Amir Y. Sajjadi

Hemodynamic signature of breast cancer under fractional mammographic compression using a dynamic diffuse optical tomography system

Near infrared dynamic diffuse optical tomography measurements of breast hemodynamics during fractional mammographic compression offer a novel contrast mechanism for detecting breast cancer and monitoring chemotherapy. Tissue viscoelastic relaxation during the compression period leads to a slow reduction in the compression force and reveals biomechanical and metabolic differences between healthy and lesion tissue. We measured both the absolute values and the temporal evolution of hemoglobin concentration during 25-35 N of compression for 22 stage II and III breast cancer patients scheduled to undergo neoadjuvant chemotherapy. 17 patients were included in the group analysis (average tumor size 3.2 cm, range: 1.3-5.7 cm). We observed a statistically significant differential decrease in total and oxy-hemoglobin, as well as in hemoglobin oxygen saturation in tumor areas vs. healthy tissue, as early as 30 seconds into the compression period. The hemodynamic contrast is likely driven by the higher tumor stiffness and different viscoelastic relaxation rate, as well as the higher tumor oxygen metabolism rate.

Expression of heat shock proteins 70 and 47 in tissues following short-pulse laser irradiation: assessment of thermal damage and healing.

In order to develop effective laser-based therapeutics, the extent of laser-induced damage must be quantified for given laser parameters. Therefore, we want to determine the spatiotemporal expression patterns of heat shock proteins, both to understand the roles of heat shock proteins in laser-induced tissue damage and repair and to develop heat shock proteins as tools to illustrate the extent of laser-induced damage and wound healing following irradiation. We exposed anesthetized mice to the focused beam of a short-pulse Nd:YAG laser (1064 nm; 200 ns pulsewidth) for 15s, while measuring temperature distribution in the skin using an infrared thermal camera. Following irradiation, we examined expression of HSP47 and HSP70 over time (0-24h) as indicators of the heat shock response and recovery from damage in the laser-irradiated region. Expression patterns of HSP70 and HSP47 as detected by immunohistochemistry and confocal microscopy delineate the extent of damage and the process of healing in tissue. Both HSP70 and HSP47 were expressed in dermis and epidermis following laser irradiation, and the spatial and temporal changes in HSP expression patterns define the laser-induced thermal damage zone and the process of healing in tissues. HSP70 may define biochemically the thermal damage zone in which cells are targeted for destruction, and HSP47 may illustrate the process of recovery from thermally induced damage. Studying the effects of different laser parameters on the expression of HSPs will allow development of effective laser therapies that provide accurate and precise tissue ablation and may promote rapid wound healing following laser-based surgery.

Rapid fibrin plug formation within cutaneous ablative fractional CO2 laser lesions

Ablative fractional laser procedures have been shown to facilitate topical drug delivery into the skin. Past studies have mainly used ex vivo models to demonstrate enhanced drug delivery and in vivo studies have investigated laser created channels over a time course of days and weeks rather than within the first few minutes and hours after exposures. We have noticed rapid in vivo fibrin plug formation within ablative fractional laser lesions impairing passage through the laser created channels.

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis

Abstract. Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In particular, the multimodal approach of combining DOT with x-ray digital breast tomosynthesis (DBT) is especially synergistic as DBT prior information can be used to enhance the DOT reconstruction. DOT, in turn, provides a functional information overlay onto the mammographic images, increasing sensitivity and specificity to cancer pathology. We describe a dynamic DOT apparatus designed for tight integration with commercial DBT scanners and providing a fast (up to 1 Hz) image acquisition rate to enable tracking hemodynamic changes induced by the mammographic breast compression. The system integrates 96 continuous-wave and 24 frequency-domain source locations as well as 32 continuous wave and 20 frequency-domain detection locations into low-profile plastic plates that can easily mate to the DBT compression paddle and x-ray detector cover, respectively. We demonstrate system performance using static and dynamic tissue-like phantoms as well as in vivo images acquired from the pool of patients recalled for breast biopsies at the Massachusetts General Hospital Breast Imaging Division.

Thermal Ablation of Mouse Skin Tissue Using Ultra-Short Pulse 1552 nm Laser

Analysis of biological tissue ablation by an ultra-short pulse laser and the corresponding mathematical modeling of ablation are of fundamental importance to the understanding of laser-tissue interaction for advancing surgical application of lasers. The objective of this paper is to analyze the thermal ablated damage zones during irradiation of freshly excised mouse skin tissue samples by a novel approach of using a focused laser beam from an ultra-short pulse laser source. Experiments are performed using Raydiance Desktop Laser having a wavelength of 1552 nm and a pulse width of 1.3 ps. Mouse tissue samples are translated in a direction perpendicular to the laser beam using three-axis automated motion-controlled stages. Scanning of the tissue sample ensures a fresh region of the tissue is irradiated each time. The surface temperature distribution is measured using a thermal imaging camera. It is observed that use of focused beam results in minimal radial heat spread to the surrounding tissue regions. The ablation phenomenon is analytically modeled by the use of two-phase transient heat conduction model. After completion of tissue irradiation experiments, histological studies are performed using frozen sectioning technique to observe morphological changes in tissue samples in response to laser irradiation. The ablation depth measurements obtained using histological studies are compared with the modeling results. A parametric study of various laser parameters such as time-average power, pulse repetition rate, and pulse energy, and as well as irradiation time and scanning velocity is performed to determine the necessary ablation threshold. Analytical modeling results are in very good agreement with experimentally measured ablation depth. The goal of this research is to develop a tool for selection of appropriate laser parameters for precise clean tissue ablation.Copyright

Spatio-temporal dynamics of cerebral capillary segments with stalling red blood cells

Optical coherence tomography (OCT) allows label-free imaging of red blood cell (RBC) flux within capillaries with high spatio-temporal resolution. In this study, we utilized time-series OCT-angiography to demonstrate interruptions in capillary RBC flux in mouse brain in vivo. We noticed ∼7.5% of ∼200 capillaries had at least one stall in awake mice with chronic windows during a 9-min recording. At any instant, ∼0.45% of capillaries were stalled. Average stall duration was ∼15 s but could last over 1 min. Stalls were more frequent and longer lasting in acute window preparations. Further, isoflurane anesthesia in chronic preparations caused an increase in the number of stalls. In repeated imaging, the same segments had a tendency to stall again over a period of one month. In awake animals, functional stimulation decreased the observance of stalling events. Stalling segments were located distally, away from the first couple of arteriolar-side capillary branches and their average RBC and plasma velocities were lower than nonstalling capillaries within the same region. This first systematic analysis of capillary RBC stalls in the brain, enabled by rapid and continuous volumetric imaging of capillaries with OCT-angiography, will lead to future investigations of the potential role of stalling events in cerebral pathologies.

Visualization of Heat Shock Proteins for Quantifying Laser-Induced Thermal Ablation of Biological Tissues

In laser-based therapeutics, it is important to ablate target tissue with minimal damage to surrounding healthy tissue. Unique properties of lasers allow precise and controlled ablation of tissue. Tightly focusing a short-pulse laser at the desired tissue region and controlling the exposure time by scanning the beam at the target can minimize corresponding collateral damage [1]. Even so, design of effective laser-based ablation procedures requires an understanding of the extent of laser-induced damage for given laser parameters (power, intensity, duration, etc.). Therefore, the instantaneous and effects over time of laser irradiation in live tissue should be studied. Instantaneous effects can be quantified by measuring thermal effects of laser irradiation on tissue. Depending on the application, threshold temperature is necessary to make permanent or temporary changes in tissue structure [1]. The temperature profile around the laser-irradiated region gives insight into radial energy spread and the extent of damage in tissue surrounding the ablation zone. In order to investigate the effects over time of laser irradiation of tissue, we studied the temporal expression patterns heat shock proteins (HSP), members of a class of proteins whose expression patterns change when cells are exposed to elevated temperature or other stressors [2]. We conducted experiments on live anesthetized mice to determine the spatiotemporal expression patterns of heat shock proteins in skin tissue after laser stimulation, both to understand the roles of heat shock proteins in laser-induced tissue damage and repair, and to develop heat shock proteins as tools to illustrate the extent of laser-induced damage and wound healing following irradiation.Copyright

Transient radiation modeling of short-pulse laser detection of tumors in animal model

The objective of this paper is to perform a comprehensive experimental and numerical analysis of the short pulse laser interaction with tissue medium with the goal of tumor / cancer diagnostics. For a short pulse laser source, the shape of the output signal is a function of the optical properties of the medium and hence the scattered temporal optical signal helps in understanding of the medium characteristics. In this paper the scattered reflected optical signals from the tissue medium are modeled using the transient radiative transport equation (RTE) solved by the discrete ordinates technique. In vivo imaging was performed on anaesthetized rats with tumorogenic agents injected inside skin tissues and on anaesthetized mouse with mammary tumors. The numerical results are compared with the experimental data to validate the model and demonstrate the feasibility of the time-resolved technique in detecting tumors in animal model.

Analysis of Short Pulse Laser Interaction With Tissues for Tumor Detection

The objective of the work is to perform both experimental and numerical analysis of short pulse laser interaction with tissue medium with the goal of tumor / cancer diagnostics. Short pulse laser probing techniques for diagnostics have distinct advantages over very large pulse width or continuous wave lasers primarily due to the additional information conveyed by the temporal distribution of the optical signals. For short pulse laser source, the shape of output signal is a function of the optical properties of the medium and hence the scattered optical signal provides information about the medium characteristics. Two laser systems are used: a mode-locked short pulse laser (wavelength = 514 nm and pulsewidth = 200 ps) and a frequency doubled diode short pulse laser (wavelength = 776 nm and pulsewidth = 1.3 ps). The scattered optical signals are measured with a Hamamatsu streak camera. First in vitro experiments are performed on mouse skin tissue samples injected with India ink in order to simulate presence of inhomogeneities. Finally, in vivo imaging is performed on anaesthetized rats with tumorogenic agents injected inside skin tissues and on anaesthetized mouse with mammary tumors. Both the temporal and the spatial profiles of the scattered reflected optical signals are compared with the numerical modeling results obtained by solving the transient radiative transport equation using the discrete ordinates technique. The goal is to demonstrate the feasibility of the time-resolved technique in detecting tumors in animal model.© 2009 ASME

Tissue Response to Short Pulse Laser Irradiation

The objective of this chapter is to analyze the transient temperature distribution in skin tissues due to short pulse laser irradiation. COMSOL Multiphysics, a finite element solver, is used to analyze the heat affected zone in a multilayer tissue geometry modeled by considering the embedded vasculature to account for the blood flow. Compared to the existing continuum model, the results predicted by the embedded vasculature simulations are in good agreement with the experimental temperature distribution measurements for experiments on live anesthetized mice. A parametric study has been performed to analyze the effects of varying blood flow velocities on the temperature distribution in tissues. Inclusion of embedded vascularity played a significant role in the analysis of short pulse laser-based therapy of soft tissues.