Autism-associated brain differences can be observed in utero using MRI.

Developmental changes that occur before birth are thought to be associated with the development of autism spectrum disorders. Identifying anatomical predictors of early brain development may contribute to our understanding of the neurobiology of autism spectrum disorders and allow for earlier and more effective identification and treatment of autism spectrum disorders. In this study, we used retrospective clinical brain magnetic resonance imaging data from fetuses who were diagnosed with autism spectrum disorders later in life (prospective autism spectrum disorders) in order to identify the earliest magnetic resonance imaging-based regional volumetric biomarkers. Our results showed that magnetic resonance imaging-based autism spectrum disorder biomarkers can be found as early as in the fetal period and suggested that the increased volume of the insular cortex may be the most promising magnetic resonance imaging-based fetal biomarker for the future emergence of autism spectrum disorders, along with some additional, potentially useful changes in regional volumes and hemispheric asymmetries.

Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography.

Lissencephaly (LIS) is a rare neurodevelopmental disorder with severe symptoms caused by abnormal neuronal migration during cortical development. It is caused by both genetic and non-genetic factors. Despite frequent studies about the cortex, comprehensive elucidation of structural abnormalities and their effects on the white matter is limited. The main objective of this study is to analyze abnormal neuronal migration pathways and white matter fiber organization in LIS1-associated LIS using diffusion MRI (dMRI) tractography. For this purpose, slabs of brain specimens with LIS (n = 3) and age and sex-matched controls (n = 4) were scanned with 3T dMRI. Our high-resolution ex vivo dMRI successfully identified common abnormalities across the samples. The results revealed an abnormal increase in radially oriented subcortical fibers likely associated with radial migration pathways and u-fibers and a decrease in association fibers in all LIS specimens.

Nonmetric Variants of Anatolian Crania: A Preliminary Study.

Analysis of nonmetric cranial variants has been essential for identifying the human population through osteologic analysis and genetic affinities. This study aimed to examine the nonmetric cranial variants to evaluate differences among sex and side correlations in Anatolian dry skulls. This study was carried out on 50 Anatolian adult dry human skulls (22 males, 28 females) with suitable features (nonfractured and/or with necessary features) out of a total of 97 dry skulls. After sex analysis, each skull was photographed from the norma frontalis, lateralis, inferior, and superior. Eleven nonmetrical cranial variants were investigated. The cranial variants and side incidences were analyzed to determine their sex differences and interside correlations. After the classification, traits were marked as "present" or "absent" on the charts. Some variants in female crania were seen more frequently than in males. Most of the variants such as the supraorbital notch, infraorbital and zygomaticofacial foramen, showed high correlations between the right and left sides. Overall, there were no statistically significant sex or side differences found in the Anatolian crania.

Comprehensive Volumetric Analysis of Mecp2-Null Mouse Model for Rett Syndrome by T2-Weighted 3D Magnetic Resonance Imaging.

Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the Mecp2 gene-deleted RTT model (Mecp2-KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of Mecp2-KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the Mecp2-deficient brain. Our analysis also revealed that the Mecp2-deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT.

Preoperative and postoperative high angular resolution diffusion imaging tractography of cerebellar pathways in posterior fossa tumors.

This study aimed to utilize high angular resolution diffusion magnetic resonance imaging (HARDI) tractography in the mapping of the pathways of the cerebellum associated with posterior fossa tumors (infratentorial neoplasms) and to determine whether it is useful for preoperative and postoperative evaluation. Retrospective data from 30 patients (age 2-16 yr) with posterior fossa tumor (17 low grade, 13 high grade) and 30 age-sex-matched healthy controls were used. Structural and diffusion-weighted images were collected at a 3-tesla scanner. Tractography was performed using Diffusion Toolkit software, Q-ball model, FACT algorithm, and angle threshold of 45 degrees. Manually assessed regions of interest were placed to identify reconstructed fiber pathways passing through the superior, medial, and inferior cerebellar peduncles for the preoperative, postoperative, and healthy control groups. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and track volume measures were obtained and analyzed. Statistically significant differences were found between the preop/postop, preop/control, and postop/control comparisons for the volume of the tracts in both groups. Displacement and disruption of the pathways seemed to differ in relation to the severity of the tumor. The loss of pathways after the operation was associated with selective resection during surgery due to tumor infiltration. There were no FA differences but significantly higher ADC in low-grade tumors, and no difference in both FA and ADC in high-grade tumors. The effects of posterior fossa tumors on cerebellar peduncles and reconstructed pathways were successfully evaluated by HARDI tractography. The technique appears to be useful not only for preoperative but also for postoperative evaluation.

Integration of structural MRI and epigenetic analyses hint at linked cellular defects of the subventricular zone and insular cortex in autism: Findings from a case study.

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, communication and repetitive, restrictive behaviors, features supported by cortical activity. Given the importance of the subventricular zone (SVZ) of the lateral ventrical to cortical development, we compared molecular, cellular, and structural differences in the SVZ and linked cortical regions in specimens of ASD cases and sex and age-matched unaffected brain. Methods: We used magnetic resonance imaging (MRI) and diffusion tractography on ex vivo postmortem brain samples, which we further analyzed by Whole Genome Bisulfite Sequencing (WGBS), Flow Cytometry, and RT qPCR. Results: Through MRI, we observed decreased tractography pathways from the dorsal SVZ, increased pathways from the posterior ventral SVZ to the insular cortex, and variable cortical thickness within the insular cortex in ASD diagnosed case relative to unaffected controls. Long-range tractography pathways from and to the insula were also reduced in the ASD case. FACS-based cell sorting revealed an increased population of proliferating cells in the SVZ of ASD case relative to the unaffected control. Targeted qPCR assays of SVZ tissue demonstrated significantly reduced expression levels of genes involved in differentiation and migration of neurons in ASD relative to the control counterpart. Finally, using genome-wide DNA methylation analyses, we identified 19 genes relevant to neurological development, function, and disease, 7 of which have not previously been described in ASD, that were significantly differentially methylated in autistic SVZ and insula specimens. Conclusion: These findings suggest a hypothesis that epigenetic changes during neurodevelopment alter the trajectory of proliferation, migration, and differentiation in the SVZ, impacting cortical structure and function and resulting in ASD phenotypes.

Small Nucleus Accumbens and Large Cerebral Ventricles in Infants and Toddlers Prior to Receiving Diagnoses of Autism Spectrum Disorder.

Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42-50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children's Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD.

Symptom-Related Differential Neuroimaging Biomarkers in Children with Corpus Callosum Abnormalities.

We aimed to identify symptom-related neuroimaging biomarkers for patients with dysgenesis of the corpus callosum (dCC) by summarizing neurological symptoms reported in clinical evaluations and correlating them with retrospectively collected structural/diffusion brain magnetic resonance imaging (MRI) measures from 39 patients/controls (mean age 8.08 ± 3.98). Most symptoms/disorders studied were associated with CC abnormalities. Total brain (TB) volume was related to language, cognition, muscle tone, and metabolic/endocrine abnormalities. Although white matter (WM) volume was not related to symptoms studied, gray matter (GM) volume was related to cognitive, behavioral, and metabolic/endocrine disorders. Right hemisphere (RH) cortical thickness (CT) was linked to language abnormalities, while left hemisphere (LH) CT was linked to epilepsy. While RH gyrification index (GI) was not related to any symptoms studied, LH GI was uniquely related to cognitive disorders. Between patients and controls, GM volume and LH/RH CT were significantly greater in dCC patients, while WM volume and LH/RH GI were significantly greater in controls. TB volume and diffusion indices for tissue microstructures did not show differences between the groups. In summary, our brain MRI-based measures successfully revealed differential links to many symptoms. Specifically, LH GI abnormality can be a predictor for dCC patients, which is uniquely associated with the patients' symptom. In addition, patients with CC abnormalities had normal TB volume and overall tissue microstructures, with potentially deteriorated mechanisms to expand/fold the brain, indicated by GI.

A Dissectional Study of the Level of Anterior Commissure of the Larynx.

PURPOSE: Precise knowledge of the level of the vocal fold as projected on the external thyroid cartilage is of critical importance for the performance of many surgical approaches. This study aims to identify the level of the anterior commissure, as well as the lengths of the vocal muscle and arytenoid cartilage in Turkish population. MATERIALS AND METHOD: Specimens were collected after autopsy from the Council of Forensic Medicine. One hundred human larynges (52 men, 48 women; age range: 25-80 years) were dissected under a stereomicroscope. Projection of the vocal fold was analyzed in relation to the superior thyroid (A) and the inferior border of the thyroid cartilage (B). Then, the larynx was dissected parallel to the level of the vocal fold to measure the length of the vocal muscle (C) and the length of the interarytenoid space (D). RESULTS: The mean value of the "a" was 9.15 ± 1.99 mm in male and 9.38 ± 3.43 mm in female. Mean value of the "b" was 10.54 ± 1.73 mm and 8.88 ± 1.81 mm in male and female, respectively. The mean value of the parameter corresponding the length of vocal muscle which was "c" was found 15.00 ± 3.18 mm in male and 12.88 ± 4.12 mm in female. The mean value of the interarytenoid space "d" was 8.31 ± 1.76 mm in male and 8.13 ± 1.90 mm in female. Comparing between genders, no statistical differences were observed in parameters of a, c, d, a + b, a + b/2 (P > .05). However, the difference with female and male for the parameters of b and c + d was statistically significant (P < .05). CONCLUSION: Our results indicate that the anterior commissure projects slightly above the midline height for male and at the level to slightly below in female subjects in Turkish population.

Tracing the papier mache anatomical models of Ottoman Turkish medicine and Louis Thomas Jerôme Auzoux.

Papier-mâché means chewed paper, and it defines a method. Various decorative products and functional tools have been produced with this method, which includes various techniques and materials. Maybe, the most interesting one among these is anatomic models developed and spread around the world by the French physician Louis Thomas Jerôme Auzoux (1797-1880) at the beginning of the nineteenth century. The purpose of this paper is to investigate the role of Dr Auzoux' human anatomical models in Ottoman-Turkish medicine. Primary and secondary sources were analysed such as Museum collections, archives, and scientific databases accessible on the Internet. This revealed that, at the beginning of the 1820s, Dr. Auzoux developed the method for papier-mâché anatomical models after a period of suffering difficulties in finding and preserving cadavers for dissection at the medical faculty which he worked. In 1825, he completed his invention, which had significant advantages over previously used methods for anatomical models, and then founded a production workshop in St. Aubin. Many medical schools in Europe, Africa, and South America utilised these models. Sources mentioned that the Ottoman Empire also purchased various anatomical models. Although it is not exactly known how many and from which models, it is known that whole male and female body models and pregnancy developmental models were purchased in 1837. In addition to human anatomic models, Dr. Auzoux's company also began to manufacture veterinary and botanical models soon. In that period of the Ottoman Empire during which cadaver dissection was forbidden and only artificial models and drawings were used for the education, Auzoux's models can be considered as very important tools for the Turkish Ottoman medical education and influential on the transition from traditional to modern medicine. Today, unfortunately, the fate of most of the human anatomical models purchased in the name of the Ottoman Empire is not known.

Does cigarette smoke exposure lead to histopathological alterations in the olfactory epithelium? An electron microscopic study on a rat model.

OBJECTIVE: This study was conducted to examine the influence of smoke exposure of variable duration on the ultrastructure of and histopathologic and morphologic alterations in the olfactory epithelium. METHODS: A total of 24 Wistar albino rats were randomly assigned to three groups and fed a standard rat chow and tap water. Experimental rats in groups I and II were exposed to cigarette smoke in a glass cabin over a period of 2 months for 5 or 15 min, respectively, four times daily; control rats (group III) were not exposed to cigarette smoke. After dissection, all tissue specimens were processed using routine procedures for TEM. RESULTS: Groups I and II exhibited the presence of intraepithelial inflammatory cells and especially deep invaginations in the nuclear membrane of supporting cells. Extended intercellular spaces, cytoplasmic protrusions on the apical surface of supporting cells, atrophy of microvilli and olfactory neuron cilia as well as numerous electron-dense granular structures and lysosome-like structures were observed to an increasing degree from group I to group II. Particularly in group II, both supporting cells and olfactory neurons exhibited a cytoplasmic edema, mitochondrial degeneration, and numerous vacuolar structures, as well as apoptotic and minimal necrotic changes. In this group, hyperplasia of basal cells was also observed. CONCLUSION: Our electron microscopic findings show that cigarette smoke leads to toxic degenerative changes in the rat olfactory mucosa.