Analytical calculation of the mean time spent by photons inside an absorptive inclusion embedded in a highly scattering medium

The mean time spent by photons inside a nonlocalized optically abnormal embedded inclusion has been derived analytically. The accuracy of the results has been tested against Monte Carlo and experimental data. We show that for quantification of the absorption coefficient of absorptive inclusions, a corrective factor that takes into account the size of the inclusion is needed. This finding suggests that perturbation methods derived for very small inclusions which are used in inverse algorithms require a corrective factor to adequately quantify the differential absorption coefficient of nonlocalized targets embedded in optically turbid media

In Vivo Fluorescence Lifetime Imaging Monitors Binding of Specific Probes to Cancer Biomarkers

One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the “image and treat” concept, especially for early evaluation of the efficacy of the therapy

Modern Trends in Imaging IX: Biophotonics Techniques for Structural and Functional Imaging, In Vivo

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as AntiBodies (MAB), has created a new demand for developing non-invasive in vivo imaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis

Single Source-Detector Separation Approach to Calculate Tissue Oxygen Saturation Using Continuous Wave Near-Infrared Spectroscopy

Currently, common optical techniques to measure tissue oxygen saturation (StO2) include time domain (TD), frequency domain (FD), and continuous wave (CW) near-infrared spectroscopy (NIRS). While TD- and FD-NIRS can provide absolute hemoglobin concentration, these systems are often complex and expensive. CW-NIRS, such as diffuse reflectance spectroscopy and spatially resolved spectroscopy (SRS), are simpler and more affordable, but they still require at least two source-detector separations. Here, we propose a single source-detector separation (SSDS) approach to measure StO2 using reflected intensities from three wavelengths. The accuracy of the SSDS-based StO2 measurement was verified using an optical simulation and an in-vivo experiment. Simulated spatially dependent reflectance was generated using the Virtual Tissue Simulator on a 1-layer model, which has StO2 ranging from 0% to 100%. SSDS calculation yielded an equivalent StO2 to the actual value (average error = 0.3% ± 0.5%). We then performed StO2 measurements on seven healthy volunteers in the prefrontal cortex during a simulated hypercapnia test using a CW-NIRS device. This device consists of a light source and two photodetectors, which are 30 mm and 40 mm away from the light source. The cerebral oxygen saturation was calculated using both the SRS approach, which uses the reflected intensities at both separations, and the SSDS approach, which employs the reflected intensities at either 30 mm or 40 mm separation. The SRS-based StO2 calculation was similar to the value calculated from the SSDS method (average difference = 5.0% ± 1.1%). This proposed method will help to advance the development of miniaturized technologies to monitor StO2 continuously