Predictors of Complicated Disease Course in Children and Adults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN.

BACKGROUND: Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC. METHODS: Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together. RESULTS: A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course. CONCLUSION: In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.

Prognostic factors of complicated disease course are vital for clinical decision-making of early escalation to intensive treatment. In this nationwide cohort, one-third of children and one-fifth of adults with UC developed complicated disease course. Disease course was predicted particularly by routinely collected laboratory tests, age, extraintestinal manifestations, and type of induction therapy at diagnosis.

Familial Mediterranean fever in patients with inflammatory bowel diseases: A nationwide study from the epi-IIRN.

BACKGROUND AND AIMS: Inflammatory Bowel Diseases (IBD) and Familial Mediterranean Fever (FMF) are auto-inflammatory diseases with common clinical and biological features. We aimed to determine their association and characterize the natural history in patients with both diagnoses. METHODS: Utilizing data from the epi-IIRN cohort, which includes 98% of Israel's population, we calculated the adjusted prevalence of FMF among IBD patients vs non-IBD controls. Case ascertainment of IBD was determined according to validated algorithms and for FMF by ICD-9 codes and colchicine purchase. RESULTS: In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 602 matched controls. Among IBD patients, 157 (0.5%) had FMF compared with 160 (0.2%) of non-IBD controls (OR = 2.68 [95%CI 2.2-3.3]; p< 0.001). Pediatric-onset IBD had a higher prevalence of FMF compared with adult-onset IBD (30/5,243 [0.6%] vs 127/29 132 [0.4%]), without statistical significanse (OR = 1.31 [0.88-1.96]; p= 0.2). FMF was more prevalent in CD (114/19 264 [0.6%]) than UC (43/15 111 [0.3%]; OR = 2.1 [1.5-3.0]), p< 0.001). FMF diagnosis preceded that of IBD in 130/157 cases (83%). FMF was associated with a more severe disease activity in UC patients at diagnosis, but not in CD patients. Outcomes were comparable between patients with CD+FMF vs CD alone; however in patients with UC+FMF, time to biologic treatment was shorter. CONCLUSION: FMF is more prevalent in IBD patients than in the general population, particularly in CD. The diagnosis of FMF precedes the diagnosis of IBD in most cases, and may be associated with a more severe course in UC.

LUNet: deep learning for the segmentation of arterioles and venules in high resolution fundus images.

Objective.This study aims to automate the segmentation of retinal arterioles and venules (A/V) from digital fundus images (DFI), as changes in the spatial distribution of retinal microvasculature are indicative of cardiovascular diseases, positioning the eyes as windows to cardiovascular health.Approach.We utilized active learning to create a new DFI dataset with 240 crowd-sourced manual A/V segmentations performed by 15 medical students and reviewed by an ophthalmologist. We then developed LUNet, a novel deep learning architecture optimized for high-resolution A/V segmentation. The LUNet model features a double dilated convolutional block to widen the receptive field and reduce parameter count, alongside a high-resolution tail to refine segmentation details. A custom loss function was designed to prioritize the continuity of blood vessel segmentation.Main Results.LUNet significantly outperformed three benchmark A/V segmentation algorithms both on a local test set and on four external test sets that simulated variations in ethnicity, comorbidities and annotators.Significance.The release of the new datasets and the LUNet model (www.aimlab-technion.com/lirot-ai) provides a valuable resource for the advancement of retinal microvasculature analysis. The improvements in A/V segmentation accuracy highlight LUNet's potential as a robust tool for diagnosing and understanding cardiovascular diseases through retinal imaging.

NPB-REC: A non-parametric Bayesian deep-learning approach for undersampled MRI reconstruction with uncertainty estimation.

The ability to reconstruct high-quality images from undersampled MRI data is vital in improving MRI temporal resolution and reducing acquisition times. Deep learning methods have been proposed for this task, but the lack of verified methods to quantify the uncertainty in the reconstructed images hampered clinical applicability. We introduce "NPB-REC", a non-parametric fully Bayesian framework, for MRI reconstruction from undersampled data with uncertainty estimation. We use Stochastic Gradient Langevin Dynamics during training to characterize the posterior distribution of the network parameters. This enables us to both improve the quality of the reconstructed images and quantify the uncertainty in the reconstructed images. We demonstrate the efficacy of our approach on a multi-coil MRI dataset from the fastMRI challenge and compare it to the baseline End-to-End Variational Network (E2E-VarNet). Our approach outperforms the baseline in terms of reconstruction accuracy by means of PSNR and SSIM (34.55, 0.908 vs. 33.08, 0.897, p<0.01, acceleration rate R=8) and provides uncertainty measures that correlate better with the reconstruction error (Pearson correlation, R=0.94 vs. R=0.91). Additionally, our approach exhibits better generalization capabilities against anatomical distribution shifts (PSNR and SSIM of 32.38, 0.849 vs. 31.63, 0.836, p<0.01, training on brain data, inference on knee data, acceleration rate R=8). NPB-REC has the potential to facilitate the safe utilization of deep learning-based methods for MRI reconstruction from undersampled data. Code and trained models are available at https://github.com/samahkh/NPB-REC.

IVIM-Morph: Motion-compensated quantitative Intra-voxel Incoherent Motion (IVIM) analysis for functional fetal lung maturity assessment from diffusion-weighted MRI data.

Quantitative analysis of pseudo-diffusion in diffusion-weighted magnetic resonance imaging (DWI) data shows potential for assessing fetal lung maturation and generating valuable imaging biomarkers. Yet, the clinical utility of DWI data is hindered by unavoidable fetal motion during acquisition. We present IVIM-morph, a self-supervised deep neural network model for motion-corrected quantitative analysis of DWI data using the Intra-voxel Incoherent Motion (IVIM) model. IVIM-morph combines two sub-networks, a registration sub-network, and an IVIM model fitting sub-network, enabling simultaneous estimation of IVIM model parameters and motion. To promote physically plausible image registration, we introduce a biophysically informed loss function that effectively balances registration and model-fitting quality. We validated the efficacy of IVIM-morph by establishing a correlation between the predicted IVIM model parameters of the lung and gestational age (GA) using fetal DWI data of 39 subjects. Our approach was compared against six baseline methods: 1) no motion compensation, 2) affine registration of all DWI images to the initial image, 3) deformable registration of all DWI images to the initial image, 4) deformable registration of each DWI image to its preceding image in the sequence, 5) iterative deformable motion compensation combined with IVIM model parameter estimation, and 6) self-supervised deep-learning-based deformable registration. IVIM-morph exhibited a notably improved correlation with gestational age (GA) when performing in-vivo quantitative analysis of fetal lung DWI data during the canalicular phase. Specifically, over 2 test groups of cases, it achieved an Rf2 of 0.44 and 0.52, outperforming the values of 0.27 and 0.25, 0.25 and 0.00, 0.00 and 0.00, 0.38 and 0.00, and 0.07 and 0.14 obtained by other methods. IVIM-morph shows potential in developing valuable biomarkers for non-invasive assessment of fetal lung maturity with DWI data. Moreover, its adaptability opens the door to potential applications in other clinical contexts where motion compensation is essential for quantitative DWI analysis. The IVIM-morph code is readily available at:https://github.com/TechnionComputationalMRILab/qDWI-Morph.

MA-RECON: Mask-aware deep-neural-network for robust fast MRI k-space interpolation.

BACKGROUND AND OBJECTIVE: High-quality reconstruction of MRI images from under-sampled 'k-space' data, which is in the Fourier domain, is crucial for shortening MRI acquisition times and ensuring superior temporal resolution. Over recent years, a wealth of deep neural network (DNN) methods have emerged, aiming to tackle the complex, ill-posed inverse problem linked to this process. However, their instability against variations in the acquisition process and anatomical distribution exposes a deficiency in the generalization of relevant physical models within these DNN architectures. The goal of our work is to enhance the generalization capabilities of DNN methods for k-space interpolation by introducing 'MA-RECON', an innovative mask-aware DNN architecture and associated training method. METHODS: Unlike preceding approaches, our 'MA-RECON' architecture encodes not only the observed data but also the under-sampling mask within the model structure. It implements a tailored training approach that leverages data generated with a variety of under-sampling masks to stimulate the model's generalization of the under-sampled MRI reconstruction problem. Therefore, effectively represents the associated inverse problem, akin to the classical compressed sensing approach. RESULTS: The benefits of our MA-RECON approach were affirmed through rigorous testing with the widely accessible fastMRI dataset. Compared to standard DNN methods and DNNs trained with under-sampling mask augmentation, our approach demonstrated superior generalization capabilities. This resulted in a considerable improvement in robustness against variations in both the acquisition process and anatomical distribution, especially in regions with pathology. CONCLUSION: In conclusion, our mask-aware strategy holds promise for enhancing the generalization capacity and robustness of DNN-based methodologies for MRI reconstruction from undersampled k-space data. Code is available in the following link: https://github.com/nitzanavidan/PD_Recon.

P2T2: A physically-primed deep-neural-network approach for robust T2 distribution estimation from quantitative T2-weighted MRI.

Estimating T2 relaxation time distributions from multi-echo T2-weighted MRI (T2W) data can provide valuable biomarkers for assessing inflammation, demyelination, edema, and cartilage composition in various pathologies, including neurodegenerative disorders, osteoarthritis, and tumors. Deep neural network (DNN) based methods have been proposed to address the complex inverse problem of estimating T2 distributions from MRI data, but they are not yet robust enough for clinical data with low Signal-to-Noise ratio (SNR) and are highly sensitive to distribution shifts such as variations in echo-times (TE) used during acquisition. Consequently, their application is hindered in clinical practice and large-scale multi-institutional trials with heterogeneous acquisition protocols. We propose a physically-primed DNN approach, called P2T2, that incorporates the signal decay forward model in addition to the MRI signal into the DNN architecture to improve the accuracy and robustness of T2 distribution estimation. We evaluated our P2T2 model in comparison to both DNN-based methods and classical methods for T2 distribution estimation using 1D and 2D numerical simulations along with clinical data. Our model improved the baseline model's accuracy for low SNR levels (SNR<80) which are common in the clinical setting. Further, our model achieved a ∼35% improvement in robustness against distribution shifts in the acquisition process compared to previously proposed DNN models. Finally, Our P2T2 model produces the most detailed Myelin-Water fraction maps compared to baseline approaches when applied to real human MRI data. Our P2T2 model offers a reliable and precise means of estimating T2 distributions from MRI data and shows promise for use in large-scale multi-institutional trials with heterogeneous acquisition protocols. Our source code is available at: https://github.com/Hben-atya/P2T2-Robust-T2-estimation.git.

Image Translation of Breast Ultrasound to Pseudo Anatomical Display by CycleGAN.

Ultrasound imaging is cost effective, radiation-free, portable, and implemented routinely in clinical procedures. Nonetheless, image quality is characterized by a granulated appearance, a poor SNR, and speckle noise. Specific for breast tumors, the margins are commonly blurred and indistinct. Thus, there is a need for improving ultrasound image quality. We hypothesize that this can be achieved by translation into a more realistic display which mimics a pseudo anatomical cut through the tissue, using a cycle generative adversarial network (CycleGAN). In order to train CycleGAN for this translation, two datasets were used, "Breast Ultrasound Images" (BUSI) and a set of optical images of poultry breast tissues. The generated pseudo anatomical images provide improved visual discrimination of the lesions through clearer border definition and pronounced contrast. In order to evaluate the preservation of the anatomical features, the lesions in both datasets were segmented and compared. This comparison yielded median dice scores of 0.91 and 0.70; median center errors of 0.58% and 3.27%; and median area errors of 0.40% and 4.34% for the benign and malignancies, respectively. In conclusion, generated pseudo anatomical images provide a more intuitive display, enhance tissue anatomy, and preserve tumor geometry; and can potentially improve diagnoses and clinical outcomes.

Development of a multimodal machine-learning fusion model to non-invasively assess ileal Crohn's disease endoscopic activity.

BACKGROUND AND OBJECTIVE: Recurrent attentive non-invasive observation of intestinal inflammation is essential for the proper management of Crohn's disease (CD). The goal of this study was to develop and evaluate a multi-modal machine-learning (ML) model to assess ileal CD endoscopic activity by integrating information from Magnetic Resonance Enterography (MRE) and biochemical biomarkers. METHODS: We obtained MRE, biochemical and ileocolonoscopy data from the multi-center ImageKids study database. We developed an optimized multimodal fusion ML model to non-invasively assess terminal ileum (TI) endoscopic disease activity in CD from MRE data. We determined the most informative features for model development using a permutation feature importance technique. We assessed model performance in comparison to the clinically recommended linear-regression MRE model in an experimental setup that consisted of stratified 2-fold validation, repeated 50 times, with the ileocolonoscopy-based Simple Endoscopic Score for CD at the TI (TI SES-CD) as a reference. We used the predictions' mean-squared-error (MSE) and the receiver operation characteristics (ROC) area under curve (AUC) for active disease classification (TI SEC-CD≥3) as performance metrics. RESULTS: 121 subjects out of the 240 subjects in the ImageKids study cohort had all required information (Non-active CD: 62 [51%], active CD: 59 [49%]). Length of disease segment and normalized biochemical biomarkers were the most informative features. The optimized fusion model performed better than the clinically recommended model determined by both a better median test MSE distribution (7.73 vs. 8.8, Wilcoxon test, p<1e-5) and a better aggregated AUC over the folds (0.84 vs. 0.8, DeLong's test, p<1e-9). CONCLUSIONS: Optimized ML models for ileal CD endoscopic activity assessment have the potential to enable accurate and non-invasive attentive observation of intestinal inflammation in CD patients. The presented model is available at https://tcml-bme.github.io/ML_SESCD.html.

NPBDREG: Uncertainty assessment in diffeomorphic brain MRI registration using a non-parametric Bayesian deep-learning based approach.

Quantification of uncertainty in deep-neural-networks (DNN) based image registration algorithms plays a critical role in the deployment of image registration algorithms for clinical applications such as surgical planning, intraoperative guidance, and longitudinal monitoring of disease progression or treatment efficacy as well as in research-oriented processing pipelines. Currently available approaches for uncertainty estimation in DNN-based image registration algorithms may result in sub-optimal clinical decision making due to potentially inaccurate estimation of the uncertainty of the registration stems for the assumed parametric distribution of the registration latent space. We introduce NPBDREG, a fully non-parametric Bayesian framework for uncertainty estimation in DNN-based deformable image registration by combining an Adam optimizer with stochastic gradient Langevin dynamics (SGLD) to characterize the underlying posterior distribution through posterior sampling. Thus, it has the potential to provide uncertainty estimates that are highly correlated with the presence of out of distribution data. We demonstrated the added-value of NPBDREG, compared to the baseline probabilistic VoxelMorph model (PrVXM), on brain MRI image registration using 390 image pairs from four publicly available databases: MGH10, CMUC12, ISBR18 and LPBA40. The NPBDREG shows a better correlation of the predicted uncertainty with out-of-distribution data (r > 0.95 vs. r < 0.5) as well as a ~ 7.3 % improvement in the registration accuracy (Dice score, 0.74 vs. 0.69, p â‰ª 0.01), and a ~ 18 % improvement in registration smoothness (percentage of folds in the deformation field, 0.014 vs. 0.017, p â‰ª 0.01). Finally, NPBDREG demonstrated a better generalization capability for data corrupted by a mixed structure noise (Dice score of 0.73 vs. 0.69, p â‰ª 0.01) compared to the baseline PrVXM approach.

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia.

OBJECTIVES: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)-derived plaque volume and positron emission tomography (PET) determined ischemia. BACKGROUND: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). METHODS: A total of 539 patients who underwent CCTA and [15O]H2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. RESULTS: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm3, CPV >110 mm3, NCPV >85 mm3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). CONCLUSIONS: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Unsupervised abnormality detection through mixed structure regularization (MSR) in deep sparse autoencoders.

PURPOSE: The purpose of this study is to introduce and evaluate the mixed structure regularization (MSR) approach for a deep sparse autoencoder aimed at unsupervised abnormality detection in medical images. Unsupervised abnormality detection based on identifying outliers using deep sparse autoencoders is a very appealing approach for computer-aided detection systems as it requires only healthy data for training rather than expert annotated abnormality. However, regularization is required to avoid overfitting of the network to the training data. METHODS: We used coronary computed tomography angiography (CCTA) datasets of 90 subjects with expert annotated centerlines. We segmented coronary lumen and wall using an automatic algorithm with manual corrections where required. We defined normal coronary cross section as cross sections with a ratio between lumen and wall areas larger than 0.8. We divided the datasets into training, validation, and testing groups in a tenfold cross-validation scheme. We trained a deep sparse overcomplete autoencoder model for normality modeling with random structure and noise augmentation. We assessed the performance of our deep sparse autoencoder with MSR without denoising (SAE-MSR) and with denoising (SDAE-MSR) in comparison to deep sparse autoencoder (SAE), and deep sparse denoising autoencoder (SDAE) models in the task of detecting coronary artery disease from CCTA data on the test group. RESULTS: The SDAE-MSR achieved the best aggregated area under the curve (AUC) with a 20% improvement and the best aggregated Average Precision (AP) with a 30% improvement upon the SAE and SDAE (AUC: 0.78 to 0.94, AP: 0.66 to 0.86) in distinguishing between coronary cross sections with mild stenosis (stenosis grade < 0.3) and coronary cross sections with severe stenosis (stenosis grade > 0.7). The improvements were statistically significant (Mann-Whitney U-test, P < 0.001). Similarly, The SDAE-MSR achieved the best aggregated AUC (AP) with an 18% (18%) improvement upon the SAE and SDAE (AUC: 0.71 to 0.84, AP: 0.68 to 0.80). The improvements were statistically significant (Mann-Whitney U-test, P < 0.05). CONCLUSION: Deep sparse autoencoders with MSR in addition to explicit sparsity regularization term and stochastic corruption of the input data with Gaussian noise have the potential to improve unsupervised abnormality detection using deep-learning compared to common deep autoencoders.

Curved planar reformatting and convolutional neural network-based segmentation of the small bowel for visualization and quantitative assessment of pediatric Crohn's disease from MRI.

BACKGROUND: Contrast-enhanced MRI of the small bowel is an effective imaging sequence for the detection and characterization of disease burden in pediatric Crohn's disease (CD). However, visualization and quantification of disease burden requires scrolling back and forth through 3D images to follow the anatomy of the bowel, and it can be difficult to fully appreciate the extent of disease. PURPOSE: To develop and evaluate a method that offers better visualization and quantitative assessment of CD from MRI. STUDY TYPE: Retrospective. POPULATION: Twenty-three pediatric patients with CD. FIELD STRENGTH/SEQUENCE: 1.5T MRI system and T1 -weighted postcontrast VIBE sequence. ASSESSMENT: The convolutional neural network (CNN) segmentation of the bowel's lumen, wall, and background was compared with manual boundary delineation. We assessed the reproducibility and the capability of the extracted markers to differentiate between different levels of disease defined after a consensus review by two experienced radiologists. STATISTICAL TESTS: The segmentation algorithm was assessed using the Dice similarity coefficient (DSC) and boundary distances between the CNN and manual boundary delineations. The capability of the extracted markers to differentiate between different disease levels was determined using a t-test. The reproducibility of the extracted markers was assessed using the mean relative difference (MRD), Pearson correlation, and Bland-Altman analysis. RESULTS: Our CNN exhibited DSCs of 75 ± 18%, 81 ± 8%, and 97 ± 2% for the lumen, wall, and background, respectively. The extracted markers of wall thickness at the location of min radius (P = 0.0013) and the median value of relative contrast enhancement (P = 0.0033) could differentiate active and nonactive disease segments. Other extracted markers could differentiate between segments with strictures and segments without strictures (P < 0.05). The observers' agreement in measuring stricture length was >3 times superior when computed on curved planar reformatting images compared with the conventional scheme. DATA CONCLUSION: The results of this study show that the newly developed method is efficient for visualization and assessment of CD. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1565-1576.

A functionally personalized boundary condition model to improve estimates of fractional flow reserve with CT (CT-FFR).

PURPOSE: The purpose of this study is to develop and evaluate a functionally personalized boundary condition (BC) model for estimating the fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) using flow simulation (CT-FFR). MATERIALS AND METHODS: The CCTA data of 90 subjects with subsequent invasive FFR in 123 lesions within 21 days (range: 0-83) were retrospectively collected. We developed a functionally personalized BC model accounting specifically for the coronary microvascular resistance dependency on the coronary outlets pressure suggested by several physiological studies. We used the proposed model to estimate the hemodynamic significance of coronary lesions with an open-loop physics-based flow simulation. We generated three-dimensional (3D) coronary tree geometries using automatic software and corrected manually where required. We evaluated the improvement in CT-FFR estimates achieved using a functionally personalized BC model over anatomically personalized BC model using k-fold cross-validation. RESULTS: The functionally personalized BC model slightly improved CT-FFR specificity in determining hemodynamic significance of lesions with intermediate diameter stenosis (30%-70%, N = 72), compared to the anatomically personalized model lesions with invasive FFR measurements as the reference (sensitivity/specificity: 0.882/0.79 vs 0.882/0.763). For the entire set of 123 coronary lesions, the functionally personalized BC model improved only the area under the curve (AUC) but not the sensitivity/specificity in determining the hemodynamic significance of lesions, compared to the anatomically personalized model (AUC: 0.884 vs 0.875, sensitivity/specificity: 0.848/0.805). CONCLUSION: The functionally personalized BC model has the potential to improve the quality of CT-FFR estimates compared to an anatomically personalized BC model.

Motion-robust parameter estimation in abdominal diffusion-weighted MRI by simultaneous image registration and model estimation.

Quantitative body DW-MRI can detect abdominal abnormalities as well as monitor response-to-therapy for applications including cancer and inflammatory bowel disease with increased accuracy. Parameter estimates are obtained by fitting a forward model of DW-MRI signal decay to the observed data acquired with several b-values. The DW-MRI signal decay models typically used do not account for respiratory, cardiac and peristaltic motion, however, which may deteriorate the accuracy and robustness of parameter estimates. In this work, we introduce a new model of DW-MRI signal decay that explicitly accounts for motion. Specifically, we estimated motion-compensated model parameters by simultaneously solving image registration and model estimation (SIR-ME) problems utilizing the interdependence of acquired volumes along the diffusion-weighting dimension. To accomplish this, we applied the SIR-ME model to the in-vivo DW-MRI data sets of 26 Crohn's disease (CD) patients and achieved improved precision of the estimated parameters by reducing the coefficient of variation by 8%, 24% and 8% for slow diffusion (D), fast diffusion (D*) and fast diffusion fraction (f) parameters respectively, compared to parameters estimated with independent registration in normal-appearing bowel regions. Moreover, the parameters estimated with the SIR-ME model reduced the error rate in classifying normal and abnormal bowel loops to 12% for D and 10% for f parameter with a reduction in error rate by 13% and 11% for D and f parameters, respectively, compared to the error rate in classifying parameter estimates obtained with independent registration. The experiments in DW-MRI of liver in 20 subjects also showed that the SIR-ME model improved the precision of parameter estimation by reducing the coefficient of variation to 7% for D, 23% for D*, and 8% for the f parameter. Using the SIR-ME model, the coefficient of variation was reduced by 4%, 14% and 6% for D, D* and f parameters, respectively, compared to parameters estimated with independent registration. These results demonstrate that the proposed SIR-ME model improves the accuracy and robustness of quantitative body DW-MRI in characterizing tissue microstructure.

Improving CCTA-based lesions' hemodynamic significance assessment by accounting for partial volume modeling in automatic coronary lumen segmentation.

PURPOSE: The goal of this study was to assess the potential added benefit of accounting for partial volume effects (PVE) in an automatic coronary lumen segmentation algorithm that is used to determine the hemodynamic significance of a coronary artery stenosis from coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: Two sets of data were used in our work: (a) multivendor CCTA datasets of 18 subjects from the MICCAI 2012 challenge with automatically generated centerlines and 3 reference segmentations of 78 coronary segments and (b) additional CCTA datasets of 97 subjects with 132 coronary lesions that had invasive reference standard FFR measurements. We extracted the coronary artery centerlines for the 97 datasets by an automated software program followed by manual correction if required. An automatic machine-learning-based algorithm segmented the coronary tree with and without accounting for the PVE. We obtained CCTA-based FFR measurements using a flow simulation in the coronary trees that were generated by the automatic algorithm with and without accounting for PVE. We assessed the potential added value of PVE integration as a part of the automatic coronary lumen segmentation algorithm by means of segmentation accuracy using the MICCAI 2012 challenge framework and by means of flow simulation overall accuracy, sensitivity, specificity, negative and positive predictive values, and the receiver operated characteristic (ROC) area under the curve. We also evaluated the potential benefit of accounting for PVE in automatic segmentation for flow simulation for lesions that were diagnosed as obstructive based on CCTA which could have indicated a need for an invasive exam and revascularization. RESULTS: Our segmentation algorithm improves the maximal surface distance error by ~39% compared to previously published method on the 18 datasets from the MICCAI 2012 challenge with comparable Dice and mean surface distance. Results with and without accounting for PVE were comparable. In contrast, integrating PVE analysis into an automatic coronary lumen segmentation algorithm improved the flow simulation specificity from 0.6 to 0.68 with the same sensitivity of 0.83. Also, accounting for PVE improved the area under the ROC curve for detecting hemodynamically significant CAD from 0.76 to 0.8 compared to automatic segmentation without PVE analysis with invasive FFR threshold of 0.8 as the reference standard. Accounting for PVE in flow simulation to support the detection of hemodynamic significant disease in CCTA-based obstructive lesions improved specificity from 0.51 to 0.73 with same sensitivity of 0.83 and the area under the curve from 0.69 to 0.79. The improvement in the AUC was statistically significant (N = 76, Delong's test, P = 0.012). CONCLUSION: Accounting for the partial volume effects in automatic coronary lumen segmentation algorithms has the potential to improve the accuracy of CCTA-based hemodynamic assessment of coronary artery lesions.

Spatially-constrained probability distribution model of incoherent motion (SPIM) for abdominal diffusion-weighted MRI.

Quantitative diffusion-weighted MR imaging (DW-MRI) of the body enables characterization of the tissue microenvironment by measuring variations in the mobility of water molecules. The diffusion signal decay model parameters are increasingly used to evaluate various diseases of abdominal organs such as the liver and spleen. However, previous signal decay models (i.e., mono-exponential, bi-exponential intra-voxel incoherent motion (IVIM) and stretched exponential models) only provide insight into the average of the distribution of the signal decay rather than explicitly describe the entire range of diffusion scales. In this work, we propose a probability distribution model of incoherent motion that uses a mixture of Gamma distributions to fully characterize the multi-scale nature of diffusion within a voxel. Further, we improve the robustness of the distribution parameter estimates by integrating spatial homogeneity prior into the probability distribution model of incoherent motion (SPIM) and by using the fusion bootstrap solver (FBM) to estimate the model parameters. We evaluated the improvement in quantitative DW-MRI analysis achieved with the SPIM model in terms of accuracy, precision and reproducibility of parameter estimation in both simulated data and in 68 abdominal in-vivo DW-MRIs. Our results show that the SPIM model not only substantially reduced parameter estimation errors by up to 26%; it also significantly improved the robustness of the parameter estimates (paired Student's t-test, p < 0.0001) by reducing the coefficient of variation (CV) of estimated parameters compared to those produced by previous models. In addition, the SPIM model improves the parameter estimates reproducibility for both intra- (up to 47%) and inter-session (up to 30%) estimates compared to those generated by previous models. Thus, the SPIM model has the potential to improve accuracy, precision and robustness of quantitative abdominal DW-MRI analysis for clinical applications.

Motion Compensated Abdominal Diffusion Weighted MRI by Simultaneous Image Registration and Model Estimation (SIR-ME).

Non-invasive characterization of water molecule's mobility variations by quantitative analysis of diffusion-weighted MRI (DW-MRI) signal decay in the abdomen has the potential to serve as a biomarker in gastrointestinal and oncological applications. Accurate and reproducible estimation of the signal decay model parameters is challenging due to the presence of respiratory, cardiac, and peristalsis motion. Independent registration of each b-value image to the b-value=0 s/mm(2) image prior to parameter estimation might be sub-optimal because of the low SNR and contrast difference between images of varying b-value. In this work, we introduce a motion-compensated parameter estimation framework that simultaneously solves image registration and model estimation (SIR-ME) problems by utilizing the interdependence of acquired volumes along the diffusion weighting dimension. We evaluated the improvement in model parameters estimation accuracy using 16 in-vivo DW-MRI data sets of Crohn's disease patients by comparing parameter estimates obtained using the SIR-ME model to the parameter estimates obtained by fitting the signal decay model to the acquired DW-MRI images. The proposed SIR-ME model reduced the average root-mean-square error between the observed signal and the fitted model by more than 50%. Moreover, the SIR-ME model estimates discriminate between normal and abnormal bowel loops better than the standard parameter estimates.

Spatially constrained incoherent motion method improves diffusion-weighted MRI signal decay analysis in the liver and spleen.

PURPOSE: To evaluate the effect of the spatially constrained incoherent motion (SCIM) method on improving the precision and robustness of fast and slow diffusion parameter estimates from diffusion-weighted MRI in liver and spleen in comparison to the independent voxel-wise intravoxel incoherent motion (IVIM) model. METHODS: We collected diffusion-weighted MRI (DW-MRI) data of 29 subjects (5 healthy subjects and 24 patients with Crohn's disease in the ileum). We evaluated parameters estimates' robustness against different combinations of b-values (i.e., 4 b-values and 7 b-values) by comparing the variance of the estimates obtained with the SCIM and the independent voxel-wise IVIM model. We also evaluated the improvement in the precision of parameter estimates by comparing the coefficient of variation (CV) of the SCIM parameter estimates to that of the IVIM. RESULTS: The SCIM method was more robust compared to IVIM (up to 70% in liver and spleen) for different combinations of b-values. Also, the CV values of the parameter estimations using the SCIM method were significantly lower compared to repeated acquisition and signal averaging estimated using IVIM, especially for the fast diffusion parameter in liver (CVIV IM = 46.61 ± 11.22, CVSCIM = 16.85 ± 2.160, p < 0.001) and spleen (CVIV IM = 95.15 ± 19.82, CVSCIM = 52.55 ± 1.91, p < 0.001). CONCLUSIONS: The SCIM method characterizes fast and slow diffusion more precisely compared to the independent voxel-wise IVIM model fitting in the liver and spleen.

Quantitative functional MRI biomarkers improved early detection of colorectal liver metastases.

PURPOSE: To implement and evaluate the performance of a computerized statistical tool designed for robust and quantitative analysis of hemodynamic response imaging (HRI) -derived maps for the early identification of colorectal liver metastases (CRLM). MATERIALS AND METHODS: CRLM-bearing mice were scanned during the early stage of tumor growth and subsequently during the advanced-stage. Three experienced radiologists marked various suspected-foci on the early stage anatomical images and classified each as either highly certain or as suspected tumors. The statistical model construction was based on HRI maps (functional-MRI combined with hypercapnia and hyperoxia) using a supervised learning paradigm which was further trained either with the advanced-stage sets (late training; LT) or with the early stage sets (early training; ET). For each group of foci, the classifier results were compared with the ground-truth. RESULTS: The ET-based classification significantly improved the manual classification of the highly certain foci (P < 0.05) and was superior compared with the LT-based classification (P < 0.05). Additionally, the ET-based classification, offered high sensitivity (57-63%), accompanied with high positive predictive value (>94%) and high specificity (>98%) for suspected-foci. CONCLUSION: The ET-based classifier can strengthen the radiologist's classification of highly certain foci. Additionally, it can aid in classifying suspected-foci, thus enabling earlier intervention which can often be lifesaving.