(Stroke. 1996;27:1648-1656.)
© 1996 American Heart Association, Inc.
Articles |
the Department of Neurology, Medical Center of Central MassachusettsMemorial (Y.H., M.F.); Department of Biomedical Engineering, Worcester Polytechnic Institute (J.E.F., L.L.L., C.H.S.); and the Departments of Neurology (M.F.) and Radiology (C.H.S., M.F.), University of Massachusetts Medical School, Worcester, Mass; the Department of Neuropathology, Henry Ford Hospital, Detroit, Mich (J.A.G., K-F. L., J.H.G.); and the Cerebrovascular Division, Research Institute, National Cardiovascular Center, Osaka, Japan (Y.H.).
| Abstract |
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Methods Fasted rats were given regular insulin (15 IU/kg IP). Rats were subjected to 15 minutes (n=5) and 50 minutes (n=5) of temporary severe hypoglycemia, causing a transiently isoelectric electroencephalogram (EEG). ADC mapping was performed every 30 seconds beginning at the onset of isoelectricity for 8.5 minutes. ADC maps were also obtained later during the isoelectric EEG period and 10, 20, 30, and 40 minutes after glucose infusion. Control images were obtained from a separate group of animals suffering cardiac arrest (n=5).
Results Abnormal ADC values were not observed before the onset of cerebral isoelectricity, except for isolated areas in the cortex and periventricular regions. Cortical ADC values globally declined at the onset of EEG isoelectricity. The ADC decline spread to subcortical regions within a few minutes. During the isoelectric period, significant declines of ADC values (27% to 45%) occurred in the entire brain. Glucose infusion normalized most of the ADC changes, even after a 50-minute period of isoelectricity.
Conclusions ADC mapping during hypoglycemia clearly demonstrates changes likely related to energy depletion. Most of these ADC declines were reversible. Hypoglycemia is a condition known to be associated with shrinkage of the extracellular space. These observations support the hypothesis that ADC reductions observed in ischemia are also related to shifts of water from the extracellular to the intracellular compartment.
Key Words: hypoglycemia magnetic resonance imaging rats
| Introduction |
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Glucose deprivation leads to severe brain energy failure and a reduction of cell membrane ionic pump activity, as does anoxia/ischemia, but the topographical and temporal evolution of hypoglycemic brain damage are different from anoxia/ischemia. A positive relationship between the density of neuronal necrosis and the duration of EEG isoelectricity is well documented in experiments of insulin-induced hypoglycemia.19 20 21 22 23 24 25 A drastic reduction of ECS volume to approximately 50% of normal (ie, the shift of water from the ECS to the ICS due to membrane ionic pump failure) occurs at the onset of the isoelectric EEG phase with insulin-induced hypoglycemia.26 In this study we evaluated topographical and temporal changes in the ADC of brain water with the rat model of insulin-induced hypoglycemia to answer the following questions: (1) Do generalized cerebral ADC reductions coincide with cerebral isoelectricity? (2) Are the changes in ADC values reversible by restoring the glucose level after various durations of EEG isoelectricity? and (3) Would ADC measurements after recovery from hypoglycemia predict the extent of neuronal damage? To answer these questions, multislice ADC mapping was serially performed with the aid of echo-planar diffusion-weighted MRI in animals subjected to transient, severe hypoglycemia with concomitant continuous EEG monitoring.
| Materials and Methods |
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Control/Cardiac Arrest Group
Five animals served as controls, and brain ADC values after cardiac arrest were measured for comparison with those in the hypoglycemic animals. After baseline physiological measurements, the head of the animal was fixed inside the 1H "birdcage" coil with a tooth bar and ear bars. Neonatal electrocardiographic electrodes were attached to the left forelimb and both hindlimbs for electrocardiographic monitoring. Body temperature was controlled at 37±0.5°C with the use of a rectal probe and a feedback-regulated heated air flow system that completely surrounded the animal. Baseline multislice ADC mapping was performed before cardiac arrest. The animals were then killed in the imaging magnet by a rapid intravenous injection of 0.4 mL of 4 mol/L potassium chloride via the femoral catheter, and ADC mapping was performed 15 and 45 minutes after cardiac arrest. We documented brain temperature changes in a separate group of three rats after inducing cardiac arrest under the same experimental conditions without MRI. The frontoparietal cranium was exposed by a midsagittal incision, and two burr holes, 1.3 mm in diameter, were made in the right parietal skull at 0.5 mm caudal, 3.5 mm and 5.0 mm lateral to the bregma. Small copper-constantan thermocouples, 0.003 inch in diameter (type IT-23, Physitemp Instruments), were inserted into the right caudoputamen and the frontoparietal cortex and fixed to the frontoparietal bone with dental cement. The temperatures in these superficial and deep brain structures were continuously monitored for 45 minutes after cardiac arrest with the use of a scanning thermocouple thermometer with 0.1°C resolution (Cole-Parmer Instrument Co).
Hypoglycemia Groups
After arterial blood sampling for baseline glucose measurements, animals were given 15 IU/kg of regular insulin (NOVO Industries) intraperitoneally. Animals were then tracheostomized and intubated with PE-240 tubing. The parietal cranium was exposed by a midcoronal incision, and two burr holes, 1.2 mm in diameter, were made in the right and left parietal regions at 1.5 mm rostral and 2.5 mm lateral to the lambda. Ag-AgCl ball electrodes were placed in the burr holes and fixed with dental cement. The reference electrode was placed on the ear lobe, and the nasal base was grounded by an Ag-AgCl plate electrode. The head of the animal was then fixed inside a 1H birdcage imaging coil with tooth bar and ear bars. Animals were immobilized with tubocurarine chloride (0.5 mg/kg IV) and mechanically ventilated at a rate adjusted to maintain PaO2 of 90 mm Hg or greater and PaCO2 of 35 to 45 mm Hg. To maintain the anesthetic state, animals inhaled 1% isoflurane throughout the experiment. The arterial pH was maintained between 7.35 and 7.45 with sodium bicarbonate.
The EEG was continuously monitored and graded as follows: stage I, normal; stage II, slowing to the theta to delta ranges; stage III, rhythmic high-amplitude delta slowing; stage IV, more slowing with a suppression phase; and stage V, isoelectricity.25 We began ADC mapping 1.5 hours after the insulin injection. Then we waited for the development of EEG stages IV and V. At the onset of the stage IV EEG pattern, we administered atropine sulfate (0.1 mg IV) to prevent cardiac arrhythmia. When the suppression phase became prolonged to 2.0 seconds during stage IV, whole brain ADC mapping was performed every 30 seconds for 8.5 minutes to detect ADC changes at the onset of the isoelectricity. The blood glucose concentration was restored at 15 minutes (Iso15 group; n=5) or 50 minutes (Iso50 group; n=5) after the onset of EEG isoelectricity with an infusion of 0.4 mL of 50% glucose, given manually over 1 minute. Twenty-five minutes after the glucose injection, 0.3 mL of the 50% glucose solution was also given to avoid a delayed decline of the blood glucose level.
ADC maps were obtained 10 minutes after the onset of isoelectricity in the Iso15 group and 15 and 45 minutes after the onset of isoelectricity in the Iso50 group. During the recovery period, follow-up ADC maps were also obtained 10, 20, 30, and 40 minutes after the initial glucose infusion. When a blood pressure increase occurred from the resting mean value of 90 to 120 mm Hg, the mean blood pressure was held between 100 and 130 mm Hg by arterial bleeding. Blood was collected from the central venous catheter into a heparinized syringe and was immediately reinfused if the pressure fell. After the last ADC mapping during the recovery phase was accomplished, transcardiac perfusion fixation of the brain was performed with 4% paraformaldehyde. After immersion fixation of the decapitated head in 4% paraformaldehyde for 24 hours, the brain was removed. Brain specimens were sectioned coronally at 3-mm intervals before tissues were embedded in paraffin. Histology sections were cut in 5-µm slices and stained with hematoxylin-eosin and GFAP. Three additional rats without insulin administration were used as controls for histological analysis. After being anesthetized with chloral hydrate and isoflurane, their brains were harvested according to the same method used for the hypoglycemic animals. Neuronal injury, GFAP reactivity, and infiltration of polymorphonuclear leukocytes in each specimen were blindly assessed and scored by two of the authors (J.A.G. and K-F.L.) who did not know either the duration of hypoglycemia or the findings of ADC maps. The histopathological changes for each category were recorded according to a numerical grading scale (grade 0, normal/absent; 1, slight; 2, moderate; and 3, severe).
The body temperature was maintained at 37±0.5°C by a heated air flow system throughout the experiment. Arterial blood pressure was monitored continuously (Parametron 7150 Monitor, Roche Medical Electronics). Arterial blood gas analysis was performed intermittently with a blood gas analyzer (Corning 170 pH blood gas analyzer, Corning). Blood glucose was measured by the glucose oxidase method (Sigma Chemical Co) before injection of insulin (baseline), during EEG stage V, and 15 minutes and 35 minutes after the initial glucose infusion.
MRI Procedure
MR experiments were performed with the use of a General Electric CSI-II 2.0 T/45 cm imaging spectrometer operating 85.56 MHz for 1H and equipped with ±20 G/cm self-shielding gradients. The multislice ADC mapping13 27 was performed on eight contiguous axial slices, encompassing the entire rat brain. An eight-slice spin-echo sequence28 was used with echo-planar acquisition.29 Each slice was 1.5 mm thick with a 25.6x25.6-mm field of view and 64x64 pixel resolution. Slice selection and diffusion gradients were applied along the z axis, ie, the anterior-posterior axis of the rat brain. The echo-planar acquisition time for each diffusion-weighted image was 65.54 milliseconds. To create ADC maps, diffusion sensitizing gradients were increased in amplitude in three different ways. In the control/cardiac arrest group, three ADC maps were acquired: while alive and at 15 minutes and 45 minutes after cardiac arrest. ADC maps were constructed with 20 different b values, ranging from 15 to 1700 s/mm2. In the Iso15 group, six ADC maps were acquired at 1.5 hours after insulin injection, 10 minutes after isoelectricity, and at 10, 20, 30, and 40 minutes after the initial glucose infusion. In the Iso50 group, seven ADC maps were acquired at 1.5 hours after insulin injection, 15 minutes and 45 minutes after isoelectricity, and at 10, 20, 30, and 40 minutes after the initial glucose infusion. Because of the large amount of data, ADC maps in these hypoglycemia groups were constructed with 10 different b values, ranging from 62 to 1900 s/mm2. When an increased time resolution was required to monitor sequential ADC changes during the transition to isoelectricity, only six b values were collected per map, ranging from 43 to 1500 s/mm2.
The raw data were transferred to a Silicon Graphics Indigo R4000 workstation (Silicon Graphics) for off-line data processing. As determined by a linear regression algorithm, analysis of the natural logarithm of the signal intensity with respect to the series of b values yielded the ADC value on a pixel-by-pixel basis.27 30 There is a tradeoff between the time resolution gained and error in the fit when the number of b values is decreased. We empirically determined that six b values and a 30-second time resolution sufficiently met our requirements for time resolution and confidence in the quality of the fit. ADC values below 0.55x10-3 mm2/s were considered abnormal diffusion coefficients based on prior studies in ischemic animals.27 31 Regions with abnormal diffusion coefficients were observed over time, and their volume was calculated at each time point.
ROI Analysis
ROI analysis was performed with a KBV image analysis program (Amerinex Artificial Intelligence) and the Silicon Graphics computer workstation. The ROI size was 3x3 pixels (1.2x1.2 mm). According to the stereotaxic coordinates,32 the following seven cerebral structures with a 5x5-pixel area on the imaging slices were selected: motor area in the frontoparietal cortex, somatosensory area in the frontoparietal cortex, caudoputamen, thalamus, lateral hypothalamic area, amygdaloid area, and hippocampus. We took another three ROIs in the dorsal lateral and medial brain stem, which roughly corresponded to superior colliculus, medial geniculate body, and substantia nigra (Fig 1
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Statistical Analysis
Values presented in this study are mean±SD. For the relationship between two parametric variables, linear regression analysis was used. Student's t test was applied to test the statistical significance between ROI values in hypoglycemic animals and those in control animals. A statistically significant difference of mean ADC values over time or among different animal groups was evaluated by ANOVA and post hoc testing with the Bonferroni correction. A value of P<.05 was considered significant.
| Results |
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Hypoglycemia Groups
Physiological parameters are shown in Table 2
. Mean arterial blood pressure, pH, PaCO2, and PaO2 were strictly controlled within a narrow range, and there were no statistically significant differences among the measured time points. Glucose levels significantly decreased during the stage V EEG phase. After the glucose infusion, blood glucose levels normalized in both the Iso15 and Iso50 groups. Although the blood glucose levels after glucose infusion in the latter group were slightly higher than those in the former group, these differences were not statistically significant.
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EEG recording and ADC mapping were initiated 1.5 hours after insulin administration. Initial EEG findings in all animals were categorized as stage II or III, ie, moderate slowing or high-amplitude delta slowing. At this time point, ADC maps revealed small areas with abnormally decreased ADC values localized in the cortex and periventricular regions, mainly in the caudoputamen. The cortical abnormalities were multiple, and the location varied among animals. The periventricular lesions were localized in slices in which the largest sections of caudoputamen and thalamus appeared, ie, Vth and VIth slices in Figs 2 and 3![]()
. Consequently, mean ADC ROI values at this EEG stage were slightly lower than control values in the motor area in the frontoparietal cortex, caudoputamen, thalamus, and lateral hypothalamic area (Table 1
). The mean volume of abnormal ADC values at this time point were 56±18.3 mm3 in the Iso15 group and 60.6±18.7 mm3 in the Iso50 group (Fig 4
). Six of 10 hypoglycemic animals showed bilaterally symmetrical and synchronous EEG changes. In four animals (40%), however, isoelectricity did not occur simultaneously in the two hemispheres. ADC changes during the transition from stage IV to stage V were obtained by frequent mapping every 30 seconds. The ADC maps during EEG stage IV exhibited findings similar to those on the initial mapping described above. Then a marked ADC decline occurred coincident with the onset of EEG isoelectricity. Fig 5
shows the ADC maps and corresponding EEG traces in a rat with an asynchronous EEG change. Once the EEG activity ceased, definite ADC declines involving almost the whole brain were observed (Figs 2 and 3![]()
). The volume of brain with abnormally decreased ADC values 10 minutes after EEG cessation in the Iso15 group was 498.9±225.9 mm3. The abnormal ADC region volumes in the Iso50 group 15 and 45 minutes after the EEG cessation were 688.3±83.1 and 737.9±152.0 mm3, respectively (Fig 4
). The tissue volume with abnormally reduced ADC values significantly increased in relation to the duration of EEG isoelectricity (P<.002, ANOVA with post hoc Bonferroni corrected t test). ROI values at 10 to 15 minutes after isoelectricity were significantly decreased in every ROI compared with those at the stage II or III EEG phase (Table 1
). At 45 minutes after isoelectricity, further declines were found in lateral hypothalamic area, amygdaloid area, superior colliculus, medial geniculate body, and substantia nigra (P<.05, Student's t test), and the same magnitudes of ADC decline were observed in all brain structures as those in the animals with cardiac arrest (P=NS versus ADC values 45 minutes after the cardiac arrest in each ROI).
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Ten minutes after the glucose infusion, ADC values in all brain regions returned to normal except in the periventricular regions (Figs 2 and 3![]()
). The mean volumes of abnormal ADC values at 40 minutes after the glucose infusion were 26.7±15.3 mm3 in the Iso15 group and 32.6±17.2 mm3 in the Iso50 group. These values were significantly smaller than the initial lesion volumes obtained during EEG stage II or III (P<.001, Student's t test). There were no significant differences in the residual lesion volume between the Iso15 and Iso50 groups during the 40-minute recovery period (Fig 4
). In two animals from the Iso15 group, low-voltage slow EEG activity was observed after glucose infusion. However, none of the animals in the Iso50 group showed EEG recovery.
Neuronal necrosis was obvious in the medial half of the CA1 sector of the hippocampus and the crest of the dentate gyrus in the Iso15 group. In the Iso50 group, neuronal necrosis was observed in the entire CA1 sector of the hippocampus, a widespread area of the dentate gyrus, striatum, and superficial layers of the neocortex. Histopathological damage scores are shown in Table 3
. The scores of mean neuronal injury, GFAP reactivity, and polymorphonuclear leukocyte infiltration in the Iso50 group were significantly higher than those in the Iso15 and control groups (P<.05, ANOVA with Bonferroni corrected t test). The Iso15 group was not significantly different from the controls.
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| Discussion |
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In contrast to the generalized ADC decline during isoelectricity, the minimal changes that appeared on the ADC maps before cessation of EEG activity may not be caused by widespread brain energy depletion but by localized imbalances between energy supply and demand, spreading depression,36 or an excitotoxic mechanism.25 One or two periods of transient impedance increase with ionic change before isoelectricity occurs in the insulin-induced hypoglycemia model, and such a phenomenon is assumed to represent spreading depression.26 36 It is likely that the early ADC changes observed in this experiment represent effects of spreading depression. The asymmetry of the ADC changes and isoelectricity in 40% of the animals may be related to an asymmetrical onset of spreading depression in severe hypoglycemia; and this asymmetry also occurred in a histopathological study.20 A specific location of brain lesions after hypoglycemic injury, ie, periventricular regions, was documented by histopathological analyses; involvement by excitotoxins, such as aspartate and glutamate, in the generation of hypoglycemic neuronal damage at selected sites was suggested.25 37 Supporting evidence for this hypothesis stems from pharmacological experiments37 38 39 and a study of glutamatergic corticostriatal projections.40 A significant ADC drop occurs in the caudoputamen after the local injection of N-methyl-D-aspartate.15 16 Further studies with ADC mapping are necessary to identify the mechanism of these early ADC changes in the preisoelectric phase.
The local ADC values during isoelectricity are similar to those observed after cardiac arrest. Brain temperature decreased by 0.3°C to 0.4°C after the cardiac arrest, and normal brain ADC changed 0.013x10-3 mm2/s per 1°C change of brain temperature.31 The observed temperature change after cardiac arrest could not explain our results. We reported a similar magnitude of ADC decline in spreading depression, as observed with hypoglycemia.13 14 In all these different pathological states, ie, global ischemia, hypoglycemia, and spreading depression, an abrupt reduction of the ECS volume up to 50% of normal has been documented,19 20 27 although the mechanisms inducing this ECS volume change differ. Similar ADC declines occur in the cortex during biccuculine-induced status epilepticus and in the striatum of neonatal rats injected with N-methyl-D-aspartate, other conditions in which the ECS volume decreases.11 16 Temporal changes in ADC values and ECS volume were observed in a global ischemia reperfusion model.41 An analysis of the trace of the diffusion tensor of the ischemic cat brain showed that the changes in water diffusion during acute stroke are directly related to changes in the relative volume of the ICS and ECS.42 Although the exact mechanisms for the ADC declines in various conditions are not completely understood, our findings support the concept that ADC measurements likely detect water shifts between ECS and ICS in a variety of conditions, including hypoglycemia, that are caused by a variety of mechanisms. It is therefore likely that ADC declines are a marker of ECS shrinkage that is nonspecific in its origin.
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| Acknowledgments |
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| Footnotes |
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Received February 27, 1996; revision received April 22, 1996; accepted June 4, 1996.
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Department of PharmacologySmooth Muscle Ion Channel GroupUniversity of Vermont Medical Research FacilityColchester, Vt
| Introduction |
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A novel finding is that ADC changes began in cortical regions, spread to the subcortex, and were often asymmetrical (40% of animals) at onset. This implies that hypoglycemia may cause perturbations that do not take place simultaneously throughout the brain. The authors note that early ionic shifts in hypoglycemia resemble spreading depression, and this process may not only spread throughout the hemisphere but may be initiated asymmetrically between the hemispheres. This may explain a longstanding conundrum in hypoglycemia, ie, how a symmetrical reduction in blood sugar supply to the brain could lead to asymmetrical necrosis (see Fig 9 in Reference 1)1R .
The authors could extend their present observations into areas not known to be damaged by even the more severe of the two insults that they studied.
The cerebellum and brain stem, for example, are notoriously resistant to hypoglycemic brain damage compared with the cerebrum. This may be related to a better influx of glucose across the capillary into those brain regions when supply is short.2R If so, one would expect a lesser degree of alteration in ADC using the methods in the present study. Alternatively, if such "resistant" brain regions in hypoglycemia show identical changes in ADC, then other factors would have to be invoked to explain the resistance of the cerebellum and brain stem to a hypoglycemic insult.
| Selected Abbreviations and Acronyms |
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PMNs indicates polymorphonuclear leukocytes.
*Score of histopathological damage ranged from 0 (normal/absent) to 3 (severe).
P<.05 vs Iso15 and control groups (one-way ANOVA with Bonferroni corrected t test in each column).
| References |
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2R. LaManna JC, Harik SI. Regional comparisons of brain glucose influx. Brain Res.. 1985;326:299-305.[Medline] [Order article via Infotrieve]
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J Maruya, H Endoh, H Watanabe, H Motoyama, and H Abe Rapid improvement of diffusion-weighted imaging abnormalities after glucose infusion in hypoglycaemic coma BMJ Case Reports, January 22, 2009; 2009(jan21_1): bcr0720080514 - bcr0720080514. [Abstract] [Full Text] |
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C. C. T. Lim, R. Gan, C. L. Chan, A. W. K. Tan, J. J. C. Khoo, S.-Y. Chia, S. L. Kao, J. Abisheganaden, and Y. Y. Sitoh Severe Hypoglycemia Associated with an Illegal Sexual Enhancement Product Adulterated with Glibenclamide: MR Imaging Findings Radiology, January 1, 2009; 250(1): 193 - 201. [Abstract] [Full Text] [PDF] |
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C. Enzinger, F. Thimary, P. Kapeller, S. Ropele, R. Schmidt, F. Ebner, and F. Fazekas Transient Global Amnesia: Diffusion-Weighted Imaging Lesions and Cerebrovascular Disease Stroke, August 1, 2008; 39(8): 2219 - 2225. [Abstract] [Full Text] [PDF] |
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C.H. Vite, S. Magnitsky, D. Aleman, P. O'Donnell, K. Cullen, W. Ding, S. Pickup, J.H. Wolfe, and H. Poptani Apparent Diffusion Coefficient Reveals Gray and White Matter Disease, and T2 Mapping Detects White Matter Disease in the Brain in Feline Alpha-Mannosidosis AJNR Am. J. Neuroradiol., February 1, 2008; 29(2): 308 - 313. [Abstract] [Full Text] [PDF] |
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J Maruya, H Endoh, H Watanabe, H Motoyama, and H Abe Rapid improvement of diffusion-weighted imaging abnormalities after glucose infusion in hypoglycaemic coma J. Neurol. Neurosurg. Psychiatry, January 1, 2007; 78(1): 102 - 103. [Full Text] [PDF] |
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S. Albayram, H. Ozer, S. Gokdemir, F. Gulsen, G. Kiziltan, N. Kocer, and C. Islak Reversible reduction of apparent diffusion coefficient values in bilateral internal capsules in transient hypoglycemia-induced hemiparesis. AJNR Am. J. Neuroradiol., September 1, 2006; 27(8): 1760 - 1762. [Abstract] [Full Text] [PDF] |
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G. Hagemann, H.-J. Mentzel, H. Weisser, A. Kunze, and C. Terborg Multiple Reversible MR Signal Changes Caused by Epstein-Barr Virus Encephalitis AJNR Am. J. Neuroradiol., August 1, 2006; 27(7): 1447 - 1449. [Abstract] [Full Text] [PDF] |
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L. Lo, C.H.A. Tan, T. Umapathi, and C.C. Lim Diffusion-Weighted MR Imaging in Early Diagnosis and Prognosis of Hypoglycemia AJNR Am. J. Neuroradiol., June 1, 2006; 27(6): 1222 - 1224. [Abstract] [Full Text] [PDF] |
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D. Le Bihan, S.-i. Urayama, T. Aso, T. Hanakawa, and H. Fukuyama Direct and fast detection of neuronal activation in the human brain with diffusion MRI PNAS, May 23, 2006; 103(21): 8263 - 8268. [Abstract] [Full Text] [PDF] |
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C. Cordonnier, C. Oppenheim, C. Lamy, J. -F. Meder, and J. -L. Mas Serial diffusion and perfusion-weighted MR in transient hypoglycemia Neurology, July 12, 2005; 65(1): 175 - 175. [Full Text] [PDF] |
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H Axer, A Ragoschke-Schumm, J Bottcher, C Fitzek, O W Witte, and S Isenmann Initial DWI and ADC imaging may predict outcome in acute disseminated encephalomyelitis: report of two cases of brain stem encephalitis J. Neurol. Neurosurg. Psychiatry, July 1, 2005; 76(7): 996 - 998. [Abstract] [Full Text] [PDF] |
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J. Bottcher, A. Kunze, C. Kurrat, P. Schmidt, G. Hagemann, O.W. Witte, and W.A. Kaiser Localized Reversible Reduction of Apparent Diffusion Coefficient in Transient Hypoglycemia-Induced Hemiparesis Stroke, March 1, 2005; 36(3): e20 - e22. [Abstract] [Full Text] [PDF] |
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A. T. Nygren and L. Kaijser Water exchange induced by unilateral exercise in active and inactive skeletal muscles J Appl Physiol, November 1, 2002; 93(5): 1716 - 1722. [Abstract] [Full Text] [PDF] |
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S. Condette-Auliac, S. Bracard, R. Anxionnat, E. Schmitt, J. C. Lacour, M. Braun, J. Meloneto, A. Cordebar, L. Yin, and L. Picard Vasospasm After Subarachnoid Hemorrhage: Interest in Diffusion-Weighted MR Imaging Stroke, August 1, 2001; 32(8): 1818 - 1824. [Abstract] [Full Text] [PDF] |
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K. Yonemura, Y. Hasegawa, K. Kimura, K. Minematsu, and T. Yamaguchi Diffusion-weighted MR Imaging in a Case of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike Episodes AJNR Am. J. Neuroradiol., February 1, 2001; 22(2): 269 - 272. [Abstract] [Full Text] [PDF] |
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M. de Tourtchaninoff, P. Hantson, P. Mahieu, and J.M. Guerit Brain death diagnosis in misleading conditions QJM, July 1, 1999; 92(7): 407 - 414. [Abstract] [Full Text] [PDF] |
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