# Integrating circulating tumor DNA assay and protein-based MRI to accurately monitor glioma therapy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $635,842

## Abstract

SUMMARY
 Glioblastoma is the most common primary brain tumor with substantial genomic, molecular and phenotypic
heterogeneity, but uniformly dismal outcomes despite the current standard treatment of concurrent
temozolomide chemo-radiotherapy (CRT). Given the pace of disease recurrence and the challenges
associated with obtaining tumor tissue, there is an unmet clinical need for the real-time, noninvasive
assessment of GBM responsiveness to CRT. As demonstrated previously, most cancers shed tumor-derived
fragmented DNA into biofluids, including plasma and cerebrospinal fluid (CSF), and these cell-free molecules
can be quantified as a measure of disease burden. The approach, named “liquid biopsy”, has recently
emerged as a breakthrough diagnostic and monitoring tool for diseases such as cancer, with the added benefit
of being minimally invasive. Through the sampling and analysis of biofluids, a number of promising glioma
biomarkers, derived from tumor-derived DNA in plasma (ctDNA) and CSF (CSF-tDNA) (together called rtDNA),
have been reported as diagnostic strategies for gliomas. Meanwhile, numerous previous studies have
demonstrated that protein-based amide proton transfer (APT) MRI can accurately identify tumor burden and
genetic markers (such as IDH, MGMT status) in gliomas. The goals of this proposal are to combine ctDNA and
CSF-tDNA with APT MRI to resolve the diagnostic challenges associated with discriminating treatment effect
from tumor progression and to develop an efficient and reliable deep-learning framework for post-treatment
monitoring. We propose the following specific aims to be performed: (1) correlate ctDNA and CSF-tDNA levels
with protein-based APT MRI characteristics when monitoring GBM treated with CRT; (2) determine the
accuracy of combined rtDNA/APT indices in identifying GBM recurrence; and (3) develop a transformer
pipeline using rtDNA and mpMRI to assess GBM prognosis. The success of this aim will help to understand
the dynamic patterns of rtDNA/APT throughout the treatment course for individuals with GBM. If our
rtDNA/APT investigation is successful, the results would dramatically improve the care of patients treated with
CRT and spare many patients from undergoing surgery for diagnostic purposes.

## Key facts

- **NIH application ID:** 10878885
- **Project number:** 5R01CA276221-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CHETAN BETTEGOWDA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,842
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878885

## Citation

> US National Institutes of Health, RePORTER application 10878885, Integrating circulating tumor DNA assay and protein-based MRI to accurately monitor glioma therapy (5R01CA276221-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10878885. Licensed CC0.

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