Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.
In diseases such as cancer, patients suffer from degenerative loss of skeletal muscle (cachexia). Muscle wasting and loss of muscle function/performance (sarcopenia) can also occur during advanced aging. Assessing skeletal muscle mass in sarcopenia and cachexia is therefore of clinical interest for risk stratification. In comparison with fat, body fluids and bone, quantifying the skeletal muscle mass is more challenging. Computed tomography (CT) is one of the gold standard techniques for cancer diagnostics and analysis of progression, and therefore a valuable source of imaging for in vivo quantification of skeletal muscle mass. In this paper, we design a novel deep neural network-based algorithm for the automated segmentation of skeletal muscle in axial CT images at the third lumbar (L3) and the fourth thoracic (T4) levels. A two-branch network with two training steps is investigated. The network's performance is evaluated for three trained models on separate datasets. These datasets were generated by different CT devices and data acquisition settings. To ensure the model's robustness, each trained model was tested on all three available test sets. Errors and the effect of labeling protocol in these cases were analyzed and reported. The best performance of the proposed algorithm was achieved on 1327 L3 test samples with an overlap Jaccard score of 98% and sensitivity and specificity greater than 99%.
Background Body composition from computed tomography (CT) scans is associated with cancer outcomes including surgical complications, chemotoxicity, and survival. Most studies manually segment CT scans, but Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) software automatically segments muscle and adipose tissues to speed analysis. Here, we externally evaluate ABACS in an independent dataset. Methods Among patients with non-metastatic colorectal (n = 3102) and breast (n = 2888) cancer diagnosed from 2005 to 2013 at Kaiser Permanente, expert raters annotated tissue areas at the third lumbar vertebra (L3). To compare ABACS segmentation results to manual analysis, we quantified the proportion of pixel-level image overlap using Jaccard scores and agreement between methods using intra-class correlation coefficients for continuous tissue areas. We examined performance overall and among subgroups defined by patient and imaging characteristics. To compare the strength of the mortality associations obtained from ABACS's segmentations to manual analysis, we computed Cox proportional hazards ratios (HRs) and 95% confidence intervals (95% CI) by tertile of tissue area. Results Mean ± SD age was 63 ± 11 years for colorectal cancer patients and 56 ± 12 for breast cancer patients. There was strong agreement between manual and automatic segmentations overall and within subgroups of age, sex, body mass index, and cancer stage: average Jaccard scores and intra-class correlation coefficients exceeded 90% for all tissues. ABACS underestimated muscle and visceral and subcutaneous adipose tissue areas by 1-2% versus manual analysis: mean differences were small at À2.35, À1.97 and À2.38 cm 2 , respectively. ABACS's performance was lowest for the <2% of patients who were underweight or had anatomic abnormalities. ABACS and manual analysis produced similar associations with mortality; comparing the lowest to highest tertile of skeletal muscle from ABACS versus manual analysis, the HRs were 1.23 (95% CI: 1.00-1.52) versus 1.38 (95% CI: 1.11-1.70) for colorectal cancer patients and 1.30 (95% CI: 1.01-1.66) versus 1.29 (95% CI: 1.00-1.65) for breast cancer patients. Conclusions In the first study to externally evaluate a commercially available software to assess body composition, automated segmentation of muscle and adipose tissues using ABACS was similar to manual analysis and associated with mortality after non-metastatic cancer. Automated methods will accelerate body composition research and, eventually, facilitate integration of body composition measures into clinical care.
When analyzing large multicenter databases, the effects of multiple confounding covariates increase the variability in the data and may reduce the ability to detect changes due to the actual effect of interest, for example, changes due to disease. Efficient ways to evaluate the effect of covariates toward the data harmonization are therefore important. In this article, we showcase techniques to assess the "goodness of harmonization" of covariates. We analyze 7,656 MR images in the multisite, multiscanner Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We present a comparison of three methods for estimating total intracranial volume to assess their robustness and correct the brain structure volumes using the residual method and the proportional (normalization by division) method. We then evaluated the distribution of brain structure volumes over the entire ADNI database before and after accounting for multiple covariates such as total intracranial volume, scanner field strength, sex, and age using two techniques: (a) Zscapes, a panoramic visualization technique to analyze the entire database and (b) empirical cumulative distributions functions. The results from this study highlight the importance of assessing the goodness of data harmonization as a necessary preprocessing step when pooling large data set with multiple covariates, prior to further statistical data analysis. K E Y W O R D Sdata harmonization, field strength, LDDMM, magnetic resonance imaging, multi-atlas fusion, total intracranial volume
Brain volume measurements extracted from structural MRI data sets are a widely accepted neuroimaging biomarker to study mouse models of neurodegeneration. Whether to acquire and analyze data in vivo or ex vivo is a crucial decision during the phase of experimental designs, as well as data analysis. In this work, we extracted the brain structures for both longitudinal in vivo and single-time-point ex vivo MRI acquired from the same animals using accurate automatic multi-atlas structural parcellation, and compared the corresponding statistical and classification analysis. We found that most gray matter structures volumes decrease from in vivo to ex vivo, while most white matter structures volume increase. The level of structural volume change also varies between different genetic strains and treatment. In addition, we showed superior statistical and classification power of ex vivo data compared to the in vivo data, even after resampled to the same level of resolution. We further demonstrated that the classification power of the in vivo data can be improved by incorporating longitudinal information, which is not possible for ex vivo data. In conclusion, this paper demonstrates the tissue-specific changes, as well as the difference in statistical and classification power, between the volumetric analysis based on the in vivo and ex vivo structural MRI data. Our results emphasize the importance of longitudinal analysis for in vivo data analysis.
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