A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size.status: publishe

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

1H‐NMR Chemical Shifts and Coupling Constants for Brain Metabolites

A detailed compilation of 1 H‐NMR chemical shift ( δ ) and coupling constant ( J ) values of 38 low‐molecular‐weight metabolites, found in mammalian brain at physiological or pathological conditions, is presented. These metabolites are detectable using in vivo 1 H magnetic resonance spectroscopy techniques and include energy metabolites (sources, intermediaries, and products), essential and nonessential amino acids, excitatory and inhibitory neurotransmitters, neuro‐modulators, and phospholipid membrane precursors and break‐down products. The values of δ and J were measured from high‐field NMR data of aqueous solutions of each metabolite acquired at typical physiological temperature and pH conditions. The spectral parameter values ( δ , J ) may be used to identify metabolites from their resonances in in vivo spectra, to simulate metabolite spectra or to generate basis functions (i.e., amplitude, frequency, and phase) for spectral fitting, and to optimize parameters in data acquisition sequences in order to improve metabolite quantitation or selectively edit different spectral components

MRS in Motor Neuron Diseases

Upper motor neurons (UMN) in the motor cortex and/or lower motor neurons (LMN) in the brainstem and spinal cord are affected in a heterogeneous group of related or pathologically similar adult-onset diseases, collectively termed as motor neuron diseases (MND). Amyotrophic lateral sclerosis (ALS) is the most predominant (85 %) among MND in which both UMN and LMN progressively degenerate. The etiology of ALS is not known in approximately 90 % of patients; however, inheritance of genetic mutations underlies in about 10 % of them. To date, neither conventional neuroimaging techniques nor laboratory tests of body fluids or biopsy samples yielded definitive biomarkers for ALS. Furthermore, molecular and cellular mechanisms involved in this disease remain poorly understood. Proton MRS is well suited to quantify metabolite alterations in the brain, and it has been used on patients with ALS in an effort to gain insight into the pathophysiology of ALS. A brief description on MND and their subtypes, limitations of clinical neuroimaging methods to diagnose ALS, a number of brain metabolites that can be quantified by in vivo MRS and their relevance to MND, and MRS techniques and their limitations are provided. Use of a whole-brain MRSI approach to fully characterize changes within the brain due to disease is described with a sample dataset obtained in a patient with ALS. Changes in the concentration or ratio of brain metabolites in patients with ALS and their pathophysiological significances are described. Finally, the use of MRS methods for longitudinal and therapeutic evaluation studies and future perspectives are discussed

Magnetic resonance neuroimaging methods and protocols

The advent of non-invasive imaging technology, such as magnetic resonance imaging (MRI), has allowed biologists and clinicians to make great strides in unraveling the secrets of the brain. In Magnetic Resonance Neuroimaging: Methods and Protocols, expert researchers in the field provide a comprehensive collection of experimental MRI protocols that can be used to non-invasively interrogate the healthy and diseased brain. The chapters are divided into general techniques, such as the measurement of relaxivity, magnetic resonance spectroscopy, diffusion tensor imaging, and MR reporter genes, as well as specific applications in brain imaging, for example, phenotyping transgenic animals, detecting amyloid plaques, and fMRI in psychiatry. As a volume in the highly successful Methods in Molecular Biology series, this work contains the type of detailed description and implementation advice that is crucial for getting optimal results. Thorough and cutting-edge, Magnetic Resonance Neuroimaging: Methods and Protocols serves neuroscientists, clinical neurologists, psychiatrists, and radiologists with an excellent compendium of methods easily applied to both animal and human studies and certain to be an excellent resource for translational research

Glutathione Conformations and Its Implications for in vivo Magnetic Resonance Spectroscopy

Glutathione (GSH) is a major antioxidant in humans that is involved in the detoxification of reactive radicals and peroxides. The molecular structural conformations of GSH depend on the surrounding micro-environment, and it has been experimentally evaluated using NMR and Raman spectroscopic techniques as well as by molecular dynamics simulation studies. The converging report indicates that GSH exists mainly in two major conformations, i.e., "extended" and "folded". The NMR-derived information on the GSH conformers is essential to obtain optimal acquisition parameters in in vivo MRS experiments targeted for GSH detection. To further investigate the implications of GSH conformers in in vivo MRS studies and their relative proportions in healthy and pathological conditions, a multi-center clinical research study is necessary with a common protocol for GSH detection and quantification

Distributions of Magnetic Resonance Diffusion and Spectroscopy Measures with Traumatic Brain Injury

Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) studies have demonstrated that measures of altered metabolism and axonal injury can be detected following traumatic brain injury. The aim of this study was to characterize and compare the distributions of altered image parameters obtained by these methods in subjects with a range of injury severity and to examine their relative sensitivity for diagnostic imaging in this group of subjects. DTI and volumetric magnetic resonance spectroscopic imaging data were acquired in 40 subjects that had experienced a closed-head traumatic brain injury, with a median of 36 d post-injury. Voxel-based analyses were performed to examine differences of group mean values relative to normal controls, and to map significant alterations of image parameters in individual subjects. The between-group analysis revealed widespread alteration of tissue metabolites that was most strongly characterized by increased choline throughout the cerebrum and cerebellum, reaching as much as 40% increase from control values for the group with the worse cognitive assessment score. In contrast, the between-group comparison of DTI measures revealed only minor differences; however, the Z-score image analysis of individual subject DTI parameters revealed regions of altered values relative to controls throughout the major white matter tracts, but with considerable heterogeneity between subjects and with a smaller extent than the findings for altered metabolite measures. The findings of this study illustrate the complimentary nature of these neuroimaging methods

Multivariate statistical mapping of spectroscopic imaging data

For magnetic resonance spectroscopic imaging studies of the brain, it is important to measure the distribution of metabolites in a regionally unbiased way; that is, without restrictions to a priori defined regions of interest. Since magnetic resonance spectroscopic imaging provides measures of multiple metabolites simultaneously at each voxel, there is furthermore great interest in utilizing the multidimensional nature of magnetic resonance spectroscopic imaging for gains in statistical power. Voxelwise multivariate statistical mapping is expected to address both of these issues, but it has not been previously employed for spectroscopic imaging (SI) studies of brain. The aims of this study were to (1) develop and validate multivariate voxel-based statistical mapping for magnetic resonance spectroscopic imaging and (2) demonstrate that multivariate tests can be more powerful than univariate tests in identifying patterns of altered brain metabolism. Specifically, we compared multivariate to univariate tests in identifying known regional patterns in simulated data and regional patterns of metabolite alterations due to amyotrophic lateral sclerosis, a devastating brain disease of the motor neurons