Voxel-wise functional-to-gray matter volume ratios reveal distinct brain patterns in cirrhosis stratified by hepatic encephalopathy history and clinical status
- 1Fuzong Teaching Hospital of Fujian University of Traditional Chinese Medicine (900th Hospital)
- 2College of Integrative Medicine, Fujian University of Traditional Chinese Medicine
- 3The Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine
Abstract
Background: Hepatic encephalopathy (HE) is associated with distributed structural and functional brain abnormalities, but how local resting-state functional signals vary relative to gray matter volume (GMV) remains uncertain.
Methods: We retrospectively analyzed previously acquired magnetic resonance imaging (MRI) and clinical data from 97 participants after motion exclusion: 38 healthy controls (HCs), 29 patients with cirrhosis who had no history of overt HE and were classified as West Haven grade 0 at enrollment (NHE), and 30 patients in an operationally defined HE group. Voxel-wise regional homogeneity-to-GMV (ReHo-to-GMV) and amplitude of low-frequency fluctuation-to-GMV (ALFF-to-GMV) ratios were assessed in separate 3-group models adjusted for age, sex, education, and mean framewise displacement. Gaussian random-field cluster inference was used for the primary analysis, with 10,000-permutation threshold-free cluster enhancement (TFCE) as a non-parametric sensitivity analysis.
Results: Corrected abnormalities were concentrated in HE versus HCs, whereas neither metric showed a corrected HE-versus-NHE difference. ReHo-to-GMV and ALFF-to-GMV each yielded 13 corrected clusters across the test-specific omnibus and directional results. Permutation and local-GMV-adjusted sensitivity analyses supported the principal HE-versus-HC effects. Cross-metric overlap was limited to 31 HCs > HE voxels (Dice = 0.0541), and none of the 48 exploratory region-of-interest clinical associations survived false-discovery-rate correction.
Conclusion: These ratios identify partly distinct group-level neuroimaging patterns of local functional signals relative to GMV in cirrhosis, but they should be interpreted as operational imaging measures rather than direct physiological coupling or validated biomarkers.
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BibTeX
@article{yu2026voxelwise,
title = {{Voxel-wise functional-to-gray matter volume ratios reveal distinct brain patterns in cirrhosis stratified by hepatic encephalopathy history and clinical status}},
author = {Zhen Yu and Minghui Mao and Qianghong Xue and Chengkun Hong and Hao Huang and Aling Shen and Liyuan Fu},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1969935},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1969935/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Voxel-wise functional-to-gray matter volume ratios reveal distinct brain patterns in cirrhosis stratified by hepatic encephalopathy history and clinical status
AU - Zhen Yu
AU - Minghui Mao
AU - Qianghong Xue
AU - Chengkun Hong
AU - Hao Huang
AU - Aling Shen
AU - Liyuan Fu
PY - 2026
DA - 2026/10/19
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1969935
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1969935/full
AB - Background: Hepatic encephalopathy (HE) is associated with distributed structural and functional brain abnormalities, but how local resting-state functional signals vary relative to gray matter volume (GMV) remains uncertain. Methods: We retrospectively analyzed previously acquired magnetic resonance imaging (MRI) and clinical data from 97 participants after motion exclusion: 38 healthy controls (HCs), 29 patients with cirrhosis who had no history of overt HE and were classified as West Haven grade 0 at enrollment (NHE), and 30 patients in an operationally defined HE group. Voxel-wise regional homogeneity-to-GMV (ReHo-to-GMV) and amplitude of low-frequency fluctuation-to-GMV (ALFF-to-GMV) ratios were assessed in separate 3-group models adjusted for age, sex, education, and mean framewise displacement. Gaussian random-field cluster inference was used for the primary analysis, with 10,000-permutation threshold-free cluster enhancement (TFCE) as a non-parametric sensitivity analysis. Results: Corrected abnormalities were concentrated in HE versus HCs, whereas neither metric showed a corrected HE-versus-NHE difference. ReHo-to-GMV and ALFF-to-GMV each yielded 13 corrected clusters across the test-specific omnibus and directional results. Permutation and local-GMV-adjusted sensitivity analyses supported the principal HE-versus-HC effects. Cross-metric overlap was limited to 31 HCs > HE voxels (Dice = 0.0541), and none of the 48 exploratory region-of-interest clinical associations survived false-discovery-rate correction. Conclusion: These ratios identify partly distinct group-level neuroimaging patterns of local functional signals relative to GMV in cirrhosis, but they should be interpreted as operational imaging measures rather than direct physiological coupling or validated biomarkers.
SN - 1664-2295
ER -