Assessment of healthy brain maturation can be useful toward better understanding natural patterns of brain growth and toward the characterization of a variety of neurodevelopmental disorders as deviations from normal growth trajectories. Structural magnetic resonance imaging (MRI) provides excellent soft-tissue contrast, which allows for the assessment of gray and white matter in the developing brain. We performed a large-scale retrospective analysis of 993 pediatric structural brain MRI examinations of healthy subjects (n = 988, aged 0–32 years) imaged clinically at 3 T, and extracted a wide variety of measurements such as white matter volumes, cortical thickness, and gyral curvature localized to subregions of the brain. All extracted structural biomarkers were tested for their correlation with subject age at time of imaging, providing measurements that may assist in the assessment of neurological maturation. Additional analyses were also performed to assess gender-based differences in the brain at a variety of developmental stages, and to assess hemispheric asymmetries. Results add to the literature by analyzing a realistic distribution of healthy participants imaged clinically, a useful cohort toward the investigation and creation of diagnostic tests for a variety of pathologies as aberrations from healthy growth trajectories. The next generation of diagnostic tests will be responsible for identifying pathological conditions from populations of healthy clinically imaged individuals.

Major long-range white matter pathways (cingulum, fornix, uncinate fasciculus [UF], inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], thalamocortical [TC], and corpus callosal [CC] pathways) were identified in eighty-three healthy humans ranging from newborn to adult ages. We tracked developmental changes using high-angular resolution diffusion MR tractography. Fractional anisotropy (FA), apparent diffusion coefficient, number, length, and volume were measured in pathways in each subject. Newborns had fewer, and more sparse, pathways than those of the older subjects. FA, number, length, and volume of pathways gradually increased with age and reached a plateau between 3 and 5 years of age. Data were further analyzed by normalizing with mean adult values as well as with each subject’s whole brain values. Comparing subjects of 3 years old and under to those over 3 years old, the studied pathways showed differential growth patterns. The CC, bilateral cingulum, bilateral TC, and the left IFOF pathways showed significant growth both in volume and length, while the bilateral fornix, bilateral ILF and bilateral UF showed significant growth only in volume. The TC and CC took similar growth patterns with the whole brain. FA values of the cingulum and IFOF, and the length of ILF showed leftward asymmetry. The fornix, ILF and UF occupied decreased space compared to the whole brain during development with higher FA values, likely corresponding to extensive maturation of the pathways compared to the mean whole brain maturation. We believe that the outcome of this study will provide an important database for future reference.

Autism is a group of complex neurodevelopmental disorders characterized by impaired social interaction, restricted and repetitive behavior. We performed a large-scale retrospective analysis of 1,996 structural magnetic resonance imaging (MRI) examinations of the brain from 1,769 autistic and neurologically typically developing patients (aged 0-32 years), and extracted regional volumetric measurements distributed across 463 brain regions of each patient. The youngest autistic patients (<2.5 years) were diagnosed after imaging and identified retrospectively. Our study demonstrates corpus callosum volumetric abnormalities among autistic patients that are associated with brain overgrowth in early childhood (0-5 years old), followed by a shift towards known decreased volumes in later ages. Results confirm known increases in ventricular volumes among autistic populations and extends those findings to increased volumes of the choroid plexus. Our study also demonstrates distributed volumetric abnormalities among autistic patients that affect a variety of key regional white and grey matter areas of the brain potentially associated with known symptoms of autism.

Autism is a group of complex neurodevelopmental disorders characterized by impaired social interaction and restricted/repetitive behavior. We performed a large-scale retrospective analysis of 1,996 clinical neurological structural magnetic resonance imaging (MRI) examinations of 781 autistic and 988 control subjects (aged 0–32 years), and extracted regionally distributed cortical thickness measurements, including average measurements as well as standard deviations which supports the assessment of intra-regional cortical thickness variability. The youngest autistic participants (<2.5 years) were diagnosed after imaging and were identified retrospectively. The largest effect sizes and the most common findings not previously published in the scientific literature involve abnormal intra-regional variability in cortical thickness affecting many (but not all) regions of the autistic brain, suggesting irregular gray matter development in autism that can be detected with MRI. Atypical developmental patterns have been detected as early as 0 years old in individuals who would later be diagnosed with autism.

IntroductionMany neurologic and psychiatric disorders are thought to be due to, or result in, developmental errors in neuronal cerebellar connectivity. In this connectivity analysis, we studied the developmental time‐course of cerebellar peduncle pathways in pediatric and young adult subjects.MethodsA cohort of 80 subjects, newborns to young adults, was studied on a 3T MR system with 30 diffusion‐weighted measurements with high‐angular resolution diffusion imaging (HARDI) tractography.ResultsQualitative and quantitative results were analyzed for age‐based variation. In subjects of all ages, the superior cerebellar peduncle pathway (SCP) and two distinct subpathways of the middle cerebellar peduncle (MCP), as described in previous ex vivo studies, were identified in vivo with this technique: pathways between the rostral pons and inferior‐lateral cerebellum (MCP cog), associated predominantly with higher cognitive function, and pathways between the caudal pons and superior‐medial cerebellum (MCP mot), associated predominantly with motor function.DiscussionOur findings showed that the inferior cerebellar peduncle pathway (ICP), involved primarily in proprioception and balance appears to have a later onset followed by more rapid development than that exhibited in other tracts. We hope that this study may provide an initial point of reference for future studies of normal and pathologic development of cerebellar connectivity.

Down syndrome (DS) is a genetic disorder caused by an extra copy of all or part of chromosome 21 and is characterized by intellectual disability. We performed a retrospective analysis of 47 magnetic resonance imaging (MRI) examinations of participants with DS (aged 5 to 22 years) and compared them with a large cohort of 854 brain MRIs obtained from neurotypical participants (aged 5 to 32 years) with the objective of assessing the clinical presentation of Down syndrome, towards better understanding the neurological development associated with the condition. An additional cohort of 26 MRI exams from patients with DS and 139 exams from neurotypical participants (aged 0–5 years) are included as part of a supplementary analysis. Regionally distributed cortical thickness measurements, including average measurements as well as standard deviations (intra-regional cortical thickness variability) were extracted from each examination. The largest effect sizes observed were associated with increased average cortical thickness in the postcentral gyrus with specific abnormalities observed in Brodmann's areas 1 and 3b in DS, which was observed across all age ranges. We also observed strong effect sizes associated with decreased cortical thickness variability in the lateral orbitofrontal gyrus, the postcentral gyrus and more in DS participants. Findings suggest regionally irregular gray matter development in DS that can be detected with MRI.

Fractional anisotropy (FA) threshold is commonly used to perform diffusion MRI tractography. However, FA threshold may be one aspect of tractography that needs additional scrutiny in accurately assessing pathways in immature, developing brains, as well as in adult brains. Using high-angular resolution diffusion MRI (HARDI) tractography without an FA threshold, we identified the arcuate fasciculus (AF) of 83 healthy subjects ranging in age from 40 gestational weeks (GW) (newborns) to 28-year-old adults. The AF was identified in both hemispheres in all subjects with high inter-rater reliability. The detected AF included regions with very low FA values. The entire AF was segmented into anterior, posterior, and long tracts. Growth and laterality patterns were investigated using tract count (number of detected streamlines), total volume of imaging voxels (touched by the detected streamlines), mean length, mean FA, and mean apparent diffusion coefficient (ADC). Comparison of subjects under 3 years old, to those that were older, revealed the three AF tracts that took different developmental courses. As expected, the anterior and long tracts showed lower ADC values in subjects over 3 years old, while the posterior tract showed higher ADC in that same age range. The posterior tract did not show age-related effect in terms of FA, tract count, length, and volume. These results suggest that the posterior AF tract shows a matured state, indexed by most of the used measurements in early postnatal developmental ages, and ADC is a measurement that can detect further maturation of the posterior tract. Interestingly, in all tracts, hemispheric asymmetries were found in raw (leftright) tract count, as well as in raw volume (left

The insula has been implicated in playing important roles in various brain functions including consciousness, homeostasis, perception, self-awareness, language processing, and interpersonal experience. Abnormalities of the insula have been observed in patients suffering from addiction, deteriorating language function, anorexia, and emotional dysregulation. We analyzed typical development of insular connections in a large-scale pediatric population using 642 magnetic resonance imaging examinations. Interpreting large quantities of acquired data is one of the major challenges in connectomics. This article focuses its analysis on the connectivity observed between the insula and many other regions throughout the brain and performs a hemispheric asymmetry analysis comparing localized connectome measurements. Results demonstrate asymmetries in the pathways connecting the insula to the superior temporal region, pars opercularis, etc. that may be representative of language lateralization in the brain. Results also demonstrate multiple fiber pathways that exhibit hemispheric dominance in tract length and an inverted hemispheric dominance in tract counts, implying the presence of asymmetric lateralization of some of the brain's insular pathways. This study illustrates the investigative potential of performing connectomics-style analyses in a clinical context across a large population of children as part of routine imaging, demonstrating the feasibility of using current technologies to perform regionally focused clinical connectivity studies.