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.
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.
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.
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.
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