Multimodal hyper-connectivity of functional networks using functionally-weighted LASSO for MCI classification

Yang Li, Jingyu Liu, Xinqiang Gao, Biao Jie, Minjeong Kim, Pew Thian Yap, Chong Yaw Wee, Dinggang Shen

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Recent works have shown that hyper-networks derived from blood-oxygen-level-dependent (BOLD) fMRI, where an edge (called hyper-edge) can be connected to more than two nodes, are effective biomarkers for MCI classification. Although BOLD fMRI is a high temporal resolution fMRI approach to assess alterations in brain networks, it cannot pinpoint to a single correlation of neuronal activity since BOLD signals are composite. In contrast, arterial spin labeling (ASL) is a lower temporal resolution fMRI technique for measuring cerebral blood flow (CBF) that can provide quantitative, direct brain network physiology measurements. This paper proposes a novel sparse regression algorithm for inference of the integrated hyper-connectivity networks from BOLD fMRI and ASL fMRI. Specifically, a least absolution shrinkage and selection operator (LASSO) algorithm, which is constrained by the functional connectivity derived from ASL fMRI, is employed to estimate hyper-connectivity for characterizing BOLD-fMRI-based functional interaction among multiple regions. An ASL-derived functional connectivity is constructed by using an Ultra-GroupLASSO-UOLS algorithm, where the combination of ultra-least squares (ULS) criterion with a group LASSO (GroupLASSO) algorithm is applied to detect the topology of ASL-based functional connectivity networks, and then an ultra-orthogonal least squares (UOLS) algorithm is used to estimate the connectivity strength. By combining the complementary characterization conveyed by rs-fMRI and ASL fMRI, our multimodal hyper-networks demonstrated much better discriminative characteristics than either the conventional pairwise connectivity networks or the unimodal hyper-connectivity networks. Experimental results on publicly available ADNI dataset demonstrate that the proposed method outperforms the existing single modality based sparse functional connectivity inference methods.

Original languageEnglish
Pages (from-to)80-96
Number of pages17
JournalMedical Image Analysis
Publication statusPublished - 2019 Feb


  • Arterial spin labeling (ASL)
  • Hyper-connectivity network
  • Mild cognitive impairment (MCI)
  • Multimodality
  • Ultra-least squares (ULS)
  • Weighted LASSO

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Computer Vision and Pattern Recognition
  • Health Informatics
  • Computer Graphics and Computer-Aided Design


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