only of the penumbra but also of large vessel occlusion. Patients with large vessel occlusion of the internal carotid and middle cerebral artery are best treated by intra-arterial thrombolytic therapy whereas branch occlusions are suitable for intravenous thrombolysis. Patient selection, based on the present and evolving MRI and CT techniques would provide a more rational application of treatment (greater chances of reperfusion and minimizing the possibility of symptomatic intracerebral hemorrhage).

Key words : Thrombolytic therapy, MR angiography, CT angiography.

Introduction

Increasing refinements in stroke management with acute thrombolytic therapy and trials of neuroprotective therapy have been paralleled by advances in neuroimaging techniques. Rapid improvement in the scanning times and more sensitive methods of defining acute ischemia continue to evolve in computerized tomography (CT) and magnetic resonance imaging (MRI) scans. The most significant advances have been in the field of newer MRI techniques; diffusion weighted imaging (DWI) with the ability to define ischemic events very early and perfusion imaging (PI) which helps to define the volume of brain tissue at risk.^1-6With the evolution of ultrafast CT scanners, perfusion CT and CT angiography are becoming important tools in acute ischemic stroke management. Current techniques seem capable of defining the ischemic penumbra as well as the site of large vessel arterial occlusion.⁷ Ischemic tissue accumulates intracellular water and this forms the basis of echoplanar DWI. The result of accumulation of intracellular water is reduction of the apparent diffusion co-efficient (ADC) with a hypointense signal on the ADC maps and a hyperintense signal on the DWI, reflective of cytotoxic edema. The combination is specific to ischemic tissue and is useful in separating other conditions that appear hyperintense on DWI. These include seizure foci, transient global ischemia, migraine, multiple sclerosis and certain tumors.^3,8,9 Unlike ischemic infarcts, ADC values are not affected in these other conditions.

Although most DWI changes reflect irreversible ischemia, several animal and clinical studies suggest that these deficits at least early on in the ischemic process may be partially reversible. Kidwell et al found that of the 9 patients with transient ischemic attacks and early DWI hyperintensity, almost half had resolution of their symptoms on follow-up studies indicating that the initial DWI lesions may not always reflect irreversible infarction.¹⁰

Current techniques of PI involve either administration of an exogenous bolus of a contrast agent that shortens T2 (BT-PI) or arterial spin labeling techniques (ASLPI). BT-PI utilizes serial multislice T2WI to monitor the signal reduction associated with the passage of the bolus. This is used to generate time curves of signal intensity change that can then be used to estimate the time to peak (TTP), relative mean transit time (MTT), relative cerebral blood flow (CBF) and cerebral blood volume (CBV). Of these, TTP and MTT are utilized to estimate the ischemic area at risk.^11-14 PI abnormalities are a composite of the area of infarction and the area at risk of infarction (penumbra). When used with DWI, PI deficit outside the area of DWI hyperintensity approximates the ischemic penumbra. This is potentially salvageable tissue and typically in untreated patients the area of infarction (DWI) will evolve into the region of the PI deficit.^15,16

Evolution of thrombolytic therapy has revolutionized stroke management. Patients with acute ischemic stroke treated with thrombolytics intravenously within 3 hours and intraarterially within 6 hours have a 30% better relative outcome as compared to patients who did not receive this treatment.^17-20 Patients treated within the first ninety minutes show a better recovery than those treated in the 90-180 minute period.²¹ However, the number of patients treated thus far is disappointingly low (10-12%). While part of the problem is in delay in arriving at the hospital, we are probably not treating all patients who may be appropriate for treatment.²² Selection of appropriate patients based on clinical examination and a CT scan can be misleading.²³ For rational thrombolytic therapy, imaging tools need to be sensitive (identify ischemic infarcts) and specific (exclude other causes of acute neurological deficits and hemorrhage). Furthermore, it should differentiate large vessel and cardioembolic small vessel strokes from lacunar infarcts and other non-embolic strokes.

DWI-PI in identification of lesions suitable for thrombolysis

Detection of acute ischemic infarcts: DWI is a very sensitive technique in identifying acute ischemic infarcts. DWI changes in ischemic tissue may be evident within minutes both in experimental and clinical studies. The changes may persist up to a week or even longer in some studies.24-26 In a study of subacute ischemic strokes, persistent abnormalities on DWI were seen in more patients than on conventional MRI after a period of 6-10 days. Furthermore DWI provided information not evident on conventional MRI in 30% of the patients.²⁷ In a large prospective study DWI increased the sensitivity of the diagnosis from 48 to 94%. Similar results have been reported by several other studies comparing DWI with CT or conventional T2 weighted MRI imaging. Since DWI usually represents irreversible damage (infarction), it gives valuable information on the size of the stroke at a time when thrombolysis is being considered. Currently, DWI hyperintensity greater than one-third of the arterial territory would be a contraindication to thrombolytic therapy.^28-30 In patients with previous strokes DWI is advantageous in differentiating acute from chronic lesions.^31-33 Fitzek reported a sensitivity and specificity approaching 100% in patients with at least one previous imaging abnormality.³³ In our experience, 9 patients imaged within the first 48 hours had a negative CT scan while all patients demonstrated a DWI abnormality. In 45% of cases DWI changed the original diagnosis to ischemic small vessel stroke, which influenced subsequent management.

Differentiation of stroke sub-types : Lacunar vs Embolic : Even though the National Institute of Neurological disorders and Stroke (NINDS) trial had demonstrated an equal benefit of thrombolytic therapy for small vessel strokes, lacunar strokes remain a relative contraindication to thrombolytic therapy because of their spontaneous potential of complete recovery and the risk of intracranial hemorrhage with rt-PA use. However, clinical differentiation of large vessel from small vessel strokes may be inaccurate in 20-30% of cases. The sensitivity of the diagnosis is increased with DWI compared to conventional CT and T2 weighted MRI techniques. This is highlighted in several studies that demonstrate that up to 50% of clinically diagnosed small vessel strokes evolved into large cortical strokes.^8,9,23,34-36 Furthermore, location of the DWI hyperintensity is helpful in delineating the extent of the irreversible ischemic lesion and by their location differentiate small vessel from large vessel stroke.²⁷ In a prospective study of stroke patients presenting with a clinically well-defined lacunar syndrome, the authors found multiple, simultaneous DWI abnormalities in nearly 16% of cases. One out of 6 cases that appear to be lacunar stroke on clinical evaluation may actually be embolic and possible candidate for thrombolytic therapy.³⁷ While perfusion CT scans and CT Angiograms (CTA) continue to evolve with faster scan times and more accurate delineation of the area of potential infarction, these techniques have not been widely tested against DWIPI.^38,39

Identification of watershed infarcts : DWI has been helpful in defining border zone infarcts that usually result from hypotensive crisis and not thromboembolism. Clinical and early CT diagnosis of watershed infarcts is notoriously inaccurate. DWI on the other hand identifies these lesions and combined with PI helps to differentiate these from similar lesions resulting from thromboembolism or critical carotid artery disease. Matching multiple DWI-PI abnormalities correlated with embolic strokes while abnormal perfusion with normal DWI correlated with transient hypoperfusion. Extensive PI deficits in one or more arterial territories suggested superimposed severe carotid artery disease.¹¹ Combined DWI-PI imaging correlated well with angiographic lesions during intra-arterial therapy.³⁶

PI imaging in itself detects early, potentially reversible ischemic changes in stroke and the extent of these deficits suggests whether the main stem or a branch occlusion has occurred. Branch occlusions correlate with a smaller PI deficit. The estimated lesion volumes correlate well with the scores on National Institute of Health Stroke Scale (NIHSS) and the Rankin Scale (RS).^40,41

Detection of Intracerebral hemorrhage : CT scan has been believed to be a more sensitive tool for detection of intracerebral hemorrhage, which is an absolute contraindication to thrombolytic therapy. However, recent techniques (echoplanar gradient recall echo sequences) have been shown to detect hemorrhage with comparable accuracy.^14,42-44 In a prospective study of patients with primary intracerebral hemorrhage, Roob et al found MRI evidence of additional micro bleeds in 54% of all cases. In the majority of patients micro bleeds were located simultaneously in multiple brain regions.⁴²

Utility of a combined DWI-PI in acute thrombolytic therapy

Although not universally accepted because of time limitation and a reported study indicating reversibility of DWI lesions within 24 hours in some cases, DWIPW imaging offers a powerful combination for rational thrombolytic therapy in acute ischemic stroke. Furthermore it is increasingly becoming possible to image patients within 3-6 hours of onset of their symptoms.⁴⁵ Arterial occlusion results in 3 zones in the involved territory. The central core of irreversibly infarcted tissue, the surrounding critically perfused potentially viable and outer zone of normally perfused tissue. This middle zone of critically perfused tissue; the ischemic penumbra is potentially salvageable tissue if reperfusion occurs in time.^3,46,47 There may be a differential susceptibly of sub-cortical and posterior circulation compared to the large anterior circulation occlusions. Ideally, before attempted re-perfusion, it is important to identify the penumbra i.e. that an area of salvageable tissue is present since there is a substantial iatrogenic risk of causing intracerebral hemorrhage. This may be achieved with DWI-PI imaging. Perfusion deficits define the potential area of infarction while to a large extent DWI identifies the area of irreversible infarction. Over time as evident from several large clinical series the DWI deficit expands to match the perfusion deficit.⁴⁵

Treatment with thrombolytic therapy should be instituted when there is a PI>DWI volume or an isolated perfusion deficit (DWI-PI mismatch). On the other hand, a DWI-PI match would imply a completed stroke and little role for thrombolysis. Even though studies of thrombolytic intervention indicate a definite time window for intervention; up to 3 hours for intravenous and up to 6 hours for intra-arterial thrombolysis there are subgroups that may fall outside this range. While the second European study ECASS-II revealed no overall benefit of rt-PA intravenously at 6 hours, it also demonstrated no significant increase in the risk of hemorrhage as compared to 3 hours. Given this information, patients who fall outside the time frames specified, but still demonstrate a DWI-PI mismatch should be candidates for thrombolysis.^43,45,48

Role of MRI in assessment of reperfusion following thrombolysis

Thrombolytic therapy can only be useful if there is effective re-perfusion established. Transcranial Doppler (TCD) has been utilized as a non-invasive tool to determine reperfusion flow. Results of several studies reveal a better outcome in patients with reestablished flow and correlates well with the NIHSS as well as functional scales.^49,50 More recently, DWIPI has been shown to be a sensitive technique in determining reperfusion. After successful reperfusion, the final PI deficits are less than or equal to the initial DWI hyperintensity and correlate with functional outcome.⁴⁰

DWI: Predicting hemorrhagic transformation

Hemorrhagic transformation of an embolic stroke is a common phenomenon seen to some degree in 50-60% of all embolic strokes. However, clinically significant hemorrhagic transformation is associated with a worse outcome. While studies of contrast extravasation on CT and perfusion deficits on HMPOA-SPECT provide some measure of the possible risk, DWI is beginning to have greater utility in this area.^51-53 In a prospective study, Tong et al assessed the utility of DWI in predicting hemorrhagic conversion. The authors analyzed 17 patients with DWI within 8 hours and at 1 week after the onset of an acute ischemic stroke. ADC for each pixel of the whole ischemic area was calculated. ADC values below 550 x 10^-6 correlated well with subsequent hemorrhagic transformation. The authors did not describe the clinical outcome in these cases. Nevertheless, if these results are consistently replicated in other studies, they may provide yet another tool to assess the safety and tailor thrombolytic therapy.⁵⁴ Other studies have shown DWI volumes to be predictive of the long term functional outcome and correlate with NIH stroke scale and Rankin Scale.^27,46-47,55

Can MRI and MRA replace preoperative conventional angiogram?

Conventional angiograms in the best of centers report a 1% morbidity and mortality. However, most vascular surgeons would like to obtain information about the extent of hemodynamic compromise and the cross collateral flow to the compromised side before planning a carotid endarterectomy(CEA). BT-PI can be utilized to obtain the same information noninvasively. The MTT, TTP, CBF and CBV are compared from side to side. On the side of the critical stenosis, MTT and TTP are increased and CBF and CBV reduced. With perfusion MRA, this allows determination of the extent of cross collateral flow. This technique if validated by the larger experience would allow for non-invasive pre-operative assessment.^56-58 TCD monitoring during CEA reveals multiple echogenic signals indicative of multiple upstream emboli during the procedure. DWI has been utilized to assess the extent of cerebral microembolism following a CEA. In 53 consecutive patients with CEA who had no apparent postoperative neurological deficits intraoperative TCD detected silent cerebral emboli in 17%; however, subsequent infarcts as evidenced by DWI hyperintensity were found in only 1%, suggesting that most microembolic signals detected on TCD are not associated with cerebral infarction.⁵⁹

Role of perfusion CT and CT angiography in acute stroke management

CT scan with its simplicity, availability and low cost is always an attractive alternative to MRI scan. Unenhanced CT scans are relatively insensitive to identifying infarcted tissue in the early period and cannot identify the tissue at risk (penumbra). More recently, perfusion (contrast enhanced CT) with rapid image acquisition made possible with recent scanners, especially helical CT are actually able to trace the contrast entry into the acquired brain slices and the mean transit time (MTT) can be calculated. MTT is equal to cerebral blood flow (CBV) / cerebral blood volume (CBF). The linear relationship between dye concentration and signal intensity is an advantage over MR perfusion where this relationship is nonlinear and leads to some overestimation of CBF.⁶⁰ In a recent study by Max Wiltermark and colleagues, CBV and CBF were measured on perfusion CT with rapid slice acquisition on 4 contiguous 10 mm slices. Results were compared to delayed MRI. CBV of < 2.5ml/100g was associated with irreversible infarction. Tissue with CBF < 34% of the contralateral side was considered as tissue at risk of infarction (equivalent of the penumbra identified on DWI-PI mismatch). Reperfusion was associated with near resolution of this impaired CBF and significant improvement in the NIHSS. The limitations of this technique are assessment based on selected slices and radiation exposure and an indirect comparison with DWI-PI MRI imaging. However, radiation exposure was not greater than 2 non-contrast CT scans and probably not significant in the overall scheme.⁷ Another technique, triphasic CT (TPCT) where after injection of a contrast bolus, helical ultrafast CT scanning is done to delineate the early, middle and late phases of contrast enhancement. The procedure requires approximately 5 minutes and a special software program. Perfusion deficits are determined in the 3 phases of TPCT and graded as severe or moderate. Severe perfusion deficits refer to decreased attenuation compared to the contralateral side with no or few leptomeningeal collaterals visible on the any of the 3 phases of imaging. Moderate perfusion deficits referred to either a) decreased attenuation on the early phase and normal attenuation on the middle and late phases and slow collateral filling on the middle and late phases or b) decreased attenuation on the early and middle phases and normal attenuation on the late phase with slow collateral filling. The extent of moderate and severe perfusion deficits were quantified to a) less than 1/3 of the presumed middle cerebral artery territory, b) less than 50% of the MCA territory and c) greater than 50% of the MCA territory. The authors posited that the zone of severe perfusion deficit was equal to the ischemic core and the zone of moderate deficit equal to the penumbra. This then represented the tissue at risk and a target for thrombolytic therapy. If this is confirmed, it may provide an alternate rapid method of determining the penumbra and more rational application of thrombolytic therapy.⁶¹

Future directions

Magnetic resonance spectroscopy (MRS) is another promising technique in the evaluation of acute stroke and assessment of patients for thrombolytic therapy. MRS is a technique of measuring metabolite peaks in applied pixels on the MRI. The common peaks are lactate, N-Acelylaspartate (NAA), Creatinine and Choline. The ratio of the NAA to lactate peaks is important in assessment of acute stroke. NAA peak is reduced with irreversible neuronal damage while lactate increases after ischemic injury and may return to normal with early re-perfusion. Animal studies indicate that a mismatch between NAA and lactate (reduced or normal NAA and elevated lactate) would suggest an incomplete lesion (ischemic penumbra) and may be another tool to assess patients for reperfusion therapy.³⁰ In a prospective study Wild et al performed MRS in addition to T2W MRI in 11 patients imaged 24 to 72 hours later. In the center of the T2 lesions, there was a sharp reduction in the NAA peak, the intermediate zone; presumably the penumbra revealed a lesser reduction and the NAA peaks were normal beyond the margins of the lesion. Unfortunately, NAA could not be correlated to DWI in this series.⁶² Other MRI techniques are finding application in the evaluation of acute stroke. Kamran et al have described a hyperintense vessel sign (HSV) on fluid attenuated inversion recovery (FLAIR). The authors correlated these findings with cerebral angiography in selected cases. HSV was an early MRI sign in 10% and indicated the need for reperfusion therapy. There was a correlation with the extent of HSV sign, NIHSS and functional outcome.⁶³ Diffusion tensor imaging (DTI) is a MRI technique that allows visualization of the DWI hyperintensity as well as its directionality. DTI has been applied to the visualization of cerebral diaschisis as well as activation of alternative regions after an acute stroke. This has the potential to provide prognostic information and along with functional MRI, promises to be a tool in assessment of long-term recovery after a stroke.⁶⁴

References

1. Moonis M , Fisher M : Imaging of acute stroke. Cerebrovasc Dis 2001; 11: 143-150.
2. Beaulieu C, D' Arceuil H, Hedehus M et al : Diffusionweighted magnetic resonance imaging: theory and potential applications to child neurology. Semin Pediatr Neurol 1999; 6 : 87-100.
3. Fisher M, Albers GW : Applications of diffusion-perfusion magnetic resonance imaging in acute ischemic stroke. Neurology 1999; 52 : 1750-1756.
4. Hillis AE, Barker PB, Beauchamp NJ et al : MR perfusion imaging reveals regions of hypoperfusion associated with aphasia and neglect. Neurology 2000; 55 : 782-788.
5. Hoehn-Berlage M : Diffusion-weighted NMR imaging: application to experimental focal cerebral ischemia. NMR biomed 1995; 8 : 345-358.
6. Jones SC, Perez-Trepichio AD, Xue M et al : Magnetic resonance diffusion-weighted imaging : sensitivity and apparent diffusion constant in stroke. Acta Neurochir Suppl 1994; 60 : 207-210.
7. Wintermark M, Reichhart M, Thiran JP et al : Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Ann Neurol 2002; 51 : 417-432.
8. Albers GW : Diffusion-weighted MRI for evaluation of acute stroke. Neurology 1998; 51 : S47-49.
9. Albers GW : Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection. Stroke 1999; 30 : 2230-2237.
10. Kidwell CS, Alger JR, Di Salle F et al : Diffusion MRI in patients with transient ischemic attacks. Stroke 1999; 30 : 1174-1180.
11. Chaves CJ, Silver B, Schlaug G et al : Diffusion-and perfusion-weighted MRI patterns in border zone infarcts. Stroke 2000; 31 : 1090-1096.
12. Albers GW, Lansberg MG, Norbash AM et al : Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients. Neurology 2000; 54 : 1562- 1567.
13. Jacobs MA, Knight RA, Soltanian-Zadeh H et al : Unsupervised segmentation of multiparameter MRI in experimental cerebral ischemia with comparison to T2, diffusion, and ADC MRI parameters and histopathological validation. J Magn Reson Imaging 2000; 11 : 425-437.
14. Linfante I, Llinas RH, Caplan LR et al : MRI features of intracerebral hemorrhage within 2 hours from symptom onset. Stroke 1999; 30: 2263-2267.
15. Neumann-Haefelin T, Moseley ME, Albers GW : New Magnetic resonance imaging methods for cerebrovascular disease: emerging clinical applications. Ann Neurol 2000; 47 : 559-570.
16. Ozsunar Y, Sorensen AG : Diffusion-and perfusionweighted magnetic resonance imaging in human acute ischemic stroke: technical considerations. Top Magn Reson Imaging 2000; 11 : 259-272.
17. Clark WM, Wissman S, Albers GW et al : Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282 : 2019-2026.
18. Furlan A, Higashida R, Wechsler L et al : Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism . JAMA 1999; 282 : 2003- 2011.
19. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of NINDS t-PA stroke trial. Stroke1997; 28 : 2119- 2125.
20. del Zoppo GJ, Higashida RT, Furlan AJ et al : PROACT : a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke 1998; 29 : 4-11.
21. Marler JR, Tilley BC, Lu M et al : Early stroke treatment associated with better outcome : the NINDS rt-PA stroke study. Neurology 2000; 55 : 1649-1655.
22. Lacy CR, Suh DC, Bueno M et al : Delay in presentation and evaluation for acute stroke : stroke time registry for outcomes knowledge and epidemiology (STROKE). Stroke 2001; 32 : 63-69.
23. Lansberg MG, Albers GW, Beaulieu C et al : Comparison of diffusion-weighted MRI and CT in acute stroke. Neurology 2000; 54 : 1557-1561.
24. Yang Q, Tress BM, Barber PA et al : Serial study of apparent diffusion coefficient and anisotropy in patients with acute stroke. Stroke 1999; 30 : 2382-2390.
25. Kohno K, Ohta S, Kumon Y et al : Early detection of cerebral ischemic lesion using diffusion-weighted MRI. J Comput Assist Tomogr 1995; 19 : 982-986.
26. Yoneda Y, Tokui K, Hanihara T et al : Diffusion-weighted magnetic resonance imaging: detection of ischemic injury 39 minutes after onset in a stroke patient. Ann Neurol 1999; 45: 794-797.
27. Augustin M, Bammer R, Simbrunner J et al : Diffusionweighted imaging of patients with subacute cerebral ischemia: comparison with conventional and contrastenhanced MR imaging. Am J Neuroradiol 2000; 21 : 1596- 1602.
28. Barber PA, Darby DG, Desmond PM et al : Identification of major ischemic change. Diffusion-weighted imaging versus computed tomography. Stroke 1999; 30 : 2059-2065.
29. Warach S, Gaa J, Siewert B et al : Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol 1995; 37 : 231- 241.
30. Wardlaw JM, Marshall I, Wild J et al : Studies of acute ischemic stroke with proton magnetic resonance spectroscopy : relation between time from onset, neurological deficit, and metabolite abnormalities in the infarct, blood flow, and clinical outcome. Stroke 1998; 29 : 1618-1624.
31. Geijer B, Brockstedt S, Lindgren A et al : Radiological diagnosis of acute stroke. Comparison of conventional MR imaging, echo-planner diffusion-weighted imaging, and spin-echo diffusion-weighted imaging. Acta Radiol 1999; 40 : 255-262.
32. Bartylla K, Hagen T, Globel H et al : [Diffusion-weighted magnetic resonance imaging in the diagnosis of cerebral infarct]. Radiologe 1997; 37 : 859-864.
33. Fitzek C, Tintera J, Muller-Forell W et al : Differentiation of recent and old cerebral infarcts by diffusion-weighted MRI. Neuroradiology 1998; 40 : 778-782.
34. Larrue V, con Kummer R, del Zoppo G et al : Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European cooperative acute stroke study. Stroke 1997; 28 : 957-960.
35. Lansberg MG, Norbash AM, Marks MP et al : Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke. Arch Neurol 2000; 57 : 1311-1316.
36. Lansberg MG, Tong DC, Norbash AM et al : Intra-arterial rtPA treatment of stroke assessed by diffusion-and perfusion-weighted MRI. Stroke1999; 30 : 678-680.
37. Ay H, Oliveira-Filho J, Buonanno FS et al : Diffusionweighted imaging identifies a subset of lacunar infarction associated with embolic source. Stroke 1999; 30 : 2644- 2650.
38. Kaufmann AM, Firlik AD, Fukui MB et al : Ischemic core and penumbra in human stroke. Stroke 1999; 30 : 93-99.
39. Rother J, Jonetz-Mentzel L, Fiala A et al : Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic perfusion imaging.Arch Neurol 2000; 57 : 1161-1166.
40. Beaulieu C, de Crespigny A, Tong DC et al : Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke : evaluation of lesion volume and correlation with clinical outcome. Ann Neurol 1999; 46 : 568-578.
41. Thijs VN, Lansberg MG, Beaulieu C et al : Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? : A multivariable analysis. Stroke 2000; 31 : 2597-2602.
42. Roob G, Lechner A, Schmidt R et al : Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000; 31 : 2665-2669.
43. Schellinger PD, Jansen O, Fiebach JB et al : A standardized MRI stroke protocol: comparison with CT in hyperacute intracerebral hemorrhage. Stroke 1999; 30 : 765-768.
44. Patel MR, Edelman RR, Warach S : Detection of hyperacute primary intraparenchymal hemorrhage by magnetic resonance imaging. Stroke 1996; 27: 2321-2324.
45. Schellinger PD, Jansen O, Fiebach JB et al : Monitoring intravenous recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke with diffusion and perfusion MRI. Stroke 2000; 31 : 1318-1328.
46. Flacke S, Urbach H, Folkers PJ et al : Ultra-fast threedimensional MR perfusion imaging of the entire brain in acute stroke assessment. J Magn Reson Imaging 2000; 11 : 250-259.
47. Heiss WD : Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab 2000; 20 : 1276-1293.
48. Raha S : ECASS-II: intravenous alteplase in acute ischemic stroke. European Co-operative Acute Stroke Study-II . Lancet 1999; 353 : 66-68.
49. Burgin WS, Malkoff M, Felberg RA et al : Transcranial Doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke. Stroke 2000; 31 : 1128-1132.
50. Demchuk AM, Christou I, Wein TH et al : Specific transcranial Doppler flow findings related to the presence and site of arterial occlusion. Stroke 2000; 31 : 140-146.
51. Alexandrov AV, Black SE, Ehrlich LE et al : Predictors of hemorrhagic transformation occurring spontaneously and on anticoagulants in patients with acute ischemic stroke. Stroke 1997; 28 : 1198-1202.
52. Alexandrov AV, Masdeu JC, Devous MD et al : Brain single photon emission CT with HMPAO and safety of thrombolytic therapy in acute ischemic stroke. Proceedings of the meeting of the SPECT Safe Thrombolysis study Collaborators and the members of the brain imaging Council of the cociety of nuclear medicine. Stroke 1997; 28 : 1830- 1834.
53. Yokogami K, Nakano S, Ohta H et al : Prediction of hemorrhagic complications after thrombolytic therapy for middle cerebral artery occlusion: value of pre-and posttherapeutic computed tomographic findings and angiographic occlusive site. Neurosurgery 1996; 39 : 1102- 1107.
54. Tong DC, Adami A, Moseley ME et al : Relationship between apparent diffusion co-efficient and subsequent hemorrhagic transformation following acute ischemic stroke. Stroke 2000; 31 : 2378-2384.
55. Nighoghossian N, Derex L, Turjman F et al : Hyperacute diffusion-weighted MRI in basilar occlusion treated with intra-arterial t-PA. Cerebrovasc Dis 1999; 9 : 351-354.
56. Maeda M, Yuh WT, Ueda T et al : Severe occlusive carotid artery disease: hemodynamic assessment by MR perfusion imaging in symptomataic patients. Am J Neuroradiol 1999; 20 : 43-51.
57. Rutgers DR, Blankensteijn JD, van Der Grond J : Preoperative MRA flow quantification in CEA patients: flow differences between patients who develop cerebral ischemia and patients who do not develop cerebral ischemia during cross-clamping of the carotid artery. Stroke 2000; 31 : 3021-3028.
58. Rutgers DR, Klijn CJ, Kappelle LJ et al : Longitudinal study of collateral flow patterns in the circle of Willis and the ophthalmic artery in patients with a symptomatic internal carotid artery occlusion. Stroke 2000; 31 : 1913-1930.
59. Barth A, Remonda L, Lovblad KO et al : Silent cerebral ischemia detected by diffusion-weighted MRI after carotid endarterectomy. Stroke 2000; 31 : 1824-1828.
60. Koroshetz WJ, Lev MH : Contrast computed tomography scan in acute stroke: 'You can't always get what you want but ....you get what you need". Ann Neurol 2002; 51 : 415- 416.
61. Lee KH, Cho SJ, Byun HS et al : Triphasic perfusion computed tomography in acute middle cerebral artery stroke : A correlation with angiographic findings. Arch Neurol 2000; 57 : 990-999.
62. Wild JM, Wardlaw JM, Marshal I et al : N-Acetylaspartate distribution in proton spectroscopic images of ischemic stroke: relationship to infarct appearance on T2-weighted magnetic resonance imaging. Stroke 2000; 31 : 3008-3014.
63. Kamran S, Bates V, Bakshi R et al : Significance of hyperintense vessels on FLAIR MRI in acute stroke. Neurology 2000; 55 : 265-269.
64. Conturo TE, Lori NF, Cull TS et al : Tracking neuronal fiber pathways in the living human brain. Proc Natl Acad Sci USA 1999; 96 : 10422-10427.

Copyright 2002 - Neurology India. Also available online at http://www.neurologyindia.com