# New treatment monitoring biomarkers for brain tumors using multiparametric MRI with machine learning

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $509,140

## Abstract

Project Summary/Abstract
The goal of this project is to develop and evaluate novel imaging biomarker(s) that use multiparameter MRI
methods to identify the true spatial extent of glial brain tumors. The standard RANO (response assessment in
neuro-oncology) criteria define tumor extent as the region of bright signal on post-contrast agent T1w (T1+C)
images, termed the contrast enhancing lesion (CEL), along with the peritumoral bright signal on T2w FLAIR
images, referred to as non-enhancing lesion (NEL). Yet, the CEL reflects the permeability of the blood-brain
barrier to contrast agent and can appear the same for both tumor and treatment effect. Likewise, though NEL
likely contains tumor, current imaging cannot distinguish tumor from edema. These difficulties result in the
inability of current anatomical MRI methods to determine the true spatial extent of glial tumors, a
serious limitation for treatment management of brain tumor patients.
We and others have shown that advanced MRI methods, including perfusion and diffusion MRI, are useful for
assessing tumor grade, predicting outcomes, or distinguishing tumor from treatment effect. Yet, almost
exclusively, the approach has been to extract mean values of a single physiological parameter from
predetermined tumor regions of interest and then measure their correlation with the desired clinical index.
Although this approach has been useful for initial biomarker development, it underutilizes the rich
multiparameter and spatial information available, thus motivating the current study. First, two multiparameter
MRI biomarkers will be developed to identify enhancing and infiltrating tumor burden. Then, they will be
evaluated individually and in combination to assess the total tumor burden in comparison with the standard
volumetric metrics in current use.
The development and testing of these biomarkers will be accomplished in several independent steps outlined
by the proposed aims. First (Aim 1), we propose to develop an MRI biomarker that gives the voxelwise
probability of enhancing tumor burden within CEL, with early results showing the ability to distinguish tumor
from treatment effect. Next, we will develop a multiparameter biomarker capable of identifying infiltrating tumor
within NEL (Aim 2). These efforts leverage our previous results using artificial intelligence, recent advances in
machine learning, and our unique brain tumor tissue bank with hundreds of biopsy samples spatially matched
to imaging. Finally (Aim 3), the spatial extent of tumor burden within CEL and NEL will be tested in their ability
to distinguish pseudo-progression/response from true progression/response, which is a primary question that
confounds treatment management today.
In summary, multiparameter advanced MRI biomarkers of enhancing and infiltrative brain tumor have the
potential to cause a paradigm shift in how treatment is managed, ultimately resulting in improved outcomes.

## Key facts

- **NIH application ID:** 10809687
- **Project number:** 5R01CA255123-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** KATHLEEN Marie SCHMAINDA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $509,140
- **Award type:** 5
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809687

## Citation

> US National Institutes of Health, RePORTER application 10809687, New treatment monitoring biomarkers for brain tumors using multiparametric MRI with machine learning (5R01CA255123-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10809687. Licensed CC0.

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