# Diffusion MRI of Treatment Response for De-escalation of Radiation Therapy

> **NIH NIH UG3** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $321,685

## Abstract

PROJECT SUMMARY
Chemo-radiation therapy is a standard treatment regimen for locally advanced head and neck squamous cell
carcinoma (HNSCC). The treatment regimen, however, is difficult for patients as they experience high rates of
grade 3 or higher toxicities including leukopenia (42%) and the need for feeding tube (52%). Recent studies
showed that a subgroup of HNSCC patients with human-papilloma virus (HPV)-positive oropharyngeal (OP)
SCC have significantly better prognosis. These clinical data lead to important considerations to de-intensify
treatment for this low-risk, younger population in order to reduce acute and chronic toxicity without
compromising disease control. It has been suggested that the adaptive de-escalation of treatment can be
tailored for individual patients based on the early tumor volume change. However, volumetric assessment is
often inadequate because the treatment response of a tumor can be heterogeneous in terms of (i) cell viability,
(ii) cellular metabolism, and (iii) perfusion that are relevant to the success of any chemoradiation therapy.
These complex changes may not be adequately represented by tumor volume change at the early stage.
The proposed study is based on a combination of the quantitative diffusion MRI (dMRI) methods with their own
technical innovations that can also be applied to other clinical studies. dMRI is a unique in vivo imaging
technique sensitive to cellular microstructures at the scale of water diffusion length on the order of a few
microns. However, quantitative dMRI remains challenging as dMRI data represent different biophysical
properties of tissue depending on diffusion weighting strength (q) and diffusion time (t) used for the
measurement. The scientific premise of the proposal is that this study will establish a quantitative way to utilize
both q- and t-dependent dMRI data as a tailored approach to quantify cell viability, cellular metabolism and
perfusion from this non-contrast MRI method. We demonstrated that both diffusion coefficient D and diffusional
kurtosis coefficient K are promising imaging markers for cell viability. Cellular metabolism can be evaluated in
terms of the water exchange τex, measured by the diffusion time-dependent K, that is regulated by the ATP-
dependent trans-membrane ion channels co-transporting water molecules. Intravoxel incoherent motion MRI
metrics (pseudo diffusivity, Dp; perfusion fraction, fp) can provide information about perfusion flow. Ultimately,
these dMRI measures will better identify patients who have the potential to benefit from adaptive de-escalation
or escalation of therapy.
In this proposal, we will further optimize and establish a set of quantitative non-contrast imaging markers of cell
viability (D and K), cellular metabolism (τex), and perfusion (fp⋅Dp) as a clinical tool for assessment of treatment
response and validate it in a clinical trial. The data acquisition and analysis software tools to be developed in
this study will enable com...

## Key facts

- **NIH application ID:** 10328699
- **Project number:** 7UG3CA228699-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Sungheon Gene Kim
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,685
- **Award type:** 7
- **Project period:** 2019-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328699

## Citation

> US National Institutes of Health, RePORTER application 10328699, Diffusion MRI of Treatment Response for De-escalation of Radiation Therapy (7UG3CA228699-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328699. Licensed CC0.

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