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 Mae Tyler, Nitish V Thakor, Arvind Pathak

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Article number99
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Brain Neoplasms
brain
animals
Cerebrovascular Circulation
Animals
Microscopes
microscopes
Imaging techniques
Acoustic Stimulation
Perfusion Imaging
Optical Imaging
Brain
Life Cycle Stages
Electroencephalography
Hemoglobins
Lasers
tumors
Anesthesia
Hemodynamics
anesthesia

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

A miniature multi-contrast microscope for functional imaging in freely behaving animals. / Senarathna, Janaka; Yu, Hang; Deng, Callie; Zou, Alice L.; Issa, John B.; Hadjiabadi, Darian H.; Gil, Stacy; Wang, Qihong; Tyler, Betty Mae; Thakor, Nitish V; Pathak, Arvind.

In: Nature communications, Vol. 10, No. 1, 99, 01.12.2019.

Research output: Contribution to journalArticle

Senarathna, Janaka ; Yu, Hang ; Deng, Callie ; Zou, Alice L. ; Issa, John B. ; Hadjiabadi, Darian H. ; Gil, Stacy ; Wang, Qihong ; Tyler, Betty Mae ; Thakor, Nitish V ; Pathak, Arvind. / A miniature multi-contrast microscope for functional imaging in freely behaving animals. In: Nature communications. 2019 ; Vol. 10, No. 1.
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