Doctor of Philosophy, Case Western Reserve University, 2007, Biomedical Engineering

This research is motivated by the need for more effective and efficient clinical application of minimally invasive thermal ablation of solid tumors. During the ablation procedure, it is important to determine the region of tissue in which the cells have been killed and to predict input changes needed to kill tumor cells with minimal damage to normal tissue. To achieve this goal, we proposed an approach that combines fast magnetic resonance image (MRI) with mathematical modeling and simulation to monitor and predict the dynamics of temperature distribution and lesion boundary. The interactive use of MRI monitoring and model prediction provides a foundation for a real-time, clinical technique. The development of this approach has been described in the following chapters. Chapter 1: Background is presented about solid cancerous tumors and methods of thermal therapy and image techniques for monitoring. Chapter 2: The combination of MRI and model simulation to monitor and predict thermal ablation dynamics is developed and validated by in vivo experiments using radio-frequency (RF) ablation in normal paraspinal muscle of rabbits. Simulations of tissue temperature distribution and cell damage dynamics are compared with data obtained from MR phase and magnitude images. Chapter 3: The validity of this approach is tested by its application to RF ablation in VX2 tumors implanted in paraspinal muscle of rabbits. Chapter 4: A model of thermal ablation with laser light as a heat source is developed. Model simulation of tissue temperature distribution dynamics is compared with MR images from in vivo experiments with laser ablation of brain tissue of rabbits. Chapter 5: The thermal model is extended to describe the effects of an internal cooled RF probe that may also allow saline leakage into tissue. Model simulations quantify the lesion-enlarging effect of this type of RF probe. Chapter 6: Cooling by a large blood vessel in tissue near the heat source is simulated to determine how (open full item for complete abstract)

Committee: Gerald Saidel (Advisor) Subjects:

PhD, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

Thermal ablation, including radiofrequency (RFA) and microwave ablation (MWA), is a potential first-line treatment for many patients with small liver tumors. Real-time monitoring and control methods can potentially reduce under- or over-treatment rates. Here, echo decorrelation imaging was expanded from two- to three-dimensional (3D) imaging, and its performance was assessed in ex vivo and in vivo. First, 3D echo decorrelation with three normalization approaches and 3D integrated backscatter (IBS) were used to monitor ex vivo bovine liver RFA. Receiver-operating characteristic (ROC) curves, comparing these imaging parameters to ablation zones, indicated that all four were potentially good predictors of local RFA. Tissue temperatures, recorded at four thermocouples locations, weakly correlated with co-located measured decorrelation. In tests predicting ablation zones using a weighted K-means clustering approach, echo decorrelation performed better than IBS, with smaller root mean square (RMS) volume errors and higher Dice coefficients between predicted and measured ablation zones. Further, RFA in samples from normal, steatotic, and cirrhotic human liver parenchyma was monitored and controlled using 3D echo decorrelation imaging feedback. For each liver type, N=14 samples underwent ablation per RFA generator's settings, monitored by echo decorrelation imaging (uncontrolled). In N>14 trials, RFA was controlled, automatically ceasing if the average cumulative decorrelation within the target region of interest surpassed the control threshold (successfully controlled), otherwise, ablation continued like the uncontrolled trials (unsuccessfully controlled). ROC curves showed good prediction performance for all liver and control conditions. Significantly higher control success rate and generally higher measured ablation volume were observed in controlling normal vs. diseased liver. The same monitoring and control algorithms were used in in vivo swine liver RFA, (open full item for complete abstract)

Committee: T. Douglas Mast Ph.D. (Committee Chair); Ali Kord M.D. M. (Committee Member); Stacey Schutte Ph.D. (Committee Member); Kevin Haworth Ph.D. (Committee Member) Subjects: Biomedical Engineering

Master of Sciences (Engineering), Case Western Reserve University, 2024, EECS - Electrical Engineering

Atrial fibrillation, a prevalent heart condition, poses significant health risks. Traditional treatment involves cardiac ablation catheters guided by x-ray fluoroscopy, which provides limited two-dimensional heart images and subjects patients to substantial radiation. Utilizing magnetic resonance imaging (MRI) in these procedures offers three-dimensional catheter visualization and eliminates radiation exposure. The MRI's magnetic field can be leveraged in order to control a robotic ablation catheter with small electromagnetic coils in the catheter tip. However, these coils may interact negatively with the MRI's radio-frequency transmitter, causing potential overheating. Prior research led to the development of a compact catheter prototype, primarily to demonstrate its fundamental operational principles. Nevertheless, this prototype's limited size renders it unsuitable for practical application within the human body. The aim of this thesis is to engineer a full-scale catheter, a task that presents considerable challenges due to the demanding conditions of the MRI environment and the occurrence of standing waves on uncoupled elongated wires. This prototype is designed to meet the kinematic workspace specifications identified in earlier studies, while also ensuring full compatibility with a human subject. The prototype maintains a low heat output and does not interfere with the MRI's functionality.

Committee: M. Cenk Cavusoglu (Committee Chair); David Kazdan (Committee Member); Mark Griswold (Committee Member) Subjects: Biomedical Engineering; Electrical Engineering; Engineering; Medical Imaging; Medicine; Robotics

MS, University of Cincinnati, 2022, Engineering and Applied Science: Electrical Engineering

Liver cancer is a significant public health burden; as of 2020, it is the second leading cause of cancer-related mortality worldwide. Hepatic resection is considered the gold standard for the treatment of liver malignancies. However, this procedure is only possible in a minority of patients, necessitating treatment modalities with comparatively worse performance, such as thermal ablation. Thermal ablation generally results in poorer clinical outcomes relative to resection, with a higher rate of recurrence and the potential for complications related to damage to healthy tissue near the ablation zone. Medical imaging techniques can improve thermal ablation procedures via assistance in preoperative planning, probe placement and postoperative evaluation, but clinicians lack a method to monitor and control thermal ablation while the procedure is ongoing. Echo decorrelation imaging is a pulse-echo ultrasound imaging technique that measures stochastic variations in echo signals arising from thermal treatment. The method has been shown to accurately predict thermal lesioning in in vivo and ex vivo studies of thermal ablation using conventional 2D ultrasound imaging. This thesis aims to apply the echo decorrelation methodology to volumetric ultrasound data to control RFA procedures in real-time. Feedback control is implemented as a bang-bang type controller that automatically stops thermal treatment if the spatial mean of the cumulative decorrelation map exceeds a set threshold. 3D echo decorrelation-based control was evaluated through a series of feedback- controlled and uncontrolled ablation trials on ex vivo bovine liver tissue using a clinical RFA system. The RFA system was set to target a 15 mm radius spherical region of tissue while decorrelation maps were computed from captured volumetric ultrasound data; if the control criterion was met, the procedure was automatically stopped using a custom- designed microcontroller circuit. Trials were divided into two groups (open full item for complete abstract)

Committee: T. Douglas Mast Ph.D. (Committee Member); Xuefu Zhou Ph.D. (Committee Member); Mehdi Norouzi Ph.D. (Committee Member) Subjects: Radiology

PhD, University of Cincinnati, 2018, Engineering and Applied Science: Biomedical Engineering

Liver cancer, including hepatocellular carcinoma and colorectal metastases, is the second greatest cause of cancer-related death worldwide. Liver transplantation is considered the gold standard for hepatic cancer treatment. However, it is limited by the availability of liver donors and by cost. Hepatic resection is another treatment option that offers a high long-term survival rate. However, the overall resectability rate is low due to chronic liver disease and tumor location. Thermal ablation, including radiofrequency ablation as well as microwave and ultrasound ablation, has become an important alternative to liver resection and transplantation. To avoid incomplete treatments and cancer recurrence while reducing morbidity, a real-time monitoring and control approach, capable of providing consistent thermal ablation in minimal time, is needed. Echo decorrelation imaging has been successfully employed to monitor ultrasound ablation and radiofrequency ablation both ex vivo and in vivo. In this dissertation, its utility for real-time control of ultrasound ablation was assessed in ex vivo bovine liver and in vivo rabbit liver with VX2 tumor. Ultrasound exposures and echo decorrelation imaging were performed using 5 MHz linear image-ablate array. Sonications were automatically ceased when the minimum or average cumulative echo decorrelation within a control region of interest (ROI) exceeded a predetermined threshold, corresponding to high specificity for prediction of local tissue ablation or complete ROI ablation. Ablation outcomes, treatment time and prediction performance were statistically compared between controlled and uncontrolled groups. For controlling ex vivo focused ultrasound treatments, a small control ROI was placed at the focal zone and the selected control threshold corresponded to 90% specificity of local ablation prediction for preliminary ex vivo experiments. Controlled trials were compared to uncontrolled trials employing 2, 5 or 9 therapy cyc (open full item for complete abstract)

Committee: T. Douglas Mast Ph.D. (Committee Chair); Syed Ahmad (Committee Member); Jing-Huei Lee Ph.D. (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Biomedical Research

Doctor of Philosophy, University of Akron, 2017, Biomedical Engineering

Real-time assessment of thermal tissue damage during ablation is necessary to achieve optimal tumor ablation. Histological assessment of thermal damage remains to be the gold standard. However, histological assessment is not real-time and requires experienced pathologists to grade thermal damage. Therefore, real-time monitoring of tissue status during thermal ablation of tumors would significantly advance the state of the art by ensuring complete destruction of tumor mass while avoiding tissue charring and excessive damage to normal tissues. Currently, Arrhenius damage model is the widely used method for real-time assessment of thermal tissue damage. This model uses a priori tissue information, such as tissue composition, empirically determined activation energy and pre-exponential factor along with the local tissue temperature, to calculate a damage index. Magnetic resonance thermometry (MRT) along with magnetic resonance imaging (MRI) is the most commonly used method for temperature mapping and assessing thermal ablation of soft tissues. However, MRT/MRI is bulky, very expensive and often subjected to motion artifacts. Light propagation within tissues is sensitive to changes in the tissue microstructure and physiology that is used to directly quantify the extent of tissue damage. In the past decade, several groups have reported differences in the absorption coefficient (µa(λ)) and reduced scattering coefficient (µs'(λ)) of native and coagulated tissues. However, a robust and low-cost system for determining µa(λ) and µs'(λ) during a thermal ablation process is yet to be realized in a clinical setting. More importantly, the relationship between microscopic changes in tissue and the resultant change in optical properties needs to be studied so that tissue damage can be predicted using changes in optical properties. The main objective of this dissertation research is to establish a correlation between changes in tissue optical properties (µa(λ) and µs'(λ)) and the s (open full item for complete abstract)

Committee: Bing Yu (Advisor); Rebecca Willits (Committee Chair); Francis Loth (Committee Member); Yang Liu (Committee Member); Qin Liu (Committee Member); Ajay Mahajan (Committee Member) Subjects: Biomedical Engineering; Biophysics; Medical Imaging; Optics

Master of Science (MS), Ohio University, 2016, Mechanical Engineering (Engineering and Technology)

This thesis evaluates the correlation between tissue injury (the ablation site depth) and its predictor (voltage change Va-b), and introduces a newly-developed feedback control system that may help to reduce the incidence of tissue thermal injury. Tissue thermal injury can have some severe consequences, however, there is currently no effective way to prevent its occurrence. Ablation tests were performed by using an impedance bridge circuit and an ablation test model, which had been introduced by Robert and Liang in their studies, respectively. The ablation site depth was measured using a laser displacement measurement device. The feedback control system was developed based on LabVIEW and Arduino programs. When the voltage change exceeds the predefined value, the feedback control system can stop further ablation operation. Both the voltage change and the ablation site depth were found to increase as the delivered heat energy increased. The correlation between the ablation site depth and voltage change was moderate when ablation tests with middle or long duration were performed (R2 = 0.49 and R2 = 0.55, respectively). It was found that the depth moderately correlated to the voltage change when ablation was performed with a proper duration (2 to 3.5 seconds), and that the newly-developed system reduced, to some extent, the incidence of tissue thermal injury.

Committee: JungHun Choi (Advisor) Subjects: Mechanical Engineering

MS, University of Cincinnati, 2015, Engineering and Applied Science: Biomedical Engineering

Echo decorrelation imaging, a pulse–echo method that maps heat-induced changes in ultrasound echoes, was investigated for in vivo monitoring of thermal ablation in a liver cancer model. In open surgical procedures, rabbit liver with implanted VX2 tumor were imaged by image-ablate arrays and treated with bulk ultrasound (unfocused) ablation (N=10) or high-intensity focused ultrasound (HIFU) (N=13). Echo decorrelation and integrated backscatter (IBS) images were formed from pulse-echo images recorded during rest periods following each sonication pulse. Echo decorrelation images were corrected for motion- and noise-induced artifacts using measured echo decorrelation from corresponding sham trials. Sectioned ablated tissue was vitally stained with triphenyl tetrazolium chloride (TTC) and binary images were constructed based on local TTC staining. Analysis was performed for the focused exposures, unfocused exposures and for all exposures combined. Motion correction significantly reduced echo decorrelation in non-ablated liver regions. The reduction was significant in non-ablated VX2 tumor regions for focused exposures and all exposures combined. The reduction was not significant in ablated VX2 tumor regions for unfocused exposures. Echo decorrelation reduction was marginally significant in ablated regions for focused and unfocused exposures and was significant for all exposures combined. Prediction of ablation by echo decorrelation and IBS imaging was assessed using receiver operating characteristic (ROC) curves. Areas under the ROC curve (AUC) were significantly greater than chance for ablated liver prediction by corrected echo decorrelation and IBS. Echo decorrelation did not predict ablated VX2 tumor significantly better than chance for focused exposures. IBS did not predict ablated VX2 tumor better than chance for focused exposures and unfocused exposures. Corrected echo decorrelation predicted ablated liver significantly better than IBS for the focused exposu (open full item for complete abstract)

Committee: T. Douglas Mast Ph.D. (Committee Chair); Syed Arif Ahmad M.D. (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Biomedical Research

PhD, University of Cincinnati, 2015, Engineering and Applied Science: Biomedical Engineering

Hepatocellular carcinoma (HCC) and colorectal metastases (CRC) are common tumors worldwide with an increasing incidence in the United States. Thermal ablation techniques such as radiofrequency ablation (RFA), high intensity focused ultrasound (HIFU), microwave and laser ablation techniques have shown potential to treat unresectable tumors. Still lacking is a treatment monitoring technique that can accurately predict ablation. Echo decorrelation imaging is a novel pulse-echo ultrasound imaging method that quantifies and maps changes in echo signals occurring over millisecond time scales during thermal ablation. In this dissertation, the utility of echo decorrelation imaging as a treatment monitoring tool was assessed during in vivo and in vitro thermal ablation. To test the utility of echo decorrelation imaging for the prediction of ablation, RFA was performed on ex vivo bovine liver (N = 9). Echo decorrelation was computed from the Hilbert transformed pulse-echo data acquired during RFA treatments. For comparison, integrated backscatter was also computed from the same data. Pixel-by-pixel comparison between the echo decorrelation and integrated backscatter maps and the ablated region from gross tissue histology was performed using receiver operating characteristic (ROC) curves. Echo decorrelation and integrated backscatter were then quantitatively evaluated as predictors of ablation. The area under the ROC curves (AUROC) was determined for both echo decorrelation and integrated backscatter imaging methods. Ablation was predicted more accurately with echo decorrelation (AUROC = 0.820) than with integrated backscatter (AUROC = 0.668). To test the utility of echo decorrelation imaging for the prediction of ablation during in vivo thermal ablation, RFA was performed on normal swine liver (N = 5) and ultrasound ablation using image-ablate arrays was performed on rabbit liver implanted with VX2 tumors (N = 2). Consistent with the in vitro studies, ab (open full item for complete abstract)

Committee: T. Douglas Mast Ph.D. (Committee Chair); Balakrishna Haridas PH.D. (Committee Member); Christy Holland Ph.D. (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Radiology

MS, University of Cincinnati, 2008, Engineering : Mechanical Engineering

A frame work has been setup for the simulation of hypersonic reentry vehicles using commercial codes FLUENT and LS-DYNA. The main goal of this work was to set up a simple approach for the heat flux prediction and evaluation of the material thermal response during the reentry of the vehicle. Fluid thermal coupling for predicting the thermal response of a reusable non-ablating thermal protection system was set up. The computational fluid dynamics code (FLUENT) and the material thermal response codes (LS-DYNA) are loosely coupled to achieve the solution. The vehicle considered in the calculation is an axisymmetric vehicle flying at zero degree angle of attack. The frame work set up was validated with the results available in the literature. Good correlation was observed between the results from the commercial codes and the results from the literature. The mesh movement capability in LS-DYNA was implemented enabling future modeling of ablating thermal protection system.

Committee: Ala Tabiei PhD (Committee Chair); David Thompson PhD (Committee Member); Prem Khosla PhD (Committee Member); Kumar Vemaganti PhD (Committee Member) Subjects: Mechanical Engineering

Doctor of Philosophy, Case Western Reserve University, 2009, Biomedical Engineering

MRI provides different types of exquisite soft tissue and functional contrast. However, depending on the desired contrast and spatial resolution properties, the acquisition time can be quite long. The long-term objective of this work is to improve methods to quickly and accurately diagnose human disease using MRI and provide resources that can be used for image-guided therapy and real-time imaging.Balanced steady state free precession (bSSFP) or True-FISP provides the highest signal-to-noise ratio efficiency of any pulse sequence. However, in bSSFP, contrast is a mixture of T1 and T2 weightings, which is often not desired clinically, and the signal from flowing blood is hyperintense, which can obscure the vessel wall and create artifacts. Also, there are obstructive saturation band artifacts at intersections of rapidly-acquired multiplanar images. The objective of this work was to modify the magnetization preparation and readout properties of the bSSFP sequence to: 1) improve methods that eliminate T1 and isolate T2 contrast, 2) suppress the signal from flowing blood, and 3) characterize and reduce the saturation banding artifacts. A new T-One insensitive Steady State Imaging (TOSSI)-bSSFP combined acquisition technique, Resolution Enhanced TOSSI (RE-TOSSI), has been developed by using a partial Fourier acquisition and eliminating the inversion pulses from TOSSI after the data around the center of k-space is acquired. Results show that TOSSI contrast is maintained, while spatial resolution degradation is reduced. Additional benefits include reduced RF power deposition and faster imaging time. Application to high-resolution, non-subtraction thermal ablation monitoring is demonstrated. An improved dark blood bSSFP pulse sequence (HEFEWEIZEN) has been developed by introducing spatial saturation in True-FISP. This method does not increase the repetition time (TR) or substantially alter stationary tissue contrast and allows for directional suppression of blood flow (e.g. (open full item for complete abstract)

Committee: Jeffrey Duerk PhD (Advisor); Mark Griswold PhD (Committee Member); Roger Marchant PhD (Committee Member); Jeffrey Sunshine MD/PhD (Committee Member) Subjects: Biomedical Research; Engineering; Health Care; Physics; Radiology; Scientific Imaging; Surgery

Doctor of Philosophy, Case Western Reserve University, 2004, Biomedical Engineering

This research project is part of a larger, long-term effort to develop a minimally invasive and cost effective method to ablate solid tumors using interventional MRI (iMRI) to guide and monitor therapy. A low-field, open magnet system is used to guide an ablation probe into the tumor and to monitor tissue destruction during the ablation procedure. Ablation may be produced by heating tissue from a radio frequency (RF) or laser energy source at the probe tip. Not only does MR provide tumor visualization, it can reveal the thermal lesion in various acquisition sequences (T2-weighted and T1-weighted with gadolinium contrast agent) and measure temperature changes. Potentially, these measurements can be used during clinical ablation procedures to determine tumor cell death and to minimize damage to normal surrounding tissue of critical importance. This research addresses how well these MR measurements predict the actual tissue response. In this work, we addressed this issue using animal models. We developed experimental and computer techniques to accurately register and correlate MR images with macroscopic tissue and histology images showing tissue response. To ascertain cell death or injury, we used various histological techniques. Ultimately, our goal was to quantitatively predict cell damage and death using MR image acquisition and analysis methods, and a cell death model that accounts for the tissue response from the temperature history. With this research, we established an analysis paradigm suitable for many future studies of ablation techniques, localized drug release, and other iMRI-guided therapies.

Committee: David Wilson (Advisor) Subjects: Engineering, Biomedical