Deep learning-based cell segmentation for rapid optical cytopathology of thyroid cancer.

Fluorescence polarization (Fpol) imaging of methylene blue (MB) is a promising quantitative approach to thyroid cancer detection. Clinical translation of MB Fpol technology requires reduction of the data analysis time that can be achieved via deep learning-based automated cell segmentation with a 2D U-Net convolutional neural network. The model was trained and tested using images of pathologically diverse human thyroid cells and evaluated by comparing the number of cells selected, segmented areas, and Fpol values obtained using automated (AU) and manual (MA) data processing methods. Overall, the model segmented 15.8% more cells than the human operator. Differences in AU and MA segmented cell areas varied between - 55.2 and + 31.0%, whereas differences in Fpol values varied from - 20.7 and + 10.7%. No statistically significant differences between AU and MA derived Fpol data were observed. The largest differences in Fpol values correlated with greatest discrepancies in AU versus MA segmented cell areas. Time required for auto-processing was reduced to 10 s versus one hour required for MA data processing. Implementation of the automated cell analysis makes quantitative fluorescence polarization-based diagnosis clinically feasible.

Genomic loci influence patterns of structural covariance in the human brain.

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.

Imaging phenotypes predict overall survival in glioma more accurate than basic demographic and cell mutation profiles.

BACKGROUND: Magnetic resonance imaging (MRI), digital pathology imaging (PATH), demographics, and IDH mutation status predict overall survival (OS) in glioma. Identifying and characterizing predictive features in the different modalities may improve OS prediction accuracy. PURPOSE: To evaluate the OS prediction accuracy of combinations of prognostic markers in glioma patients. MATERIALS AND METHODS: Multi-contrast MRI, comprising T1-weighted, T1-weighted post-contrast, T2-weighted, T2 fluid-attenuated-inversion-recovery, and pathology images from glioma patients (n = 160) were retrospectively collected (1983-2008) from TCGA alongside age and sex. Phenotypic profiling of tumors was performed by quantifying the radiographic and histopathologic descriptors extracted from the delineated region-of-interest in MRI and PATH images. A Cox proportional hazard model was trained with the MRI and PATH features, IDH mutation status, and basic demographic variables (age and sex) to predict OS. The performance was evaluated in a split-train-test configuration using the concordance-index, computed between the predicted risk score and observed OS. RESULTS: The average age of patients was 51.2years (women: n = 77, age-range=18-84years; men: n = 83, age-range=21-80years). The median OS of the participants was 494.5 (range,3-4752), 481 (range,7-4752), and 524.5 days (range,3-2869), respectively, in complete dataset, training, and test datasets. The addition of MRI or PATH features improved prediction of OS when compared to models based on age, sex, and mutation status alone or their combination (p < 0.001). The full multi-omics model integrated MRI, PATH, clinical, and genetic profiles and predicted the OS best (c-index= 0.87). CONCLUSION: The combination of imaging, genetic, and clinical profiles leads to a more accurate prognosis than the clinical and/or mutation status.

Applications of generative adversarial networks in neuroimaging and clinical neuroscience.

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to the broader family of generative methods, which learn to generate realistic data with a probabilistic model by learning distributions from real samples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review critically appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

Atri-U: assisted image analysis in routine cardiovascular magnetic resonance volumetry of the left atrium.

BACKGROUND: Artificial intelligence can assist in cardiac image interpretation. Here, we achieved a substantial reduction in time required to read a cardiovascular magnetic resonance (CMR) study to estimate left atrial volume without compromising accuracy or reliability. Rather than deploying a fully automatic black-box, we propose to incorporate the automated LA volumetry into a human-centric interactive image-analysis process. METHODS AND RESULTS: Atri-U, an automated data analysis pipeline for long-axis cardiac cine images, computes the atrial volume by: (i) detecting the end-systolic frame, (ii) outlining the endocardial borders of the LA, (iii) localizing the mitral annular hinge points and constructing the longitudinal atrial diameters, equivalent to the usual workup done by clinicians. In every step human interaction is possible, such that the results provided by the algorithm can be accepted, corrected, or re-done from scratch. Atri-U was trained and evaluated retrospectively on a sample of 300 patients and then applied to a consecutive clinical sample of 150 patients with various heart conditions. The agreement of the indexed LA volume between Atri-U and two experts was similar to the inter-rater agreement between clinicians (average overestimation of 0.8 mL/m2 with upper and lower limits of agreement of - 7.5 and 5.8 mL/m2, respectively). An expert cardiologist blinded to the origin of the annotations rated the outputs produced by Atri-U as acceptable in 97% of cases for step (i), 94% for step (ii) and 95% for step (iii), which was slightly lower than the acceptance rate of the outputs produced by a human expert radiologist in the same cases (92%, 100% and 100%, respectively). The assistance of Atri-U lead to an expected reduction in reading time of 66%-from 105 to 34 s, in our in-house clinical setting. CONCLUSIONS: Our proposal enables automated calculation of the maximum LA volume approaching human accuracy and precision. The optional user interaction is possible at each processing step. As such, the assisted process sped up the routine CMR workflow by providing accurate, precise, and validated measurement results.

DEEPMIR: a deep neural network for differential detection of cerebral microbleeds and iron deposits in MRI.

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84-0.88 and 0.40-0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75-0.81 and 0.62-0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies.

Combining MRI and Histologic Imaging Features for Predicting Overall Survival in Patients with Glioma.

Purpose To test the hypothesis that combined features from MR and digital histopathologic images more accurately predict overall survival (OS) in patients with glioma compared with MRI or histopathologic features alone. Materials and Methods Multiparametric MR and histopathologic images in patients with a diagnosis of glioma (high- or low-grade glioma [HGG or LGG]) were obtained from The Cancer Imaging Archive (original images acquired 1983-2008). An extensive set of engineered features such as intensity, histogram, and texture were extracted from delineated tumor regions in MR and histopathologic images. Cox proportional hazard regression and support vector machine classification (SVC) models were applied to (a) MRI features only (MRIcox/svc), histopathologic features only (HistoPathcox/svc), and (c) combined MRI and histopathologic features (MRI+HistoPathcox/svc) and evaluated in a split train-test configuration. Results A total of 171 patients (mean age, 51 years ± 15; 91 men) were included with HGG (n = 75) and LGG (n = 96). Median OS was 467 days (range, 3-4752 days) for all patients, 350 days (range, 15-1561 days) for HGG, and 595 days (range, 3-4752 days) for LGG. The MRI+HistoPathcox model demonstrated higher concordance index (C-index) compared with MRIcox and HistoPathcox models on all patients (C-index, 0.79 vs 0.70 [P = .02; MRIcox] and 0.67 [P = .01; HistoPathcox]), patients with HGG (C-index, 0.78 vs 0.68 [P = .03; MRIcox] and 0.64 [P = .01; HistoPathcox]), and patients with LGG (C-index, 0.88 vs 0.62 [P = .008; MRIcox] and 0.62 [P = .006; HistoPathcox]). In binary classification, the MRI+HistoPathsvc model (area under the receiver operating characteristic curve [AUC], 0.86 [95% CI: 0.80, 0.95]) had higher performance than the MRIsvc model (AUC, 0.68 [95% CI: 0.50, 0.81]; P = .01) and the HistoPathsvc model (AUC, 0.72 [95% CI: 0.60, 0.85]; P = .04). Conclusion The model combining features from MR and histopathologic images had higher accuracy in predicting OS compared with the models with MR or histopathologic images alone. Keywords: Survival Prediction, Gliomas, Digital Pathology Imaging, MR Imaging, Machine Learning Supplemental material is available for this article.