Dataset Information

Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy 1H-MRS in amyotrophic lateral sclerosis.

ABSTRACT: Objective:To determine the relationship between brain tissue metabolites measured by in vivo magnetic resonance spectroscopy (1H-MRS), and glial activation assessed with [11C]-PBR28 uptake in people with amyotrophic lateral sclerosis (ALS). Methods:Forty ALS participants were evaluated clinically using the revised ALS functional rating scale (ALSFRS-R) and upper motor neuron burden (UMNB). All participants underwent simultaneous brain [11C]-PBR28 PET and MR imaging including diffusion tensor imaging to acquire fractional anisotropy (FA). [11C]-PBR28 uptake was measured as standardized uptake values normalized by whole brain mean (SUVR). 1H-MRS metabolite ratios (myo-inositol/creatine, mI/Cr; N-acetylaspartate/creatine, NAA/Cr) were measured within the precentral gyri and brain stem (regions known to be involved in ALS pathophysiology), and precuneus (which served as a control region). Whole brain voxel-wise correlation analyses were employed to identify brain regions exhibiting an association between metabolites within the VOIs and [11C]-PBR28 uptake. Results:In the precentral gyri, [11C]-PBR28 uptake correlated positively with mI/Cr and negatively with NAA/Cr. The same correlations were not statistically significant in the brain stem, or in the control precuneus region. Whole brain voxel-wise correlation analyses between the estimated brain metabolites within the VOIs and SUVR were highly correlated in the precentral gyri. Decreased FA values in the precentral gyri were correlated with reduced NAA/Cr and elevated mI/Cr. Higher UMNB was correlated with increased [11C]-PBR28 uptake and mI/Cr, and decreased NAA/Cr. ALSFRS-R total score correlated positively with NAA/Cr and negatively with mI/Cr. Conclusion:Integrated PET-MR and 1H-MRS imaging demonstrates associations between markers for neuronal integrity and neuroinflammation and may provide valuable insights into disease mechanisms in ALS.

SUBMITTER: Ratai EM

PROVIDER: S-EPMC6092554 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrated imaging of [<sup>11</sup>C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy <sup>1</sup>H-MRS in amyotrophic lateral sclerosis.

Ratai Eva-Maria EM Alshikho Mohamad J MJ Zürcher Nicole R NR Loggia Marco L ML Cebulla Catherine L CL Cernasov Paul P Reynolds Beverly B Fish Jennifer J Seth Raghav R Babu Suma S Paganoni Sabrina S Hooker Jacob M JM Atassi Nazem N

NeuroImage. Clinical 20180809

<h4>Objective</h4>To determine the relationship between brain tissue metabolites measured by <i>in vivo</i> magnetic resonance spectroscopy (<sup>1</sup>H-MRS), and glial activation assessed with [<sup>11</sup>C]-PBR28 uptake in people with amyotrophic lateral sclerosis (ALS).<h4>Methods</h4>Forty ALS participants were evaluated clinically using the revised ALS functional rating scale (ALSFRS-R) and upper motor neuron burden (UMNB). All participants underwent simultaneous brain [<sup>11</sup>C]- ...[more]

PMID: 30112276

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Project description:Increasing evidence suggests that inflammation is one pathophysio-logical mechanism in Alzheimer's disease (AD). Recent studies have identifiedan association between the poly (ADP-ribose) polymerase 1 (PARP1) gene and AD. This gene encodes a protein that is involved in many biological functions, including DNA repair and chromatin remodeling, and is a mediator of inflammation. Therefore, we performed a targeted genetic association analysis to investigate the relationship between the PARP1 polymorphisms and brain micro-glial activity as indexed by [11C]PBR28 positron emission tomography (PET). Participants were 26 non-Hispanic Caucasians in the Indiana Memory and Aging Study (IMAS). PET data were intensity-normalized by injected dose/total body weight. Average PBR standardized uptake values (SUV) from 6 bilateral regions of interest (thalamus, frontal, parietal, temporal, and cingulate cortices, and whole brain gray matter) were used as endophenotypes. Single nucleotide polymorphisms (SNPs) with 20% minor allele frequency that were within +/- 20 kb of the PARP1 gene were included in the analyses. Gene-level association analyses were performed using a dominant genetic model with translocator protein (18-kDa) (TSPO) genotype, age at PET scan, and gender as covariates. Analyses were performed with and without APOE ?4 status as a covariate. Associations with PBR SUVs from thalamus and cingulate were significant at corrected p<0.014 and <0.065, respectively. Subsequent multi-marker analysis with cingulate PBR SUV showed that individuals with the "C" allele at rs6677172 and "A" allele at rs61835377 had higher PBR SUV than individuals without these alleles (corrected P<0.03), and individuals with the "G" allele at rs6677172 and "G" allele at rs61835377 displayed the opposite trend (corrected P<0.065). A previous study with the same cohort showed an inverse relationship between PBR SUV and brain atrophy at a follow-up visit, suggesting possible protective effect of microglial activity against cortical atrophy. Interestingly, all 6 AD and 2 of 3 LMCI participants in the current analysis had one or more copies of the "GG" allele combination, associated with lower cingulate PBR SUV, suggesting that this gene variant warrants further investigation.

Dataset Information

Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy 1H-MRS in amyotrophic lateral sclerosis.

Publications

Integrated imaging of [<sup>11</sup>C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy <sup>1</sup>H-MRS in amyotrophic lateral sclerosis.

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