Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome.

Background: Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is difficult to assess, and its regulation is known to involve nucleus accumbens (NAc) subregions. We investigated waiting impulsivity using the "jumping the gun" (JTG) sign, which is defined as premature initiation of clapping before the start signal in the three-clap test and compared clinical features of PSP-RS patients with and without the sign and analyzed neural connectivity and microstructural changes in NAc subregions. Materials and methods: A positive JTG sign was defined as the participant starting to clap before the start sign in the three-clap test. We classified participants into the JTG positive (JTG +) and JTG negative (JTG-) groups and compared their clinical features, microstructural changes, and connectivity between NAc subregions using diffusion tension imaging. The NAc was parcellated into core and shell subregions using data-driven connectivity-based methods. Results: Seventy-seven patients with PSP-RS were recruited, and the JTG + group had worse frontal lobe battery (FAB) scores, more frequent falls, and more occurrence of the applause sign than the JTG- group. A logistic regression analysis revealed that FAB scores were associated with a positive JTG sign. The mean fiber density between the right NAc core and right medial orbitofrontal gyrus was higher in the JTG + group than the JTG- group. Discussion: We show that the JTG sign is a surrogate marker of waiting impulsivity in PSP-RS patients. Our findings enrich the current literature by deepening our understanding of waiting impulsivity in PSP patients and introducing a novel method for its evaluation.

Tumor-Attentive Segmentation-Guided GAN for Synthesizing Breast Contrast-Enhanced MRI Without Contrast Agents.

OBJECTIVE: Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a sensitive imaging technique critical for breast cancer diagnosis. However, the administration of contrast agents poses a potential risk. This can be avoided if contrast-enhanced MRI can be obtained without using contrast agents. Thus, we aimed to generate T1-weighted contrast-enhanced MRI (ceT1) images from pre-contrast T1 weighted MRI (preT1) images in the breast. METHODS: We proposed a generative adversarial network to synthesize ceT1 from preT1 breast images that adopted a local discriminator and segmentation task network to focus specifically on the tumor region in addition to the whole breast. The segmentation network performed a related task of segmentation of the tumor region, which allowed important tumor-related information to be enhanced. In addition, edge maps were included to provide explicit shape and structural information. Our approach was evaluated and compared with other methods in the local (n = 306) and external validation (n = 140) cohorts. Four evaluation metrics of normalized mean squared error (NRMSE), Pearson cross-correlation coefficients (CC), peak signal-to-noise ratio (PSNR), and structural similarity index map (SSIM) for the whole breast and tumor region were measured. An ablation study was performed to evaluate the incremental benefits of various components in our approach. RESULTS: Our approach performed the best with an NRMSE 25.65, PSNR 54.80 dB, SSIM 0.91, and CC 0.88 on average, in the local test set. CONCLUSION: Performance gains were replicated in the validation cohort. SIGNIFICANCE: We hope that our method will help patients avoid potentially harmful contrast agents. Clinical and Translational Impact Statement-Contrast agents are necessary to obtain DCE-MRI which is essential in breast cancer diagnosis. However, administration of contrast agents may cause side effects such as nephrogenic systemic fibrosis and risk of toxic residue deposits. Our approach can generate DCE-MRI without contrast agents using a generative deep neural network. Thus, our approach could help patients avoid potentially harmful contrast agents resulting in an improved diagnosis and treatment workflow for breast cancer.

Extra-Basal Ganglia Brain Structures Are Related to Motor Reserve in Parkinson's Disease.

BACKGROUND: The "motor reserve" is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. OBJECTIVE: We investigated brain structures relevant to the motor reserve in Parkinson's disease (PD) in this study. METHODS: Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson's Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. RESULTS: We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. CONCLUSION: Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures.

Disrupted stepwise functional brain organization in overweight individuals.

Functional hierarchy establishes core axes of the brain, and overweight individuals show alterations in the networks anchored on these axes, particularly in those involved in sensory and cognitive control systems. However, quantitative assessments of hierarchical brain organization in overweight individuals are lacking. Capitalizing stepwise functional connectivity analysis, we assess altered functional connectivity in overweight individuals relative to healthy weight controls along the brain hierarchy. Seeding from the brain regions associated with obesity phenotypes, we conduct stepwise connectivity analysis at different step distances and compare functional degrees between the groups. We find strong functional connectivity in the somatomotor and prefrontal cortices in both groups, and both converge to transmodal systems, including frontoparietal and default-mode networks, as the number of steps increased. Conversely, compared with the healthy weight group, overweight individuals show a marked decrease in functional degree in somatosensory and attention networks across the steps, whereas visual and limbic networks show an increasing trend. Associating functional degree with eating behaviors, we observe negative associations between functional degrees in sensory networks and hunger and disinhibition-related behaviors. Our findings suggest that overweight individuals show disrupted functional network organization along the hierarchical axis of the brain and these results provide insights for behavioral associations.

Radiomics-guided deep neural networks stratify lung adenocarcinoma prognosis from CT scans.

Deep learning (DL) is a breakthrough technology for medical imaging with high sample size requirements and interpretability issues. Using a pretrained DL model through a radiomics-guided approach, we propose a methodology for stratifying the prognosis of lung adenocarcinomas based on pretreatment CT. Our approach allows us to apply DL with smaller sample size requirements and enhanced interpretability. Baseline radiomics and DL models for the prognosis of lung adenocarcinomas were developed and tested using local (n = 617) cohort. The DL models were further tested in an external validation (n = 70) cohort. The local cohort was divided into training and test cohorts. A radiomics risk score (RRS) was developed using Cox-LASSO. Three pretrained DL networks derived from natural images were used to extract the DL features. The features were further guided using radiomics by retaining those DL features whose correlations with the radiomics features were high and Bonferroni-corrected p-values were low. The retained DL features were subject to a Cox-LASSO when constructing DL risk scores (DRS). The risk groups stratified by the RRS and DRS showed a significant difference in training, testing, and validation cohorts. The DL features were interpreted using existing radiomics features, and the texture features explained the DL features well.

A Cascaded Neural Network for Staging in Non-Small Cell Lung Cancer Using Pre-Treatment CT.

BACKGROUND AND AIM: Tumor staging in non-small cell lung cancer (NSCLC) is important for treatment and prognosis. Staging involves expert interpretation of imaging, which we aim to automate with deep learning (DL). We proposed a cascaded DL method comprised of two steps to classification between early- and advanced-stage NSCLC using pretreatment computed tomography. METHODS: We developed and tested a DL model to classify between early- and advanced-stage using training (n = 90), validation (n = 8), and two test (n = 37, n = 26) cohorts obtained from the public domain. The first step adopted an autoencoder network to compress the imaging data into latent variables and the second step used the latent variable to classify the stages using the convolutional neural network (CNN). Other DL and machine learning-based approaches were compared. RESULTS: Our model was tested in two test cohorts of CPTAC and TCGA. In CPTAC, our model achieved accuracy of 0.8649, sensitivity of 0.8000, specificity of 0.9412, and area under the curve (AUC) of 0.8206 compared to other approaches (AUC 0.6824-0.7206) for classifying between early- and advanced-stages. In TCGA, our model achieved accuracy of 0.8077, sensitivity of 0.7692, specificity of 0.8462, and AUC of 0.8343. CONCLUSION: Our cascaded DL model for classification NSCLC patients into early-stage and advanced-stage showed promising results and could help future NSCLC research.

Are radiomics features universally applicable to different organs?

BACKGROUND: Many studies have successfully identified radiomics features reflecting macroscale tumor features and tumor microenvironment for various organs. There is an increased interest in applying these radiomics features found in a given organ to other organs. Here, we explored whether common radiomics features could be identified over target organs in vastly different environments. METHODS: Four datasets of three organs were analyzed. One radiomics model was constructed from the training set (lungs, n = 401), and was further evaluated in three independent test sets spanning three organs (lungs, n = 59; kidneys, n = 48; and brains, n = 43). Intensity histograms derived from the whole organ were compared to establish organ-level differences. We constructed a radiomics score based on selected features using training lung data over the tumor region. A total of 143 features were computed for each tumor. We adopted a feature selection approach that favored stable features, which can also capture survival. The radiomics score was applied to three independent test data from lung, kidney, and brain tumors, and whether the score could be used to separate high- and low-risk groups, was evaluated. RESULTS: Each organ showed a distinct pattern in the histogram and the derived parameters (mean and median) at the organ-level. The radiomics score trained from the lung data of the tumor region included seven features, and the score was only effective in stratifying survival for other lung data, not in other organs such as the kidney and brain. Eliminating the lung-specific feature (2.5 percentile) from the radiomics score led to similar results. There were no common features between training and test sets, but a common category of features (texture category) was identified. CONCLUSION: Although the possibility of a generally applicable model cannot be excluded, we suggest that radiomics score models for survival were mostly specific for a given organ; applying them to other organs would require careful consideration of organ-specific properties.

Machine learning-based automated classification of headache disorders using patient-reported questionnaires.

Classification of headache disorders is dependent on a subjective self-report from patients and its interpretation by physicians. We aimed to apply objective data-driven machine learning approaches to analyze patient-reported symptoms and test the feasibility of the automated classification of headache disorders. The self-report data of 2162 patients were analyzed. Headache disorders were merged into five major entities. The patients were divided into training (n = 1286) and test (n = 876) cohorts. We trained a stacked classifier model with four layers of XGBoost classifiers. The first layer classified between migraine and others, the second layer classified between tension-type headache (TTH) and others, and the third layer classified between trigeminal autonomic cephalalgia (TAC) and others, and the fourth layer classified between epicranial and thunderclap headaches. Each layer selected different features from the self-reports by using least absolute shrinkage and selection operator. In the test cohort, our stacked classifier obtained accuracy of 81%, sensitivity of 88%, 69%, 65%, 53%, and 51%, and specificity of 95%, 55%, 46%, 48%, and 51% for migraine, TTH, TAC, epicranial headache, and thunderclap headaches, respectively. We showed that a machine-learning based approach is applicable in analyzing patient-reported questionnaires. Our result could serve as a baseline for future studies in headache research.

DEEP NETWORK-BASED FEATURE SELECTION FOR IMAGING GENETICS: APPLICATION TO IDENTIFYING BIOMARKERS FOR PARKINSON'S DISEASE.

Imaging genetics is a methodology for discovering associations between imaging and genetic variables. Many studies adopted sparse models such as sparse canonical correlation analysis (SCCA) for imaging genetics. These methods are limited to modeling the linear imaging genetics relationship and cannot capture the non-linear high-level relationship between the explored variables. Deep learning approaches are underexplored in imaging genetics, compared to their great successes in many other biomedical domains such as image segmentation and disease classification. In this work, we proposed a deep learning model to select genetic features that can explain the imaging features well. Our empirical study on simulated and real datasets demonstrated that our method outperformed the widely used SCCA method and was able to select important genetic features in a robust fashion. These promising results indicate our deep learning model has the potential to reveal new biomarkers to improve mechanistic understanding of the studied brain disorders.

Demographic and Practice Characteristics of Physicians Who Care for Medically Underserved People: A National Survey.

OBJECTIVES: Few national studies have examined the influence of role models as a potential predictor for caring for medically underserved (MUS) patients. This study tested associations between previous physician role model exposure and caring for MUS populations, as well as examines the practice environments of these physicians. METHODS: Between October and December 2011, we mailed a confidential questionnaire to a representative sample of 2000 US physicians from various specialties. The primary criterion variable was "Is your patient population considered medically underserved?" We assessed demographic and other personal characteristics (calling, spirituality, and reporting a familial role model). We also asked about their practice characteristics, including a validated measure that assessed whether their work environment was considered chaotic/hectic or calm. RESULTS: The survey response rate was 64.5% (1289/2000). Female physicians and African American physicians were more likely to report working in MUS settings (multivariate odds ratio [OR] 1.32, confidence interval [CI] 1.00-1.76 and OR 2.65, CI 1.28-5.46, respectively). Physicians with high spirituality (OR 1.69, CI 1.02-2.79) and who reported familial role model exposure (OR 1.91, CI 1.11-3.30) also were associated with working with MUS populations. Physicians who worked in academic medical centers (OR 1.93, CI 1.45-2.56) and in chaotic work environments (OR 3.25, CI 1.64-6.44) also were more likely to report working with MUS patients. CONCLUSIONS: Familial role models may be influencing physicians to work with MUS patients, but the quality of their current work environments raises concerns about the long-term retention of physicians in MUS settings.