Diffusion-weighted imaging of the orbit.

Orbital lesions compose a heterogeneous group of pathologies that often present with non-specific imaging findings on conventional magnetic resonance imaging (MRI) sequences (T1-and T2-weighted). Accordingly, the application of diffusion MRI offers an opportunity to further distinguish between lesions along this spectrum. Diffusion-weighted imaging (DWI) represents the simplest and most frequent clinically utilised diffusion imaging technique. Recent advances in DWI techniques have extended its application to the evaluation of a wider spectrum of neurological pathology, including orbital lesions. This review details the manifestations of select orbital pathology on DWI and underscores specific situations where diffusion imaging allows for increased diagnostic sensitivity compared to more conventional MRI techniques. These examples also describe preferred management for orbital lesions identified by DWI.

ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology.

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.

Alterations in the Magnetoencephalography Default Mode Effective Connectivity following Concussion.

BACKGROUND AND PURPOSE: Magnetoencephalography is sensitive to functional connectivity changes associated with concussion. However, the directional influences between functionally related regions remain unexplored. In this study, we therefore evaluated concussion-related magnetoencephalography-based effective connectivity changes within resting-state default mode network regions. MATERIALS AND METHODS: Resting-state magnetoencephalography was acquired for 8 high school football players with concussion at 3 time points (preseason, postconcussion, postseason), as well as 8 high school football players without concussion and 8 age-matched controls at 2 time points (preseason, postseason). Time-series from the default mode network regions were extracted, and effective connectivity between them was computed for 5 different frequency bands. The default mode network regions were grouped into anterior and posterior default mode networks. The combined posterior-to-anterior and anterior-to-posterior effective connectivity values were averaged to generate 2 sets of values for each subject. The effective connectivity values were compared using a repeated measures ANOVA across time points for the concussed, nonconcussed, and control groups, separately. RESULTS: A significant increase in posterior-to-anterior effective connectivity from preseason to postconcussion (corrected P value = .013) and a significant decrease in posterior-to-anterior effective connectivity from postconcussion to postseason (corrected P value = .028) were observed in the concussed group. Changes in effective connectivity were only significant within the delta band. Anterior-to-posterior connectivity demonstrated no significant change. Effective connectivity in the nonconcussed group and controls did not show significant differences. CONCLUSIONS: The unidirectional increase in effective connectivity postconcussion may elucidate compensatory processes, invoking use of posterior regions to aid the function of susceptible anterior regions following brain injury. These findings support the potential value of magnetoencephalography in exploring directional changes of the brain network following concussion.

MRI-Based Deep-Learning Method for Determining Glioma MGMT Promoter Methylation Status.

BACKGROUND AND PURPOSE: O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation confers an improved prognosis and treatment response in gliomas. We developed a deep learning network for determining MGMT promoter methylation status using T2 weighted Images (T2WI) only. MATERIALS AND METHODS: Brain MR imaging and corresponding genomic information were obtained for 247 subjects from The Cancer Imaging Archive and The Cancer Genome Atlas. One hundred sixty-three subjects had a methylated MGMT promoter. A T2WI-only network (MGMT-net) was developed to determine MGMT promoter methylation status and simultaneous single-label tumor segmentation. The network was trained using 3D-dense-UNets. Three-fold cross-validation was performed to generalize the performance of the networks. Dice scores were computed to determine tumor-segmentation accuracy. RESULTS: The MGMT-net demonstrated a mean cross-validation accuracy of 94.73% across the 3 folds (95.12%, 93.98%, and 95.12%, [SD, 0.66%]) in predicting MGMT methylation status with a sensitivity and specificity of 96.31% [SD, 0.04%] and 91.66% [SD, 2.06%], respectively, and a mean area under the curve of 0.93 [SD, 0.01]. The whole tumor-segmentation mean Dice score was 0.82 [SD, 0.008]. CONCLUSIONS: We demonstrate high classification accuracy in predicting MGMT promoter methylation status using only T2WI. Our network surpasses the sensitivity, specificity, and accuracy of histologic and molecular methods. This result represents an important milestone toward using MR imaging to predict prognosis and treatment response.

Prevalence and Incidence of Microhemorrhages in Adolescent Football Players.

BACKGROUND AND PURPOSE: SWI is an advanced imaging modality that is especially useful in cerebral microhemorrhage detection. Such microhemorrhages have been identified in adult contact sport athletes, and the sequelae of these focal bleeds are thought to contribute to neurodegeneration. The purpose of this study was to utilize SWI to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are significantly greater than those of adolescent noncontact athletes. MATERIALS AND METHODS: Preseason and postseason SWI was performed and evaluated on 78 adolescent football players. SWI was also performed on 27 adolescent athletes who reported no contact sport history. Two separate one-tailed Fisher exact tests were performed to determine whether the prevalence and incidence of microhemorrhages in adolescent football players are greater than those of noncontact athlete controls. RESULTS: Microhemorrhages were observed in 12 football players. No microhemorrhages were observed in any controls. Adolescent football players demonstrated a significantly greater prevalence of microhemorrhages than adolescent noncontact controls (P = .02). Although 2 football players developed new microhemorrhages during the season, microhemorrhage incidence during 1 football season was not statistically greater in the football population than in noncontact control athletes (P = .55). CONCLUSIONS: Adolescent football players have a greater prevalence of microhemorrhages compared with adolescent athletes who have never engaged in contact sports. While microhemorrhage incidence during 1 season is not significantly greater in adolescent football players compared to adolescent controls, there is a temporal association between playing football and the appearance of new microhemorrhages.

Evaluating the impact of spatio-temporal smoothness constraints on the BOLD hemodynamic response function estimation: an analysis based on Tikhonov regularization.

Recently we have proposed the use of Tikhonov regularization with temporal smoothness constraints to estimate the BOLD fMRI hemodynamic response function (HRF). The temporal smoothness constraint was imposed on the estimates by using second derivative information while the regularization parameter was selected based on the generalized cross-validation function (GCV). Using one-dimensional simulations, we previously found this method to produce reliable estimates of the HRF time course, especially its time to peak (TTP), being at the same time fast and robust to over-sampling in the HRF estimation. Here, we extend the method to include simultaneous temporal and spatial smoothness constraints. This method does not need Gaussian smoothing as a pre-processing step as usually done in fMRI data analysis. We carried out two-dimensional simulations to compare the two methods: Tikhonov regularization with temporal (Tik-GCV-T) and spatio-temporal (Tik-GCV-ST) smoothness constraints on the estimated HRF. We focus our attention on quantifying the influence of the Gaussian data smoothing and the presence of edges on the performance of these techniques. Our results suggest that the spatial smoothing introduced by regularization is less severe than that produced by Gaussian smoothing. This allows more accurate estimates of the response amplitudes while producing similar estimates of the TTP. We illustrate these ideas using real data.

Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan.

BACKGROUND AND PURPOSE: Therapeutic intervention during the early stages of an intracerebral hemorrhage (ICH) might have value in improving clinical outcomes. During the 73-site International Recombinant Activated Factor VII Intracerebral Hemorrhage Trial, CT techniques were used to monitor the change in hematoma volume in response to treatment. The use of CT imaging technology served 3 functions: to provide accurate measurements of the change in hematoma volume, intraventricular volume (IVH), and edema volume; to evaluate the use of CT scans as a predictor of patient outcomes; and to demonstrate that hematoma volume can serve as a surrogate marker for ICH clinical progression. METHODS: The multicenter clinical trial received institutional review board approval and obtained informed consent from the patient or a legally acceptable representative (waived in a few cases of incapacity, according to local and national regulations). CT scans were used to quantify volumes of hemorrhage and to monitor evolution over a 72-hour period in patients with ICH treated with placebo or 40, 80, or 160 microg/kg of recombinant activated factor VII (rFVIIa). CT image data were transmitted digitally to an imaging laboratory and analyzed by 2 readers masked to patient and treatment data, by using Analyze software, a fully integrated toolkit for interactive display, processing, and measurement of biomedical image data. The use of this software enabled the evaluation of intraclass variability of CT scan interpretations. RESULTS: Interpretations of ICH and IVH volumes of CT scans in patients treated in this study showed minimal intraclass variability. Variability was greatest for interpretations of edema volume. CONCLUSION: These CT assessments of lesions could have value in future early hemostatic interventions in ICH patients.

Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American-Diabetes Heart Study MIND.

BACKGROUND AND PURPOSE: Rates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes-associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population. MATERIALS AND METHODS: African Americans with type 2 diabetes enrolled in the African American-Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models. RESULTS: Lower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume. CONCLUSIONS: Markers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population.

MRI identification of early white matter injury in anoxic-ischemic encephalopathy.

BACKGROUND: Anoxic-ischemic encephalopathy (AIE) affects the gray matter more than the white matter. Recent animal experiments suggest that the white matter is more sensitive to ischemia than previously thought. The authors describe the MRI findings in seven patients with AIE who demonstrate early preferential involvement of the white matter. MATERIALS AND METHODS: A retrospective case series study was performed, including seven patients with AIE who underwent MRI of the brain within 7 days of insult. Demographic information, type of insult, clinical examination findings, EEG findings, and clinical outcome were obtained. MRI studies were reviewed with specific attention to the cortex, deep gray matter, and the white matter structures. Mean apparent diffusion coefficient (ADC) was calculated in regions of interest placed in the cerebellar hemispheres, putamen, thalamus, splenium of corpus callosum, centrum semiovale, and medial frontal cortex. RESULTS: The causes of AIE were cardiac arrhythmias in two patients, myocardial infarction in one, drug overdose in two, carbon monoxide poisoning in one, and respiratory failure and sepsis in one. The median time to MRI was 2.5 days. Symmetric areas of restricted diffusion were found in the periventricular white matter tracts (7/7 patients), the corpus callosum (6/7 patients), internal capsule (5/7 patients), and the subcortical association fibers (3/7 patients). ADC maps confirmed the restricted diffusion. Gray matter involvement was seen in three patients, and was more prominent on conventional imaging sequences compared with diffusion-weighted imaging. A subtle decrease in mean ADC was seen in cortex. CONCLUSIONS: Prominent, symmetric restricted diffusion can occur early after AIE in white matter, whereas gray matter involvement may be less prominent. Further studies involving a larger sample and serial imaging are required to confirm these preliminary findings.

Functional activation of the left amygdala and hippocampus during associative encoding.

The human hippocampus is critical to episodic encoding, but the role of the amygdala in memory is less clear. Animal research suggests a role for the amygdala in associative memory, but this has not been examined systematically in humans. Using fMRI, we compared amygdala and hippocampus activation for seven healthy subjects during two visual encoding tasks: serially presented single faces and faces presented as pairs. Single faces activated bilateral hippocampi, but not the amygdala. Paired faces activated bilateral amygdala, but only the left hippocampus. Subtraction of the two conditions revealed greater activation within the left amygdala and hippocampus during paired face encoding, suggesting that associative encoding activates a left-lateralized limbic network including the hippocampus and amygdala.

Mapping of secondary somatosensory cortex activation induced by vibrational stimulation: an fMRI study.

Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a vibratory stimulus applied to the pad of the first finger of the left hand. The data was normalized to a standard atlas, and individual and group statistical parametric maps were computed. Robust bilateral activation was demonstrated in the secondary somatosensory cortex (SII), indicating a bilateral representation of SII in humans. Greater maxima and activation volumes were achieved in contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay for probing the nature and function of SII in vivo.

Gender effects on odor-stimulated functional magnetic resonance imaging.

On standardized tests of odor identification and odor detection, women tend to score better than men at nearly all age groups. We sought to determine if these findings would translate to differences between the sexes in the volume of activated brain when odors are presented to subjects as the stimulants for functional magnetic resonance imaging (FMRI) experiments. The activation maps of eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years) were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D. 6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T. Olfactory stimuli were delivered to the patients in a passive fashion using a Burghart OM4-B olfactometer with a nose piece inserted into the patients' nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol alternating with hydrogen sulfide) that were selective for olfactory nerve stimulation in the nose. The odorants were delivered to both nostrils for 1 s every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient received room air at the same flow rate. The women's group-averaged activation maps showed up to eight times more activated voxels than men for specific regions of the brain (frontal and perisylvian regions). The left and right inferior frontal regions showed a statistically significant increase in activation in women at p<0.01. In general, more women showed activation than men. The results suggest that (1) FMRI activation maps in subject groups can demonstrate correlates to psychophysical tests of olfaction, and (2) one must control for gender when performing odor-stimulated FMRI experiments.

Multiple sclerosis: comparison of trace apparent diffusion coefficients with MR enhancement pattern of lesions.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging and the trace apparent diffusion coefficient (ADC) provide important structural information about tissues. The purpose of this study was to investigate the relationship between trace ADC values and the enhancement pattern of multiple sclerosis (MS) lesions. METHODS: Ninety-six lesions, identified in 24 patients with MS, were characterized by their enhancement pattern on contrast-enhanced T1-weighted MR images. There were 57 nonenhancing lesions (NELs), 28 homogeneously enhancing lesions (HELs), and 11 ring-enhancing lesions (RELs). The trace ADC means for each type of lesion and for normal-appearing white matter (NAWM) were calculated and compared using Student's t-test. RESULTS: The mean trace ADC values for HELs (mean, 7.7 x 1(-10) m2s(-1); SD, 1.4 x 10(-10) m2s(-1)) were less than those for RELs (mean, 1.2 x 10(-9) m2s(-1); SD, 3.5 x 10(-10)m2s(-1)) and NELs (mean, 1.3 x 10(-9) m2(s-1); SD, 2.6 x 10(-10) m2(s-1)). There was a significant difference between the mean trace ADC values of HELs and RELs as well as between those for HELs and NELs. There was also a significant difference in the mean trace ADC values between all lesion types and NAWM (mean, 6.9 x 10(-10) m2s(-1); SD, 5.0 x 10(-11) m2s(-1)). CONCLUSION: We found a predictable relationship between mean trace ADC and the pattern of enhancement in MS lesions, corresponding to reported histopathologic differences in myelination between lesion types and magnetization transfer ratios.

Computing diffusion rates in T2-dark hematomas and areas of low T2 signal.

BACKGROUND AND PURPOSE: It has been suggested that restricted diffusion is present within hematomas with intact red cell membranes; however, computing apparent diffusion coefficient (ADC) values in areas of low T2 signal can be problematic. Our purpose was to show the pitfalls of measuring diffusion within hematomas with intracellular blood products and to present a framework based on the properties of expected values for computing ADC values from regions with signal intensities close to that of the background noise (ie, T2-dark hematomas). METHODS: Twelve patients with intracranial hematomas who had undergone diffusion imaging were retrospectively identified during a 2-year period (four intracellular oxyhemoglobin, seven intracellular deoxyhemoglobin, one intracellular methemoglobin). Regions of interest were drawn on the hematomas, the contralateral white matter, and over the background. ADC values were computed using a variety of methods: 1) using expected values incorporating the variance of the background, 2) computing the mean of the regions of interest before taking the natural log, 3) masking negative values, and 4) masking the background at 0.5% increments from 0.5 to 5.5% and including the masked voxels (an intrinsically flawed method). Two-tailed Student's t test was performed between the white matter and the hematoma ADC values. RESULTS: There was no statistically significant difference between the hematomas and the white matter for methods 1 through 3 (P = .14, P = .23, and P = .83, respectively). Only method 4 revealed a statistically significant difference, beginning at 0.5% masking (P = .04) and becoming progressively more significant with increased masking (P = 4.14 x 10(-7) at 5.5% masking). The effect of masking was limited to the T2-dark hematomas. CONCLUSION: There is no restriction of diffusion for in vivo hematomas with intracellular blood products. The T2 blackout effect for T2-dark hematomas on diffusion-weighted images should not be interpreted as fast diffusion. The method of expected values can be used to obtain measurements for regions with signal intensities near the background noise. Using literature values for RBC self-diffusion, we computed lower limits of diffusion for hematomas with intracellular blood products to be 0.3 x 10(-3) mm2/s.

Inflammatory pseudotumor of the maxillary sinus in a 15-year-old boy.

Inflammatory pseudotumor is a benign neoplasm composed of fibroblasts, histiocytes, and inflammatory cells. Its occurrence in the paranasal sinuses is rare. We report a case of a 15-year-old boy with a maxillary sinus inflammatory pseudotumor that simulated an aggressive neoplasm on CT scan.

Decreased BOLD functional MR activation of the motor and sensory cortices adjacent to a glioblastoma multiforme: implications for image-guided neurosurgery.

A patient with a glioblastoma multiforme and mild sensorimotor deficits had significantly less activation of the motor and sensory cortices on the side with the tumor than on the contralateral side on blood oxygen level-dependent (BOLD) functional MR images. This difference, which may be due to pressure effects or loss of vascular autoregulation, should be considered in preoperative planning in which BOLD functional MR imaging is used to identify eloquent cortices to be avoided during brain tumor surgery.

The effect of brain tumors on BOLD functional MR imaging activation in the adjacent motor cortex: implications for image-guided neurosurgery.

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging data coregistered to a neurosurgical navigation system have been proposed as guides for the resection of brain tumor in or adjacent to eloquent cortices. The purpose of this study was to compare data obtained from the side of the brain affected by tumor with the contralateral side and to determine if there are physiological limitations of fMR imaging in accurately determining the location of the primary motor cortex. METHODS: Ten patients with tumors in or directly adjacent to the motor cortex were studied with fMR imaging (finger-tapping paradigm). fMR imaging data were analyzed using multiple R values. These data were coregistered to a real-time intraoperative neurosurgical navigation system. RESULTS: Significant variability of motor cortex activation patterns was noted among individual patients. The activation volumes on the side of the tumor were significantly smaller compared with the contralateral side for all tumors not previously resected (0.66+/-0.47). This was most pronounced in glioblastomas (0.27+/-0.21). We propose that these differences were caused by a loss of autoregulation in the tumor vasculature of glioblastomas and venous effects. CONCLUSION: Notwithstanding the differences noted, the motor cortex was identified successfully in all patients. This was confirmed by intraoperative physiological identification of the motor cortex and a lack of postoperative neurologic deficit.

Automated CT segmentation and analysis for acute middle cerebral artery stroke.

BACKGROUND AND PURPOSE: The quantitative nature of CT should make it amenable to semiautomated analysis using modern neuroimaging methods. The purpose of this study was to begin to develop automated methods of analysis of CT scans to identify putative hypodensity within the lentiform nucleus and insula in patients with acute middle cerebral artery stroke. METHODS: Thirty-five CT scans were retrospectively selected from our CT archive (scans of 20 normal control participants and 15 patients presenting with acute middle cerebral artery stroke symptoms). The DICOM data for each participant were interpolated to a single volume, scalp stripped, normalized to a standard atlas, and segmented into anatomic regions. Voxel densities in the lentiform nucleus and insula were compared with the contralateral side at P <.01 using the Wilcoxon two-sample rank sum statistic, corrected for spatial autocorrelation. RESULTS: The quality of the registration for the anatomic regions was excellent. The control group had two false-positive results. The patient group had two false-negative results in the lentiform nucleus, two false-negative results in the insular cortex, and one false-positive finding for the insular cortex. The remainder of the infarcts were correctly identified. The original clinical reading, performed at the time of presentation, produced five false-negative interpretations for the patient group, all of which were correctly identified by the automated algorithm. CONCLUSION: We present an automated method for identifying potential areas of acute ischemia on CT scans. This approach can be extended to other brain regions and vascular territories and may aid in the interpretation of CT scans in cases of hyperacute stroke.

Incidence and clinical significance of frontal sinus or orbital entry during pterional (frontotemporal) craniotomy.

BACKGROUND AND PURPOSE: Frontal sinus entry, orbital entry, or both may occur during pterional craniotomy for microsurgical clipping of aneurysms. We sought to determine the incidence and clinical significance of these findings on postoperative CT scans. METHODS: Eighty-two postoperative CT scans of the head obtained from 81 patients (64 women, 17 men; age range, 25-80 years) were retrospectively reviewed over a 1-year period. These scans were reviewed independently by two blinded neuroradiologists for the presence and degree of orbit and frontal sinus entry that may have occurred during craniotomy. Clinical charts, operative notes, and discussions with the patients' neurosurgeons were reviewed to determine the clinical management and significance of these findings. RESULTS: Of the total 82 craniotomies reviewed, 77 (94%) had been performed via the pterional approach (43 right, 34 left). Twenty-three (30%) of these 77 studies revealed some evidence of penetration into the orbit or frontal sinus (orbit=65.2% [15/23]; frontal sinus=30.4% [7/23]; both=4.4% [1/23]). Only five of 16 patients with radiographic orbital penetration had evidence of involvement of intraorbital contents (ie, thickened lateral rectus, fat herniation, intraorbital air). Chart review revealed no complication or change in management. Of the seven patients with frontal sinus entry, three had mucosal exenteration and packing with antibiotic-coated gelfoam. No delayed complications (ie, persistent fever, mucocele, cerebrospinal fluid leak, air leak, or meningitis) were identified (follow-up period, 18-29 months). CONCLUSION: Frontal sinus or orbital entry is not uncommon after pterional craniotomy, but the incidence of immediate complications is rare.

Traumatic brain injury: diffusion-weighted MR imaging findings.

BACKGROUND AND PURPOSE: Diffuse axonal injury (DAI) accounts for a significant portion of primary intra-axial lesions in cases of traumatic brain injury. The goal of this study was to use diffusion-weighted MR imaging to characterize DAI in the setting of acute and subacute traumatic brain injury. METHODS: Nine patients ranging in age from 26 to 78 years were examined with conventional MR imaging (including fast spin-echo T2-weighted, fluid-attenuated inversion-recovery, and gradient-echo sequences) as well as echo-planar diffusion-weighted MR imaging 1 to 18 days after traumatic injury. Lesions were characterized as DAI on the basis of their location and their appearance on conventional MR images. Trace apparent diffusion coefficient (ADC) maps were computed off-line with the diffusion-weighted and base-line images. Areas of increased signal were identified on the diffusion-weighted images, and regions of interests were used to obtain trace ADC values. RESULTS: In the nine patients studied, isotropic diffusion-weighted images showed areas of increased signal with correspondingly decreased ADC. In one case, decreased ADC was seen 18 days after the initial event. CONCLUSION: Decreased ADC can be demonstrated in patients with DAI in the acute setting and may persist into the subacute period, beyond that described for cytotoxic edema in ischemia.