Synthetic CT images of the thoracic-lumbar spine were validated using BoneMRI. This was then integrated into an adolescent idiopathic scoliosis specific MRI protocol of 8 sequences, making it possible to quickly and completely image all spinal structures, even with children of limited attention spans. These were used in clinical studies of sister/daughter subjects and 22q11.2DS patients (Earlybird 1 & 2). Currently, there are 31 sister/daughter and 11 microdeletions patient inclusions.
To correlate disc biomechanical properties to disc and growth plate maturity, we focused on establishing methodologies for assessment of structural, mechanical, and compositional properties of the disc and growth plate. While waiting for the collection of sufficient number and age range of human adolescent segments, we used bovine segments. Most interestingly, a 7T MRI 3D assessment of collagen fiber microarchitecture of the complete disc in an unaltered state, while quantifying water content noninvasively was achieved.
For eventual subject-specific biomechanical assessment of the spine, machine learning algorithms were developed for automatic segmentation of discs, vertebrae and facet joints. A new, faster, and more robust method for the automatic creation of subject-specific spine models was set up using an algorithm for mesh morphing. These methods are now being applied to build models specific to the subjects in the Earlybird studies.
As a first step towards a spinal biomechnical model, a generic spinal motion segment model with multiphasic discs was developed. After confirming model accuracy, a L4-L5 segment model was validated in all three rotational degrees-of-freedom against an experimental study. Then the model was adapted to subject-specific T11-12 segment models of a cohort of Earlybird subjects to assess effects of spinal instability with retroversion on ‘unlocking’ of the facet joints increasing rotationally instability and whether this could lead to higher strains in the annulus fibrosus in our cohort of subjects.
To identify growth plate morphogens (GPMs) responsible for negatively affecting IVD deformity during tissue remodelling, we narrowed our focus to seven cytokines most likely responsible for contributing to scoliosis. The ability of these morphogens to elicit a gene expression response in AF cells were explored. It was observed that three of the morphogens induced downstream pathway activation. An innovative 2.5D platform was developed such that AF cells could be cultured while preserving their native phenotype. Subsequently, a screening study to assess the impact of GPMs on AF cellular capacity for tissue remodeling was investigated. We are currently awaiting results from RNA sequencing. The most interesting results will be further verified at the protein level.
