Pratik Samant

Transurethral Photoacoustic Endoscopy for Prostate Cancer: A Simulation Study

The purpose of this study was to optimize the configuration of a photoacoustic endoscope (PAE) for prostate cancer detection and therapy monitoring. The placement of optical fiber bundles and ultrasound detectors was chosen to maximize the photoacoustic imaging penetration depth. We performed both theoretical calculations and simulations of this optimized PAE configuration on a prostate-sized phantom containing tumor and various photosensitizer concentrations. The optimized configuration of PAE with transurethral light delivery simultaneously increases the imaging penetration depth and improves image quality. Thermal safety, investigated via COMSOL Multiphysics, shows that there is only a 4 mK temperature rise in the urethra during photoacoustic imaging, which will cause no thermal damage. One application of this PAE has been demonstrated for quasi-quantifying photosensitizer concentrations during photodynamic therapy. The sensitivity of the photoacoustic detection for TOOKAD was 0.18 ng/mg at a 763 nm laser wavelength. Results of this study will greatly enhance the potential of prostate PAE for in vivo monitoring of drug delivery and guidance of the laser-induced therapy for future clinical use.

Characterization of the temperature rise in a single cell during photoacoustic tomography at the nanoscale.

Abstract. We are developing a label-free nanoscale photoacoustic tomography (nPAT) for imaging a single living cell. nPAT uses a laser-induced acoustic pulse to generate a nanometer-scale image. The primary motivation behind this imaging technique is the imaging of biological cells in the context of diagnosis without fluorescent tagging. During this procedure, thermal damage due to the laser pulse is a potential risk that may damage the cells. A physical model is built to estimate the temperature rise and thermal relaxation during the imaging procedure. Through simulations using finite element methods, two lasers (532 nm at 5 ps pulse duration and 830 nm at 0.2 ps pulse duration) were simulated for imaging red blood cells (RBCs). We demonstrate that a single 5-ps pulse laser with a 400-Hz repetition rate will generate a steady state temperature rise of less than a Kelvin on the surface of the RBCs. All the simulation results show that there is no significant temperature rise in an RBC in either single pulse or multiple pulse illumination with a 532-nm laser with 219 W fluence. Therefore, our simulation results demonstrate the thermal safety of an nPAT system. The photoacoustic signal generated by this laser is on the order of 2.5 kPa, so it should still be large enough to generate high-resolution images with nPAT. Frequency analysis of this signal shows a peak at 1.47 GHz, with frequencies as high as 3.5 GHz still being present in the spectrum. We believe that nPAT will open an avenue for disease diagnosis and cell biology studies at the nanometer-level.

X-ray-induced acoustic computed tomography of concrete infrastructure

X-ray-induced Acoustic Computed Tomography (XACT) takes advantage of both X-ray absorption contrast and high ultrasonic resolution in a single imaging modality by making use of the thermoacoustic effect. In XACT, X-ray absorption by defects and other structures in concrete create thermally induced pressure jumps that launch ultrasonic waves, which are then received by acoustic detectors to form images. In this research, XACT imaging was used to non-destructively test and identify defects in concrete. For concrete structures, we conclude that XACT imaging allows multiscale imaging at depths ranging from centimeters to meters, with spatial resolutions from sub-millimeter to centimeters. XACT imaging also holds promise for single-side testing of concrete infrastructure and provides an optimal solution for nondestructive inspection of existing bridges, pavement, nuclear power plants, and other concrete infrastructure.

Nanoscale Photoacoustic Tomography (nPAT) for label-free super-resolution 3D imaging of red blood cells

We present our results in developing nanoscale photoacoustic tomography (nPAT) for label-free super-resolution imaging in 3D. We have made progress in the development of nPAT, and have acquired our first signal. We have also performed simulations that demonstrate that nPAT is a viable imaging modality for the visualization of malaria infected red blood cells (RBCs). Our results demonstrate that nPAT is both feasible and powerful for the high resolution labelfree imaging of RBCs.

Photoacoustic image-guided drug delivery in the prostate

Image guided drug delivery is a novel strategy that combines the effect of therapy and visibility into one system. Here we apply photoacoustic (PA) imaging to visualize the drug delivery process, and perform a simulation study on monitoring the photosensitizer concentration in a prostate tumor during photodynamic therapy (PDT). A 3D optical model of the human prostate is developed, and the light absorption distribution in the prostate is estimated by the Monte Carlo simulation method. The filtered back-projection algorithm is used to reconstruct PA images. PA images of transurethral laser/transrectal ultrasound are compared to those of transrectal laser/ultrasound. Results show that the transurethral laser has a better penetration depth in the prostate compared with transrectal one. Urethral thermal safety is investigated via COMSOL Multiphysics, and the results show that the proposed pulsed transurethral laser will cause no thermal damage on the urethral surface. Regression analysis for PA signal amplitude and drug concentration demonstrates that the PA technique has the potential to monitor drug distributions in PDT, as well as in other laser-based prostate therapy modalities.

Sub-mSV breast XACT scanner: concept and design

Excessive exposure to radiation increases the risk of cancer. We present the concept and design of a new imaging paradigm, X-ray induced acoustic computed tomography (XACT). Applying this innovative technology to breast imaging, one single X-ray exposure can generate a 3D acoustic image, which dramatically reduces the radiation dose to patients when compared to beast CT. A theoretical model is developed to analyze the sensitivity of XACT. A noise equivalent pressure model is used for calculating the minimal radiation dose in XACT imaging. Furthermore, K-Wave simulation is employed to study the acoustic wave propagation in breast tissue. Theoretical analysis shows that the X-ray induced acoustic signal has a 100% relative sensitivity to the X-ray absorption (given that the percentage change in the X-ray absorption coefficient yields the same percentage change in the acoustic signal amplitude), but not to X-ray scattering. The final detection sensitivity is primarily limited by the thermal noise. The radiation dose can be reduced by a factor of 100 compared with the newly FDA approved breast CT. Reconstruction result shows that breast calcification with diameter of 80 μm can be observed in XACT image by using ultrasound transducers with 5.5 MHz center frequency. Therefore, with the proposed innovative technology, one can potentially reduce radiation dose to patient in breast imaging as compared with current x-ray modalities.

Real-time in-situ monitoring of electrotherapy process using electric pulse-induced acoustic tomography (EpAT)

The use of electrical energy in applying reversible or irreversible electropermobilization for biomedical therapies is growing rapidly. This technique uses an ultra-short and high-voltage electric pulse (μs-to-nsEP) to improve the permeability of cell membranes, thus allowing drug delivery to the cytosol via nanopores in the membrane. Since the treatment subject varies in size, location, shape and tissue environment, it is necessary to visualize this mechanism by monitoring electric field distributions in real-time. Previous studies suggested various techniques for monitoring electroporation, however, none of these techniques are so far capable for real-time monitoring of the electric field. In this study, we propose an innovative real-time, monitoring technique of electric field distributions based on electric field-induced acoustic emissions. For the first time, we demonstrate the capability of an electric field that used in electrotherapy to induce acoustic waves, which can be suggested for realtime monitoring. We tested this technique by generating a variety of electric field distributions (μs-to-nsEP with intensity up to 120V/cm) to energize two electrodes in a bi-polar configuration (d1=100μm and d2=200μm). The electric field transmits a short burst of ultrasonic energy. We used ultrasonic receivers for collecting acoustic signals around the subject under test. Acoustic signals were collected through different intensities of electric field distributions and repositioning the electric field from the receiver in 3D structure. An electric field utilized in electrotherapy produces high resolution images that directly can improve the efficiency of electrotherapy treatments in real-time.

Real-time, in situ monitoring of nanoporation using electric field-induced acoustic signal

The use of nanoporation in reversible or irreversible electroporation, e.g. cancer ablation, is rapidly growing. This technique uses an ultra-short and intense electric pulse to increase the membrane permeability, allowing non-permeant drugs and genes access to the cytosol via nanopores in the plasma membrane. It is vital to create a real-time in situ monitoring technique to characterize this process and answer the need created by the successful electroporation procedure of cancer treatment. All suggested monitoring techniques for electroporation currently are for pre-and post-stimulation exposure with no real-time monitoring during electric field exposure. This study was aimed at developing an innovative technology for real-time in situ monitoring of electroporation based on the typical cell exposure-induced acoustic emissions. The acoustic signals are the result of the electric field, which itself can be used in realtime to characterize the process of electroporation. We varied electric field distribution by varying the electric pulse from 1μ - 100ns and varying the voltage intensity from 0 − 1.2ܸ݇ to energize two electrodes in a bi-polar set-up. An ultrasound transducer was used for collecting acoustic signals around the subject under test. We determined the relative location of the acoustic signals by varying the position of the electrodes relative to the transducer and varying the electric field distribution between the electrodes to capture a variety of acoustic signals. Therefore, the electric field that is utilized in the nanoporation technique also produces a series of corresponding acoustic signals. This offers a novel imaging technique for the real-time in situ monitoring of electroporation that may directly improve treatment efficiency.

Photoacoustic tomography of unlabelled red blood cell at the nanoscale

In this letter, we present the principle behind nanoscale photoacoustic tomography (nPAT), in addition to simulation results demonstrating the thermal safety and the diagnostic potential of such a modality. Nanoscale photoacoustic tomography is a novel biomedical imaging modality that can allow for the 3D imaging of cells at nanometer resolutions. This modality also allows for the imaging of single red blood cells (RBCs) such that the hemoglobin concentration quantities can be visualized within the cell. As a result, we believe that nPAT can allow for diagnostic information at unprecedented resolutions and enable the visualization of previously unseen phenomenon in RBCs.

TH-AB-209-08: Next Generation Dedicated 3D Breast Imaging with XACT

PURPOSE Exposure to radiation increases the risk of cancer. We have designed a new imaging paradigm, X-ray induced acoustic computed tomography (XACT). Applying this innovative technology to breast imaging, an X-ray exposure can generate a 3D acoustic image, which dramatically reduces the radiation dose to patients when compared to conventional breast CT. METHODS Theoretical calculations are done to determine the appropriate X-ray energy and ultrasound frequency in breast XACT imaging. A series of breast CT image along the coronal plane from a patient with calcifications in the breast tissue are used as the source image. HU value based segmentation is done to distinguish the skin, adipose tissue, glandular tissue, breast calcification, and chest bone from each CT image. X-ray dose deposition in each pixel is calculated based on the tissue type by using GEANT4 Monte Carlo toolkits. The initial pressure rise caused by X-ray energy deposition is calculated according to tissue properties. Then, the X-ray induced acoustic wave propagation is simulated by K-WAVE toolkit. Breast XACT images are reconstructed from the recorded time-dependent ultrasound waves. RESULTS For imaging a breast with large size (16cm in diameter at chest wall), the photon energy of X-ray source and the central frequency of ultrasound detector is determined as 20keV and 5.5MHz. Approximately 10 times contrast between a calcification and the breast tissue can be acquire from XACT image. The calcification can be clearly identified from the reconstructed XACT image. CONCLUSION XACT technique takes the advantages of X-ray absorption contrast and high ultrasonic resolution. With the proposed innovative technology, one can potentially reduce radiation dose to patient in 3D breast imaging as compared with current x-ray modalities, while still maintaining high imaging contrast and spatial resolution.