Risk score model to automatically detect prostate cancer patients by integrating diagnostic parameters.

Introduction: Prostate cancer (PCa) is one of the prevailing forms of cancer among men. At present, multiparametric MRI is the imaging method for localizing tumors and staging cancer. Radiomics plays a key role and hold potential for PCa detection, reducing the need for unnecessary biopsies, characterizing tumor aggression, and overseeing PCa recurrence post-treatment. Methods: Furthermore, the integration of radiomics data with clinical and histopathological data can further enhance the understanding and management of PCa and decrease unnecessary transfers to specialized care for expensive and intrusive biopsies. Therefore, the aim of this study is to develop a risk model score to automatically detect PCa patients by integrating non-invasive diagnostic parameters (radiomics and Prostate-Specific Antigen levels) along with patient's age. Results: The proposed approach was evaluated using a dataset of 189 PCa patients who underwent bi-parametric MRI from two centers. Elastic-Net Regularized Generalized Linear Model achieved 91% AUC to automatically detect PCa patients. The model risk score was also used to assess doubt cases of PCa at biopsy and then compared to bi-parametric PI-RADS v2. Discussion: This study explored the relative utility of a well-developed risk model by combining radiomics, Prostate-Specific Antigen levels and age for objective and accurate PCa risk stratification and supporting the process of making clinical decisions during follow up.

Classifying breast cancer and fibroadenoma tissue biopsies from paraffined stain-free slides by fractal biomarkers in Fourier Ptychographic Microscopy.

Breast cancer is one of the most spread and monitored pathologies in high-income countries. After breast biopsy, histological tissue is stored in paraffin, sectioned and mounted. Conventional inspection of tissue slides under benchtop light microscopes involves paraffin removal and staining, typically with H&E. Then, expert pathologists are called to judge the stained slides. However, paraffin removal and staining are operator-dependent, time and resources consuming processes that can generate ambiguities due to non-uniform staining. Here we propose a novel method that can work directly on paraffined stain-free slides. We use Fourier Ptychography as a quantitative phase-contrast microscopy method, which allows accessing a very wide field of view (i.e., mm2) in one single image while guaranteeing high lateral resolution (i.e., 0.5 µm). This imaging method is multi-scale, since it enables looking at the big picture, i.e. the complex tissue structure and connections, with the possibility to zoom-in up to the single-cell level. To handle this informative image content, we introduce elements of fractal geometry as multi-scale analysis method. We show the effectiveness of fractal features in describing and classifying fibroadenoma and breast cancer tissue slides from ten patients with very high accuracy. We reach 94.0 ± 4.2% test accuracy in classifying single images. Above all, we show that combining the decisions of the single images, each patient's slide can be classified with no error. Besides, fractal geometry returns a guide map to help pathologist to judge the different tissue portions based on the likelihood these can be associated to a breast cancer or fibroadenoma biomarker. The proposed automatic method could significantly simplify the steps of tissue analysis and make it independent from the sample preparation, the skills of the lab operator and the pathologist.

Current status of magnetic resonance imaging radiomics in hepatocellular carcinoma: A quantitative review with Radiomics Quality Score.

BACKGROUND: Radiomics is a promising tool that may increase the value of magnetic resonance imaging (MRI) for different tasks related to the management of patients with hepatocellular carcinoma (HCC). However, its implementation in clinical practice is still far, with many issues related to the methodological quality of radiomic studies. AIM: To systematically review the current status of MRI radiomic studies concerning HCC using the Radiomics Quality Score (RQS). METHODS: A systematic literature search of PubMed, Google Scholar, and Web of Science databases was performed to identify original articles focusing on the use of MRI radiomics for HCC management published between 2017 and 2023. The methodological quality of radiomic studies was assessed using the RQS tool. Spearman's correlation (ρ) analysis was performed to explore if RQS was correlated with journal metrics and characteristics of the studies. The level of statistical signi-ficance was set at P < 0.05. RESULTS: One hundred and twenty-seven articles were included, of which 43 focused on HCC prognosis, 39 on prediction of pathological findings, 16 on prediction of the expression of molecular markers outcomes, 18 had a diagnostic purpose, and 11 had multiple purposes. The mean RQS was 8 ± 6.22, and the corresponding percentage was 24.15% ± 15.25% (ranging from 0.0% to 58.33%). RQS was positively correlated with journal impact factor (IF; ρ = 0.36, P = 2.98 × 10-5), 5-years IF (ρ = 0.33, P = 1.56 × 10-4), number of patients included in the study (ρ = 0.51, P < 9.37 × 10-10) and number of radiomics features extracted in the study (ρ = 0.59, P < 4.59 × 10-13), and time of publication (ρ = -0.23, P < 0.0072). CONCLUSION: Although MRI radiomics in HCC represents a promising tool to develop adequate personalized treatment as a noninvasive approach in HCC patients, our study revealed that studies in this field still lack the quality required to allow its introduction into clinical practice.

Standardizing digital biobanks: integrating imaging, genomic, and clinical data for precision medicine.

Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine.

A customized anthropomorphic 3D-printed phantom to reproducibility assessment in computed tomography: an oncological case study.

Introduction: Studies on computed tomography (CT) reproducibility at different acquisition parameters have to take into account radiation dose administered and related ethical issues. 3D-printed phantoms provide the possibility to investigate these features deeply and to foster CT research, also taking advantage by outperforming new generation scanners. The aim of this study is to propose a new anthropomorphic 3D-printed phantom for chest lesions, tailored on a real patient CT scan, to investigate the variability of volume and Hounsfield Unit (HU) measurements at different CT acquisition parameters. Methods: The chest CT of a 75-year-old patient with a paramediastinal lung lesion was segmented based on an eight-compartment approach related to HU ranges (air lung, lung interstitium, fat, muscle, vascular, skin, bone, and lesion). From each mask produced, the 3D.stl model was exported and linked to a different printing infill value, based on a preliminary test and HU ratios derived from the patient scan. Fused deposition modeling (FDM) technology printing was chosen with filament materials in polylactic acid (PLA). Phantom was acquired at 50 mAs and three different tube voltages of 80, 100, and 120 kVp on two different scanners, namely, Siemens Somatom Force (Siemens Healthineers, Erlangen, Germany; same setting of real patient for 80 kVp acquisition) and GE 750 HD CT (GE Healthcare, Chicago, IL). The same segmentation workflow was then applied on each phantom acquisition after coregistration pipeline, and Dice Similarity Coefficient (DSC) and HU averages were extracted and compared for each compartment. Results: DSC comparison among real patient versus phantom scans at different kVp, and on both CT scanners, demonstrated a good overlap of different compartments and lesion vascularization with a higher similarity for lung and lesion masks for each setting (about 0.9 and 0.8, respectively). Although mean HU was not comparable with real data, due to the PLA material, the proportion of intensity values for each compartment remains respected. Discussion: The proposed approach demonstrated the reliability of 3D-printed technology for personalized approaches in CT research, opening to the application of the same workflow to other oncological fields.

Beyond conventional microscopy: Observing kidney tissues by means of fourier ptychography.

Kidney microscopy is a mainstay in studying the morphological structure, physiology and pathology of kidney tissues, as histology provides important results for a reliable diagnosis. A microscopy modality providing at same time high-resolution images and a wide field of view could be very useful for analyzing the whole architecture and the functioning of the renal tissue. Recently, Fourier Ptychography (FP) has been proofed to yield images of biology samples such as tissues and in vitro cells while providing high resolution and large field of view, thus making it a unique and attractive opportunity for histopathology. Moreover, FP offers tissue imaging with high contrast assuring visualization of small desirable features, although with a stain-free mode that avoids any chemical process in histopathology. Here we report an experimental measuring campaign for creating the first comprehensive and extensive collection of images of kidney tissues captured by this FP microscope. We show that FP microscopy unlocks a new opportunity for the physicians to observe and judge renal tissue slides through the novel FP quantitative phase-contrast microscopy. Phase-contrast images of kidney tissue are analyzed by comparing them with the corresponding renal images taken under a conventional bright-field microscope both for stained and unstained tissue samples of different thicknesses. In depth discussion on the advantages and limitations of this new stain-free microscopy modality is reported, showing its usefulness over the classical light microscopy and opening a potential route for using FP in clinical practice for histopathology of kidney.

A pathomic approach for tumor-infiltrating lymphocytes classification on breast cancer digital pathology images.

Background and objectives: The detection of tumor-infiltrating lymphocytes (TILs) could aid in the development of objective measures of the infiltration grade and can support decision-making in breast cancer (BC). However, manual quantification of TILs in BC histopathological whole slide images (WSI) is currently based on a visual assessment, thus resulting not standardized, not reproducible, and time-consuming for pathologists. In this work, a novel pathomic approach, aimed to apply high-throughput image feature extraction techniques to analyze the microscopic patterns in WSI, is proposed. In fact, pathomic features provide additional information concerning the underlying biological processes compared to the WSI visual interpretation, thus providing more easily interpretable and explainable results than the most frequently investigated Deep Learning based methods in the literature. Methods: A dataset containing 1037 regions of interest with tissue compartments and TILs annotated on 195 TNBC and HER2+ BC hematoxylin and eosin (H&E)-stained WSI was used. After segmenting nuclei within tumor-associated stroma using a watershed-based approach, 71 pathomic features were extracted from each nucleus and reduced using a Spearman's correlation filter followed by a nonparametric Wilcoxon rank-sum test and least absolute shrinkage and selection operator. The relevant features were used to classify each candidate nucleus as either TILs or non-TILs using 5 multivariable machine learning classification models trained using 5-fold cross-validation (1) without resampling, (2) with the synthetic minority over-sampling technique and (3) with downsampling. The prediction performance of the models was assessed using ROC curves. Results: 21 features were selected, with most of them related to the well-known TILs properties of having regular shape, clearer margins, high peak intensity, more homogeneous enhancement and different textural pattern than other cells. The best performance was obtained by Random-Forest with ROC AUC of 0.86, regardless of resampling technique. Conclusions: The presented approach holds promise for the classification of TILs in BC H&E-stained WSI and could provide support to pathologists for a reliable, rapid and interpretable clinical assessment of TILs in BC.

A Two-Step Feature Selection Radiomic Approach to Predict Molecular Outcomes in Breast Cancer.

Breast Cancer (BC) is the most common cancer among women worldwide and is characterized by intra- and inter-tumor heterogeneity that strongly contributes towards its poor prognosis. The Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER2), and Ki67 antigen are the most examined markers depicting BC heterogeneity and have been shown to have a strong impact on BC prognosis. Radiomics can noninvasively predict BC heterogeneity through the quantitative evaluation of medical images, such as Magnetic Resonance Imaging (MRI), which has become increasingly important in the detection and characterization of BC. However, the lack of comprehensive BC datasets in terms of molecular outcomes and MRI modalities, and the absence of a general methodology to build and compare feature selection approaches and predictive models, limit the routine use of radiomics in the BC clinical practice. In this work, a new radiomic approach based on a two-step feature selection process was proposed to build predictors for ER, PR, HER2, and Ki67 markers. An in-house dataset was used, containing 92 multiparametric MRIs of patients with histologically proven BC and all four relevant biomarkers available. Thousands of radiomic features were extracted from post-contrast and subtracted Dynamic Contrast-Enanched (DCE) MRI images, Apparent Diffusion Coefficient (ADC) maps, and T2-weighted (T2) images. The two-step feature selection approach was used to identify significant radiomic features properly and then to build the final prediction models. They showed remarkable results in terms of F1-score for all the biomarkers: 84%, 63%, 90%, and 72% for ER, HER2, Ki67, and PR, respectively. When possible, the models were validated on the TCGA/TCIA Breast Cancer dataset, returning promising results (F1-score = 88% for the ER+/ER- classification task). The developed approach efficiently characterized BC heterogeneity according to the examined molecular biomarkers.

The relationship between radiomics and pathomics in Glioblastoma patients: Preliminary results from a cross-scale association study.

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.

An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. RESULTS: After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023). CONCLUSIONS: In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.

A Systematic Review of the Current Status and Quality of Radiomics for Glioma Differential Diagnosis.

Radiomics is a promising tool that may increase the value of imaging in differential diagnosis (DDx) of glioma. However, implementation in clinical practice is still distant and concerns have been raised regarding the methodological quality of radiomic studies. Therefore, we aimed to systematically review the current status of radiomic studies concerning glioma DDx, also using the radiomics quality score (RQS) to assess the quality of the methodology used in each study. A systematic literature search was performed to identify original articles focused on the use of radiomics for glioma DDx from 2015. Methodological quality was assessed using the RQS tool. Spearman's correlation (ρ) analysis was performed to explore whether RQS was correlated with journal metrics and the characteristics of the studies. Finally, 42 articles were selected for the systematic qualitative analysis. Selected articles were grouped and summarized in terms of those on DDx between glioma and primary central nervous system lymphoma, those aiming at differentiating glioma from brain metastases, and those based on DDx of glioma and other brain diseases. Median RQS was 8.71 out 36, with a mean RQS of all studies of 24.21%. Our study revealed that, despite promising and encouraging results, current studies on radiomics for glioma DDx still lack the quality required to allow its introduction into clinical practice. This work could provide new insights and help to reach a consensus on the use of the radiomic approach for glioma DDx.

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial.

BACKGROUND: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or ß-oxidation. METHODS: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma ß-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. RESULTS: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma ß-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). CONCLUSIONS: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.

MRI-Based Radiomic Features Help Identify Lesions and Predict Histopathological Grade of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Radiomics is a promising tool that may increase the value of magnetic resonance imaging (MRI) in the management of HCC. The purpose of our study is to develop an MRI-based radiomics approach to preoperatively detect HCC and predict its histological grade. Thirty-eight HCC patients at staging who underwent axial T2-weighted and dynamic contrast-enhanced MRI (DCE-MRI) were considered. Three-dimensional volumes of interest (VOIs) were manually placed on HCC lesions and normal hepatic tissue (HT) on arterial phase post-contrast images. Radiomic features from T2 images and arterial, portal and tardive post-contrast images from DCE-MRI were extracted by using Pyradiomics. Feature selection was performed using correlation filter, Wilcoxon-rank sum test and mutual information. Predictive models were constructed for HCC differentiation with respect to HT and HCC histopathologic grading used at each step an imbalance-adjusted bootstrap resampling (IABR) on 1000 samples. Promising results were obtained from radiomic prediction models, with best AUCs ranging from 71% to 96%. Radiomics MRI based on T2 and DCE-MRI revealed promising results concerning both HCC detection and grading. It may be a suitable tool for personalized treatment of HCC patients and could also be used to develop new prognostic biomarkers useful for HCC assessment without the need for invasive procedures.

Evaluation of a Whole-Liver Dixon-Based MRI Approach for Quantification of Liver Fat in Patients with Type 2 Diabetes Treated with Two Isocaloric Different Diets.

Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman's correlation (ρ). Before-after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients.

A Framework of Analysis to Facilitate the Harmonization of Multicenter Radiomic Features in Prostate Cancer.

Pooling radiomic features coming from different centers in a statistical framework is challenging due to the variability in scanner models, acquisition protocols, and reconstruction settings. To remove technical variability, commonly called batch effects, different statistical harmonization strategies have been widely used in genomics but less considered in radiomics. The aim of this work was to develop a framework of analysis to facilitate the harmonization of multicenter radiomic features extracted from prostate T2-weighted magnetic resonance imaging (MRI) and to improve the power of radiomics for prostate cancer (PCa) management in order to develop robust non-invasive biomarkers translating into clinical practice. To remove technical variability and correct for batch effects, we investigated four different statistical methods (ComBat, SVA, Arsynseq, and mixed effect). The proposed approaches were evaluated using a dataset of 210 prostate cancer (PCa) patients from two centers. The impacts of the different statistical approaches were evaluated by principal component analysis and classification methods (LogitBoost, random forest, K-nearest neighbors, and decision tree). The ComBat method outperformed all other methods by achieving 70% accuracy and 78% AUC with the random forest method to automatically classify patients affected by PCa. The proposed statistical framework enabled us to define and develop a standardized pipeline of analysis to harmonize multicenter T2W radiomic features, yielding great promise to support PCa clinical practice.

A Systematic Review on the Role of the Perfusion Computed Tomography in Abdominal Cancer.

BACKGROUND AND PURPOSE: Perfusion Computed Tomography (CTp) is an imaging technique which allows quantitative and qualitative evaluation of tissue perfusion through dynamic CT acquisitions. Since CTp is still considered a research tool in the field of abdominal imaging, the aim of this work is to provide a systematic summary of the current literature on CTp in the abdominal region to clarify the role of this technique for abdominal cancer applications. MATERIALS AND METHODS: A systematic literature search of PubMed, Web of Science, and Scopus was performed to identify original articles involving the use of CTp for clinical applications in abdominal cancer since 2011. Studies were included if they reported original data on CTp and investigated the clinical applications of CTp in abdominal cancer. RESULTS: Fifty-seven studies were finally included in the study. Most of the included articles (33/57) dealt with CTp at the level of the liver, while a low number of studies investigated CTp for oncologic diseases involving UGI tract (8/57), pancreas (8/57), kidneys (3/57), and colon-rectum (5/57). CONCLUSIONS: Our study revealed that CTp could be a valuable functional imaging tool in the field of abdominal oncology, particularly as a biomarker for monitoring the response to anti-tumoral treatment.

How does DICOM support big data management? Investigating its use in medical imaging community.

The diagnostic imaging field is experiencing considerable growth, followed by increasing production of massive amounts of data. The lack of standardization and privacy concerns are considered the main barriers to big data capitalization. This work aims to verify whether the advanced features of the DICOM standard, beyond imaging data storage, are effectively used in research practice. This issue will be analyzed by investigating the publicly shared medical imaging databases and assessing how much the most common medical imaging software tools support DICOM in all its potential. Therefore, 100 public databases and ten medical imaging software tools were selected and examined using a systematic approach. In particular, the DICOM fields related to privacy, segmentation and reporting have been assessed in the selected database; software tools have been evaluated for reading and writing the same DICOM fields. From our analysis, less than a third of the databases examined use the DICOM format to record meaningful information to manage the images. Regarding software, the vast majority does not allow the management, reading and writing of some or all the DICOM fields. Surprisingly, if we observe chest computed tomography data sharing to address the COVID-19 emergency, there are only two datasets out of 12 released in DICOM format. Our work shows how the DICOM can potentially fully support big data management; however, further efforts are still needed from the scientific and technological community to promote the use of the existing standard, encouraging data sharing and interoperability for a concrete development of big data analytics.

Impact of radiogenomics in esophageal cancer on clinical outcomes: A pilot study.

BACKGROUND: Esophageal cancer (ESCA) is the sixth most common malignancy in the world, and its incidence is rapidly increasing. Recently, several microRNAs (miRNAs) and messenger RNA (mRNA) targets were evaluated as potential biomarkers and regulators of epigenetic mechanisms involved in early diagnosis. In addition, computed tomography (CT) radiomic studies on ESCA improved the early stage identification and the prediction of response to treatment. Radiogenomics provides clinically useful prognostic predictions by linking molecular characteristics such as gene mutations and gene expression patterns of malignant tumors with medical images and could provide more opportunities in the management of patients with ESCA. AIM: To explore the combination of CT radiomic features and molecular targets associated with clinical outcomes for characterization of ESCA patients. METHODS: Of 15 patients with diagnosed ESCA were included in this study and their CT imaging and transcriptomic data were extracted from The Cancer Imaging Archive and gene expression data from The Cancer Genome Atlas, respectively. Cancer stage, history of significant alcohol consumption and body mass index (BMI) were considered as clinical outcomes. Radiomic analysis was performed on CT images acquired after injection of contrast medium. In total, 1302 radiomics features were extracted from three-dimensional regions of interest by using PyRadiomics. Feature selection was performed using a correlation filter based on Spearman's correlation (ρ) and Wilcoxon-rank sum test respect to clinical outcomes. Radiogenomic analysis involved ρ analysis between radiomic features associated with clinical outcomes and transcriptomic signatures consisting of eight N6-methyladenosine RNA methylation regulators and five up-regulated miRNA. The significance level was set at P < 0.05. RESULTS: Of 25, five and 29 radiomic features survived after feature selection, considering stage, alcohol history and BMI as clinical outcomes, respectively. Radiogenomic analysis with stage as clinical outcome revealed that six of the eight mRNA regulators and two of the five up-regulated miRNA were significantly correlated with ten and three of the 25 selected radiomic features, respectively (-0.61 < ρ < -0.60 and 0.53 < ρ < 0.69, P < 0.05). Assuming alcohol history as clinical outcome, no correlation was found between the five selected radiomic features and mRNA regulators, while a significant correlation was found between one radiomic feature and three up-regulated miRNAs (ρ = -0.56, ρ = -0.64 and ρ = 0.61, P < 0.05). Radiogenomic analysis with BMI as clinical outcome revealed that four mRNA regulators and one up-regulated miRNA were significantly correlated with 10 and two radiomic features, respectively (-0.67 < ρ < -0.54 and 0.53 < ρ < 0.71, P < 0.05). CONCLUSION: Our study revealed interesting relationships between the expression of eight N6-methyladenosine RNA regulators, as well as five up-regulated miRNAs, and CT radiomic features associated with clinical outcomes of ESCA patients.

The impact of MR-based attenuation correction in spinal cord FDG-PET/MR imaging for neurological studies.

PURPOSE: Positron emission tomography (PET) attenuation correction (AC) in positron emission tomography-magnetic resonance (PET/MR) scanners constitutes a critical and barely explored issue in spinal cord investigation, mainly due to the limitations in accounting for highly attenuating bone structures which surround the spinal canal. Our study aims at evaluating the clinical suitability of MR-driven AC (MRAC) for 18-fluorodeoxy-glucose positron emission tomography (18 F-FDG-PET) in spinal cord. METHODS: Thirty-six patients, undergoing positron emission tomography-computed tomography (PET/CT) and PET/MR in the same session for oncological examination, were retrospectively analyzed. For each patient, raw PET data from PET/MR scanner were reconstructed with 4- and 5-class MRAC maps, generated by hybrid PET/MR system (PET_MRAC4 and PET_MRAC5, respectively, where PET_MRAC is PET images reconstructed using MR-based attenuation correction map), and an AC map derived from CT data after a custom co-registration pipeline (PET_rCTAC, where PET_rCTAC is PET images reconstructed using CT-based attenuation correction map), which served as reference. Mean PET standardized uptake values ( SU V m ) were extracted from the three reconstructed PET images by regions of interest (ROIs) identified on T2-weighted MRI, in the spinal cord, lumbar cerebrospinal fluid (CSF), and vertebral marrow at five levels (C2, C5, T6, T12, and L3). SU V m values from PET_MRAC4 and PET_MRAC5 were compared with each other and with the reference by means of paired t-test, and correlated using Pearson's correlation (r) to assess their consistency. Cohen's d was calculated to assess the magnitude of differences between PET images. RESULTS: SU V m values from PET_MRAC4 were lower than those from PET_MRAC5 in almost all analyzed ROIs, with a mean difference ranging from 0.03 to 0.26 (statistically significant in the vertebral marrow at C2 and C5, spinal cord at T6 and T2, and CSF at L3). This was also confirmed by the effect size, with highest values at low spinal levels (d = 0.45 at T12 in spinal cord, d = 0.95 at L3 in CSF). S U V m values from PET_MRAC4 and PET_MRAC5 showed a very good correlation (0.81 < r < 0.97, p < 0.05) in all spinal ROIs. Underestimation of SU V m between PET_MRAC4 and PET_rCTAC was observed at each level, with a mean difference ranging from 0.02 to 0.32 (statistically significant in the vertebral marrow at C2 and T6, and CSF at L3). Although PET_MRAC5 underestimates PET_rCTAC (mean difference ranging from 0.02 to 0.3), an overall decrease in effect size could be observed for PET_MRAC5, mainly at lower spinal levels (T12, L3). SU V m from both PET_MRAC4 and PET_MRAC5 methods showed r value from good to very good with respect to PET_rCTAC (0.67 < r < 0.9 and 0.73 < r < 0.94, p < 0.05, respectively). CONCLUSIONS: Our results showed that neglecting bones in AC can underestimate the FDG uptake measurement of the spinal cord. The inclusion of bones in MRAC is far from negligible and improves the AC in spinal cord, mainly at low spinal levels. Therefore, care must be taken in the spinal canal region, and the use of AC map reconstruction methods accounting for bone structures could be beneficial.

The Role of Non-Gaussian Models of Diffusion Weighted MRI in Hepatocellular Carcinoma: A Systematic Review.

The importance of Diffusion Weighted Imaging (DWI) in hepatocellular carcinoma (HCC) has been widely handled in the literature. Due to the mono-exponential model limitations, several studies recently investigated the role of non-Gaussian DWI models in HCC. However, their results are variable and inconsistent. Therefore, the aim of this systematic review is to summarize current knowledge on non-Gaussian DWI techniques in HCC. A systematic search of the literature, including PubMed, Google Scholar, MEDLINE, and ScienceDirect databases, was performed to identify original articles since 2010 that evaluated the role of non-Gaussian DWI models for HCC diagnosis, grading, response to treatment, and prognosis. Studies were grouped and summarized according to the non-Gaussian DWI models investigated. We focused on the most used non-Gaussian DWI models (Intravoxel Incoherent Motion (IVIM), Diffusion Kurtosis Imaging (DKI), and Stretched Exponential-SE). The quality of included studies was evaluated by using QUADAS-2 and QUIPS tools. Forty-three articles were included, with IVIM and DKI being the most investigated models. Although the role of non-Gaussian DWI models in clinical settings has not fully been established, our findings showed that their parameters may potentially play a role in HCC. Further studies are required to identify a standardized DWI acquisition protocol for HCC diagnosis, grading, response to treatment, and prognosis.