Radiomics in Cross-Sectional Adrenal Imaging: A Systematic Review and Quality Assessment Study

In this study, we aimed to systematically review the current literature on radiomics applied to cross-sectional adrenal imaging and assess its methodological quality. Scopus, PubMed and Web of Science were searched to identify original research articles investigating radiomics applications on cross-sectional adrenal imaging (search end date February 2021). For qualitative synthesis, details regarding study design, aim, sample size and imaging modality were recorded as well as those regarding the radiomics pipeline (e.g., segmentation and feature extraction strategy). The methodological quality of each study was evaluated using the radiomics quality score (RQS). After duplicate removal and selection criteria application, 25 full-text articles were included and evaluated. All were retrospective studies, mostly based on CT images (17/25, 68%), with manual (19/25, 76%) and two-dimensional segmentation (13/25, 52%) being preferred. Machine learning was paired to radiomics in about half of the studies (12/25, 48%). The median total and percentage RQS scores were 2 (interquartile range, IQR = −5–8) and 6% (IQR = 0–22%), respectively. The highest and lowest scores registered were 12/36 (33%) and −5/36 (0%). The most critical issues were the absence of proper feature selection, the lack of appropriate model validation and poor data openness. The methodological quality of radiomics studies on adrenal cross-sectional imaging is heterogeneous and lower than desirable. Efforts toward building higher quality evidence are essential to facilitate the future translation into clinical practice

Antibody Profile, Gene Expression and Serum Cytokines in At-Risk Infants before the Onset of Celiac Disease

Immunological events that precede the development of villous atrophy in celiac disease (CeD) are still not completely understood. We aimed to explore CeD-associated antibody production (anti-native gliadin (AGA), anti-deamidated gliadin (DGP) and anti-tissue transglutaminase (anti-tTG)) in infants at genetic risk for CeD from the Italian cohorts of the PREVENT-CD and Neocel projects, as well as the relationship between antibody production and systemic inflammation. HLA DQ2 and/or DQ8 infants from families with a CeD case were followed from birth. Out of 220 at-risk children, 182 had not developed CeD by 6 years of age (CTRLs), and 38 developed celiac disease (CeD). The profiles of serum cytokines (INFγ, IL1β, IL2, IL4, IL6, IL10, IL12p70, IL17A and TNFα) and the expression of selected genes (FoxP3, IL10, TGFβ, INFγ, IL4 and IL2) were evaluated in 46 children (20 CeD and 26 CTRLs). Among the 182 healthy CTRLs, 28 (15.3%) produced high levels of AGA-IgA (AGA+CTRLs), and none developed anti-tTG-IgA or DGP-IgA, compared to 2/38 (5.3%) CeD infants (Chi Sq. 5.97, p = 0.0014). AGAs appeared earlier in CTRLs than in those who developed CeD (19 vs. 28 months). Additionally, the production of AGAs in CeD overlapped with the production of DGP and anti-tTG. In addition, gene expression as well as serum cytokine levels discriminated children who developed CeD from CTRLs. In conclusion, these findings suggest that the early and isolated production of AGA-IgA antibodies is a CeD-tolerogenic marker and that changes in gene expression and cytokine patterns precede the appearance of anti-tTG antibodies

Pancreatic Neuroendocrine Tumors in patients with Multiple Endocrine Neoplasia Type 1: Diagnostic Value of Different MRI Sequences

Background: Magnetic Resonance Imaging (MRI) is a useful imaging modality to assess the presence of Pancreatic Neuroendocrine Tumors (PNETs), allowing repeat monitoring examinations in MEN-1 patients. Objectives: We aimed to compare the diagnostic accuracy of conventional MRI sequences identifying which better depict the presence of PNETs in MEN-1 patients. Method: We performed a retrospective analysis of consecutive MEN-1 patients who underwent a conventional MRI protocol to monitor previously proven PNETs. MRI sequences T1-w Chemical-Shift (CS), T2-w HASTE, fat-suppressed (FS) T2-w HASTE, Diffusion Weighted Imaging (DWI), pre- and post-contrast FS T1-w sequences were independently analyzed by two experienced radiologists using a three-grade score (no lesion, uncertain lesion, certain lesion); lesion size and signal intensity were recorded. ANOVA Friedman and a Wilcoxon pairwise tests for the post-hoc analysis were used. The sensitivity of each sequence was measured; the results were analyzed with the Chi-squared test. Results: We included 21 patients with a total of 45 PNETs proven by histology, EUS guided fine needle aspiration, CT and nuclear medicine studies. A statistically significant (p<0.01) difference was observed in the detection performance of each MRI sequence, particularly between both DWI (91%) and T2-w FS (85%) sequences in comparison to the others (T1-w CS, T2-w, pre- and post-contrast FS T1-w, ≤56% for all); no significant (p=0.5) difference was found between the detection performance of DWI and T2-w FS sequences. No correlation was observed between the qualitative score of each sequence and lesion tumor size. Conclusions: DWI and T2-w FS sequences proved to be the most accurate in the detection of PNETs, thus suggesting a role for an abbreviated MRI protocol without contrast medium administration for monitoring MEN-1 patients

Characterization of Atypical Pheochromocytomas with Correlative MRI and Planar/Hybrid Radionuclide Imaging: A Preliminary Study

Pheochromocytomas may show atypical imaging findings leading to diagnostic pitfalls. We correlated the results of magnetic resonance imaging (MRI) with those of radionuclide studies in patients with pheochromocytomas. T2-weighted (-w), T1-w chemical-shift and T1-w dynamic contrast enhanced (DCE) MRI sequences were evaluated to assess tumor structure. 131Iodine metaiodobenzylguanidine (MIBG) scintigraphy, 18fluoro (F) deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or FDG PET/MRI were evaluated for direct comparison. Of a total of 80 adrenal lesions in 73 patients, 20 in 18 patients were pheochromocytomas. More than half (55%) of the pheochromocytomas (n = 11) had the typical increased signal intensity on T2-w and T1-w DCE, while the remaining (n = 9) lesions showed atypical findings; of these nine latter atypical lesions, seven (35%) were cystic (two totally, three predominantly and two partially) and two (10%) were hemorrhagic on MRI. In these atypical lesions, MIBG scintigraphy (n = 5), FDG PET/CT (n = 6) or FDG PET/MRI (n = 2) showed inhomogeneous tracer uptake in the residual viable tissue providing tumor characterization; however, one predominantly cystic pheochromocytoma showed false negative MIBG scan. Our preliminary results show that cystic degeneration may be frequent in pheochromocytoma being so marked that only a thin rim of viable cells may residue to disclose the true nature of the tumor. MRI findings together with those of correlative planar/hybrid radionuclide images are helpful to characterize these atypical pheochromocytomas. In particular, tumor accumulation of MIBG and/or FDG is able to classify these lesions as not simple cysts; in detail, the presence of partial MIBG uptake allows the diagnosis of pheochromocytomas, while the presence of partial FDG uptake generically reflects the presence of viable solid tissue of such cystic tumors

MRI to assess deep myometrial invasion in patients with endometrial cancer:A multi-reader study to evaluate the diagnostic role of different sequences

Objective: The identification of deep myometrial invasion (DMI) represents a fundamental aspect in patients with endometrial cancer (EC) for accurate disease staging. It can be detected on MRI using T2-weighted (T2-w), diffusion weighted (DWI) and dynamic contrast enhanced sequences (DCE). Aim of the study was to perform a multi-reader evaluation of such sequences to identify the most accurate and its reliability for the best protocol. Methods: In this multicenter retrospective study, MRI were independently evaluated by 4 radiologists (2 senior and 2 novice) with a sequence-based approach to identify DMI. The performance of the entire protocol was also evaluated. A comparison between the different sequences assessed by the same reader was performed using receiver operating curve and post-hoc analysis. Intraclass Correlation Coefficient (ICC) was used to assess interand intra-observer variability. Results: A total of 92 patients were included. The performance of the readers did not show significant differences among DWI, DCE and the entire protocol. For only one senior radiologist, who reached the highest diagnostic accuracy with the entire protocol (82,6 %), both DWI (p = 0,0197) and entire protocol (p = 0,0039) were found significantly superior to T2-w. The highest inter-observer agreement was obtained with the entire protocol by expert readers (ICC = 0,77). Conclusions: For the detection of DMI, the performances of DWI and DCE alone and that of a complete protocol do not significantly differ, even though the latter ensures the highest reliability particularly for expert readers. In cases in which T2-w and DWI are consistent, an unenhanced protocol could be proposed

Handcrafted MRI radiomics and machine learning: Classification of indeterminate solid adrenal lesions

Purpose To assess a radiomic machine learning (ML) model in classifying solid adrenal lesions (ALs) without fat signal drop on chemical shift (CS) as benign or malignant. Method 55 indeterminate ALs (21 lipid poor adenomas, 15 benign pheocromocytomas, 1 oncocytoma, 12 metastases, 6 primary tumors) showing no fat signal drop on CS were retrospectively included. Manual 3D segmentation on T2-weighted and CS images was performed for subsequent radiomic feature extraction. After feature stability testing and an 80–20% train-test split, the train set was balanced via oversampling. Following a multi-step feature selection, an Extra Trees model was tuned with 5-fold stratified cross-validation in the train set and then tested on the hold-out test set. Results A total of 3396 features were extracted from each AL, of which 133 resulted unstable while none had low variance ( 0.8) features were also excluded, leaving 440 parameters. Among these, Support Vector Machine 5-fold stratified cross-validated recursive feature elimination selected a subset of 6 features. ML obtained a cross-validation accuracy of 0.94 on the train and 0.91 on the test sets. Precision, recall and F1 score were respectively 0.92, 0.91 and 0.91. Conclusions Our MRI handcrafted radiomics and ML pipeline proved useful to characterize benign and malignant solid indeterminate adrenal lesions

A Celiac Cellular Phenotype, with Altered LPP Sub-Cellular Distribution, Is Inducible in Controls by the Toxic Gliadin Peptide P31-43.

Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides P31-43 and P57-68 induce innate and adaptive T cell-mediated immune responses, respectively. Alterations in the cell shape and actin cytoskeleton are present in celiac enterocytes, and gliadin peptides induce actin rearrangements in both the CD mucosa and cell lines. Cell shape is maintained by the actin cytoskeleton and focal adhesions, sites of membrane attachment to the extracellular matrix. The locus of the human Lipoma Preferred Partner (LPP) gene was identified as strongly associated with CD using genome-wide association studies (GWAS). The LPP protein plays an important role in focal adhesion architecture and acts as a transcription factor in the nucleus. In this study, we examined the hypothesis that a constitutive alteration of the cell shape and the cytoskeleton, involving LPP, occurs in a cell compartment far from the main inflammation site in CD fibroblasts from skin explants. We analyzed the cell shape, actin organization, focal adhesion number, focal adhesion proteins, LPP sub-cellular distribution and adhesion to fibronectin of fibroblasts obtained from CD patients on a Gluten-Free Diet (GFD) and controls, without and with treatment with A-gliadin peptide P31-43. We observed a "CD cellular phenotype" in these fibroblasts, characterized by an altered cell shape and actin organization, increased number of focal adhesions, and altered intracellular LPP protein distribution. The treatment of controls fibroblasts with gliadin peptide P31-43 mimics the CD cellular phenotype regarding the cell shape, adhesion capacity, focal adhesion number and LPP sub-cellular distribution, suggesting a close association between these alterations and CD pathogenesis

Qualitative Heterogeneous Signal Drop on Chemical Shift (CS) MR Imaging: Correlative Quantitative Analysis between CS Signal Intensity Index and Contrast Washout Parameters Using T1-Weighted Sequences

The aim of this study was to calculate MRI quantitative parameters extracted from chemical-shift (CS) and dynamic contrast-enhanced (DCE) T1-weighted (T1-WS) images of adrenal lesions (AL) with qualitative heterogeneous signal drop on CS T1-WS and compare them to those of AL with homogeneous or no signal drop on CS T1-WS. On 3 T MRI, 65 patients with a total of 72 AL were studied. CS images were qualitatively assessed for grouping AL as showing homogeneous (Group 1, n = 19), heterogeneous (Group 2, n = 23), and no (Group 3, n = 30) signal drop. Histopathology or follow-up data served as reference standard to classify AL. ROIs were drawn both on CS and DCE images to obtain adrenal CS signal intensity index (ASII), absolute (AWO), and relative washout (RWO) values. Quantitative parameters (QP) were compared with ANOVA analysis and post hoc Dunn&rsquo;s test. The performance of QP to classify AL was assessed with receiver operating characteristic analysis. CS ASII values were significantly different among the three groups (p &lt; 0.001) with median values of 71%, 53%, and 3%, respectively. AWO/RWO values were similar in Groups 1 (adenomas) and 2 (benign AL) but significantly (p &lt; 0.001) lower in Group 3 (20 benign AL and 10 malignant AL). With cut-offs, respectively, of 60% (Group 1 vs. 2), 20% (Group 2 vs. 3), and 37% (Group 1 vs. 3), CS ASII showed areas under the curve of 0.85, 0.96, and 0.93 for the classification of AL, overall higher than AWO/RWO. In conclusion, AL with qualitative heterogeneous signal drop at CS represent benign AL with QP by DCE sequence similar to those of AL with homogeneous signal drop at CS, but different to those of AL with no signal drop at CS; ASII seems to be the only quantitative parameter able to differentiate AL among the three different groups