Diffusion-weighted Magnetic Resonance Imaging Lesions Research Articles

Persistent Infarct Hyperintensity on Diffusion-Weighted Imaging Late After Stroke Indicates Heterogeneous, Delayed, Infarct Evolution

Some infarcts have persistently hyperintense areas on diffusion-weighted MRI (DWI) even at 1 month after stroke, whereas others have become isointense to normal brain. We hypothesized that late DWI hyperintensity reflected different infarct evolution compared with areas that were isointense by 1 month. We recruited patients prospectively with ischemic stroke, performed DWI and perfusion-weighted MRI (PWI) on admission, at 5 days, 14 days, and 1 month after stroke, and assessed functional outcome at 3 months (Rankin Scale). Patient characteristics and DWI/PWI values were compared for patients with or without "still hyperintense" infarct areas on 1-month DWI. Among 42 patients, 27 (64%) had "still hyperintense" infarct regions at 1 month, mostly in white matter. Patients with "still hyperintense" regions at 1 month had lower baseline apparent diffusion coefficient ratio (ADCr; mean+/-SD 0.76+/-0.12 versus 0.85+/-0.12; hyperintense versus isointense; P<0.05), prolonged reduction of ADCr (repeated-measures ANOVA; P<0.01), no difference in baseline perfusion but delayed normalization of mean transit time (P<0.05) and cerebral blood flow ratios (repeated measures ANOVA; P<0.05), initially more severe stroke, and worse 3-month outcome than patients whose lesions were isointense by 1 month. The late DWI lesion hyperintensity emphasizes the heterogeneity in temporal evolution of stroke injury and suggests ongoing "ischemia." Lower baseline ADCr precedes delayed perfusion normalization, suggesting that worse cell swelling impedes reperfusion. Further study is required to determine underlying mechanisms and any potential for subacute intervention to improve recovery.

Do Acute Diffusion- and Perfusion-Weighted MRI Lesions Identify Final Infarct Volume in Ischemic Stroke?

An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the "tissue-at-risk." It is unclear which "semiquantitative" perfusion parameter most closely identifies final infarct volume. Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T2-weighted imaging (T2WI) at 1 or 3 months after stroke. "Semiquantitative" mean transit time (MTTsq=first moment of concentration/time curve), cerebral blood volume (CBVsq=area under concentration/time curve), and cerebral blood flow (CBFsq=CBVsq/MTTsq) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T2WI acquired > or =1 month after stroke. Baseline DWI, CBFsq, and MTTsq lesion volumes were compared with final T2WI lesion volume. Among 46 patients, baseline DWI and CBFsq lesions were not significantly different from final T2WI lesion volume, but baseline MTTsq lesions were significantly larger. The correlation with final T2WI lesion volume was strongest for DWI (Spearman rank correlation coefficient rho=0.68), intermediate for CBFsq (rho=0.55), and weakest for MTTsq (rho=0.49) baseline lesion volumes. Neither DWI/CBFsq nor DWI/MTTsq mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch. Of the 2 PWI parameters, CBFsq lesions most closely identifies, and MTTsq overestimates, final T2WI lesion volume. "DWI/PWI mismatch" does not identify lesion growth. Patients without "DWI/PWI mismatch" are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.

Invited commentary

Using diffusion-weighted magnetic resonance imaging (DWI), Hammer et al have demonstrated an alarming rate (40%) of new microinfarcts after filter-protected carotid artery stenting (CAS). These data support previous studies that have demonstrated new microinfarcts in 20% to 43% of patients after CAS.1Schluter M. Tubler T. Steffens J.C. Mathey D.G. Schofer J. Focal ischemia of the brain after neuroprotected carotid artery stenting.J Am Coll Cardiol. 2003; 42: 1007-1013Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 2Flach H.Z. Ouhlous M. Hendriks J.M. et al.Cerebral ischemia after carotid intervention.J Endovasc Ther. 2004; 11: 251-257Crossref PubMed Scopus (112) Google Scholar They are to be commended on their overall results: there were only two (4%) minor strokes that resolved completely, no myocardial infarctions, and no deaths. The pattern of these cerebral infarcts suggests that they are not due to failure of the embolic protection device. Ipsilateral DWI infarcts occurred with equal frequency in cases with and without visible debris captured in the filter. More importantly, the DWI lesions frequently involved the contralateral cerebral hemisphere, thus suggesting that many occurred before cannulation of the target carotid artery. The occurrence of these DWI lesions seems, on the basis of Hammer and associates’ analysis, to correlate with difficult arch anatomy, supra-aortic carotid torutuosity, and the performance of contralateral brachiocephalic selective catheterization. Thankfully, most of these lesions seem clinically silent, but this would be better evaluated with formal neuropsychiatric testing. These results argue against routine contraleral diagnostic arteriography as part of a CAS procedure, especially because one of the two strokes did occur in the contralateral occipital lobe. In our center, like many, we are careful to minimize manipulations in the aortic arch and attempt to cannulate only the target carotid artery during CAS. Proper patient selection and technical skill will be critical in decreasing CAS neurologic event rates to those seen with carotid endarterectomy, especially in older patient populations, in which CAS stroke and death rates have exceeded 12%.3Hobson II, R.W. Howard V.J. Roubin G.S. et al.Carotid artery stenting is associated with increased complications in octogenarians 30-day stroke and death rates in the CREST lead-in phase.J Vasc Surg. 2004; 40: 1106-1111Abstract Full Text Full Text PDF PubMed Scopus (503) Google Scholar We use computed tomographic angiography to screen patients for difficult arch anatomy, evaluate aortic arch plaque burden, and evaluate the carotid lesion length and calcification. We have used this information to exclude some patients from further consideration for CAS on the basis of anatomic concerns. This study by Hammer et al supports the concepts that minimal, focused catheter manipulation within the aortic arch and careful patient selection based on evaluation of aortic arch/carotid anatomy will limit the incidence of neurologic events during CAS. CorrectionJournal of Vascular SurgeryVol. 42Issue 6PreviewFor the article “Interval Gangrene Complicating Superficial Femoral Artery Stent Placement” published in J Vasc Surg 2005:42;564-66, one author was inadvertently left off, Dr. Neal Cayne. The correct order of authors should read: Full-Text PDF Open Archive

Acute small subcortical infarctions on diffusion weighted MRI: clinical presentation and aetiology

Objective: To determine the clinical presentation and aetiology of small subcortical infarctions as found on diffusion weighted magnetic resonance imaging (DWI). DWI is both sensitive and specific in the early...

Multiparametric MRI and ultrasound findings in patients with internal carotid artery dissection

In this study, clinical, MRI, and ultrasound findings in 33 patients with 37 MRI-confirmed internal carotid artery dissections (ICADs) were investigated. In 24 of 37 (64.9%) diffusion-weighted MRI (DWI) revealed acute ischemic brain lesions. ICADs with subsequent DWI lesions usually had a concentric position of the mural hematoma (14 of 24; 58.3%). In contrast, ICADs without DWI lesions (13 of 37; 35.1%) demonstrated an eccentric position of the mural hematoma (10 of 13; 76.9%), sometimes without ultrasound abnormality (5 of 13; 38.5%), while nonischemic clinical signs were frequent (11 of 13; 84.6%). A hemodynamic stroke pattern with comparatively large ischemic lesions along the hemodynamic risk zones was noted in 7 of 24 patients (29.2%).

Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity

BackgroundRecent trials suggest that angiotensin-converting enzyme inhibitors (ACEI) are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity.MethodsWe retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI). We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7), moderate (NIHSS 8–13) or severe (NIHSS [greater than or equal to] 14). We analyzed demographic data, risk-factor profile, blood pressure (BP) and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not.ResultsThirty- three patients (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2–21) among ACEI-treated patients vs. 9 (range 1–36) in non-ACEI patients (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03). Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups.ConclusionOur results suggest that ACE-inhibitors may reduce the clinical severity of stroke, as measured by NIHSS score. Further, larger-scale, prospective studies areneeded to validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits in patients with ischemic stroke.

Reduction of Diffusion-Weighted MRI Lesion Volume After Early Moderate Hypothermia in Ischemic Stroke

Large areas of restricted diffusion in the middle cerebral artery (MCA) territory are highly predictive of severe and potentially space-occupying MCA stroke. A reduction of diffusion-weighted MRI (DWI) lesions occurs in 20% to 40% of acute stroke patients with early reperfusion. We report of a patient with a severe stroke syndrome who was treated with early moderate hypothermia but not thrombolysis. The initially large DWI deficit of the whole MCA territory contrasted to the relatively small final lesion restricted to the basal ganglia on MRI and computed tomography scan. This case describes an unexpected reduction of a DWI lesion after early moderate hypothermia and spontaneous recanalization 3 days after stroke onset. We discuss potential reasons for the unexpected DWI lesion reduction.

Development of brain infarct volume as assessed by magnetic resonance imaging (MRI): follow-up of diffusion-weighted MRI lesions.

To investigate the development of ischemic brain lesions, as present in the acute stroke phase, by diffusion-weighted magnetic resonance imaging (DWI), and in the subacute and chronic phases until up to four months after stroke, in fluid-attenuated inversion recovery (FLAIR)- and T2-weighted (T2W) magnetic resonance (MR) images. Twelve consecutive patients with their first middle cerebral artery (MCA) infarction were included. Lesion volumes were assessed on T2W images recorded with a turbo spin echo (TSE) and on images recorded with the FLAIR sequence on average on day 8 and after about four months. They were compared with acute lesion volumes in perfusion and DWI images taken within 24 hours of stroke onset. On day 8, lesion volumes in images obtained with FLAIR exceeded the acute infarct volumes in DWI. The chronic lesion volumes were almost identical in T2W and FLAIR images but significantly reduced compared with the acute DWI lesions. The lesion volumes assessed on DWI images correlated highly with the lesions in the images obtained with TSE or FLAIR, as did the lesions in the images obtained with FLAIR and TSE. The secondary lesion shrinkage was accompanied by ventricular enlargement and perilesional sulcal widening, as most clearly visible in the images obtained with FLAIR. Our results show that the acute DWI lesions are highly predictive for the infarct lesion in the chronic stage after stroke despite a dynamic lesion evolution most evident in MR images obtained with FLAIR.

Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume.

Hemorrhagic transformation (HT) is a potentially dangerous complication of thrombolytic therapy. Recent studies suggest that diffusion-weighted MRI (DWI) can help to predict the risk of intracerebral hemorrhage (ICH) after thrombolysis. We sought to examine which pretreatment DWI parameters and clinical data are predictive of ICH after intravenous thrombolysis. We retrospectively reviewed our prospective stroke database for patients with ischemic stroke treated with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours from symptom onset who had DWI before treatment and MRI with T2* sequence or CT 24 to 48 hours later to assess for ICH over the past 4 years. We measured the volumes and voxel-by-voxel apparent diffusion coefficient (ADC) values of the initial DWI lesions and retrieved demographic data, risk factors, National Institutes of Health Stroke Scale (NIHSS) scores on admission, and blood tests results. We examined several variables using univariate and multivariate regression analyses to determine predictors of ICH. Twenty-nine patients fulfilled our inclusion criteria; 17 patients (58%) had ICH, and of these 4 (13%) had symptomatic ICH and fatal outcome. On univariate analysis, higher systolic blood pressure, NIHSS score, serum glucose level, volume of initial DWI lesion, and absolute number of voxels with ADC value < or =550x10(-6) mm2/s were statistically associated with ICH, and all were subjected to multivariate analysis. However, only the absolute number of voxels, ie, volume of ischemic tissue on DWI, with ADC < or =550x10(-6) mm2/s emerged as an independent predictor of ICH. Our findings suggest that volumetric ADC analysis can be used to assess ICH risk after thrombolysis. This may be particularly helpful if rtPA is to be given outside the 3-hour window.

Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue salvage in experimental cerebral ischemia.

Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal. Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72). DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion. After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.

Advances in intravenous thrombolytic therapy for treatment of acute stroke.

Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.

Pharmacologic reversal of acute changes in diffusion-weighted magnetic resonance imaging in focal cerebral ischemia.

Recently, diffusion-weighted magnetic resonance imaging (DWI) has been shown to visualize acute ischemic lesions in the brain before changes are observable with conventional magnetic resonance imaging. However, the underlying mechanisms of these acute DWI changes are unclear and may include both reversible and irreversible damage. In this study, we demonstrate that acute DWI lesions may be reversed with MK801 therapy postischemia. Sprague-Dawley rats (n = 12) were subjected to middle cerebral artery occlusion and DWI scans were obtained beginning 60 min postocclusion. Distinct regions of hyperintensity were observed in the basal ganglia and cortex, corresponding with the expected distribution of ischemia in this model. After the first scan, animals were treated with MK801 (0.5 mg/kg i.v.) or normal saline and subsequently scanned again 30 and 60 min after treatment. In the control group, the area of hyperintense lesions continued to increase, by 55% in the cortex and 57% in the basal ganglia. MK801 therapy significantly (p < 0.01) reduced the area of damage by the third DWI scan at 60 min posttreatment (-50% cortex, -22% basal ganglia, -41% total hemisphere) compared to pretreatment scans. Tetrazolium (TTC) stains at 24 h confirmed that MK801 significantly reduced the volumes of infarction (p < 0.05). These results demonstrate that significant portions of the acute ischemic lesion on DWI are reversible with pharmacologic intervention.