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Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
A Wireless, Multicolor Fluorescence Image Sensor Implant for Real-Time Monitoring in Cancer Therapy
Micah Roschelle1, Rozhan Rabbani1, Surin Gweon1
1Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, Berkeley CA 94720 USA.
Abstract:
Real-time monitoring of dynamic biological processes in the body is critical to understanding disease progression and treatment response. This data, for instance, can help address the lower than 50% response rates to cancer immunotherapy. However, current clinical imaging modalities lack the molecular contrast, resolution, and chronic usability for rapid and accurate response assessments. Here, we present a fully wireless image sensor featuring a 2.5×5 mm2 CMOS integrated circuit for multicolor fluorescence imaging deep in tissue. The sensor operates wirelessly via ultrasound (US) at 5 cm depth in oil, harvesting energy with 221 mW/cm2 incident US power density (31% of FDA limits) and backscattering data at 13 kbps with a bit error rate <10-6. In-situ fluorescence excitation is provided by microlaser diodes controlled with a programmable on-chip driver. An optical frontend combining a multi-bandpass interference filter and a fiber optic plate provides >6 OD excitation blocking and enables three-color imaging for detecting multiple cell types. A 36×40-pixel array captures images with resolution. We demonstrate wireless, dual-color fluorescence imaging of both effector and suppressor immune cells in ex vivo mouse tumor samples with and without immunotherapy. These results show promise for providing rapid insight into therapeutic response and resistance, guiding personalized medicine.
Insights
Researchers developed a wireless, implantable sensor for real-time, multicolor fluorescence imaging deep within tissue. This technology offers a novel approach for monitoring immune cells and assessing cancer immunotherapy response.
Area of Science:
- Biomedical Engineering
- Optical Imaging
- Immunology
Background:
- Real-time monitoring of biological processes is crucial for understanding disease and treatment efficacy, especially for cancer immunotherapy with low response rates.
- Current imaging methods lack the necessary molecular contrast, resolution, and chronic usability for timely assessment of treatment response.
- There is a need for advanced imaging tools capable of deep-tissue, high-resolution, multicolor visualization of cellular dynamics.
Purpose of the Study:
- To develop and demonstrate a fully wireless, implantable image sensor for multicolor fluorescence imaging deep within biological tissues.
- To enable real-time monitoring of cellular dynamics, specifically immune cells, for assessing therapeutic responses.
- To overcome the limitations of existing clinical imaging modalities in terms of molecular contrast, resolution, and chronic usability.
Main Methods:
- A wireless CMOS image sensor (2.5×5 mm²) was designed for multicolor fluorescence imaging.
- Ultrasound (US) was used for wireless operation up to 5 cm depth, energy harvesting (221 mW/cm²), and data backscattering (13 kbps, BER <10⁻⁶).
- In-situ fluorescence excitation was achieved using microlaser diodes and an optical frontend with a multi-bandpass filter and fiber optic plate for three-color imaging and excitation blocking (>6 OD).
Main Results:
- The sensor achieved wireless operation at 5 cm depth with efficient energy harvesting and high-speed data transmission.
- A resolution of <125 μm was achieved with the 36×40-pixel array.
- Demonstrated wireless, dual-color fluorescence imaging of effector and suppressor immune cells in ex vivo mouse tumor samples, with and without immunotherapy.
Conclusions:
- The developed wireless image sensor provides deep-tissue, multicolor fluorescence imaging capabilities.
- This technology shows significant promise for rapid assessment of therapeutic response and resistance in cancer immunotherapy.
- The findings support the potential for guiding personalized medicine through real-time monitoring of dynamic biological processes.

