A miniature multi-contrast microscope for functional imaging in freely behaving animals

• DOI: 10.1038/s41467-018-07926-z
• Publication Date: 2019-01-03T12:29:49Z
• Authors: Janaka Senarathna; Hang Yu; Callie Deng; Alice L. Zou; John B. Issa; Darian H. Hadjiabadi; Stacy Gil; Qihong Wang; Betty M. Tyler; Nitish V. Thakor; Arvind P. Pathak
• Keywords: 0301 basic medicine; Microscopy; 0303 health sciences; Miniaturization; Brain Neoplasms; Science; Q; Monitoring, Ambulatory; Neuroimaging; Equipment Design; Mice, SCID; Article; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Female

AbstractNeurovascular coupling, cerebrovascular remodeling and hemodynamic changes are critical to brain function, and dysregulated in neuropathologies such as brain tumors. Interrogating these phenomena in freely behaving animals requires a portable microscope with multiple optical contrast mechanisms. Therefore, we developed a miniaturized microscope with: a fluorescence (FL) channel for imaging neural activity (e.g., GCaMP) or fluorescent cancer cells (e.g., 9L-GFP); an intrinsic optical signal (IOS) channel for imaging hemoglobin absorption (i.e., cerebral blood volume); and a laser speckle contrast (LSC) channel for imaging perfusion (i.e., cerebral blood flow). Following extensive validation, we demonstrate the microscope’s capabilities via experiments in unanesthetized murine brains that include: (i) multi-contrast imaging of neurovascular changes following auditory stimulation; (ii) wide-area tonotopic mapping; (iii) EEG-synchronized imaging during anesthesia recovery; and (iv) microvascular connectivity mapping over the life-cycle of a brain tumor. This affordable, flexible, plug-and-play microscope heralds a new era in functional imaging of freely behaving animals.