Image analysis tool for the characterisation of bone turnover in the appendicular skeleton

Osteoporosis is a disease characterised by reduced bone mass and altered microarchitecture leading to an increased risk of fracture. The consequences of osteoporosis include reduced quality of life and pain, associated with fractures. Its financial burden on health services are significant. Characterisation of osteoporosis using imaging techniques is therefore important. Peripheral Quantitative Computed Tomography (pQCT) is a cross-sectional imaging method which is used to scan bones in the appendicular skeleton. pQCT imaging may be particularly useful in clinical groups where changes in bone mineral density (BMD) and structure are known to occur in the limbs. Two such groups are patients following spinal cord injury (SCI) or anterior cruciate ligament (ACL) injury. Aims. This project aimed to develop analysis techniques to characterise bone in pQCT images. Their purpose was to describe localised changes within pQCT images of the bone, as opposed to the standard global measurements. Methods. Fully automated segmentation and registration software was developed and tested followed by two independent processing algorithms. The first generates spatial maps to characterise local changes in BMD. This is achieved using both quadrant analysis software and a voxel-based approach, the latter comparing pairs of images and generating a voxel-by-voxel ΔBMD map of changes in BMD. The second processing algorithm uses morphological granulometries to investigate the bone microarchitecture. Results. Evaluation of these image analysis methods was carried out using two clinical studies. The first investigates acute longitudinal changes in the distal tibia (DT) and distal femur (DF) post-motor-complete-SCI using pQCT. Images from 15 subjects (13M, 2F) with a mean age of 36y±19y, were acquired at 4-monthly intervals during the first year post-injury. The second comprises of ACL injury subjects, with imaging of the injured and contralateral proximal tibia (PT) and distal femur before (n=19, 18M 1F, 30y±9y of age) and after (n=8, 8M 0F, 31y±9y of age) surgical ACL reconstruction. The software developed to automatically segment bone from surrounding structures was successful: 98% success rate for epiphyseal tibial regions, 67% success rate for the distal femur. Registration of images was then performed and the spatial analysis methods to automatically produce quadrants of trabecular bone were applied, displaying individual results graphically. The voxel based analysis method was developed, tested and applied to produce ΔBMD maps, utilising statistical inference and corrections for multiple comparisons using a false-discovery rate technique. These maps characterised localised changes in BMD between pairs of both longitudinal and contralateral images. Software was also developed to apply morphological granulometries to pQCT images, calculating global and local pattern spectrum moments. On application of the analysis methods to the longitudinal SCI images, the BMD and microarchitecture findings were observed to be disparate amongst subjects, with large variations in bone characteristics both globally and regionally. The quadrant and voxel based analysis methods provided information on longitudinal regional changes in each subject, indicating individual patterns of change. Structural analysis of bone microarchitecture using granulometries was demonstrated to have potential as a useful adjunct to BMD in identifying SCI subjects more susceptible to rapid bone loss. The analysis methods were also successfully applied to the ACL injury subjects. Following segmentation and registration, the total and trabecular BMD in the injured knee was observed to be significantly lower than that of the contralateral control knee pre-operatively for both the PT and DF (p<0.05). Post-operatively the total and trabecular BMD in the injured DF remained significantly low (p<0.05), however the PT demonstrated significantly lower BMD in the injured leg for the trabecular bone only (p<0.05). Reduced BMD in the PT post-operatively in humans is a novel observation, and indicates a benefit afforded by segmenting trabecular from cortical bone. Regional analysis using quadrants indicated some anatomical variation in bone loss within the injured limb, although it is acknowledged that these are preliminary findings which would require to be confirmed in larger studies. The voxel ΔBMD maps generally indicated global losses across the bones of the ACL injured leg both pre-operatively and post-operatively. No consistent patterns were obtained in the ΔBMD maps for these subjects, suggesting individual patterns of response to ACL injury. The structural information provided by granulometric analysis was limited for the ACL study. Conclusions. Automated software has been developed to characterise bone in pQCT images of the appendicular skeleton. It has been successfully applied to two clinical studies, facilitating localised changes in bone density to be demonstrated and descriptions of microarchitecture to be provided. The SCI subjects appear to have individualistic responses to injury, with a wide range of changes in bone density and microarchitecture observed. ACL injury patients all lost bone mass, but patterns of change were variable. The analysis methods developed to permit characterisation of bones in individual subjects, are proposed to be of value in both clinical and research domains exploring bone mass and microarchitecture, with the ultimate goals being the prediction of fracture risk and tailoring therapy for the individual.