Development of Clinical Radiomics-Based Models to Predict Survival Outcome in Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study.

PURPOSE: This multicenter retrospective study aims to identify reliable clinical and radiomic features to build machine learning models that predict progression-free survival (PFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Between 2010 and 2020 pre-treatment contrast-enhanced CT scans of 287 pathology-confirmed PDAC patients from two sites of the Hopital Universitaire de Bruxelles (HUB) and from 47 hospitals within the HUB network were retrospectively analysed. Demographic, clinical, and survival data were also collected. Gross tumour volume (GTV) and non-tumoral pancreas (RPV) were semi-manually segmented and radiomics features were extracted. Patients from two HUB sites comprised the training dataset, while those from the remaining 47 hospitals of the HUB network constituted the testing dataset. A three-step method was used for feature selection. Based on the GradientBoostingSurvivalAnalysis classifier, different machine learning models were trained and tested to predict OS and PFS. Model performances were assessed using the C-index and Kaplan-Meier curves. SHAP analysis was applied to allow for post hoc interpretability. RESULTS: A total of 107 radiomics features were extracted from each of the GTV and RPV. Fourteen subgroups of features were selected: clinical, GTV, RPV, clinical & GTV, clinical & GTV & RPV, GTV-volume and RPV-volume both for OS and PFS. Subsequently, 14 Gradient Boosting Survival Analysis models were trained and tested. In the testing dataset, the clinical & GTV model demonstrated the highest performance for OS (C-index: 0.72) among all other models, while for PFS, the clinical model exhibited a superior performance (C-index: 0.70). CONCLUSIONS: An integrated approach, combining clinical and radiomics features, excels in predicting OS, whereas clinical features demonstrate strong performance in PFS prediction.

Computational methods for metastasis detection in lymph nodes and characterization of the metastasis-free lymph node microarchitecture: A systematic-narrative hybrid review.

Background: Histological examination of tumor draining lymph nodes (LNs) plays a vital role in cancer staging and prognostication. However, as soon as a LN is classed as metastasis-free, no further investigation will be performed and thus, potentially clinically relevant information detectable in tumor-free LNs is currently not captured. Objective: To systematically study and critically assess methods for the analysis of digitized histological LN images described in published research. Methods: A systematic search was conducted in several public databases up to December 2023 using relevant search terms. Studies using brightfield light microscopy images of hematoxylin and eosin or immunohistochemically stained LN tissue sections aiming to detect and/or segment LNs, their compartments or metastatic tumor using artificial intelligence (AI) were included. Dataset, AI methodology, cancer type, and study objective were compared between articles. Results: A total of 7201 articles were collected and 73 articles remained for detailed analyses after article screening. Of the remaining articles, 86% aimed at LN metastasis identification, 8% aimed at LN compartment segmentation, and remaining focused on LN contouring. Furthermore, 78% of articles used patch classification and 22% used pixel segmentation models for analyses. Five out of six studies (83%) of metastasis-free LNs were performed on publicly unavailable datasets, making quantitative article comparison impossible. Conclusions: Multi-scale models mimicking multiple microscopy zooms show promise for computational LN analysis. Large-scale datasets are needed to establish the clinical relevance of analyzing metastasis-free LN in detail. Further research is needed to identify clinically interpretable metrics for LN compartment characterization.

A clinically relevant computed tomography (CT) radiomics strategy for intracranial rodent brain tumour monitoring.

Here, we establish a CT-radiomics based method for application in invasive, orthotopic rodent brain tumour models. Twenty four NOD/SCID mice were implanted with U87R-Luc2 GBM cells and longitudinally imaged via contrast enhanced (CE-CT) imaging. Pyradiomics was employed to extract CT-radiomic features from the tumour-implanted hemisphere and non-tumour-implanted hemisphere of acquired CT-scans. Inter-correlated features were removed (Spearman correlation > 0.85) and remaining features underwent predictive analysis (recursive feature elimination or Boruta algorithm). An area under the curve of the receiver operating characteristic curve was implemented to evaluate radiomic features for their capacity to predict defined outcomes. Firstly, we identified a subset of radiomic features which distinguish the tumour-implanted hemisphere and non- tumour-implanted hemisphere (i.e, tumour presence from normal tissue). Secondly, we successfully translate preclinical CT-radiomic pipelines to GBM patient CT scans (n = 10), identifying similar trends in tumour-specific feature intensities (E.g. 'glszm Zone Entropy'), thereby suggesting a mouse-to-human species conservation (a conservation of radiomic features across species). Thirdly, comparison of features across timepoints identify features which support preclinical tumour detection earlier than is possible by visual assessment of CT scans. This work establishes robust, preclinical CT-radiomic pipelines and describes the application of CE-CT for in-depth orthotopic brain tumour monitoring. Overall we provide evidence for the role of pre-clinical 'discovery' radiomics in the neuro-oncology space.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

An Interpretable Radiomics Model Based on Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to develop and validate an interpretable radiomics model based on two-dimensional shear wave elastography (2D-SWE) for symptomatic post-hepatectomy liver failure (PHLF) prediction in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 345 consecutive patients were enrolled. A five-fold cross-validation was performed during training, and the models were evaluated in the independent test cohort. A multi-patch radiomics model was established based on the 2D-SWE images for predicting symptomatic PHLF. Clinical features were incorporated into the models to train the clinical-radiomics model. The radiomics model and the clinical-radiomics model were compared with the clinical model comprising clinical variables and other clinical predictive indices, including the model for end-stage liver disease (MELD) score and albumin-bilirubin (ALBI) score. Shapley Additive exPlanations (SHAP) was used for post hoc interpretability of the radiomics model. RESULTS: The clinical-radiomics model achieved an AUC of 0.867 (95% CI 0.787-0.947) in the five-fold cross-validation, and this score was higher than that of the clinical model (AUC: 0.809; 95% CI: 0.715-0.902) and the radiomics model (AUC: 0.746; 95% CI: 0.681-0.811). The clinical-radiomics model showed an AUC of 0.822 in the test cohort, higher than that of the clinical model (AUC: 0.684, p = 0.007), radiomics model (AUC: 0.784, p = 0.415), MELD score (AUC: 0.529, p < 0.001), and ALBI score (AUC: 0.644, p = 0.016). The SHAP analysis showed that the first-order radiomics features, including first-order maximum 64 × 64, first-order 90th percentile 64 × 64, and first-order 10th percentile 32 × 32, were the most important features for PHLF prediction. CONCLUSION: An interpretable clinical-radiomics model based on 2D-SWE and clinical variables can help in predicting symptomatic PHLF in HCC.

The clinical importance of the host anti-tumour reaction patterns in regional tumour draining lymph nodes in patients with locally advanced resectable gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear. METHODS: A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC). RESULTS: A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH. CONCLUSIONS: This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy.

MSCDA: Multi-level semantic-guided contrast improves unsupervised domain adaptation for breast MRI segmentation in small datasets.

Deep learning (DL) applied to breast tissue segmentation in magnetic resonance imaging (MRI) has received increased attention in the last decade, however, the domain shift which arises from different vendors, acquisition protocols, and biological heterogeneity, remains an important but challenging obstacle on the path towards clinical implementation. In this paper, we propose a novel Multi-level Semantic-guided Contrastive Domain Adaptation (MSCDA) framework to address this issue in an unsupervised manner. Our approach incorporates self-training with contrastive learning to align feature representations between domains. In particular, we extend the contrastive loss by incorporating pixel-to-pixel, pixel-to-centroid, and centroid-to-centroid contrasts to better exploit the underlying semantic information of the image at different levels. To resolve the data imbalance problem, we utilize a category-wise cross-domain sampling strategy to sample anchors from target images and build a hybrid memory bank to store samples from source images. We have validated MSCDA with a challenging task of cross-domain breast MRI segmentation between datasets of healthy volunteers and invasive breast cancer patients. Extensive experiments show that MSCDA effectively improves the model's feature alignment capabilities between domains, outperforming state-of-the-art methods. Furthermore, the framework is shown to be label-efficient, achieving good performance with a smaller source dataset. The code is publicly available at https://github.com/ShengKuangCN/MSCDA.

Combining Deep Learning and Handcrafted Radiomics for Classification of Suspicious Lesions on Contrast-enhanced Mammograms.

Background Handcrafted radiomics and deep learning (DL) models individually achieve good performance in lesion classification (benign vs malignant) on contrast-enhanced mammography (CEM) images. Purpose To develop a comprehensive machine learning tool able to fully automatically identify, segment, and classify breast lesions on the basis of CEM images in recall patients. Materials and Methods CEM images and clinical data were retrospectively collected between 2013 and 2018 for 1601 recall patients at Maastricht UMC+ and 283 patients at Gustave Roussy Institute for external validation. Lesions with a known status (malignant or benign) were delineated by a research assistant overseen by an expert breast radiologist. Preprocessed low-energy and recombined images were used to train a DL model for automatic lesion identification, segmentation, and classification. A handcrafted radiomics model was also trained to classify both human- and DL-segmented lesions. Sensitivity for identification and the area under the receiver operating characteristic curve (AUC) for classification were compared between individual and combined models at the image and patient levels. Results After the exclusion of patients without suspicious lesions, the total number of patients included in the training, test, and validation data sets were 850 (mean age, 63 years ± 8 [SD]), 212 (62 years ± 8), and 279 (55 years ± 12), respectively. In the external data set, lesion identification sensitivity was 90% and 99% at the image and patient level, respectively, and the mean Dice coefficient was 0.71 and 0.80 at the image and patient level, respectively. Using manual segmentations, the combined DL and handcrafted radiomics classification model achieved the highest AUC (0.88 [95% CI: 0.86, 0.91]) (P < .05 except compared with DL, handcrafted radiomics, and clinical features model, where P = .90). Using DL-generated segmentations, the combined DL and handcrafted radiomics model showed the highest AUC (0.95 [95% CI: 0.94, 0.96]) (P < .05). Conclusion The DL model accurately identified and delineated suspicious lesions on CEM images, and the combined output of the DL and handcrafted radiomics models achieved good diagnostic performance. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bahl and Do in this issue.

External validation of 18 F-FDG PET-based radiomic models on identification of residual oesophageal cancer after neoadjuvant chemoradiotherapy.

OBJECTIVES: Detection of residual oesophageal cancer after neoadjuvant chemoradiotherapy (nCRT) is important to guide treatment decisions regarding standard oesophagectomy or active surveillance. The aim was to validate previously developed 18 F-FDG PET-based radiomic models to detect residual local tumour and to repeat model development (i.e. 'model extension') in case of poor generalisability. METHODS: This was a retrospective cohort study in patients collected from a prospective multicentre study in four Dutch institutes. Patients underwent nCRT followed by oesophagectomy between 2013 and 2019. Outcome was tumour regression grade (TRG) 1 (0% tumour) versus TRG 2-3-4 (≥1% tumour). Scans were acquired according to standardised protocols. Discrimination and calibration were assessed for the published models with optimism-corrected AUCs >0.77. For model extension, the development and external validation cohorts were combined. RESULTS: Baseline characteristics of the 189 patients included [median age 66 years (interquartile range 60-71), 158/189 male (84%), 40/189 TRG 1 (21%) and 149/189 (79%) TRG 2-3-4] were comparable to the development cohort. The model including cT stage plus the feature 'sum entropy' had best discriminative performance in external validation (AUC 0.64, 95% confidence interval 0.55-0.73), with a calibration slope and intercept of 0.16 and 0.48 respectively. An extended bootstrapped LASSO model yielded an AUC of 0.65 for TRG 2-3-4 detection. CONCLUSION: The high predictive performance of the published radiomic models could not be replicated. The extended model had moderate discriminative ability. The investigated radiomic models appeared inaccurate to detect local residual oesophageal tumour and cannot be used as an adjunct tool for clinical decision-making in patients.

From Head and Neck Tumour and Lymph Node Segmentation to Survival Prediction on PET/CT: An End-to-End Framework Featuring Uncertainty, Fairness, and Multi-Region Multi-Modal Radiomics.

Automatic delineation and detection of the primary tumour (GTVp) and lymph nodes (GTVn) using PET and CT in head and neck cancer and recurrence-free survival prediction can be useful for diagnosis and patient risk stratification. We used data from nine different centres, with 524 and 359 cases used for training and testing, respectively. We utilised posterior sampling of the weight space in the proposed segmentation model to estimate the uncertainty for false positive reduction. We explored the prognostic potential of radiomics features extracted from the predicted GTVp and GTVn in PET and CT for recurrence-free survival prediction and used SHAP analysis for explainability. We evaluated the bias of models with respect to age, gender, chemotherapy, HPV status, and lesion size. We achieved an aggregate Dice score of 0.774 and 0.760 on the test set for GTVp and GTVn, respectively. We observed a per image false positive reduction of 19.5% and 7.14% using the uncertainty threshold for GTVp and GTVn, respectively. Radiomics features extracted from GTVn in PET and from both GTVp and GTVn in CT are the most prognostic, and our model achieves a C-index of 0.672 on the test set. Our framework incorporates uncertainty estimation, fairness, and explainability, demonstrating the potential for accurate detection and risk stratification.

Automated detection and delineation of lymph nodes in haematoxylin & eosin stained digitised slides.

Treatment of patients with oesophageal and gastric cancer (OeGC) is guided by disease stage, patient performance status and preferences. Lymph node (LN) status is one of the strongest prognostic factors for OeGC patients. However, survival varies between patients with the same disease stage and LN status. We recently showed that LN size from patients with OeGC might also have prognostic value, thus making delineations of LNs essential for size estimation and the extraction of other imaging biomarkers. We hypothesized that a machine learning workflow is able to: (1) find digital H&E stained slides containing LNs, (2) create a scoring system providing degrees of certainty for the results, and (3) delineate LNs in those images. To train and validate the pipeline, we used 1695 H&E slides from the OE02 trial. The dataset was divided into training (80%) and validation (20%). The model was tested on an external dataset of 826 H&E slides from the OE05 trial. U-Net architecture was used to generate prediction maps from which predefined features were extracted. These features were subsequently used to train an XGBoost model to determine if a region truly contained a LN. With our innovative method, the balanced accuracies of the LN detection were 0.93 on the validation dataset (0.83 on the test dataset) compared to 0.81 (0.81) on the validation (test) datasets when using the standard method of thresholding U-Net predictions to arrive at a binary mask. Our method allowed for the creation of an "uncertain" category, and partly limited false-positive predictions on the external dataset. The mean Dice score was 0.73 (0.60) per-image and 0.66 (0.48) per-LN for the validation (test) datasets. Our pipeline detects images with LNs more accurately than conventional methods, and high-throughput delineation of LNs can facilitate future LN content analyses of large datasets.

Deep learning based identification of bone scintigraphies containing metastatic bone disease foci.

PURPOSE: Metastatic bone disease (MBD) is the most common form of metastases, most frequently deriving from prostate cancer. MBD is screened with bone scintigraphy (BS), which have high sensitivity but low specificity for the diagnosis of MBD, often requiring further investigations. Deep learning (DL) - a machine learning technique designed to mimic human neuronal interactions- has shown promise in the field of medical imaging analysis for different purposes, including segmentation and classification of lesions. In this study, we aim to develop a DL algorithm that can classify areas of increased uptake on bone scintigraphy scans. METHODS: We collected 2365 BS from three European medical centres. The model was trained and validated on 1203 and 164 BS scans respectively. Furthermore we evaluated its performance on an external testing set composed of 998 BS scans. We further aimed to enhance the explainability of our developed algorithm, using activation maps. We compared the performance of our algorithm to that of 6 nuclear medicine physicians. RESULTS: The developed DL based algorithm is able to detect MBD on BSs, with high specificity and sensitivity (0.80 and 0.82 respectively on the external test set), in a shorter time compared to the nuclear medicine physicians (2.5 min for AI and 30 min for nuclear medicine physicians to classify 134 BSs). Further prospective validation is required before the algorithm can be used in the clinic.

Machine learning-based combined nomogram for predicting the risk of pulmonary invasive fungal infection in severely immunocompromised patients.

Background: Early and accurate diagnosis of invasive fungal infection (IFI) is pivotal for the initiation of effective antifungal therapy for patients with hematologic malignancies. Methods: This retrospective study involved 235 patients with hematologic malignancies and pulmonary infections diagnosed as IFIs (n=118) or bacterial pneumonia (n=117). Patients were randomly divided into training (n=188) and validation (n=47) datasets. Four feature selection methods with nine classifiers were implemented to select the optimal machine learning (ML) model using five-fold cross-validation. A radiomic signature was constructed using a linear ML algorithm, and a radiomic score (Radscore) was calculated. The combined model was developed with the Radscore, the significant clinical and radiologic factors were selected using multivariable logistic regression, and the results were presented as a clinical radiomic nomogram. A prospective pilot study was also conducted to compare the classification performance of the combined nomogram with practicing radiologists. Results: Significant differences were found in the Radscore between IFI and bacterial pneumonia patients in the training (0.683 vs. -0.724, P<0.001) and validation set (0.353 vs. -0.717, P=0.002). The combined model showed good discrimination performance in the validation cohort [area under the curve (AUC) =0.844] and outperformed the clinical (AUC =0.696) and radiomics (AUC =0.767) model alone (both P<0.05). Conclusions: The clinical radiomic nomogram can serve as a promising predictive tool for IFI in patients with hematologic malignancies.

Predicting Adverse Radiation Effects in Brain Tumors After Stereotactic Radiotherapy With Deep Learning and Handcrafted Radiomics.

Introduction: There is a cumulative risk of 20-40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT. Methods: Gadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated. Results: The best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient. Conclusion: Machine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.

Investigation of the added value of CT-based radiomics in predicting the development of brain metastases in patients with radically treated stage III NSCLC.

Introduction: Despite radical intent therapy for patients with stage III non-small-cell lung cancer (NSCLC), cumulative incidence of brain metastases (BM) reaches 30%. Current risk stratification methods fail to accurately identify these patients. As radiomics features have been shown to have predictive value, this study aims to develop a model combining clinical risk factors with radiomics features for BM development in patients with radically treated stage III NSCLC. Methods: Retrospective analysis of two prospective multicentre studies. Inclusion criteria: adequately staged [18F-fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG-PET-CT), contrast-enhanced chest CT, contrast-enhanced brain magnetic resonance imaging/CT] and radically treated stage III NSCLC, exclusion criteria: second primary within 2 years of NSCLC diagnosis and prior prophylactic cranial irradiation. Primary endpoint was BM development any time during follow-up (FU). CT-based radiomics features (N = 530) were extracted from the primary lung tumour on 18-FDG-PET-CT images, and a list of clinical features (N = 8) was collected. Univariate feature selection based on the area under the curve (AUC) of the receiver operating characteristic was performed to identify relevant features. Generalized linear models were trained using the selected features, and multivariate predictive performance was assessed through the AUC. Results: In total, 219 patients were eligible for analysis. Median FU was 59.4 months for the training cohort and 67.3 months for the validation cohort; 21 (15%) and 17 (22%) patients developed BM in the training and validation cohort, respectively. Two relevant clinical features (age and adenocarcinoma histology) and four relevant radiomics features were identified as predictive. The clinical model yielded the highest AUC value of 0.71 (95% CI: 0.58-0.84), better than radiomics or a combination of clinical parameters and radiomics (both an AUC of 0.62, 95% CIs of 0.47-076 and 0.48-0.76, respectively). Conclusion: CT-based radiomics features of primary NSCLC in the current setup could not improve on a model based on clinical predictors (age and adenocarcinoma histology) of BM development in radically treated stage III NSCLC patients.

Diagnosis of Idiopathic Pulmonary Fibrosis in High-Resolution Computed Tomography Scans Using a Combination of Handcrafted Radiomics and Deep Learning.

Purpose: To develop handcrafted radiomics (HCR) and deep learning (DL) based automated diagnostic tools that can differentiate between idiopathic pulmonary fibrosis (IPF) and non-IPF interstitial lung diseases (ILDs) in patients using high-resolution computed tomography (HRCT) scans. Material and Methods: In this retrospective study, 474 HRCT scans were included (mean age, 64.10 years ± 9.57 [SD]). Five-fold cross-validation was performed on 365 HRCT scans. Furthermore, an external dataset comprising 109 patients was used as a test set. An HCR model, a DL model, and an ensemble of HCR and DL model were developed. A virtual in-silico trial was conducted with two radiologists and one pulmonologist on the same external test set for performance comparison. The performance was compared using DeLong method and McNemar test. Shapley Additive exPlanations (SHAP) plots and Grad-CAM heatmaps were used for the post-hoc interpretability of HCR and DL models, respectively. Results: In five-fold cross-validation, the HCR model, DL model, and the ensemble of HCR and DL models achieved accuracies of 76.2 ± 6.8, 77.9 ± 4.6, and 85.2 ± 2.7%, respectively. For the diagnosis of IPF and non-IPF ILDs on the external test set, the HCR, DL, and the ensemble of HCR and DL models achieved accuracies of 76.1, 77.9, and 85.3%, respectively. The ensemble model outperformed the diagnostic performance of clinicians who achieved a mean accuracy of 66.3 ± 6.7% (p < 0.05) during the in-silico trial. The area under the receiver operating characteristic curve (AUC) for the ensemble model on the test set was 0.917 which was significantly higher than the HCR model (0.817, p = 0.02) and the DL model (0.823, p = 0.005). The agreement between HCR and DL models was 61.4%, and the accuracy and specificity for the predictions when both the models agree were 93 and 97%, respectively. SHAP analysis showed the texture features as the most important features for IPF diagnosis and Grad-CAM showed that the model focused on the clinically relevant part of the image. Conclusion: Deep learning and HCR models can complement each other and serve as useful clinical aids for the diagnosis of IPF and non-IPF ILDs.

Data harmonisation for information fusion in digital healthcare: A state-of-the-art systematic review, meta-analysis and future research directions.

Removing the bias and variance of multicentre data has always been a challenge in large scale digital healthcare studies, which requires the ability to integrate clinical features extracted from data acquired by different scanners and protocols to improve stability and robustness. Previous studies have described various computational approaches to fuse single modality multicentre datasets. However, these surveys rarely focused on evaluation metrics and lacked a checklist for computational data harmonisation studies. In this systematic review, we summarise the computational data harmonisation approaches for multi-modality data in the digital healthcare field, including harmonisation strategies and evaluation metrics based on different theories. In addition, a comprehensive checklist that summarises common practices for data harmonisation studies is proposed to guide researchers to report their research findings more effectively. Last but not least, flowcharts presenting possible ways for methodology and metric selection are proposed and the limitations of different methods have been surveyed for future research.

Automated detection and segmentation of non-small cell lung cancer computed tomography images.

Detection and segmentation of abnormalities on medical images is highly important for patient management including diagnosis, radiotherapy, response evaluation, as well as for quantitative image research. We present a fully automated pipeline for the detection and volumetric segmentation of non-small cell lung cancer (NSCLC) developed and validated on 1328 thoracic CT scans from 8 institutions. Along with quantitative performance detailed by image slice thickness, tumor size, image interpretation difficulty, and tumor location, we report an in-silico prospective clinical trial, where we show that the proposed method is faster and more reproducible compared to the experts. Moreover, we demonstrate that on average, radiologists & radiation oncologists preferred automatic segmentations in 56% of the cases. Additionally, we evaluate the prognostic power of the automatic contours by applying RECIST criteria and measuring the tumor volumes. Segmentations by our method stratified patients into low and high survival groups with higher significance compared to those methods based on manual contours.

CT Reconstruction Kernels and the Effect of Pre- and Post-Processing on the Reproducibility of Handcrafted Radiomic Features.

Handcrafted radiomics features (HRFs) are quantitative features extracted from medical images to decode biological information to improve clinical decision making. Despite the potential of the field, limitations have been identified. The most important identified limitation, currently, is the sensitivity of HRF to variations in image acquisition and reconstruction parameters. In this study, we investigated the use of Reconstruction Kernel Normalization (RKN) and ComBat harmonization to improve the reproducibility of HRFs across scans acquired with different reconstruction kernels. A set of phantom scans (n = 28) acquired on five different scanner models was analyzed. HRFs were extracted from the original scans, and scans were harmonized using the RKN method. ComBat harmonization was applied on both sets of HRFs. The reproducibility of HRFs was assessed using the concordance correlation coefficient. The difference in the number of reproducible HRFs in each scenario was assessed using McNemar's test. The majority of HRFs were found to be sensitive to variations in the reconstruction kernels, and only six HRFs were found to be robust with respect to variations in reconstruction kernels. The use of RKN resulted in a significant increment in the number of reproducible HRFs in 19 out of the 67 investigated scenarios (28.4%), while the ComBat technique resulted in a significant increment in 36 (53.7%) scenarios. The combination of methods resulted in a significant increment in 53 (79.1%) scenarios compared to the HRFs extracted from original images. Since the benefit of applying the harmonization methods depended on the data being harmonized, reproducibility analysis is recommended before performing radiomics analysis. For future radiomics studies incorporating images acquired with similar image acquisition and reconstruction parameters, except for the reconstruction kernels, we recommend the systematic use of the pre- and post-processing approaches (respectively, RKN and ComBat).

Deep Learning-based Automatic Lung Segmentation on Multiresolution CT Scans from Healthy and Fibrotic Lungs in Mice.

Purpose: To develop a model to accurately segment mouse lungs with varying levels of fibrosis and investigate its applicability to mouse images with different resolutions. Materials and Methods: In this experimental retrospective study, a U-Net was trained to automatically segment lungs on mouse CT images. The model was trained (n = 1200), validated (n = 300), and tested (n = 154) on longitudinally acquired and semiautomatically segmented CT images, which included both healthy and irradiated mice (group A). A second independent group of 237 mice (group B) was used for external testing. The Dice score coefficient (DSC) and Hausdorff distance (HD) were used as metrics to quantify segmentation accuracy. Transfer learning was applied to adapt the model to high-spatial-resolution mouse micro-CT segmentation (n = 20; group C [n = 16 for training and n = 4 for testing]). Results: The trained model yielded a high median DSC in both test datasets: 0.984 (interquartile range [IQR], 0.977-0.988) in group A and 0.966 (IQR, 0.955-0.972) in group B. The median HD in both test datasets was 0.47 mm (IQR, 0-0.51 mm [group A]) and 0.31 mm (IQR, 0.30-0.32 mm [group B]). Spatially resolved quantification of differences toward reference masks revealed two hot spots close to the air-tissue interfaces, which are particularly prone to deviation. Finally, for the higher-resolution mouse CT images, the median DSC was 0.905 (IQR, 0.902-0.929) and the median 95th percentile of the HD was 0.33 mm (IQR, 2.61-2.78 mm). Conclusion: The developed deep learning-based method for mouse lung segmentation performed well independently of disease state (healthy, fibrotic, emphysematous lungs) and CT resolution.Keywords: Deep Learning, Lung Fibrosis, Radiation Therapy, Segmentation, Animal Studies, CT, Thorax, Lung Supplemental material is available for this article. Published under a CC BY 4.0 license.