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

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 and Arvind P. Pathak ()
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Janaka Senarathna: Johns Hopkins University School of Medicine
Hang Yu: Johns Hopkins University School of Medicine
Callie Deng: Johns Hopkins University School of Medicine
Alice L. Zou: Johns Hopkins University School of Medicine
John B. Issa: Johns Hopkins University School of Medicine
Darian H. Hadjiabadi: Johns Hopkins University School of Medicine
Stacy Gil: Johns Hopkins University School of Medicine
Qihong Wang: Johns Hopkins University School of Medicine
Betty M. Tyler: Johns Hopkins University School of Medicine
Nitish V. Thakor: Johns Hopkins University School of Medicine
Arvind P. Pathak: Johns Hopkins University School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Neurovascular 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.

Date: 2019
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DOI: 10.1038/s41467-018-07926-z

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