Robust Computation of Subcortical Functional Connectivity Guided by Quantitative Susceptibility Mapping: An Application in Parkinson's Disease Diagnosis.

Journal: NeuroImage
Published Date: May 8, 2025

Abstract

Previous resting state functional MRI (rs-fMRI) analyses of the basal ganglia in Parkinson's disease heavily relied on T1-weighted imaging (T1WI) atlases. However, subcortical structures are characterized by subtle contrast differences, making their accurate delineation challenging on T1WI. In this study, we aimed to introduce and validate a method that incorporates quantitative susceptibility mapping (QSM) into the rs-fMRI analytical pipeline to achieve precise subcortical nuclei segmentation and improve the stability of RSFC measurements in Parkinson's disease. A total of 321 participants (148 patients with Parkinson's Disease and 173 normal controls) were enrolled. We performed cross-modal registration at the individual level for rs-fMRI to QSM (FUNC2QSM) and T1WI (FUNC2T1), respectively.The consistency and accuracy of resting state functional connectivity (RSFC) measurements in two registration approaches were assessed by intraclass correlation coefficient and mutual information. Bootstrap analysis was performed to validate the stability of the RSFC differences between Parkinson's disease and normal controls. RSFC-based machine learning models were constructed for Parkinson's disease classification, using optimized hyperparameters (RandomizedSearchCV with 5-fold cross-validation). The consistency of RSFC measurements between the two registration methods was poor, whereas the QSM-guided approach showed better mutual information values, suggesting higher registration accuracy. The disruptions of RSFC identified with the QSM-guided approach were more stable and reliable, as confirmed by bootstrap analysis. In classification models, the QSM-guided method consistently outperformed the T1WI-guided method, achieving higher test-set ROC-AUC values (FUNC2QSM: 0.87-0.90, FUNC2T1: 0.67-0.70). The QSM-guided approach effectively enhanced the accuracy of subcortical segmentation and the stability of RSFC measurement, thus facilitating future biomarker development in Parkinson's disease.

Authors

  • Jianmei Qin
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Haoting Wu
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Chenqing Wu
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Tao Guo
    Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, Zhejiang, China.
  • Cheng Zhou
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xiaojie Duanmu
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Sijia Tan
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jiaqi Wen
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Qianshi Zheng
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Weijin Yuan
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zihao Zhu
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jingwen Chen
    Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, China. Electronic address: jwchen@dlut.edu.cn.
  • Jingjing Wu
    Department of Infections，Beijing Hospital of Traditional Chinese Medicine, Affiliated to the Capital Medical University, No. 23, Back Road of the Art Gallery, Dongcheng District, Beijing 100010, China.
  • Chenyu He
    State Key Laboratory of Computer-aided Design & Computer Graphics, Zhejiang University College of Computer Science and technology, Hangzhou, China.
  • Yiran Ma
    State Key Laboratory of Industrial Control Technology, Zhejiang University College of Control Science and Engineering, Hangzhou, China.
  • Chunlei Liu
    Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.; Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
  • Xiaojun Xu
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Xiaojun Guan
    Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Joint Laboratory of Clinical Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: xiaojunguan1102@zju.edu.cn.
  • Minming Zhang
    Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. zhangminming@zju.edu.cn.

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