MRI Signatures of Brain Macrostructural Atrophy and Microstructural Degradation in Frontotemporal Lobar Degeneration Subtypes

Abstract

Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy.

Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations

“…This pattern was consistent with the results of previous VBM studies performed in FTLDcontrol series where the underlying genetic causes were not known [15]. The temporal atrophic clusters were located in the left middle temporal gyrus, temporal pole and superior temporal gyrus and in frontal regions.…”

“…Although, we have previously identified patterns of regional brain atrophy associated with other genetic variants with similar study designs to the present one [15,17,18], our study still has several limitations: the number of subjects is low, but this was expected considering the low frequency of SQSTM1 mutations among FTD patients. In addition, the distribution of the three populations studied (FTD/SQSTM1 carriers, Sporadic FTD and HC/SQSTM1 noncarriers) was not homogeneous among centers.…”

“…For this purpose we used VBM MRI, which we have used successfully in the past to identify regional brain atrophy associated with other genetic variants, even in relatively small samples [17,18]. In these studies, we reported that morphometric neuroimaging studies could identify brain regions sensitive to the damaging effects of specific genetic variants [15,17,18,19].…”

Based on the Network Degeneration Hypothesis: Separating Individual Patients with Different Neurodegenerative Syndromes in a Preliminary Hybrid PET/MR Study

“…For example, a previous study applied VBM and diffusion tensor imaging (DTI) to separate FTLD subtypes (i.e., bvFTD, SD, and PNFA) from healthy controls. The authors revealed that DTI measurement, particularly radial diffusivity, provided better accuracies (67.6%-81.4%) than gray matter atrophy (45.7%-65.7%) or white matter atrophy (47.4%-59.2%) (41). Moreover, Dukart et al demonstrated classification accuracy of 60.0% using structural MRI, 80.0% using 18 F-FDG PET, and 94.3% using combined 18 F-FDG PET and structural MRI to separate AD from FTLD patients (18).…”

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

“…Nine whole-brain studies of FTD were included (Zhang, Schuff et al 2009, Hornberger, Geng et al 2011, Zhang, Tartaglia et al 2013, Tovar-Moll, de Oliveira-Souza et al 2014, Downey, Mahoney et al 2015. When FTD patients were compared to ALS and ALS-FTD patients, TBSS revealed significant changes involving the callosal tracts; the forceps minor, and ILF than in CST .…”