# Fluorescence lifetime technique for intraoperative identification of IDH mutations in brain cancer

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $386,565

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this proposal is to demonstrate that brain tumors which harbor isocitrate dehydrogenases (IDH) gene
mutations can be distinguished from IDH wild-type (WT) tumors intraoperatively and in real-time, based on their
autofluorescence emission properties. Mutation of the IDH1/2 genes is common in low-grade gliomas (LGG) and
occur infrequently in glioblastoma multiforme (GBM). The presence of IDH mutations is the greatest prognostic
marker for GBM patients. Patients with IDH mutant gliomas have improved survival compared to their grade
matched, WT counterparts. Importantly, recent studies suggest that the benefit of aggressive surgical resection
differs between IDH-WT and IDH-mutant tumors; thus, intraoperative identification of IDH mutations will change
the operative goals. Subsequently, there is a considerable interest in developing rapid, intraoperative methods
to identify IDH mutations.
IDH mutations cause global changes in cellular metabolism by impairing the conversion alpha-ketoglutarate
(αKG) to isocitrate, which normally reduces NADP+ to NADPH. Instead, αKG is converted to 2-hydroxyglutarate,
consuming NADPH to produce NADP+. Brain autofluorescence properties are highly interlinked with changes in
cellular metabolism. In particular, the variation in autofluorescence emission intensity of brain tissue has been
attributed to differences in NAD(P)H concentration and redox state. Also, differences in the lifetime (or decay) of
autofluorescent intensities between glioma and normal brain tissues have been attributed to disparities between
free- and bound-NAD(P)H. Therefore, we hypothesize that optical parameters derived from autofluorescence
lifetime measurements of gliomas can be correlated to changes in cellular metabolism caused by IDH mutations.
This proposal will build on previous clinical studies that demonstrate gliomas of distinct phenotypes have distinct
fluorescence lifetime characteristics and our expertise with moving fluorescence lifetime imaging (FLIm)
techniques into clinical settings. To accomplish our goal, we propose 2 specific aims. Aim 1: Conduct FLIm
intraoperative measurements in LLG and HGG patients (N=80) undergoing conventional neurosurgical
procedures. This will provide an extensive database of FLIm parameters (retrieved from both in vivo and ex vivo
measurements) correlated with tissue pathology including IDH mutation status. Aim 2: Validate the utilization of
FLIm as a means for real-time detection of IDH mutations. This will demonstrate the predictive value of FLIm for
detection of IDH mutation status and for potential guidance during brain tumor surgery.
In summary, this study will demonstrate the clinical utility of FLIm for intraoperative, real-time assessment of IDH
mutation status to improve surgical outcomes. Since the FLIm apparatus is characterized by simple, fast and
flexible data acquisition and display, and allows for seamless integration with existing imaging techniques use...

## Key facts

- **NIH application ID:** 10044980
- **Project number:** 1R21CA252510-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Orin Bloch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,565
- **Award type:** 1
- **Project period:** 2020-06-17 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044980

## Citation

> US National Institutes of Health, RePORTER application 10044980, Fluorescence lifetime technique for intraoperative identification of IDH mutations in brain cancer (1R21CA252510-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10044980. Licensed CC0.

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