67 research outputs found
VISUALIZATION OF ULTRASOUND INDUCED CAVITATION BUBBLES USING SYNCHROTRON ANALYZER BASED IMAGING
Ultrasound is recognized as the fastest growing medical modality for imaging and therapy. Being noninvasive, painless, portable, X-ray radiation-free and far less expensive than magnetic resonance imaging, ultrasound is widely used in medicine today. Despite these benefits, undesirable bioeffects of high-frequency sound waves have raised concerns; particularly, because ultrasound imaging has become an integral part of prenatal care today and is increasingly used for therapeutic applications. As such, ultrasound bioeffects must be carefully considered to ensure optimal benefits-to-risk ratio. In this context, few studies have been done to explore the physics (i.e. âcavitationâ) behind the risk factors. One reason may be associated with the challenges in visualization of ultrasound-induced cavitation bubbles in situ. To address this issue, this research aims to develop a synchrotron-based assessment technique to enable visualization and characterization of ultrasound-induced microbubbles in a physiologically relevant medium under standard ultrasound operating conditions.
The first objective is to identify a suitable synchrotron X-ray imaging technique for visualization of ultrasound-induced microbubbles in water. Two synchrotron X-ray phase-sensitive imaging techniques, in-line phase contrast imaging (PCI) and analyzer-based imaging (ABI), were evaluated. Results revealed the superiority of the ABI method compared to PCI for visualization of ultrasound-induced microbubbles.
The second main objective is to employ the ABI method to assess the effects of ultrasound acoustic frequency and power on visualization and mapping of ultrasound-induced microbubble patterns in water. The time-averaged probability of ultrasound-induced microbubble occurrence along the ultrasound beam propagation in water was determined using the ABI method. Results showed the utility of synchrotron ABI for visualizing cavitation bubbles formed in water by clinical ultrasound systems working at high frequency and output powers as low as used for therapeutic systems. It was demonstrated that the X-ray ABI method has great potential for mapping ultrasound-induced microbubble patterns in a fluidic environment under different ultrasound operating conditions of clinical therapeutic devices.
Taken together, this research represents an advance in detection techniques for visualization and mapping of ultrasound-induced microbubble patterns using the synchrotron X-ray ABI method without usage of contrast agents. Findings from this research will pave the road toward the development of a synchrotron-based detection technique for characterization of ultrasound-induced cavitation microbubbles in soft tissues in the future
PHOTOREFRACTIVE CRYSTAL-BASED ACOUSTO-OPTIC IMAGING IN THE NEAR-INFRARED AND ITS APPLICATIONS
Acousto-optic (AO) sensing and imaging (AOI) is a dual-wave modality that
combines ultrasound with diffusive light to measure and/or image the optical properties of optically diffusive media, including biological tissues such as breast and brain. The light passing through a focused ultrasound beam undergoes a phase modulation at the ultrasound frequency that is detected using an adaptive interferometer scheme employing a GaAs photorefractive crystal (PRC). The PRC-based AO system operating at 1064 nm is described, along with the underlying theory, validating experiments, characterization, and optimization of this sensing and imaging apparatus. The spatial resolution of AO sensing, which is determined by spatial dimensions of the ultrasound beam or pulse, can be sub-millimeter for megahertz-frequency sound waves.A modified approach for quantifying the optical properties of diffuse media with AO sensing employs the ratio of AO signals generated at two different ultrasound focal pressures. The resulting âpressure contrast signalâ (PCS), once calibrated for a particular set of pressure pulses, yields a direct measure of the spatially averaged optical transport attenuation coefficient within the interaction volume between light and sound. This is a significant improvement over current AO sensing methods since it produces a quantitative measure of the optical properties of optically diffuse media without a priori knowledge of the background illumination. It can also be used to generate images based on spatial variations in both optical scattering and absorption.
Finally, the AO sensing system is modified to monitor the irreversible optical changes associated with the tissue heating from high intensity focused ultrasound (HIFU) therapy, providing a powerful method for noninvasively sensing the onset and growth of thermal lesions in soft tissues. A single HIFU transducer is used to simultaneously generate tissue damage and pump the AO interaction. Experimental results performed in excised chicken breast demonstrate that AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposure parameters, results in more predictable lesion formation.Bernard M. Gordon Center for Subsurface and Imaging Systems (CenSSIS) via the NSF ERC award number EEC-9986821
A modeling-based assessment of acousto-optic sensing for monitoring high-intensity focused ultrasound lesion formation
Real-time acousto-optic (AO) sensing - a dual-wave modality that combines ultrasound with diffuse light to probe the optical properties of turbid media - has been demonstrated to non-invasively detect changes in ex vivo tissue optical properties during high-intensity focused ultrasound (HIFU) exposure. The AO signal indicates the onset of lesion formation and predicts resulting lesion volumes. Although proof-of-concept experiments have been successful, many of the underlying parameters and mechanisms affecting thermally induced optical property changes and the AO detectability of HIFU lesion formation are not well understood. In thesis, a numerical simulation was developed to model the AO sensing process and capture the relevant acoustic, thermal, and optical transport processes.
The simulation required data that described how optical properties changed with heating. Experiments were carried out where excised chicken breast was exposed to thermal bath heating and changes in the optical absorption and scattering spectra (500 nm - 1100 nm) were measured using a scanning spectrophotometer and an integrating sphere assembly. Results showed that the standard thermal dose model currently used for guiding HIFU treatments needs to be adjusted to describe thermally induced optical property changes.
To model the entire AO process, coupled models were used for ultrasound propagation, tissue heating, and diffusive light transport. The angular spectrum method was used to model the acoustic field from the HIFU source. Spatial-temporal temperature elevations induced by the absorption of ultrasound were modeled using a finite-difference time-domain solution to the Pennes bioheat equation. The thermal dose model was then used to determine optical properties based on the temperature history. The diffuse optical field in the tissue was then calculated using a GPU-accelerated Monte Carlo algorithm, which accounted for light-sound interactions and AO signal detection. The simulation was used to determine the optimal design for an AO guided HIFU system by evaluating the robustness of the systems signal to changes in tissue thickness, lesion optical contrast, and lesion location. It was determined that AO sensing is a clinically viable technique for guiding the ablation of large volumes and that real-time sensing may be feasible in the breast and prostate
PHOTOREFRACTIVE CRYSTAL-BASED ACOUSTO-OPTIC IMAGING IN THE NEAR-INFRARED AND ITS APPLICATIONS
Acousto-optic (AO) sensing and imaging (AOI) is a dual-wave modality that
combines ultrasound with diffusive light to measure and/or image the optical properties of optically diffusive media, including biological tissues such as breast and brain. The light passing through a focused ultrasound beam undergoes a phase modulation at the ultrasound frequency that is detected using an adaptive interferometer scheme employing a GaAs photorefractive crystal (PRC). The PRC-based AO system operating at 1064 nm is described, along with the underlying theory, validating experiments, characterization, and optimization of this sensing and imaging apparatus. The spatial resolution of AO sensing, which is determined by spatial dimensions of the ultrasound beam or pulse, can be sub-millimeter for megahertz-frequency sound waves.A modified approach for quantifying the optical properties of diffuse media with AO sensing employs the ratio of AO signals generated at two different ultrasound focal pressures. The resulting âpressure contrast signalâ (PCS), once calibrated for a particular set of pressure pulses, yields a direct measure of the spatially averaged optical transport attenuation coefficient within the interaction volume between light and sound. This is a significant improvement over current AO sensing methods since it produces a quantitative measure of the optical properties of optically diffuse media without a priori knowledge of the background illumination. It can also be used to generate images based on spatial variations in both optical scattering and absorption.
Finally, the AO sensing system is modified to monitor the irreversible optical changes associated with the tissue heating from high intensity focused ultrasound (HIFU) therapy, providing a powerful method for noninvasively sensing the onset and growth of thermal lesions in soft tissues. A single HIFU transducer is used to simultaneously generate tissue damage and pump the AO interaction. Experimental results performed in excised chicken breast demonstrate that AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposure parameters, results in more predictable lesion formation.Bernard M. Gordon Center for Subsurface and Imaging Systems (CenSSIS) via the NSF ERC award number EEC-9986821
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Design and development of magnetic resonance imaging (MRI) compatible tissue mimicking phantoms for evaluating focused ultrasound thermal protocols
Animal models are often used to test the efficacy and safety of clinical applications employing focused ultrasound that range in various stages of research, development and commercialization. The animals are usually subjected to conditions that cause pain, distress and euthanasia. Access to cadaveric models is not easy and affordable for all research institutions, whereas conservation and changes of their physical properties over time can be a delimiting factor for translational research. The above set the motivation for this project, which its primary objective is to design and develop appropriate tissue mimicking phantoms using a simplistic and cost effective methodology. These phantoms are expected to contribute in reducing the need for animal testing and allow researchers to get hands experience with tools that will promote and accelerate testing in focused ultrasound thermal protocols. The main requirements for these phantoms are to be geometrically accurate, compatible with magnetic resonance imaging (MRI) and to be composed of materials that approximate the acoustic and thermal properties of the replicated tissues.
Throughout the duration of the project three ultrasonic composite phantoms (head, femur bone-muscle and breast-rib) were developed. The acoustic properties of candidate materials were assessed using pulse-echo immersion and through transmission techniques. The thermal properties were estimated by observing the rate of heat diffusion following a sonication in the soft tissue parts with MR thermometry. Acrylonitrile butadiene styrene (ABS) was used to replicate bone tissue, where its acoustic attenuation coefficient was found to be 16.01 ± 6.18 dB/cm at 1 MHz and the speed of sound at 2048 ± 79 m/s. Soft tissue parts consisted out of agar-based gels doped with varying concentrations of additives that controlled the relative contribution of acoustic absorption (evaporated milk) and scatter (silica dioxide) to total attenuation independently. Brain tissue phantom (2 % w/v agar - 1.2 % w/v SiO2 - 25 % v/v evaporated milk) matched an attenuation coefficient of 0.59 ± 0.05 dB/cm-MHz whereas muscle and breast mimicking phantom (2 % w/v agar - 2 % w/v SiO2 - 40 % v/v evaporated milk) were estimated of inducing an attenuation coefficient of the order of 0.99 ±0.08 dB/cm-MHz. The speed of sound for the brain and muscle/breast recipe were estimated at 1485 ± 12 m/s and 1529 ± 13 m/s respectively. The thermal conductivity of the brain phantom was estimated to be 0.52 ± 0.06 W/mÂș-C and 0.57 ± 0.10 W/mÂș-C for the muscle/breast phantom. The acoustic and thermal properties of candidate materials were within range of the replicated tissues extracted from literature, except the speed of sound in ABS compared which was lower compared to bone (~3000 m/s).
Three dimensional models of bone parts (skull, femur, rib) were reconstructed in Standard Tessellation Language (STL) format by segmenting bony tissue of interest from adult human computed tomography (CT) images. The STL bone models were 3D printed in ABS using a fused deposition modelling (FDM) machine. The final composite phantoms were fabricated by molding the agar based soft tissue phantoms inside/around the ABS bone phantoms. The functionality of all three composite phantoms was assessed with focused ultrasound sonications applied by a 1 MHz single element transducer while temperature was monitored with 1.5 Tesla MRI scanner. A spoiled gradient recalled (SPGR) pulse sequence was used to produce phase images that were analyzed using a custom coded software developed in Matlab that employed proton-resonance frequency shift (PRFS) thermometry
New Image Processing Methods for Ultrasound Musculoskeletal Applications
In the past few years, ultrasound (US) imaging modalities have received increasing interest as diagnostic tools for orthopedic applications. The goal for many of these novel ultrasonic methods is to be able to create three-dimensional (3D) bone visualization non-invasively, safely and with high accuracy and spatial resolution. Availability of accurate bone segmentation and 3D reconstruction methods would help correctly interpreting complex bone morphology as well as facilitate quantitative analysis. However, in vivo ultrasound images of bones may have poor quality due to uncontrollable motion, high ultrasonic attenuation and the presence of imaging artifacts, which can affect the quality of the bone segmentation and reconstruction results.
In this study, we investigate the use of novel ultrasonic processing methods that can significantly improve bone visualization, segmentation and 3D reconstruction in ultrasound volumetric data acquired in applications in vivo. Specifically, in this study, we investigate the use of new elastography-based, Doppler-based and statistical shape model-based methods that can be applied to ultrasound bone imaging applications with the overall major goal of obtaining fast yet accurate 3D bone reconstructions. This study is composed to three projects, which all have the potential to significantly contribute to this major goal.
The first project deals with the fast and accurate implementation of correlation-based elastography and poroelastography techniques for real-time assessment of the mechanical properties of musculoskeletal tissues. The rationale behind this project is that,
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in the future, elastography-based features can be used to reduce false positives in ultrasonic bone segmentation methods based on the differences between the mechanical properties of soft tissues and the mechanical properties of hard tissues. In this study, a hybrid computation model is designed, implemented and tested to achieve real time performance without compromise in elastographic image quality .
In the second project, a Power Doppler-based signal enhancement method is designed and tested with the intent of increasing the contrast between soft tissue and bone while suppressing the contrast between soft tissue and connective tissue, which is often a cause of false positives in ultrasonic bone segmentation problems. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method.
In the third project, a statistical shape model based bone surface segmentation method is proposed and investigated. This method uses statistical models to determine if a curve detected in a segmented ultrasound image belongs to a bone surface or not. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method.
I conclude this Dissertation with a discussion on possible future work in the field of ultrasound bone imaging and assessment
Drug Delivery Strategies for Platinum Based Chemotherapy
Few chemotherapeutics have had such an impact on cancer management as cis-diamminedichloridoplatinum(II) (CDDP), also known as cisplatin. The first member of the platinum based drug family, CDDP's potent toxicity in disrupting DNA replication has led to its widespread use in multi-drug therapies, with particular benefit in patients with testicular cancers. However, CDDP also produces significant side effects that limit the maximum systemic dose. Various strategies have been developed to address this challenge including encapsulation within micro- or nanocarriers and the use of external stimuli such as ultrasound to promote uptake and release. The aim of this article is to look at these strategies and recent scientific and clinical developments
Medical Robotics
The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently âmedical roboticistsâ or not
Spectral Ultrasound Characterization of Tissues and Tissue Engineered Constructs.
Even though ultrasound imaging is widely used in clinical diagnosis and image-guided interventions, the field is far behind other areas of clinical quantitative image analysis, such as MRI, CT and X-ray mammography. In this thesis, non-destructive and non-invasive ultrasound characterization techniques were developed to study the tissue micro-structural details using high frequency spectral ultrasound imaging (SUSI). The techniques were explored in in-vitro conditions of acellular and cellular tissue engineered constructs and then on ex-vivo tissues for their characterization. SUSI was used to assess the amount of hydroxyl-apatite (HA) mineral, differentiate HA mineral types and study their distribution in acellular tissue engineered constructs. The process of mineral deposition from surrounding mineralizing media onto simple collagen constructs was also studied and characterized with SUSI. 3D morphological changes of the constructs with MC3t3 cells was monitored and characterized for the developmental changes such as net cell proliferation/apoptosis and cell differentiation process through mineral production by the early osteoblastic MC3t3-cell constructs in-situ. A novel method was introduced using SUSI to estimate the amount of mineral secreted by the differentiated osteoblast cells in a non-destructive method. Then, SUSI was investigated in ex-vivo cardiac tissues to monitor and characterize the cellular changes during high-intensity focused ultrasound ablation with high-frame-rate and high-resolution ultrasound imaging. The mechanistic hypotheses behind the improvement in lesion detection were investigated and best identification methods to assess lesion formation and transient gas body activities were proposed to provide a method for visualizing spatiotemporal evolution of lesion and gasâbody activity and for predicting macroscopic cavity formation upon its implementation as a real-time monitoring technique with feedback control system for HIFU treatment of atrial fibrillation to improve the ablation process. Even though the results from the developed techniques show great promise in in-vitro and ex-vivo settings, additional work needs to be carried out to demonstrate the applicability of the techniques in in-vivo.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/99788/1/msreddy_1.pd
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