# In vivo dual-axis confocal microscopy of 5-ALA-induced PpIX to guide low-grade glioma resections

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $607,334

## Abstract

Summary
Extent-of-resection is correlated with glioma patient outcomes such as progression-free survival. Image-
guidance technologies, based on MRI and now fluorescence-guided surgery (FGS), have been developed to
improve the surgeon’s ability to visualize gross tumor margins. However, there are fundamental limitations to
wide-field imaging methods such as MRI and FGS, such as poor sensitivity to detect disseminated tumor cells
at the infiltrative margins of diffuse gliomas, as well as the non-quantitative and subjective nature of image
interpretation. With the emergence of FGS using 5-ALA, and its recent approval by the FDA in 2017, the gap
between low-grade glioma (LGG) and high-grade glioma (HGG) patients, in terms of extent of resection, will
likely widen since LGGs rarely generate sufficient PpIX fluorescence to be detected via wide-field FGS.
Consequently, there is a clear need for improved intraoperative techniques with the sensitivity to detect and
quantify residual LGGs at the margins of the tumor cavity in order to improve the extent of resection and delay
recurrence. We have shown that high-resolution confocal microscopy has the sensitivity to visualize the sparse
sub-cellular expression of PpIX in LGG patients treated with 5-ALA, even beyond the radiographic margins.
Therefore, we will optimize a handheld optical-sectioning microscope to image 5-ALA-induced PpIX at the final
resection margins in LGG patients, together with real-time video mosaicking to facilitate the imaging of large
tissue areas, which will minimize sampling bias when imaging heterogeneous brain tissues (Aim 1). In order to
facilitate the clinical acceptance of these techniques, we will establish a relationship between the microscopic
patterns of PpIX expression and well-established biological metrics such as tumor burden and proliferative index
(Aim 2). Finally, we will explore the hypothesis that quantitative microscopic imaging of PpIX of the resection
margins is predictive of extent of resection, as currently defined by post-operative MRI, which would suggest that
it has value for optimizing resections to minimize and/or delay recurrence (Aim 3). Collectively, these results
will pave the way for future randomized controlled clinical studies to optimize resection procedures and outcomes
for LGG patients (adults and children), many of whom can have good survival outcomes and quality of life.

## Key facts

- **NIH application ID:** 9859167
- **Project number:** 1R01CA244170-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jonathan T.C. Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $607,334
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859167

## Citation

> US National Institutes of Health, RePORTER application 9859167, In vivo dual-axis confocal microscopy of 5-ALA-induced PpIX to guide low-grade glioma resections (1R01CA244170-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9859167. Licensed CC0.

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