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Mitochondrial encephalomyopathy--two years follow-up by MRI.

A case of mitochondrial encephalomyopathy (MEM) followed-up by MRI for 2 1/2 y is presented. MRI showed gross, diffusely distributed white matter lesions in both hemispheres predominantly in frontal, parietal, temporal and occipital locations a marked ventriculomegaly indicative of cerebral atrophy. Except a slight increase of the cerebral atrophy there were no changes in the follow-up examinations. There are no specific MRI findings in MEM, the diagnosis is established by the synopsis of MRI, laboratory data and muscle biopsy.

Atrophy↗

Neurophysiologic evaluation of cyclosporine toxicity associated with bone marrow transplantation.

INTRODUCTION: Cortical blindness, a rare form of cyclosporine (CSA) neurotoxicity, has previously been described in only nine bone marrow transplant (BMT) recipients. METHODS: Our institution averages 35 allogeneic BMT's per year. In the past year we have seen two women with reversible cortical blindness secondary to CSA toxicity. RESULTS: Age (years) (Case 1; Case 2): 32; 22. Day post-BMT: 41; 50. Peak CSA level (ng/ml): 1159; 632. Both had a history of renal toxicity requiring adjustment of CSA dosage. MRI - both with diffuse while matter changes. EEG - both with moderate to severe generalized slowing. Visual evoked potentials were markedly prolonged in both. Auditory evoked potentials: minimally abnormal; normal. Somatosensory evoked potentials - both normal. Prompt improvement occurred with discontinuation of CSA. Followup neurophysiologic evaluations were normal, however structural changes remained on MRI. CONCLUSION: As neurophysiologic studies closely follow the clinical status they should be included in the evaluation and followup of CSA neurotoxicity.

Adult↗

Comparison of magnetic resonance imaging with neuropathological findings in the diagnosis of HIV and CMV associated CNS disease in AIDS.

OBJECTIVES: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease. METHODS: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI. RESULTS: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP. CONCLUSION: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.

Acquired Immunodeficiency Syndrome↗

Late MRI after head injury in children: relationship to clinical features and outcome.

To characterize the brain pathology in relation to long-term outcome after pediatric head injury, 55 children were studied by magnetic resonance imaging (MRI) at least 3 months after sustaining moderate to severe closed head injury (CHI). Thirty-nine of the patients had abnormal signal intensity consistent with residual brain lesions, including 28 children with lesions involving the frontal lobes. The clinical features of children with frontal lesions, extrafrontal lesions, and diffuse injury were compared. The analysis disclosed that children with frontal lobe lesions were more frequently disabled than children who sustained diffuse injury. Our MRI findings indicate that residual brain lesions are more common after moderate to severe CHI in children than previously thought and that the frontal lobes are most frequently involved. Further investigation is indicated to elucidate whether distinctive cognitive and behavioral sequelae are associated with frontal lobe lesions in children.

Adolescent↗

Neurophysiologic evaluation of cyclosporine toxicity associated with bone marrow transplantation.

INTRODUCTION: Cortical blindness, a rare form of cyclosporine (CSA) neurotoxicity, has previously been described in only nine bone marrow transplant (BMT) recipients. METHODS: Our institutions averages 35 allogeneic BMT's per year. In the past year we have seen two women with reversible cortical blindness secondary to CSA toxicity. RESULTS: Age (years) (Case 1; Case 2): 32; 22. Day post-BMT: 41: 50. Peak CSA level (ng/ml): 1159; 632. Both had a history of renal toxicity requiring adjustment of CSA dosage. MRI - both with diffuse white matter changes. EEG-both with moderate to severe generalized slowing. Visual evoked potentials were markedly prolonged in both. Auditory evoked potentials: minimally abnormal; normal. Somatosensory evoked potential - both normal. Prompt improvement occurred with discontinuation of CSA. Followup neurophysiologic evaluations were normal, however structural changes remain on MRI. CONCLUSION: As neurophysiologic studies closely follow the clinical status they should be included in the evaluation and followup of CSA neurotoxicity.

Adult↗

Regional pattern of increased water diffusivity in hippocampus and corpus callosum in mild cognitive impairment.

BACKGROUND: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer's disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. OBJECTIVE: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. METHODS: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. RESULTS: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. CONCLUSION: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.

Aged↗

[Recent clinical applications of MR medicine as functional medical imaging in the brain and heart].

This paper reviewed recent clinical applications of MR medicine as functional imaging in the brain and heart. Functional and metabolic imaging of brain and heart can be evaluated by the development of fast MR technique (fast SE, echo planar imaging, etc) and chemical shift imaging. The clinical applications of MR medicine to the brain are follows. 1. higher nerve activity assessment using functional MRI, 2. brain perfusion imaging by dynamic contrast MRI, 3. brain diffusion imaging and 4. brain metabolic function by 1H and 31P-MRS. Those of MR medicine to the heart are as follows. 1. left ventricular function assessment by snapshot and/or echo planar imaging. 2. regional wall motion assessment by magnetic tagging, 3. myocardial perfusion imaging by dynamic contrast MRI, 4. coronary flow reserve assessment and 5. cardiac metabolic function by 31P and 1H MRS. Most of these data are thought to be compatible with nuclear medicine technique such as PET and SPECT. In the future, MR medicine may be used as the tool of functional and metabolic diagnosis in addition to anatomical diagnosis in the field of cerebral and cardiac disorders.

Brain↗

[A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration].

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.

Acyclovir↗

Regional assessment of tissue oxygenation and the temporal evolution of hemodynamic parameters and water diffusion during acute focal ischemia in rat brain.

We assessed the temporal and spatial correlation between perfusion deficits and tissue damage in the first hours of focal cerebral ischemia in the rat. Repetitive dynamic susceptibility contrast-enhanced ('bolus track') and diffusion-weighted (DW) MRI, performed from ca. 0.5 up to 6 h after intraluminal middle cerebral artery occlusion (MCA-O), allowed the determination of the time course of various hemodynamic parameters and ischemic tissue damage in specific brain regions. In addition, blood oxygenation level dependent (BOLD) MRI combined with a respiratory challenge provided complementary information on brain hemodynamics. Within the territory of reduced blood flow, the degree of the hemodynamic disturbances was heterogeneous. Interestingly, the spatial pattern of perfusion deficiencies remained essentially the same from ca. 0.5 to 6 h post-MCA-O. However, the area and the extent of ischemic tissue damage, as expressed by reductions in the apparent diffusion coefficient (ADC) of tissue water, tended to progress with increasing occlusion time. Different ADC profiles correlated with different degrees of hemodynamic disturbances. In the ischemic core, which showed severely compromized perfusion, the ADC dropped significantly within 1 h. In perifocal areas, ADC reductions were delayed and less pronounced. Data from the bolus track and BOLD MRI experiments revealed the existence of residual flow, particularly in perifocal regions. Our data point to a time-dependent change in the relationship between ADC reductions and hemodynamic alterations and, therefore, agree with the concept of a progressively increasing perfusion threshold for ischemic tissue damage as a function of time of ischemia.

Animals↗

Imaging of acute stroke.

Thrombolytic therapy has led to a higher proportion of patients presenting to hospital early, and this, with parallel developments in imaging technology, has greatly improved the understanding of acute stroke pathophysiology. Additionally, MRI, including diffusion-weighted imaging (DWI) and gradient echo, or T2*, imaging is important in understanding basic structural information--such as distinguishing acute ischaemia from haemorrhage. It has also greatly increased sensitivity in the diagnosis of acute cerebral ischaemia. The pathophysiology of the ischaemic penumbra can now be assessed with CT or MRI-based perfusion imaging techniques, which are widely available and clinically applicable. Pathophysiological information from CT or MRI increasingly helps clinical trial design, may allow targeted therapy in individual patients, and may extend the time scale for reperfusion therapy.

Animals↗

More accurate identification of reversible ischemic injury in human stroke by cerebrospinal fluid suppressed diffusion-weighted imaging.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) derived from diffusion-weighted (DWI) MRI has been used to differentiate reversible from irreversible ischemic injury. However, the ADC can be falsely elevated by partial volume averaging of cerebrospinal fluid (CSF) with parenchyma, limiting the accuracy of this approach. This study tested the hypothesis that the accuracy of differentiating reversible from irreversible ischemic injury could be improved by CSF suppression at image acquisition. METHODS: Sixteen patients presenting within 6 hours from symptoms, and having partial reversal of the acute lesion on DWI were studied using conventional CSF-suppressed DWI. Lesions were segmented from coregistered acute DWI and follow-up fluid-attenuated inversion recovery (FLAIR) series. The segmented volumes were applied to conventional (ADC(C)) and CSF-suppressed ADC (ADC(FLIPD)) maps to classify each voxel as progressed to infarct or reversed. Individual voxel ADC values were pooled across all patients. Sensitivity to predict reversal, specificity, and accuracy were calculated for both methods. RESULTS: A total of 25 313 voxels were classified as progressed and 31 952 voxels reversed. Across all lesion voxels, ADC(FLIPD) values more accurately depicted tissue fate compared with ADC(C) values (P<0.0001). The largest difference in the two methods was in voxels with <75% parenchyma, where the accuracy of ADC(C) was only 50% compared with 62% for ADC(FLIPD.) CONCLUSIONS: CSF-suppressed ADC measurements gave a more accurate identification of reversible ischemic injury in this sample. We predict that multimodal MRI models of tissue viability in ischemic stroke will be more accurate if CSF-suppressed ADC measurements are used.

Adult↗

Preoperative assessment of motor cortex and pyramidal tracts in central cavernoma employing functional and diffusion-weighted magnetic resonance imaging.

BACKGROUND: Functional MRI (fMRI) combines anatomic with functional information and has therefore been widely used for preoperative planning of patients with mass lesions affecting functionally important brain regions. However, the courses of functionally important fiber tracts are not visualized. We therefore propose to combine fMRI with diffusion-weighted MRI (DWI) that allows visualization of large fiber tracts and to implement this data in a neuronavigation system. METHODS: DWI was successfully performed at a field strength of 1.5 Tesla, employing a spin-echo sequence with gradient sensitivity in six noncollinear directions to visualize the course of the pyramidal tracts, and was combined with echo-planar T2* fMRI during a hand motor task in a patient with central cavernoma. RESULTS: Fusion of both data sets allowed visualization of the displacement of both the primary sensorimotor area (M1) and its large descending fiber tracts. Intraoperatively, these data were used to aid in neuronavigation. Confirmation was obtained by intraoperative electrical stimulation. Postoperative MRI revealed an undisrupted pyramidal tract in the neurologically intact patient. CONCLUSION: The combination of fMRI with DWI allows for assessment of functionally important cortical areas and additional visualization of large fiber tracts. Information about the orientation of fiber tracts in normal appearing white matter in patients with tumors within the cortical motor system cannot be obtained by other functional or conventional imaging methods and is vital for reducing operative morbidity as the information about functional cortex. This technique might, therefore, have the prospect of guiding neurosurgical interventions, especially when linked to a neuronavigation system.

Adult↗

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.

Animals↗

Diffusion-weighted imaging in acute stroke--a tool of uncertain value?

The concept of a mismatch between the lesion volume in diffusion- and perfusion-weighted magnetic resonance imaging (MRI) indicating 'tissue at risk of infarction' is based on the assumption that tissue with diffusion slowing in diffusion-weighted MRI (DWI) or decreased values of the apparent diffusion coefficient represents irreversibly damaged tissue. Recent experimental as well as clinical studies, however, have shown that tissue with diffusion slowing may well normalize if the hypoperfusion is moderate or transient. We will interpret these findings in the light of experimental data and suggest a way for the interpretation of different time courses of lesion development in DWI within a clinical MRI protocol. MR stroke imaging delivers important information in acute stroke, particularly in defining the 'tissue at risk of infarction'.

Brain Ischemia↗

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years.

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

Adult↗

[31-year-old gravid woman of reversible posterior leukoencephalopathy syndrome associated with HELLP syndrome after labor].

We report on a 31-year-old gravid woman with reversible posterior leukoencephalopathy syndrome (RPLS) associated with HELLP syndrome. The patient was hospitalized and underwent an emergency cesarean section at the 34th week of pregnancy due to severe toxemia. After labor her blood pressure acutely increased to 180/100 mmHg and a generalized convulsion occurred. Laboratory data revealed hemolysis, elevated liver enzymes, and low platelets, consistent with HELLP syndrome. FLAIR and Apparent Diffusion Coefficient images on MRI showed hyperintense lesions bilaterally in the posterior white matter, however Diffusion-Weighted images revealed slightly hyperintense changes in the same locations. With the use of diltiazem for blood pressure control, and anticonvulsants, convulsions disappeared and consciousness level improved. Moreover the MRI abnormalities also improved after therapy. This case was diagnosed as RPLS associated with HELLP syndrome and is the first case of an investigation utilizing Diffusion-Weighted and Apparent Diffusion Coefficient images to establish this diagnosis. Based on these results, possible mechanisms of RPLS may be vasogenic edema mediated by a cerebrovascular endothelial disturbance of cerebral vessels and a rapid blood-pressure increase due to HELLP syndrome.

Adult↗

Diffusion-weighted magnetic resonance imaging in radiation-induced cerebral necrosis. Apparent diffusion coefficient in lesion components.

OBJECTIVE: The objective of this retrospective study was to investigate the diffusivity of different components of radiation-induced cerebral necrosis with the hypothesis that the diffusivity of the various components is elevated to different degrees. METHODS: Twenty-two patients (18 men, 4 women, aged 34-72 years) with radiation injury to the temporal lobes after radiation therapy (RT) for nasopharyngeal carcinoma with diagnosis confirmed on serial magnetic resonance imaging (MRI) were studied with coronal T2-weighted, diffusion-weighted, and gadolinium-enhanced MRI. Using three diffusion directions for diffusion-weighted MRI, the apparent diffusion coefficients (ADCs) of the enhanced component, the cystic or liquefied component, and the edema component were measured. RESULTS: ADCs of all components of RT-induced cerebral necrosis (154 +/- 21.6 x 10(-5) mm2/s for contrast-enhanced component; 188 +/- 47.4 x 10(-5) mm2/s for cystic/liquefied component; 177 +/- 35.4 x 10(-5) mm2/s for edema component) were all significantly higher (P<0.00001) than ADC of the normal frontal lobe white matter (82 +/- 12.4 x 10(-5) mm2/s). The ADC of the enhanced component was significantly lower than that of the cystic/liquefied component (P=0.0096) and the edema component (P=0.003). A significantly lower ADC was shown in the enhanced component in temporal lobes showing both short-term morphologic deterioration (P=0.024) and occurrence of deterioration on long-term follow-up (P=0.04) compared with the temporal lobes that showed improvement or stable morphology. CONCLUSIONS: ADCs of the contrast-enhanced component, cystic/liquefied component, and edema in RT-induced cerebral necrosis was significantly higher than in normal brain parenchyma. There is association between a lower ADC in the contrast-enhanced component and morphologic deterioration.

Brain↗

Elucidation of structure-function relationships in the lung: contributions from hyperpolarized 3helium MRI.

Magnetic resonance imaging (MRI) using hyperpolarized 3helium (He) gas as the source of signal provides new physiological insights into the structure-function relationships of the lung. Traditionally, lung morphology has been visualized by chest radiography and computed tomography, whereas lung function was assessed by using nuclear medicine. As all these techniques rely on ionizing radiation, MRI has some inherent advantages. 3He MRI is based on 'optical pumping' of the 3He gas which increases the nuclear spin polarization by four to five orders of magnitude translating into a massive gain in signal. Hyperpolarized 3He gas is administered as an inhaled 'contrast agent' and allows for selective visualization of airways and airspaces. Straightforward gas density images demonstrate the homogeneity of ventilation with high spatial resolution. In patients with lung diseases 3He MRI has shown a high sensitivity to depict ventilation defects. As 3He has some more exciting properties, a comprehensive four-step functional imaging protocol has been established. The dynamic distribution of ventilation during continuous breathing can be visualized after inhalation of a single breath of 3He gas using magnetic resonance (MR) sequences with high temporal resolution. Diffusion weighted 3He MRI provides a new measure for pulmonary microstructure because the degree of restriction of the Brownian motion of the 3He atoms reflects lung structure. Since the decay of 3He hyperpolarization is dependent on the ambient oxygen concentration, regional and temporal analysis of intrapulmonary pO2 becomes feasible. Thus, pulmonary perfusion, ventilation /perfusion ratio and oxygen uptake can be indirectly assessed. Further research will determine the significance of the functional information with regard to physiology and patient management.

Animals↗