A modified transorbital baboon model of reperfused stroke.

BACKGROUND AND PURPOSE: Although pathophysiological studies of focal cerebral ischemia in nonhuman primates can provide important information not obtainable in rodent models, primate experimentation is limited by considerations of cost, availability, effort, and ethics. A reproducible and quantitative model that minimizes the number of animals necessary to detect differences between treatment groups is therefore crucial. METHODS: Eight male baboons (weight, 22+/-2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid artery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (A1) proximal to the anterior communicating artery. A tightly controlled nitrous oxide-narcotic anesthetic allowed for intraoperative motor evoked potential confirmation of middle cerebral artery (MCA) territory ischemia. Animals survived to 72 hours or 10 days if successfully self-caring. Outcomes were assessed with a 100-point neurological grading system, and infarct volume was quantified by planimetric analysis of both MRI and triphenyltetrazolium chloride-stained sections. RESULTS: Infarction volumes (on T2-weighted images) were 32+/-7% (mean+/-SEM) of the ipsilateral hemisphere, and neurological scores averaged 29+/-9. All animals demonstrated evidence of hemispheric infarction, with damage evident in both cortical and subcortical regions in the MCA vascular territory. Histologically determined infarction volumes differed by <3% and correlated with absolute neurological scores (r=0.9, P:=0.003). CONCLUSIONS: Transorbital temporary occlusion of the entire anterior cerebral circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential number of animals required to distinguish between 2 treatment regimens. The anatomic distribution of the infarct and associated functional deficits offer comparability to human hemispheric strokes.

Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation.

Cerebral arteriovenous malformations (AVMs) are frequently evaluated before therapeutic embolization by superselective injection of anesthetics into individual arterial branches so as to determine whether permanent occlusion would affect eloquent function. In Experiment 1, we used this adaptation of the Wada procedure to study three right-handed adult patients with left frontal cerebral AVMs by injecting vessels in Wernicke's and Broca's areas, respectively, and assessing language functions. The results showed that superselective testing in the inferior division of the left MCA in all three patients produced a dense Wernicke's aphasia. Injections into the left frontal regions, however, resulted in right paresis in all patients, but no language deficits including no loss of fluency. In Experiment 2, Patient 2 underwent fMRI activation for spontaneous word-list generation using multi-slice echo planar BOLD techniques at 1.5 Tesla. A voxel-by-voxel comparison of rest vs activation for each task was performed with a Z-score threshold of 2.5 SD for activated voxels. There was activation in the right hemisphere in the insula, frontal operculum pars opercularis, and inferior frontal gyrus, an area homologous to Broca's area in the left hemisphere. There was also activation in the left hemisphere in the Rolandic region, but language function was unaffected during Wada testing in this area. These data suggested that features of expressive language were no longer controlled by the left frontal lobe where the AVM was located, and provided new evidence for interhemispheric re-organization under conditions of chronic neurovascular disease.

Evolution of cortical activation during recovery from corticospinal tract infarction.

BACKGROUND AND PURPOSE: Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. METHODS: Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. RESULTS: Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. CONCLUSIONS: The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.

Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.

Advances in brain tumor diagnostic imaging.

In this review I will discuss recent developments in diagnostic magnetic resonance imaging of brain neoplasms, including refinements of clinically accepted methods and experimental techniques with as yet unproven clinical applications. The techniques and applications to be discussed are (1) fast magnetic resonance imaging methods to assess tumor perfusion (blood volume), blood-brain barrier and blood-tumor barrier, and diffusion status; (2) a specialized magnetic resonance imaging method, magnetization transfer, which is sensitive to microscopic structural changes in tissue and may also be used to improve paramagnetic contrast enhancement; (3) new magnetic resonance imaging paramagnetic contrast agents including recent sensitivity and efficacy trials; and (4) magnetic resonance spectroscopy and magnetic resonance spectroscopic imaging.

Illusory contours activate specific regions in human visual cortex: evidence from functional magnetic resonance imaging.

The neural basis for perceptual grouping operations in the human visual system, including the processes which generate illusory contours, is fundamental to understanding human vision. We have employed functional magnetic resonance imaging to investigate these processes noninvasively. Images were acquired on a GE Signa 1.5T scanner equipped for echo planar imaging with an in-plane resolution of 1.5 x 1.5 mm and slice thicknesses of 3.0 or 5.0 mm. Visual stimuli included nonaligned inducers (pacmen) that created no perceptual contours, similar inducers at the corners of a Kanizsa square that created illusory contours, and a real square formed by continuous contours. Multiple contiguous axial slices were acquired during baseline, visual stimulation, and poststimulation periods. Activated regions were identified by a multistage statistical analysis of the activation for each volume element sampled and were compared across conditions. Specific brain regions were activated in extrastriate cortex when the illusory contours were perceived but not during conditions when the illusory contours were absent. These unique regions were found primarily in the right hemisphere for all four subjects and demonstrate that specific brain regions are activated during the kind of perceptual grouping operations involved in illusory contour perception.

Echo-planar imaging.

Echo-planar imaging is a fast magnetic resonance (MR) imaging technique that allows acquisition of single images in as little as 20 msec and performance of multiple-image studies in as little as 20 seconds. Echo-planar imaging achieves its speed by obtaining all spatial-encoding information after a single radio-frequency (RF) excitation. Conventional imaging requires multiple-RF excitations, separated by the repetition time (TR), to acquire this information. An "infinite" TR, routine lipid suppression, and sensitivity to magnetic susceptibility are other features of echo-planar imaging. Standard pulse sequences are used to obtain echo-planar images, which have diagnostic utility similar to that of conventional MR images. Echo-planar imaging is less sensitive to motion than is conventional MR imaging and allows imaging of rapidly changing physiologic processes such as blood flow and kinetic activity. Echo-planar imaging is opening new areas of MR imaging research and clinical applications.

High-dose single-fraction brain irradiation: MRI, cerebral blood flow, electrophysiological, and histological studies.

Radiation-induced alterations in cerebrovascular and metabolic function form the basis for the radiosurgical treatment of selected intracranial vascular malformations and tumors in human patients. However, the underlying mechanisms, temporal progression, and modifying factors involved in the radiosurgical obliteration of these intracranial lesions as well as the risks of delayed radiation injury to surrounding normal brain remain poorly understood. In this report, the rabbit brain was used as an animal model to examine the effects of high-dose single-fraction X-irradiation on magnetic resonance imaging (MRI) appearance, neurophysiologic function, and histological integrity. At approximately 10 weeks following left-hemisphere irradiation with 60 Gy (225 kVp) X rays, MRI studies showed radiation-induced changes including blood-brain barrier (BBB) perturbations in the white matter regions and the hippocampus. Significant reductions in regional cerebral blood flow (rCBF) ratios were found in the hippocampus and certain regions of the cortex in irradiated animals. However, no changes in somatosensory evoked potentials (SEP) were observed. Histological studies demonstrated telangiectatic vessels, spreading edema in the white matter, and focal regions of necrosis and hemorrhage in the irradiated cortices and hippocampi. These results demonstrate that the irradiated rabbit brain may be used as an experimental model to correlate the spatiotemporal pattern of functional changes with radiologic and histological changes in delayed radiation injury.

MRI and PET of delayed heavy-ion radiation injury in the rabbit brain.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques were used to obtain in vivo scans of delayed (30 GyE helium ion, 230 MeV/u) radiation injury in rabbit brain. T2-weighted (T2W) MRI scans demonstrated alterations that were restricted primarily to the white matter tracts and the deep perithalamic and thalamic regions. Quantitative measurements of T2 and T1 values demonstrated wide variations in absolute values. However, paired comparisons in hemibrain-irradiated rabbits revealed significant increases in T2 (p less than 0.001) and T1 (p less than 0.01) in irradiated versus unirradiated brain. Gadolinium DTPA (GdDTPA) enhanced MRI and 82Rubidium (82Rb) PET detected focal regions of blood-brain barrier (BBB) disruption restricted to the deep white matter and thalamic regions. Sequential GdDTPA enhanced MRI scans showed the spreading of the tracer from the initial site of contrast enhancement. 18Fluorodeoxyglucose (18FDG) PET studies demonstrated the markedly depressed metabolic profiles of irradiated brain. Histological findings of tissue edema and necrosis correlated well with the in vivo imaging abnormalities. These initial studies demonstrate that the irradiated rabbit brain is a suitable animal model for examining the delayed effects of radiation injury in the brain.

MR anatomy and pathology of the hypothalamus.

The hypothalamus, the ventral-most portion of the diencephalon, surrounds the anterior inferior portion of the third ventricle (Fig. 1). It functions primarily as an integrative mechanism for various autonomic and neuroendocrine activities including temperature regulation, water balance, behavior, and appetite. This pictorial essay illustrates the value of MR in depicting the normal anatomy and abnormalities of the hypothalamic region.

Acute cerebral ischemia in rabbits: correlation between MR and histopathology.

The histologic description of cerebral ischemia is complex, and within most lesions there are regional variations in degrees of neuronal cell injury, edema, and neuropil disruption. These parameters of tissue injury were analyzed histopathologically in transient and permanent experimental cerebral ischemia in 15 rabbits and the results were spatially correlated with MR images of pre- and postmortem (formalin-fixed) brains. MR was performed at 1.5 T (eight animals) and at 0.38 T (seven animals). Areas of high signal on T2-weighted MR images were closely correlated with histologic signs of cytotoxic glial edema and with disruption of the neuropil (widening of the interstitial spaces in the background matrix of glial and neuronal cellular processes), but MR tended to underestimate the extent of ischemic neuronal injury, especially low-grade histologic changes (mild neuronal shrinkage and nuclear basophilia). Low-grade ischemic neuronal changes were often found in the penumbra zone of ischemic lesions in areas that appeared normal on T2-weighted MR. High-grade neuronal injury was also seen occasionally in areas of normal signal on MR, especially in the striatum. No significant differences were seen on T2-weighted MR between the experimental groups with respect to transient vs permanent occlusion, in vivo vs in vitro MR, and low vs high magnetic field. In the setting of suspected acute cerebral ischemia, an abnormal T2-weighted MR study often underestimates the extent of neuronal ischemic injury, especially potentially reversible injury; and a normal MR study does not completely exclude significant neuronal ischemic injury.

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury.

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.

Cerebral blood flow evaluation of arteriovenous malformations with stable xenon CT.

Twenty patients with supratentorial arteriovenous malformations (AVMs) were evaluated with angiography, conventional CT, and stable xenon CT to determine cerebral blood flow. Contralateral and ipsilateral regions of interest relative to the AVM were evaluated from cerebral blood flow maps and correlated with angiography. A significant decrease in cerebral blood flow was observed in the ipsilateral cortical gray matter adjacent to the AVM relative to the corresponding contralateral cortex (mean difference = 9.52 ml/100 g/min, p less than .01). The larger AVMs (greater than 8 cm3) were associated with a more marked decrease with a mean difference of 12.22 ml/100 g/min (p less than .02). Regions of interest were also chosen on the basis of angiographic findings, which suggested areas of decreased flow. Comparison of these areas with analogous contralateral areas also showed a significant decline in cerebral blood flow (mean difference = 8.86 ml/100 g/min); this decline was greater with larger AVMs (volume greater than 8 cm3), which had a mean difference of 11.38 ml/100 g/min (p less than .01). Our correlative study enabled us to pinpoint the regions most likely to have reduced flow from an AVM.

Intracranial vascular malformations: imaging of charged-particle radiosurgery. Part I. Results of therapy.

Twenty-four patients with intracranial vascular malformations were examined before and after helium ion radiosurgical treatment with angiography, computed tomography (CT), and magnetic resonance (MR) imaging. Twenty patients had high-flow arteriovenous malformations (AVMs). After treatment 18 of 20 AVMs (90%) showed a significant reduction in size on angiograms or MR images. Eleven of 20 (55%) had complete resolution on angiograms or MR images, 35% had partial resolution, and 10% showed no size change. Before treatment, the size range of the AVMs was 0.86-383 cm3 (median, 21.7 cm3). Smaller AVMs (less than 8 cm3) were more likely to resolve completely than medium-sized AVMs (8-64 cm3) or larger AVMs (greater than 64 cm3). Four additional patients had slow-flow vascular malformations: One had a venous angioma; one, a probable cavernous hemangioma; and two, malformations that were not seen on angiograms. CT proved inaccurate in demonstrating the boundaries of the AVM after treatment because it showed persistent contrast enhancement even when the AVM was completely obliterated on angiograms. MR imaging and angiography were complementary in the evaluation of therapeutic results and should be the primary modalities in the examination of patients with AVMs.

Intracranial vascular malformations: imaging of charged-particle radiosurgery. Part II. Complications.

Seven of 24 patients with intracranial vascular malformations who were treated with helium-ion Bragg-peak radiosurgery had complications of therapy. New symptoms and corresponding radiologic abnormalities developed 4-28 months after therapy. Five patients had similar patterns of white matter changes and mass effect on computed tomographic scans and magnetic resonance images. The abnormalities were centered in the radiation field. Gray matter changes and abnormal enhancement in the thalamus and hypothalamus outside the radiation field developed in one patient. This patient also had vasculopathic changes on angiograms. Rapidly progressive large vessel vasculopathy developed in another patient and caused occlusion of major vessels. Thus, different mechanisms may be involved in the complications of heavy-ion radiosurgery.

Mamillary body atrophy in Wernicke's encephalopathy: antemortem identification using magnetic resonance imaging.

We used magnetic resonance imaging to determine the volume of the mamillary bodies in 9 patients with chronic Wernicke's encephalopathy, 7 patients with presumed Alzheimer's disease, and 37 control patients. The mean mamillary body volume (+/- standard error) was 21.3 +/- 5.8 mm3 in Wernicke patients, 40.1 +/- 3.7 mm3 in Alzheimer patients, and 51.7 +/- 2.5 mm3 in control patients. Seven of nine (78%) patients with chronic Wernicke's encephalopathy had smaller mamillary bodies than 36 of 37 control patients and 7 of 7 Alzheimer patients. The decrease in mamillary body volume was related neither to patient age nor to degree of ventricular enlargement, and most likely reflects the mamillary body atrophy that is grossly apparent at autopsy in up to 81% of Wernicke patients. This technique provides a means of identifying the most specific macroscopic lesion of chronic Wernicke's encephalopathy.

Combined surface display and reformatting for the three-dimensional analysis of tomographic data.

Radiologic examinations increasingly are based on sequences of cross-sectional images. In current clinical applications, the three-dimensional (3D) relationships contained in these examinations must be inferred by the observer through analysis of multiple two-dimensional (2D) images. In this article, methods for the direct display of 3D gray-level data are investigated. In the chosen approach, the 3D presentation of bone and skin surface serves to orient the viewer, while planar reformation and/or transparent projections can be applied for the assessment of soft-tissue structures in regions of interest. The resulting images represent the original image data in a way that is more suitable for observation of 3D relationships than the conventional cross-sectional viewing mode. This may facilitate the diagnostic process and enhance the interpretability of the images. Routine clinical application of this technique requires special computer hardware. Research applications, however, can be performed within tolerable times (10-30 sec/view) with computers found in radiologic research environments.

Glucose metabolism in human gliomas: correspondence of in situ and in vitro metabolic rates and altered energy metabolism.

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by fluorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I-III gliomas had a glucose consumption rate of 2-3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by 18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measured in situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the glioma-derived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomas in situ and (2) are significantly altered in several aspects of their glycolytic metabolism.

NMR imaging of intracranial hemorrhage.

Twenty-one intracranial hemorrhagic lesions were imaged at 0.15 and 0.6 T using inversion recovery (IR), spin echo (SE), and multiple SE (Carr-Purcell-Meiboom-Gill, CPMG) pulse sequences. Two subarachnoid hemorrhages (SAH), nine acute intraparenchymal hemorrhages (IPH), ten chronic IPH, and one subdural hematoma were studied. Acute SAH could not be identified on the T1-weighted, IR images but was clearly seen on a T2-weighted, CPMG image. Acute (7 days or less) intraparenchymal hematoma showed signal intensity on IR and CPMG images similar to white matter. The T1 and T2 times of acute intraparenchymal hematoma were also similar to white matter. Some small acute hematomas could not be distinguished from white matter on IR and CPMG images. Acute hemorrhagic tissue showed image intensities and relaxation times similar to gray matter. All acute hemorrhages were identified on CT. Chronic IPH lesions (14 days or more) showed high signal intensity, greater than white matter, on IR, SE, and CPMG images. The T1 of the chronic lesions was similar to the acute lesions but T2 was significantly longer (p less than 0.05). Available evidence suggests that the nonspecificity of acute IPH signal and relaxation times may not be restricted to our pulse sequences or magnetic field strengths.

Central pontine myelinolysis: demonstration by nuclear magnetic resonance.

An alcoholic, hyponatremic woman developed central pontine myelinolysis (CPM) and improved from a decerebrate, comatose state to alertness and full ambulation. NMR, using inversion-recovery and spin-echo pulse sequences, was performed sequentially from 4 weeks to 8 months after onset of symptoms and revealed a well-defined lesion with prolonged relaxation times. The lesion was anatomically consistent with CPM and was initially also visualized by CT. NMR showed no definite temporal change in the qualitative appearance of the lesion until the 8-month scan; however, quantitatively, a reduction of relaxation times was noted with each serial study.