# Imaging Biomarkers of Lymphatic Dysfunction

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $395,000

## Abstract

ABSTRACT
The goal of this work is to apply novel, noninvasive magnetic resonance imaging (MRI) methods for visualizing
lymphatic circulation dysfunction to test fundamental hypotheses about lymphedema risk factors and therapies.
Breast cancer treatment-related lymphedema (BCRL) arises secondary to surgical axillary lymph node (LN)
dissection and irritation, and is a chronic and lifelong condition affecting a high 21.4% of patients receiving
common breast cancer therapies. Reducing condition onset and improving management represent major
unmet clinical needs for these 50,000 - 80,000 new patients per year, and emerging efforts focus on improving
quality of life through more informed LN dissection and biopsy decisions, optimizing post-surgical complex
decongestive therapy (CDT), and exploring novel pharmacological and surgical procedures. However,
fundamental gaps in our knowledge persist regarding optimized implementation of these therapies and details
of the physiological changes they elicit. The major underlying limitation is that there is a shortage of imaging
methods available that can be used to evaluate lymphatic function directly, and there is currently no consensus
regarding effective outcome measures for therapeutic efficacy evaluation. Rather, LN removal is frequently
based on sentinel LN biopsy and additional subjectivity of the surgeon. Therapy evaluation is frequently based
on coarse measurements such as changes in limb volume or patient-reported symptoms, which provide little
information on underlying mechanistic changes that could be used to further refine these therapies. As part of
our ongoing INFORM clinical trial of BCRL progression and therapy, we have demonstrated potential for new,
noninvasive MRI approaches to identify BCRL risk in sub-clinical disease stages, as well as to visualize
internal changes in lymphatic functioning as a result of emerging therapies. Here, we propose to extend these
studies to improve abilities for BCRL theranostics. (Aim 1) Prevention. We will apply new anatomical and
functional LN imaging approaches to identify LN profiles specific to biopsy-confirmed metastatic LNs; findings
could be used to better inform LN dissection and reduce the incidence of benign LN removal. (Aim 2)
Progression. We will improve our understanding of BCRL risk progression by testing the hypothesis that
superficial tissue profiles and subcutaneous adipose accumulation are more prevalent in patients experiencing
BCRL progression, and thereby could be used to triage patients for aggressive therapies prior to overt
symptoms and irreversible damage. (Aim 3) Therapy. We will perform a repeated-measures cross-over trial to
test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure
therapy in conjunction CDT is superior to standard CDT alone. The overall goal is to develop objective markers
of lymphatic dysfunction that can be used in emerging therapeutic trials of cancer and BCRL therap...

## Key facts

- **NIH application ID:** 10171920
- **Project number:** 5R01NR015079-08
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Manus J Donahue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2014-07-14 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171920

## Citation

> US National Institutes of Health, RePORTER application 10171920, Imaging Biomarkers of Lymphatic Dysfunction (5R01NR015079-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171920. Licensed CC0.

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