Imaging-based representation and stratification of intra-tumor heterogeneity via tree-edit distance

Personalized medicine is the future of medical practice. In oncology, tumor heterogeneity assessment represents a pivotal step for effective treatment planning and prognosis prediction. Despite new procedures for DNA sequencing and analysis, non-invasive methods for tumor characterization are needed to impact on daily routine. On purpose, imaging texture analysis is rapidly scaling, holding the promise to surrogate histopathological assessment of tumor lesions. In this work, we propose a tree-based representation strategy for describing intra-tumor heterogeneity of patients affected by metastatic cancer. We leverage radiomics information extracted from PET/CT imaging and we provide an exhaustive and easily readable summary of the disease spreading. We exploit this novel patient representation to perform cancer subtyping according to hierarchical clustering technique. To this purpose, a new heterogeneity-based distance between trees is defined and applied to a case study of prostate cancer. Clusters interpretation is explored in terms of concordance with severity status, tumor burden and biological characteristics. Results are promising, as the proposed method outperforms current literature approaches. Ultimately, the proposed method draws a general analysis framework that would allow to extract knowledge from daily acquired imaging data of patients and provide insights for effective treatment planning

Radiomics-Based Inter-Lesion Relation Network to Describe [18F]FMCH PET/CT Imaging Phenotypes in Prostate Cancer

Advanced image analysis, specifically radiomics, has been recognized as a potential source of biomarkers for cancers. However, there are challenges to its application in the clinic, such as proper description of diseases where multiple lesions coexist. In this study, we aimed to characterize the intra-tumor heterogeneity of metastatic prostate cancer using an innovative approach. This approach consisted of a transformation method to build a radiomic profile of lesions extracted from [18F]FMCH PET/CT images, a qualitative assessment of intra-tumor heterogeneity of patients, and a quantitative representation of the intra-tumor heterogeneity of patients in terms of the relationship between their lesions’ profiles. We found that metastatic prostate cancer patients had lesions with different radiomic profiles that exhibited intra-tumor radiomic heterogeneity and that the presence of many radiomic profiles within the same patient impacted the outcome

Methodological framework for radiomics applications in Hodgkin’s lymphoma

Background: According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet. Purpose: The study aimed at setting up a methodological framework in radiomics applications in Hodgkin’s lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions’ similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients. Methods: We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19–74). LIFEx (www.lifexsoft.org) was used for [18F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis-transformed features were used to build the fingerprints that were tested to assess lesions’ similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE). Results: HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity). Conclusions: Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used

Methodological framework for radiomics applications in Hodgkin’s lymphoma

According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet. The study aimed at setting up a methodological framework in radiomics applications in Hodgkin’s lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions’ similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients. We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19–74). LIFEx (www.lifexsoft.org) was used for [18F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis transformed features were used to build the fingerprints that were tested to assess lesions’ similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE). HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity). Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used

Role of molecular imaging in the management of patients affected by inflammatory bowel disease: State-of-the-art

To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease (IBD)

Recurrence-specific supervised graph clustering for subtyping Hodgkin Lymphoma radiomic phenotypes

: The prediction at baseline of patients at high risk for therapy failure or recurrence would significantly impact on Hodgkin Lymphoma patients treatment, informing clinical practice. Current literature is extensively searching insights in radiomics, a promising framework for high-throughput imaging feature extraction, to derive biomarkers and quantitative prognostic factors from images. However, existing studies are limited by intrinsic radiomic limitations, high dimensionality among others. We propose an exhaustive patient representation and a recurrence-specific multi-view supervised clustering algorithm for estimating patient-to-patient similarity graph and learning recurrence probability. We stratified patients in two risk classes and characterize each group in terms of clinical variables

Substance P and bradykinin activate different types of KCa currents to hyperpolarize cultured porcine coronary artery endothelial cells

Substance P and bradykinin, endothelium-dependent vasodilators of pig coronary artery, trigger in endothelial cells a rise in cytosolic Ca2+ concentration ([Ca2+]i) and membrane hyperpolarization. The aim of the present study was to determine the type of Ca2+-dependent K+ (KCa) currents underlying the endothelial cell hyperpolarization.The substance P-induced increase in [Ca2+]i was 30 % smaller than that induced by bradykinin, although the two peptides triggered a membrane hyperpolarization of the same amplitude. The two agonists evoked a large outward K+ current of the same conductance at maximal stimulation. Agonists applied together produced the same maximal current amplitude as either one applied alone.Iberiotoxin (50 nM) reduced by about 40 % the K+ current activated by bradykinin without modifying the substance P response. Conversely, apamin (1 μm) inhibited the substance P-induced K+ current by about 65 %, without affecting the bradykinin response. Similar results were obtained on peptide-induced membrane hyperpolarization.Bradykinin-induced, but not substance P-induced, endothelium-dependent relaxation resistant to NG-nitro-L-arginine and indomethacin was partly inhibited by 3 μm 17-octadecynoic acid (17-ODYA), an inhibitor of cytochrome P450 epoxygenase. Similarly, the bradykinin-induced K+ current was reduced by 17-ODYA.Our results show that responses to substance P and bradykinin result in a hyperpolarization due to activation of different KCa currents. A current consistent with the activation of large conductance (BKCa) channels was activated only by bradykinin, whereas a current consistent with the activation of small conductance (SKCa) channels was stimulated only by substance P. The observation that a similar electrical response is produced by different pools of channels implies distinct intracellular pathways leading to KCa current activation

L'impiego di due protesi in contemporanea nella riparazione delle grosse perdite di sostanza reale nella parete addominale

The Authors report ten cases of complicated large incisional hernias, that have been operated according to different techniques, using two prostheses. Particularly, they report their personal technique, used in cases of large incisional hernia and in other abdominal wall diseases, where there is an important loss of soft tissue. In these cases, two prostheses are used at the same time. A slow-resorption mesh is sutured to the peritoneum, in direct contact with the previous one, or in the retromuscular space. The retentive function is good, whereas the chest-wall functionality, examined by trans-diaphragmatic manometry, is not complete. The Authors consider the cause of this to be the incomplete reinsertion of broad muscles, due to interposition of the slow-resorption mesh to close the defect

18F-FDG PET/CT versus bone scintigraphy in the follow-up of gastric cancer

A 53-year-old patient underwent a positron emission tomography/computed tomography with 2-fluoro-2-deoxy-d-glucose (18F-FDG PET/CT) in the suspicious of gastric tumor recurrence (mediastinal and abdominal lymph nodes). PET/CT identified only an area of 18F-FDGuptake in the twelfth thoracic vertebrae. Unexpectedly, a bone scintigraphy revealed many "hot" spots changing the diagnosis (single metastasis versus plurimetastatic disease) and impacting on patient's management