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Background: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN‐INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects. Methods: We have conducted large‐scale statistical analyses of the RDCRN‐INC database to characterize CMT1A severity across multiple metrics. Results: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age‐normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies. Interpretation: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost‐efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally. [ABSTRACT FROM AUTHOR]

Quantitative T2‐weighted MRI (T2W) interpretation is impeded by the variability of acquisition‐related features, such as field strength, coil type, signal amplification, and pulse sequence parameters. The main purpose of this work is to develop an automated method for prostate T2W intensity normalization. The procedure includes the following: (i) a deep learning‐based network utilizing MASK R‐CNN for automatic segmentation of three reference tissues: gluteus maximus muscle, femur, and bladder; (ii) fitting a spline function between average intensities in these structures and reference values; and (iii) using the function to transform all T2W intensities. The T2W distributions in the prostate cancer regions of interest (ROIs) and normal appearing prostate tissue (NAT) were compared before and after normalization using Student's t‐test. The ROIs' T2W associations with the Gleason Score (GS), Decipher genomic score, and a three‐tier prostate cancer risk were evaluated with Spearman's correlation coefficient (rS). T2W differences in indolent and aggressive prostate cancer lesions were also assessed. The MASK R‐CNN was trained with manual contours from 32 patients. The normalization procedure was applied to an independent MRI dataset from 83 patients. T2W differences between ROIs and NAT significantly increased after normalization. T2W intensities in 231 biopsy ROIs were significantly negatively correlated with GS (rS = −0.21, p = 0.001), Decipher (rS = −0.193, p = 0.003), and three‐tier risk (rS = −0.235, p < 0.001). The average T2W intensities in the aggressive ROIs were significantly lower than in the indolent ROIs after normalization. In conclusion, the automated triple‐reference tissue normalization method significantly improved the discrimination between prostate cancer and normal prostate tissue. In addition, the normalized T2W intensities of cancer exhibited a significant association with tumor aggressiveness. By improving the quantitative utilization of the T2W in the assessment of prostate cancer on MRI, the new normalization method represents an important advance over clinical protocols that do not include sequences for the measurement of T2 relaxation times. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we built clinical- and radiomics-based models to predict lesions/patients at low risk based on a combined clinical-genomic classification system. Eighty-three multi-parametric MRI exams from 78 men were analyzed. Several models for lesion classification were built using a minimal clinical variables subset and radiomic features from the lesion and normal tissues. The models were also evaluated for patient classification. In all cases, the radiomic features improved the performance. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients' risk using combined clinical-genomic classification. The utilization of multi-parametric MRI (mpMRI) in clinical decisions regarding prostate cancer patients' management has recently increased. After biopsy, clinicians can assess risk using National Comprehensive Cancer Network (NCCN) risk stratification schema and commercially available genomic classifiers, such as Decipher. We built radiomics-based models to predict lesions/patients at low risk prior to biopsy based on an established three-tier clinical-genomic classification system. Radiomic features were extracted from regions of positive biopsies and Normally Appearing Tissues (NAT) on T2-weighted and Diffusion-weighted Imaging. Using only clinical information available prior to biopsy, five models for predicting low-risk lesions/patients were evaluated, based on: 1: Clinical variables; 2: Lesion-based radiomic features; 3: Lesion and NAT radiomics; 4: Clinical and lesion-based radiomics; and 5: Clinical, lesion and NAT radiomic features. Eighty-three mpMRI exams from 78 men were analyzed. Models 1 and 2 performed similarly (Area under the receiver operating characteristic curve were 0.835 and 0.838, respectively), but radiomics significantly improved the lesion-based performance of the model in a subset analysis of patients with a negative Digital Rectal Exam (DRE). Adding normal tissue radiomics significantly improved the performance in all cases. Similar patterns were observed on patient-level models. To the best of our knowledge, this is the first study to demonstrate that machine learning radiomics-based models can predict patients' risk using combined clinical-genomic classification. [ABSTRACT FROM AUTHOR]

The recent integration of open-source data with machine learning models, especially in the medical field, has opened new doors to studying disease progression and/or regression. However, the ability to use medical data for machine learning approaches is limited by the specificity of data for a particular medical condition. In this context, the most recent technologies, like generative adversarial networks (GANs), are being looked upon as a potential way to generate high-quality synthetic data that preserve the clinical variability of a condition. However, despite some success, GAN model usage remains largely minimal when depicting the heterogeneity of a disease such as prostate cancer. Previous studies from our group members have focused on automating the quantitative multi-parametric magnetic resonance imaging (mpMRI) using habitat risk scoring (HRS) maps on the prostate cancer patients in the BLaStM trial. In the current study, we aimed to use the images from the BLaStM trial and other sources to train the GAN models, generate synthetic images, and validate their quality. In this context, we used T2-weighted prostate MRI images as training data for Single Natural Image GANs (SinGANs) to make a generative model. A deep learning semantic segmentation pipeline trained the model to segment the prostate boundary on 2D MRI slices. Synthetic images with a high-level segmentation boundary of the prostate were filtered and used in the quality control assessment by participating scientists with varying degrees of experience (more than ten years, one year, or no experience) to work with MRI images. Results showed that the most experienced participating group correctly identified conventional vs. synthetic images with 67% accuracy, the group with one year of experience correctly identified the images with 58% accuracy, and the group with no prior experience reached 50% accuracy. Nearly half (47%) of the synthetic images were mistakenly evaluated as conventional. Interestingly, in a blinded quality assessment, a board-certified radiologist did not significantly differentiate between conventional and synthetic images in the context of the mean quality of synthetic and conventional images. Furthermore, to validate the usability of the generated synthetic images from prostate cancer MRIs, we subjected these to anomaly detection along with the original images. Importantly, the success rate of anomaly detection for quality control-approved synthetic data in phase one corresponded to that of the conventional images. In sum, this study shows promise that high-quality synthetic images from MRIs can be generated using GANs. Such an AI model may contribute significantly to various clinical applications which involve supervised machine-learning approaches. [ABSTRACT FROM AUTHOR]

Background/Hypothesis: MRI-guided online adaptive radiotherapy (MRI-g-OART) improves target coverage and organs-at-risk (OARs) sparing in radiation therapy (RT). For patients with locally advanced cervical cancer (LACC) undergoing RT, changes in bladder and rectal filling contribute to large inter-fraction target volume motion. We hypothesized that deep learning (DL) convolutional neural networks (CNN) can be trained to accurately segment gross tumor volume (GTV) and OARs both in planning and daily fractions' MRI scans. Materials/Methods: We utilized planning and daily treatment fraction setup (RT-Fr) MRIs from LACC patients, treated with stereotactic body RT to a dose of 45-54 Gy in 25 fractions. Nine structures were manually contoured. MASK R-CNN network was trained and tested under three scenarios: (i) Leave-one-out (LOO), using the planning images of N- 1 patients for training; (ii) the same network, tested on the RT-Fr MRIs of the "left-out" patient, (iii) including the planning MRI of the "left-out" patient as an additional training sample, and tested on RT-Fr MRIs. The network performance was evaluated using the Dice Similarity Coefficient (DSC) and Hausdorff distances. The association between the structures' volume and corresponding DSCs was investigated using Pearson's Correlation Coefficient, r. Results: MRIs from fifteen LACC patients were analyzed. In the LOO scenario the DSC for Rectum, Femur, and Bladder was >0.8, followed by the GTV, Uterus, Mesorectum and Parametrium (0.6-0.7). The results for Vagina and Sigmoid were suboptimal. The performance of the network was similar for most organs when tested on RT-Fr MRI. Including the planning MRI in the training did not improve the segmentation of the RT-Fr MRI. There was a significant correlation between the average organ volume and the corresponding DSC (r = 0.759, p = 0.018). Conclusion: We have established a robust workflow for training MASK R-CNN to automatically segment GTV and OARs in MRI-g-OART of LACC. Albeit the small number of patients in this pilot project, the network was trained to successfully identify several structures while challenges remain, especially in relatively small organs. With the increase of the LACC cases, the performance of the network will improve. A robust auto-contouring tool would improve workflow efficiency and patient tolerance of the OART process. [ABSTRACT FROM AUTHOR]

Purpose: Develop a deep-learning-based segmentation algorithm for prostate and its peripheral zone (PZ) that is reliable across multiple MRI vendors. Methods: This is a retrospective study. The dataset consisted of 550 MRIs (Siemens-330, General Electric[GE]-220). A multistream 3D convolutional neural network is used for automatic segmentation of the prostate and its PZ using T2-weighted (T2-w) MRI. Prostate and PZ were manually contoured on axial T2‑w. The network uses axial, coronal, and sagittal T2‑w series as input. The preprocessing of the input data includes bias correction, resampling, and image normalization. A dataset from two MRI vendors (Siemens and GE) is used to test the proposed network. Six different models were trained, three for the prostate and three for the PZ. Of the three, two were trained on data from each vendor separately, and a third (Combined) on the aggregate of the datasets. The Dice coefficient (DSC) is used to compare the manual and predicted segmentation. Results: For prostate segmentation, the Combined model obtained DSCs of 0.893 ± 0.036 and 0.825 ± 0.112 (mean ± standard deviation) on Siemens and GE, respectively. For PZ, the best DSCs were from the Combined model: 0.811 ± 0.079 and 0.788 ± 0.093. While the Siemens model underperformed on the GE dataset and vice versa, the Combined model achieved robust performance on both datasets. Conclusion: The proposed network has a performance comparable to the interexpert variability for segmenting the prostate and its PZ. Combining images from different MRI vendors on the training of the network is of paramount importance for building a universal model for prostate and PZ segmentation. [ABSTRACT FROM AUTHOR]