Pamela W. Schaefer

Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI

Objective: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. Methods: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. Results: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. Conclusions: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.

Diffusion-Weighted Imaging Discriminates Between Cytotoxic and Vasogenic Edema in a Patient With Eclampsia

BACKGROUND The pathophysiology of eclampsia remains unclear. While the majority of patients develop reversible T2 hyperintense signal abnormalities on MR scans and reversible neurological deficits, some patients do develop infarctions (permanent T2 hyperintense abnormalities) and permanent neurological impairment. Routine MRI cannot prospectively differentiate between these two patient groups. Echo-planar diffusion-weighted imaging, however, is a new technique that clearly differentiates between cytotoxic and vasogenic edema. CASE DESCRIPTION A 30-year-old woman developed symptoms consistent with eclampsia 24 hours after delivering premature twins. An MRI demonstrated extensive, diffuse T2 hyperintense signal abnormalities involving subcortical white matter and adjacent gray matter with a posterior predominance, consistent with either infarction or hypertensive ischemic encephalopathy. Diffusion-weighted images demonstrated increased diffusion, consistent with vasogenic edema and hypertensive ischemic encephalopathy. CONCLUSIONS Unlike routine MRI, diffusion-weighted imaging reliably differentiates between vasogenic edema and cytotoxic edema. Consequently, in eclamptic patients diffusion-weighted imaging can afford clear differentiation between hypertensive ischemic encephalopathy and infarction, two very different entities with very different treatment protocols. Diffusion-weighted imaging should be performed in all eclamptic patients and should greatly affect their management.

Regional Ischemia and Ischemic Injury in Patients With Acute Middle Cerebral Artery Stroke as Defined by Early Diffusion-Weighted and Perfusion-Weighted MRI

BACKGROUND AND PURPOSE We sought to map early regional ischemia and infarction in patients with middle cerebral artery (MCA) stroke and compare them with final infarct size using advanced MRI techniques. MRI can now delineate very early infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by perfusion-weighted imaging (PWI). METHODS Seventeen patients seen within 12 hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI MRI. PWI maps were generated by analysis of the passage of intravenous contrast bolus through the brain. Cerebral blood volume (CBV) was determined after quantitative analysis of PWI data. Volumes of the initial DWI and PWI lesion were calculated and compared with a final infarct volume from a follow-up imaging study (CT scan or MRI). RESULTS Group 1 (10 patients) had MCA stem (M1) occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of CBV abnormality. In 7 patients the final stroke volume was larger or the same, and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the initial DWI lesion matched the initial CBV abnormality and the final infarct. CONCLUSIONS Most patients with M1 occlusion showed progression of infarction into the region of abnormal perfusion. In contrast, patients with open M1 had strokes consistent with distal branch occlusion and had maximal extent of injury on DWI at initial presentation. Application of these MRI techniques should improve definition of different acute stroke syndromes and facilitate clinical decision making.

Normal diffusion-weighted MRI during stroke-like deficits

Background: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. Objective: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. Methods: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. Results: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). Conclusions: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

MRI-Based Selection for Intra-Arterial Stroke Therapy Value of Pretreatment Diffusion-Weighted Imaging Lesion Volume in Selecting Patients With Acute Stroke Who Will Benefit From Early Recanalization

Background and Purpose— Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm3 predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts <70 cm3, we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. Methods— We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess differences in clinical and imaging outcomes. Good clinical outcome was defined as a 3-month modified Rankin Scale score ≤2. Results— Among patients with initial infarcts >70 cm3, all had poor outcomes despite a 50% recanalization rate with mean infarct growth of 114 cm3. These patients also had the largest mean transit time volumes (P<0.04). Patients with initial infarct volumes <70 cm3 who recanalized early had the best clinical outcomes (P<0.008) with a 64% rate of modified Rankin Scale score ≤2 and the least infarct growth (P<0.03) with mean growth of 18 cm3. Conclusion— This study supports the use of an acute diffusion-weighted imaging lesion volume threshold as an imaging selection criterion for intra-arterial therapy. It also confirms the importance of early reperfusion in selected patients.

ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes

Background: Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometric models generated accurate estimates of these volumes. Methods: Acute diffusion-weighted image (DWI) and perfusion (mean transit time [MTT]) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as MTT/DWI ≥ 1.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B, and C. Geometric estimates of sphere, ellipsoid, bicone, and cylinder were compared to planimetric volume by least-squares linear regression. Results: The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16, 95% confidence interval [CI] 0.94 to 1.38; R2 = 0.91, p = 0.001) and MTT (slope 1.11, 95% CI 0.99 to 1.23; R2 = 0.89, p = 0.001). The intrarater and interrater reliability for ABC/2 was high for both DWI (0.992 and 0.965) and MTT (0.881 and 0.712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95% CI 0.98 to 1.19; R2 = 0.74, p = 0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%. Conclusions: Of the models tested, ABC/2 is reproducible, is accurate, and provides the best simple geometric estimate of infarction and mean transit time volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment.

Petechial hemorrhages accompanying lobar hemorrhage Detection by gradient-echo MRI

Based on the pathologic observation that severe cerebral amyloid angiopathy is often accompanied by multiple petechial hemorrhages, we prospectively obtained gradient-echo MRI on 15 elderly patients with lobar hemorrhage on CT. Nine of the 15 demonstrated accompanying petechial hemorrhages restricted to the cortical or corticosubcortical regions. No similar lesions were present on gradient-echo MRI in 10 elderly control patients. These findings suggest that cerebral amyloid angiopathy might be neuroradiologically diagnosed and staged during life. NEUROLOGY 1996;46: 1751-1754

A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Background and Purpose— Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods— We randomized patients with acute stroke (<12 hours) and perfusion-diffusion “mismatch” on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results— Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (±SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8±22% versus 149.1±41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline “ischemic” to 4-hour “non-ischemic” values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These “during-therapy” benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6). Conclusions— High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Diffusion-weighted imaging for the evaluation of diffuse axonal injury in closed head injury

Purpose The purpose of this work was to compare diffusion-weighted imaging (DWI) with conventional MRI in the detection of shearing injuries in acute closed head injuries. Method Twenty-five patients (19 male, 6 female) were examined within 48 h of trauma. Conventional MRI included T2-weighted fast spin echo, fluid-attenuated inversion recovery (FLAIR), and T2*-weighted gradient echo sequences. Full tensor DWI with calculation of apparent diffusion coefficient (ADC) maps was also performed. Lesions were identified and compared on all sequences. Results Four hundred twenty-seven lesions were counted by the combined use of all sequences. DWI identified 70 lesions not seen on conventional MRI. DWI identified 310 shearing injuries, followed by T2/FLAIR (n = 248) and T2* (n = 202). The majority of DWI-positive lesions showed decreased diffusion (65%). Conclusion DWI is valuable in closed head injury because it identifies additional shearing injuries not visible on T2/FLAIR or T2* sequences. Furthermore, DWI/ADC maps differentiate between lesions with decreased or increased diffusion. DWI is less sensitive than T2* imaging for detecting hemorrhagic lesions.

Comparison of Diameter and Perimeter Methods for Tumor Volume Calculation

PURPOSE Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.