Abstract
Osteoarthritis (OA) is a degenerative disease which affects both bone and cartilage as it progresses, however imaging modalities are not currently able to quantitatively assess both tissues simultaneously. Furthermore, it is difficult to monitor bone and cartilage repair treatments using imaging due to a lack of radiopacity and/or artefact produced. Spectral photon-counting computed tomography (SPCCT), with the ability to identify and separate multiple materials, may provide a technique for quantitative evaluation of cartilage and bone health as well as analysis of repair strategies in a single scan. The overall aim of this thesis was to non-destructively evaluate the degeneration of bone and cartilage from OA, as well as the implants used for bone and cartilage repair using SPCCT.
Firstly, common contrast agents (iodine- and gadolinium- based) were evaluated for use with SPCCT imaging for biomarker quantification of cartilage health using healthy bovine explants and osteoarthritic human explants. An inverse relationship between each contrast agent concentration and glycosaminoglycan (GAG) content in the cartilage was established in healthy tissue. Subsequently, contrast agents were used to visualize areas of osteoarthritic cartilage devoid of GAG, indicating OA progression. Building on this preliminary work, a systematic investigation into the optimisation of SPCCT imaging for gadolinium identification was completed. Calibration phantoms, biological phantoms and protocol parameters were evaluated in order to define a minimum detectable gadolinium concentration with SPCCT as well as an acceptable concentration for a sensitive measurement of cartilage health. High concentration calibration phantoms and isolating the spectral response of gadolinium gave the best identification and quantification of gadolinium. When measuring cartilage health, contrast agents with concentrations ≥ 80 mg/mL and a linear chemical structure were able to distinguish statistically significant differences in GAG content in healthy cartilage. To assess bone, SPCCT measurements of subchondral bone structure and composition were validated against clinical gold standard imaging modalities, including dual X-ray absorptiometry (DXA), computed tomography and micro computed tomography. Additionally, the ability of SPCCT to detect changes in bone parameters through OA was examined. SPCCT was able to measure bone mineral density comparable to DXA, and while not at the resolution of micro-CT, SPCCT was able to match trends in bone structure quantification. Bone structure and composition changes at all OA stages were detectable with SPCCT, noting an increase in the subchondral bone plate thickness as well as fluctuations in bone mineral density.
Progressing from OA diagnosis, the longitudinal assessment of tissue quality or effectiveness of treatments including tissue repair and replacement strategies is required. Hydrogel-based engineered cartilage tissue constructs are being developed as a regenerative medicine strategy to repair cartilage, however these constructs are currently quantitatively assessed using destructive techniques and biochemical assays, and therefore tissue growth and quality cannot be easily monitored over time. To determine whether SPCCT was a suitable platform to assess tissue quality in these constructs, a contrast agent incubation and SPCCT scanning study was undertaken. Neither the SPCCT scan nor the contrast agent incubation (gadolinium- or iodine-based) altered the cell viability or functionality of cell-laden constructs. Furthermore, SPCCT was able to identify and separate the construct biomaterial (hydrogel), from water and contrast agents, making material and tissue assessment possible in a single scan.
For bone repair, metallic orthopaedic implants are currently used in the clinic for replacing damaged or diseased tissues and joints. However, when imaged these implants produce large artefacts, interfering with the visualization of the implant and quantification of surrounding bone, both of which are needed to determine implant success. The aim of the final study in this thesis was to reduce artefact from both solid and porous titanium implants while simultaneously quantifying the surrounding calcium content using SPCCT. SPCCT was able to reduce the artefact using an optimised high energy protocol and quantify calcium in the bone around a solid surgical screw. Calcium was also quantifiable adjacent to the porous implant but within the pores, calcium concentration was over-estimated making the assessment of osseointegration difficult.
In conclusion, this thesis has demonstrated significant advancement in the ability of SPCCT to image and quantify cartilage and bone health through OA progression by measuring biomarkers such as GAG content, cartilage thickness, bone mineral density and subchondral bone plate thickness in a single scan. Furthermore, work in the thesis evaluates the potential of a novel technique for non-destructive assessment of engineered cartilage tissue constructs as well as the possibility of SPCCT to reduce metal artefact and quantify surrounding calcium for bone repair success.