Category: Basic Science

At the end of the session, participants will be able to:

  1. Describe a multimodal approach to studying the human brain by integrating premortem neuromonitoring
    with rapid postmortem tissue analysis and ex vivo organotypic culture.
  2. Explain how correlating physiological data with cellular and molecular findings can advance
    understanding of neurological disease mechanisms and therapeutic development.

COI Disclosure:

I have a relationship with a for-profit and/or a not-for-profit organization to disclose. 

Any direct financial payments including receipt of honoraria:
Name of for-profit or not-for-profit organization(s) : CANP, Free Neuropathology
Description of relationship(s) : Secretary-Treasurer, Associate Editor

Presenter

Veronica Hirsch-Reinshagen

Rachel Boyd¹, Jordan Bird2, N. Catie Futhey3, Pushwant Mattu4, Mark Cembrowski1,2, Mypinder Sekhon2, Veronica Hirsch-Reinshagen2,4

1Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada

2Division of Critical Care Medicine, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada

3MD/PhD Program, University of British Columbia, Vancouver, BC, Canada

4Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada

Target Audience:

Pathologists
Residents
Medical Students

CanMEDS:

Medical Expert (the integrating role)
Collaborator
Scholar
Professional

Precision neuroscience across the dying process: Linking in-vivo monitoring with ex-vivo human brain analysis

Abstract

Understanding human brain function at cellular and molecular scales remains a major barrier to advancing effective therapies for neurological disease. This work proposes a within-patient precision neuroscience platform that integrates premortem clinical assessment with rapid postmortem tissue analysis. The objective is to directly link premortem neurological function with ex vivo cellular and molecular phenotypes derived from organotypic brain tissue cultures. In a prospective study at Vancouver General Hospital, critically ill patients and individuals undergoing medical assistance in dying undergo multimodal evaluation, including neuroimaging, electrophysiology, invasive neuromonitoring, and biomarker profiling before and after withdrawal of life-sustaining therapies or MAiD. Following death, rapid autopsy enables recovery of high-quality brain tissue, which is subsequently used in organotypic culture systems for functional interrogation. Comprehensive analyses—including neuropathology, spatial transcriptomics, and real-time imaging—are used to characterize disease-related cellular signatures and enable experimental manipulation, including pharmacological testing. Preliminary results demonstrate the feasibility of this approach and provide unprecedented data on premortem brain activity and ex vivo tissue physiology. This integrated platform provides a unique capacity to correlate physiological, cellular, and molecular features within individuals, bridging a critical translational gap in neuroscience research.