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Abstract Background Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns. Results The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient’s liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient’s sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking. Conclusions We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient’s tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient’s liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients. Graphical Abstract

Preclinical high-field magnetic resonance imaging (MRI) systems offer a diverse array of MRI techniques, providing rich multiparametric MRI (mpMRI) platforms for studying numerous biological parameters. mpMRI platforms prove particularly indispensable when investigating tumors that exhibit profound intratumoral heterogeneity, such as breast cancer. A thoughtful comprehension of the origins of intratumoral heterogeneity is imperative for the judicious assessment of new targeted therapies and treatment interventions. Furthermore, when data from mpMRI are complemented with data from other in vivo imaging modalities, such as positron emission tomography (PET), and correlated with data from ex vivo modalities, such as matrix-assisted laser desorption imaging mass spectrometry (MALDI IMS), the in vivo parameters can be further elucidated at a molecular level and microscopic scale. Nevertheless, extracting meaningful scientific insights from such complex datasets necessitates the utilization of machine learning (ML) approaches to discern region-specific radiomic features. The development of correlative, multimodal imaging (CMI) workflows, such as one incorporating MRI, PET and MALDI IMS, is inherently challenging, given the many technological and methodological challenges related to multimodal data acquisition as well as the physiological limitations of the laboratory mice of the investigation. Standardization efforts in image acquisition and processing are required to increase the reproducibility and translatability of CMI data. To address the challenges of developing standardized CMI workflows and stimulate dialog regarding this area of need, we present a practical workflow to investigate tumor heterogeneity in breast cancer xenografts across various spatial scales. Our workflow entails simultaneous functional MRI and PET acquisitions in living mice, followed by correlation with post-imaging MALDI IMS and histologic data. Additionally, we propose data preprocessing steps for potential ML applications. We illustrate the feasibility of this workflow through two examples, showcasing its effectiveness in comparing in vivo and ex vivo images to evaluate tumor metabolism and hypoxia in mice with breast cancer xenografts.

Abstract Background International societies have issued guidelines for high-risk breast cancer (BC) screening, recommending contrast-enhanced magnetic resonance imaging (CE-MRI) of the breast as a supplemental diagnostic tool. In our study, we tested the applicability of deep learning-based anomaly detection to identify anomalous changes in negative breast CE-MRI screens associated with future lesion emergence. Methods In this prospective study, we trained a generative adversarial network on dynamic CE-MRI of 33 high-risk women who participated in a screening program but did not develop BC. We defined an anomaly score as the deviation of an observed CE-MRI scan from the model of normal breast tissue variability. We evaluated the anomaly score’s association with future lesion emergence on the level of local image patches (104,531 normal patches, 455 patches of future lesion location) and entire CE-MRI exams (21 normal, 20 with future lesion). Associations were analyzed by receiver operating characteristic (ROC) curves on the patch level and logistic regression on the examination level. Results The local anomaly score on image patches was a good predictor for future lesion emergence (area under the ROC curve 0.804). An exam-level summary score was significantly associated with the emergence of lesions at any location at a later time point (p = 0.045). Conclusions Breast cancer lesions are associated with anomalous appearance changes in breast CE-MRI occurring before the lesion emerges in high-risk women. These early image signatures are detectable and may be a basis for adjusting individual BC risk and personalized screening. Relevance statement Anomalies in screening MRI preceding lesion emergence in women at high-risk of breast cancer may inform individualized screening and intervention strategies. Key points • Breast lesions are associated with preceding anomalies in CE-MRI of high-risk women. • Deep learning-based anomaly detection can help to adjust risk assessment for future lesions. • An appearance anomaly score may be used for adjusting screening interval times. Graphical Abstract

Abstract Background Residual fibroglandular breast tissue (RFGT) following a mastectomy has been claimed to be associated with the occurrence of an in-breast local recurrence (IBLR) or new primary tumor (NP). Yet, scientific evidence proving this assumption is lacking. The primary aim of the study was to verify whether RFGT following a mastectomy is a risk factor for an IBLR or NP. Methods This retrospective analysis included all patients that underwent a mastectomy and were followed up at the Department of Obstetrics and Gynecology of the Medical University of Vienna between 01.01.2015 and 26.02.2020. RFGT volume (assessed on magnetic resonance imaging) was correlated with the prevalence of an IBLR and a NP. Results A total of 105 patients (126 breasts) following a therapeutic mastectomy were included. After a mean follow-up of 46.0 months an IBLR had occurred in 17 breasts and a NP in 1 breast. A significant difference in RFGT volume was observed between the disease-free cohort and the subgroup with an IBLR or NP (p = .017). A RFGT volume of ≥ 1153 mm3 increased the risk by the factor 3.57 [95%CI 1.27; 10.03]. Conclusions RFGT volume is associated with an increased risk for an IBLR or NP.

“Hot spot” 19F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, 19F-MRI’s direct detection has a unique advantage in vivo, as the human body exhibits a negligible background 19F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent 19F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the 19F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents.

Hyperoxic BOLD-MRI targeting tumor hypoxia may provide imaging biomarkers that represent breast cancer molecular subtypes without the use of injected contrast agents. However, the diagnostic performance of hyperoxic BOLD-MRI using different levels of oxygen remains unclear. We hypothesized that molecular subtype characterization with hyperoxic BOLD-MRI is feasible independently of the amount of oxygen. Twenty-three nude mice that were inoculated into the flank with luminal A (n = 9), Her2+ (n = 5), and triple-negative (n = 9) human breast cancer cells were imaged using a 9.4 T Bruker BioSpin system. During BOLD-MRI, anesthesia was supplemented with four different levels of oxygen (normoxic: 21%; hyperoxic: 41%, 71%, 100%). The change in the spin–spin relaxation rate in relation to the normoxic state, ΔR2*, dependent on the amount of erythrocyte-bound oxygen, was calculated using in-house MATLAB code. ΔR2* was significantly different between luminal A and Her2+ as well as between luminal A and triple-negative breast cancer, reflective of the less aggressive luminal A breast cancer’s ability to better deliver oxygen-rich hemoglobin to its tissue. Differences in ΔR2* between subtypes were independent of the amount of oxygen, with robust distinction already achieved with 41% oxygen. In conclusion, hyperoxic BOLD-MRI may be used as a biomarker for luminal A breast cancer identification without the use of exogenous contrast agents.

Abstract Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team.

Purpose: To analyze the rate of potentially avoidable needle biopsies in mammographically suspicious calcifications if supplementary Contrast-Enhanced MRI (CE-MRI) is negative. Methods: Using predefined criteria, a systematic review was performed. Studies investigating the use of supplemental CE-MRI in the setting of mammographically suspicious calcifications undergoing stereotactic biopsy and published between 2000 and 2020 were eligible. Two reviewers extracted study characteristics and true positives (TP), false positives, true negatives and false negatives (FN). Specificity, in this setting equaling the number of avoidable biopsies and FN rates were calculated. The maximum pre-test probability at which post-test probabilities of a negative CE-MRI met with BI-RADS benchmarks was determined by a Fagan nomogram. Random-effects models, I2-statistics, Deek’s funnel plot testing and meta-regression were employed. P-values

Abstract We summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as “high-risk” or B3 lesions). Finally, seven frequently asked questions are answered.

There is limited information about whether the level of enhancement on contrast-enhanced mammography (CEM) can be used to predict malignancy. The purpose of this study was to correlate the level of enhancement with the presence of malignancy and breast cancer (BC) aggressiveness on CEM. This IRB-approved, cross-sectional, retrospective study included consecutive patients examined with CEM for unclear or suspicious findings on mammography or ultrasound. Excluded were examinations performed after biopsy or during neoadjuvant treatment for BC. Three breast radiologists who were blinded to patient data evaluated the images. The enhancement intensity was rated from 0 (no enhancement) to 3 (distinct enhancement). ROC analysis was performed. Sensitivity and negative likelihood ratio (LR-) were calculated after dichotomizing enhancement intensity as negative (0) versus positive (1–3). A total of 156 lesions (93 malignant, 63 benign) in 145 patients (mean age 59 ± 11.6 years) were included. The mean ROC curve was 0.827. Mean sensitivity was 95.4%. Mean LR- was 0.12%. Invasive cancer presented predominantly (61.8%) with distinct enhancement. A lack of enhancement was mainly observed for ductal carcinoma in situ. Stronger enhancement intensity was positively correlated with cancer aggressiveness, but the absence of enhancement should not be used to downgrade suspicious calcifications.

Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.

Inherited deficiency in ether lipids, a subgroup of glycerophospholipids with unique biochemical and biophysical properties, evokes severe symptoms in humans resulting in a multi-organ syndrome. Mouse models with defects in ether lipid biosynthesis have widely been used to understand the pathophysiology of human disease and to study the roles of ether lipids in various cell types and tissues. However, little is known about the function of these lipids in cardiac tissue. Previous studies included case reports of cardiac defects in ether-lipid-deficient patients, but a systematic analysis of the impact of ether lipid deficiency on the mammalian heart is still missing. Here, we utilize a mouse model of complete ether lipid deficiency (Gnpat KO) to accomplish this task. Similar to a subgroup of human patients with rhizomelic chondrodysplasia punctata (RCDP), a fraction of Gnpat KO fetuses present with defects in ventricular septation, presumably evoked by a developmental delay. We did not detect any signs of cardiomyopathy but identified increased left ventricular end-systolic and end-diastolic pressure in middle-aged ether-lipid-deficient mice. By comprehensive electrocardiographic characterization, we consistently found reduced ventricular conduction velocity, as indicated by a prolonged QRS complex, as well as increased QRS and QT dispersion in the Gnpat KO group. Furthermore, a shift of the Wenckebach point to longer cycle lengths indicated depressed atrioventricular nodal function. To complement our findings in mice, we analyzed medical records and performed electrocardiography in ether-lipid-deficient human patients, which, in contrast to the murine phenotype, indicated a trend towards shortened QT intervals. Taken together, our findings demonstrate that the cardiac phenotype upon ether lipid deficiency is highly heterogeneous, and although the manifestations in the mouse model only partially match the abnormalities in human patients, the results add to our understanding of the physiological role of ether lipids and emphasize their importance for proper cardiac development and function.

Abstract Background Available data proving the value of DWI for breast cancer diagnosis is mainly for enhancing masses; DWI may be less sensitive and specific in non-mass enhancement (NME) lesions. The objective of this study was to assess the diagnostic accuracy of DWI using different ROI measurement approaches and ADC metrics in breast lesions presenting as NME lesions on dynamic contrast-enhanced (DCE) MRI. Methods In this retrospective study, 95 patients who underwent multiparametric MRI with DCE and DWI from September 2007 to July 2013 and who were diagnosed with a suspicious NME (BI-RADS 4/5) were included. Twenty-nine patients were excluded for lesion non-visibility on DWI (n = 24: 12 benign and 12 malignant) and poor DWI quality (n = 5: 1 benign and 4 malignant). Two readers independently assessed DWI and DCE-MRI findings in two separate randomized readings using different ADC metrics and ROI approaches. NME lesions were classified as either benign (> 1.3 × 10−3 mm2/s) or malignant (≤ 1.3 × 10−3 mm2/s). Histopathology was the standard of reference. ROC curves were plotted, and AUCs were determined. Concordance correlation coefficient (CCC) was measured. Results There were 39 malignant (59%) and 27 benign (41%) lesions in 66 (65 women, 1 man) patients (mean age, 51.8 years). The mean ADC value of the darkest part of the tumor (Dptu) achieved the highest diagnostic accuracy, with AUCs of up to 0.71. Inter-reader agreement was highest with Dptu ADC max (CCC 0.42) and lowest with the point tumor (Ptu) ADC min (CCC = − 0.01). Intra-reader agreement was highest with Wtu ADC mean (CCC = 0.44 for reader 1, 0.41 for reader 2), but this was not associated with the highest diagnostic accuracy. Conclusions Diagnostic accuracy of DWI with ADC mapping is limited in NME lesions. Thirty-one percent of lesions presenting as NME on DCE-MRI could not be evaluated with DWI, and therefore, DCE-MRI remains indispensable. Best results were achieved using Dptu 2D ROI measurement and ADC mean.

Combining therapeutic with diagnostic agents (theranostics) can revolutionize the course of malignant diseases. Chemotherapy, hyperthermia, or radiation are used together with diagnostic methods such as magnetic resonance imaging (MRI). In contrast to conventional contrast agents (CAs), which only enable non-specific visualization of tissues and organs, the theranostic probe offers targeted diagnostic imaging and therapy simultaneously. Methods: Novel salinomycin (Sal)-based theranostic probes comprising two different paramagnetic metal ions, gadolinium(III) (Gd(III)) or manganese(II) (Mn(II)), as signal emitting motifs for MRI were synthesized and characterized by elemental analysis, infrared spectral analysis (IR), electroparamagnetic resonance (EPR), thermogravimetry (TG) differential scanning calorimetry (DSC) and electrospray ionization mass spectrometry (ESI-MS). To overcome the water insolubility of the two Sal-complexes, they were loaded into empty bacterial ghosts (BGs) cells as transport devices. The potential of the free and BGs-loaded metal complexes as theranostics was evaluated by in vitro relaxivity measurements in a high-field MR scanner and in cell culture studies. Results: Both the free Sal-complexes (Gd(III) salinomycinate (Sal-Gd(III) and Mn(II) salinomycinate (Sal-Mn(II)) and loaded into BGs demonstrated enhanced cytotoxic efficacy against three human tumor cell lines (A549, SW480, CH1/PA-1) relative to the free salinomycinic acid (Sal-H) and its sodium complex (Sal-Na) applied as controls with IC50 in a submicromolar concentration range. Moreover, Sal-H, Sal-Gd(III), and Sal-Mn(II) were able to induce perturbations in the cell cycle of treated colorectal and breast human cancer cell lines (SW480 and MCF-7, respectively). The relaxivity (r1) values of both complexes as well as of the loaded BGs, were higher or comparable to the relaxivity values of the clinically applied contrast agents gadopentetate dimeglumine and gadoteridol. Conclusion: This research is the first assessment that demonstrates the potential of Gd(III) and Mn(II) complexes of Sal as theranostic agents for MRI. Due to the remarkable selectivity and mode of action of Sal as part of the compounds, they could revolutionize cancer therapy and allow for early diagnosis and monitoring of therapeutic follow-up.

Obesity is associated with leptin resistance and rising blood leptin levels while central leptin exposure may be limited. Here, the authors show that brain leptin infusion reduces hepatic lipid content in rats by increasing hepatic VLDL secretion and lowering liver de novo lipogenesis via a vagal mechanism.

Abstract Background Multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) shows clinical potential for detection and classification of breast lesions. Yet, the contribution of features for computer-aided segmentation and diagnosis (CAD) need to be better understood. We proposed a data-driven machine learning approach for a CAD system combining dynamic contrast-enhanced (DCE)-MRI, diffusion-weighted imaging (DWI), and 18F-fluorodeoxyglucose (18F-FDG)-PET. Methods The CAD incorporated a random forest (RF) classifier combined with mpPET/MRI intensity-based features for lesion segmentation and shape features, kinetic and spatio-temporal texture features, for lesion classification. The CAD pipeline detected and segmented suspicious regions and classified lesions as benign or malignant. The inherent feature selection method of RF and alternatively the minimum-redundancy-maximum-relevance feature ranking method were used. Results In 34 patients, we report a detection rate of 10/12 (83.3%) and 22/22 (100%) for benign and malignant lesions, respectively, a Dice similarity coefficient of 0.665 for segmentation, and a classification performance with an area under the curve at receiver operating characteristics analysis of 0.978, a sensitivity of 0.946, and a specificity of 0.936. Segmentation but not classification performance of DCE-MRI improved with information from DWI and FDG-PET. Feature ranking revealed that kinetic and spatio-temporal texture features had the highest contribution for lesion classification. 18F-FDG-PET and morphologic features were less predictive. Conclusion Our CAD enables the assessment of the relevance of mpPET/MRI features on segmentation and classification accuracy. It may aid as a novel computational tool for exploring different modalities/features and their contributions for the detection and classification of breast lesions.

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO3)2) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone.

Abstract This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. Teaching Points • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method.

The purpose of this multicenter retrospective study was to evaluate radiomics analysis coupled with machine learning (ML) of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) radiomics models separately and combined as multiparametric MRI for improved breast cancer detection. Consecutive patients (Memorial Sloan Kettering Cancer Center, January 2018–March 2020; Medical University Vienna, from January 2011–August 2014) with a suspicious enhancing breast tumor on breast MRI categorized as BI-RADS 4 and who subsequently underwent image-guided biopsy were included. In 93 patients (mean age: 49 years ± 12 years; 100% women), there were 104 lesions (mean size: 22.8 mm; range: 7–99 mm), 46 malignant and 58 benign. Radiomics features were calculated. Subsequently, the five most significant features were fitted into multivariable modeling to produce a robust ML model for discriminating between benign and malignant lesions. A medium Gaussian support vector machine (SVM) model with five-fold cross validation was developed for each modality. A model based on DWI-extracted features achieved an AUC of 0.79 (95% CI: 0.70–0.88), whereas a model based on DCE-extracted features yielded an AUC of 0.83 (95% CI: 0.75–0.91). A multiparametric radiomics model combining DCE- and DWI-extracted features showed the best AUC (0.85; 95% CI: 0.77–0.92) and diagnostic accuracy (81.7%; 95% CI: 73.0–88.6). In conclusion, radiomics analysis coupled with ML of multiparametric MRI allows an improved evaluation of suspicious enhancing breast tumors recommended for biopsy on clinical breast MRI, facilitating accurate breast cancer diagnosis while reducing unnecessary benign breast biopsies.