A systematic evaluation of the neurosurgical application of perioperative and intraoperative diffusion MR tractography in paediatric epilepsy surgery

2015 Dr. Joseph Yuan-Mou YangEpilepsy is a serious health condition affecting children worldwide. In a subset of these children, the epilepsy is refractory despite maximum appropriate medical therapies. Neurosurgical interventions aiming at resecting the seizure generating (epileptogenic) tissue provides the potential for seizure freedom in these children. The principle of epilepsy surgery is to maximally resect the epileptogenic tissues without injuring the eloquent brain regions, which includes both the cortical grey matter (GM) and the subcortical white matter tracts (WMTs). Injuries to these structures can lead to permanent neurological deficits. The surgical success depends on concordant preoperative and intraoperative localisation of both the seizure focus and the eloquent brain through the use of multimodal brain structural and functional neuroimaging techniques. Diffusion MR tractography is an increasingly utilised neuroimaging adjunct in epilepsy surgery that uniquely provides non-invasive virtual reconstructions of the WMT anatomy. Despite the growing popularity, its application in paediatric epilepsy surgery requires judicious evaluation, particularly with respect to its inherent technical limitations relevant to this age group. There is also a paucity of information regarding usefulness of a more sophisticated diffusion model and tractography algorithm in this clinical population. Using a cohort of 20 paediatric epilepsy surgical candidates, this PhD consists of three study experiments addressing both the technical and the clinical aspects of the diffusion MR tractography. Study experiment one (Chapter Five and Six) demonstrates the feasibility of developing a novel tractography methodology by adopting a more sophisticated diffusion model and the tractography algorithm. The study demonstrates highly accurate tractography results when validate against a set of predefined WMT anatomical criteria. Tractography generated in WMTs with distorted anatomy corresponds well with the functional MRI data and the direct brain electrostimulation findings. Study experiment two (Chapter Seven) evaluates the role of diffusion MR tractography to assess the degree of intraoperative WMT shift, and the intraoperative factors impacting on this shift. The study shows WMT shift is dynamic and occurs at both the global hemispheric and the regional WMT-based levels. The durotomy size, the resected lesion size and the presence of brain oedema are significant independent intraoperative variables affecting the WMT shift. Study experiment three (Chapter Eight) evaluates the association between the tractography-derived quantitative metrics and the perioperative functional states of the participants. The incomplete clinical data restricts the analysis to subgroup and case-based observations. The results suggest the adopted quantitative metrics are sensitive but non-specific imaging biomarkers of the underlying WMT microstructure changes, and do not consistently reflect the child’s postoperative function. Further methodological refinements are required to substantiate and to improve on this finding. This PhD provides a reliable technical framework for performing diffusion MR tractography in children. It also highlights the pertinent technical factors that need to be considered when utilising and interpreting diffusion MR tractography results in paediatric epilepsy surgery over both the perioperative and the intraoperative settings. Importantly, this PhD provides the basis for future research while continue searches for a more specific WMT imaging biomarker associating with the child’s postoperative functional state that is of both diagnostic and interventional significance