Biomedical subjects
Publications and source records attributed to J M Constans.
We report the fourth case of combined D-and L-2-hydroxyglutaric aciduria presenting with neonatal encephalopathy and subependymal cysts.
UNLABELLED: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man. METHODS: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.
Texture analysis was performed in three different MRI units on T1 and T2-weighted MR images from 10 healthy volunteers and 63 patients with histologically confirmed intracranial tumors. The goal of this study was a multicenter evaluation of the usefulness of this quantitative approach for the characterization of healthy and pathologic human brain tissues (white matter, gray matter, cerebrospinal fluid, tumors and edema). Each selected brain region of interest was characterized with both its mean gray level values and several texture parameters. Multivariate statistical analyses were then applied in order to discriminate each brain tissue type represented by its own set of texture parameters. Texture analysis was previously performed on test objects to evaluate the method dependence on acquisition parameters and consequently the interest of a multicenter evaluation. Even obtained on different sites with their own acquisition routine protocol, MR brain images contain textural features that can reveal discriminant factors for tissue classification and image segmentation. It can also offer additional information in case of undetermined diagnosis or to develop a more accurate tumor grading.
This paper presents a method for the detection, representation and visualisation of the cerebral vascular tree and its application to magnetic resonance angiography (MRA) images. The detection method is an iterative tracking of the vessel centreline with subvoxel accuracy and precise orientation estimation. This tracking algorithm deals with forks. Centrelines of the vessels are modelled by second-order B-spline. This method is used to obtain a high-level description of the whole vascular network. Applications to real angiographic data are presented. An MRA sequence has been designed, and a global segmentation of the whole vascular tree is realised in three steps. Applications of this work are accurate 3D representation of the vessel centreline and of the vascular tree, and visualisation. The tracking process is also successfully applied to 3D contrast enhanced MR digital subtracted angiography (3D-CE-MRA) of the inferior member vessels. In addition, detection of artery stenosis for routine clinical use is possible due to the high precision of the tracking algorithm.
Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, mid-anterior and mid-posterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and mid-anterior CC atrophy in the former, and posterior CC atrophy in the latter. Our findings could indicate that CC atrophy is associated with cerebral ischaemia.
OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome. METHOD: The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex. RESULTS: The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients. CONCLUSIONS: As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.
We present a method to correct intensity variations and voxel shifts caused by non-linear gradient fields in magnetic resonance images. The principal sources of distortion are briefly discussed, as well as the methods of correction currently in use. The implication of the gradient field non-linearities on the signal equations are described in a detailed way for the case of two- and three-dimensional Fourier imaging. A model of these non-linearities, derived from the geometry of the gradient coils, is proposed and then applied in post-processing to correct any images regardless of the acquisition sequence. Initial position errors, as large as 4 mm (i.e., four voxels of 1 x 1 x 1.4 mm3) before correction, are reduced to less than the voxel sizes after correction.
Stereotaxic brain lesioning is widely used to develop experimental models of human brain disease in the nonhuman primate. To avoid intraoperative vascular complications such as intracranial hemorrhage, we developed a methodology that is easy to implement. This method combines T1-weighted magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). This technique is applied to produce bilateral neurotoxic lesions of the rhinal cortex, a structure located medially in the temporal lobe, in eight baboons (including five sham-operated animals with needle descents but no ibotenic acid injection). Two other baboons were lesioned before the MRA technology was available. The MRA sequence (two-dimensional time-of-flight, axial acquisition) was used to localize the blood vessels in the needle trajectories, i.e., the highly vascularized sylvian fissure and temporal gyri. The vessel coordinates were transposed onto the coronal MRI-TI images, onto which the injection sites were determined and the planned needle tracks drawn. In the eight baboons that had MRA, 26.8% of these needle tracks had to be slightly displaced because of the presence of blood vessels. The stereotaxic coordinates of the final target sites were then calculated with respect to six skull landmarks that also served as a reference during surgery. No intracranial hemorrhage occurred in any of the eight baboons in which MRA was performed, in contrast to one of the two baboons not studied with MRA. The histological analysis showed a good extent of the rhinal lesions in all lesioned animals, with minimal damage to areas other than those that were targeted. Thus, combined use of MRI-TI and MRA proved to be reliable in reducing vascular complications, affording new advances for stereotaxic surgery in nonhuman primates.
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OBJECTIVE: To use 1H magnetic resonance spectroscopic imaging to study differences in neuron density (N-acetylaspartate [NAA]), membrane phospholipid metabolites (choline [Cho]), and creatine-containing metabolites (creatine plus phosphocreatine [Cr]) in subjects with Alzheimer's disease (AD), with subcortical ischemic vascular dementia (SIVD), and elderly controls. DESIGN: Cross-sectional, between groups. SETTING: A Veterans Affairs medical center and university memory clinic. PARTICIPANTS: Forty elderly subjects with AD (n = 14), with SIVD (n = 8), and elderly controls (n = 18). MAIN OUTCOME MEASURES: We used 1H magnetic resonance spectroscopic imaging to acquire spectra from a 80 x 100 x 17-mm volume superior to the lateral ventricles. Spectra were analyzed from voxels in anterior, medial, and posterior gray and white matter using nuclear magnetic resonance-1 and the results were compared between groups using repeated measures analysis of variance (ANOVA), Tukey's test, and individual Student's t tests. RESULTS: Using ANOVA, significantly lower levels of NAA/Cho and NAA/Cr and significantly higher levels of Cho/Cr were observed across both gray and white matter voxels in subjects with AD. Using individual Student's t tests, a significantly lower level of NAA/Cho and a higher level of Cho/Cr were observed in the posterior gray matter in subjects with AD. Using ANOVA in subjects with SIVD, significantly lower gray and white matter NAA/Cr levels were observed. Using Tukey's test, the NAA/Cr level was significantly lower in frontal white matter voxels in subjects with SIVD compared with controls. CONCLUSIONS: Our findings in subjects with AD suggest neuron loss in gray matter, axon loss in white matter, and altered Cho metabolism in posterior brain regions. Our findings in subjects with SIVD are consistent with higher levels of creatine-containing metabolites and/or lower levels of NAA in frontal white matter.
An image-processing strategy for functional magnetic resonance imaging (fMRI) data sets consisting of sequential images of the same slice of brain tissue is considered. An algorithm of detection based on the likelihood-ratio test and the noise properties in fMRI is introduced. Since the data have a poor signal-to-noise ratio, and in order to make detection reliable, the algorithm is organized in two steps: (1) pixel detection, which detects all pixels having significant changes, thus building regions of interest (ROIs), and (2) region detection, which selects the most likely activated region from obtained ROIs. The detection method is applied to experimental fMRI data from the motor cortex and compared with the cross-correlation method and Student's t test commonly applied by others. The results obtained using the likelihood-ratio test show improvement in the detection of activated regions.
White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly subjects. The purpose of this study was to characterize metabolic changes in the white matter of elderly subjects with extensive WMSH. We used water-suppressed proton (1H) magnetic resonance spectroscopic imaging (MRSI) to compare six subjects with extensive WMSH with eight age-matched elderly subjects with minimal or absent WMSH, and phosphorus (31P) MRSI to compare nine subjects with extensive WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to region-matched tissue in elderly controls, extensive WMSH were associated with increased signal from choline-containing metabolites, no significant change of signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME) resonance. These findings suggest that WMSH may be associated with an alteration of brain myclin phospholipids in the absence of axonal damage. There were no differences in energy phosphates, consistent with lack of ongoing brain ischemia. Within the group with extensive WMSH, PME resonance measures were significantly lower in WMSH than in contralateral normal-appearing white matter. These results provide information on pathophysiology of WMSH and a basis for comparison with WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other diseases.
PURPOSE: To investigate the association of white matter signal hyperintensities (WMSHs) with changes in hydrogen-1 metabolites. MATERIALS AND METHODS: T2-weighted magnetic resonance (MR) imaging and H-1 MR spectroscopic imaging were performed in 21 elderly control subjects without or with minimal WMSHs, eight elderly subjects with substantial WMSHs, 11 probable Alzheimer disease patients with WMSHs, and eight ischemic vascular dementia (IVD) patients with WMSHs. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and creatine-containing metabolites (Cr) were analyzed. RESULTS: Differences in regional metabolite levels were found within the supraventricular brain of elderly control subjects. In Alzheimer disease patients, extensive WMSHs showed a lower percentage of NAA and a higher percentage of Cho compared with contralateral normal-appearing white matter (NAWM); in IVD patients, extensive and large WMSHs were associated with a higher percentage of Cho and a lower percentage of Cr compared with contralateral NAWM. CONCLUSION: Regional metabolite variation and the presence of WMSHs are important covariants that must be accounted for in analysis of MR spectroscopic data.
We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolites, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate-choline ratio) and creatine-containing metabolites (N-acetylaspartate-creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline-N-acetylaspartate ratios with the N-acetylaspartate-creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.
Numerous studies have shown alterations of some structures and/or cerebral functions in patients with schizophrenia. However, the nature of the neurobiological process which could be at the origin of schizophrenic symptoms is still unknown. Magnetic resonance spectroscopy (MRS) is a unique technique which allows us to estimate the concentrations of endogenous substances which contain natural paramagnetic nuclei such as phosphorus (31P) and hydrogen (proton or 1H). The non invasive character of this technique, the absence of side effects, and the possibility of repetitive evaluations allowing for longitudinal studies, make possible MRS studies on the in vivo cerebral metabolism in schizophrenia. The prefrontal cortex, the hippocampus and the basal ganglia have all been implicated in the pathophysiology of schizophrenia. Therefore these brain regions have been frequently studied using MRS. Both proton and phosphorus spectroscopy have been used to study schizophrenia. Compounds that are detectable by 1H-MRS include N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (ml). A deficit in NAA has been consistently shown in both the frontal and temporal lobes suggesting neuronal loss in these areas. Compounds detectable by 31P-MRS include phosphomonoesters (PMEs) and phosphodiesters (PDEs), which largely represent metabolites generated by lipid turnover. 31P-MRS can also detect certain energy-containing phosphorus metabolites such as phosphocreatine (PCr) and nucleotide triphosphates. Decreased levels of PMEs and increased levels of PDEs have been consistently described in the prefrontal lobes suggesting an alteration of phospholipid metabolism. The purpose of this review is to summarize the research on schizophrenia using MRS, to show the utility of this technique in understanding schizophrenia.