MODELLING AND VERIFICATION OF THERMOACOUSTIC MEDICAL IMAGING FROM NANOSCOPIC TO MACROSCOPIC RESOLUTIONS

In this thesis, three main questions regarding the potential of thermoacoustic imaging are answered: 1) what are the conventional resolution limitations of photoacoustic imaging and how can they be extended to enable high-resolution imaging, 2) Can photoacoustic imaging resolution be brought down to nanoscopic levels, and 3) As laser based photoacoustic imaging has been deployed with great success, is it also possible for other radiation to generate useful ultrasound signals for imaging? Whereas laser-induced photoacoustic tomography has been widely explored for a diverse range of biomedical contexts, there remain some fundamental limits to the resolution levels in which it can operate. Namely, the axial resolution of photoacoustic imaging remains restricted by the fact that ultrasonic transducers are not able to detect high-frequency signals that encode nanoscale resolution information. Therefore, there is a lingering question about how photoacoustic imaging can truly enter the realm of nanoscale imaging, as has been done by other modalities such as STED microscopy, structured illumination microscopy, and STORM microscopy. It is believed that laser-based detection in lieu of a transducer may enable a super-resolution photoacoustic imaging modality. However, there remain important questions about the reach and feasibility of nanoscale photoacoustic imaging. Specifically: will highly focused lasers directed at single cells result in thermal damage of biological samples? Will the axial imaging resolution of laser based detection truly be able to overcome the conventional optical diffraction limit of ~200nm? Will optical detection be sensitive enough to detect photoacoustic signals? Consequently, models are developed for thermoacoustic imaging for nanoscale imaging at super-resolutions exceeding that of the optical diffraction limit (~200nm), that show the potential for thermoacoustic imaging to enable super-resolution imaging of single cells. The models confirm that such imaging is possible while simultaneously ensuring the thermal safety of cells as the laser-induced temperature rise of such imaging is only within mK, potentially allowing for high-resolution imaging in vivo. It is also confirmed that a laser of 7ps duration should generate frequencies high enough to enable super-resolutions. Models are also developed for the estimation of the sensitivity and resolution of these high-resolution imaging, and it is predicted that super-resolution photoacoustic imaging may be able to image at axial resolutions of 10nm at noise equivalent number of molecules of 292 in the case of imaging hemoglobin in red blood cells. A length-scale and time-scale generalizable simulation workflow is developed and deployed to generate simulated images of super-resolution photoacoustic imaging, showing the potential of 3D super-resolution achievable via thermoacoustic imaging. This numerical simulation workflow is generalizable to multiple length scales as well as to other sources of radiation. The model predictions regarding detectable high frequency photoacoustic signal generation is experimentally confirmed via the creation and testing of a pump-probe based preliminary photoacoustic imaging system. The system is shown to be capable of detecting a clear and repeatable signal. Acquired A-lines from this system confirm that GHz frequencies can be detected using pump-probe detection in photoacoustics, thereby opening the door for nanoscale photoacoustic imaging However, the experimental results also demonstrate that feasible and convenient nanoscale imaging will require a more stable laser than is available, as pulse to pulse intensity fluctuations in the laser greatly limit the imaging speed and necessary number of averages for a single A-line scan. The developed models show promise and use towards the development of novel thermoacoustic imaging modalities and can be deployed to assess feasibility of different configurations of thermoacoustic imaging prior to the expenditure of resources on experimental realization. In this way, the developed models have the potential to enable the development of various thermoacoustic imaging modalities via a single generalizable framework through which imaging characteristics can be predicted at multiple length and time scales

Nanoscale photoacoustic tomography for label-free super-resolution imaging: simulation study (Erratum).

The erratum corrects an error in the article, “Nanoscale photoacoustic tomography for label-free super-resolution imaging: simulation study,” by P. Samant et al

3-D Protoacoustic Imaging Through a Planar Ultrasound Array: A Simulation Workflow

Bragg peak range uncertainties are a persistent constraint in proton therapy. Pulsed proton beams generate protoacoustic emissions proportional to absorbed proton energy, thereby encoding dosimetry information in a detectable acoustic wave. Here, we seek to derive and model 3D protoacoustic imaging with an ultrasound array and examine the frequency characteristics of protoacoustic emissions. A formalism is presented through which protoacoustic signals can be characterized considering transducer bandwidth as well as pulse duration of the incident beam. We have also collected an experimental proton beam intensity signal from a Mevion S250 clinical machine to analyze our formalism. We also show that proton-acoustic image reconstruction is possible even when the noise amplitude is larger than the signal amplitude on individual transducers. We find that a 4μ s Gaussian proton pulse can generate a signal in the range of MHz as long as the spatial heating function has sufficiently high temperature gradients

X-Ray-Induced Acoustic Computed Tomography (XACT): Initial Experiment on Bone Sample

X-ray-induced acoustic computed tomography (XACT) is a unique hybrid imaging modality that combines high X-ray absorption contrast with high ultrasonic resolution. X-ray radiography and computerized tomography (CT) are currently the gold standards for 2-D and 3-D imaging of skeletal tissues though there are important properties of bone, such as elasticity and speed of sound (SOS), that these techniques cannot measure. Ultrasound is capable of measuring such properties though current clinical ultrasound scanners cannot be used to image the interior morphology of bones because they fail to address the complicated physics involved for exact image reconstruction; bone is heterogeneous and composed of layers of both cortical and trabecular bone, which violates assumptions in conventional ultrasound imaging of uniform SOS. XACT, in conjunction with the time-reversal algorithm, is capable of generating precise reconstructions, and by combining elements of both X-ray and ultrasound imaging, XACT is potentially capable of obtaining more information than any single of these techniques at low radiation dose. This article highlights X-ray-induced acoustic detection through linear scanning of an ultrasound transducer and the time-reversal algorithm to produce the first-ever XACT image of a bone sample. The results of this study should prove to enhance the potential of XACT imaging in the evaluation of bone diseases for future clinical use

3-D X-Ray-Induced Acoustic Computed Tomography With a Spherical Array: A Simulation Study on Bone Imaging

X-ray-induced acoustic computed tomography (XACT) is a promising imaging modality combining high X-ray absorption contrast with the 3-D propagation advantages provided by high-resolution ultrasound waves. The purpose of this study was to optimize the configuration of a 3-D XACT imaging system for bone imaging. A 280 ultrasonic sensors with peak frequency of 10 MHz was designed to distribute on a spherical surface to optimize the 3-D volumetric imaging capability. We performed both theoretical calculations and simulations of this optimized XACT imaging configuration on a mouse-sized digital phantom containing various X-ray absorption coefficients. Iteration algorithm based on total variation has been used for 3-D XACT image reconstruction. The spatial resolution of imaging was estimated to about [Formula: see text] along both axial and lateral directions. We simulate XACT imaging of bone microstructures using digital phantoms generated from micro-CT images of real biological samples, showing that XACT imaging can provide high-resolution imaging of the mouse paw. Results of this study will greatly enhance the potential of XACT imaging in the evaluation of bone diseases for future clinical use

Nanotechnology and Nanocapsule-Based Approaches for the Diagnosis and Therapeutics of Diabetes Mellitus: A Concise Survey

A serious health concern of frightening proportions is diabetes mellitus, a common metabolic illness marked by increased blood sugar levels as a result of insufficient insulin production or response. Nanosensors and nanomaterials have recently shown tremendous promise for enhancing glucose detection for the treatment of diabetes. Significant improvements in glucose sensor sensitivity, specificity, and reversibility have been achieved through the incorporation of nanoscale carbon structures, nanocomposites, and other nanomaterials. The use of these tailored nanocarriers offers a viable technique to enhance patient compliance and diabetes management by addressing the difficulties associated with oral peptide medication delivery for the treatment of diabetes caused by adverse circumstances in the gastrointestinal system. Nanocapsules are a promising approach for effective medication transportation via biological barriers by protecting drug molecules from the biological environment. A workable solution to problems with oral peptide medicine distribution for treating diabetes, particularly when it comes to unfavorable gastrointestinal conditions, is the use of customized nanocarriers. These nanocarriers have a flexible design and special in vivo characteristics that make it possible to go beyond cellular and tissue absorption barriers while improving the stability and effectiveness of therapeutic peptides. The management of diabetes mellitus has a great deal of potential for targeted lipid-based nanoparticles, which operate as an efficient drug delivery technique for oral administration of therapeutic peptides. With these developments in nanotechnology and nanocapsule-based techniques, diabetes treatment might be improved, patient compliance could be increased, and drug administration frequency could be decreased, potentially changing the field. This article presents a comprehensive review of recent advances in nanotechnology for diabetes mellitus diagnosis and the utilization of nanocapsules in diabetes treatment Keywords: Nanotechnology, Nanocapsules, Diabetes Mellitus, Nanocarriers, Nanomaterial, Nanotub

X‐ray‐induced acoustic computed tomography for guiding prone stereotactic partial breast irradiation: a simulation study

PurposeThe aim of this study is to investigate the feasibility of x-ray-induced acoustic computed tomography (XACT) as an image guidance tool for tracking x-ray beam location and monitoring radiation dose delivered to the patient during stereotactic partial breast irradiation (SPBI).MethodsAn in-house simulation workflow was developed to assess the ability of XACT to act as an in vivo dosimetry tool for SPBI. To evaluate this simulation workflow, a three-dimensional (3D) digital breast phantom was created by a series of two-dimensional (2D) breast CT slices from a patient. Three different tissue types (skin, adipose tissue, and glandular tissue) were segmented and the postlumpectomy seroma was simulated inside the digital breast phantom. A treatment plan was made with three beam angles to deliver radiation dose to the seroma in breast to simulate SPBI. The three beam angles for 2D simulations were 17°, 90° and 159° (couch angles were 0 degrees) while the angles were 90 degrees (couch angles were 0°, 27°, 90°) in 3D simulation. A multi-step simulation platform capable of modelling XACT was developed. First, the dose distribution was converted to an initial pressure distribution. The propagation of this pressure disturbance in the form of induced acoustic waves was then modeled using the k-wave MATLAB toolbox. The waves were then detected by a hemispherical-shaped ultrasound transducer array (6320 transducer locations distributed on the surface of the breast). Finally, the time-varying pressure signals detected at each transducer location were used to reconstruct an image of the initial pressure distribution using a 3D time-reversal reconstruction algorithm. Finally, the reconstructed XACT images of the radiation beams were overlaid onto the structure breast CT.ResultsIt was found that XACT was able to reconstruct the dose distribution of SPBI in 3D. In the reconstructed 3D volumetric dose distribution, the average doses in the GTV (Gross Target Volume) and PTV (Planning Target Volume) were 86.15% and 80.89%, respectively. When compared to the treatment plan, the XACT reconstructed dose distribution in the GTV and PTV had a RMSE (root mean square error) of 2.408 % and 2.299 % over all pixels. The 3D breast XACT imaging reconstruction with time-reversal reconstruction algorithm can be finished within several minutes.ConclusionsThis work explores the feasibility of using the novel imaging modality of XACT as an in vivo dosimeter for SPBI radiotherapy. It shows that XACT imaging can provide the x-ray beam location and dose information in deep tissue during the treatment in real time in 3D. This study lays the groundwork for a variety of future studies related to the use of XACT as a dosimeter at different cancer sites

Toward in vivo Dosimetry for Prostate Radiotherapy With a Transperineal Ultrasound Array: A Simulation Study

X-ray-induced acoustic computed tomography (XACT) is a promising imaging modality to monitor the position of the radiation beam and the deposited dose during external beam radiotherapy delivery. The purpose of this study was to investigate the feasibility of using a transperineal ultrasound transducer array for XACT imaging to guide the prostate radiotherapy. A customized two-dimensional (2D) matrix ultrasound transducer array with 10000 (100×100 elements) ultrasonic sensors with a central frequency of 1 MHz was designed on a 5 cm×5 cm plane to optimize three-dimensional (3D) volumetric imaging. The CT scan and dose treatment plan for a prostate patient undergoing intensity modulated radiation therapy (IMRT) were obtained. In-house simulation was developed to model the time varying X-ray induced acoustic (XA) signals detected by the transperineal ultrasound array. A 3D filtered back projection (FBP) algorithm has been used for 3D XACT image reconstruction. Results of this study will greatly enhance the potential of XACT imaging for real time in vivo dosimetry during radiotherapy