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Cited by 15Advanced Neuroimaging Techniques and ApplicationsHIV Research and TreatmentHIV-related health complications and treatments

Fixel-based analysis and free water corrected DTI evaluation of hiv associated neurocognitive disorders.

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Finkelstein, Alan, Faiyaz, Abrar, Weber, Miriam T., Qiu, Xing, Uddin, Md Nasir, Zhong, Jianhui, Schifitto, Giovanni·2021·Frontiers in Neurology
DOI 10.3389/fneur.2021.725059PMC PMC8600320

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Abstract

Background: White matter (WM) damage is a consistent finding in HIV-infected (HIV+) individuals. Previous studies have evaluated WM fiber tract-specific brain regions in HIV-associated neurocognitive disorders (HAND) using diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) have recently emerged as useful techniques to quantify abnormalities in WM. Here, we sought to evaluate FBA and fwcDTI metrics between HIV+ and healthy controls (HIV−) individuals. Using machine learning classifiers, we compared the specificity of both FBA and fwcDTI metrics in their ability to distinguish between individuals with and without cognitive impairment in HIV+ individuals. Methods: Forty-two HIV+ and 52 HIV– participants underwent MRI exam, clinical, and neuropsychological assessments. FBA metrics included fiber density (FD), fiber bundle cross section (FC), and fiber density and cross section (FDC). We also obtained fwcDTI metrics such as fractional anisotropy (FA T ) and mean diffusivity (MD T ). Tract-based spatial statistics (TBSS) was performed on FA T and MD T . We evaluated the correlations between MRI metrics with cognitive performance and blood markers, such as neurofilament light chain (NfL), and Tau protein. Four different binary classifiers were used to show the specificity of the MRI metrics for classifying cognitive impairment in HIV+ individuals. Results: Whole-brain FBA showed significant reductions (up to 15%) in various fiber bundles, specifically the cerebral peduncle, posterior limb of internal capsule, middle cerebellar peduncle, and superior corona radiata. TBSS of fwcDTI metrics revealed decreased FA T in HIV+ individuals compared to HIV– individuals in areas consistent with those observed in FBA, but these were not significant. Machine learning classifiers were consistently better able to distinguish between cognitively normal patients and those with cognitive impairment when using fixel-based metrics as input features as compared to fwcDTI metrics. Conclusion: Our findings lend support that FBA may serve as a potential in vivo biomarker for evaluating and monitoring axonal degeneration in HIV+ patients at risk for neurocognitive impairment.

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Authors
Finkelstein, A., Faiyaz, A., Weber, M. T., Qiu, X., Uddin, M. N., Zhong, J., & Schifitto, G.
Affiliations
  • University of Rochester (US)
  • University of Rochester Medicine (US)
Corresponding author
  • Uddin, Md Nasir
  • Schifitto, Giovanni
ORCID
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2021-11-04
Volume
12
Pages
725059-725059
ISSN
1664-2295 (ISSN-L)
DOI
10.3389/fneur.2021.725059
PMC
PMC8600320
OpenAlex
W3211100651
Cited by
15
References
7
Citations by year
2026: 2 · 2025: 6 · 2024: 1 · 2023: 2 · 2022: 4
FWCI
0.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (R01-AG054328, R01-MH099921, R01-MH118020)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Keywords
HIV-associated neurocognitive disorders, fixel-based analysis, white matter injury, axonal degeneration, cognitive impairment, fractional anisotropy, mean diffusivity, fiber density, neurofilament light chain, tau protein, cerebral peduncle, internal capsule, superior corona radiata, machine learning classification, MRI biomarkers

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