Quantifying the Tibiofemoral Joint Space Using X-ray Tomosynthesis

Purpose: Digital x-ray tomosynthesis (DTS) has the potential to provide 3D information about the knee joint in a load-bearing posture, which may improve diagnosis and monitoring of knee osteoarthritis compared with projection radiography, the current standard of care. Manually quantifying and visualizing the joint space width (JSW) from 3D tomosynthesis datasets may be challenging. This work developed a semiautomated algorithm for quantifying the 3D tibiofemoral JSW from reconstructed DTS images. The algorithm was validated through anthropomorphic phantom experiments and applied to three clinical datasets. Methods: A user-selected volume of interest within the reconstructed DTS volume was enhanced with 1D multiscale gradient kernels. The edge-enhanced volumes were divided by polarity into tibial and femoral edge maps and combined across kernel scales. A 2D connected components algorithm was performed to determine candidate tibial and femoral edges. A 2D joint space width map (JSW) was constructed to represent the 3D tibiofemoral joint space. To quantify the algorithm accuracy, an adjustable knee phantom was constructed, and eleven posterior–anterior (PA) and lateral DTS scans were acquired with the medial minimum JSW of the phantom set to 0–5 mm in 0.5 mm increments (VolumeRadTM, GE Healthcare, Chalfont St. Giles, United Kingdom). The accuracy of the algorithm was quantified by comparing the minimum JSW in a region of interest in the medial compartment of the JSW map to the measured phantom setting for each trial. In addition, the algorithm was applied to DTS scans of a static knee phantom and the JSW map compared to values estimated from a manually segmented computed tomography (CT) dataset. The algorithm was also applied to three clinical DTS datasets of osteoarthritic patients. Results: The algorithm segmented the JSW and generated a JSW map for all phantom and clinical datasets. For the adjustable phantom, the estimated minimum JSW values were plotted against the measured values for all trials. A linear fit estimated a slope of 0.887 (R2¼0.962) and a mean error across all trials of 0.34 mm for the PA phantom data. The estimated minimum JSW values for the lateral adjustable phantom acquisitions were found to have low correlation to the measured values (R2¼0.377), with a mean error of 2.13 mm. The error in the lateral adjustable-phantom datasets appeared to be caused by artifacts due to unrealistic features in the phantom bones. JSW maps generated by DTS and CT varied by a mean of 0.6 mm and 0.8 mm across the knee joint, for PA and lateral scans. The tibial and femoral edges were successfully segmented and JSW maps determined for PA and lateral clinical DTS datasets. Conclusions: A semiautomated method is presented for quantifying the 3D joint space in a 2D JSW map using tomosynthesis images. The proposed algorithm quantified the JSW across the knee joint to sub-millimeter accuracy for PA tomosynthesis acquisitions. Overall, the results suggest that x-ray tomosynthesis may be beneficial for diagnosing and monitoring disease progression or treatment of osteoarthritis by providing quantitative images of JSW in the load-bearing knee

A new quantitative 3D approach to imaging of structural joint disease.

Imaging of joints with 2D radiography has not been able to detect therapeutic success in research trials while 3D imaging, used regularly in the clinic, has not been approved for this purpose. We present a new 3D approach to this challenge called joint space mapping (JSM) that measures joint space width in 3D from standard clinical computed tomography (CT) data, demonstrating its analysis steps, technical validation, and reproducibility. Using high resolution peripheral quantitative CT as gold standard, we show a marginal over-estimation in accuracy of +0.13 mm and precision of ±0.32 mm. Inter-operator reproducibility bias was near-zero at -0.03 mm with limits of agreement ±0.29 mm and a root mean square coefficient of variation 7.5%. In a technical advance, we present results from across the hip joint in 3D with optimum validation and reproducibility metrics shown at inner joint regions. We also show JSM versatility using different imaging data sets and discuss potential applications. This 3D mapping approach provides information with greater sensitivity than reported for current radiographic methods that could result in improved patient stratification and treatment monitoring

A diagnostic imaging technique and therapeutic strategy for early osteoarthritis

Thesis (Ph.D.)--Boston UniversityOsteoarthritis (OA) is a chronic, progressive disease of diarthrodial joints arising from the breakdown of articular cartilage. As one of the leading causes of disability and lifestyle limitations in the United States, osteoarthritis is estimated to affect 27 million people in the U.S. and cost the economy $128 billion annually. Current diagnostic techniques detect OA only in its later stages, when irreversible cartilage damage has already occurred. A reliable, non-invasive method for diagnosing OA in its early stages would provide an opportunity to intervene and potentially to stay disease progression. Likewise, the field of OA research would benefit from a technique that allows tissue engineering and small molecule therapies to be evaluated longitudinally. Contrast-enhanced computed tomography (CECT) of cartilage is a developing medical imaging technique for evaluating cartilage biochemical and biomechanical properties. CECT has been shown to accurately quantify measures of cartilage integrity such as glycosaminoglycan (GAG) content, equilibrium compressive modulus, and coefficients of friction. In the studies presented herein, cationic iodinated contrast agents are developed for quantitative cartilage CECT, a technique predicated on the diffusion and partitioning of a charged contrast agent into the cartilage. The experiments show that cationic contrast agents lack specific interactions with anionic GAGs and are highly taken up in cartilage due, instead, to their electrostatic attraction. At diffusion equilibrium, both anionic and cationic agents indicate GAG content and biomechanical properties as measured by microcomputed tomography, though cationic contrast agents were found to diffuse through cartilage more slowly than anionic ones. Translating CECT to intact joints with clinically available helical CT scanners bears promising results, but concerns remain regarding in vivo applicability. Anionic contrast agents enable GAG content quantification following brief contrast agent exposure, whereas cationic agents require full equilibration within the tissue. To explore treatment modalities for early OA, a novel interpenetrating hydrogel method was developed to reconstitute the mechanical properties of cartilage models for early OA. Preliminary results show that the interpenetrating network strengthened cartilage with respect to compressive loading suggesting that the treatment could potentially serve as a functional replacement for GAG lost in the early stages of OA

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

Doctor of Philosophy

dissertationAltered mechanics are believed to initiate osteoarthritis in hips with acetabular dysplasia. Periacetabular osteotomy (PAO) is the preferred surgical treatment; however, it is unknown if the procedure normalizes joint anatomy and mechanics. Changes in three-dimensional (3D) morphology and chondrolabral mechanics were quantified after PAO. Finite element (FE) models demonstrated that PAO improved the distribution of coverage, reduced stress, increased congruity, and prevented cartilage thinning. However, changes in mechanics were not consistent. In fact, one patient exhibited increased stress after surgery, which was believed to be a result of over-correction. Therefore, methods to integrate morphologic and biomechanical analysis with clinical care could standardize outcomes of PAO. FE simulations are time-intensive and require significant computing resources. Therefore, the second aim was to implement an efficient method to estimate mechanics. An enhanced discrete element analysis (DEA) model of the hip that accurately incorporated cartilage geometry and efficiently calculated stress was developed and analyzed. Although DEA model estimates predicted elevated magnitudes of contact stress, the distribution corresponded well with FE models. As a computationally efficient platform, DEA could assist in diagnosis and surgical planning. Imaging is a precursor to analyzing morphology and biomechanics. Ideally, an imaging protocol would visualize bone and soft-tissue at high resolution without ionizing radiation. Magnetic resonance imaging (MRI) with 3D dual-echo-steady-state (DESS) is a promising sequence to image the hip noninvasively, but its accuracy has not been quantified. Therefore, the final aim was to implement and validate the use of 3D DESS MRI in the hip. Using direct measurements of cartilage thickness as the standard, 3D DESS MRI imaged cartilage to ~0.5 mm of the physical measurements with 95% confidence, which is comparable to the most accurate hip imaging protocol presented to date. In summary, this dissertation provided unique insights into the morphologic and biomechanical features following PAO. In the future, DEA could be combined with 3D DESS MRI to efficiently analyze contact stress distributions. These methods could be incorporated into preoperative planning software, where the algorithm would predict the optimal relocation of the acetabulum to maximize femoral head coverage while minimizing contact stress, and thereby improve long-term outcomes of PAO