Abstract
Torpor is a regulated state of reduced metabolic demand that enables animals to conserve energy under unfavorable environmental conditions. The controlled induction of a similar state, termed synthetic torpor, has potential applications in ischemic protection, organ preservation, cancer treatment, radiation protection, and long-term spaceflight. Although neuronal populations within the preoptic hypothalamus have been shown to initiate hypothermic and hypometabolic states, the distributed cerebral hemodynamic dynamics accompanying their induction and maintenance remain poorly understood. In this thesis, we developed an accessible functional ultrasound imaging (fUSI) acquisition and analysis pipeline and applied it to investigate cerebral hemodynamics during chemogenetic activation of the medial preoptic area (MPOA) in mice.
The completed pipeline integrated chronic cranial-window preparation, awake head fixation, reproducible imaging-plane localization, ultrafast Power Doppler acquisition, physiological monitoring, motion-quality assessment, anatomical registration, atlas-based segmentation, and interactive analysis within a custom MATLAB graphical user interface. The platform supported regional time-course analysis, seed-based correlation, functional connectivity, epoch and group analysis, and hierarchical clustering. Whisker-stimulation experiments validated the pipeline by detecting reproducible hemodynamic responses within the contralateral primary somatosensory cortex and ventral posteromedial thalamic nucleus.
The pipeline was then used to image three female C57BL/6 mice following chemogenetic activation of excitatory MPOA neurons using AAV5-CaMKIIα-hM3D(Gq)-mCherry and deschloroclozapine (DCZ). Chemogenetic activation reduced brown adipose tissue surface temperature from approximately 36 °C to 30 °C. MPOA relative cerebral blood volume initially increased during induction but subsequently declined as hypothermia progressed. Hierarchical clustering of paired DCZ-minus-saline regional time courses identified four distinct response patterns. The MPOA belonged to an induction-associated cluster, whereas the periventricular hypothalamic nucleus, triangular nucleus of the septum, and septofimbrial nucleus maintained elevated hemodynamic responses throughout both induction and maintenance. MPOA seed-based analysis further revealed broad early coupling, pronounced decoupling during the 5–10-min post-injection interval, and progressively widespread coupling during later maintenance periods.
Together, these results establish a flexible fUSI platform for investigating distributed cerebral hemodynamics and support a temporally organized model of chemogenetically induced torpor-like states in which the MPOA contributes primarily to induction, while the PeVH, TRS, and SF are candidate regions involved in maintenance.
Committee Chair
Hong Chen
Committee Members
Song Hu Adam Bauer
Degree
Master of Science (MS)
Author's Department
Biomedical Engineering
Document Type
Thesis
Date of Award
Summer 8-13-2026
Language
English (en)
Author's ORCID
https://orcid.org/0009-0003-8011-8948
Recommended Citation
Culver, Owen J., "A Functional Ultrasound Imaging (fUSI) Pipeline for Investigating Brain-Wide Hemodynamics During Torpor-Like Hypothermia" (2026). McKelvey School of Engineering Graduate Student Theses & Dissertations. 1396.
https://openscholarship.wustl.edu/eng_etds/1396
Included in
Bioelectrical and Neuroengineering Commons, Bioimaging and Biomedical Optics Commons, Biological Engineering Commons, Other Biomedical Engineering and Bioengineering Commons