Multishell diffusion MRI reveals whole-brain white matter changes in HIV

Area of Science:

• Neuroimaging
• Biophysics
• Medical Science

Background:

• Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have limitations in specificity for detecting white matter alterations in HIV infection.
• The Combined Hindered and Restricted Model of Diffusion (CHARMED) offers enhanced microstructural specificity.

Purpose of the Study:

• To evaluate microstructural differences in white matter between HIV-positive patients and healthy controls using DTI, DKI, and CHARMED.
• To assess the utility of these diffusion models, particularly CHARMED and DKI, in identifying widespread brain changes associated with HIV.
• To employ machine learning for discriminating HIV patients from controls using diffusion imaging metrics.

Main Methods:

• Diffusion-weighted imaging with three b-values was performed on 35 HIV-positive patients and 20 healthy controls.
• Analysis included DTI, DKI, and CHARMED models to assess white matter microstructural integrity.
• An XGBoost machine learning algorithm with Shapley Explanation values was used for classification and feature importance analysis.

Main Results:

• Significant group differences in diffusion metrics were observed across all models.
• CHARMED and DKI revealed broader white matter tract involvement (80%) in HIV infection compared to DTI (20%).
• Restricted fraction analysis identified specific tract differences, impacting functions like motor control, proprioception, and equilibrium.
• CHARMED and DKI metrics, analyzed via machine learning, demonstrated superior performance in discriminating HIV patients from controls.

Conclusions:

• Biophysical multishell imaging, particularly CHARMED and DKI, provides greater sensitivity and specificity for detecting microstructural brain changes in HIV infection.
• These advanced diffusion models highlight widespread white matter alterations affecting cognitive and attentive networks often impaired in HIV.
• CHARMED and DKI show promise as advanced neuroimaging biomarkers for understanding and potentially managing HIV-associated neurological complications.