Advances in penumbra imaging with MR

The concept of the ischaemic penumbra as critically hypoperfused and functionally impaired, but potentially viable brain, was introduced over 25 years ago. Recent studies have used a combination of perfusion-weighted magnetic resonance imaging (PWI) and diffusion-weighted imaging (DWI) to delineate the putative penumbra. PWI provides semiquantitative cerebral blood flow imaging and DWI is an index of the largely irreversible ischaemic core. PWI > DWI mismatch is an operational definition of the penumbra that was introduced in the late 1990s. This definition has been modified in recent years with the recognition that the PWI boundary includes a region of benign oligaemia and that a portion of the DWI core is potentially salvageable with rapid reperfusion. An MRI penumbral signature is present in the majority of patients within 6 h of stroke onset, often but not invariably associated with proximal arterial occlusion on magnetic resonance angiography, and is strictly time dependent. It has been postulated that penumbral imaging using MRI can provide a physiological 'tissue clock' and be used to predict benefit from thrombolytic therapy beyond the established 3-hour window. This has been suggested by pilot studies, but confirmation will rely on ongoing, prospective, randomized trials. The presence and extent of the penumbra may also predict the opportunity for tissue salvage with neuroprotection strategies. DWI and PWI parameters are being used in proof-of-principle stroke trials. Such trials can be performed with 100-200 patients randomized between treated and control groups and provide a biological signal of efficacy with only 10% of the sample size required for a Phase III study.     

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth.

BACKGROUND AND PURPOSE: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.     

表观弥散系数对确定急性缺血性卒中缺血半暗带的潜在价值

目的 探讨表观弥散系数（apparent diffusion coefficient,ADC）对确定急性缺血性卒中缺血半暗带的潜在价值。 方法 选择发病9 h内完成多模式磁共振成像（magnetic resonance imaging,MRI）检查的前循环急性缺血性卒中患者49例。应用自制软件进行灌注加权像（perfusion-weighted imaging,PWI）和弥散加权像（diffusion-weighted imaging,DWI）异常区域的体积测量。缺血半暗带以PWI/DWI错配表示。同时采用全自动图像分析系统,以DWI图像计算得到的ADC图作为输入数据,来判断缺血半暗带的存在（以下简称为ADC方法）,然后比较这两种方法在判断缺血半暗带方面的差异。 结果 入选的49例患者中,存在PWI/DWI错配者为43例,符合ADC方法判断缺血半暗带标准者有41例。这两种方法在判断是否存在缺血半暗带的结果中有41例相符,对判断缺血半暗带的差异无统计学意义（P>0.05）。ADC方法判断缺血半暗带的敏感度为88.4%、特异度为50.0%。 结论 由于不需做PWI检查,ADC方法对确定缺血半暗带具有潜在的临床实用价值,有可能成为一种简便易行的确定缺血半暗带的方法。     

Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia

We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.     

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke

Objective: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. Methods: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. Results: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ～5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. Conclusion: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.     

Diffusion- and perfusion-weighted MRI: influence of severe carotid artery stenosis on the DWI/PWI mismatch in acute stroke

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) have been used increasingly in recent years to evaluate acute stroke in the emergency setting. In the present study, we compared DWI and PWI findings in acute stroke patients with and without severe extracranial internal carotid artery (ICA) disease. METHODS: Twenty-seven patients with nonlacunar ischemic stroke were selected for this analysis. DWI, PWI, and conventional MRI were performed in all patients within 24 hours of symptom onset and after 1 week. To exclude patients with partial or complete reperfusion, we included only patients with a PWI deficit larger than the DWI lesion. Severe ICA disease (>70% stenosis) was present unilaterally in 9 and bilaterally in 2 patients. Acute DWI lesion volume, the size of the acute PWI/DWI mismatch, and final infarct size (on T2-weighted images) were determined. RESULTS: The PWI/DWI mismatch was significantly larger in patients with severe ICA disease than in patients without extracranial carotid stenosis, both when time-to-peak and mean transit time maps (P<0.01) were used to calculate the mismatch. Quantitative analysis of the time-to-peak delay in the mismatch indicated that a relatively smaller fraction of the total mismatch was critically ischemic in patients with carotid stenosis than in those without. Average lesion volume increased less in the stenosis group (P=0.14), despite the larger PWI/DWI mismatch, and final infarct size was smaller in the stenosis group (P<0.05). In the 2 patients with bilateral ICA disease, variable hemodynamic involvement of the contralateral hemisphere was found in addition to the ipsilateral PWI deficit. CONCLUSIONS: In most acute stroke patients with severe ICA stenosis, a considerably smaller fraction of the total PWI/DWI mismatch is at risk than in patients without carotid disease.     

Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection.

BACKGROUND: Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset. SUMMARY OF REVIEW: Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth. CONCLUSIONS: Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.     

SB 234551 selective ET(A) receptor antagonism: perfusion/diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection

Mismatches between tissue perfusion-weighted imaging (PWI; an index of blood flow deficit) and cellular diffusion-weighted imaging (DWI; an index of tissue injury) provide information on potentially salvageable penumbra tissue in focal stroke and can identify “treatable” stroke patients. The present pre-clinical studies were conducted to: a.) Determine PWI (using perfusion delay) and DWI measurements in two experimental stroke models, b.) Utilize these measurements to characterize selective ET_A receptor antagonism (i.e., determine efficacy, time-to-treatment and susceptibility to treatment in the different stroke models), and c.) Determine if increasing the reduced blood flow following a stroke is a mechanism of protection. Permanent middle cerebral artery occlusion (MCAO) or sham surgeries were produced in Sprague Dawley rats (SD; proximal MCAO; hypothesized to be a model of slowly evolving brain injury with a significant penumbra) and in spontaneously hypertensive rats (SHR; distal MCAO; hypothesized to be a model of rapidly evolving brain injury with little penumbra). Infusions of vehicle or SB 234551 (3, 10, or 30 µg/kg/min) were initiated at 0, 75, and/or 180 min post-surgery and maintained for the remainder of 24 h post-surgery. Hyper-intense areas of perfusion delay (PWI) in the forebrain were measured using Gadolinium (Gd) bolus contrast. DWI hyper-intense areas were also measured, and the degree of forebrain DWI-PWI mismatch was determined. Region specific analyses (ROI) were also conducted in the core ischemic and low perfusion/penumbra areas to provide indices of perfusion and changes in the degree of tissue perfusion due to SB 234551 treatment. At 24 h post-surgery, final infarct volume was measured by DWI and by staining forebrain slices. Following SD proximal MCAO, there was a significant mismatch in the ischemic forebrain PWI compared to DWI (PWI > DWI) at 60 min which was maintained up to 150 min (all p < 0.05). By 24 h post-stroke, infarct volume was identical to the area of early perfusion deficit/PWI, suggesting a slow progression of infarct development that expanded into the significant, earlier cortical penumbra (i.e., model with salvageable tissue with potential for intervention). When SB 234551 was administered within the period of peak mismatch (i.e., at 75 min post-stroke), SB 234551 provided significant dose-related reductions in cortical (penumbral) progression to infarction (p < 0.05). Cortical protection was related to an increased/normalization of the stroke-induced decrease in tissue perfusion in cortical penumbra areas (p < 0.05). No SB 234551-induced changes in reduced tissue perfusion were observed in the striatum core ischemic area. Also, when SB-234551 was administered beyond the time of mismatch, no effect on cortical penumbra progression to infarct was observed. In comparison and strikingly different, following SHR distal MCAO there was no mismatch between PWI and DWI (PWI = DWI) as early as 60 min post-stroke, with this early change in SHR DWI being identical to the final infarct volume at 24 h, suggesting a rapidly occurring brain injury with little cortical penumbra (i.e., model with little salvageable tissue or potential for intervention). In distal MCAO, SB 234551 administered immediately at the time of stroke did not have any effect on infarct volume in SHR. These data demonstrate that selective blockade of ET_A receptors is protective following proximal MCAO in SD (i.e. a model similar to “treatable” clinical patients). The protective mechanism appears to be due to enhanced collateral blood flow and salvage of penumbra. Therefore, the use of PWI-DWI mismatch signatures can identify treatable stroke models characterized by a salvageable penumbra and can define appropriate time to treatment protocols. In addition, tissue perfusion information obtained under these conditions might clarify mechanism of protection in the evaluation of protective compounds for focal stroke.     

Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be "tissue at risk." The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. METHODS: Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with "time-to-peak" (TTP) delays of >/=2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score. RESULTS: In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of >/=6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay >/=6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay >/=6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of >/=4 s correlated better with ESS (r=-0.88, P<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of approximately 4 s might be the threshold for functional impairment of brain tissue. CONCLUSIONS: Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of >/=6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays >/=4 and <6 s) appear to also contribute to the acute clinical deficit.     

Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance imaging

BACKGROUND: Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models. OBJECTIVES: To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke. DESIGN: Case series. SETTING: Referral center. METHODS: We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score. RESULTS: Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02). CONCLUSION: Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.     

MR perfusion imaging reveals regions of hypoperfusion associated with aphasia and neglect

OBJECTIVE: To evaluate diffusion-weighted imaging (DWI) and MR perfusion imaging (MRPI) as tools for identifying regions of infarct and hypoperfusion associated with aphasia and neglect in hyperacute stroke. Secondary goal: to establish a functional correlate of a radiologically defined "ischemic penumbra." METHODS: Forty subjects underwent DWI, MRPI, and standardized tests for lexical deficits or hemispatial neglect within 24 hours of stroke onset or progression. Ten patients had repeat DWI, MRPI, and cognitive testing after 3 days (in some cases after reperfusion therapy). Pearson correlations between error rate on cognitive testing and volume of abnormality on DWI versus MRPI were determined at each time period, and regions of hypoperfusion corresponding to specific cognitive deficits were identified. RESULTS: Error rate was more strongly correlated with volume of hypoperfused tissue on MRPI (r = 0.65 to 0.93; p < 0.01 to p < 0.0003) than with volume of lesion on DWI (r = 0.54 to 0.75; p = 0.14 to p < 0.01) for dominant and nondominant hemisphere stroke, at each time point. Forty-eight percent of aphasic patients and 67% of those with hemispatial neglect had either no infarct or only small subcortical infarct on DWI, but had focal cortical hypoperfusion. Patients who had successful reperfusion therapy showed resolution of the hypoperfused territory beyond the infarction on repeat MRPI and showed resolution of corresponding deficits. CONCLUSIONS: MRPI shows regions of hypoperfused cortex associated with lexical deficits or hemispatial neglect, even when DWI shows no infarct or only small subcortical infarct. MRPI-DWI mismatch indicates regions of functionally salvageable tissue.     

Correlation between diffusion- and perfusion-weighted MRI and neurological deficit measured by the Scandinavian Stroke Scale and Barthel Index in hyperacute subcortical stroke (< or = 6 hours)

OBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.     

Role of neuroimaging before reperfusion therapy. Part 1 – IV thrombolysis – Review

This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5 hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.     

Penumbra detection using PWI/DWI mismatch MRI in a rat stroke model with and without comorbidity: comparison of methods

Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n=12, SHRSP n=15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T₂ scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31±50 mm³, WKY: 22±59 mm³, mean±s.d.) compared with spatial assessment (SHRSP: 36±15 mm³, WKY: 43±43 mm³) and ADC lesion expansion (SHRSP: 41±45 mm³, WKY: 65±41 mm³), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke.     

3-Tesla versus 1.5-Tesla magnetic resonance diffusion and perfusion imaging in hyperacute ischemic stroke

BACKGROUND: Clinical 3-tesla magnetic resonance imaging systems are becoming widespread. No studies have examined differences between 1.5-tesla and 3-tesla imaging for the assessment of hyperacute ischemic stroke (<6 h from symptom onset). Our objective was to compare 1.5-tesla and 3-tesla diffusion and perfusion imaging for hyperacute stroke using optimized protocols. METHODS: Three patients or their surrogate provided informed consent. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) was performed sequentially at 1.5 T and 3 T. DWI, apparent diffusion coefficient (ADC) maps and relative time-to-peak (TTP) maps were registered and assessed. DWI contrast-to-noise ratio (CNR) and ADC contrast were measured and compared. The infarct lesion volume (ILV) and thresholded ischemic volume (TIV) were estimated on the ADC and TTP maps, respectively, with the penumbral volume being defined as the difference between these volumes. RESULTS: Qualitatively, the 3-tesla TTP images exhibited greater feature detail. Quantitatively, the DWI CNR and ILV were similar at both field strengths, the ADC contrast was greater at 3 T and the TIV and penumbral volumes were much smaller at 3 T. CONCLUSIONS: Overall, the 3-tesla diffusion and perfusion images were at least as good and in some ways superior to the 1.5-tesla images for assessing hyperacute stroke. The TTP maps showed greater feature detail at 3 T. The ischemic and penumbra volumes were much greater at 1.5 T, indicating a potential difference in the diagnostic utility of the PWI-DWI mismatch between field strengths.     

Tissue at risk concept for endovascular treatment of severe vasospasm after aneurysmal subarachnoid haemorrhage

OBJECTIVE: To report a case of severe vasospasm after subarachnoid haemorrhage (SAH) where "tissue at risk" was identified by magnetic resonance imaging (MRI), and to demonstrate the haemodynamic consequences with either resolution of the perfusion-diffusion mismatch by balloon angioplasty or evolution of an infarct. METHODS: A 45 year old women with SAH underwent surgical treatment of a ruptured middle cerebral artery (MCA) aneurysm. On day 3 she became obtunded and developed a right hemiparesis. Diffusion weighted (DWI) and perfusion weighted (PWI) imaging were done before and after transluminal balloon angioplasty (TBA) of multifocal proximal vasospasm. RESULTS: The initial MRI revealed no DWI lesion but PWI showed a severe perfusion deficit of 6.7 to 16.4 seconds in the complete left MCA territory. Digital subtraction angiography confirmed severe segmental narrowing of left C1 and M1. The spastic segments were successfully dilated by TBA. Follow up MRI showed that the PWI-DWI mismatch resolved in the anterior and middle MCA territory with no tissue infarction, whereas in the terminal dorsal MCA territory a severe mismatch remained and cerebral infarction evolved. CONCLUSIONS: PWI/DWI can identify tissue at risk for infarction in severe vasospasm following SAH. This may allow selection of patients for angioplasty and the monitoring of treatment effects.     

急性脑梗死缺血半暗带演变的磁共振成像研究

目的：探讨应用磁共振弥散／灌注成像技术判断急性脑梗死后缺血半暗带IP存在的范围和时间规律。方法：对72例发病时间在1～24h的急性脑梗死患者行常规MRI、磁共振弥散加权成像（DWI）和磁共振灌注加权成像（PWI）确定IP的范围，计算梗死中心区、IP区及对侧镜像区的ADC值和rADC值并加以比较。结果：26例发病时间〈6h的患者PWI显示存在低灌注区者，其中PWI〉DWI者21例，30例发病时间在6～24h的患者PWI显示存在低灌注区者，其中PWI〉DWI者2例；PWI〉DWI者病灶中心ADC值与IP区及对侧镜像区ADC值差异有统计学意义，其IP区ADC值与其对侧镜像区差异无统计学意义。结论：DWI和PWI结合能灵敏的判断IP的存在，IP存在的时间窗有一定的个体差异。     

Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats.

Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered for 3 h (P>0.05) and by 44% when administered for 6 h (P<0.05). In experiment 2, NBO acutely (390 mins, P<0.05) reduced in situ end labeling (ISEL) positivity in the ipsilesional penumbra but increased contralesional necrotic as well as caspase-3-mediated apoptotic cell death. In experiment 3, CBF characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the apparent diffusion coefficient (ADC)-derived lesion volume essentially stopped progressing during NBO treatment, resulting in a persistent PWI/DWI mismatch that could be salvaged by delayed (3 h) reperfusion. In conclusion, NBO (1) acutely preserved the perfusion/diffusion mismatch without altering CBF, (2) significantly extended the time window for reperfusion, (3) induced lasting neuroprotection in permanent ischemia, and (4) although capable of reducing cell death in hypoperfused tissue it also induced cell death in otherwise unaffected areas. Our data suggest that NBO may represent a promising strategy for acute stroke treatment.     

Advances in the diagnosis and treatment of cerebral ischemia during the acute phase]

Recent advances in MRI technology and the development of effective neuroprotective agents has improved the outcome of stroke. In order to salvage tissue after an ischemic insult it is important to differentiate the core and penumbra area of the ischemic lesion. The penumbra surrounds the ischemic core, damage in this area is reversible if effective neuroprotective agents are given and reperfusion occurs. In this symposium detection of penumbra in an ischemic lesion using diffusion weighted imaging (DWI) and perfusion imaging (PI), diffusion-perfusion mismatch, and indications for thrombolytic therapy are discussed. If a hypoperfusion area is revealed with PI without a corresponding lesion indicated with DWI or when the DWI lesion is less than one third of the PI lesion, combined thrombolytic and neuroprotective therapies are recommended. In contrast, when both PI and DWI show an identical lesion, only neuroprotective therapy is advised. Additionally, newly developed neuroprotective agents, especially the combined effect of rt-PA and the immunosuppressant, FK506, on an embolic infarct model are discussed.     

Patients with Diffusion-Perfusion Mismatch on Magnetic Resonance Imaging 48 Hours or More After Stroke Symptom Onset: Clinical and Imaging Features

BACKGROUND: Abnormalities in diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) are thought to reflect the presence of brain tissue at risk for ischemic stroke. Many patients with acute ischemic stroke have a mismatch pattern in which the PWI volume is larger than the DWI lesion. This mismatch typically resolves over 24-48 hours. Little is known about the presence of DWI-PWI mismatch in later stages of stroke. METHODS: This is a retrospective study of 122 patients admitted with a diagnosis of acute ischemic stroke who had DWI and PWI abnormalities on studies performed within 7 days of onset of symptoms. Patients were divided into two groups: those with MRI performed <48 hours and those with MRI performed >or=48 hours from onset of symptoms. RESULTS: Among 42 patients with MRI performed >or=48 hours after onset of stroke symptoms, 15 of 42 (36%) showed a mismatch pattern, compared to 45 of 80 (56%) in the <48 hours group (P < 0.05). Most of the patients in the >or=48 hours group with mismatch had large artery occlusive disease and many had neurological fluctuations. A subset of these patients were treated with induced hypertension and showed clinical improvement. CONCLUSIONS: Some patients have persistent DWI-PWI mismatch up to several days after stroke onset. Further studies are needed to determine if these patients should be candidates for reperfusion therapy.