# Development of A High Throughput Image-Guided IMRT System for Preclinical Research

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $441,662

## Abstract

Project Summary/Abstract
Preclinical radiobiology experiments on small animals are crucial to test the safety and efficacy before human
clinical trials. However, limited by currently available technologies, preclinical animal studies substantially differ
from state-of-the-art human treatments in dose conformity. Consequently, the animal studies poorly mimic the
radiobiological, radioimmunological, and toxicity environment of human therapies. The disparity adversely affects
our ability to meaningfully test hypotheses that are intended for human translation. With decades of
advancement, human radiotherapy has achieved high targeting accuracy and dose conformality based on
technological breakthroughs, including intensity-modulated radiotherapy (IMRT), which is unavailable for mouse
experiments. A practical device and algorithm to modulate the x-ray intensity for the scale of small animals is the
first step to bridge the gap. With the support of an NIH R21 grant, we engineered a novel small animal IMRT
dose modulator termed sparse orthogonal collimator (SOC). Equally important as the hardware, we created the
enabling mathematical tools to deliver SOC IMRT plans with higher achievable resolution than a theoretically
miniaturized MLC-based IMRT. We commissioned and tested prototypical SOCs to deliver highly modulated
doses in silico and on phantoms. Nonetheless, there are still large gaps between an intensity modulation device
and a small animal IMRT system suitable for broad adoption and impact. The required time, resources, and
training to create sophisticated SOC-IMRT plans are incompatible with preclinical settings. Furthermore, without
automation, the existing image-guided small animal IMRT treatment is prohibitively slow for treating live animals
under anesthesia. Lastly, the current manual method to switch between imaging and therapy modes results in
intractable uncertainties in dose delivery. We propose to fill these gaps using automation, robotics, and system
optimization. We propose the following specific aims. Specific Aim 1 (SA1). Automated organ segmentation for
mice using deep learning neural networks. Specific Aim 2 (SA2). Development of a fully functional, automated,
and efficient IMRT system. Specific Aim 3 (SA3). Development and validation of a robotic Multi Mouse Automated
Treatment Environment (Multi-MATE) for automated imaging and treatment. Besides dosimetry, we will quantify
the time performance, which is critical to small animal IMRT system. As a result, in addition to improving the
hardware accuracy and reliability, the proposed project will provide a fully automated planning and delivery
system, thus removing the last barriers towards the broad adoption of small animal IMRT. The success of the
proposed project will help existing research to achieve the full potential for human translation and enable future
hypotheses testing where accurate complex dose distribution is critical.

## Key facts

- **NIH application ID:** 10317441
- **Project number:** 1R01CA259008-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ke Sheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,662
- **Award type:** 1
- **Project period:** 2021-06-18 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317441

## Citation

> US National Institutes of Health, RePORTER application 10317441, Development of A High Throughput Image-Guided IMRT System for Preclinical Research (1R01CA259008-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10317441. Licensed CC0.

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