Medical robots for MRI guided diagnosis and therapy

Magnetic Resonance Imaging (MRI) provides the capability of imaging tissue with fine resolution and superior soft tissue contrast, when compared with conventional ultrasound and CT imaging, which makes it an important tool for clinicians to perform more accurate diagnosis and image guided therapy. Medical robotic devices combining the high resolution anatomical images with real-time navigation, are ideal for precise and repeatable interventions. Despite these advantages, the MR environment imposes constraints on mechatronic devices operating within it. This thesis presents a study on the design and development of robotic systems for particular MR interventions, in which the issue of testing the MR compatibility of mechatronic components, actuation control, kinematics and workspace analysis, and mechanical and electrical design of the robot have been investigated. Two types of robotic systems have therefore been developed and evaluated along the above aspects. (i) A device for MR guided transrectal prostate biopsy: The system was designed from components which are proven to be MR compatible, actuated by pneumatic motors and ultrasonic motors, and tracked by optical position sensors and ducial markers. Clinical trials have been performed with the device on three patients, and the results reported have demonstrated its capability to perform needle positioning under MR guidance, with a procedure time of around 40mins and with no compromised image quality, which achieved our system speci cations. (ii) Limb positioning devices to facilitate the magic angle effect for diagnosis of tendinous injuries: Two systems were designed particularly for lower and upper limb positioning, which are actuated and tracked by the similar methods as the first device. A group of volunteers were recruited to conduct tests to verify the functionality of the systems. The results demonstrate the clear enhancement of the image quality with an increase in signal intensity up to 24 times in the tendon tissue caused by the magic angle effect, showing the feasibility of the proposed devices to be applied in clinical diagnosis

DYNAMIC MEASUREMENT OF THREE-DIMENSIONAL MOTION FROM SINGLE-PERSPECTIVE TWO-DIMENSIONAL RADIOGRAPHIC PROJECTIONS

The digital evolution of the x-ray imaging modality has spurred the development of numerous clinical and research tools. This work focuses on the design, development, and validation of dynamic radiographic imaging and registration techniques to address two distinct medical applications: tracking during image-guided interventions, and the measurement of musculoskeletal joint kinematics. Fluoroscopy is widely employed to provide intra-procedural image-guidance. However, its planar images provide limited information about the location of surgical tools and targets in three-dimensional space. To address this limitation, registration techniques, which extract three-dimensional tracking and image-guidance information from planar images, were developed and validated in vitro. The ability to accurately measure joint kinematics in vivo is an important tool in studying both normal joint function and pathologies associated with injury and disease, however it still remains a clinical challenge. A technique to measure joint kinematics from single-perspective x-ray projections was developed and validated in vitro, using clinically available radiography equipmen

Teleoperation of MRI-Compatible Robots with Hybrid Actuation and Haptic Feedback

Image guided surgery (IGS), which has been developing fast recently, benefits significantly from the superior accuracy of robots and magnetic resonance imaging (MRI) which is a great soft tissue imaging modality. Teleoperation is especially desired in the MRI because of the highly constrained space inside the closed-bore MRI and the lack of haptic feedback with the fully autonomous robotic systems. It also very well maintains the human in the loop that significantly enhances safety. This dissertation describes the development of teleoperation approaches and implementation on an example system for MRI with details of different key components. The dissertation firstly describes the general teleoperation architecture with modular software and hardware components. The MRI-compatible robot controller, driving technology as well as the robot navigation and control software are introduced. As a crucial step to determine the robot location inside the MRI, two methods of registration and tracking are discussed. The first method utilizes the existing Z shaped fiducial frame design but with a newly developed multi-image registration method which has higher accuracy with a smaller fiducial frame. The second method is a new fiducial design with a cylindrical shaped frame which is especially suitable for registration and tracking for needles. Alongside, a single-image based algorithm is developed to not only reach higher accuracy but also run faster. In addition, performance enhanced fiducial frame is also studied by integrating self-resonant coils. A surgical master-slave teleoperation system for the application of percutaneous interventional procedures under continuous MRI guidance is presented. The slave robot is a piezoelectric-actuated needle insertion robot with fiber optic force sensor integrated. The master robot is a pneumatic-driven haptic device which not only controls the position of the slave robot, but also renders the force associated with needle placement interventions to the surgeon. Both of master and slave robots mechanical design, kinematics, force sensing and feedback technologies are discussed. Force and position tracking results of the master-slave robot are demonstrated to validate the tracking performance of the integrated system. MRI compatibility is evaluated extensively. Teleoperated needle steering is also demonstrated under live MR imaging. A control system of a clinical grade MRI-compatible parallel 4-DOF surgical manipulator for minimally invasive in-bore prostate percutaneous interventions through the patient’s perineum is discussed in the end. The proposed manipulator takes advantage of four sliders actuated by piezoelectric motors and incremental rotary encoders, which are compatible with the MRI environment. Two generations of optical limit switches are designed to provide better safety features for real clinical use. The performance of both generations of the limit switch is tested. MRI guided accuracy and MRI-compatibility of whole robotic system is also evaluated. Two clinical prostate biopsy cases have been conducted with this assistive robot

Doctor of Philosophy

dissertationFemoroacetabular impingement (FAI) describes subtle structural abnormalities, including femoral asphericity and acetabular overcoverage, which reduce clearance in the hip joint. FAI is a common cause of hip pain for young, athletic adults. The first theme of this dissertation investigated if FAI morphology is more prevalent in athletes and if physical exams could be used to identify individuals with underlying FAI morphology. In a cohort of collegiate football players, 95% were found to have radiographic abnormalities consistent with those seen in FAI patients. This finding not only suggests that athletes, such as football players, may have an increased risk for developing symptomatic FAI, but also highlights that FAI morphology may frequently occur in asymptomatic subjects. In the same cohort, radiographic measures of femoral asphericity and femoral head-neck offset were mildly correlated to maximum internal rotation. As such, athletes with diminished internal rotation in whom hip pain develops should be evaluated for FAI. Altered articulation in FAI hips is believed to cause chondrolabral damage and may lead to osteoarthritis, but FAI kinematics have not been accurately quantified. To this end, the second theme of this dissertation focused on developing, validating, and applying a dual fluoroscopy and model-based tracking protocol to accurately quantify three-dimensional in vivo hip kinematics. In a cadaver experiment, model-based tracking was compared to the reference standard, dynamic radiostereometric analysis. Model-based tracking was found to have a positional error less than 0.48 mm and rotational error was less than 0.58°. The methodology was then applied to evaluate a cohort of asymptomatic control subjects and three patients with differing FAI morphology. The results, which represent the most accurate data collected on hip kinematics to date, demonstrate that hip articulation is a highly complex process, including translation, pelvic motion, no bone contact, and labrum involvement in large ranges of motion. Collected data provide necessary baseline results for future comparison studies and could be used to validate computer simulations of impingement, guide pre-operative planning, and serve as boundary conditions in finite element models investigating chondrolabral mechanics

New Technology and Techniques for Needle-Based Magnetic Resonance Image-Guided Prostate Focal Therapy

The most common diagnosis of prostate cancer is that of localized disease, and unfortunately the optimal type of treatment for these men is not yet certain. Magnetic resonance image (MRI)-guided focal laser ablation (FLA) therapy is a promising potential treatment option for select men with localized prostate cancer, and may result in fewer side effects than whole-gland therapies, while still achieving oncologic control. The objective of this thesis was to develop methods of accurately guiding needles to the prostate within the bore of a clinical MRI scanner for MRI-guided FLA therapy. To achieve this goal, a mechatronic needle guidance system was developed. The system enables precise targeting of prostate tumours through angulated trajectories and insertion of needles with the patient in the bore of a clinical MRI scanner. After confirming sufficient accuracy in phantoms, and good MRI-compatibility, the system was used to guide needles for MRI-guided FLA therapy in eight patients. Results from this case series demonstrated an improvement in needle guidance time and ease of needle delivery compared to conventional approaches. Methods of more reliable treatment planning were sought, leading to the development of a systematic treatment planning method, and Monte Carlo simulations of needle placement uncertainty. The result was an estimate of the maximum size of focal target that can be confidently ablated using the mechatronic needle guidance system, leading to better guidelines for patient eligibility. These results also quantified the benefit that could be gained with improved techniques for needle guidance

Improving Radiotherapy Targeting for Cancer Treatment Through Space and Time

Radiotherapy is a common medical treatment in which lethal doses of ionizing radiation are preferentially delivered to cancerous tumors. In external beam radiotherapy, radiation is delivered by a remote source which sits several feet from the patient\u27s surface. Although great effort is taken in properly aligning the target to the path of the radiation beam, positional uncertainties and other errors can compromise targeting accuracy. Such errors can lead to a failure in treating the target, and inflict significant toxicity to healthy tissues which are inadvertently exposed high radiation doses. Tracking the movement of targeted anatomy between and during treatment fractions provides valuable localization information that allows for the reduction of these positional uncertainties. Inter- and intra-fraction anatomical localization data not only allows for more accurate treatment setup, but also potentially allows for 1) retrospective treatment evaluation, 2) margin reduction and modification of the dose distribution to accommodate daily anatomical changes (called `adaptive radiotherapy\u27), and 3) targeting interventions during treatment (for example, suspending radiation delivery while the target it outside the path of the beam). The research presented here investigates the use of inter- and intra-fraction localization technologies to improve radiotherapy to targets through enhanced spatial and temporal accuracy. These technologies provide significant advancements in cancer treatment compared to standard clinical technologies. Furthermore, work is presented for the use of localization data acquired from these technologies in adaptive treatment planning, an investigational technique in which the distribution of planned dose is modified during the course of treatment based on biological and/or geometrical changes of the patient\u27s anatomy. The focus of this research is directed at abdominal sites, which has historically been central to the problem of motion management in radiation therapy

Maximising the mutual interoperability of an MRI scanner and a cancer therapy particle accelerator

The work described in this PhD thesis was undertaken as part of a much larger research project: The Australian MRI-Linac program. The goal of this program is to merge two existing medical technologies – an MRI scanner and a Linear Accelerator (Linac) – thereby creating an advanced form of cancer treatment incorporating cutting edge anatomical and physiological imaging techniques. An overview of the background information necessary to understand the work presented in this thesis is provided in chapters 1 (overview of radiotherapy) and 2 (overview of electromagnetism and accelerator physics). The work in the remainder of this thesis can be split into two distinct sections, corresponding to the two quite different (but ultimately related) projects I worked on throughout this thesis: modelling the impact of external magnetic fields on electron beam transport within the linear accelerator, and the implementation of patient rotation in radiotherapy. The former project is the focus of Chapters 3-6. In Chapter 3 a finite element model of a clinical gridded electron gun is developed based on 3D laser scanning and electrical measurements, and the sensitivity of this gun in magnetic fields characterised. The results complement the existing literature in showing that conventional linear accelerator components are very sensitive to external magnetic fields – in fact this gun is over twice as sensitive to axial magnetic fields than the less realistic models existing in the literature. A first order approach to overcoming this sensitivity is to use magnetic shielding – however magnetic shielding of the linear accelerator can negatively impact on the performance of the MRI scanner. This magnetic shielding problem is explored in Chapter 4, where the fundamental principles of passive magnetic shielding are explored, and magnetic shields are implemented for the two possible MRI-linac configurations (in-line and perpendicular) for the 1.0 Tesla MRI magnet used in the Australian MRI Linac program. The efficacy of the shielding and the impact on the MRI is quantified, with the conclusion that passive shielding could be successfully implemented to allow acceptable operation of the linac without overly degrading the magnet performance of the MRI scanner. An alternative approach to magnetic shielding which would not have any impact on the magnet is to redesign the linear accelerator such that it functions robustly in an MRI environment without the need for shielding. This approach is explored in chapter 5, where a novel electron accelerator concept based on an RF-electron gun configuration is detailed. It is shown via particle in cell simulations that such a design would be able to operate in a wide range of axial magnetic fields with minimal current loss. In chapter 6, an experimental beam line based on this concept was constructed at Stanford Linear Accelerator Center (SLAC). This project is ongoing but progress so far is described in Chapter 6. In the second part of this thesis, a completely different project is explored, patient rotation. Patient rotation would be very beneficial for MRI-Linac systems as it would eliminate the complicated engineering that is used in conventional systems to rotate the beam around the patient, and the MRI could be used to adapt in real time for the resultant anatomic deformation. Patient rotation would also minimise some of the sources of electromagnetic interference explored in chapters 3-7. The two major obstacles to patient rotation are (1) Page 11 patient tolerance to rotation, and (2) anatomical deformation due to rotation. To quantify patient rotation, a clinical study of 15 patients was carried out and is detailed in chapter 7. The results of this study suggest that patient tolerance to rotation may not be a major issue, although this result needs to be verified in larger patient cohorts. In chapter 8, the design and construction of an MRI-compatible patient rotation device is detailed. This device is the first of its kind, and will allow data on anatomic deformation under rotation to be collected, enabling strategies to adapt for this motion to be developed. Thus far, MRI compatibility has been assessed and a volunteer imaging study undertaken, in which pelvic images were acquired under rotation angles of 360⁰ every 45⁰. In summary: In chapters 3-5, the impact of magnetic fields on conventional accelerator components was quantified; and two independent approaches to compensating for these effects (magnetic shielding and bespoke accelerator design) were explored. In chapter 6, an experimental beam is constructed to verify and support the findings of chapter 6. In chapter 7, a clinical study was undertaken quantifying patient tolerance of slow, single arc rotation. Finally, in chapter 8 a unique medical device was designed, constructed and tested, and through this device MRI images of anatomical distortion under lying rotation were collected and quantified

Dynamic Thermal Imaging for Intraoperative Monitoring of Neuronal Activity and Cortical Perfusion

Neurosurgery is a demanding medical discipline that requires a complex interplay of several neuroimaging techniques. This allows structural as well as functional information to be recovered and then visualized to the surgeon. In the case of tumor resections this approach allows more fine-grained differentiation of healthy and pathological tissue which positively influences the postoperative outcome as well as the patient's quality of life. In this work, we will discuss several approaches to establish thermal imaging as a novel neuroimaging technique to primarily visualize neural activity and perfusion state in case of ischaemic stroke. Both applications require novel methods for data-preprocessing, visualization, pattern recognition as well as regression analysis of intraoperative thermal imaging. Online multimodal integration of preoperative and intraoperative data is accomplished by a 2D-3D image registration and image fusion framework with an average accuracy of 2.46 mm. In navigated surgeries, the proposed framework generally provides all necessary tools to project intraoperative 2D imaging data onto preoperative 3D volumetric datasets like 3D MR or CT imaging. Additionally, a fast machine learning framework for the recognition of cortical NaCl rinsings will be discussed throughout this thesis. Hereby, the standardized quantification of tissue perfusion by means of an approximated heating model can be achieved. Classifying the parameters of these models yields a map of connected areas, for which we have shown that these areas correlate with the demarcation caused by an ischaemic stroke segmented in postoperative CT datasets. Finally, a semiparametric regression model has been developed for intraoperative neural activity monitoring of the somatosensory cortex by somatosensory evoked potentials. These results were correlated with neural activity of optical imaging. We found that thermal imaging yields comparable results, yet doesn't share the limitations of optical imaging. In this thesis we would like to emphasize that thermal imaging depicts a novel and valid tool for both intraoperative functional and structural neuroimaging

Functional MRI Data Analysis Techniques and Strategies to Map the Olfactory System of a Rat Brain.

Understanding mysteries of a brain represents one of the great challenges for modern science. Functional magnetic resonance imaging (fMRI) has two features that make it unique amongst other imaging modalities used in behavioral neuroscience. First, it can be entirely non-invasive and second, fMRI has the spatial and temporal resolution to resolve patterns of neuronal activity across the entire brain in less than a minute. fMRI indirectly detects neural activity in different parts of the brain by comparing contrast in MR signal intensity prior to and following stimulation. Areas of the brain with increased synaptic and neuronal activity require increased levels of oxygen to sustain this activity. Enhanced brain activity is accompanied by an increase in metabolism followed by increases in blood flow and blood volume. The enhanced blood flow usually exceeds the metabolic demand exposing the active brain area to high level of oxygenated hemoglobin. Oxygenated hemoglobin increases the MR signal intensity that can be detected in MR scanner. This relatively straight forward scenario is, unfortunately, oversimplified. The fMRI signal change to noise ratio is extremely small. In this work a quantitative analysis strategy to analyze fMRI data was successfully developed, implemented and optimized for the rat brain. Therein, each subject is registered or aligned to a complete volume-segmented rat atlas. The matrices that transformed the subject\u27s anatomy to the atlas space are used to embed each slice within the atlas. All transformed pixel locations of the anatomy images are tagged with the segmented atlas major and minor regions creating a fully segmented representation of each subject. This task required the development of a full 3D surface atlas based upon 2D non-uniformly spaced 2D slices from an existing atlas. A multiple materials marching cube (M3C) algorithm was used to generate these 1277 subvolumes. After this process, they were coalesced into a dozen major zones of the brain (amygdaloid complex, cerebrum, cerebellum, hypothalamus, etc.). Each major brain category was subdivided into approximately 10 sub-major zones. Many scientists are interested in behavior and reactions to pain, pleasure, smell, for example. Consequently, the 3D volume atlas was segmented into functional zones as well as the anatomical regions. A utility (program) called Tree Browser was developed to interactively display and choose different anatomical and/or functional areas. Statistical t-tests are performed to determine activation on each subject within their original coordinate system. Due to the multiple t-test analyses performed, a false-positive detection controlling mechanism was introduced. A statistical composite of five components was created for each group. The individual analyses were summed within groups. The strategy developed in this work is unique as it registers segments and analyzes multiple subjects and presents a composite response of the whole group. This strategy is robust, incredibly fast and statistically powerful. The power of this system was demonstrated by mapping the olfactory system of a rat brain. Synchronized changes in neuronal activity across multiple subjects and brain areas can be viewed as functional neuro-anatomical circuits coordinating the thoughts, memories and emotions for particular behaviors using this fMRI module