# Quantitative bioluminescence tomography for pre-clinical radiotherapy research

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $68,935

## Abstract

PROJECT SUMMARY/ABSTRACT
Several groups, including ours, have initiated efforts to develop small-animal irradiators that mimic radiation
therapy (RT) for human treatment. The major image modality used to guide irradiation is cone-beam CT (CBCT),
and our CBCT-small animal radiation research platform (SARRP) was commercialized in 2010. Our system, and
others, were transformative for pre-clinical RT research, and 115 machines are now in use world-wide by some
600 investigators. While CBCT provides excellent guidance capability, it is less adept at localizing soft tissue
targets growing in a low image contrast environment. In contrast, bioluminescence imaging (BLI), provides strong
image contrast and thus is an attractive solution for soft tissue targeting. However, commonly used 2D BLI on
an animal surface is inadequate to guide irradiation, because optical transport from an internal bioluminescent
tumor is highly susceptible to the effects of irregular torso and tissue optical properties. Recognition of these
limitations led us to integrate 3D bioluminescence tomography (BLT) with SARRP. Our first BLT was designed
to localize the center of mass (CoM) of an optical target for irradiation. This advance was received with much
intrigue, however there was little practical adoption of the BLT system by SARRP users. It was clear that the
investigators required two key unmet needs to be addressed, to significantly enhance their conduct of research:
1) knowledge of target shape is a fundamental need for RT. Without such information to guide radiation, large
portions of normal tissue can be irradiated unnecessarily, leading to undesired experimental uncertainties. It is
imperative that we advance BLT guidance beyond CoM, to a new and precise level of 3D target shape
delineation; and 2) clinical practice recognizes the importance of complementary use of functional and
anatomical image for RT. BLI measures cellular viability, thus it is an ideal imaging modality for longitudinally
monitoring treatment outcome. However, the quantitative information that surface BLI provides for assessment
is currently limited or even inaccurate. With the novel reconstruction algorithm and calibration methods proposed
in this application, we will establish a new quantitative BLT (QBLT) to address this need. We hypothesize that
the QBLT/CBCT-guided small animal radiation system will provide investigators new capabilities to localize soft
tissue target, define its shape for conformal irradiation, and non-invasively quantify treatment outcome. Our aims
are: Aim 1: design and construct a standalone QBLT system readily adapted to commercial radiation platform;
Aim 2: optimize input data, and develop calibration method and reconstruction algorithm for target shape
delineation and quantitative imaging; Aim 3: validate the QBLT-guided RT in vivo and assess its suitability for
treatment assessment. The success of this proposal will significantly enhance small animal radiotherapy
research...

## Key facts

- **NIH application ID:** 9960461
- **Project number:** 5R01CA240811-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ken Kang-Hsin Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,935
- **Award type:** 5
- **Project period:** 2019-08-01 → 2020-10-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960461

## Citation

> US National Institutes of Health, RePORTER application 9960461, Quantitative bioluminescence tomography for pre-clinical radiotherapy research (5R01CA240811-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9960461. Licensed CC0.

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