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Updated: Jul 5, 2025
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor
Arthur F Petusseau1, Samuel S Streeter2, Arin Ulku3
1Dartmouth College, Thayer School of Engineering and Dartmouth Cancer Center, Hanover, New Hampshire, United States.
Significance:
Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided.
Aim:
We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration.
Approach:
The technology is based on a large-format (), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18 ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data.
Results:
After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5 mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations.
Conclusions:
LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon's efficacy and efficiency, and ultimately improving patient outcomes.
Insights
We developed a novel depth-sensing fluorescence imaging technique using LiDAR time-of-flight (TOF) to precisely locate fluorescent targets within tissue. This advancement offers improved surgical guidance and better patient outcomes by visualizing subsurface malignancy.
Area of Science:
- Biomedical Optics
- Surgical Technology
- Medical Imaging
Background:
- Conventional fluorescence-guided surgery lacks depth information, limiting visualization of subsurface structures.
- Current methods struggle to differentiate fluorescence signals from varying tissue optical properties.
Purpose of the Study:
- To develop a depth-sensing fluorescence imaging technique using LiDAR time-of-flight (TOF).
- To overcome limitations of conventional fluorescence imaging by providing crucial depth information.
Main Methods:
- Utilized a large-format, binary, gated, single-photon avalanche diode (SPAD) sensor with picosecond time-gate steps.
- Synchronized the SPAD sensor with a picosecond pulsed laser for time-of-flight measurements.
- Employed analytical model fitting of temporal remission data to quantify fluorescence depth and tissue optical properties.
Main Results:
- Achieved sub-millimeter resolution depth sensing of fluorescent inclusions up to 5 mm deep in tissue phantoms.
- Demonstrated robust depth sensing independent of variable tissue optical properties (absorption and scattering).
- Successfully separated fluorescence depth from optical property variations.
Conclusions:
- LiDAR TOF fluorescence imaging with SPAD cameras provides both intensity and depth information.
- This technique offers higher depth penetration and spatial precision compared to standard fluorescence imaging methods.
- Integration into surgical tools can enhance resection boundary estimation, improving surgical efficacy and patient outcomes.
