# Ultrahigh-Resolution Quantitative Optical Coherence Elastography of the Tumor Microenvironment In Vivo

> **NIH NIH R21** · CORNELL UNIVERSITY · 2021 · $400,639

## Abstract

The understanding of cancer has evolved rapidly over the last decade. One of the key findings is that altered
mechanical properties is not just a symptom of tumors, but can trigger the actual onset of malignancy, and
promote tumor progression. The clinical impact of cancer mechanics research, however, is currently hampered
by a lack of methods to image the mechanical properties of the tumor microenvironment with micrometer
resolution in vivo. Consequently, research studies on the role of extracellular matrix (ECM) mechanics in
carcinogenesis have been restricted to in vitro experiments or ex vivo measurements of tissue biomechanics.
This proposal will develop and demonstrate a new imaging platform for time-lapse in vivo imaging studies of the
mechanical properties of the tumor microenvironment. Acoustic radiation force (ARF) will be utilized for highly
localized ‘palpation’, and ultra-precise phase-sensitive optical coherence tomography (OCT) will be employed to
detect the resulting nanometer-to-micrometer scale displacements. The main hypothesis, based on a recent
paper by our group, is that the use of highly localized mechanical excitation (via ‘palpation’ with tightly-focused
ultrasound), combined with mechanical excitation at higher frequencies in the kilohertz regime, can be leveraged
to overcome the resolution limitations of shear-wave-based approaches, and thereby enable the
highest-resolution OCE imaging of the complex shear modulus, i.e. both shear storage and loss modulus. A
further hypothesis is that implementation of our approach for an epi-illumination imaging geometry will enable
the dynamic variations in local mechanical properties during tumor development in vivo to be quantified. Specific
Aim 1 will demonstrate our approach for ultrahigh-resolution ARF-OCE that combines quantitative shear wave
propagation methods with ultrahigh-resolution axial strain imaging (this utilizes an imaging scheme we have
demonstrated that detects ARF-induced displacements at the same location of a tightly-focused ultrasound
‘palpation’ spot). Our ultrahigh-resolution quantitative ARF-OCE approach and a novel epi-illumination imaging
setup suitable for in vivo ARF-OCE studies will be validated in side-by-side and tumor mimicking phantoms by
comparison to AFM imaging of mechanical properties over the same excitation frequency range. Specific Aim 2
will apply our novel ARF-OCE system and reconstruction methods validated in Aim 1 to perform in vivo imaging
of the tumor microenvironment. We will demonstrate, for the first time, longitudinal OCE imaging of the shear
storage and loss moduli of the tumor microenvironment in vivo. These quantitative OCE images will be correlated
to gold-standard histological analysis and second-harmonic generation (SHG) imaging of resected tumor tissues.
We expect that our new approach for ultrahigh-resolution OCE will enable the burgeoning field of cancer
mechanobiology to transition towards, and emphasize in vivo imaging stu...

## Key facts

- **NIH application ID:** 10225877
- **Project number:** 1R21CA253197-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Steven Graham Adie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,639
- **Award type:** 1
- **Project period:** 2021-04-26 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225877

## Citation

> US National Institutes of Health, RePORTER application 10225877, Ultrahigh-Resolution Quantitative Optical Coherence Elastography of the Tumor Microenvironment In Vivo (1R21CA253197-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10225877. Licensed CC0.

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