Christian Beaulieu

Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome

A prospective longitudinal diffusion‐weighted and perfusion‐weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia‐induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

Comparison of diffusion-weighted MRI and CT in acute stroke

Objective: To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume. Method:— Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the “gold standard” for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume. Results: The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume. Conclusion: When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI

Objective: To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury. Methods: Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received IV rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images. Results: PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received IV tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 ± 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015). Conclusion: Early reperfusion is seen more frequently with IV tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with IV tPA therapy.

Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis

Background and Purpose The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome. Methods We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score ≥85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis. Results Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score ≥85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI. Conclusions DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

Dynamics of cerebral injury, perfusion, and blood-brain barrier changes after temporary and permanent middle cerebral artery occlusion in the rat

By means of magnetic resonance imaging (MRI) we longitudinally monitored the evolution of ischemic injury, changes in cerebral hemodynamics and alterations of the blood-brain barrier (BBB) during permanent or temporary middle cerebral artery occlusion (MCAO) in rats. Using the intraluminal suture occlusion model, male Sprague-Dawley rats were subjected to either permanent MCAO (Group A, n = 6), reperfusion after 1 h (Group B, n = 5), or reperfusion after 3 h (Group C, n = 5). Diffusion- and perfusion-weighted MRI and Gd-DTPA enhanced T1-weighted images were performed at six time points from 0.5 to 6 h post-MCAO. The lesion volume increased progressively in group A, decreased significantly in group B (P<0.01), and only showed a tendency toward reduction in group C. Perfusion-weighted MRI delineated severe perfusion deficits in the ischemic core, confirmed early and late reperfusion, and was able to demonstrate postischemic hyperperfusion in group C. Gd-DTPA extravasation was found in all animals with permanent MCAO and initially became grossly visible between 4.5 and 6 h post-MCAO. While only 2 animals demonstrated contrast enhancement in group B, widespread BBB changes were detected immediately following late reperfusion (Group C). Our results demonstrate that with advanced MRI techniques, alterations of the BBB can be correlated with the hemodynamic and biophysical consequences of reperfusion.

Rapid Monitoring of Diffusion, DC Potential, and Blood Oxygenation Changes During Global Ischemia Effects of Hypoglycemia, Hyperglycemia, and TTX

BACKGROUND AND PURPOSE The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia. METHODS Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease. RESULTS The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups. CONCLUSIONS While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis.

Magnetic Resonance Imaging Assessment of Cerebral Hemodynamics during Spreading Depression in Rats

High-speed magnetic resonance imaging was used to perform simultaneous measurements of relative cerebral blood volume (rCBV) and water diffusion changes during spreading depression (SD) induced by cortical potassium chloride application. Rats were fitted epidurally with a rubber chamber. Potassium chloride was perfused through the chamber until SD was indicated by a negative direct current (DC) potential shift. Magnetic resonance imaging scans used echo planar diffusion and T2-weighted images. Iron dextran was injected as a blood pool contrast agent to make subsequent changes in T2 (or T2*) directly proportional to changes in CBV. Multislice maps of apparent diffusion coefficient (ADC) and rCBV were generated with 6- to 16-second time resolution, which revealed transient ADC and rCBV changes propagating over the cortex after potassium chloride application. Transient ADC declines appeared simultaneously with the DC shift, whereas rCBV increase followed with a delay of 16.4 ± 14.9 seconds. Prolonged rCBV decrease was observed after the initial increase during the SD in half of the animals. The delayed rCBV response after the ADC change supports the observation of increased energy demand because of repolarization. Simultaneous DC potential recording and ADC measurements in corresponding sites of the cortex indicate that transient ADC decreases during SD reflect water shifts associated with cell depolarization.

Polynitroxyl albumin reduces infarct size in transient focal cerebral ischemia in the rat : Potential mechanisms studied by magnetic resonance imaging

Nitroxide free radicals are known to protect cells from oxidative damage. Diffusion-weighted and perfusion-weighted magnetic resonance imaging was used to evaluate the effects of polynitroxyl albumin(PNA) in a middle cerebral artery intraluminal suture model of transient focal cerebral ischemia in the rat. Three groups of Sprague-Dawley rats were investigated: (1) PNA(N = 6), (2) human serum albumin (N = 6), and (3) saline (N = 7). The middle cerebral artery was occluded for 2 hours. Treatment was started 30 minutes after induction of ischemia. A total dose of 1% body weight (volume/weight) of PNA (23.5 mg/dL protein and 110 mmol/L nitroxide), albumin (23.5 mg/dL), or saline was injected intravenously at three time points: 0.5% at 0.5 hours, 0.25% at 2 hours (i.e., just before reperfusion), and 0.25% at 4 hours after occlusion. Six sets of diffusion- and perfusion-weighted magnetic resonance images were acquired throughout the 2 hours of ischemia and the 2 hours of reperfusion. The rats were killed at 24 hours, and the brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC). Diffusion-weighted imaging showed that the growth of the ischemic lesion was suppressed in the PNA-treated group. The 4 hours diffusion-weighted imaging-derived hemispheric lesion volume in the PNA-treated group (25% ± 9%) was significantly smaller than that in the saline-treated(43% ± 13%; P = 0.016) or albumintreated groups (38% ± 6%; P = 0.017). A larger difference was observed for the 24-hour TTC-derived lesion volumes in the PNA (8% ± 7%), saline (35% ± 8%; P< 0.001), and albumin (31% ± 6%; P < 0.001) groups. Perfusion-weighted imaging demonstrated a marked improvement in cerebral perfusion in the PNA-treated group during ischemia and reperfusion. In conclusion, treatment with PNA results in an improvement in perfusion and a reduction of infarct volume in a model of transient focal cerebral ischemia in the rat.

Diffusion-weighted magnetic resonance imaging: theory and potential applications to child neurology.

Magnetic resonance imaging (MRI) is an excellent tool for the investigation of neurological disorders in children. Diffusion-weighted MRI (DWI) is sensitive to the diffusion (or molecular displacement) of water in tissue. The purpose of this article is to describe briefly the basic theory behind DWI and to discuss its potential applications to neurological disorders in children. We demonstrate that DWI is a sensitive technique for the detection of acute brain injury, and that it is well suited for monitoring brain development, particularly myelination and white matter changes.

Hyperglycemia Delays Terminal Depolarization and Enhances Repolarization after Peri-Infarct Spreading Depression as Measured by Serial Diffusion MR Mapping

We investigated the effect of hyperglycemia on the initiation and propagation of spreading depression-like peri-infarct ischemic depolarization (SD) induced by focal cerebral ischemia in rats. Peri-infarct SD were monitored during the initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO) using serial diffusion weighted magnetic resonance imaging. Maps of the apparent diffusion coefficient (ADC) were calculated and ADC decreases were monitored over time. Hyperglycemic rats (n = 6) had a significant prolongation of the time from induction of MCAO to the start of the ADC decrease as compared with normoglycemic control rats. The time to the maximal ADC decrease was significantly delayed and recovery of transient ADC declines in the area adjacent to the ischemic core was significantly faster in hyperglycemic rats. We conclude that hyperglycemia delays the terminal depolarization in the ischemic core and supports a faster repolarization in severely mal-perfused penumbral tissue after SD, which reflects the increased availability of energy substrates in the state of hyperglycemia.