UNASSIGNED: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data.
UNASSIGNED: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS).
UNASSIGNED: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies.
UNASSIGNED: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Lymph node metastasis (LNM) is a prognostic biomarker and affects therapeutic selection in colorectal cancer (CRC). Current evaluation methods are not adequate for estimating LNM in CRC. H&E images contain much pathological information, and collagen also affects the biological behavior of tumor cells. Hence, the objective of the study is to investigate whether a fully quantitative pathomics-collagen signature (PCS) in the tumor microenvironment can be used to predict LNM.
Patients with histologically confirmed stage I-III CRC who underwent radical surgery were included in the training cohort (n = 329), the internal validation cohort (n = 329), and the external validation cohort (n = 315). Fully quantitative pathomics features and collagen features were extracted from digital H&E images and multiphoton images of specimens, respectively. LASSO regression was utilized to develop the PCS. Then, a PCS-nomogram was constructed incorporating the PCS and clinicopathological predictors for estimating LNM in the training cohort. The performance of the PCS-nomogram was evaluated via calibration, discrimination, and clinical usefulness. Furthermore, the PCS-nomogram was tested in internal and external validation cohorts.
By LASSO regression, the PCS was developed based on 11 pathomics and 9 collagen features. A significant association was found between the PCS and LNM in the three cohorts (P < 0.001). Then, the PCS-nomogram based on PCS, preoperative CEA level, lymphadenectasis on CT, venous emboli and/or lymphatic invasion and/or perineural invasion (VELIPI), and pT stage achieved AUROCs of 0.939, 0.895, and 0.893 in the three cohorts. The calibration curves identified good agreement between the nomogram-predicted and actual outcomes. Decision curve analysis indicated that the PCS-nomogram was clinically useful. Moreover, the PCS was still an independent predictor of LNM at station Nos. 1, 2, and 3. The PCS nomogram displayed AUROCs of 0.849-0.939 for the training cohort, 0.837-0.902 for the internal validation cohort, and 0.851-0.895 for the external validation cohorts in the three nodal stations.
This study proposed that PCS integrating pathomics and collagen features was significantly associated with LNM, and the PCS-nomogram has the potential to be a useful tool for predicting individual LNM in CRC patients.

BACKGROUND: Recent advances in cancer biomarker development have led to a surge of distinct data modalities, such as medical imaging and histopathology. To develop predictive immunotherapy biomarkers, these modalities are leveraged independently, despite their orthogonality. This study aims to explore the cross-scale association between radiological scans and digitalized pathology images for immunotherapy-treated non-small cell lung cancer (NSCLC) patients.
METHODS: This study involves 36 NSCLC patients who were treated with immunotherapy and for whom both radiology and pathology images were available. A total of 851 and 260 features were extracted from CT scans and cell density maps of histology images at different resolutions. We investigated the radiopathomics relationship and their association with clinical and biological endpoints. We used the Kolmogorov-Smirnov (KS) method to test the differences between the distributions of correlation coefficients with the two imaging modality features. Unsupervised clustering was done to identify which imaging modality captures poor and good survival patients.
RESULTS: Our results demonstrated a significant correlation between cell density pathomics and radiomics features. Furthermore, we also found a varying distribution of correlation values between imaging-derived features and clinical endpoints. The KS test revealed that the two imaging feature distributions were different for PFS and CD8 counts, while similar for OS. In addition, clustering analysis resulted in significant differences in the two clusters generated from the radiomics and pathomics features with respect to patient survival and CD8 counts.
CONCLUSIONS: The results of this study suggest a cross-scale association between CT scans and pathology H&E slides among ICI-treated patients. These relationships can be further explored to develop multimodal immunotherapy biomarkers to advance personalized lung cancer care.

Glioblastoma multiforme (GBM) typically exhibits substantial intratumoral heterogeneity at both microscopic and radiological resolution scales. Diffusion Weighted Imaging (DWI) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) are two functional MRI techniques that are commonly employed in clinic for the assessment of GBM tumor characteristics. This work presents initial results aiming at determining if radiomics features extracted from preoperative ADC maps and post-contrast T1 (T1C) images are associated with pathomic features arising from H&E digitized pathology images. 48 patients from the public available CPTAC-GBM database, for which both radiology and pathology images were available, were involved in the study. 91 radiomics features were extracted from ADC maps and post-contrast T1 images using PyRadiomics. 65 pathomic features were extracted from cell detection measurements from H&E images. Moreover, 91 features were extracted from cell density maps of H&E images at four different resolutions. Radiopathomic associations were evaluated by means of Spearman\'s correlation (ρ) and factor analysis. p values were adjusted for multiple correlations by using a false discovery rate adjustment. Significant cross-scale associations were identified between pathomics and ADC, both considering features (n = 186, 0.45 < ρ < 0.74 in absolute value) and factors (n = 5, 0.48 < ρ < 0.54 in absolute value). Significant but fewer ρ values were found concerning the association between pathomics and radiomics features (n = 53, 0.5 < ρ < 0.65 in absolute value) and factors (n = 2, ρ = 0.63 and ρ = 0.53 in absolute value). The results of this study suggest that cross-scale associations may exist between digital pathology and ADC and T1C imaging. This can be useful not only to improve the knowledge concerning GBM intratumoral heterogeneity, but also to strengthen the role of radiomics approach and its validation in clinical practice as \"virtual biopsy\", introducing new insights for omics integration toward a personalized medicine approach.

Whole slide images contain a magnitude of quantitative information that may not be fully explored in qualitative visual assessments. We propose: (1) a novel pipeline for extracting a comprehensive set of visual features, which are detectable by a pathologist, as well as sub-visual features, which are not discernible by human experts and (2) perform detailed analyses on renal images from mice with experimental unilateral ureteral obstruction. An important criterion for these features is that they are easy to interpret, as opposed to features obtained from neural networks. We extract and compare features from pathological and healthy control kidneys to learn how the compartments (glomerulus, Bowman\'s capsule, tubule, interstitium, artery, and arterial lumen) are affected by the pathology. We define feature selection methods to extract the most informative and discriminative features. We perform statistical analyses to understand the relation of the extracted features, both individually, and in combinations, with tissue morphology and pathology. Particularly for the presented case-study, we highlight features that are affected in each compartment. With this, prior biological knowledge, such as the increase in interstitial nuclei, is confirmed and presented in a quantitative way, alongside with novel findings, like color and intensity changes in glomeruli and Bowman\'s capsule. The proposed approach is therefore an important step towards quantitative, reproducible, and rater-independent analysis in histopathology.

Development and validation of a quantitative radiomic risk score (QuRiS) and associated nomogram (QuRNom) for early-stage non-small cell lung cancer (ES-NSCLC) that is prognostic of disease-free survival (DFS) and predictive of the added benefit of adjuvant chemotherapy (ACT) following surgery.
QuRiS was developed using radiomic texture features derived from within and outside the primary lung nodule on chest CT scans using a cohort D1 of 329 patients from the Cleveland Clinic. A LASSO-Cox regularization model was used for data dimension reduction, feature selection, and QuRiS construction. QuRiS was independently validated on D2(N=114; University of Pennsylvania) and D3(N=82; TCIA). QuRNom was constructed by integrating QuRiS with T-, N-Descriptors, and LVI. The added benefit of ACT using QuRiS and QuRNom was validated by comparing patients who received ACT against patients who underwent surgery alone in D1-D3. To explore the underlying morphologic basis of the QuRiS, we explored associations with corresponding whole-slide tissue scans (WSIs) and mRNA sequencing data using subsets of D1 and D3.
QuRiS consisted three intra- and ten peri-tumoral CT-radiomic features and was found to be significantly associated with DFS (D1: HR=1.60 [1.10-2.20];p<·05; D2:HR=2.70 [1.40-5.10]; p<·01; D3:HR=2.70 [1.20-5.70];p<·01). Patients were partitioned into three risk groups (QH, QI, QL) based off their corresponding QuRiS score. High QuRiS group, QH, patients were observed to have significantly prolonged survival with ACT when compared to surgery alone (D1: HR=0·27[0.07-0.95],p<0.05; D2+D3: HR=0·08[0.01-0.42],p<0.01). For developed QuRNom, the actual efficacy of ACT was predictive of nomogram-estimated survival benefit (D1: HR= D1:0·25 [0·12-0·55], D3: HR=0·13 [0·004-0·99]). QuRiS features were found to be associated with the spatial arrangement of TILs and cancer nuclei on corresponding WSIs (D1: Rho=0·23,p<0·05, N=70). They were also observed to have an association with biological pathways implicated in chemotaxis (D3,p<0·05, N=86) and other immune specific biological pathways.
QuRiS and QuRNom were validated as being prognostic of DFS and predictive of the added benefit of ACT.