Alison E. Baird

The ischemic penumbra Operationally defined by diffusion and perfusion MRI

BACKGROUNDnIdentifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged.nnnOBJECTIVEnTo operationally define and characterize cerebral tissue at risk for stroke progression.nnnMETHODSnWe retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study. We applied a logistic regression model using maps of the relative mean transit time and relative cerebral blood flow (rCBF) as well as three different maps of the relative cerebral blood volume (rCBV) to predict an operationally defined penumbra (region of mismatch between the diffusion lesion on day 1 and its extension 24 to 72 hours later).nnnRESULTSnMaps of the rCBF and initial rCBV were significant predictors for identifying penumbral tissue. Our operationally defined penumbral region was characterized by a reduction in the initial rCBV (47% of contralateral control region [CCR]), an increase (163% of CCR) in the total rCBV, and a reduction (37% of CCR) in the rCBF, whereas the operationally defined ischemic core showed a more severe reduction in the rCBF (12% of CCR) and in the initial rCBV (19% of CCR).nnnCONCLUSIONnThese MR indexes may allow the identification and quantification of viable but ischemically threatened cerebral tissue amenable to therapeutic interventions in the hyperacute care of stroke patients.

Magnetic resonance imaging of acute stroke

In the investigation of ischemic stroke, conventional structural magnetic resonance (MR) techniques (e.g., T1-weighted imaging, T2-weighted imaging, and proton density-weighted imaging) are valuable for the assessment of infarct extent and location beyond the first 12 to 24 hours after onset, and can be combined with MR angiography to noninvasively assess the intracranial and extracranial vasculature. However, during the critical first 6 to 12 hours, the probable period of greatest therapeutic opportunity, these methods do not adequately assess the extent and severity of ischemia. Recent developments in functional MR imaging are showing great promise for the detection of developing focal cerebral ischemic lesions within the first hours. These include (1) diffusion-weighted imaging, which provides physiologic information about the self-diffusion of water, thereby detecting one of the first elements in the pathophysiologic cascade leading to ischemic injury; and (2) perfusion imaging. The detection of acute intraparenchymal hemorrhagic stroke by susceptibility weighted MR has also been reported. In combination with MR angiography, these methods may allow the detection of the site, extent, mechanism, and tissue viability of acute stroke lesions in one imaging study. Imaging of cerebral metabolites with MR spectroscopy along with diffusion-weighted imaging and perfusion imaging may also provide new insights into ischemic stroke pathophysiology. In light of these advances in structural and functional MR, their potential uses in the study of the cerebral ischemic pathophysiology and in clinical practice are described, along with their advantages and limitations.

Multiple acute stroke syndrome: Marker of embolic disease?

Objective: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke. Background: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions. Methods: The MRI scans of 59 consecutively studied patients were reviewed to determine the frequency and etiologic significance of multiple acute ischemic lesions on DWI. Results: Multiple acute ischemic lesions were present in 10 (17%) of 59 patients. The lesions usually occurred within one major circulation (anterior or posterior), but in two patients (3%), lesions occurred in both cerebral hemispheres or in the anterior and the posterior circulations. The lesions often were small and resulted from presumed multiple emboli or the break-up of an embolus. Two patients had internal carotid artery occlusive disease and four had a cardiac or aortic source. In the other four patients the source was not determined. Lesions larger than 1 cm in diameter progressed to infarction, but some smaller lesions were not seen on follow-up T2-weighted imaging. Conclusions: Multiple acute stroke lesions on DWI are common and could be caused by multiple emboli or the breakup of an embolus. In some cases it might become possible to make early inferences concerning the stroke mechanism that could be of use for immediately directing the clinical work-up and treatment of the patient.

Clinical correlations of diffusion and perfusion lesion volumes in acute ischemic stroke

The aim of this study was to describe the clinico-radiological correlations of magnetic resonance (MR) perfusion and diffusion-weighted imaging (DWI) abnormalities in ischemic stroke. Eighteen patients had undergone MR imaging and clinical evaluation within 24 h of symptom onset and at or after 7 days. During the first 24 h the volume of perfusion abnormality (measured on the relative mean transit time map) was larger than the DWI lesion in 12/18 patients. In 6/18 patients the DWI lesion volume was larger. Acutely (<24 h) all lesion volumes showed a significant correlation with acute clinical severity measured by the National Institutes of Health Stroke Scale score. The correlations of the hypoperfusion volume (rho = 0.86, p = 0.0001) and the volume ‘tissue at risk’ (larger than the DWI and perfusion lesion volumes, rho = 0.86, p = 0.0001) with acute clinical severity were slightly higher than for the DWI lesion volume (rho = 0.76, p = 0.0001). The difference between the volume of tissue at risk (acutely) and the infarct on follow-up T2-weighted imaging correlated significantly with change in clinical severity from acute to chronic time points (rho = 0.72, p = 0.001). Such clinico-radiological relationships may support the use of DWI and perfusion MR in decisions concerning the administration and evaluation of stroke therapies.

Differences in Stroke Subtypes Among Natives and Caucasians in Boston and Buenos Aires

Background and Purpose Several issues regarding ethnic-cultural factors, sex-related variation, and risk factors for stroke have been described in the literature. However, there have been no prospective studies comparing ethnic differences and stroke subtypes between populations from South America and North America. It has been suggested that natives from Buenos Aires, Argentina, may have higher frequency of hemorrhagic strokes and penetrating artery disease than North American subjects. The aim of this study was to validate this hypothesis. Methods We studied the database of all consecutive acute stroke patients admitted to the Ramos Mejia Hospital (RMH) in Buenos Aires and to the Beth Israel Deaconess Medical Center (BIMC) in Boston, Massachusetts, from July 1997 to March 1999. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All information on patients (demographic, clinical, and radiographic) was recorded prospective to the assessment of the stroke subtype. Results Three hundred sixty-one and 479 stroke patients were included at RMH and BIMC stroke data banks, respectively. Coronary artery disease was significantly more frequent in BIMC (P <0.001), whereas tobacco and alcohol intake were significantly more frequent in RMH (P <0.001). Intracerebral hemorrhage (P <0.001) and penetrating artery disease (P <0.001) were significantly more frequent in the RMH registry, whereas large-artery disease (P <0.02) and cardioembolism (P <0.001) were more common in the BIMC data bank. Conclusions Penetrating artery disease and intracerebral hemorrhage were the most frequent stroke subtypes in natives from Buenos Aires. Lacunar strokes and intracerebral hemorrhage were more frequent among Caucasians from Buenos Aires than Caucasians from Boston. Poor risk factor control and dietary habits could explain these differences.

Significance of early CT signs in acute stroke. A CT scan-diffusion MRI study.

Objective: To study the pathophysiology of early CT signs. Background: Early CT signs, due to an increase in tissue water content, are commonly attributed to cytotoxic edema and development of irreversible injury. This may have important implications for thrombolysis. Methods: In patients with acute ischemic stroke in the middle cerebral artery territory, the areas of early CT signs and diffusion weighted imaging (DWI) hypersignal were independently assessed and drawn on a standardized atlas. Then, patients were classified into three groups (early CT signs larger than, similar to or smaller than DWI hypersignal) and compared with perfusion weighted imaging (PWI). Results: Of 16 patients, CT scanning was performed with a median time of 3 h after onset and early CT scan signs were recorded in 10/16 patients (62.5%). DWI signal hyperintensity was present in 15/16 (94%) patients. In 7/16 (43%) patients, the area with early CT scan signs was larger than the DWI lesion (‘CT-larger group’). Only in 2/16 (12%) patients were the areas matching (‘matching group’). In 7/16 (43%) the DWI lesion was larger than the early CT scan signs area (‘DWI-larger group’). When compared with PWI, the areas of early CT signs were larger than DWI hypersignal and were matching with PWI abnormalities (rMTT) in 2 cases, suggesting that they may represent a reversible process. Conclusions: Early CT signs might have a potential dual fate: infarction or reversibility. Other techniques of recognizing reversible ischemic damage, such as DWI-PWI, are needed to improve acute stroke diagnosis and management.

Computed tomography in acute ischemic stroke

Stroke remains the third most important cause of mortality in industrialized countries; this has prompted research for improvements in both diagnostic and therapeutic strategies for patients with signs of acute cerebral ischemia. Over the last decade, there has been a parallel in progress in techniques in both diagnostic and therapeutic options. While previously only used for excluding hemorrhage, imaging now has the possibility to detect ischemia, vascular occlusion, as well as detect tissue at risk in one setting. It should also allow to monitor treatment and predict/exclude therapeutic complications. Parallel to advances in magnetic resonance imaging of stroke, computed tomography has improved immensely over the last decade due to the development of CT scanners that are faster and that allow to acquire studies such as CT perfusion or CT angiography in a reliable way. CT can detect many signs that might help us detect impending signs of massive infarction, but we still lack the experience to use these alone to prevent a patient from benefitting from possible therapy.

Actual diagnostic approach to the acute stroke patient

Since acute stroke is now considered a potentially treatable medical emergency, a rapid and correct diagnosis must be made. The first step is to exclude hemorrhage, then to visualize any early ischemic changes, demonstrate the presence of hypoperfusion and locate the presence of a vascular underlying pathology as well as elucidate the presence of a potential penumbra (tissue at risk). Thanks to improvements and advances in both MR and CT technology, this can now be done in a number of ways. At the moment, CT is the most widely available and fast method for obtaining imaging of the brain and neck vessels of patients presenting with acute stroke. MRI can provide more precise information, although it remains slightly more time-consuming, but is, however, the method of choice for follow-up imaging. The main point is to take the one-stop-shopping approach where imaging of the vessels and brain is done from the aortic arch to the circle of Willis in one single session in order to have all the necessary information in the acute phase.

IMAGING DEVELOPING BRAIN INFARCTION

Continued advances in neuroimaging technology have made it practical to image multiple aspects of evolving brain infarction during the potential window period of therapeutic opportunity in stroke. Recent methodologic developments include computed tomography angiography and perfusion, and the description of quantitative parameters for magnetic resonance blood oxygen level-dependent perfusion imaging. In pathophysiologic studies, metabolism and function in the ischemic focus and the peri-infarct tissue have been further characterized. Clinical studies have focused on the applications of computed tomography and magnetic resonance imaging for prethrombolysis patient selection. These methods have an important role in the evaluation and development of new pharmaceutical agents and will be increasingly used in clinical practice as new therapies become available.

Genetics and Genomics of Stroke: Novel Approaches

Evidence for a genetic basis for stroke comes from twin and family studies and from the occurrence of a number of uncommon monogenic disorders, but the contribution of genetic factors identified for stroke so far is small. Advances in genetics and genomics may permit new insights. In recent genome-wide association studies, a number of single-nucleotide polymorphisms have been associated with specific stroke subtypes and major stroke risk factors such as diabetes and atrial fibrillation. These await replication. Studies of messenger ribonucleic acid expression have also shown promise for the development of genomic signatures for stroke classification. Stroke and coronary heart disease share some features of pathophysiology, risk, and treatment, and their genetic and genomic bases also appear to overlap.