Magnetization Transfer Ratio Imaging Research Articles

Improvement of physiological and quantitative diagnosis of knee disorders: Colour image enhancement, multiplane reformatting, and magnetization transfer ratio imaging.

Improvement of physiological and quantitative diagnosis of knee disorders: Colour image enhancement, multiplane reformatting, and magnetization transfer ratio imaging.

Gender differences in MRI studies on multiple sclerosis

Magnetic resonance imaging (MRI) provides objective and detailed insights into morphologic changes of the central nervous system associated with multiple sclerosis (MS). Therefore, it also appears an ideal tool to investigate the possible impact of gender on MS course and severity. Only more recently some studies have specifically addressed this issue and we, therefore, reviewed the literature for investigations which analysed the impact of various factors including gender on MS-related morphologic changes and their evolution. Treatment trials were excluded and the available data refer mainly to relapsing MS with or without secondary progression. A few mostly smaller studies suggest a higher frequency of contrast-enhancing lesions in women. This was not seen in the analysis of a large and pooled dataset of untreated MS patients of the Sylvia Lawry Centre for MS Research. Other large cross-sectional and longitudinal studies found no effects of gender on T2 or T1 lesion burden or on brain atrophy. Findings between male and female MS patients also did not differ when including magnetisation transfer ratio and diffusion tensor imaging for morphologic information. Our review thus indicates no independent gender differences on brain MRI beyond demographic and clinical variables such as age, duration of disease and grade of disability.

Magnetization transfer phenomenon in the human brain at 7 T

Magnetization transfer is an important source of contrast in magnetic resonance imaging which is sensitive to the concentration of macromolecules and other solutes present in the tissue. Magnetization transfer effects can be visualized in magnetization transfer ratio images or quantified via the z-spectrum. This paper presents methods of measuring the z-spectrum and of producing high-resolution MTR images and maps of z-spectrum asymmetry in vivo at 7 T, within SAR limits. It also uses a 3-compartment model to measure chemical exchange and magnetization transfer parameters from the z-spectrum data. The peak in the z-spectrum associated with chemical exchange between amide and water protons (amide proton transfer, APT, effects) is much more apparent at 7 T than at 3 T. Furthermore at 7 T quantitative APT results varied between the corpus callosum and other white matter structures, suggesting that quantitative APT imaging could be used as a method of measuring myelination. The results also suggest that chemical exchange is not responsible for the phase shift observed in susceptibility weighted images between grey matter and white matter.

The establishment of a multiple sclerosis model for clinical MRI study

Objective To establish a rat model of multiple sclerosis (MS) for clinical MRI study. Methods The Lewis (LEW) rats were immunized by myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) emulsified with complete Freunds adjuvant/incomplete Freunds adjuvant. Twenty LEW rats were selected. Group A rats were 5, group B rats were 10 and control group rats were 5. MRI and histopathology analysis were observed on group A and control group, and clinical course were observed on group B. The clinical course was observed and the brain and spinal cord of EAE rats were scanned on 3. 0 T MR system with quadrature wrist joint coil on the third day of the acute stage of disease. The T2/T1 weighted images and Gadolinium enhanced T1 weighted images in 3D volume were obtained respectively. The magnetization transfer ratio (MTR) images were calculated with special software in workstation. Rats were sacrificed within 24 h after MRI, and the histopathological changes of central nervous system were observed. Results Twice immunization of MOG35-55 was used and a rat model of MS was successfully induced with all the rats. The model had varied clinical symptoms. The lesions of central nervous system at acute stage on group A (5 rats) were depicted on MRI. The lesions located in the brain and the spinal cord with main manifestation of hyperintensity on T2 weighed images and hypointensity on T1 weighted images. Some lesions had Gd-DTPA enhancement, and the value of MTR decreased. The infiltration of mononuclear cells around blood vessels and the extensive distribution of lesions of demyelination in brain and spinal cord were verified by histological examination. Conclusions Twice immunization of MOG35-55 could produce a rat model which mimics MS.The model is stable with higher incidence, and the antigen is cheap and obtained easily. The intravital monitoring of brain and spinal cord lesions in MOG35-55 induced rat model is possible on 3.0 T clinical whole-body MR scanner with a quadrature wrist joint coil. MOG35-55 induced rat model is an ideal MS model for clinical MRI study. Key words: Multiple sclerosis; Models; animal; Rats; Magnetic resonance imaging

Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: A pilot study

Background Measurement of retinal nerve fiber layer (RNFL) thickness in multiple sclerosis (MS) is gaining increasing attention. Objectives To explore the relationship between RNFL thickness as measured by optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDx), and conventional and non-conventional optic nerve and brain MRI measures. Methods Twelve relapsing–remitting (RR) MS patients (12 affected and 12 unaffected eyes) and 4 age- and sex-matched normal controls (NC) (8 unaffected eyes) were enrolled. Four MS patients had a history of bilateral optic neuritis (ON), four had a history of unilateral ON, and 4 had no history of ON. Optic nerve MRI measurements included the length of T2 lesions, measurement of optic nerve atrophy, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) measures. Optic nerve atrophy was measured by a novel method with high reproducibility. Brain MRI measurements included T1 and T2 lesion volumes (LVs) and their relative MTRs, and tissue class specific atrophy, MTR and DTI measures. Measures of RNFL were evaluated with OCT and GDx. We also evaluated both high and low contrast letter acuities (LCLA) in order to determine the relationship between vision, MRI metrics, and retinal structural architecture. Results LCLA, RNFL-OCT and optic nerve radius measures showed more robust differences between NC and MS patients, and between MS patients with affected and unaffected eyes. T2-LV and T1-LV, as well as gray matter atrophy, DTI and MTR measures were related to LCLA and RNFL thickness. Unique additive variance regression models showed that both brain and optic nerve MRI measures independently accounted for about 50% of the variance in LCLA and RNFL thickness. In reverse models, about 20% of the additional independent variance was explained by optic nerve or brain MRI metrics. Conclusions Measurement of RNFL thickness and radius of the optic nerve should be preferred to the other optic nerve MRI measures in clinical studies. Whole brain lesion and GM measures are predictive of impaired visual function with corresponding structural concomitants.

Tract-based Analysis of Magnetization Transfer Ratio and Diffusion Tensor Imaging of the Frontal and Frontotemporal Connections in Schizophrenia

In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown. DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus. A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants. Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity.

Growth of White Matter in the Adolescent Brain: Role of Testosterone and Androgen Receptor

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.

Macromolecular White Matter Abnormalities in Geriatric Depression: A Magnetization Transfer Imaging Study

<h3>Objective</h3> Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression. <h3>Design</h3> The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions. <h3>Setting</h3> The study was conducted in a university-based, geriatric psychiatry clinic. <h3>Participants</h3> Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. <h3>Measurement</h3> Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. <h3>Results</h3> Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions. <h3>Conclusion</h3> These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

Macromolecular White Matter Abnormalities in Geriatric Depression: A Magnetization Transfer Imaging Study

Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression. The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions. The study was conducted in a university-based, geriatric psychiatry clinic. Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions. These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

Multiple Sclerosis, Cannabinoids, and Cognition

Multiple Sclerosis, Cannabinoids, and Cognition

Discussion, Part II

Dr. ARNOLD: To assess neuroprotection, it's important to be able to measure changes in myelin. Magnetization transfer ratio (MTR) imaging is a very sensitive method for measuring both myelin injury and myelin repair on a voxel-by-voxel basis, which can be used for evaluating this aspect of neuroprotection. Dr. ZIVADINOV: Are the data you've presented here only for original gadolinium-enhancing lesions or for all lesions that appear? Dr. ARNOLD: These data are strictly the percentage of the initial gadolinium-enhancing lesion volume. It's effectively the percentage of the voxels that were gadolinium enhancing on the original scan that show these changes over time. That's a very important point, because it's what gives MTR its power: you can do this for all the lesions. Atrophy is an important measure of neuroprotection, so touching on the atrophy data thus far is relevant. The conventional MRI data that exist show that the rate of atrophy in patients can be related to the frequency of contrast-enhancing lesions. In the Richert group study, patients who had no contrast-enhancing lesions had very low rates of atrophy over the subsequent 5 years, whereas those with more than three contrast-enhancing lesions had much higher rates of atrophy over the subsequent 5 years. This implies that there is some dependence of atrophy on focal inflammation, which you might think obvious, but as Gary [Birnbaum] said earlier, there's a tendency now to attribute the loss of brain volume to diffuse degenerative processes that don't necessarily involve the lesions. My group was interested in this dependency of atrophy on the lesions, in part for the reasons I just hinted at and in part because of the phenomenon of T2 lesion volume plateauing and even decreasing over time in patients with MS. I tried to get our investigators to look at lesion formation and …

Imaging correlates of axonal swelling in chronic multiple sclerosis brains

T2-weighted magnetic resonance imaging is a sensitive tool for monitoring progression of multiple sclerosis, but it does not provide information on the severity of the underlying tissue damage. Measurement of T1 hypointensities and magnetization transfer ratio (MTR) can potentially distinguish lesions with more severe tissue damage. The objective of this study was to use image-guided pathology to determine histological differences between lesions that are abnormal only on T2-weighted images versus lesions that are abnormal on T2-weighted, T1-weighted, and MTR images. A total of 110 regions were selected from postmortem magnetic resonance images of 10 multiple sclerosis patients. Regions were classified into three magnetic resonance imaging-defined categories: normal-appearing white matter; abnormal on T2-weighted image only (T2-only); and abnormal on T2-weighted, T1-weighted, and MTR images (T2T1MTR). Myelin status, lesion activity, astrocytosis, serum protein distribution, axonal area, and axonal loss were evaluated histopathologically. Comparisons between groups showed that T2T1MTR regions were more likely to be demyelinated (83% compared with 55% of T2-only regions) and more likely to be chronic inactive lesions (68% compared with 0% of demyelinated T2-only regions). There was no difference between T2-only and T2T1MTR regions in axonal area, but there was a significant difference in axonal count, indicating that axons in the T2T1MTR regions were enlarged relative to those in T2-only regions. Axonal swelling and axonal loss were major pathological features that distinguish T2T1MTR regions from T2-only regions.

Comparing MR image intensity standardization against tissue characterizability of magnetization transfer ratio imaging

To evaluate existing methods of standardization by exploiting the well-known tissue characterizing property of magnetization transfer ratio (MTR) values obtained from MT imaging, and compare the tissue characterizability of standardized T2, proton density (PD), and T1 images against the MTR images. Image intensity standardization is a postprocessing method that was designed to correct for acquisition-to-acquisition signal intensity variations (nonstandardness) inherent in magnetic resonance (MR) images. The main idea of this technique is to deform the volume image histogram of each study to match a standard histogram, and to utilize the resulting transformations to map the image intensities into a standard scale. The method has been shown to produce a significant gain in similarity of resulting images and to achieve numeric tissue characterization. In this work we compared PD-, T2-, and T1-weighted images before and after standardization with the corresponding MT images for 10 patient MRI studies of the brain, in terms of the normalized median values on the corresponding image histograms. No statistically significant difference was observed between the standardized PD-, T2-, and T1-weighted images and the corresponding MTR images. However, a statistically significant difference was found between the pre- and poststandardized PD-, T2-, and T1-weighted images, and between the prestandardized PD-, T2-, and T1-weighted images and the corresponding MTR images. These results suggest that standardized T2, PD, and T1 images and their tissue-specific intensity signatures may be useful for characterizing disease.

Magnetization transfer analysis of cartilage repair tissue: a preliminary study

To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31+/-0.07) was not significantly different from normal cartilage MTR (0.34+/-0.05). The MTR of MFR repaired cartilage (0.28+/-0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair).

Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis

Following our previous reports based on parametric MRI methods (T 2-weighted MRI, statistical mapping analysis of magnetization transfer ratio images and functional MRI) applied to a population of 18 patients with clinically isolated syndrome suggestive of multiple sclerosis, we have reviewed the possible structural and functional surrogates of MS that could explain the subtle cognitive impairment related to attention and working memory deficits evaluated with paced auditory serial addition test (PASAT). We propose that the brain substrates underlying cognitive impairment observed at the very early stage of MS are multifactorial. Several components could influence PASAT performances in patients: i) the extent of diffuse white matter damage, ii) the location of visible and non visible lesions, iii) the connectivity efficiency between distant brain functional areas involved in working memory processes and iv) the cortical reorganization. Nevertheless, individually, each of these parameters may have few influences on PASAT performance in patients. Using a multiregression model built with independent MR parameters, a very good evaluation of PASAT scores has been obtained in this limited number of patients explaining 90% of the variance. In conclusion, the different aspects of tissue and functional pathological brain underpinnings must be accounted to monitor accurately new therapeutic strategies for the treatment of early cognitive deficits related to MS.

Interplay between intensity standardization and inhomogeneity correction in MR image processing

Image intensity standardization is a postprocessing method designed for correcting acquisition-to-acquisition signal intensity variations (nonstandardness) inherent in magnetic resonance (MR) images. Inhomogeneity correction is a process used to suppress the low frequency background nonuniformities (inhomogeneities) of the image domain that exist in MR images. Both these procedures have important implications in MR image analysis. The effects of these postprocessing operations on improvement of image quality in isolation has been well documented. However, the combined effects of these two processes on MR images and how the processes influence each other have not been studied thus far. In this paper, we evaluate the effect of inhomogeneity correction followed by standardization and vice-versa on MR images in order to determine the best sequence to follow for enhancing image quality. We conducted experiments on several clinical and phantom data sets (nearly 4000 three-dimensional MR images were analyzed) corresponding to four different MRI protocols. Different levels of artificial nonstandardness, and different models and levels of artificial background inhomogeneity were used in these experiments. Our results indicate that improved standardization can be achieved by preceding it with inhomogeneity correction. There is no statistically significant difference in image quality obtained between the results of standardization followed by correction and that of correction followed by standardization from the perspective of inhomogeneity correction. The correction operation is found to bias the effect of standardization. We demonstrate this bias both qualitatively and quantitatively by using two different methods of inhomogeneity correction. We also show that this bias in standardization is independent of the specific inhomogeneity correction method used. The effect of this bias due to correction was also seen in magnetization transfer ratio (MTR) images, which are naturally endowed with the standardness property. Standardization, on the other hand, does not seem to influence the correction operation. It is also found that longer sequences of repeated correction and standardization operations do not considerably improve image quality. These results were found to hold for the clinical and the phantom data sets, for different MRI protocols, for different levels of artificial nonstandardness, for different models and levels of artificial inhomogeneity, for different correction methods, and for images that were endowed with inherent standardness as well as for those that were standardized by using the intensity standardization method. Overall, we conclude that inhomogeneity correction followed by intensity standardization is the best sequence to follow from the perspective of both image quality and computational efficiency.

Altered Functional Connectivity Related to White Matter Changes inside the Working Memory Network at the Very Early Stage of MS

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T(2) lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.

Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.

Identification of HIV-associated progressive multifocal leukoencephalopathy: magnetic resonance imaging and spectroscopy.

Cover. Companion axial fluid-attenuated inversion recovery (FLAIR) images (top left) and magnetization transfer ratio (MTR) images (top right) of progressive multifocal leukoencephalopathy (PML). A representative proton magnetic resonance spectrum (bottom left) is also shown. Figure 1. The histological characteristics of PML include destruction of myelin (A, myelin-stained section of subcortical white matter), loss of oligodendrocytes (B, enlarged oligodendrocytes harboring intranuclear eosinophilic inclusion bodies, at arrow), and bizarre reactive astrocytes (C, transformed bizarre reactive astrocyte). Companion normal images are shown beneath each panel for comparison.