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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session E

S1 - Developing A Novel Frequency Domain Diffuse Optical Spectroscopy for Early Prediction of Neoadjuvant Chemotherapy Efficacy in Breast Cancer

Saturday, October 11, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

BH

Brayden Hirotsu

Student
University of Rochester, United States

Co-Author(s)

JM

Joseph Majeski

Post Doctoral Researcher
University of Pennsylvania, United States

Last Author(s)

RC

Regine Choe, PhD

Associate Professor of Biomedical Engineering
University of Rochester, United States

Primary Investigator(s)

RC

Regine Choe, PhD

Associate Professor of Biomedical Engineering
University of Rochester, United States

Co-Author(s)

VC

Vincent Ching-Roa

PhD Student
University of Rochester, United States
PW

Prashant Waiba

PhD Student
University of Rochester, United States
MG

Michael Giacomelli

Associate Professor of Biomedical Engineering
University of Rochester, United States
Devin C. Johnson

Undergraduate Student
University of California, Irvine, United States

Introduction: : In 2022, the World Health Organization recorded 670,000 deaths due to breast cancer, and 1 in 12 women will be diagnosed with breast cancer over their lifetimes, the most common form of cancer in women globally [1]. When a malignant tumor is too large to be directly removed by surgery, neoadjuvant chemotherapy (NAC) is often used to decrease the size of the tumor before surgical removal. However, this treatment lasts four to six months [2]. If the treatment is not effective, the patient suffers unnecessary side effects, and cancer may still progress during this time, and angiogenesis continues. This highlights the importance of developing methods to predict the effectiveness of treatment early so that doctors can switch to an alternative treatment if NAC is ineffective.
Diffuse optical spectroscopy (DOS) presents a non-invasive monitoring method by quantifying the total hemoglobin concentration (THC) and blood oxygen saturation (StO2) to track tumor metabolism. However, a typical frequency domain diffuse optical spectroscopy system (FD-DOS) is both costly and bulky, limiting the adoption of this technique despite the numerous applications.
To address this barrier to entry, we developed a compact, low-cost FD-DOS instrument that is modular and expandable. This was achieved through thoughtful circuit design and the use of off-the-shelf integrated chips. We will validate the instrument’s performance through dynamic range measurements and demonstrate the ability to recover the optical properties of tissue phantoms accurately. This instrument is a promising step towards predicting NAC effectiveness in breast cancer.

Materials and

Methods: : The instrument under development is a two-wavelength, four-detector heterodyne FD system, designed to retrieve both scattering and absorption coefficients using multiple source-detector separations (SDs).

The instrument uses 785nm and 830nm laser diodes, enabling accurate quantification of absorption coefficients at both wavelengths. This, in turn, enables the quantification of THC and StO2 based on the Beer-Lambert law. Laser diode power is sinusoidally modulated at 130MHz [3].

Silicone Photomultipliers (SiPM) were selected for high gain, ideal for low-light detection, with greater durability compared to other detectors [4]. Low light sensitivity is important as power at larger SDs is low, yet it provides information for deeper tissue depths. Our system is designed to have four detectors to acquire data from different depths.

Dynamic range measurements will be performed using an optical attenuator, followed by a 50:50 fiber splitter. One output goes into an optical power meter, and the other to a detection channel [3]. The light power will be gradually increased using the optical attenuator to characterize the dark noise, the linear operating range, and the saturation point.

A probe interfacing the tissue and the instrument using optical fibers will be constructed for tissue phantom measurements. The accuracy of optical property recovery will be tested by varying Nigrosine ink for absorption and Intralipid for scattering. To test the imaging capability, a 2cm hollow sphere filled with a higher-absorbing solution immersed in the liquid phantom will simulate a tumor with higher THC. Varying the sphere depth will characterize detection limits and penetration depth.

Results, Conclusions, and Discussions:: The system construction is completed. At the conference, we will present the results from the dynamic range testing as well as the tissue phantom experiments. The dynamic range tests will characterize the SiPM’s linear operating range. After the initial dynamic range test, we will further optimize the system to increase the dynamic range. Achieving a large dynamic range enables simultaneous measurements at different SDs, which increases sensitivity to tumors at different depths and image fidelity. The liquid phantom tests will demonstrate the instrument’s ability to accurately recover the absorption and reduced scattering coefficients. We will then test the sensitivity of the instrument to detect a 2cm diameter sphere, simulating a tumor of varying absorption and reduced scattering coefficients. Testing the instrument in a tissue phantom of known optical properties allows us to characterize and optimize the system.

Successful recovery of the absorption coefficients at two wavelengths will enable us to quantify THC. A significantly higher tumor-to-normal contrast of THC is a hallmark of tumor angiogenesis. A decrease in THC contrast as early as one to four weeks after the start of treatment was observed in breast cancer NAC [5]. DOS is appealing for frequent monitoring due to its non-invasive nature and lack of ionizing radiation [5]. Our instrument is modular, scalable, and inexpensive, allowing for the addition of more detectors in the future, and is easy to assemble, making it ideal for clinical applications. This offers a promising step toward accessible and effective breast cancer therapy monitoring.

Acknowledgements and/or References (Optional): : [1] World Health Organization. (n.d.). Breast cancer. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
[2] Standish, L. J., Dowd, F., Sweet, E., Dale, L., Weaver, M., Osborne, B., & Andersen, M. R. (2016). Breast cancer integrative oncology care and its costs. Integrative Cancer Therapies, 16(1), 85–95.
[3] Majeski, J. B., Ching-Roa, V. D., Giacomelli, M. G., & Choe, R. (2023). Design for a low-cost heterodyne frequency domain-diffuse optical spectroscopy system. Biomedical Optics Express, 14(6), 2873-2888.
[4] Ching-Roa, V. D., Olson, E. M., Ibrahim, S. F., Torres, R., Giacomelli, M. G. (2021). Ultrahigh-speed Point Scanning Two-Photon Microscopy Using High Dynamic Range Silicon Photomultipliers. Scientific Reports, 11, 5248.
[5] Choe, R., Durduran, T. (2012). Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy. IEEE Journal of Selected Topics in Quantum Electronics, 18, 1367-1386.