Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis.

OBJECTIVES: To assess the ability of a previously trained deep-learning algorithm to identify the presence of inflammation on MRI of sacroiliac joints (SIJ) in a large external validation set of patients with axial spondyloarthritis (axSpA). METHODS: Baseline SIJ MRI scans were collected from two prospective randomised controlled trials in patients with non-radiographic (nr-) and radiographic (r-) axSpA (RAPID-axSpA: NCT01087762 and C-OPTIMISE: NCT02505542) and were centrally evaluated by two expert readers (and adjudicator in case of disagreement) for the presence of inflammation by the 2009 Assessment of SpondyloArthritis International Society (ASAS) definition. Scans were processed by the deep-learning algorithm, blinded to clinical information and central expert readings. RESULTS: Pooling the patients from RAPID-axSpA (n=152) and C-OPTIMISE (n=579) yielded a validation set of 731 patients (mean age: 34.2 years, SD: 8.6; 505/731 (69.1%) male), of which 326/731 (44.6%) had nr-axSpA and 436/731 (59.6%) had inflammation on MRI per central readings. Scans were obtained from over 30 scanners from 5 manufacturers across over 100 clinical sites. Comparing the trained algorithm with the human central readings yielded a sensitivity of 70% (95% CI 66% to 73%), specificity of 81% (95% CI 78% to 84%), positive predictive value of 84% (95% CI 82% to 87%), negative predictive value of 64% (95% CI 61% to 68%), Cohen's kappa of 0.49 (95% CI 0.43 to 0.55) and absolute agreement of 74% (95% CI 72% to 77%). CONCLUSION: The algorithm enabled acceptable detection of inflammation according to the 2009 ASAS MRI definition in a large external validation cohort.

ZeBraInspector, a platform for the automated segmentation and analysis of body and brain volumes in whole 5 days post-fertilization zebrafish following simultaneous visualization with identical orientations.

In recent years, the zebrafish has become a well-established laboratory model. We describe here the ZeBraInspector (ZBI) platform for high-content 3D imaging (HCI) of 5 days post-fertilization zebrafish eleuthero-embryos (EEs). This platform includes a mounting method based on 3D-printed stamps to create a grid of wells in an agarose cast, facilitating batch acquisitions with a fast-confocal laser scanning microscope. We describe reference labeling in cleared fish with a fluorescent lipophilic dye. Based on this labeling, the ZBI software registers. EE 3D images, making it possible to visualize numerous identically oriented EEs on a single screen, and to compare their morphologies and any fluorescent patterns at a glance. High-resolution 2D snapshots can be extracted. ZBI software is therefore useful for diverse high-content analyses (HCAs). Following automated segmentation of the lipophilic dye signal, the ZBI software performs volumetric analyses on whole EEs and their nervous system white matter. Through two examples, we illustrate the power of these analyses for obtaining statistically significant results from a small number of samples: the characterization of a phenotype associated with a neurodevelopmental mutation, and of the defects caused by treatments with a toxic anti-cancer compound.

Deep learning-enabled imaging flow cytometry for high-speed Cryptosporidium and Giardia detection.

Imaging flow cytometry has become a popular technology for bioparticle image analysis because of its capability of capturing thousands of images per second. Nevertheless, the vast number of images generated by imaging flow cytometry imposes great challenges for data analysis especially when the species have similar morphologies. In this work, we report a deep learning-enabled high-throughput system for predicting Cryptosporidium and Giardia in drinking water. This system combines imaging flow cytometry and an efficient artificial neural network called MCellNet, which achieves a classification accuracy >99.6%. The system can detect Cryptosporidium and Giardia with a sensitivity of 97.37% and a specificity of 99.95%. The high-speed analysis reaches 346 frames per second, outperforming the state-of-the-art deep learning algorithm MobileNetV2 in speed (251 frames per second) with a comparable classification accuracy. The reported system empowers rapid, accurate, and high throughput bioparticle detection in clinical diagnostics, environmental monitoring and other potential biosensing applications.

Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

BACKGROUND: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors. METHODS: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden. Progression-free survival (PFS) was assessed, and variables were selected through Recursive Feature Elimination. Cutoff values were determined using maximally selected rank statistics to binarize features, forming a risk score with hazard ratio-derived weights. RESULTS: In total, 2258 lesions were annotated with excellent reproducibility. Key variables in the training cohort included: total tumor volume (cutoff: 73 cm3), lesion count (cutoff: 20), age (cutoff: 60) and the presence of peritoneal carcinomatosis. Their respective weights were 1.13, 0.96, 0.91, and 0.38, resulting in a risk score cutoff of 1.36. Low-score patients showed similar overall survival and PFS regardless of treatment, while those with a high-score had significantly worse survivals with mono vs combo (P = 0.004 and P = 0.0001). In the validation set, low-score patients exhibited no significant difference in overall survival and PFS with mono or combo. However, patients with a high-score had worse PFS with mono (P = 0.046). CONCLUSIONS: A score based on total tumor volume, lesion count, the presence of peritoneal carcinomatosis, and age can guide MSI-H mCRC treatment decisions, allowing oncologists to identify suitable candidates for mono and combo ICI therapies.

Detection and characterization of pancreatic lesion with artificial intelligence: The SFR 2023 artificial intelligence data challenge.

PURPOSE: The purpose of the 2023 SFR data challenge was to invite researchers to develop artificial intelligence (AI) models to identify the presence of a pancreatic mass and distinguish between benign and malignant pancreatic masses on abdominal computed tomography (CT) examinations. MATERIALS AND METHODS: Anonymized abdominal CT examinations acquired during the portal venous phase were collected from 18 French centers. Abdominal CT examinations were divided into three groups including CT examinations with no lesion, CT examinations with benign pancreatic mass, or CT examinations with malignant pancreatic mass. Each team included at least one radiologist, one data scientist, and one engineer. Pancreatic lesions were annotated by expert radiologists. CT examinations were distributed in balanced batches via a Health Data Hosting certified platform. Data were distributed into four batches, two for training, one for internal evaluation, and one for the external evaluation. Training used 83 % of the data from 14 centers and external evaluation used data from the other four centers. The metric (i.e., final score) used to rank the participants was a weighted average of mean sensitivity, mean precision and mean area under the curve. RESULTS: A total of 1037 abdominal CT examinations were divided into two training sets (including 500 and 232 CT examinations), an internal evaluation set (including 139 CT examinations), and an external evaluation set (including 166 CT examinations). The training sets were distributed on September 7 and October 13, 2023, and evaluation sets on October 15, 2023. Ten teams with a total of 93 members participated to the data challenge, with the best final score being 0.72. CONCLUSION: This SFR 2023 data challenge based on multicenter CT data suggests that the use of AI for pancreatic lesions detection is possible on real data, but the distinction between benign and malignant pancreatic lesions remains challenging.

Detection and severity quantification of pulmonary embolism with 3D CT data using an automated deep learning-based artificial solution.

PURPOSE: The purpose of this study was to propose a deep learning-based approach to detect pulmonary embolism and quantify its severity using the Qanadli score and the right-to-left ventricle diameter (RV/LV) ratio on three-dimensional (3D) computed tomography pulmonary angiography (CTPA) examinations with limited annotations. MATERIALS AND METHODS: Using a database of 3D CTPA examinations of 1268 patients with image-level annotations, and two other public datasets of CTPA examinations from 91 (CAD-PE) and 35 (FUME-PE) patients with pixel-level annotations, a pipeline consisting of: (i), detecting blood clots; (ii), performing PE-positive versus negative classification; (iii), estimating the Qanadli score; and (iv), predicting RV/LV diameter ratio was followed. The method was evaluated on a test set including 378 patients. The performance of PE classification and severity quantification was quantitatively assessed using an area under the curve (AUC) analysis for PE classification and a coefficient of determination (R²) for the Qanadli score and the RV/LV diameter ratio. RESULTS: Quantitative evaluation led to an overall AUC of 0.870 (95% confidence interval [CI]: 0.850-0.900) for PE classification task on the training set and an AUC of 0.852 (95% CI: 0.810-0.890) on the test set. Regression analysis yielded R² value of 0.717 (95% CI: 0.668-0.760) and of 0.723 (95% CI: 0.668-0.766) for the Qanadli score and the RV/LV diameter ratio estimation, respectively on the test set. CONCLUSION: This study shows the feasibility of utilizing AI-based assistance tools in detecting blood clots and estimating PE severity scores with 3D CTPA examinations. This is achieved by leveraging blood clots and cardiac segmentations. Further studies are needed to assess the effectiveness of these tools in clinical practice.

A deep learning model for the diagnosis of sacroiliitis according to Assessment of SpondyloArthritis International Society classification criteria with magnetic resonance imaging.

PURPOSE: The purpose of this study was to develop and evaluate a deep learning model to detect bone marrow edema (BME) in sacroiliac joints and predict the MRI Assessment of SpondyloArthritis International Society (ASAS) definition of active sacroiliitis in patients with chronic inflammatory back pain. MATERIALS AND METHODS: MRI examinations of patients from the French prospective multicenter DESIR cohort (DEvenir des Spondyloarthropathies Indifférenciées Récentes) were used for training, validation and testing. Patients with inflammatory back pain lasting three months to three years were recruited. Test datasets were from MRI follow-ups at five years and ten years. The model was evaluated using an external test dataset from the ASAS cohort. A neuronal network classifier (mask-RCNN) was trained and evaluated for sacroiliac joints detection and BME classification. Diagnostic capabilities of the model to predict ASAS MRI active sacroiliitis (BME in at least two half-slices) were assessed using Matthews correlation coefficient (MCC), sensitivity, specificity, accuracy and AUC. The gold standard was experts' majority decision. RESULTS: A total of 256 patients with 362 MRI examinations from the DESIR cohort were included, with 27% meeting the ASAS definition for experts. A total of 178 MRI examinations were used for the training set, 25 for the validation set and 159 for the evaluation set. MCCs for DESIR baseline, 5-years, and 10-years follow-up were 0.90 (n = 53), 0.64 (n = 70), and 0.61 (n = 36), respectively. AUCs for predicting ASAS MRI were 0.98 (95% CI: 0.93-1), 0.90 (95% CI: 0.79-1), and 0.80 (95% CI: 0.62-1), respectively. The ASAS external validation cohort included 47 patients (mean age 36 ± 10 [SD] years; women, 51%) with 19% meeting the ASAS definition. MCC was 0.62, sensitivity 56% (95% CI: 42-70), specificity 100% (95% CI: 100-100) and AUC 0.76 (95% CI: 0.57-0.95). CONCLUSION: The deep learning model achieves performance close to those of experts for BME detection in sacroiliac joints and determination of active sacroiliitis according to the ASAS definition.

Bone mineral density estimation from a plain X-ray image by learning decomposition into projections of bone-segmented computed tomography.

Osteoporosis is a prevalent bone disease that causes fractures in fragile bones, leading to a decline in daily living activities. Dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) are highly accurate for diagnosing osteoporosis; however, these modalities require special equipment and scan protocols. To frequently monitor bone health, low-cost, low-dose, and ubiquitously available diagnostic methods are highly anticipated. In this study, we aim to perform bone mineral density (BMD) estimation from a plain X-ray image for opportunistic screening, which is potentially useful for early diagnosis. Existing methods have used multi-stage approaches consisting of extraction of the region of interest and simple regression to estimate BMD, which require a large amount of training data. Therefore, we propose an efficient method that learns decomposition into projections of bone-segmented QCT for BMD estimation under limited datasets. The proposed method achieved high accuracy in BMD estimation, where Pearson correlation coefficients of 0.880 and 0.920 were observed for DXA-measured BMD and QCT-measured BMD estimation tasks, respectively, and the root mean square of the coefficient of variation values were 3.27 to 3.79% for four measurements with different poses. Furthermore, we conducted extensive validation experiments, including multi-pose, uncalibrated-CT, and compression experiments toward actual application in routine clinical practice.

Synergic prognostic value of 3D CT scan subcutaneous fat and muscle masses for immunotherapy-treated cancer.

BACKGROUND: Our aim was to explore the prognostic value of anthropometric parameters in a large population of patients treated with immunotherapy. METHODS: We retrospectively included 623 patients with advanced non-small cell lung cancer (NSCLC) (n=318) or melanoma (n=305) treated by an immune-checkpoint-inhibitor having a pretreatment (thorax-)abdomen-pelvis CT scan. An external validation cohort of 55 patients with NSCLC was used. Anthropometric parameters were measured three-dimensionally (3D) by a deep learning software (Anthropometer3DNet) allowing an automatic multislice measurement of lean body mass, fat body mass (FBM), muscle body mass (MBM), visceral fat mass (VFM) and sub-cutaneous fat mass (SFM). Body mass index (BMI) and weight loss (WL) were also retrieved. Receiver operator characteristic (ROC) curve analysis was performed and overall survival was calculated using Kaplan-Meier (KM) curve and Cox regression analysis. RESULTS: In the overall cohort, 1-year mortality rate was 0.496 (95% CI: 0.457 to 0.537) for 309 events and 5-year mortality rate was 0.196 (95% CI: 0.165 to 0.233) for 477 events. In the univariate Kaplan-Meier analysis, prognosis was worse (p<0.001) for patients with low SFM (<3.95 kg/m2), low FBM (<3.26 kg/m2), low VFM (<0.91 kg/m2), low MBM (<5.85 kg/m2) and low BMI (<24.97 kg/m2). The same parameters were significant in the Cox univariate analysis (p<0.001) and, in the multivariate stepwise Cox analysis, the significant parameters were MBM (p<0.0001), SFM (0.013) and WL (0.0003). In subanalyses according to the type of cancer, all body composition parameters were statistically significant for NSCLC in ROC, KM and Cox univariate analysis while, for melanoma, none of them, except MBM, was statistically significant. In multivariate Cox analysis, the significant parameters for NSCLC were MBM (HR=0.81, p=0.0002), SFM (HR=0.94, p=0.02) and WL (HR=1.06, p=0.004). For NSCLC, a KM analysis combining SFM and MBM was able to separate the population in three categories with the worse prognostic for the patients with both low SFM (<5.22 kg/m2) and MBM (<6.86 kg/m2) (p<0001). On the external validation cohort, combination of low SFM and low MBM was pejorative with 63% of mortality at 1 year versus 25% (p=0.0029). CONCLUSIONS: 3D measured low SFM and MBM are significant prognosis factors of NSCLC treated by immune checkpoint inhibitors and can be combined to improve the prognostic value.

Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy.

PURPOSE: The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation. EXPERIMENTAL DESIGN: This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1. Clinical, radiological, and biological data at baseline and first evaluation were analyzed. An external validation set consisting of 31 patients with similar baseline characteristics was used for the validation of the score. RESULTS: Variables were analyzed in a univariate study. The iPD score was constructed using only independent variables, each considered as a worsening factor for the survival of patients. The patients were stratified in three groups: good prognosis (GP), poor prognosis (PP), and critical prognosis (CP). Each group showed significantly different survivals (GP: 11.4, PP: 4.4, CP: 2.3 months median overall survival, P < 0.001, log-rank test). Moreover, the iPD score was able to detect the pseudoprogressors better than other scores. On the validation set, CP patients had significantly worse survival than PP and GP patients (P < 0.05, log-rank test). CONCLUSIONS: The iPD score provides oncologists with a new evaluation, computable at first progression, to decide whether treatment should be continued (for the GP group), or immediately changed for the PP and CP groups. Further validation on larger cohorts is needed to prove its efficacy in clinical practice.

Generative adversarial networks (GAN)-based data augmentation of rare liver cancers: The SFR 2021 Artificial Intelligence Data Challenge.

PURPOSE: The 2021 edition of the Artificial Intelligence Data Challenge was organized by the French Society of Radiology together with the Centre National d'Études Spatiales and CentraleSupélec with the aim to implement generative adversarial networks (GANs) techniques to provide 1000 magnetic resonance imaging (MRI) cases of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC), a rare and aggressive subtype of HCC, generated from a limited number of real cases from multiple French centers. MATERIALS AND METHODS: A dedicated platform was used by the seven inclusion centers to securely upload their anonymized MRI examinations including all three cross-sectional images (one late arterial and one portal-venous phase T1-weighted images and one fat-saturated T2-weighted image) in compliance with general data protection regulation. The quality of the database was checked by experts and manual delineation of the lesions was performed by the expert radiologists involved in each center. Multidisciplinary teams competed between October 11th, 2021 and February 13th, 2022. RESULTS: A total of 91 MTM-HCC datasets of three images each were collected from seven French academic centers. Six teams with a total of 28 individuals participated in this challenge. Each participating team was asked to generate one thousand 3-image cases. The qualitative evaluation was performed by three radiologists using the Likert scale on ten randomly selected cases generated by each participant. A quantitative evaluation was also performed using two metrics, the Frechet inception distance and a leave-one-out accuracy of a 1-Nearest Neighbor algorithm. CONCLUSION: This data challenge demonstrates the ability of GANs techniques to generate a large number of images from a small sample of imaging examinations of a rare malignant tumor.

Synthetic MR image generation of macrotrabecular-massive hepatocellular carcinoma using generative adversarial networks.

PURPOSE: The purpose of this study was to develop a method for generating synthetic MR images of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). MATERIALS AND METHODS: A set of abdominal MR images including fat-saturated T1-weighted images obtained during the arterial and portal venous phases of enhancement and T2-weighted images of 91 patients with MTM-HCC, and another set of MR abdominal images from 67 other patients were used. Synthetic images were obtained using a 3-step pipeline that consisted in: (i), generating a synthetic MTM-HCC tumor on a neutral background; (ii), randomly selecting a background among the 67 patients and a position inside the liver; and (iii), merging the generated tumor in the background at the specified location. Synthetic images were qualitatively evaluated by three radiologists and quantitatively assessed using a mix of 1-nearest neighbor classifier metric and Fréchet inception distance. RESULTS: A set of 1000 triplets of synthetic MTM-HCC images with consistent contrasts were successfully generated. Evaluation of selected synthetic images by three radiologists showed that the method gave realistic, consistent and diversified images. Qualitative and quantitative evaluation led to an overall score of 0.64. CONCLUSION: This study shows the feasibility of generating realistic synthetic MR images with very few training data, by leveraging the wide availability of liver backgrounds. Further studies are needed to assess the added value of those synthetic images for automatic diagnosis of MTM-HCC.

Detection and quantification of pulmonary embolism with artificial intelligence: The SFR 2022 artificial intelligence data challenge.

PURPOSE: In 2022, the French Society of Radiology together with the French Society of Thoracic Imaging and CentraleSupelec organized their 13th data challenge. The aim was to aid in the diagnosis of pulmonary embolism, by identifying the presence of pulmonary embolism and by estimating the ratio between right and left ventricular (RV/LV) diameters, and an arterial obstruction index (Qanadli's score) using artificial intelligence. MATERIALS AND METHODS: The data challenge was composed of three tasks: the detection of pulmonary embolism, the RV/LV diameter ratio, and Qanadli's score. Sixteen centers all over France participated in the inclusion of the cases. A health data hosting certified web platform was established to facilitate the inclusion process of the anonymized CT examinations in compliance with general data protection regulation. CT pulmonary angiography images were collected. Each center provided the CT examinations with their annotations. A randomization process was established to pool the scans from different centers. Each team was required to have at least a radiologist, a data scientist, and an engineer. Data were provided in three batches to the teams, two for training and one for evaluation. The evaluation of the results was determined to rank the participants on the three tasks. RESULTS: A total of 1268 CT examinations were collected from the 16 centers following the inclusion criteria. The dataset was split into three batches of 310, 580 and 378 C T examinations provided to the participants respectively on September 5, 2022, October 7, 2022 and October 9, 2022. Seventy percent of the data from each center were used for training, and 30% for the evaluation. Seven teams with a total of 48 participants including data scientists, researchers, radiologists and engineering students were registered for participation. The metrics chosen for evaluation included areas under receiver operating characteristic curves, specificity and sensitivity for the classification task, and the coefficient of determination r2 for the regression tasks. The winning team achieved an overall score of 0.784. CONCLUSION: This multicenter study suggests that the use of artificial intelligence for the diagnosis of pulmonary embolism is possible on real data. Moreover, providing quantitative measures is mandatory for the interpretability of the results, and is of great aid to the radiologists especially in emergency settings.

Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial.

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2-drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3-81) in cohort 1, 37.5% (95% CI 26.4-49.7) in cohort 2 and 29.7% (95% CI 15.9-47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8-64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7-65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960 .).

Toward semi-automatic biologically effective dose treatment plan optimisation for Gamma Knife radiosurgery.

Objective.Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence.Approach.We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans' objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED95(BED delivered to 95% of the target volume) values.Main results.When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours-days) while typically reaching within 1.2% (0.02-2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments.Significance.We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality.

Prediction of Early Response to Immunotherapy: DCE-US as a New Biomarker.

PURPOSE: The objective of our study is to propose fast, cost-effective, convenient, and effective biomarkers using the perfusion parameters from dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of immune checkpoint inhibitors (ICI) early response. METHODS: The retrospective cohort used in this study included 63 patients with metastatic cancer eligible for immunotherapy. DCE-US was performed at baseline, day 8 (D8), and day 21 (D21) after treatment onset. A tumor perfusion curve was modeled on these three dates, and change in the seven perfusion parameters was measured between baseline, D8, and D21. These perfusion parameters were studied to show the impact of their variation on the overall survival (OS). RESULTS: After the removal of missing or suboptimal DCE-US, the Baseline-D8, the Baseline-D21, and the D8-D21 groups included 37, 53, and 33 patients, respectively. A decrease of more than 45% in the area under the perfusion curve (AUC) between baseline and D21 was significantly associated with better OS (p = 0.0114). A decrease of any amount in the AUC between D8 and D21 was also significantly associated with better OS (p = 0.0370). CONCLUSION: AUC from DCE-US looks to be a promising new biomarker for fast, effective, and convenient immunotherapy response evaluation.

Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume.

Background: Anti-PD-(L)1 treatment is indicated for patients with mismatch repair-deficient (MMRD) tumors, regardless of tumor origin. However, the response rate is highly heterogeneous across MMRD tumors. The objective of the study is to find a score that predicts anti-PD-(L)1 response in patients with MMRD tumors. Methods: Sixty-one patients with various origin of MMRD tumors and treated with anti-PD-(L)1 were retrospectively included in this study. An expert radiologist annotated all tumors present at the baseline and first evaluation CT-scans for all the patients by circumscribing them on their largest axial axis (single slice), allowing us to compute an approximation of their tumor volume. In total, 2120 lesions were annotated, which led to the computation of the total tumor volume for each patient. The RECIST sum of target lesions' diameters and neutrophile-to-lymphocyte (NLR) were also reported at both examinations. These parameters were determined at baseline and first evaluation and the variation between the first evaluation and baseline was calculated, to determine a comprehensive score for overall survival (OS) and progression-free survival (PFS). Results: Total tumor volume at baseline was found to be significantly correlated to the OS (p-value: 0.005) and to the PFS (p-value:<0.001). The variation of the RECIST sum of target lesions' diameters, total tumor volume and NLR were found to be significantly associated to the OS (p-values:<0.001, 0.006,<0.001 respectively) and to the PFS (<0.001,<0.001, 0.007 respectively). The concordance score combining total tumor volume and NLR variation was better at stratifying patients compared to the tumor volume or NLR taken individually according to the OS (pairwise log-rank test p-values: 0.033,<0.001, 0.002) and PFS (pairwise log-rank test p-values: 0.041,<0.001, 0.003). Conclusion: Total tumor volume appears to be a prognostic biomarker of anti-PD-(L)1 response to immunotherapy in metastatic patients with MMRD tumors. Combining tumor volume and NLR with a simple concordance score stratifies patients well according to their survival and offers a good predictive measure of response to immunotherapy.

Rare bioparticle detection via deep metric learning.

Recent deep neural networks have shown superb performance in analyzing bioimages for disease diagnosis and bioparticle classification. Conventional deep neural networks use simple classifiers such as SoftMax to obtain highly accurate results. However, they have limitations in many practical applications that require both low false alarm rate and high recovery rate, e.g., rare bioparticle detection, in which the representative image data is hard to collect, the training data is imbalanced, and the input images in inference time could be different from the training images. Deep metric learning offers a better generatability by using distance information to model the similarity of the images and learning function maps from image pixels to a latent space, playing a vital role in rare object detection. In this paper, we propose a robust model based on a deep metric neural network for rare bioparticle (Cryptosporidium or Giardia) detection in drinking water. Experimental results showed that the deep metric neural network achieved a high accuracy of 99.86% in classification, 98.89% in precision rate, 99.16% in recall rate and zero false alarm rate. The reported model empowers imaging flow cytometry with capabilities of biomedical diagnosis, environmental monitoring, and other biosensing applications.

Myocardial Perfusion Simulation for Coronary Artery Disease: A Coupled Patient-Specific Multiscale Model.

Patient-specific models of blood flow are being used clinically to diagnose and plan treatment for coronary artery disease. A remaining challenge is bridging scales from flow in arteries to the micro-circulation supplying the myocardium. Previously proposed models are descriptive rather than predictive and have not been applied to human data. The goal here is to develop a multiscale patient-specific model enabling blood flow simulation from large coronary arteries to myocardial tissue. Patient vasculatures are segmented from coronary computed tomography angiography data and extended from the image-based model down to the arteriole level using a space-filling forest of synthetic trees. Blood flow is modeled by coupling a 1D model of the coronary arteries to a single-compartment Darcy myocardium model. Simulated results on five patients with non-obstructive coronary artery disease compare overall well to [[Formula: see text]O][Formula: see text]O PET exam data for both resting and hyperemic conditions. Results on a patient with severe obstructive disease link coronary artery narrowing with impaired myocardial blood flow, demonstrating the model's ability to predict myocardial regions with perfusion deficit. This is the first report of a computational model for simulating blood flow from the epicardial coronary arteries to the left ventricle myocardium applied to and validated on human data.

Automatic coronary artery calcium scoring from unenhanced-ECG-gated CT using deep learning.

PURPOSE: The purpose of this study was to develop and evaluate an algorithm that can automatically estimate the amount of coronary artery calcium (CAC) from unenhanced electrocardiography (ECG)-gated computed tomography (CT) cardiac volume acquisitions by using convolutional neural networks (CNN). MATERIALS AND METHODS: The method used a set of five CNN with three-dimensional (3D) U-Net architecture trained on a database of 783 CT examinations to detect and segment coronary artery calcifications in a 3D volume. The Agatston score, the conventional CAC scoring, was then computed slice by slice from the resulting segmentation mask and compared to the ground truth manually estimated by radiologists. The quality of the estimation was assessed with the concordance index (C-index) on CAC risk category on a separate testing set of 98 independent CT examinations. RESULTS: The final model yielded a C-index of 0.951 on the testing set. The remaining errors of the method were mainly observed on small-size and/or low-density calcifications, or calcifications located near the mitral valve or ring. CONCLUSION: The deep learning-based method proposed here to compute automatically the CAC score from unenhanced-ECG-gated cardiac CT is fast, robust and yields accuracy similar to those of other artificial intelligence methods, which could improve workflow efficiency, eliminating the time spent on manually selecting coronary calcifications to compute the Agatston score.