Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain.
Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females.
HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease.
A robust multi-modal tool, for automated registration, bias correction, and tissue classification, has been implemented for large-scale heterogeneous multi-site longitudinal MR data analysis. This work focused on improving the an iterative optimization framework between bias-correction, registration, and tissue classification inspired from previous work. The primary contributions are robustness improvements from incorporation of following four elements: (1) utilize multi-modal and repeated scans, (2) incorporate high-deformable registration, (3) use extended set of tissue definitions, and (4) use of multi-modal aware intensity-context priors. The benefits of these enhancements were investigated by a series of experiments with both simulated brain data set (BrainWeb) and by applying to highly-heterogeneous data from a 32 site imaging study with quality assessments through the expert visual inspection. The implementation of this tool is tailored for, but not limited to, large-scale data processing with great data variation with a flexible interface. In this paper, we describe enhancements to a joint registration, bias correction, and the tissue classification, that improve the generalizability and robustness for processing multi-modal longitudinal MR scans collected at multi-sites. The tool was evaluated by using both simulated and simulated and human subject MRI images. With these enhancements, the results showed improved robustness for large-scale heterogeneous MRI processing.
Multicenter longitudinal neuroimaging has great potential to provide efficient and consistent biomarkers for research of neurodegenerative diseases and aging. In rare disease studies it is of primary importance to have a reliable tool that performs consistently for data from many different collection sites to increase study power. A multi-atlas labeling algorithm is a powerful brain image segmentation approach that is becoming increasingly popular in image processing. The present study examined the performance of multi-atlas labeling tools for subcortical identification using two types of in-vivo image database: Traveling Human Phantom (THP) and PREDICT-HD. We compared the accuracy (Dice Similarity Coefficient; DSC and intraclass correlation; ICC), multicenter reliability (Coefficient of Variance; CV), and longitudinal reliability (volume trajectory smoothness and Akaike Information Criterion; AIC) of three automated segmentation approaches: two multi-atlas labeling tools, MABMIS and MALF, and a machine-learning-based tool, BRAINSCut. In general, MALF showed the best performance (higher DSC, ICC, lower CV, AIC, and smoother trajectory) with a couple of exceptions. First, the results of accumben, where BRAINSCut showed higher reliability, were still premature to discuss their reliability levels since their validity is still in doubt (DSC < 0.7, ICC < 0.7). For caudate, BRAINSCut presented slightly better accuracy while MALF showed significantly smoother longitudinal trajectory. We discuss advantages and limitations of these performance variations and conclude that improved segmentation quality can be achieved using multi-atlas labeling methods. While multi-atlas labeling methods are likely to help improve overall segmentation quality, caution has to be taken when one chooses an approach, as our results suggest that segmentation outcome can vary depending on research interest.
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