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Updated: Dec 29, 2025
Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers
Published on: July 17, 2012
Localization of Fluorescent Targets in Deep Tissue With Expanded Beam Illumination for Studies of Cancer and the
Abstract:
Imaging fluorescence through millimeters or centimeters of tissue has important in vivo applications, such as guiding surgery and studying the brain. Often, the important information is the location of one of more optical reporters, rather than the specifics of the local geometry, motivating the need for a localization method that provides this information. We present an optimization approach based on a diffusion model for the fast localization of fluorescent inhomogeneities in deep tissue with expanded beam illumination that simplifies the experiment and the reconstruction. We show that the position of a fluorescent inhomogeneity can be estimated while assuming homogeneous tissue parameters and without having to model the excitation profile, reducing the computational burden and improving the utility of the method. We perform two experiments as a demonstration. First, a tumor in a mouse is localized using a near infrared folate-targeted fluorescent agent (OTL38). This result shows that localization can quickly provide tumor depth information, which could reduce damage to healthy tissue during fluorescence-guided surgery. Second, another near infrared fluorescent agent (ATTO647N) is injected into the brain of a rat, and localized through the intact skull and surface tissue. This result will enable studies of protein aggregation and neuron signaling.
Insights
This study introduces a fast method for locating fluorescent agents deep within tissue using a diffusion model. The approach simplifies experiments and accurately pinpoints reporter locations for applications like surgery and brain studies.
Area of Science:
- Biomedical Optics
- Medical Imaging
- Fluorescence Imaging
Background:
- In vivo fluorescence imaging is crucial for surgical guidance and brain research.
- Accurate localization of optical reporters in deep tissue is essential for these applications.
Purpose of the Study:
- To develop a fast and computationally efficient method for localizing fluorescent inhomogeneities in deep tissues.
- To simplify experimental setup and reconstruction processes for deep tissue fluorescence imaging.
Main Methods:
- An optimization approach based on a diffusion model was employed for localization.
- Expanded beam illumination was used to simplify the experimental setup.
- The method estimates reporter position assuming homogeneous tissue and without modeling the excitation profile.
Main Results:
- Successfully localized a tumor in a mouse using a near-infrared folate-targeted fluorescent agent (OTL38), providing depth information.
- Localized a near-infrared fluorescent agent (ATTO647N) in a rat brain through intact skull and surface tissue.
- Demonstrated reduced computational burden and improved utility compared to traditional methods.
Conclusions:
- The developed method enables rapid and accurate localization of fluorescent agents in deep tissues.
- This technique has significant potential for improving fluorescence-guided surgery by providing critical depth information.
- The method facilitates advanced in vivo studies of biological processes, such as protein aggregation and neuron signaling.
