Zheng Zhong^{1,2}, Muge Karaman^{1,2}, Kaibao Sun^{1}, and Xiaohong Joe Zhou^{1,2,3}

Aging is considered a major factor in the development of neurodegenerative disease. The aging process can result in brain tissue microstructural alterations, particularly in regions relevant to neurodegeneration, such as the substantia nigra (SN). In this study, we employed a non-Gaussian diffusion model – the continuous-time random-walk (CTRW) model – together with a high-resolution diffusion acquisition technique to investigate the possible microstructural changes in the SN in normal aging. Two CTRW model parameters have exhibited significant differences in the SN between young and elderly healthy human subjects.

Subjects:

With IRB approval, 18 elderly and 15 young healthy subjects were recruited in the study. The characteristics of all subjects are summarized in Table 1.

Image Acquisition:

All subjects underwent diffusion MRI on a
3T GE MR750 scanner. Diffusion images were acquired from the brainstem using a
customized reduced field-of-view sequence^{6} with seven *b*-values: 0_{4}, 50_{2},
200_{2}, 500_{4}, 1000_{4}, 2000_{4}, and 3000_{4}
s/mm^{2}
(the subscript denotes NEXs). The other
parameters were: TR/TE=3080/86ms, slice thickness=3mm, FOV=10cm×6cm, and matrix
size=160×96, producing a voxel size of 0.6×0.6×3mm^{3}. At each non-zero *b*-value, trace-weighted images were obtained to minimize the effect
of diffusion anisotropy.

Image and Statistical Analysis:

The
CTRW model describes the diffusion-weighted (DW) signal using a Mittag-Leffler
function E_{α}:
$$M(b)=M_{0}E_{\alpha}(-(bD_{m})^{\beta}), [1] $$ where *D _{m}*
is an anomalous diffusion coefficient, and

For
each subject, regions-of-interest (ROIs) were drawn on each side of the SN as
well as in the
tegmentum which served as an internal reference to
exclude other confound factors^{8}. The mean value of each
diffusion parameter within the ROIs was calculated and compared between the young
and the elderly groups using a 2-tailed Student’s *t*-test.

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