Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

John A. Persing

Second Advisor

John Geibel

Subject Area(s)

Medicine, Surgery

Abstract

Craniosynostosis (CSO) is the premature fusion of one or more cranial sutures. When a cranial suture fuses prematurely, skull growth is altered and the cranium takes on a characteristic pathological shape determined by the suture(s) that fuses. Surgery is performed in the first year of life to correct for a more normalized head shape and brain growth. Even after surgical treatment craniosynostosis may be associated with an increased rate of learning disability later in life. Still, little remains known about 1) the brain basis of neurocognitive deficits in CSO; 2) the role of surgery in improving cognitive deficits in CSO; and 3) whether the primary goal of surgery, that is, to allow for more normalized brain development, is actually achieved years after surgery. The aims of this study are to use functional MRI (fMRI) and diffusion tensor imaging (DTI) to 1) characterize brain structure and function in previously treated children with the most common CSO form, sagittal nonsyndromic craniosynostosis ( sNSC); 2) develop and validate a protocol for evaluating surgery's role in brain structure and function in CSO infants; and 3) determine the extent to which, years after intervention, brains of sNSC adolescents normalize in shape compared to matched controls.

Using a 3-T Siemens Trio MRI system, authors collected DTI and resting-state functional connectivity MRI data in 8 sNSC adolescents (mean age 12.3 years) who had undergone corrective total vault cranioplasty and 8 controls (mean age 12.3 years) without CSO. Data were also collected on 7 unoperated sNSC infants and 2 matched controls (mean age 6.1 months). Data were analyzed using the FMRIB Software Library and BioImageSuite. Morphometry brain analyses utilized voxel-wise Jacobian mapping.

fMRI revealed decreased altered connectivity in areas of executive control (prefrontal cortex), language and visuospatial processing (left lateral parietal cortex), and the default mode brain network (DMN) in sNSC adolescents compared to controls (p < 0.05). DTI revealed trends toward diffuse altered white matter connectivity (p < 0.10). An infant scanning protocol was developed, resulting in an overall scan success rate of 66%, and 85% when protocol was strictly followed. Finally, morphometric brain analysis revealed no areas of pronounced or localized group brain shape differences between treated sNSC adolescents and controls who were treated by comprehensive cranioplasty techniques.

Sagittal craniosynostosis is associated with an increased rate of learning disability. This study lends evidence to the fact that this learning disability is rooted in a diffuse functional and microstructural abnormality. Morphometry analysis reveals previously treated sNSC children achieve complete, or near-complete, brain shape normalization by adolescence. The morphometry results also support fMRI and DTI findings that commonly reported sNSC neurocognitive difficulties likely arise from subtle parenchymal insults. Finally, ability to assess surgical impact on CSO infant brain structure and function with new scanning protocols, with scan success of >80% with strict guideline adherence, was achieved so that measuring surgical parameters such as timing and type of surgery are feasible.

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