# Overcoming Tumor Resistance to Chemotherapy with Multiscale Diffuse and Nonlinear Imaging

> **NIH NIH K00** · UNIVERSITY OF WASHINGTON · 2020 · $25,762

## Abstract

PROJECT SUMMARY/ABSTRACT
 In 2016, an estimated 250,000 new cases of female breast cancer were diagnosed in the U.S., causing
an estimated 40,000 deaths. Almost all breast cancer deaths are due to tumor progressive resistance to systemic
therapies, followed by metastasis. Anticipating breast cancer chemoresistance is a significant clinical challenge
because the changes in commonly monitored parameters, including tumor volume or glucose-analog uptake,
have been shown to be poor predictors of resistance and often manifest only after resistance has occurred. The
ability to accurately predict the onset of chemoresistance would allow physicians to make evidence based
treatment changes in a timely manner, which could substantially improve patient outcomes. New preclinical
imaging techniques designed to track resistance over the appropriate spatial and temporal scales could provide
key insights into the effective management of chemoresistance in the clinic. The goal of the F99 phase is to
develop a novel imaging technique called Diffuse and Nonlinear Imaging (DNI) that combines two different
contrast mechanisms over spatial scales ranging from cm to μm to monitor resistance in vivo. DNI utilizes multiply
scattered photons for widefield mapping of tumor metabolism, and multiphoton interactions to achieve molecular,
structural, and metabolic tumor imaging with cellular resolution in 3D. These techniques will be combined to
make an integrated preclinical imaging system that is co-registered, providing unprecedented evaluation of tumor
heterogeneity over a range of spatial scales and contrast mechanisms. DNI will integrate exogenous and
molecularly targeted imaging agents with endogenous sources of imaging contrast to obtain a more complete
picture of the in vivo tumor state. The first aim is to co-register nonlinear sectioning of vascular organization with
oxygenation maps from diffuse imaging of preclinical mammary tumors through a window chamber. The second
aim is to identify optical signatures of chemoresistance via DNI monitoring of treated preclinical mammary
tumors. Lastly, the third aim is to link optical resistance metrics to heterogeneity in tumor vascular organization.
The goal of the K00 phase is to study how the scheduling and spatial distribution of treatment affect the time-to-
resistance. This entails tracking distinct clonal populations, and their complex dynamics and competition during
drug-tumor interactions. Genetic and phenotypic markers of resistance and heterogeneity will be labeled with
engineered nano-optical probes. These will enable longitudinal and simultaneous multiplexing and imaging of
complex clonal interactions, and capturing of individual clonal dynamics in vivo in preclinical and clinical tumors.
An optical technique will then be developed to use photorelease technology to control spatiotemporal treatment
parameters and track drug distribution among clonal nests to study the effects of drug-tumor interactions on
long-term ...

## Key facts

- **NIH application ID:** 10073652
- **Project number:** 4K00CA223014-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kavon Karrobi
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,762
- **Award type:** 4N
- **Project period:** 2020-02-01 → 2020-06-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073652

## Citation

> US National Institutes of Health, RePORTER application 10073652, Overcoming Tumor Resistance to Chemotherapy with Multiscale Diffuse and Nonlinear Imaging (4K00CA223014-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073652. Licensed CC0.

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