# MAPPING FUNCTIONAL CONNECTIVITY WITH FLUORESCENCE MOLECULAR TOMOGRAPHY

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $567,048

## Abstract

Project Summary:
Functional mapping of spontaneous brain activity with resting-state functional connectivity (FC) analysis
of fMRI data has recently become a dominant approach to mapping human brain function and continues
to gain momentum. However fMRI is based on cerebral hemodynamics that is relatively indirectly
coupled to neuronal activity and much slower (~0.3 Hz). Further the physiological underpinnings of FC
are relatively un-resolved, such that the mechanisms and implications altered FC are often unclear. For
example in ischemic stroke, it is well known that the penumbra surrounding the ischemic core has altered
neurovascular coupling (NVC), complicating the interpretation of the FC deficits. As FC measures are
extended further into studies of brain development, aging and disease, the importance of understanding
the fundamental basis for FC will grow. We recently developed hemodynamic mapping of functional
connectivity in mice using optical intrinsic signal imaging (fcOIS), and found fcOIS sensitive to several
neurological diseases, including mouse models of stroke and Alzheimer's disease. However, with the
advent of genetic engineering techniques for mice, there are new opportunities for extending optical
wide-field imaging to calcium activity, which is >10x faster and more directly coupled to neural activity
than hemoglobin. By combining calcium and hemodynamic imaging, there is the potential to quantify the
relationship between cell-specific calcium dynamics and hemodynamics throughout brain regions.
Further concurrent calcium and hemoglobin imaging could help resolve questions about the impact of
altered NVC in diseases such as stroke, and in early brain development. However, as yet, no imaging
system has been developed to examine these rich relationships throughout the mouse cortex. In this
project, we will develop optical imaging hardware and software for characterizing calcium dynamics in
mice engineered for genetically encoded calcium indicators (GECI's). For exemplar applications where
the functional networks are changing quickly, we will quantify FC during stroke recovery and brain
development, tracking the progression of both functional connectivity and neurovascular coupling (NVC).
Aim 1 will develop fluorescence molecular tomography (FMT) and diffuse optical tomography (DOT)
instrumentation for concurrent mapping of calcium and hemoglobin in mice. Aim 2 will optimize system
performance for high speed FMT/DOT of mouse brain function. Aim 3 will establish FMT/DOT for
mapping the functional networks of cell-specific calcium signals in mice with GECIs. Concurrent imaging
with hemoglobin will enable mapping of neurovascular coupling. In aim 4, with establish feasibility of
FMT/DOT in both stroke recovery and brain developmental. In both applications we will quantify calcium-
FC and the influence of altered NVC on hemoglobin-FC.

## Key facts

- **NIH application ID:** 10160971
- **Project number:** 5R01NS099429-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JOSEPH P CULVER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $567,048
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160971

## Citation

> US National Institutes of Health, RePORTER application 10160971, MAPPING FUNCTIONAL CONNECTIVITY WITH FLUORESCENCE MOLECULAR TOMOGRAPHY (5R01NS099429-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10160971. Licensed CC0.

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