David I. Rosen

Toward noninvasive measurement of blood hematocrit using spectral domain low coherence interferometry and retinal tracking.

We demonstrate in vivo measurements in human retinal vessels of an experimental parameter, the slope of the low coherence interferometry (LCI) depth reflectivity profile, which strongly correlates with the real value of blood hematocrit. A novel instrument that combines two technologies, spectral domain low coherence interferometry (SDLCI) and retinal tracking, has been developed and used for these measurements. Retinal tracking allows a light beam to be stabilized on retinal vessels, while SDLCI is used for obtaining depth-reflectivity profiles within the investigated vessel. SDLCI backscatter extinction rates are obtained from the initial slope of the A-scan profile within the vessel lumen. The differences in the slopes of the depth reflectivity profiles for different subjects are interpreted as the difference in the scattering coefficient, which is correlated with the number density of red blood cells (RBC) in blood. With proper calibration, it is possible to determine hematocrit in retinal vessels. Ex vivo measurements at various RBC concentrations were performed to calibrate the instrument. Preliminary measurements on several healthy volunteers show estimated hematocrit values within the normal clinical range.

Pulsed diode laser-based monitor for singlet molecular oxygen

Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1Delta) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling.

Preliminary evaluation of a nanotechnology-based approach for the more effective diagnosis of colon cancers.

AIM The goal of this research was to develop and preliminarily test a novel technology and instrumentation that could help to significantly increase the diagnostic yield of current colon cancer screening procedures. This technology is based on a combined fluorescence-optical coherence tomography (OCT) imaging, and topical delivery of a cancer-targeting agent. MATERIALS & METHODS Gold colloid-adsorbed poly(ε-caprolactone) microparticles were labeled with a near-infrared dye, and functionalized with argentine-glycine-aspartic acid (RGD peptide) to effectively target cancer tissue, and enhance fluorescence-imaging contrast. The RGD peptide recognizes the α(v)β(3)-integrin receptor, which is overexpressed by epithelial cancer cells. OCT was used under fluorescence guidance to visualize tissue morphology and, thus, to serve as a confirmatory tool for cancer presence. RESULTS A preliminary testing of this technology on human colon cancer cell lines, a mouse model of colon cancer, as well as human colon tissue specimens, was performed. Strong binding of microparticles to cancer cells and no binding to cells that do not significantly express integrins, such as mouse fibroblasts, was observed. Preferential binding to cancer tissue was also observed. Strong fluorescence signals were obtained from cancer tissue, owing to the efficient binding of the contrast agent. OCT imaging was capable of revealing clear differences between normal and cancer tissue. CONCLUSION A dual-modality imaging approach combined with topical delivery of a cancer-targeting contrast agent has been preliminarily tested for colon cancer diagnosis. Preferential binding of the contrast agent to cancer tissue allowed the cancer-suspicious locations to be highlighted and, thus, guided OCT imaging to visualize tissue morphology and determine tissue type. If successful, this multimodal approach might help to increase the sensitivity and the specificity of current colon cancer-screening procedures in the future.

Diode laser monitor for singlet molecular oxygen

Monitoring singlet molecular oxygen (1O2) produced by photodynamic therapy (PDT) can lead more precise and effective cancer treatment. Physical Sciences Inc. (PSI) has developed a singlet oxygen monitor based on a pulsed diode laser technology. In this paper, we present results of singlet oxygen detection in the solution phase and in a rat prostate cancer cell line, as well as PDT mechanism modeling. We describe an improved detection approach for singlet oxygen monitoring that employs a fiber-coupled optical set-up and fast data acquisition system.

Modeling Of The Laser-Induced Ablation And Thermal Damage Of Biological Tissue

Detailed calculations of the thermal response and ablation of biological tissue exposed to 10p laser radiation are presented. For most of the calculations shown, tissue response was modeled using generalized computer codes that were originally developed to model the laser-induced response of a variety of non-biological materials. The models are applicable at any wavelength for which the absorption cross section in the tissue is large compared to the scattering cross section. In this initial study, soft tissue has been modeled as a single component material with thermal and optical properties very similar to that of water. The predominant phenomena treated are in-depth laser absorption, thermal conduction, and surface vaporization. In-depth thermal damage of tissue is calculated by incorporating into the codes a reaction for the thermal denaturation of tissue protein. Model calculations are presented for exposures ranging from low power CW exposures of a few watts per cm and exposure times of tens of seconds to single-pulse exposures with peak irradiances of several megawatts per cm2 and microsecond exposure durations. Where possible, model predictions are compared to available experimental data and the implications of the comparisons are discussed. Recommendations for future modeling improvements are also presented.

High-power laser applications to medicine

Abstract In this paper, we briefly summarize the processes that occur during the coupling of laser energy to biological tissue and review the parameters that control this interaction. We then consider three separate and recent applications of lasers to medicine. First, we present the results of a series of numerical simulations of the use of CO2 lasers for surgical applications. Then, we discuss spectroscopic issues related to the use of hematoporphyrin derivative (HPD) as a selective laser absorber and diagnostic for treatment of tumors. Use of pulsed dye lasers to fragment kidney stones and gallstones is then reviewed, mechanisms that control the process identified, and an interaction model is suggested.

Ultrasensitive diode-laser-based monitor for singlet oxygen

In this paper we present results from experiments to develop a real-time, optical monitor for singlet molecular oxygen produced during photodynamic therapy. Using a pulsed diode laser and a sensitive photomultiplier tube, we have obtained signals from singlet oxygen during and following pulsed laser excitation. Several photosensitizers were used, and we obtained strong signals even in the presence of protein laden environments. Values obtained for the lifetimes of the singlet oxygen state and the photosensitizer triplet state are compared to literature values.

Noninvasive monitoring of blood composition

A novel instrument for real-time in vivo measurement of blood composition is presented. Two optical technologies are combined in this instrument: spectral domain low coherence interferometry (SD-LCI) and retinal tracking. Retinal tracking is used to stabilize the LCI beam on vessels. SD-LCI is used to get depth-reflectivity profiles within the vessels. Multiple signals are rapidly acquired, averaged and processed. Differences in the slopes of the depth reflectivity profiles for different subjects correspond to the difference in the scattering coefficient, which is proportional to the concentration of red blood cells per cubic mm of blood (hematocrit). Preliminary measurements on several healthy volunteers show a good correlation with the normal range of the hematocrit.

Mechanistic and diagnostic aspects of photodynamic enhancement and stone fragmentation

Metastable oxygen molecules in the singlet delta state O2(1Δ), are believed to be the active species that are produced upon laser irradiation of hematoporphyrin derivative (HPD), attached to tumors, and are responsible for cancer cell destruction. Although the presence of O2(1Δ) has been inferred by indirect chemical measurements, it has not been detected in real time. In this work, we review the optical characteristics of O2(1Δ) and describe an optical diagnostic procedure for its real‐time detection during laser irradiation. Additionally, recent work has been presented whereby repetitively pulsed dye laser radiation can be delivered through a fiber optic probe to induce fragmentation of kidney stones and gallstones. In this paper, we review this work and describe experiments whose objective is to detect the fragmentation process in situ by acoustic emission.

New heat pipe oven devices for broad band excitation laser studies

A heat pipe oven type device was designed and operated with sodium at temperatures up to 450° C without significant deposit on the window that was within 2 to 3 cm of the sodium vapor. The uniformity of sodium vapor in the device was such that laser action in the Na2 A→X transitions was achieved.