Apparent Diffusion Coefficient Lesion Volume Research Articles

Clinical-imaging metrics for the diagnosis of prostate cancer in PI-RADS 3 lesions

ObjectiveTo explore the feasibility and efficacy of clinical-imaging metrics in the diagnosis of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in prostate imaging-reporting and data system (PI-RADS) category 3 lesions. MethodsA retrospective analysis was conducted on lesions diagnosed as PI-RADS 3. They were categorized into benign, non-csPCa and csPCa groups. Apparent diffusion coefficient (ADC), T2-weighted imaging signal intensity (T2WISI), coefficient of variation of ADC and T2WISI, prostate-specific antigen density (PSAD), ADC density (ADCD), prostate-specific antigen lesion volume density (PSAVD) and ADC lesion volume density (ADCVD) were measured and calculated. Univariate and multivariate analyses were used to identify risk factors associated with PCa and csPCa. Receiver operating characteristic curve (ROC) and decision curves were utilized to assess the efficacy and net benefit of independent risk factors. ResultsAmong 202 patients, 133 had benign prostate disease, 25 non-csPCa and 44 csPCa. Age, PSA and lesion location showed no significant differences (P > 0.05) among the groups. T2WISI and coefficient of variation of ADC (ADCcv) were independent risk factors for PCa in PI-RADS 3 lesions, yielding an area under the curve (AUC) of 0.68. ADC was an independent risk factor for csPCa in PI-RADS 3 lesions, yielding an AUC of 0.65. Decision curve analysis showed net benefit for patients at certain probability thresholds. ConclusionsT2WISI and ADCcv, along with ADC, respectively showed considerable promise in enhancing the diagnosis of PCa and csPCa in PI-RADS 3 lesions.

Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented.

Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.

Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes.

The influence of gender on ‘tissue at risk’ in acute stroke: A diffusion-weighted magnetic resonance imaging study in a rat model of focal cerebral ischaemia

This is the first study to assess the influence of sex on the evolution of ischaemic injury and penumbra. Permanent middle cerebral artery occlusion was induced in male (n = 9) and female (n = 10) Sprague-Dawley rats. Diffusion-weighted imaging was acquired over 4 h and infarct determined from T2 images at 24 h post-permanent middle cerebral artery occlusion. Penumbra was determined retrospectively from serial apparent diffusion coefficient lesions and T2-defined infarct. Apparent diffusion coefficient lesion volume was significantly smaller in females from 0.5 to 4 h post permanent middle cerebral artery occlusion as was infarct volume. Penumbral volume, and its loss over time, was not significantly different despite the sex difference in acute and final lesion volumes.

Abstract 2550: Early 3 Hour Imaging Demonstrates Substantial Diffusion Reversal with Lower Infarction Risk Compared to Tissue without Diffusion Reversal

Background: Literature suggests that diffusion reversal--determined by visually inspecting diffusion-weighted images which reverse on subsequent imaging--is uncommon. However, these studies performed the initial scan 3 to 6 hrs from onset which may miss lesions that have already undergone reversal. We measured apparent diffusion coefficient (ADC) reversal between 2 scans obtained at 3 and 6 hrs from onset comparing infarct probability in reversed regions to brain regions with persistent ADC lesions. Methods: Ischemic stroke patients underwent 3 MRI’s: <4.5 hrs (tp1), at 6 hrs (tp2), and at 1 mo (tp3) after onset. Co-registered maps measured ADC lesions (tp1, tp2) and FLAIR infarct (tp3). Diffusion lesions were manually outlined as hypointense regions on ADC. A population-derived ADC threshold to distinguish abnormal from normal ADC was calculated based on the maximum ADC value capturing >90% of voxels within the outlined lesions. ADC values less than or greater than this threshold were defined as abnormal and normal, respectively. ADC “reversal” was defined as voxels with abnormal tp1 ADC and normal tp2 ADC, whereas ADC “non-reversal” was defined as abnormal ADC on both tp1 and tp2. Final infarcts were outlined as hyperintense regions on tp3 FLAIR. Infarct probability (% of the tp1 ADC lesion which infarcted on tp3) was compared between reversed and non-reversed tissue using a Mann-Whitney test. Leukoariosis or CSF voxels due to infarct atrophy were excluded from the infarct analysis. Results: 39 patients were prospectively scanned at 2.8hr (tp1), 6.4hr (tp2), and 1mo (tp3) after stroke onset (NIHSS=14, 74% received tPA). The population-derived ADC threshold to distinguish between abnormal and normal was 71 × 10 -5 mm 2 /s. Median ADC lesion volume at tp1 was 34ml [15, 70] and at tp2 was 34ml [14, 65]. Median ADC reversal volume was 6.6ml [5, 17], accounting for 34% [11, 44] of the tp1 ADC lesion volume (ADC non-reversal volume was 21ml [6, 50]). 31 of 39 (79%) and 20 of 39 (51%) patients had reversal volumes >10% and >33% of their initial ADC lesion, respectively. Infarct probability was lower (57%) in ADC reversal tissue compared to tissue with non-reversal (82%, p<0.0001) ( Figure ). To confirm that the derived ADC threshold distinguished abnormal tissue on tp1 from normal tissue on tp2, ADC tp1 and tp2 values were compared and differed (66 vs. 77, p<0.0001). Conclusion: While ADC closely approximates infarct core, during early ischemia, a substantial proportion of the initial ADC lesion may reverse. Brain tissue with this MR signature carries a significantly lower risk of infarction than tissue without ADC reversal.

Does Acute Behavioral Testing Reflect Successful Ischemia in Rats with Transient Middle Cerebral Artery Occlusion?

Models of intraluminal middle cerebral artery occlusion present an intrinsic variability in infarct size. Behavioral evaluation is frequently performed during arterial occlusion to confirm success of surgery. We compared the value of behavioral testing and multimodal magnetic resonance imaging performed during arterial occlusion for identifying successfully operated animals. Rats were tested with behavioral assessment (using three scoring scales and the adhesive removal test) and multimodal magnetic resonance imaging (including magnetic resonance angiography, diffusion-weighted and perfusion-weighted imaging), both performed during the two-hours of middle cerebral artery occlusion using the intraluminal suture model. Behavioral assessment was repeated 24 h after reperfusion, followed by sacrifice. Acute apparent diffusion coefficient lesion volume was correlated with both 2,3,5-triphenyl tetrazolium chloride infarct size (r = 0·75, P = 0·02) and behavioral status (r = 0·66, P = 0·05) on day one. Conversely, no correlation was found between acute behavioral examination and day one outcomes (2,3,5-triphenyl tetrazolium chloride infarct volume, r = 0·40, P = 0·28; behavioral examination, r = 0·39, P = 0·30). Day zero apparent diffusion coefficient volumes (P = 0·04), but not behavioral assessment (P = 0·60), discriminated animals with day one corticostriatal infarcts from these with subcortical infarcts. Acute behavioral testing performed during arterial occlusion fails to identify successfully operated animals. Acute diffusion magnetic resonance imaging may be more appropriate to assess and reduce infarct size variability in this model.

Regional Very Low Cerebral Blood Volume Predicts Hemorrhagic Transformation Better Than Diffusion-Weighted Imaging Volume and Thresholded Apparent Diffusion Coefficient in Acute Ischemic Stroke

Currently, diffusion-weighted imaging (DWI) lesion volume is the most useful magnetic resonance imaging predictor of hemorrhagic transformation (HT). Preliminary studies have suggested that very low cerebral blood volume (VLCBV) predicts HT. We compared HT prediction by VLCBV and DWI using data from the EPITHET study. Normal-percentile CBV values were calculated from the nonstroke hemisphere. Whole-brain masks with CBV thresholds of the <0, 2.5, 5, and 10th percentiles were created. The volume of tissue with VLCBV was calculated within the acute DWI ischemic lesion. HT was graded as per ECASS criteria. HT occurred in 44 of 91 patients. Parenchymal hematoma (PH) occurred in 13 (4 symptomatic) and asymptomatic hemorrhagic infarction (HI) in 31. The median volume of VLCBV was significantly higher in cases with PH. VLCBV predicted HT better than DWI lesion volume and thresholded apparent diffusion coefficient lesion volume in receiver operating characteristic analysis and logistic regression. A cutpoint at 2 mL VLCBV with the <2.5th percentile had 100% sensitivity for PH and, in patients treated with tissue plasminogen activator, defined a population with a 43% risk of PH (95% CI, 23% to 66%, likelihood ratio=16). VLCBV remained an independent predictor of PH in multivariate analysis with traditional clinical risk factors for HT. VLCBV predicted HT after thrombolysis better than did DWI or apparent diffusion coefficient volume in this large patient cohort. The advantage was greatest in patients with smaller DWI volumes. Prediction was better in patients who recanalized. If validated in an independent cohort, the addition of VLCBV to prethrombolysis decision making may reduce the incidence of HT.

Granulocyte-Colony Stimulating Factor Delays PWI/DWI Mismatch Evolution and Reduces Final Infarct Volume in Permanent-Suture and Embolic Focal Cerebral Ischemia Models in the Rat

Granulocyte-colony stimulating factor (G-CSF) is used clinically to attenuate neutropenia after chemotherapy. G-CSF acts as a growth factor in the central nervous system, counteracts apoptosis, and is neuroprotective in rodent transient ischemia models. We assessed the effect of G-CSF on ischemic lesion evolution in a rat permanent-suture occlusion model with diffusion- and perfusion-weighted magnetic resonance imaging and the neuroprotective effect of G-CSF in a rat embolic stroke model. With a constant perfusion deficit, vehicle-treated animals showed an expanding apparent diffusion coefficient lesion volume that matched the perfusion deficit volume at approximately 3 hours, with the 24-hour infarct volume equivalent to the perfusion deficit. In G-CSF-treated rats, the apparent diffusion coefficient lesion volume did not increase after treatment initiation, and the infarct volume at 24 hours reflected the initial apparent diffusion coefficient lesion volume. In the embolic model, we observed a significant decrease in infarct volume in G-CSF-treated animals compared with the vehicle-treated group. These results confirm the potent neuroprotective activity of G-CSF in different focal ischemia models. The magnetic resonance imaging data demonstrate that G-CSF preserved the perfusion/diffusion mismatch.

Why Does Acute Hyperglycemia Worsen the Outcome of Transient Focal Cerebral Ischemia?

Hyperglycemia adversely affects the outcome of stroke. Global ischemia data support that the harmful effect of hyperglycemia is mediated by glucose-induced elevated plasma glucocorticoids. Here we sought to evaluate the negative effects of hyperglycemia on transient focal ischemia in the rat, and to test whether these could be prevented by inhibition of either corticosteroid production or neutrophil infiltration. Sprague-Dawley rats (n=217) were used. Ischemia was induced by 1 hour middle cerebral artery occlusion (n=196). Acute hyperglycemia was induced by IP injection of dextrose 30 minutes before ischemia. Neutrophil infiltration was blocked by neutropenia with vinblastine. Corticosterone synthesis was inhibited by chemical adrenalectomy with metyrapone. We measured MRI lesion and tissue infarct volumes, evaluated the neurological function, brain myeloperoxidase and matrix metalloproteinase-9 activities, and protein O-glycosylation. Hyperglycemia significantly enhanced MRI diffusion-weighted imaging alterations, increased cortical, but not subcortical, infarct volume, worsened neurological score, and enhanced brain myeloperoxidase and matrix metalloproteinase-9 activities. Metyrapone did not prevent hyperglycemic brain damage despite successful reduction of plasma corticosterone. Yet, metyrapone tended to reduce cortical infarction and apparent diffusion coefficient lesion volume, indicating some negative contribution of corticosterone. Blocking neutrophil infiltration was also ineffective to prevent the harmful effect of hyperglycemia. A new finding was that O-linked glycosylation of cerebral proteins was increased under hyperglycemia. In transient middle cerebral artery occlusion, the hyperglycemia-exacerbated brain damage cannot be fully explained by the negative effects of plasma corticosteroids or neutrophil infiltration. The contribution of other intrinsic effects of high glucose, such as brain protein O-glycosylation, deserves further investigation.

Comparison of Ischemic Lesion Evolution in Embolic Versus Mechanical Middle Cerebral Artery Occlusion in Sprague Dawley Rats Using Diffusion and Perfusion Imaging

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague Dawley rats after permanent suture MCAO (sMCAO; n=8) and embolic MCAO (eMCAO; n=8). Serial measurements of quantitative cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed up to 180 minutes after MCAO. ADC and CBF values within 5 different brain regions were analyzed. ADC and CBF lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO. Compared with sMCAO animals, the threshold-derived CBF lesion volume was significantly larger in eMCAO at all time points (P<0.01), remained relatively constant over time, and was highly correlated with the 2,3,5-triphenyltetrazolium chloride-defined infarct size. The ADC lesion volume did not differ between models at any time point. A diffusion/perfusion mismatch was present significantly longer in eMCAO animals (P<0.05), and these rats demonstrated larger absolute mismatch volumes that were statistically significant at 30, 60, and 90 minutes (P<0.05). In both models, CBF and ADC declines were highly correlated. This study demonstrated substantial differences in acute ischemic lesion evolution between the eMCAO and sMCAO models.

The Evolution of Cerebral Ischemia in a Rat Model of Complete Unilateral Carotid Artery Occlusion With Severe Hypotension as Detected By Diffusion-, T2-, and Postcontrast T1-Weighted Magnetic Resonance Images

Severe internal carotid artery stenosis or occlusion is considered to be one of the important causes of stroke. The authors created a complete unilateral carotid artery occlusion model in 15 Sprague-Dawley rats, induced severe hypotension for at least 36 minutes by exsanguination with the target mean arterial pressure being equal or less than 35 mmHg, and investigated the temporal and spatial evolution of cerebral ischemia by diffusion-, T2-, and postcontrast T1-weighted magnetic resonance images. Cerebral ischemia was detected in most regions of the right middle cerebral artery territory during exsanguination. There was no significant relationship between ischemic lesion volume detected on apparent diffusion coefficient (ADC) map (ADC lesion volume) and infarction volume found on histopathology. However, there was a linear relationship between the change in ADC lesion volume at blood reinfusion (after reinfusion minus before reinfusion) and the enlargement of the lesion volume during the postreinfusion period (Y = 0.4X + 161.7, P = 0.0066) and a significant logarithmic correlation between the volume of vasogenic edema found on postcontrast T1-weighted image at 1 hour of the postreinfusion period and the enlargement of the lesion volume during the postreinfusion period (Y = 62.1 x logX - 115.4, P = 0.022). In conclusion, although it may be difficult to predict the outcome of cerebral ischemia (infarction volume) from the lesion volume during exsanguination, the evolution of cerebral ischemia may be partly predicted by lesion volume changes seen on the ADC maps at the time of the blood reinfusion or by the severity of blood-brain barrier disruption at the early stage of the postreinfusion period.

Apparent diffusion coefficient mapping predicts mortality and outcome in rats with intracerebral haemodynamic disturbance: potential role of intraoperative diffusion and perfusion weighted magnetic resonance imaging to detect cerebral ischaemia

Usefulness and ability of diffusion and perfusion weighted magnetic resonance images (DWI and PWI) to detect intracerebral haemodynamic disturbance have not been fully evaluated. After the right common carotid artery had been ligated, rats were exsanguinated to maintain a mean arterial pressure of 35, 42, or 50 mm Hg (n=6, each group). Apparent diffusion coefficient (ADC) maps were calculated from DWIs and lesion volume (area) was defined based on ADC values (ADC lesion volume (area)). ADC lesion volume during exsanguination in the 35 mm Hg group (417 (111) mm(3), P<0.01) was significantly larger than in the 42 mm Hg group (87 (84) mm(3)) and 50 mm Hg group (42 (58) mm(3)). The low relative cerebral blood flow area, calculated from PWI, was significantly larger during exsanguination in the 35 mm Hg group than in the other groups. ADC lesion volume in the six rats that died within 3 days of the MRI study was significantly larger (median 421 mm(3), range 205-476 mm(3), P<0.005) than in the 12 rats that survived for 3 days (median 26 mm(3), range 3-517 mm(3)). Rats with an ADC lesion area over 14 mm(2) on the coronal slice including the caudate putamen during exsanguination died within 3 days or revealed a more severe histopathological outcome than those that survived for 3 days. Incomplete cerebral ischaemia created by the combination of common carotid artery occlusion and exsanguination could be detected by DWI and PWI both qualitatively and quantitatively. The size of the lesion on ADC mapping was found to correlate with mortality and outcome.

Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke.

Hyperbaric oxygen therapy is considered an important stroke treatment strategy. To determine whether normobaric oxygen is neuroprotective, and, if so, what the therapeutic time window is. Experiment 1-Serial diffusion- and perfusion-weighted MRI (DWI and PWI) was performed after middle cerebral artery filament occlusion (MCAO) in rats randomized to FiO(2) 30% (normoxia) or FiO(2) 100% (hyperoxia). Experiment 2-48-hour lesion volumes were analyzed in rats subjected to 2-hour MCAO and randomized to normoxia or hyperoxia starting 15, 30, or 45 minutes after MCAO and ending 15 minutes after reperfusion. Experiment 1-Lesion apparent diffusion coefficient (ADC) values were persistently low in normoxic animals. In hyperoxia-treated rats, ADC values in cortical border zones showed progressive recovery from 66 +/- 3% of contralateral before hyperoxia, to 104 +/- 20% at approximately 2 hours. Striatal ADC values showed early but ill-sustained improvement. ADC lesion volumes increased progressively in the normoxia group. In the hyperoxia group, ADC lesion volumes tended to decrease after starting hyperoxia; however, lesions later increased in size, and 2-hour lesion volumes were not significantly different from baseline. PWI showed stable right MCA hypoperfusion in all animals. Experiment 2-Hyperoxia within 30 minutes significantly reduced total and cortical lesion volumes at 48 hours after stroke. Striatal lesion volumes were significantly reduced in the hyperoxia-15 group. In rats subjected to transient stroke, 100% oxygen administered within 30 minutes salvages ischemic brain tissue, especially in the cerebral cortex. Reducing the time to treatment enhances the degree of neuroprotection.

Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.

Inhibition of nonselective cation channels reduces focal ischemic injury of rat brain.

The effect of the novel inhibitor of receptor-activated and calcium store-operated nonselective cation channels, (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma 1)-2-phenyl-N, N-di-[2(2,3,4-trimethoxyphenyl) ethyl]acetamide (LOE 908 MS), on focal cerebral ischemia was studied in halothane-anesthetized rats submitted to permanent suture occlusion of the right middle cerebral artery (MCA). The treated group (n = 7) received subcutaneous injections of 30 mg/kg LOE 908 MS (in 1 ml saline) 10 min after vascular occlusion and again after 3 h. The untreated group (n = 11) was injected subcutaneously with 1 ml saline at the same times. Evolution of infarct was monitored by electrophysiological recording of EEG and cortical steady potential and by diffusion-weighted magnetic resonance imaging during the initial 6 h of vascular occlusion. The hemodynamic, biochemical, and morphological changes were studied after 6 h by combining autoradiographic measurement of blood flow with histological stainings and pictorial measurements of ATP, glucose, and tissue pH. In the untreated animals, the ischemic lesion volume [defined as the region in which the apparent diffusion coefficient (ADC) of water declined to below 80% of control] steadily increased by approximately 50% during the initial 6 h of vascular occlusion relative to the first set of data 10 min postocclusion. In the treated animals, in contrast, the ADC lesion volume declined by approximately 20% during the same interval. Treatment also led to a significant reduction in the number of periinfarct depolarizations. After 6 h of vascular occlusion, blood flow was significantly higher in the treated animals, and the volume of ATP-depleted and morphologically injured tissue representing the infarct core was 60-70% smaller. The volume of severely acidic tissue, in contrast, did not differ, indicating that LOE 908 MS does not reduce the size of ischemic penumbra. These findings demonstrate that postocclusion treatment of permanent focal ischemia with LOE 908 MS delays the expansion of the infarct core into the penumbra for a duration of at least 6 h and therefore substantially prolongs the window of opportunity for the reversal of the ischemic impact in the peripheral parts of the evolving infarct.