Table 1.
Demographic characteristics of Parkinson’s disease (PD) and control subjects.
Mean values are provided with standard deviations denoted in parentheses. PD patients were observed to differ from the control group in UPDRS total and and motor sub scores.
Fig 1.
TSPOON Processing of relaxometry maps Illustrative diagram depicting the TSPOON processing used to help compensate for the smoothing of images and potential partial volume effects.
A native-space white matter mask is first calculated from by segmenting subject’s high flip ange SPGR image. Parameter maps and the native-space white matter mask are then smoothed with a Gaussian kernel and the template-aligned parameter maps are divided by the white matter mask. Lastly, an overall white matter mask calculated from the population averaged VFM map is applied to the relaxometry maps.
Fig 2.
VFM, T1, T2 Differences between PD Subjects and Controls.
(A) Compared with age-matched controls, PD subjects had higher VFM in bilateral thalamus and posterior limb of the internal capsule, left inferior temporal gyrus, right superior longitudinal fasciculus, and portions of the genu of the corpus callosum (shown in red). (B) R1 was found to be be increased within the left and right thalmus of the PD group. (C) R2 was found to be increased in the PD group in superior and inferior frontal white matter, anterior limb of the internal capsule, and genu of corpus callosum, as well as portions of the anterior putamen and pallidum. (D) Re-analyzing the VFM group differences with R1 and R2 as covariates yielded increased VFM in superior frontal white matter and genu of the corpus callosum in the PD group. Statistical images are overlaid on the study-specific T1-weighted template and results are shown p<0.05, corrected for multiple comparisons at the cluster extent. An anatomical reference for each representative figure is additionally provided. The magnitude and atlas locations of maximally significant differences in regional VFM are shown in Table 2.
Table 2.
Regions in which significant VFM differences were observed between PD patients and age-matched controls.
Abbreviations: R: Right; L: Left; WM: White Matter; Sup: Superior; Inf: Inferior; Ant: Anterior; Mid: Middle; Med: Medial; Lat: Lateral;
Fig 3.
Significant associations between relaxometry measures and age.
The negative effect of age on VFM, R1, and R2 was widespread throughout cerebral white matter in this middle- to late- age sample (p<0.05, cluster-corrected).
Fig 4.
Group differences in the relationship of age to VFM.
A. Differences in the relationship of age to VFM (i.e. age-by-group interaction) between PD and control subjects were primarily localized to the left putamen left inferior longitudinal fasciculus. B. Significant age-by-group interactions were additionally found with R1 within left fusiform gyrus, subcallosal cortex, and orbitofrontal white matter.
Table 3.
Brain regions in which a significant (p<0.05, cluster-corrected) positive age-by-group interaction was observed.
Shown are the anatomic location, MNI coordinates, t-statistic, and cluster extent. Abbreviations: L: Left; WM: White Matter; Post: Posterior; Ant: Anterior; Inf: Inferior, Mid: Middle.
Fig 5.
Age-by-group differences correcting for R1 and R2.
Including R1 and R2 in the age-by-group interaction model for VFM did not alter the significant interaction of the left putamen. To illustrate these age-by-group interactions, mean VFM and R1 were calculated from the significant clusters for each individual and plotted as a function of age amd group (PD and age-matched control).
Fig 6.
Associations between VFM and Parkinson’s disease severity measures.
Significant (p<0.05, cluster-corrected) correlations between VFM and disease severity measures, including disease severity composite (first row), disease duration (second row), daily levodopa equivalent dose levels (third row) and UPDRS score (fourth row). Positive associations (increased VFM with increased clinical score) are shown in red, while negative associations (decreased VFM with increased clinical score) are shown in blue.
Table 4.
Brain regions in which significant (p<0.05, cluster-corrected) associations between VFM and disease severity measures were observed.
Abbreviations: R: Right; L: Left; WM: White Matter; Sup: Superior; Inf: Inferior; Ant: Anterior; Pos: Posterior; Mid: Middle; Med: Medial; Lat: Lateral.