Doctor of Philosophy

dissertationThe spinal cord provides the major pathway for the signal transmission between the brain and peripheral nervous system. Any injury on the spinal cord may disrupt the signal transmission partially or completely, and lead to the permanent disability of the patient. Therefore, a technique which can evaluate the spinal cord disease burden and monitor the treatment progress noninvasively is very essential. Magnetic resonance imaging (MRI) has emerged as a powerful tool for imaging of the spinal cord because of its high soft-tissue contrast and specificity to the pathologic cord. However, using the conventional MRI methods such as T1-weighted and T2-weighted imaging, the disease burden and monitoring process cannot always be assessed accurately. An advanced imaging method, the diffusion MRI of spinal cord, has been proven as a more successful imaging method than the conventional MRI methods to detect the lesions in earliest stages; however, diffusion MRI of spinal cord is challenging. The major technical challenges for the high-resolution diffusion MRI of the spinal cord include the low signal-to-noise ratio (SNR) from the small cross-sectional area and deep location of the cord, large field inhomogeneity in the static magnetic field due to the magnetic susceptibility difference between tissue-bone interface, and patient’s involuntary as well as voluntary motions. In addition to the above technical challenges, the signal behavior and outcomes of the diffusion MRI cannot be easily interpreted in the spinal cord because of its complex microscopic structure. This dissertation contributes significantly in three areas to overcome the difficulties currently faced in diffusion MRI of the spinal cord. A Monte Carlo simulation (MCS) of water diffusion in white matter (WM) has been developed and performed. The simulation provides the deeper understanding of the signal measured in diffusion MRI, which facilitates easier interpretation of the outcomes of diffusion MRI. The results of the ultrahigh-b radial diffusion-weighted imaging (UHB-rDWI) of excised pig cervical spinal cord (CSC) agree fairly well with the results of the simulation. An improvement in the SNR of the spinal cord images was achieved by constructing an 8-channel CSC dedicated coil, which does not require a commonly used preamplifier decoupling technique to minimize the interaction between nonadjacent elements. The newly constructed coil provides 1.4âˆ'2 time SNR improvement compared with the manufacturer’s coil (Siemens’ head neck and spine matrix). A new sequence, 2D single-shot diffusion-weighted stimulated echo planar imaging with reduced field of view (2D ss-DWSTEPI-rFOV), has been developed for the UHB-rDWI of the spinal cord. The 2D ss-DWSTEPI-rFOV sequence acquires an image in a single excitation, and thereby reduces motion related artefacts. The reduced phase field of view imaging capability of the new sequence minimizes the off-resonance (field inhomogeneity and chemical shift) related artefacts. The time efficient sequence acquires stimulated echoes (STE) for the high-resolution UHB-rDWI of the spinal cord

Doctor of Philosophy

dissertationThis dissertation comprises two separate studies: 1) efficacy of an anabolic steroid, oxandrolone, on the energy utilization of the heart of a lamb born with single ventricle (SV) physiology using 31P MR spectroscopy (MRS) and 2) signal behavior of ultra-high-b radial diffusion weighted imaging (UHb-rDWI) in healthy and multiple sclerosis (MS) subjects. SV infants have the highest mortality of all infants that have congenital heart defects. Their inability to gain weight appropriately may be due to high cardiac energy requirements from their shunt dependent physiology. We hypothesize that oxandrolone, which is already known to markedly improve the nutritional state of burn patients, will improve the energy utilization in the heart. We tested our hypothesis on SV modelled lambs using 31P MRS, home built 1H/31P double tuned radio frequency (RF) coil, and 1H and 31P T/R switches. We monitored cardiac energy in the lamb by quantitatively evaluating the first-order forward reaction rate (kf) of the creatine-kinase (CK) reaction in the heart. Spinal cord injury due to pathologies, such as MS, may include demyelination and/or axonal damage and lead to varying degrees of neurologic deficit. Noninvasive imaging biomarkers for earlier disease detection and monitoring in the follow-up and treatment stages would be a significant advancement in patient care. Moreover, imaging of the cervical spinal cord (CSC) is technically challenging because of the low signal to noise ratio from the small cross section of the cord, susceptibility artifact due to tissue-bone interface, and motion induced artifact from breathing and swallowing. To resolve these challenges, we used the UHb-rDWI technique and a CSC dedicated phased array RF coil. We studied the behavior of UHb-rDWI signal over the range of b-values from 0 sec/mm2 to 7348 sec/mm2 in the CSC of healthy and MS subjects over multiple time points. In the normal CSC, the signal decays fast at low b and slowly at UHb (b>4000 sec/mm2). In MS patients, the region affected by active lesions revealed a marked decrease in signal intensities in UHb region. UHb-rDWI could, therefore, be used for establishing an imaging biomarker to distinguish inflammation, demyelination, and axonal loss in the CSC

Antenna Design, Radiobiological Modelling, and Non-invasive Monitoring for Microwave Hyperthermia

The death toll of cancers is on the rise worldwide and surviving patients suffer significant side effects from conventional therapies. To reduce the level of toxicity in patients treated with the conventional treatment modalities, hyperthermia (HT) has been investigated as an adjuvant modality and shown to be a potent tumor cell sensitizer for radio- and chemotherapy. During the past couple of decades, several clinical radiofrequency HT systems, aka applicators, have been developed to heat tumors. Systems based on radiative applicators are the most widely used within the hyperthermic community. They consist of a conformal antenna array and need a beamforming method in order to focus EM energy on the tumor through constructive interference while sparing the healthy tissue from excessive heating. Therefore, a hyperthermia treatment planning (HTP) stage is required before each patient\u27s first treatment session to optimize and control the EM power deposition as well as the resultant temperature distribution. Despite the vast amount of effort invested in HTP and the progress made in this regard during recent years, the clinical exploitation of HT is still hampered by technical limitations and patients can still experience discomfort during clinical trials. This, therefore, calls for a more efficient hardware design, better control of EM power deposition to minimize unwanted hotspots, and more accurate quantification and monitoring of the treatment outcome. Given these demands, the present report tries to address some of the above-mentioned challenges by proposing - A new antenna model customized for HT applications that surpasses previously proposed models from several points of view.- A hybrid beamforming method for faster convergence and a versatile, robust thermal solver for handling sophisticated scenarios.- A radiobiological model to quantify the outcome of a combined treatment modality of the Gamma Knife radiosurgery and HT.- A differential image reconstruction method to assess the feasibility of using the same system for both heating and microwave thermometry

Intensity modulated radiation therapy and arc therapy: validation and evolution as applied to tumours of the head and neck, abdominal and pelvic regions

Intensiteitsgemoduleerde radiotherapie (IMRT) laat een betere controle over de dosisdistributie (DD) toe dan meer conventionele bestralingstechnieken. Zo is het met IMRT mogelijk om concave DDs te bereiken en om de risico-organen conformeel uit te sparen. IMRT werd in het UZG klinisch toegepast voor een hele waaier van tumorlocalisaties. De toepassing van IMRT voor de bestraling van hoofd- en halstumoren (HHT) vormt het onderwerp van het eerste deel van deze thesis. De planningsstrategie voor herbestralingen en bestraling van HHT, uitgaande van de keel en de mondholte wordt beschreven, evenals de eerste klinische resultaten hiervan. IMRT voor tumoren van de neus(bij)holten leidt tot minstens even goede lokale controle (LC) en overleving als conventionele bestralingstechnieken, en dit zonder stralingsgeïnduceerde blindheid. IMRT leidt dus tot een gunstiger toxiciteitprofiel maar heeft nog geen bewijs kunnen leveren van een gunstig effect op LC of overleving. De meeste hervallen van HHT worden gezien in het gebied dat tot een hoge dosis bestraald werd, wat erop wijst dat deze “hoge dosis” niet volstaat om alle clonogene tumorcellen uit te schakelen. We startten een studie op, om de mogelijkheid van dosisescalatie op geleide van biologische beeldvorming uit te testen. Naast de toepassing en klinische validatie van IMRT bestond het werk in het kader van deze thesis ook uit de ontwikkeling en het klinisch opstarten van intensiteitgemoduleerde arc therapie (IMAT). IMAT is een rotationele vorm van IMRT (d.w.z. de gantry draait rond tijdens de bestraling), waarbij de modulatie van de intensiteit bereikt wordt door overlappende arcs. IMAT heeft enkele duidelijke voordelen ten opzichte van IMRT in bepaalde situaties. Als het doelvolume concaaf rond een risico-orgaan ligt met een grote diameter, biedt IMAT eigenlijk een oneindig aantal bundelrichtingen aan. Een planningsstrategie voor IMAT werd ontwikkeld, en type-oplossingen voor totaal abdominale bestraling en rectumbestraling werden onderzocht en klinisch toegepast

Advances in Bioengineering

The technological approach and the high level of innovation make bioengineering extremely dynamic and this forces researchers to continuous updating. It involves the publication of the results of the latest scientific research. This book covers a wide range of aspects and issues related to advances in bioengineering research with a particular focus on innovative technologies and applications. The book consists of 13 scientific contributions divided in four sections: Materials Science; Biosensors. Electronics and Telemetry; Light Therapy; Computing and Analysis Techniques

Proceedings, MSVSCC 2015

The Virginia Modeling, Analysis and Simulation Center (VMASC) of Old Dominion University hosted the 2015 Modeling, Simulation, & Visualization Student capstone Conference on April 16th. The Capstone Conference features students in Modeling and Simulation, undergraduates and graduate degree programs, and fields from many colleges and/or universities. Students present their research to an audience of fellow students, faculty, judges, and other distinguished guests. For the students, these presentations afford them the opportunity to impart their innovative research to members of the M&S community from academic, industry, and government backgrounds. Also participating in the conference are faculty and judges who have volunteered their time to impart direct support to their students’ research, facilitate the various conference tracks, serve as judges for each of the tracks, and provide overall assistance to this conference. 2015 marks the ninth year of the VMASC Capstone Conference for Modeling, Simulation and Visualization. This year our conference attracted a number of fine student written papers and presentations, resulting in a total of 51 research works that were presented. This year’s conference had record attendance thanks to the support from the various different departments at Old Dominion University, other local Universities, and the United States Military Academy, at West Point. We greatly appreciated all of the work and energy that has gone into this year’s conference, it truly was a highly collaborative effort that has resulted in a very successful symposium for the M&S community and all of those involved. Below you will find a brief summary of the best papers and best presentations with some simple statistics of the overall conference contribution. Followed by that is a table of contents that breaks down by conference track category with a copy of each included body of work. Thank you again for your time and your contribution as this conference is designed to continuously evolve and adapt to better suit the authors and M&S supporters. Dr.Yuzhong Shen Graduate Program Director, MSVE Capstone Conference Chair John ShullGraduate Student, MSVE Capstone Conference Student Chai

Robotics-Assisted Needle Steering for Percutaneous Interventions: Modeling and Experiments

Needle insertion and guidance plays an important role in medical procedures such as brachytherapy and biopsy. Flexible needles have the potential to facilitate precise targeting and avoid collisions during medical interventions while reducing trauma to the patient and post-puncture issues. Nevertheless, error introduced during guidance degrades the effectiveness of the planned therapy or diagnosis. Although steering using flexible bevel-tip needles provides great mobility and dexterity, a major barrier is the complexity of needle-tissue interaction that does not lend itself to intuitive control. To overcome this problem, a robotic system can be employed to perform trajectory planning and tracking by manipulation of the needle base. This research project focuses on a control-theoretic approach and draws on the rich literature from control and systems theory to model needle-tissue interaction and needle flexion and then design a robotics-based strategy for needle insertion/steering. The resulting solutions will directly benefit a wide range of needle-based interventions. The outcome of this computer-assisted approach will not only enable us to perform efficient preoperative trajectory planning, but will also provide more insight into needle-tissue interaction that will be helpful in developing advanced intraoperative algorithms for needle steering. Experimental validation of the proposed methodologies was carried out on a state of-the-art 5-DOF robotic system designed and constructed in-house primarily for prostate brachytherapy. The system is equipped with a Nano43 6-DOF force/torque sensor (ATI Industrial Automation) to measure forces and torques acting on the needle shaft. In our setup, an Aurora electromagnetic tracker (Northern Digital Inc.) is the sensing device used for measuring needle deflection. A multi-threaded application for control, sensor readings, data logging and communication over the ethernet was developed using Microsoft Visual C 2005, MATLAB 2007 and the QuaRC Toolbox (Quanser Inc.). Various artificial phantoms were developed so as to create a realistic medium in terms of elasticity and insertion force ranges; however, they simulated a uniform environment without exhibiting complexities of organic tissues. Experiments were also conducted on beef liver and fresh chicken breast, beef, and ham, to investigate the behavior of a variety biological tissues

Investigation of magnetic resonance imaging biomarkers of radiation effects on healthy mice brain tissue and Glioblastoma treatment

In the field of clinical oncology, radiotherapy is one of the most extensively applied anticancer treatments. However, the ionizing radiation (IR) is absorbed not only by the targeted cells, but also by the surrounding normal cells as well. Consequently, patients may experience symptoms associated with a damage to normal tissues a few weeks, months or years after a course of radiotherapy. We applied a right brain hemisphere radiation technique for mice that mimics radiation exposure during radiotherapy. We investigated several possible brain imaging biomarkers for radiation-induced damage, such as demyelination, axonal injury and inflammation, at different time points post-irradiation (IR). Because Glioblastoma Multiform (GBM) can provoke a more infiltrative phenotype in GBM cells which survive treatment, scans of the brain were obtained using different Magnetic Resonance Imaging (MRI) modalities, including Diffusion Tensor Imaging (DTI), T2 weighted high resolution and T2 mapping) at several time points (pre-IR and 15, 50, 90 and 180 days post-IR). We also investigated the ability of MRI to assess the early stage effect of ionising radiation treatment on the invasiveness of an infiltrative rodent GBM model by using T2 weighted imaging