Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease.

BACKGROUND: Krabbe disease is a fatal neurodegenerative disease caused by rapid demyelination of the central and peripheral nervous systems. The only available treatment, unrelated umbilical cord blood transplantation, is effective only if performed before clinical symptoms appear. Phenotypic expressions of disease-causing mutations vary widely, but genotype-phenotype relationships are unclear. Therefore, we evaluated diffusion tensor imaging (DTI) tractography with volumetric analysis as a biomarker of early white matter changes and functional disability in presymptomatic infants. METHODS: We obtained DTI and structural scans of newborns with early-infantile Krabbe disease (n = 9) diagnosed by family history or newborn screening. We compared white matter fiber tract properties to those of normal controls (n = 336) and assessed the ability of tract-based properties to predict longitudinal development in four functional domains (cognitive, fine motor, gross motor, adaptive behavior) after treatment with unrelated umbilical cord blood transplantation. We also assessed the relationship between the standard evaluation (modified Loes score) and DTI results, and the volumetric differences between the Krabbe subjects and normal controls. FINDINGS: Reductions in fractional anisotropy were significant in the corticospinal tract in the Krabbe patients compared to controls, which strongly correlated with motor and cognitive outcomes after transplantation. Significant regional differences were observed in the splenium and uncinate fasciculus in Krabbe patients and these differences correlated only with cognitive outcomes. Regional brain volumes of Krabbe patients were slightly larger than controls. Loes scores did not correlate with DTI results. INTERPRETATION: Neonatal microstructural abnormalities correlate with neurodevelopmental treatment outcomes in patients treated for infantile Krabbe disease. DTI with quantitative tractography is an excellent biomarker for evaluating infants with Krabbe disease identified through newborn screening.

Superimposition of 3D cone-beam CT models of orthognathic surgery patients.

OBJECTIVES: To evaluate the registration of 3D models from cone-beam CT (CBCT) images taken before and after orthognathic surgery for the assessment of mandibular anatomy and position. METHODS: CBCT scans were taken before and after orthognathic surgery for ten patients with various malocclusions undergoing maxillary surgery only. 3D models were constructed from the CBCT images utilizing semi-automatic segmentation and manual editing. The cranial base was used to register 3D models of pre- and post-surgery scans (1 week). After registration, a novel tool allowed the visual and quantitative assessment of post-operative changes via 2D overlays of superimposed models and 3D coloured displacement maps. RESULTS: 3D changes in mandibular rami position after surgical procedures were clearly illustrated by the 3D colour-coded maps. The average displacement of all surfaces was 0.77 mm (SD=0.17 mm), at the posterior border 0.78 mm (SD=0.25 mm), and at the condyle 0.70 mm (SD=0.07 mm). These displacements were close to the image spatial resolution of 0.60 mm. The average interobserver differences were negligible. The range of the interobserver errors for the average of all mandibular rami surface distances was 0.02 mm (SD=0.01 mm). CONCLUSION: Our results suggest this method provides a valid and reproducible assessment of craniofacial structures for patients undergoing orthognathic surgery. This technique may be used to identify different patterns of ramus and condylar remodelling following orthognathic surgery.

Computer-assisted ankle joint arthroplasty using bio-engineered autografts.

Bio-engineered cartilage has made substantial progress over the last years. Preciously few cases, however, are known where patients were actually able to benefit from these developments. In orthopaedic surgery, there are two major obstacles between in-vitro cartilage engineering and its clinical application: successful integration of an autologuous graft into a joint and the high cost of individually manufactured implants. Computer Assisted Surgery techniques can potentially address both issues at once by simplifying the therapy, allowing pre-fabrication of bone grafts according to a shape model, individual operation planning based on CT images and providing optimal accuracy during the intervention. A pilot study was conducted for the ankle joint, comprising a simplified rotational symmetric bone surface model, a dedicated planning software and a complete cycle of treatment on one cadaveric human foot. The outcome was analysed using CT and MRI images; the post-operative CT was further segmented and registered with the implant shape to prove the feasibility of computer assisted arthroplasty using bio-engineered autografts.