High-Resolution Quantitative Cone-Beam Computed Tomography: Systems, Modeling, and Analysis for Improved Musculoskeletal Imaging

This dissertation applies accurate models of imaging physics, new high-resolution imaging hardware, and novel image analysis techniques to benefit quantitative applications of x-ray CT in in vivo assessment of bone health. We pursue three Aims: 1. Characterization of macroscopic joint space morphology, 2. Estimation of bone mineral density (BMD), and 3. Visualization of bone microstructure. This work contributes to the development of extremity cone-beam CT (CBCT), a compact system for musculoskeletal (MSK) imaging. Joint space morphology is characterized by a model which draws an analogy between the bones of a joint and the plates of a capacitor. Virtual electric field lines connecting the two surfaces of the joint are computed as a surrogate measure of joint space width, creating a rich, non-degenerate, adaptive map of the joint space. We showed that by using such maps, a classifier can outperform radiologist measurements at identifying osteoarthritic patients in a set of CBCT scans. Quantitative BMD accuracy is achieved by combining a polyenergetic model-based iterative reconstruction (MBIR) method with fast Monte Carlo (MC) scatter estimation. On a benchtop system emulating extremity CBCT, we validated BMD accuracy and reproducibility via a series of phantom studies involving inserts of known mineral concentrations and a cadaver specimen. High-resolution imaging is achieved using a complementary metal-oxide semiconductor (CMOS)-based x-ray detector featuring small pixel size and low readout noise. A cascaded systems model was used to performed task-based optimization to determine optimal detector scintillator thickness in nominal extremity CBCT imaging conditions. We validated the performance of a prototype scanner incorporating our optimization result. Strong correlation was found between bone microstructure metrics obtained from the prototype scanner and µCT gold standard for trabecular bone samples from a cadaver ulna. Additionally, we devised a multiresolution reconstruction scheme allowing fast MBIR to be applied to large, high-resolution projection data. To model the full scanned volume in the reconstruction forward model, regions outside a finely sampled region-of-interest (ROI) are downsampled, reducing runtime and cutting memory requirements while maintaining image quality in the ROI

Analysis of Subchondral Bone and Microvessels Using a Novel Vascular Perfusion Contrast Agent and Optimized Dual-Energy Computed Tomography

Osteoarthritis (OA), is a chronic debilitating disease that affects millions of individuals and is characterized by the degeneration of joint subchondral bone and cartilage. These tissue degenerations manifest as joint pain, limited range of joint motion, and overall diminished quality of life. Currently, the exact mechanism(s) and cause(s) by which OA initiates and progresses remain unknown. The multi-factorial complex nature of OA (i.e. age, diabetes, obesity, and prior injuries have all been shown to play a role in OA) contributes to the current lack of a cure or effective long-term treatment for OA. One re-emerging and interesting hypothesis revolves around the delicate homeostatic microvascular environment around the cartilage – an avascular tissue. The absence of blood vessels within cartilage stresses the importance of nutrient and oxygen delivery from the neighbouring synovium and subchondral bone. Currently, the effects of changes in the subchondral bone microvessel density on cartilage health remain unknown due to the difficulties in simultaneously studying dense bone and the associated small microvessels. Computed tomography (CT) is widely used in the diagnosis of OA, as the use of x-rays provide detailed images of the bone degeneration associated with OA. However, the study of microvessels using CT has been exceptionally difficult due to their small (\u3c 10 µm) size, lack of contrast from neighbouring soft tissues, and proximity to dense bone. The purpose of this thesis was to develop a novel dual-energy micro-computed tomography (DECT) compatible vascular perfusion contrast agent and the associated instrumentation to optimize DECT on pre-clinical, cone-beam micro-CT scanners. The combination of these two techniques would facilitate the simultaneous visualization and quantification of subchondral bone and microvessels within the bone underlining the cartilage (i.e. distal femoral epiphysis and proximal tibial epiphysis) of rats that have undergone an OA-induced surgery. Results gained from this study will further provide information into the role that microvessels may play in OA

Changes in Femoral Structure and Function Following Anterior Cruciate Ligament Injury and with Aging

The ACL, a ligament connected to the distal femur, has little regenerative capacity. In consequence, surgical intervention is required if a patient hopes to remain active following ACL injury. In addition to the long recovery time and associated morbidities (e.g., osteoarthritis) following surgery, up to 12% of the primary reconstructed ACL grafts will fail within 15 years. Revision reconstructions are inferior to primary ACL reconstructions, thus, understanding the mechanism of failure is critical to mitigating worst-case outcomes. Reasons for revision risk have largely focused on technical errors despite that biological factors may also be a cause. Bone, a biological factor, decreases in mass following ACL injury. However, how bone microstructure changes following injury has remained largely unexplored. It was determined in this study that bone microstructure differs on a patient-by-patient basis undergoing ACL reconstructive surgery. Differences in microarchitecture could not be explained by time from injury to operation (i.e. time of disuse) or activity the patient was participating in at the moment of injury. Thus, differences in bone quality are due to variability present at baseline, in response to injury, and/or activity level following injury. Clinically, these findings are important because we are the first to show that bone quality varies across patient groups, pointing out that microstructure may be an important factor to consider in assessing ACL injury risk and surgical outcomes. The second half of this thesis compared age-related and sex-specific differences in bone microstructure to whole bone strength in the proximal femur with the long term goal of improving diagnostic methods to assess osteoporotic hip fracture risk. Hip fragility fractures are costly, associated with a severe decrease in the quality of life, and nearly half of patients (>65 years) who suffer a hip fracture never regain normal function. Unfortunately, approximately fifty percent of patients that experience a hip fracture receive no prophylactic treatment prior to fragility fracture because they are not diagnosed as osteoporotic using current clinical diagnostic methods. Both bone mass and microstructure change with age and the progression of osteoporosis. However, technical limitations have made it difficult to measure fracture risk from a biomechanical perspective - relating proximal femur bone strength and microstructure in synergy. The second study determined that the magnitude of sex-specific differences in bone strength was greater than age-related strength loss endured throughout life. Further, there was no sex-specific difference in the rate of loss observed herein. Clinically, these findings demonstrate that if females could maximize bone quality early in life, they may be able to maintain the structural strength later on, even with bone loss, to mitigate fragility fractures altogether. Further, mechanical variables (i.e., stiffness and post-yield-displacement) and demographic data (i.e., age and sex) could not adequately explain variability in whole bone strength. Microstructural analysis in the femoral neck improved our ability to predict whole bone strength but demonstrated that sub-regional microstructural detail only modestly improved strength predictability in comparison to average measures across the femoral neck. Despite this, we found that increased levels of micro-architectural detail are needed to identify sex-specific differences in whole bone strength. Clinically, these findings demonstrate that regional analysis may be useful for identifying those at greatest risk of fracture earlier in life and in a sex-specific manner.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155081/1/pattondm_1.pd

The Application of Digital Volume Correlation Bone Strain Measurements in the Osteoarthritic Glenohumeral Joint

This thesis investigates the accuracy and precision of digital volume correlation measurements derived from micro-computed tomography imagery of interfaces in the upper extremity of clinical relevance, namely, the implant-cement-bone interface of glenoid implants used in total shoulder arthroplasties and the implant-bone interface of shoulder hemiarthroplasties. The works within derive relationships between measurement accuracy and precision and parameters of practical interest such as image quality and measurement spatial resolution. It also analyzes the effects of micro-computed tomography image artifact-inducing materials on the accuracy and precision of digital volume correlation-based measurements and the spatial relationship between distance between the artifacting material and the magnitude of change in accuracy and precision. Finally, it also contains an in-vitro model of the peripheral glenoid peg-cement-bone interface which is subsequently analyzed through digital volume correlation; the relationship between peg/bone region and strain magnitude is elucidated