Fetal cerebellar development: 3D morphometric analysis of fetal postmortem MRI among Chinese fetuses.

The development of the cerebellum starts from early gestational period and extends postnatal. Because of its protracted development, the cerebellum is susceptible to developmental anomalies such as Dandy-Walker malformations, Blakes pouch cysts and vermin hypoplasia. Measurements of fetal cerebellar parameters of a normal growing fetus in each week of gestation is important for setting up morphometric standards and hence used as clinical reference data. Any deviation from the normal cerebellar parameters alerts the clinicians for the possibility of presence of cerebellar malformations. Study objective: The objective of this study was to assess the fetal cerebellar growth by quantifying the following parameters; fetal cerebellar volume, anterior-posterior diameter and superior-inferior diameter. Methods: We used 3T and 7T MRI to scan the postmortem fetal brains at different stages of development and subsequently analyze the images using ITK-SNAP software. Results: The mean superior-inferior cerebellar diameter was found to be 19.12+2. 70mm.The linear(y=bo+b1t) model was the best fit (r2=0.996, F=32022.961) to describe the relationship between the gestational age and the superior-inferior diameter(y=5.89+0.49t). There was significant correlation between the superior-inferior cerebellar diameter and the gestation age, Pearson correlation coefficient of 0.999, r=0.001. The median cerebellar volume was 8607.7mm, the mean rank high among males(78.12) as compared to female(68.25). There was no statistically significant difference of the cerebellar volume between males and females (u=2193.5,p=0.16). The quadratic(y=bo+b1t+b2t2) model was the best fit regression equation (r2=0.994,F=10791.157) describing the relationship between the cerebellar volume and the gestational age. The median anterior-posterior diameter was 12.45 mm. There was significant correlation between anterior-posterior diameter and the gestational age with Spearmans rho of (0.997, p=0.01). The linear model was the best fit the best fit model (y=bo+b1t) describing the relationship between anterior-posterior diameter and the gestational age(y=3.31+0.5t) r2=0.998, F=70646.838. Conclusion: Significant correlation between the superior-inferior cerebellar diameters, the anterior-posterior cerebellar diameter and the gestational age was found. These two linear parameters follow the first-degree polynomial in relation to the gestational age. The cerebellar volume follows the second-degree polynomial as it increases with the gestational age and correlate significantly with the gestational age. This study has provided new insight to the development of the cerebellum, and setup a benchmark data of which the deviation from it will alert the clinicians for the possibility of presence of cerebellar malformations. Key words: Cerebellar Development, Cranial Magnetic Resonance imaging, Cerebellar Malformations

Regional Cerebellar Volume Loss Predicts Future Disability in Multiple Sclerosis Patients

Cerebellar symptoms in multiple sclerosis (MS) are well described; however, the exact contribution of cerebellar damage to MS disability has not been fully explored. Longer-term observational periods are necessary to better understand the dynamics of pathological changes within the cerebellum and their clinical consequences. Cerebellar lobe and single lobule volumes were automatically segmented on 664 3D-T1-weighted MPRAGE scans (acquired at a single 1.5 T scanner) of 163 MS patients (111 women; mean age: 47.1 years; 125 relapsing–remitting (RR) and 38 secondary progressive (SP) MS, median EDSS: 3.0) imaged annually over 4 years. Clinical scores (EDSS, 9HPT, 25FWT, PASAT, SDMT) were determined per patient per year with a maximum clinical follow-up of 11 years. Linear mixed-effect models were applied to assess the association between cerebellar volumes and clinical scores and whether cerebellar atrophy measures may predict future disability progression. SPMS patients exhibited faster posterior superior lobe volume loss over time compared to RRMS, which was related to increase of EDSS over time. In RRMS, cerebellar volumes were significant predictors of motor scores (e.g. average EDSS, T25FWT and 9HPT) and SDMT. Atrophy of motor-associated lobules (IV-VI + VIII) was a significant predictor of future deterioration of the 9HPT of the non-dominant hand. In SPMS, the atrophy rate of the posterior superior lobe (VI + Crus I) was a significant predictor of future PASAT performance deterioration. Regional cerebellar volume reduction is associated with motor and cognitive disability in MS and may serve as a predictor for future disease progression, especially of dexterity and impaired processing speed.

Decreased brain volumes in infants with prenatal opioid exposure

Background/Objective: Previous small studies have shown that prenatal opioid-exposed (POE) infants and older children display decreased cerebral, cerebellar, or subcortical brain volumes. However, these studies are plagued by suboptimal reference standards or were unable to correct for the influence of other environmental factors in older children. Therefore, our goal was to study differences in brain volume of POE infants when compared to a geographically matched population. We hypothesized that there will be a significant decrease in total brain volume of the POE infants in comparison to the non-opioid exposed control infants, including a reduction in the cerebellar volume. Methods: This was an IRB approved prospective study of mothers and infants with POE and controls without POE. All recruited infants underwent MRI scans of the brain before they reached a corrected age of 2 months. The T1-weighted MRI images were analyzed by Infant FreeSurfer and segmented into ROIs. The segmentations were manually checked and edited. An ANOVA analysis was performed to compare the cerebellar and total brain volume datasets. We corrected for gender, corrected gestational age at MRI scan, and total brain volume where necessary. Results: 42 infants were included in the study, 21 with POE and 21 control infants. There was a significant difference in the mean gestational age of POE infants (38.28±2.13) compared to control infants (39.42±0.72). On quantitative analysis, the POE group had a significantly reduced total brain and supratentorial volume in comparison to the controls. The cerebellar volume was also significantly smaller in POE, but this significance did not persist when the total brain volume was included in the model. Conclusion: The supratentorial region is affected disproportionately more than the cerebellum in POE. Specific reductions in cortical, subcortical, and white matter volume need to be further investigated and their influence on developmental outcomes need to be studied.

Identifying genetic variants associated with cerebellar volume in 33,265 individuals from the UK-Biobank

There is expanding interest in researching the cerebellum given accumulating evidence of its important contributions to cognitive and emotional functions, in addition to more established sensorimotor roles. While large genome-wide association studies (GWAS) have shed light on the common allele architecture of cortical and subcortical brain structures, the cerebellum remains under investigated. We conducted a meta-GWAS of cerebellar volume in 33,265 UK-Biobank European participants. Results show cerebellar volume to be moderately heritable (h2SNP=50.6%). We identified 33 independent genome-wide associated SNPs with total cerebellar volume, with 6 of these SNPs mapped to protein-coding genes and 5 more shown to alter cerebellar gene expression. We highlight 21 unique candidate genes for follow-up analysis. Cerebellar volume showed significant genetic correlation with brainstem, pallidum and thalamus volumes, but no significant correlations with neuropsychiatric phenotypes. Our results provide important new knowledge of the genetic architecture of cerebellar volume and its relationship with other brain phenotypes.