A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

Personalized connectome fingerprints: Their importance in cognition from childhood to adult years.

Structural neural network architecture patterns in the human brain could be related to individual differences in phenotype, behavior, genetic determinants, and clinical outcomes from neuropsychiatric disorders. Recent studies have indicated that a personalized neural (brain) fingerprint can be identified from structural brain connectomes. However, the accuracy, reproducibility and translational potential of personalized fingerprints in terms of cognition is not yet fully determined. In this study, we introduce a dynamic connectome modeling approach to identify a critical set of white matter subnetworks that can be used as a personalized fingerprint. Several individual variable assessments were performed that demonstrate the accuracy and practicality of personalized fingerprint, specifically predicting the identity and IQ of middle age adults, and the developmental quotient in toddlers. Our findings suggest the fingerprint found by our dynamic modeling approach is sufficient for differentiation between individuals, and is also capable of predicting general intellectual ability across human development.

Mapping White Matter Microstructure in the One Month Human Brain.

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

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.