Sopa: a technology-invariant pipeline for analyses of image-based spatial omics.

Spatial omics data allow in-depth analysis of tissue architectures, opening new opportunities for biological discovery. In particular, imaging techniques offer single-cell resolutions, providing essential insights into cellular organizations and dynamics. Yet, the complexity of such data presents analytical challenges and demands substantial computing resources. Moreover, the proliferation of diverse spatial omics technologies, such as Xenium, MERSCOPE, CosMX in spatial-transcriptomics, and MACSima and PhenoCycler in multiplex imaging, hinders the generality of existing tools. We introduce Sopa ( https://github.com/gustaveroussy/sopa ), a technology-invariant, memory-efficient pipeline with a unified visualizer for all image-based spatial omics. Built upon the universal SpatialData framework, Sopa optimizes tasks like segmentation, transcript/channel aggregation, annotation, and geometric/spatial analysis. Its output includes user-friendly web reports and visualizer files, as well as comprehensive data files for in-depth analysis. Overall, Sopa represents a significant step toward unifying spatial data analysis, enabling a more comprehensive understanding of cellular interactions and tissue organization in biological systems.

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 .).

Dosiomics-Based Prediction of Radiation-Induced Valvulopathy after Childhood Cancer.

Valvular Heart Disease (VHD) is a known late complication of radiotherapy for childhood cancer (CC), and identifying high-risk survivors correctly remains a challenge. This paper focuses on the distribution of the radiation dose absorbed by heart tissues. We propose that a dosiomics signature could provide insight into the spatial characteristics of the heart dose associated with a VHD, beyond the already-established risk induced by high doses. We analyzed data from the 7670 survivors of the French Childhood Cancer Survivors' Study (FCCSS), 3902 of whom were treated with radiotherapy. In all, 63 (1.6%) survivors that had been treated with radiotherapy experienced a VHD, and 57 of them had heterogeneous heart doses. From the heart-dose distribution of each survivor, we extracted 93 first-order and spatial dosiomics features. We trained random forest algorithms adapted for imbalanced classification and evaluated their predictive performance compared to the performance of standard mean heart dose (MHD)-based models. Sensitivity analyses were also conducted for sub-populations of survivors with spatially heterogeneous heart doses. Our results suggest that MHD and dosiomics-based models performed equally well globally in our cohort and that, when considering the sub-population having received a spatially heterogeneous dose distribution, the predictive capability of the models is significantly improved by the use of the dosiomics features. If these findings are further validated, the dosiomics signature may be incorporated into machine learning algorithms for radiation-induced VHD risk assessment and, in turn, into the personalized refinement of follow-up guidelines.

Influence of Lung Reconstruction Algorithms on Interstitial Lung Pattern Recognition on CT.

Despite current recommendations, there is no recent scientific study comparing the influence of CT reconstruction kernels on lung pattern recognition in interstitial lung disease (ILD).To evaluate the sensitivity of lung (i70) and soft (i30) CT kernel algorithms for the diagnosis of ILD patterns.We retrospectively extracted between 15-25 pattern annotations per case (1 annotation = 15 slices of 1 mm) from 23 subjects resulting in 408 annotation stacks per lung kernel and soft kernel reconstructions. Two subspecialized chest radiologists defined the ground truth in consensus. 4 residents, 2 fellows, and 2 general consultants in radiology with 3 to 13 years of experience in chest imaging performed a blinded readout. In order to account for data clustering, a generalized linear mixed model (GLMM) with random intercept for reader and nested for patient and image and a kernel/experience interaction term was used to analyze the results.The results of the GLMM indicated, that the odds of correct pattern recognition is 12 % lower with lung kernel compared to soft kernel; however, this was not statistically significant (OR 0.88; 95%-CI, 0.73-1.06; p = 0.187). Furthermore, the consultants' odds of correct pattern recognition was 78 % higher than the residents' odds, although this finding did not reach statistical significance either (OR 1.78; 95%-CI, 0.62-5.06; p = 0.283). There was no significant interaction between the two fixed terms kernel and experience. Intra-rater agreement between lung and soft kernel was substantial (κ = 0.63 ±â€Š0.19). The mean inter-rater agreement for lung/soft kernel was κ = 0.37 ±â€Š0.17/κ = 0.38 ±â€Š0.17.There is no significant difference between lung and soft kernel reconstructed CT images for the correct pattern recognition in ILD. There are non-significant trends indicating that the use of soft kernels and a higher level of experience lead to a higher probability of correct pattern identification. · There is no significant difference between lung and soft kernel reconstructed CT images for the correct pattern recognition in interstitial lung disease.. · There are even non-significant tendencies that the use of soft kernels lead to a higher probability of correct pattern identification.. · These results challenge the current recommendations and the routinely performed separate lung kernel reconstructions for lung parenchyma analysis.. CITATION FORMAT: · Klaus JB, Christodoulidis S, Peters AA et al. Influence of Lung Reconstruction Algorithms on Interstitial Lung Pattern Recognition on CT. Fortschr Röntgenstr 2023; 195: 47 - 54.

Deep learning for lung disease segmentation on CT: Which reconstruction kernel should be used?

PURPOSE: The purpose of this study was to determine whether a single reconstruction kernel or both high and low frequency kernels should be used for training deep learning models for the segmentation of diffuse lung disease on chest computed tomography (CT). MATERIALS AND METHODS: Two annotated datasets of COVID-19 pneumonia (323,960 slices) and interstitial lung disease (ILD) (4,284 slices) were used. Annotated CT images were used to train a U-Net architecture to segment disease. All CT slices were reconstructed using both a lung kernel (LK) and a mediastinal kernel (MK). Three different trainings, resulting in three different models were compared for each disease: training on LK only, MK only or LK+MK images. Dice similarity scores (DSC) were compared using the Wilcoxon signed-rank test. RESULTS: Models only trained on LK images performed better on LK images than on MK images (median DSC = 0.62 [interquartile range (IQR): 0.54, 0.69] vs. 0.60 [IQR: 0.50, 0.70], P < 0.001 for COVID-19 and median DSC = 0.62 [IQR: 0.56, 0.69] vs. 0.50 [IQR 0.43, 0.57], P < 0.001 for ILD). Similarly, models only trained on MK images performed better on MK images (median DSC = 0.62 [IQR: 0.53, 0.68] vs. 0.54 [IQR: 0.47, 0.63], P < 0.001 for COVID-19 and 0.69 [IQR: 0.61, 0.73] vs. 0.63 [IQR: 0.53, 0.70], P < 0.001 for ILD). Models trained on both kernels performed better or similarly than those trained on only one kernel. For COVID-19, median DSC was 0.67 (IQR: =0.59, 0.73) when applied on LK images and 0.67 (IQR: 0.60, 0.74) when applied on MK images (P < 0.001 for both). For ILD, median DSC was 0.69 (IQR: 0.63, 0.73) when applied on LK images (P = 0.006) and 0.68 (IQR: 0.62, 0.72) when applied on MK images (P > 0.99). CONCLUSION: Reconstruction kernels impact the performance of deep learning-based models for lung disease segmentation. Training on both LK and MK images improves the performance.

Perspectives and Preferences of Adult Smartphone Users Regarding Nutrition and Diet Apps: Web-Based Survey Study.

BACKGROUND: Digital technologies have evolved dramatically in recent years, finding applications in a variety of aspects of everyday life. Smartphones and mobile apps are being used for a steadily increasing number of tasks, including health monitoring. A large number of nutrition and diet apps are available, and some of them are very popular in terms of user downloads, highlighting a trend toward diet monitoring and assessment. OBJECTIVE: We sought to explore the perspectives of end users on the features, current use, and acceptance of nutrition and diet mHealth apps with a survey. We expect that this study can provide user insights to assist researchers and developers in achieving innovative dietary assessments. METHODS: A multidisciplinary team designed and compiled the survey. Before its release, it was pilot-tested by 18 end users. A 19-question survey was finally developed and was translated into six languages: English, German, French, Spanish, Italian, and Greek. The participants were mainly recruited via social media platforms and mailing lists of universities, university hospitals, and patient associations. RESULTS: A total of 2382 respondents (1891 female, 79.4%; 474 male, 19.9%; and 17 neither, 0.7%) with a mean age of 27.2 years (SD 8.5) completed the survey. Approximately half of the participants (1227/2382, 51.5%) had used a nutrition and diet app. The primary criteria for selecting such an app were ease of use (1570/2382, 65.9%), free cost (1413/2382, 59.3%), and ability to produce automatic readings of caloric content (1231/2382, 51.7%) and macronutrient content (1117/2382, 46.9%) (ie, food type and portion size are estimated by the system without any contribution from the user). An app was less likely to be selected if it incorrectly estimated portion size, calories, or nutrient content (798/2382, 33.5%). Other important limitations included the use of a database that does not include local foods (655/2382, 27.5%) or that may omit major foods (977/2382, 41%). CONCLUSIONS: This comprehensive study in a mostly European population assessed the preferences and perspectives of potential nutrition and diet app users. Understanding user needs will benefit researchers who develop tools for innovative dietary assessment as well as those who assist research on behavioral changes related to nutrition.

Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment.

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.

AI-driven quantification, staging and outcome prediction of COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) emerged in 2019 and disseminated around the world rapidly. Computed tomography (CT) imaging has been proven to be an important tool for screening, disease quantification and staging. The latter is of extreme importance for organizational anticipation (availability of intensive care unit beds, patient management planning) as well as to accelerate drug development through rapid, reproducible and quantified assessment of treatment response. Even if currently there are no specific guidelines for the staging of the patients, CT together with some clinical and biological biomarkers are used. In this study, we collected a multi-center cohort and we investigated the use of medical imaging and artificial intelligence for disease quantification, staging and outcome prediction. Our approach relies on automatic deep learning-based disease quantification using an ensemble of architectures, and a data-driven consensus for the staging and outcome prediction of the patients fusing imaging biomarkers with clinical and biological attributes. Highly promising results on multiple external/independent evaluation cohorts as well as comparisons with expert human readers demonstrate the potentials of our approach.

What Healthcare Professionals Think of "Nutrition & Diet" Apps: An International Survey.

Accurate dietary assessment is crucial for both the prevention and treatment of nutrition-related diseases. Since mobile-based dietary assessment solutions are promising, we sought to examine the acceptability of "Nutrition and Diet" (ND) apps by Healthcare Professionals (HCP), explore their preferences on apps' features and identify predictors of acceptance. A 23 question survey was developed by an interdisciplinary team and pilot-tested. The survey was completed by 1001 HCP from 73 countries and 6 continents. The HCP (dietitians: 833, doctors: 75, nurses: 62, other: 31/females: 847, males: 150, neither: 4) had a mean age (SD) of 34.4 (10.2) years and mean job experience in years (SD): 7.7 (8.2). There were 45.5% who have recommended ND apps to their clients/patients. Of those who have not yet recommended an app, 22.5% do not know of their existence. Important criteria for selecting an app were ease of use (87.1%), apps being free of charge (72.6%) and validated (69%). Significant barriers were the use of inaccurate food composition database (52%), lack of local food composition database support (48.2%) and tech-savviness (43.3%). Although the adoption of smartphones is growing and mobile health research is advancing, there is room for improvement in the recommendation of ND apps by HCP.

Deep Learning-Based Concurrent Brain Registration and Tumor Segmentation.

Image registration and segmentation are the two most studied problems in medical image analysis. Deep learning algorithms have recently gained a lot of attention due to their success and state-of-the-art results in variety of problems and communities. In this paper, we propose a novel, efficient, and multi-task algorithm that addresses the problems of image registration and brain tumor segmentation jointly. Our method exploits the dependencies between these tasks through a natural coupling of their interdependencies during inference. In particular, the similarity constraints are relaxed within the tumor regions using an efficient and relatively simple formulation. We evaluated the performance of our formulation both quantitatively and qualitatively for registration and segmentation problems on two publicly available datasets (BraTS 2018 and OASIS 3), reporting competitive results with other recent state-of-the-art methods. Moreover, our proposed framework reports significant amelioration (p < 0.005) for the registration performance inside the tumor locations, providing a generic method that does not need any predefined conditions (e.g., absence of abnormalities) about the volumes to be registered. Our implementation is publicly available online at https://github.com/TheoEst/joint_registration_tumor_segmentation.

Meta-analysis of the radiological and clinical features of Usual Interstitial Pneumonia (UIP) and Nonspecific Interstitial Pneumonia (NSIP).

PURPOSE: To conduct a meta-analysis to determine specific computed tomography (CT) patterns and clinical features that discriminate between nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). MATERIALS AND METHODS: The PubMed/Medline and Embase databases were searched for studies describing the radiological patterns of UIP and NSIP in chest CT images. Only studies involving histologically confirmed diagnoses and a consensus diagnosis by an interstitial lung disease (ILD) board were included in this analysis. The radiological patterns and patient demographics were extracted from suitable articles. We used random-effects meta-analysis by DerSimonian & Laird and calculated pooled odds ratios for binary data and pooled mean differences for continuous data. RESULTS: Of the 794 search results, 33 articles describing 2,318 patients met the inclusion criteria. Twelve of these studies included both NSIP (338 patients) and UIP (447 patients). NSIP-patients were significantly younger (NSIP: median age 54.8 years, UIP: 59.7 years; mean difference (MD) -4.4; p = 0.001; 95% CI: -6.97 to -1.77), less often male (NSIP: median 52.8%, UIP: 73.6%; pooled odds ratio (OR) 0.32; p<0.001; 95% CI: 0.17 to 0.60), and less often smokers (NSIP: median 55.1%, UIP: 73.9%; OR 0.42; p = 0.005; 95% CI: 0.23 to 0.77) than patients with UIP. The CT findings from patients with NSIP revealed significantly lower levels of the honeycombing pattern (NSIP: median 28.9%, UIP: 73.4%; OR 0.07; p<0.001; 95% CI: 0.02 to 0.30) with less peripheral predominance (NSIP: median 41.8%, UIP: 83.3%; OR 0.21; p<0.001; 95% CI: 0.11 to 0.38) and more subpleural sparing (NSIP: median 40.7%, UIP: 4.3%; OR 16.3; p = 0.005; 95% CI: 2.28 to 117). CONCLUSION: Honeycombing with a peripheral predominance was significantly associated with a diagnosis of UIP. The NSIP pattern showed more subpleural sparing. The UIP pattern was predominantly observed in elderly males with a history of smoking, whereas NSIP occurred in a younger patient population.

Computer-Aided Diagnosis of Pulmonary Fibrosis Using Deep Learning and CT Images.

OBJECTIVES: The objective of this study is to assess the performance of a computer-aided diagnosis (CAD) system (INTACT system) for the automatic classification of high-resolution computed tomography images into 4 radiological diagnostic categories and to compare this with the performance of radiologists on the same task. MATERIALS AND METHODS: For the comparison, a total of 105 cases of pulmonary fibrosis were studied (54 cases of nonspecific interstitial pneumonia and 51 cases of usual interstitial pneumonia). All diagnoses were interstitial lung disease board consensus diagnoses (radiologically or histologically proven cases) and were retrospectively selected from our database. Two subspecialized chest radiologists made a consensual ground truth radiological diagnosis, according to the Fleischner Society recommendations. A comparison analysis was performed between the INTACT system and 2 other radiologists with different years of experience (readers 1 and 2). The INTACT system consists of a sequential pipeline in which first the anatomical structures of the lung are segmented, then the various types of pathological lung tissue are identified and characterized, and this information is then fed to a random forest classifier able to recommend a radiological diagnosis. RESULTS: Reader 1, reader 2, and INTACT achieved similar accuracy for classifying pulmonary fibrosis into the original 4 categories: 0.6, 0.54, and 0.56, respectively, with P > 0.45. The INTACT system achieved an F-score (harmonic mean for precision and recall) of 0.56, whereas the 2 readers, on average, achieved 0.57 (P = 0.991). For the pooled classification (2 groups, with and without the need for biopsy), reader 1, reader 2, and CAD had similar accuracies of 0.81, 0.70, and 0.81, respectively. The F-score was again similar for the CAD system and the radiologists. The CAD system and the average reader reached F-scores of 0.80 and 0.79 (P = 0.898). CONCLUSIONS: We found that a computer-aided detection algorithm based on machine learning was able to classify idiopathic pulmonary fibrosis with similar accuracy to a human reader.

An Artificial Intelligence-Based System for Nutrient Intake Assessment of Hospitalised Patients.

Regular nutrient intake monitoring in hospitalised patients plays a critical role in reducing the risk of disease-related malnutrition (DRM). Although several methods to estimate nutrient intake have been developed, there is still a clear demand for a more reliable and fully automated technique, as this could improve the data accuracy and reduce both the participant burden and the health costs. In this paper, we propose a novel system based on artificial intelligence to accurately estimate nutrient intake, by simply processing RGB depth image pairs captured before and after a meal consumption. For the development and evaluation of the system, a dedicated and new database of images and recipes of 322 meals was assembled, coupled to data annotation using innovative strategies. With this database, a system was developed that employed a novel multi-task neural network and an algorithm for 3D surface construction. This allowed sequential semantic food segmentation and estimation of the volume of the consumed food, and permitted fully automatic estimation of nutrient intake for each food type with a 15% estimation error.

Semantic Segmentation of Pathological Lung Tissue With Dilated Fully Convolutional Networks.

Early and accurate diagnosis of interstitial lung diseases (ILDs) is crucial for making treatment decisions, but can be challenging even for experienced radiologists. The diagnostic procedure is based on the detection and recognition of the different ILD pathologies in thoracic CT scans, yet their manifestation often appears similar. In this study, we propose the use of a deep purely convolutional neural network for the semantic segmentation of ILD patterns, as the basic component of a computer aided diagnosis system for ILDs. The proposed CNN, which consists of convolutional layers with dilated filters, takes as input a lung CT image of arbitrary size and outputs the corresponding label map. We trained and tested the network on a data set of 172 sparsely annotated CT scans, within a cross-validation scheme. The training was performed in an end-to-end and semisupervised fashion, utilizing both labeled and nonlabeled image regions. The experimental results show significant performance improvement with respect to the state of the art.

Multisource Transfer Learning With Convolutional Neural Networks for Lung Pattern Analysis.

Early diagnosis of interstitial lung diseases is crucial for their treatment, but even experienced physicians find it difficult, as their clinical manifestations are similar. In order to assist with the diagnosis, computer-aided diagnosis systems have been developed. These commonly rely on a fixed scale classifier that scans CT images, recognizes textural lung patterns, and generates a map of pathologies. In a previous study, we proposed a method for classifying lung tissue patterns using a deep convolutional neural network (CNN), with an architecture designed for the specific problem. In this study, we present an improved method for training the proposed network by transferring knowledge from the similar domain of general texture classification. Six publicly available texture databases are used to pretrain networks with the proposed architecture, which are then fine-tuned on the lung tissue data. The resulting CNNs are combined in an ensemble and their fused knowledge is compressed back to a network with the original architecture. The proposed approach resulted in an absolute increase of about 2% in the performance of the proposed CNN. The results demonstrate the potential of transfer learning in the field of medical image analysis, indicate the textural nature of the problem and show that the method used for training a network can be as important as designing its architecture.

Lung Pattern Classification for Interstitial Lung Diseases Using a Deep Convolutional Neural Network.

Automated tissue characterization is one of the most crucial components of a computer aided diagnosis (CAD) system for interstitial lung diseases (ILDs). Although much research has been conducted in this field, the problem remains challenging. Deep learning techniques have recently achieved impressive results in a variety of computer vision problems, raising expectations that they might be applied in other domains, such as medical image analysis. In this paper, we propose and evaluate a convolutional neural network (CNN), designed for the classification of ILD patterns. The proposed network consists of 5 convolutional layers with 2 × 2 kernels and LeakyReLU activations, followed by average pooling with size equal to the size of the final feature maps and three dense layers. The last dense layer has 7 outputs, equivalent to the classes considered: healthy, ground glass opacity (GGO), micronodules, consolidation, reticulation, honeycombing and a combination of GGO/reticulation. To train and evaluate the CNN, we used a dataset of 14696 image patches, derived by 120 CT scans from different scanners and hospitals. To the best of our knowledge, this is the first deep CNN designed for the specific problem. A comparative analysis proved the effectiveness of the proposed CNN against previous methods in a challenging dataset. The classification performance ( ~ 85.5%) demonstrated the potential of CNNs in analyzing lung patterns. Future work includes, extending the CNN to three-dimensional data provided by CT volume scans and integrating the proposed method into a CAD system that aims to provide differential diagnosis for ILDs as a supportive tool for radiologists.