Liver T1 and T2 mapping in a large cohort of healthy subjects: normal ranges and correlation with age and sex.

OBJECTIVE: We established normal ranges for native T1 and T2 values in the human liver using a 1.5 T whole-body imager (General Electric) and we evaluated their variation across hepatic segments and their association with age and sex. MATERIALS AND METHODS: One-hundred healthy volunteers aged 20-70 years (50% females) underwent MRI. Modified Look-Locker inversion recovery and multi-echo fast-spin-echo sequences were used to measure hepatic native global and segmental T1 and T2 values, respectively. RESULTS: T1 and T2 values exhibited good intra- and inter-observer reproducibility (coefficient of variation < 5%). T1 value over segment 4 was significantly lower than the T1 values over segments 2 and 3 (p < 0.0001). No significant regional T2 variability was detected. Segmental and global T1 values were not associated with age or sex. Global T2 values were independent from age but were significantly lower in males than in females. The lower and upper limits of normal for global T1 values were, respectively, 442 ms and 705 ms. The normal range for global T2 values was 35 ms-54 ms in males and 39 ms-54 ms in females. DISCUSSION: Liver T1 and T2 mapping is feasible and reproducible and the provided normal ranges may help to establish diagnosis and progression of various liver diseases.

Development of a Thalassemia International Prognostic Scoring System (TIPSS).

A prognostic scoring system that can differentiate ß-thalassemia patients based on mortality risk is lacking. We analysed data from 3145 ß-thalassemia patients followed through a retrospective cohort design for the outcome of death. An a priori list of prognostic variables was collected. ß Coefficients from a multivariate cox regression model were used from a development dataset (n = 2516) to construct a formula for a Thalassemia International Prognostic Scoring System (TIPSS) which was subsequently applied to a validation dataset (n = 629). The median duration of observation was 10.0 years. The TIPSS score formula was constructed as exp (1.4 × heart disease + 0.9 × liver disease + 0.9 × diabetes + 0.9 × sepsis + 0.6 × alanine aminotransferase ≥42 IU/L + 0.6 × hemoglobin ≤9 g/dL + 0.4 × serum ferritin ≥1850 ng/mL). TIPSS score thresholds of greatest differentiation were assigned as <2.0 (low-risk), 2.0 to <5.0 (intermediate-risk), and ≥5.0 (high-risk). The TIPSS score was a good predictor for the outcome of death in the validation dataset (AUC: 0.722, 95%CI: 0.641-0.804) and survival was significantly different between patients in the three risk categories (P < 0.001). Compared to low-risk patients, the hazard ratio for death was 2.778 (95%CI: 1.335-5.780) in patients with intermediate-risk and 6.431 (95%CI: 3.151-13.128) in patients with high-risk. This study provides a novel tool to support mortality risk categorization for patients with ß-thalassemia that could help management and research decisions.

Deep Learning Staging of Liver Iron Content From Multiecho MR Images.

BACKGROUND: MRI represents the most established liver iron content (LIC) evaluation approach by estimation of liver T2* value, but it is dependent on the choice of the measurement region and the software used for image analysis. PURPOSE: To develop a deep-learning method for unsupervised classification of LIC from magnitude T2* multiecho MR images. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: A total of 1069 thalassemia major patients enrolled in the core laboratory of the Myocardial Iron Overload in Thalassemia (MIOT) network, which were included in the training (80%) and test (20%) sets. Twenty patients from different MRI vendors included in the external test set. FIELD STRENGTH/SEQUENCE: A5 T, T2* multiecho magnitude images. ASSESSMENT: Four deep-learning convolutional neural networks (HippoNet-2D, HippoNet-3D, HippoNet-LSTM, and an ensemble network HippoNet-Ensemble) were used to achieve unsupervised staging of LIC using five classes (normal, borderline, middle, moderate, severe). The training set was employed to construct the deep-learning model. The performance of the LIC staging model was evaluated in the test set and in the external test set. The model's performances were assessed by evaluating the accuracy, sensitivity, and specificity with respect to the ground truth labels obtained by T2* measurements and by comparison with operator-induced variability originating from different region of interest (ROI) placements. STATISTICAL TESTS: The network's performances were evaluated by single-class accuracy, specificity, and sensitivity and compared by one-way repeated measures analysis of variance (ANOVA) and one-way ANOVA. RESULTS: HippoNet-Ensemble reached an accuracy significantly higher than the other networks, and a sensitivity and specificity higher than HippoNet-LSTM. Accuracy, sensitivity, and specificity values for the LIC stages were: normal: 0.96/0.93/0.97, borderline: 0.95/0.85/0.98, mild: 0.96/0.88/0.98, moderate: 0.95/0.89/0.97, severe: 0.97/0.95/0.98. Correctly staging of cases was in the range of 85%-95%, depending on the LIC class. Multiclass accuracy was 0.90 against 0.92 for the interobserver variability. DATA CONCLUSION: The proposed HippoNet-Ensemble network can perform unsupervised LIC staging and achieves good prognostic performance. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Prognostic value of multiparametric cardiac magnetic resonance in sickle cell patients.

The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67 years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* < 20 ms). During a mean follow-up of 63.01 ± 24.95 months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88; p = 0.025) and right ventricular (RV) mass index (HR = 1.09; p = 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction < 58.9% and an RV mass index > 31 g/m2 were optimal cut-off values. Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that CMR may be added as a screening tool for identifying SCD patients at high risk for cardiopulmonary and vascular diseases.

Nodal staging with MRI after neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: a fast and reliable method.

OBJECTIVES: In patients with locally advanced rectal carcinoma (LARC), negative nodal status after neoadjuvant chemoradiotherapy (nCRT) may allow for rectum-sparing protocols rather than total mesorectal excision; however, current MRI criteria for nodal staging have suboptimal accuracy. The aim of this study was to compare the diagnostic accuracy of different MRI dimensional criteria for nodal staging after nCRT in patients with LARC. MATERIALS AND METHODS: Patients who underwent MRI after nCRT for LARC followed by surgery were retrospectively included and divided into a training and a validation cohort of 100 and 39 patients, respectively. Short-, long-, and cranial-caudal axes and volume of the largest mesorectal node and nodal status based on European Society of Gastrointestinal Radiology consensus guidelines (i.e., ESGAR method) were assessed by two radiologists independently. Inter-reader agreement was assessed in the training cohort. Histopathology was the reference standard. ROC curves and the best cut-off were calculated, and accuracies compared with the McNemar test. RESULTS: The study population included 139 patients (median age 62 years [IQR 55-72], 94 men). Inter-reader agreement was high for long axis (κ = 0.81), volume (κ = 0.85), and ESGAR method (κ = 0.88) and low for short axis (κ = 0.11). Accuracy was similar (p > 0.05) for long axis, volume, and ESGAR method both in the training (71%, 74%, and 65%, respectively) and in the validation (83%, 78%, and 75%, respectively) cohorts. CONCLUSION: Accuracy of the measurement of long axis and volume of the largest lymph node is not inferior to the ESGAR method for nodal staging after nCRT in LARC. CLINICAL RELEVANCE STATEMENT: In MRI restaging of rectal cancer, measurement of the long axis or volume of largest mesorectal lymph node after preoperative chemoradiotherapy is a faster and reliable alternative to ESGAR criteria for nodal staging. KEY POINTS: • Current MRI criteria for nodal staging in locally advanced rectal cancer after chemo-radiotherapy have suboptimal accuracy and are time-consuming. • Measurement of long axis or volume of the largest mesorectal lymph node on MRI showed good accuracy for assessment of loco-regional nodal status in locally advanced rectal cancer. • MRI measurement of the long axis and volume of largest mesorectal lymph node after chemo-radiotherapy could be a faster and reliable alternative to ESGAR criteria for nodal staging.

Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major.

OBJECTIVES: Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) is a surrogate marker of diffuse fibrosis. We evaluated the association between ECV and demographics, CMR findings, and cardiac involvement in patients with thalassemia major (TM). METHODS: A total of 108 ß-TM patients (62 females, 40.16 ± 8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, and 16 healthy subjects (6 females, 37.12 ± 16.13 years) underwent CMR. The protocol included assessment of T2*, native T1, and T2 values in all 16 myocardial segments for myocardial iron overload (MIO) quantification, cine images for left ventricular (LV) function quantification, post-contrast T1 mapping for ECV calculation, and late gadolinium enhancement (LGE) technique for replacement myocardial fibrosis detection. RESULTS: Global ECV values were significantly higher in females than in males. Global ECV values were significantly higher in patients with significant MIO (global heart T2* < 20 ms) than in patients without significant MIO, and both groups exhibited higher global ECV values than healthy subjects. No association was detected between native T1 and ECV values, while patients with reduced global heart T2 values showed significantly higher global ECV values than patients with normal and increased global heart T2. Global ECV values were not correlated with LV function/size and were comparable between patients with and without LGE. Compared to patients without heart failure, patients with a history of heart failure (N = 10) showed significantly higher global heart ECV values. CONCLUSION: In TM, increased myocardial ECV, potentially reflecting diffuse interstitial fibrosis, is associated with MIO and heart failure. KEY POINTS: • CMR-derived myocardial extracellular volume is increased in thalassemia major patients, irrespective of the presence of late gadolinium enhancement. • In thalassemia major, myocardial iron overload contributes to the increase in myocardial ECV, which potentially reflects diffuse interstitial fibrosis and is significantly associated with a history of heart failure.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major.

OBJECTIVES: This multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM). METHODS: We considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Pancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002). CONCLUSION: Pancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease. KEY POINTS: • In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism. • In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

National networking in rare diseases and reduction of cardiac burden in thalassemia major.

AIMS: A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). METHODS AND RESULTS: Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. CONCLUSION: Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients.

Development of an HPLC-MS/MS Method for the Determination of Alkaloids in Lupins.

Lupin alkaloids (LAs) represent a class of toxic secondary metabolites in plants, in particular in Lupinus spp.; they are produced as a defense mechanism due to their strong bitter taste and are very dangerous for human and animals. In this work, a sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analytical method for the identification and quantification of thirteen lupin alkaloids was developed and validated according to FDA guidelines. Efficient extraction and clean-up steps, carried out by solid-phase extraction, were finely tuned on the basis of the characteristics of the analytes and lupin samples, providing good selectivity with minimized matrix interference. The effectiveness of the method was proven by the satisfactory recovery values obtained for most of the analytes and a matrix effect ≤23% for all tested levels. In addition, a sensitive and reliable determination of the target compounds was obtained; LOQs were between 1 and 25 µg Kg-1, i.e., below the requested maximum levels (<200 mg Kg-1). The method was applied to evaluate the LAs profile in different batches of raw L. albus L. samples, varying in size and across farming treatments.

Primary HBB gene mutation severity and long-term outcomes in a global cohort of ß-thalassaemia.

In ß-thalassaemia, the severity of inherited ß-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 ß-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as ß0 /ß0 , ß0 /ß+ , ß+ /ß+ , ß0 /ß++ , ß+ /ß++ , and ß++ /ß++ . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, ß0 and ß+ mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with ß0 /ß0 , ß0 /ß+ , or ß+ /ß+ had a 2·104-increased risk of death [95% confidence interval (CI): 1·176-3·763, P = 0·011] and 2·956-increased odds of multiple morbidity (95% CI: 2·310-3·784, P < 0·001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65 years were 36·8% for this subgroup compared with 90·2% for patients in lower genotype severity groups (P < 0·001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with ß-thalassaemia and suggests inclusion of both ß+ and ß0 mutations in strata of greatest severity.

Frequency, pattern, and associations of renal iron accumulation in sickle/ß-thalassemia patients.

We evaluated frequency, pattern, and associations of renal iron accumulation in sickle/ß-thalassemia. Thirty-three sickle/ß-thalassemia patients (36.5 ± 14.7 years; 13 females), 14 homozygous sickle cell disease (SCD) patients, and 71 thalassemia major (TM) patients, enrolled in the E-MIOT Network, underwent magnetic resonance imaging. Iron overload (IO) was quantified by the T2* technique. Sickle/ß-thalassemia patients had a significantly lower frequency of renal IO (T2* < 31 ms) than homozygous SCD patients (9.1% vs. 57.1%; P = 0.001), besides having similar hepatic, cardiac and pancreatic IO. Kidney T2* values were comparable between regularly transfused sickle/ß-thalassemia and TM patients but were significantly lower in regularly transfused homozygous SCD patients than in the other two groups. In sickle/ß-thalassemia patients, global renal T2* values were not associated with age, gender, splenectomy, and presence of regular transfusions or chelation. No correlation was detected between renal T2* values and serum ferritin levels or iron load in the other organs. Global renal T2* values were not associated with serum creatinine levels but showed a significant inverse correlation with serum lactate dehydrogenase (R = - 0.709; P < 0.0001) and indirect bilirubin (R = - 0.462; P = 0.012). Renal IO is not common in sickle/ß-thalassemia patients, with a prevalence significantly lower compared to that of homozygous SCD patients, but with a similar underlying mechanism due to the chronic hemolysis.

Relationship between pancreatic iron overload, glucose metabolism and cardiac complications in sickle cell disease: An Italian multicentre study.

OBJECTIVES: Evidence about the cross-talk between iron, glucose metabolism, and cardiac disease is increasing. We aimed to explore the link of pancreatic iron by Magnetic Resonance Imaging (MRI) with glucose metabolism and cardiac complications (CC) in sickle cell disease (SCD) patients. METHODS: We considered 70 SCD patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified by R2* technique and biventricular function by cine images. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement technique. Glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Patients with an altered glucose metabolism showed a significantly higher pancreas R2* than patients with normal glucose metabolism. Pancreatic siderosis emerged as a risk factor for the development of metabolic alterations (OddsRatio 8.25, 95%confidence intervals 1.51-45.1; p = .015). Global pancreas R2* values were directly correlated with mean serum ferritin levels and liver iron concentration. Global pancreas R2* was not significantly associated with global heart R2* and macroscopic myocardial fibrosis. Patients with history of CC showed a significantly higher global pancreas R2* than patients with no CC. CONCLUSIONS: Our findings support the evaluation of pancreatic R2* by MRI in SCD patients to prevent the development of metabolic and cardiac disorders.

Myocardial T2 values at 1.5 T by a segmental approach with healthy aging and gender.

OBJECTIVES: Our aims were to obtain myocardial regional and global T2 values as a reference for normality for the first time using a GE scanner and to assess their association with physiological variables. METHODS: One hundred healthy volunteers aged 20-70 years (50% females) underwent cardiovascular magnetic resonance. Basal, mid-ventricular, and apical short-axis slices of the left ventricle were acquired by a multi-echo fast-spin-echo (MEFSE) sequence. Image analysis was performed with a commercially available software package. The T2 value was assessed in all 16 myocardial segments and the global value was the mean. RESULTS: The global T2 value averaged across all subjects was 52.2 ± 2.5 ms (range: 47.0-59.9 ms). Inter-study, intra-observer, and inter-observer reproducibility was good (coefficient of variation < 5%). 3.6% of the segments was excluded because of artifacts and/or partial-volume effects. Segmental T2 values differed significantly (p < 0.0001), with the lowest value in the basal anterolateral segment (50.0 ± 3.5 ms) and the highest in the apical lateral segment (54.9 ± 5.1 ms). Mean T2 was significantly lower in the basal slice compared to both mid-ventricular and apical slices and in the mid-ventricular slice than in the apical slice. Aging was associated with increased segmental and global T2 values. Females showed higher T2 values than males. T2 values were not correlated to heart rate. A significant inverse correlation was detected between global T2 values and mean wall thickness. CONCLUSIONS: The optimized MEFSE sequence allows for robust and reproducible quantification of segmental T2 values. Gender- and age-specific segmental reference values must be defined for distinguishing healthy and diseased myocardium. KEY POINTS: • In healthy subjects, T2 values differ among myocardial segments and are influenced by age and gender. • Normal T2 values in the myocardium, usable as a benchmark by other GE sites, were established.

Global longitudinal strain for detection of cardiac iron overload in patients with thalassemia: a meta-analysis of observational studies with individual-level participant data.

BACKGROUND: Although cardiac magnetic resonance (CMR) is the most reliable tool for assessment of CIO in patients with thalassemia, it is not always readily available. Recent studies have explored the potential of GLS as an alternative for diagnosis of CIO. We aimed to investigate the efficacy of global longitudinal strain (GLS) for detection of cardiac iron level (CIO). METHODS: We searched SCOPUS, MEDLINE, and Embase to identify the studies which used GLS for assessment of CIO. We searched for individual participant data (IPD) in eligible studies to perform ROC curve analysis. CMR with a T2* cut-off value of 20 ms was considered as the gold standard. A meta-analysis was performed and the risk of bias was assessed using the JBI Checklist. RESULTS: A total of 14 studies with 789 thalassemia patients (310 and 430 with and without CIO respectively and 49 with undetermined condition) were considered eligible for meta-analysis. IPDs of 405 participants were available. GLS was significantly lower in patients with CIO (-17.5 ± 2.7%) compared to those without CIO (-19.9 ± 2.3%; WMD = 1.6%, 95% CI = [0.76-2.4], p = 0.001, I2 = 77.1%) and to normal population (-20.61 ± 2.26%; WMD = 2.2%, 95% CI = [0.91-3.5], p = 0.001, I2 = 83.9%). A GLS < -19.5% could predict CIO with 92.8% sensitivity and 34.63% specificity (AUC = 0.659, 95% CI = [0.6-0.72], p-value < 0.0001). A GLS value < -6% has 100% positive predictive and ≥ -24.5% has 100% negative predictive values for detection of CIO. CONCLUSIONS: According to our study, GLS is a strong predictor of CIO and when CMR is not available, it may be a useful screening method for identification of CIO in thalassemia patients.

Diagnostic Accuracy of CT Texture Analysis in Adrenal Masses: A Systematic Review.

Adrenal incidentalomas (AIs) are incidentally discovered adrenal neoplasms. Overt endocrine secretion (glucocorticoids, mineralocorticoids, and catecholamines) and malignancy (primary or metastatic disease) are assessed at baseline evaluation. Size, lipid content, and washout characterise benign AIs (respectively, <4 cm, <10 Hounsfield unit, and rapid release); nonetheless, 30% of adrenal lesions are not correctly indicated. Recently, image-based texture analysis from computed tomography (CT) may be useful to assess the behaviour of indeterminate adrenal lesions. We performed a systematic review to provide the state-of-the-art of texture analysis in patients with AI. We considered 9 papers (from 70 selected), with a median of 125 patients (range 20-356). Histological confirmation was the most used criteria to differentiate benign from the malignant adrenal mass. Unenhanced or contrast-enhanced data were available in all papers; TexRAD and PyRadiomics were the most used software. Four papers analysed the whole volume, and five considered a region of interest. Different texture features were reported, considering first- and second-order statistics. The pooled median area under the ROC curve in all studies was 0.85, depicting a high diagnostic accuracy, up to 93% in differentiating adrenal adenoma from adrenocortical carcinomas. Despite heterogeneous methodology, texture analysis is a promising diagnostic tool in the first assessment of patients with adrenal lesions.

Ex Vivo Evaluation of Ethosomes and Transethosomes Applied on Human Skin: A Comparative Study.

In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome's mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%, w/w, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%, w/w. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed.

Predictive Multi Experiment Approach for the Determination of Conjugated Phenolic Compounds in Vegetal Matrices by Means of LC-MS/MS.

Polyphenols (PCs) are a numerous class of bioactive molecules and are known for their antioxidant activity. In this work, the potential of the quadrupole/linear ion trap hybrid mass spectrometer (LIT-QqQ) was exploited to develop a semi-untargeted method for the identification of polyphenols in different food matrices: green coffee, Crocus sativus L. (saffron) and Humulus lupulus L. (hop). Several conjugate forms of flavonoids and hydroxycinnamic acid were detected using neutral loss (NL) as a survey scan coupled with dependent scans with enhanced product ion (EPI) based on information-dependent acquisition (IDA) criteria. The presented approach is focused on a specific class of molecules and provides comprehensive information on the different conjugation models that are related to specific base molecules, thus allowing a quick and effective identification of all possible combinations, such as mono-, di-, or tri-glycosylation or another type of conjugation such as quinic acid esters.

A complication risk score to evaluate clinical severity of thalassaemia syndromes.

The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operating characteristic curve was 84·5%, 82·1% and 80·0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermediate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients' treatment.

Myocardial T1 Values at 1.5 T: Normal Values for General Electric Scanners and Sex-Related Differences.

BACKGROUND: No data are available about normal ranges for native T1 in human myocardium using General Electric (GE) scanners. PURPOSE: To establish normal ranges for myocardial T1 values and evaluate regional variability and the influence of physiological factors. STUDY TYPE: Prospective. SUBJECTS: One hundred healthy volunteers with normal electrocardiogram, no cardiovascular/systemic diseases, or risk factors (age range: 20-70 years; 50 females). FIELD STRENGTH/SEQUENCE: 1.5 T/Steady-state free precession cine and a modified Look-Locker inversion recovery sequence in diastole (also in systole for 61 volunteers). ASSESSMENT: Image analysis was performed by operators with >10 years experience in cardiac MR using commercially available software. T1 values were calculated for 16 myocardial segments, and the global value was the mean. Segments were grouped according to circumferential region (anterior, septal, inferior, and lateral) and to level (basal, medial, apical). Twenty images were analyzed twice by the same operator and by a different operator to assess reproducibility. STATISTICAL TESTS: Independent-samples t-test or Mann-Whitney test; paired sample t-test or Wilcoxon signed-rank test; one-way repeated measures ANOVA or Friedman tests; Pearson's or Spearman's correlation. Reproducibility evaluated using coefficient of variability (CoV). RESULTS: Due to artifacts and/or partial-volume effects, 45/1600 (2.8%) segments were excluded. A good intra- and inter-operator reproducibility was detected (CoV < 5%). There were significant differences in segmental T1 values (P < 0.05). A significant circumferential variability was present (P < 0.05): the mean native T1 value over the lateral region was significantly lower than in the other three regions. An increasing gradient from basal to apical slices was detected (P < 0.05). Segmental and global T1 values were not associated with age (range P = 0.052-0.911) but were significantly lower in males than in females (global: 993 ± 32 vs. 1037 ± 27 ms; P < 0.05) and significantly correlated with heart rate (range R for segmental values = 0.247-0.920; P < 0.05). Almost all segmental T1 values were inversely correlated with wall thickness (R from -0.233 to -0.514; P < 0.05). Systolic T1 values were significantly lower than diastolic values in basal anteroseptal segment, in all medial segments except the inferior one, and in all apical segments (P < 0.05). DATA CONCLUSION: Myocardial T1 values differ among myocardial regions, are influenced by sex, heart rate, and wall thickness and vary according to the cardiac cycle in healthy adults. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Biventricular Reference Values by Body Surface Area, Age, and Gender in a Large Cohort of Well-Treated Thalassemia Major Patients Without Heart Damage Using a Multiparametric CMR Approach.

BACKGROUND: Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE: To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (ß-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE: Retrospective/cohort study. POPULATION: In all, 251 ß-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE: 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT: Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS: Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS: Compared to controls, males with ß-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between ß-TM patients and healthy subjects in all the age groups. In the male ß-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In ß-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P < 0.0001 in all cases). The LV and the RV EF were comparable between the sexes (P = 0.568 and P = 0.268, respectively). DATA CONCLUSION: Appropriate "normal" reference ranges normalized to BSA, sex, and age are recommended to avoid misdiagnosis of cardiomyopathy in ß-TM patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.