PURPOSE: Multiple system atrophy (MSA) is a rare neurodegenerative disease that remains poorly understood, and the diagnosis of MSA continues to be challenging. We endeavored to improve the diagnostic process and understanding of in vivo characteristics of MSA by diffusion tensor imaging (DTI). MATERIALS AND METHODS: Twenty MSA subjects, ten parkinsonian dominant (MSA-P), ten cerebellar dominant (MSA-C), and 20 healthy volunteer subjects were recruited. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity maps were processed using tract-based spatial statistics. Diffusion data were additionally evaluated in the basal ganglia. A support vector machine was used to assess diagnostic utility, leave-one-out cross-validation in the evaluation of classification schemes, and receiver operating characteristic analyses to determine cutoff values. RESULTS: We detected widespread changes in the brain white matter of MSA subjects; however, no group-wise differences were found between MSA-C and MSA-P subgroups. Altered DTI metrics in the putamen and middle cerebellar peduncles were associated with a positive parkinsonian and cerebellar phenotype, respectively. Concerning clinical applicability, we achieved high classification performance on mean diffusivity data in the combined bilateral putamen and middle cerebellar peduncle (accuracy 90.3%±9%, sensitivity 86.5%±11%, and specificity 99.3%±4%). CONCLUSION: DTI in the middle cerebellar peduncle and putamen may be used in the diagnosis of MSA with a high degree of accuracy.

• Keywords
• diagnostic imaging, diffusion tensor imaging, magnetic resonance imaging, multiple system atrophy, neuroimaging,
• Publication type
• Journal Article MeSH

Huntington's disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.

• MeSH
• Basal Ganglia pathology   MeSH
• Adult MeSH
• DNA Repeat Expansion MeSH
• Globus Pallidus metabolism   pathology   MeSH
• Huntington Disease genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Spectroscopy MeSH
• Aged MeSH
• Iron metabolism   MeSH
• Diffusion Tensor Imaging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Iron MeSH

Pantothenate-kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by iron deposits in basal ganglia. The aim of this study was to quantify iron concentrations of deep gray matter structures in heterozygous PANK2 mutation carriers and in PKAN patients using quantitative susceptibility mapping MRI. By determining iron concentration, we intended to find mutation-specific brain parenchymal stigmata in heterozygous PANK2 mutation carriers in comparison to age-matched healthy volunteers. We studied 11 heterozygous PANK2 gene mutation carriers (mean age: 43.4 years; standard deviation [SD]: 10.5), who were found to be clinically asymptomatic by neurological examination. These carriers were compared to 2 clinically affected PKAN patients 21 and 32 years of age and to 13 age-matched, healthy controls (mean age: 39.7; SD, 13.6). Scanning was performed on a 7.0-Tesla whole-body scanner applying three-dimensional susceptibility-weighted gradient echo acquisitions. Susceptibility maps were calculated by threshold-based k-space division with single-orientation acquisition. Magnetic susceptibility values, relative to the occipital white matter, were determined for the following regions of interest (ROI): globus pallidus (GP), thalamus, putamen, internal capsule (IC), caudate nucleus, substantia nigra (SN), and red nucleus. Heterozygous PANK2 mutation carriers did not show increased brain iron concentrations, compared to healthy controls (P > 0.05), in any of the examined ROIs. In PKAN patients, more than 3 times higher concentrations of iron were found in the GP, SN, and IC. Our results suggest that heterozygous mutations in PANK2 gene do not cause brain iron accumulation nor do they cause movement disorders.

• Keywords
• 7‐Tesla MRI, iron, neurodegeneration with brain iron accumulation (NBIA), pantothenate kinase associated neurodegeneration (PKAN), quantitative susceptibility mapping,
• Publication type
• Journal Article MeSH

Fractional anisotropy (FA) is the most commonly used quantitative measure of diffusion in the brain. Changes in FA have been reported in many neurological disorders, but the implementation of diffusion tensor imaging (DTI) in daily clinical practice remains challenging. We propose a novel color look-up table (LUT) based on normative data as a tool for screening FA changes. FA was calculated for 76 healthy volunteers using 12 motion-probing gradient directions (MPG), a subset of 59 subjects was additionally scanned using 30 MPG. Population means and 95% prediction intervals for FA in the corpus callosum, frontal gray matter, thalamus and basal ganglia were used to create the LUT. Unique colors were assigned to inflection points with continuous ramps between them. Clinical use was demonstrated on 17 multiple system atrophy (MSA) patients compared to 13 patients with Parkinson disease (PD) and 17 healthy subjects. Four blinded radiologists classified subjects as MSA/non-MSA. Using only the LUT, high sensitivity (80%) and specificity (84%) were achieved in differentiating MSA subjects from PD subjects and controls. The LUTs generated from 12 and 30 MPG were comparable and accentuate FA abnormalities.

• MeSH
• Algorithms MeSH
• Anisotropy * MeSH
• Color * MeSH
• Basal Ganglia physiology   MeSH
• Frontal Lobe physiology   MeSH
• Corpus Callosum physiology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain Mapping methods   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Brain physiology   MeSH
• Multiple System Atrophy diagnosis   pathology   MeSH
• Parkinson Disease diagnosis   pathology   MeSH
• Signal-To-Noise Ratio MeSH
• Reference Values MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Software MeSH
• Thalamus physiology   MeSH
• Healthy Volunteers MeSH
• Diffusion Tensor Imaging methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH