A CT-analogous scheme for time-domain diffuse fluorescence tomography
ABSTRACT A fiber-based non-contact scheme of the time-domain diffuse fluorescence yield and lifetime tomography is described that combines the time-correlated single photon counting technique for high-sensitive, time-resolved detection and CT-analogous configuration for large data-set collection. A pilot validation of the methodology is performed for two-dimensional scenarios using simulated and experimental data. The results demonstrated the efficacy of the proposed scheme in improving the image quality.
SourceAvailable from: Hari Krishna Sajja[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE: To demonstrate diffuse optical tomography (DOT) corrected fluorescence molecular tomography (FMT) for quantitatively imaging tumor-targeted contrast agents in a 4T1 mouse mammary tumor model. PROCEDURES: In the first set of experiments, we validated our DOT corrected FMT method using subcutaneously injected 4T1 cells pre-labeled with a near-infrared (NIR) Cy 5.5 dye labeled recombinant amino-terminal fragment (ATF) of the receptor binding domain of urokinase plasminogen activator (uPA), which binds to uPA receptor (uPAR) that is highly expressed in breast cancer tissues. Next, we apply the DOT corrected FMT method to quantitatively evaluate the ability of sensitive tumor imaging after systemic delivery of new uPAR-targeted optical imaging probes in the mice bearing 4T1 mammary tumors. These uPAR-targeted optical imaging probes are ATF peptides labeled with a newly developed NIR-830 dye being conjugated to magnetic iron oxide nanoparticles (IONPs). RESULTS: Our results have shown that DOT corrected FMT can accurately quantify and localize the injected imaging probe labeled 4T1 cells. Following systemic delivery of the targeted imaging nanoprobes into the mice bearing orthotopic mammary tumors, specific accumulation of the imaging probes in the orthotopic mammary tumors was detected in the mice that received uPAR targeted NIR-830-ATF-IONP probes but not in the mice injected with non-targeted NIR-830-mouse serum albumin (MSA)-IONPs. Additionally, DOT corrected FMT also enables the detection of both locally recurrent tumor and lung metastasis in the mammary tumor model 72 hrs after systemic administration of the uPAR-targeted NIR-830-labeled ATF peptide imaging probes. CONCLUSIONS: DOT corrected FMT and uPAR-targeted optical imaging probes have great potential for detection of breast cancer, recurrent tumor and metastasis in small animals.Journal of X-Ray Science and Technology 01/2013; 21(1):43-52. DOI:10.3233/XST-130365 · 1.46 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The combined system of micro-CT and fluorescence molecular tomography (FMT) offers a new tool to provide anatomical and functional information of small animals in a single study. To take advantages of the combined system, a data preprocessing method is proposed to extract the valid data for FMT reconstruction algorithms using a priori information provided by CT. The boundary information of the animal and animal holder is extracted from reconstructed CT volume data. A ray tracing method is used to trace the path of the excitation beam, calculate the locations and directions of the optional sources and determine whether the optional sources are valid. To accurately calculate the projections of the detectors on optical images and judge their validity, a combination of perspective projection and inverse ray tracing method are adopted to offer optimal performance. The imaging performance of the combined system with the presented method is validated through experimental rat imaging.Journal of X-Ray Science and Technology 01/2012; 20(4):459-68. DOI:10.3233/XST-2012-00352 · 1.46 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The importance of cellular pH has been shown clearly in the study of cell activity, pathological feature, and drug metabolism. Monitoring pH changes of living cells and imaging the regions with abnormal pH-values, in vivo, could provide invaluable physiological and pathological information for the research of the cell biology, pharmacokinetics, diagnostics, and therapeutics of certain diseases such as cancer. Naturally, pH-sensitive fluorescence imaging of bulk tissues has been attracting great attentions from the realm of near infrared diffuse fluorescence tomography (DFT). Herein, the feasibility of quantifying pH-induced fluorescence changes in turbid medium is investigated using a continuous-wave difference-DFT technique that is based on the specifically designed computed tomography-analogous photon counting system and the Born normalized difference image reconstruction scheme. We have validated the methodology using two-dimensional imaging experiments on a small-animal-sized phantom, embedding an inclusion with varying pH-values. The results show that the proposed approach can accurately localize the target with a quantitative resolution to pH-sensitive variation of the fluorescent yield, and might provide a promising alternative method of pH-sensitive fluorescence imaging in addition to the fluorescence-lifetime imaging.Journal of Biomedical Optics 09/2012; 17(9):96011-1. DOI:10.1117/1.JBO.17.9.096011 · 2.75 Impact Factor