Invasive fractional flow reserve (FFRinvasive ), although gold standard to identify hemodynamically relevant coronary stenoses, is time consuming and potentially associated with complications. We ...developed and evaluated a new approach to determine lesion-specific FFR on the basis of coronary anatomy as visualized by invasive coronary angiography (FFRangio ): 100 coronary lesions (50% to 90% diameter stenosis) in 73 patients (48 men, 25 women; mean age 67 ± 9 years) were studied. On the basis of coronary angiograms acquired at rest from 2 views at angulations at least 30° apart, a PC-based computational fluid dynamics modeling software used personalized boundary conditions determined from 3-dimensional reconstructed angiography, heart rate, and blood pressure to derive FFRangio . The results were compared with FFRinvasive . Interobserver variability was determined in a subset of 25 narrowings. Twenty-nine of 100 coronary lesions were hemodynamically significant (FFRinvasive ≤0.80). FFRangio identified these with an accuracy of 90%, sensitivity of 79%, specificity of 94%, positive predictive value of 85%, and negative predictive value of 92%. The area under the receiver operating characteristic curve was 0.93. Correlation between FFRinvasive (mean: 0.84 ± 0.11) and FFRangio (mean: 0.85 ± 0.12) was r = 0.85. Interobserver variability of FFRangio was low, with a correlation of r = 0.88. In conclusion, estimation of coronary FFR with PC-based computational fluid dynamics modeling on the basis of lesion morphology as determined by invasive angiography is possible with high diagnostic accuracy compared to invasive measurements.
The heterogeneous pathogenesis and treatment response of non-small cell lung cancer (NSCLC) has led clinical treatment decisions to be guided by NSCLC subtypes, with lung adenocarcinoma and lung ...squamous cell carcinoma being the most common subtypes. While histology-based subtyping remains challenging, NSCLC subtypes were found to be distinct at the transcriptomic level. However, unlike genomic alterations, gene expression is generally not assessed in clinical routine. Since subtyping of NSCLC has remained elusive using mutational data, we aimed at developing a neural network model that simultaneously learns from adenocarcinoma and squamous cell carcinoma samples of other tissue types and is regularized using a neural network model trained from gene expression data. While substructures of the expression-based manifold were captured in the mutation-based manifold, NSCLC classification accuracy did not significantly improve. However, performance was increased when rejecting inconclusive samples using an ensemble-based approach capturing prediction uncertainty. Importantly, SHAP analysis of misclassified samples identified co-occurring mutations indicative of both NSCLC subtypes, questioning the current NSCLC subtype classification to adequately represent inherent mutational heterogeneity. Since our model captures mutational patterns linked to clinical heterogeneity, we anticipate it to be suited as foundational model of genomic data for clinically relevant prognostic or predictive downstream tasks.
Background: Radiotherapy continues to be delivered without consideration of individual tumour characteristics. To advance towards more precise treatments in radiotherapy, we queried the lung ...CT-derived feature space to identify radiation sensitivity parameters that can predict treatment failure and hence guide the individualisation of radiotherapy dose. Methods: An institutional review board-approved study (IRB 14-562) was used to identify patients treated with lung stereotactic body radiotherapy. Patients with primary (stage IA–IV) or recurrent lung cancer and patients with other cancer types with solitary metastases or oligometastases to the lung were included. Patients without digitally accessible CT image or radiotherapy structure data were excluded. The internal study cohort received treatment at the main campus of the Cleveland Clinic (Cleveland, OH, USA). The independent validation cohort received treatment at seven affiliate regional or national sites. We input pre-therapy lung CT images into Deep Profiler, a multi-task deep neural network that has radiomics incorporated into the training process, to generate an image fingerprint that predicts time-to-event treatment outcomes and approximates classical radiomic features. We validated our findings with the independent study cohort. Deep Profiler was combined with clinical variables to derive iGray, an individualised dose that estimates treatment failure probability to be below 5%. Findings: A total of 1275 patients were assessed for eligibility and 944 met our eligibility criteria; 849 were in the internal study cohort and 95 were in the independent validation cohort. Radiation treatments in patients with high Deep Profiler scores failed at a significantly higher rate than in patients with low scores; 3-year cumulative incidence of local failure in the internal study cohort was 20·3% (16·0–24·9) in patients with high Deep Profiler scores and 5·7% (95% CI 3·5–8·8) in patients with low Deep Profiler scores (hazard ratio HR=3·64 95% CI 2·19–6·05, p<0·0001). Deep Profiler independently predicted local failure (HR=1·65 1·02–2·66, p=0·042). Models that included Deep Profiler and clinical variables predicted treatment failures with a concordance index (C-index) of 0·72 (95% CI 0·67–0·77), a significant improvement compared with classical radiomics (p<0·0001) or clinical variables (p<0·0001) alone. Deep Profiler performed well in the independent validation cohort, predicting treatment failures across diverse clinical settings and CT scanner types (C-index 0·77, 95% CI 0·69–0·92). iGray had a wide dose range (21·1–277 Gy) and suggested dose reductions in 23·3% of patients. Our results also showed that iGray can be safely delivered in the majority of cases. Interpretation: Our results indicate that there are image-distinct subpopulations that have differential sensitivity to radiotherapy. The image-based deep learning framework proposed herein is the first opportunity to use medical images to individualise radiotherapy dose. Our results signify a new roadmap for deep learning-guided predictions and treatment guidance in the image-replete and highly standardised discipline of radiation oncology. Funding: Siemens Medical Solutions USA.
Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification ...and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders.
State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics and hemodynamics was estimated using a robust framework. The model was computed on n=46 HF patients, showing for the first time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters.
This paper illustrates how advanced multi-scale models can complement cardiovascular imaging and how they could be applied in patient care. Based on obtained results, it becomes conceivable that, after thorough validation, such heart failure models could be applied for patient management and therapy planning in the future, as we illustrate in one patient of our cohort who received CRT-D implantation.
This paper presents an approach to predict the deformation of the lungs and surrounding organs during respiration. The framework incorporates a computational model of the respiratory system, which ...comprises an anatomical model extracted from computed tomography (CT) images at end-expiration (EE), and a biomechanical model of the respiratory physiology, including the material behavior and interactions between organs. A personalization step is performed to automatically estimate patient-specific thoracic pressure, which drives the biomechanical model. The zone-wise pressure values are obtained by using a trust-region optimizer, where the estimated motion is compared to CT images at end-inspiration (EI). A detailed convergence analysis in terms of mesh resolution, time stepping and number of pressure zones on the surface of the thoracic cavity is carried out. The method is then tested on five public datasets. Results show that the model is able to predict the respiratory motion with an average landmark error of 3.40 ±1.0 mm over the entire respiratory cycle. The estimated 3-D lung motion may constitute as an advanced 3-D surrogate for more accurate medical image reconstruction and patient respiratory analysis.
Background: Opportunistic prostate cancer (PCa) screening is a controversial topic. Magnetic resonance imaging (MRI) has proven to detect prostate cancer with a high sensitivity and specificity, ...leading to the idea to perform an image-guided prostate cancer (PCa) screening; Methods: We evaluated a prospectively enrolled cohort of 49 healthy men participating in a dedicated image-guided PCa screening trial employing a biparametric MRI (bpMRI) protocol consisting of T2-weighted (T2w) and diffusion weighted imaging (DWI) sequences. Datasets were analyzed both by human readers and by a fully automated artificial intelligence (AI) software using deep learning (DL). Agreement between the algorithm and the reports—serving as the ground truth—was compared on a per-case and per-lesion level using metrics of diagnostic accuracy and k statistics; Results: The DL method yielded an 87% sensitivity (33/38) and 50% specificity (5/10) with a k of 0.42. 12/28 (43%) Prostate Imaging Reporting and Data System (PI-RADS) 3, 16/22 (73%) PI-RADS 4, and 5/5 (100%) PI-RADS 5 lesions were detected compared to the ground truth. Targeted biopsy revealed PCa in six participants, all correctly diagnosed by both the human readers and AI. Conclusions: The results of our study show that in our AI-assisted, image-guided prostate cancer screening the software solution was able to identify highly suspicious lesions and has the potential to effectively guide the targeted-biopsy workflow.
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•Data-driven estimation of electrical diffusivity from ECG using polynomial regression.•Fast, patient-specific forward model of cardiac electrophysiology and ECG.•Analysis of ...intrinsic uncertainty of the inverse ECG problem.•QRS duration and electrical axis, available from 12-lead ECG, are used as features.•Quantitative validation on synthetic database with 9500 datasets and 19 DCM patients.
Diagnosis and treatment of dilated cardiomyopathy (DCM) is challenging due to a large variety of causes and disease stages. Computational models of cardiac electrophysiology (EP) can be used to improve the assessment and prognosis of DCM, plan therapies and predict their outcome, but require personalization. In this work, we present a data-driven approach to estimate the electrical diffusivity parameter of an EP model from standard 12-lead electrocardiograms (ECG). An efficient forward model based on a mono-domain, phenomenological Lattice-Boltzmann model of cardiac EP, and a boundary element-based mapping of potentials to the body surface is employed. The electrical diffusivity of myocardium, left ventricle and right ventricle endocardium is then estimated using polynomial regression which takes as input the QRS duration and electrical axis. After validating the forward model, we computed 9500 EP simulations on 19 different DCM patients in just under three seconds each to learn the regression model. Using this database, we quantify the intrinsic uncertainty of electrical diffusion for given ECG features and show in a leave-one-patient-out cross-validation that the regression method is able to predict myocardium diffusion within the uncertainty range. Finally, our approach is tested on the 19 cases using their clinical ECG. 84% of them could be personalized using our method, yielding mean prediction errors of 18.7ms for the QRS duration and 6.5° for the electrical axis, both values being within clinical acceptability. By providing an estimate of diffusion parameters from readily available clinical data, our data-driven approach could therefore constitute a first calibration step toward a more complete personalization of cardiac EP.
Deep-learning-based computer-aided diagnosis (DL-CAD) systems using MRI for prostate cancer (PCa) detection have demonstrated good performance. Nevertheless, DL-CAD systems are vulnerable to high ...heterogeneities in DWI, which can interfere with DL-CAD assessments and impair performance. This study aims to compare PCa detection of DL-CAD between zoomed-field-of-view echo-planar DWI (z-DWI) and full-field-of-view DWI (f-DWI) and find the risk factors affecting DL-CAD diagnostic efficiency.
This retrospective study enrolled 354 consecutive participants who underwent MRI including T2WI, f-DWI, and z-DWI because of clinically suspected PCa. A DL-CAD was used to compare the performance of f-DWI and z-DWI both on a patient level and lesion level. We used the area under the curve (AUC) of receiver operating characteristics analysis and alternative free-response receiver operating characteristics analysis to compare the performances of DL-CAD using f- DWI and z-DWI. The risk factors affecting the DL-CAD were analyzed using logistic regression analyses. P values less than 0.05 were considered statistically significant.
DL-CAD with z-DWI had a significantly better overall accuracy than that with f-DWI both on patient level and lesion level (AUC
: 0.89 vs. 0.86; AUC
: 0.86 vs. 0.76; P < .001). The contrast-to-noise ratio (CNR) of lesions in DWI was an independent risk factor of false positives (odds ratio OR = 1.12; P < .001). Rectal susceptibility artifacts, lesion diameter, and apparent diffusion coefficients (ADC) were independent risk factors of both false positives (OR
= 5.46; OR
= 1.12; OR
= 0.998; all P < .001) and false negatives (OR
= 3.31; OR
= 0.82; OR
= 1.007; all P ≤ .03) of DL-CAD.
Z-DWI has potential to improve the detection performance of a prostate MRI based DL-CAD.
ChiCTR, NO. ChiCTR2100041834 . Registered 7 January 2021.
All viruses, including SARS-CoV-2, the virus responsible for COVID-19, continue to evolve, which can lead to new variants. The objective of this study is to assess the agreement between real-world ...clinical data and an algorithm that utilizes laboratory markers and age to predict the progression of disease severity in COVID-19 patients during the pre-Omicron and Omicron variant periods. The study evaluated the performance of a deep learning (DL) algorithm in predicting disease severity scores for COVID-19 patients using data from the USA, Spain, and Turkey (Ankara City Hospital (ACH) data set). The algorithm was developed and validated using pre-Omicron era data and was tested on both pre-Omicron and Omicron-era data. The predictions were compared to the actual clinical outcomes using a multidisciplinary approach. The concordance index values for all datasets ranged from 0.71 to 0.81. In the ACH cohort, a negative predictive value (NPV) of 0.78 or higher was observed for severe patients in both the pre-Omicron and Omicron eras, which is consistent with the algorithm's performance in the development cohort.
The SARS-CoV-2 virus has caused tremendous healthcare burden worldwide. Our focus was to develop a practical and easy-to-deploy system to predict the severe manifestation of disease in patients with ...COVID-19 with an aim to assist clinicians in triage and treatment decisions. Our proposed predictive algorithm is a trained artificial intelligence-based network using 8,427 COVID-19 patient records from four healthcare systems. The model provides a severity risk score along with likelihoods of various clinical outcomes, namely ventilator use and mortality. The trained model using patient age and nine laboratory markers has the prediction accuracy with an area under the curve (AUC) of 0.78, 95% CI: 0.77–0.82, and the negative predictive value NPV of 0.86, 95% CI: 0.84–0.88 for the need to use a ventilator and has an accuracy with AUC of 0.85, 95% CI: 0.84–0.86, and the NPV of 0.94, 95% CI: 0.92–0.96 for predicting in-hospital 30-day mortality.
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•Algorithm using 9 laboratory markers & age may predict severity in patients with COVID-19•Model was trained and tested on a multicenter sample of 10,937 patients•Algorithm can predict ventilator use (NPV, 0.86) and mortality (NPV, 0.94)•High NPV suggests utility as an adjunct to aid in triaging of patients with COVID-19
Classification Description: Virology; Diagnostics; Artificial intelligence; Machine learning