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Wenzhen Zhu

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4 papers

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YNICL Journal 2025 Journal Article

Neurotransmitter imbalance, glutathione depletion and concomitant susceptibility increase in Parkinson’s disease

Su Yan
Bingfang Duan
Yuanhao Li
Hongquan Zhu
Zhaoqi Shi
Xiaoxiao Zhang
Yuanyuan Qin
Wenzhen Zhu

BACKGROUND: Emerging insights into the pathophysiology of Parkinson's disease (PD) underscore the involvement of dysregulated neurotransmission, iron accumulation and oxidative stress. Nonetheless, the excitatory and inhibitory neurometabolites, the antioxidant glutathione (GSH), and magnetic susceptibility are seldom studied together in the clinical PD literature. METHODS: We acquired MEGA-PRESS and multi-echo gradient echo sequences from 60 PD patients and 47 healthy controls (HCs). Magnetic resonance spectroscopy voxels were respectively positioned in the midbrain to quantify neurotransmitter including γ-aminobutyric acid (GABA) and glutamate plus glutamine, and in the left striatum to estimate GSH levels. Group differences in metabolite levels normalized to total creatine (Cr) and their clinical relevance were determined. Furthermore, relationships among GSH levels, neurotransmitter estimates and susceptibility values were explored in both PD patients and HCs. RESULTS: < 0.001). Mesencephalic choline levels were correlated with the severity of rapid eye movement sleep behavior disorders symptoms, whereas striatal N-acetylaspartate levels were linked to Hoehn-Yahr stage and motor symptom severity. Notably, the disruption of associations between striatal GSH levels and susceptibility values in globus pallidus, as well as midbrain GABA levels, were evident in PD. CONCLUSIONS: These findings offer compelling evidence for metabolic dysregulation in PD, characterized by a concomitant reduction in GABA and GSH levels, alongside iron deposition.

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YNIMG Journal 2025 Journal Article

Potential separation of multiple system atrophy and Parkinson’s disease by susceptibility-derived components

Su Yan
Jun Lu
Bingfang Duan
Shun Zhang
Dong Liu
Yuanyuan Qin
Alexey V. Dimov
Junghun Cho

BACKGROUND: Substantial evidence emphasizes the dysregulation of iron homeostasis, demyelination and oxidative stress in the neurodegenerative process of multiple system atrophy (MSA) and Parkinson's disease (PD), although its clinical implications remain unclear. Recent MRI post-processing techniques leveraging magnetic susceptibility properties provide a noninvasive means to characterize iron, myelin content and oxygen metabolism alterations. This study aims to investigate subcortical alterations of susceptibility-derived metrics in these two synucleinopathies. METHODS: A cohort comprising 180 patients (122 with PD and 58 with MSA) and 77 healthy controls (HCs) underwent clinical evaluation and multi-echo gradient echo MRI scans. Susceptibility source separation, susceptibility-based oxygen extraction fraction (OEF) mapping and semiautomatic subcortical nuclei segmentation were utilized to derive parametric values of deep gray matter in all subjects. RESULTS: MSA patients showed markedly elevated paramagnetic susceptibility values in the putamen, globus pallidus (GP) and thalamus; increased diamagnetic susceptibility values in the putamen and dentate nucleus; and reduced OEF values across all nuclei compared with PD patients and HCs. Whereas PD exhibited increased positive susceptibility values in the substantia nigra and enhancing negative values in the GP, similar to MSA. Notably, age-related reductions in OEF were evident in HCs, which was altered by the MSA pathology. Paramagnetic susceptibility was correlated with disease severity. Moreover, the susceptibility-derived metrics of striatum and midbrain nuclei proved to be effective predictors to distinguish PD from MSA (AUC = 0.833). CONCLUSION: Susceptibility-derived metrics could detect pathological involvement distinct to each disease, offering significant potential for differentiating between MSA and PD in clinical settings.

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YNIMG Journal 2024 Journal Article

Trajectories and sex differences of brain structure, oxygenation and perfusion functions in normal aging

Di Wu
Yuanhao Li
Shun Zhang
Qiuyue Chen
Jiayu Fang
Junghun Cho
Yi Wang
Su Yan

BACKGROUND: Brain structure, oxygenation and perfusion are important factors in aging. Coupling between regional cerebral oxygen consumption and perfusion also reflects functions of neurovascular unit (NVU). Their trajectories and sex differences during normal aging important for clinical interpretation are still not well defined. In this study, we aim to investigate the relationship between brain structure, functions and age, and exam the sex disparities. METHOD: < 0.05 was considered statistically significant. RESULTS: < 0.05). CONCLUSION: The sex disparities, age trajectories of brain structure and functions as well as the coupling of NVU in healthy individuals provide insights into normal aging which are potential targets for study of pathological conditions.

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AAAI Conference 2022 Conference Paper

Invariant Information Bottleneck for Domain Generalization

Bo Li
Yifei Shen
Yezhen Wang
Wenzhen Zhu
Colorado Reed
Dongsheng Li
Kurt Keutzer
Han Zhao

Invariant risk minimization (IRM) has recently emerged as a promising alternative for domain generalization. Nevertheless, the loss function is difficult to optimize for nonlinear classifiers and the original optimization objective could fail when pseudo-invariant features and geometric skews exist. Inspired by IRM, in this paper we propose a novel formulation for domain generalization, dubbed invariant information bottleneck (IIB). IIB aims at minimizing invariant risks for nonlinear classifiers and simultaneously mitigating the impact of pseudo-invariant features and geometric skews. Specifically, we first present a novel formulation for invariant causal prediction via mutual information. Then we adopt the variational formulation of the mutual information to develop a tractable loss function for nonlinear classifiers. To overcome the failure modes of IRM, we propose to minimize the mutual information between the inputs and the corresponding representations. IIB significantly outperforms IRM on synthetic datasets, where the pseudo-invariant features and geometric skews occur, showing the effectiveness of proposed formulation in overcoming failure modes of IRM. Furthermore, experiments on DomainBed show that IIB outperforms 13 baselines by 0. 9% on average across 7 real datasets.

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