Postcranial skeletal pneumaticity (PSP) is common in the presacral vertebrae of sauropod dinosaurs, but seemingly rare in their caudal vertebrae. Where identified, evidence for caudal vertebral PSP in sauropods is primarily based on the presence of external features, such as lateral fossae. However, such fossae can only be regarded as unequivocally pneumatic if communication between them and internal pneumatic bone texture can be confirmed. Based upon evidence from internal imaging, caudal vertebral PSP was previously known only in a rebbachisaurid diplodocoid (anterior caudal centrum and neural arch), some somphospondylan titanosauriforms (anterior caudal neural arches only) and saltasaurine titanosaurs (anterior-posterior caudal centra and neural arches). Here, we present novel CT scan data of caudal vertebrae of six Middle-Late Jurassic sauropods, representing several eusauropod lineages. We synthesise these new data with a comprehensive critical appraisal of purported external and internal evidence for caudal vertebral PSP in Sauropodomorpha. Newly sampled specimens of the non-neosauropod eusauropods Cetiosaurus sp. (anterior caudal centrum), 'Cetiosaurus glymptonensis' (middle caudal centrum) and the mamenchisaurid Wamweracaudia keranjei (anterior-middle caudal vertebrae), as well as the dicraeosaurine diplodocoid Dicraeosaurus sattleri (anterior caudal vertebra), are apneumatic. By contrast, the anterior-posterior caudal centra and neural arches of the diplodocine diplodocoid Tornieria africana possess deeply invasive external fossae that communicate with internal pneumatic chambers. Shallow external fossae on the centra and neural arches of at least the anteriormost 24 caudal vertebrae of the brachiosaurid titanosauriform Giraffatitan brancai communicate with internal pneumatic chambers. We observe a repeated pattern of PSP invading the anterior caudal vertebrae, with at least five independent acquisitions and/or reversals within Neosauropoda. Furthermore, for the first time, we demonstrate that extreme caudal vertebral PSP, in which pneumaticity extends into the middle-posterior region of the tail, is not restricted to saltasaurines, with this having also evolved independently in diplodocines and brachiosaurids. Finally, we find that both small- and large-bodied sauropods, including those with relatively short and long tails, evolved (and lost) caudal vertebral PSP. Therefore, the development of caudal vertebral PSP in sauropods does not appear to correspond with changes in body shape or mass. Instead, it might result from the opportunistic nature of pneumatic diverticula. However, given the high degree of inter- and intraspecific plasticity in its phylogenetic and serial distribution, we recognise that the evolution of PSP into the tail of sauropods might have been driven by a set of as-yet unknown, complex selective pressures.

Abstract Objectives Extraprostatic extension (EPE) significantly impacts surgical planning for prostate cancer (PCa) patients, influencing nerve-sparing surgery and neoadjuvant therapy decisions. However, Likert-scale-based radiological (r)EPE assessment lacks sufficient diagnostic accuracy for reliable clinical decision-making. Therefore, the aim was to evaluate rEPE scoring alongside clinical parameters to develop a clinically feasible decision tree for preoperative risk stratification. Methods This retrospective single-center study included 429 consecutive PCa patients undergoing radical prostatectomy between January 2012 and October 2018. All patients underwent multiparametric MRI with PI-RADS scoring and rEPE grading (grades 0–3). Clinical parameters included PSA density (PSAD) and ISUP grade group (GG) at biopsy. Univariate and multivariate logistic regression identified predictors of EPE. A clinical decision tree was developed using binary classification to stratify patients into risk groups. Results EPE was confirmed in 145 patients (33.8%). Multivariate analysis identified rEPE grade (OR 2.64, p < 0.001) and GG at biopsy (OR 1.41, p < 0.001) as independent predictors. The decision tree assigned 48% of patients to the high-risk (rEPE grade 3: 89% EPE risk) and low-risk group (rEPE < 3 + PSAD < 0.2 ng/mL² + GG < 4: 13% EPE risk), while 52% showed intermediate risk (28–45% EPE risk). Conclusions The developed decision tree combining MRI-derived rEPE grading, PSAD, and biopsy GG enables reliable identification of patients at high and low risk for EPE. This tool supports informed decision-making regarding nerve-sparing surgery and neoadjuvant therapy, potentially contributing to personalized treatment planning. Critical relevance statement Decision tree combining routine MRI-based and clinical markers reliably stratifies prostate cancer patients into high-risk and low-risk groups for EPE, supporting personalized surgical planning. Key Points EPE affects surgical planning decisions in prostate cancer patients. Combining EPE grade at MRI, PSAD, and biopsy grade improves risk stratification. The developed decision tree reliably stratified every second patient into distinct EPE-risk groups, potentially improving personalized surgical planning. Graphical Abstract

Abstract MRI has a central role in the diagnosis and management of prostate cancer, including active surveillance (AS) of low- and favourable intermediate-risk cancer. Robust evidence supports its use to guide biopsies and stratify the risk of progression at the inclusion stage. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria provide the foundation for standardised assessment on serial imaging during AS. Despite potential reductions in the number of unnecessary follow-up biopsies, uncertainty about the degree to which follow-up strategies can be defined by MRI leads to variation in international guidelines and their implementation. Here, the European Society of Urogenital Radiology (ESUR)–Prostate MRI Working Group reviews the evidence for the use of MRI in AS and provides practical guidance on its use. Additional research is needed to personalise AS strategies by integrating patient-specific factors, including family history and ethnicity, as well as emerging biomarkers such as genomic profiling and technological innovations like artificial intelligence. Critical relevance statement MRI is an integral part of AS, and initiatives to standardise image acquisition and reporting are underway. Further research is needed to better define MRI’s role during follow-up and to personalise AS, which could help achieve better harmonisation among international guidelines. The European Society of Urogenital Radiology (ESUR) prostate working group provides suggestions for practical implementation. Patient summary Active surveillance is a safe and effective management strategy for indolent prostate cancer. It avoids complications associated with surgery and radiation treatment. MRI has a central role in selecting which patients will benefit most from active surveillance and helping choose the most appropriate follow-up strategy. Acquiring standardised images and using reporting systems like PRECISE improves prostate cancer assessment and may help reduce the number of unnecessary biopsies. Key Points MRI plays a central role during active surveillance, but its implementation varies widely across centres. This ESUR position statement offers practical guidance on MRI acquisition, reporting, and interpretation tailored to active surveillance. Use of MRI—including the PRECISE score for active surveillance and the PI-QUAL score for image quality—can improve consistency and accuracy in monitoring prostate cancer over time. Graphical Abstract

The seminal vesicles (SVs) are important for reproductive health and prostate cancer (PCa) staging. Nevertheless, their biophysical properties remain largely unexplored. This secondary analysis investigates the feasibility and potential of multifrequency magnetic resonance elastography (MRE) in characterizing viscoelastic properties of the SVs across healthy subjects, men with benign prostatic hyperplasia (BPH), and patients with PCa. Sixty-two male participants (24 healthy, 25 BPH, 13 PCa) underwent pelvic MRE and diffusion-weighted imaging (DWI). We assessed shear wave speed (SWS), phase angle φ, apparent diffusion coefficient (ADC) and normalized ADC (nADC). Statistical comparisons across groups were performed using Kruskal–Wallis and Dunn tests. Test-retest and bilateral agreement were analyzed using intraclass correlation coefficients (ICCs). MRE of the SVs was technically feasible with excellent reproducibility, particularly for φ (ICC = 0.989), which was also significantly higher in BPH (p = 0.022) and PCa patients (p = 0.019), compared to healthy controls, showing elevated tissue fluidity in disease. While SWS and ADC did not differ significantly across groups, nADC was significantly reduced in BPH and PCa patients compared to healthy subjects (p < 0.001). No significant differences were detected between PCa patients with and without seminal vesicle invasion. Multifrequency MRE of the SVs is feasible and highly reproducible, allowing reliable assessment of their viscoelastic properties. Tissue fluidity may serve as a sensitive imaging biomarker. Further studies are warranted to explore the role of SV fluidity in disease progression and diagnosis. Multifrequency MRE enables the in vivo viscoelastic characterization of the SVs. It demonstrates disease-related increases in tissue fluidity in BPH and PCa. These findings showcase φ as a promising imaging biomarker for pathologies of the SVs and the prostate.

OBJECTIVES:Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging. Concerns exist regarding gadolinium deposition and its potential histopathologic tissue alterations, especially after repeated administrations of linear, less stable GBCAs. This study aimed to quantify gadolinium mass fractions in liver specimens of subjects exposed to GBCAs in correlation with histopathologic features. MATERIALS AND METHODS:In this Institutional Review Board-approved study, mass fractions of gadolinium in human liver specimens ω(Gd) from 25 subjects who underwent liver tumor resection surgery and had received GBCA (1 to 9 times over 4 y), were quantitatively analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). Histomorphology was assessed based on the nonalcoholic fatty liver disease activity score (NAS). Linear regression analyses were performed with ω(Gd), time and dosage metrics, and histopathologic parameters. RESULTS:The median interval between last GBCA administration and surgery (T) was 14 days (range: 1 to 69 d). Gadolinium was detected in all liver samples (ω(Gd), median: 0.348 µg/g; range: 0.120 to 0.874 µg/g). No significant correlation was found between ω(Gd) and histologic scores, including inflammation and fibrosis. A strong negative correlation was found between ω(Gd) and ln(T) ( P < 0.001). A positive correlation existed between ω(Gd) and the number ( P = 0.010) but not the cumulative dose of previous GBCA administrations ( P = 0.205). CONCLUSIONS:Our results suggest that after intravenous administration of GBCA, a small fraction of gadolinium is retained in the liver over a time period of at least several weeks. A relationship was observed between Gadolinium retention and the number of GBCA administrations, but not with the cumulative dose and the degree of fatty liver disease.

BACKGROUND:Men with suspected prostate cancer undergo magnetic resonance imaging (MRI) before biopsy. However, approximately 30%-50% of MRIs are negative (Prostate Imaging-Reporting and Data System [PI-RADS] score 1-2), representing a challenge for MRI resource utilization. This study evaluates prostate cancer polygenic risk scores and clinical markers to optimize MRI utilization. METHODS:In this prospective study, 500 cancer-suspected men of Western European descent scheduled for MRI (September 2017-December 2022) were enrolled. Exclusions included prior prostate cancer diagnosis, missing serum prostate-specific antigen (PSA), or PSA levels of at least 25 ng/mL. Patient-specific prostate cancer polygenic risk scores were calculated using genotype data obtained from saliva-derived DNA samples. Participants were grouped as MRI negative and positive (PI-RADS score 3-5). Logistic regression was used to calculate odds ratios (ORs) and to build multivariable risk models, including age, PSA, and polygenic risk scores for MRI positivity. Clinical utility was tested in a holdout test set using decision curve analysis. RESULTS:A total of 386 men (median age = 65 years, interquartile range [IQR] = 53-77 years) were eligible for analysis, which showed statistically significant associations between prostate cancer polygenic risk scores (OR = 1.56, 95% confidence interval [CI] = 1.23 to 1.98; P < .001) with MRI positivity, while PSA alone did not (OR = 1.17, 95% CI = 0.93 to 1.46; P = .18). The highest net benefit was shown using a multivariable age and prostate cancer polygenic risk score model, increasing the proportion of MRI-positive men by 14% compared with PSA alone (60% and 46%, respectively; P = .011). CONCLUSIONS:Genotype-informed risk stratification using prostate cancer polygenic risk scores could increase the proportion of cancer-suspicious findings at MRI, while identifying those who could safely avoid unnecessary MRI.

Prostate MRI has become integral to prostate cancer diagnosis and management, extending beyond prebiopsy triage to biopsy guidance, local staging, active surveillance, focal therapy planning, posttreatment surveillance, and evaluation of biochemical recurrence. As MRI use expands, image quality has emerged as a critical determinant of diagnostic reliability. Suboptimal prostate MRI quality can reduce cancer detection, increase equivocal PI-RADS assessments, compromise staging and longitudinal assessment, and undermine referring clinician confidence in MRI-directed care. The Prostate Imaging Quality System, or PI-QUAL, provides a standardized framework for assessing the diagnostic adequacy of prostate MRI examinations. Initially developed as a research quality-control tool using data from the multicenter PRECISION trial, PI-QUAL has been refined by the European Society of Urogenital Radiology into a more practical version applicable to both multiparametric and biparametric MRI examinations. In this Special Series Review, we describe the rationale for PI-QUAL, summarize evidence linking image quality with prostate MRI performance and patient management, and propose a stepwise approach for clinical implementation, including multidisciplinary training, retrospective audits, protocol optimization, structured reporting, quality dashboards, benchmark development, and artificial intelligence tools. Incorporating PI-QUAL into routine practice can make prostate MRI quality easier to measure, communicate, and improve.

Background:Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with an increased risk of liver fibrosis, liver cirrhosis, and the development of hepatocellular carcinoma. Magnetic resonance elastography (MRE) has been established for non-invasively grading hepatic fibrosis and is increasingly used for assessing inflammation in research studies. The first pharmaceutical treatment of MASH -Resmetirom - was approved in the United States in March 2024 and received approval in Europe in August 2025. This circumstance will increase the demand for clinical and research MRE examinations. Therefore, this scoping review aims to provide an overview of the current research on the use of MRE in MASH for assessing fibrosis and inflammation. Materials and Methods:A structured literature search was carried out within the MEDLINE and Embase + Embase Classic databases. A total of 11 studies within the last five years were included based on predefined criteria, such as prospective study design, histopathological validation as reference standard or comparisons with other non-invasive procedures. Results:The included studies encompassed diverse populations, methods, and outcome criteria. MRE demonstrated excellent diagnostic performance for liver fibrosis (AUC up to 0.97), outperforming many other non-invasive fibrosis tests. Additionally, preliminary studies suggest good performance for hepatic inflammation (AUC up to 0.83). Multiparametric approaches that combine MRE with other quantitative MRI-based methods, such as proton density fat fraction (PDFF) and corrected T1 (cT1), could further improve diagnostic performance in MASH. Conclusion:These findings show that MRE is a reliable tool for non-invasively assessing hepatic fibrosis in MASH and shows promise to assess inflammation in the future. Key Points:· MRE shows excellent accuracy for fibrosis and good accuracy for inflammation in MASH.. · Multiparametric MRI improves diagnostic accuracy for steatosis, fibrosis, and inflammation.. · Further research needed to establish MRE as biopsy alternative for MASH.. Citation Format:· Widmann FP, Häseli SP, Schattenfroh J et al. Current Evidence on MR Elastography in Metabolic Dysfunction-Associated Steatohepatitis: A Scoping Review. Rofo 2024; DOI 10.1055/a-2807-9946.

Objective A finding in a fossil mysticete rib is used to get insights into biomechanical limits of extinct whales. Materials The investigated specimen from the Miocene (Serravallian/Tortonian boundary) of Groß Pampau, North Germany, comprises a 252 mm distal fragment of a right posterior rib exhibiting distinctive pathological features including extensive periosteal new bone formation and a prominent 69 mm bony spur. Methods The internal morphology was analysed with a clinical CT-scanner. Results Morphological examination and computed tomography analysis revealed irregular cortical thickening, excentric bone proliferation with a 17° anterior deviation, and trabecular bone continuity at the spur base, consistent with a healed stress fracture. Differential diagnoses including acute trauma, osteomyelitis, neoplasia, and dysbaric osteonecrosis were systematically excluded based on morphological criteria and the absence of associated lesions throughout the skeleton. Conclusions The combination of an isolated rib fracture with periosteal reaction and the presence of an adaptive bony spur strongly suggests a stress fracture etiology resulting from repetitive biomechanical overload, analogous to stress injuries observed in human athletes, e.g., intensive swimming activities. Significance Stress fractures are underreported in cetaceans. Our findings enhance our understanding of bone remodeling processes providing evidence for chronic, repetitive mechanical overload and highlight that fossil bone can be used to demonstrate long-term physiological strain in deep-time. Limitations To date, there have been few comparable studies on marine mammals. Suggestions for Further Research Further research into the locomotory behavior and biomechanical stress patterns of Miocene cetaceans is needed.

Magnetic resonance elastography (MRE) allows noninvasive measurement of tissue viscoelasticity and is increasingly applied to characterize soft tissue biomechanics. This study investigates unfertilized chicken eggs as a biologically significant and cost-effective prostate phantom for combined MRE and diffusion-weighted imaging (DWI). Eggs were measured in two thermal states (soft-boiled and hard-boiled) to systematically alter the protein network structure and thus the mechanical properties of the phantom. All specimens were embedded in agarose gel and scanned using a 3T clinical MRI scanner equipped with multifrequency MRE and DWI. Quantitative parameters including shear wave speed (SWS), mechanical phase angle (φ), and apparent diffusion coefficient (ADC) as surrogates for stiffness, fluidity and water diffusivity, respectively, were analyzed in distinct anatomic compartments (yolk, egg white and germinal disc). Across both thermal states, egg white consistently demonstrated significantly higher values for SWS (medians ranging from 2.56 to 3.50 m/s), φ (0.85-0.86 rad), and ADC (1745.7-1529.1 μm2/s) compared to yolk (SWS: 1.25-1.44 m/s; φ: 0.63-0.67 rad; ADC: 278.8-214.8 μm2/s; all p < 0.01). Thermal processing induced biophysical parameter changes but did not eliminate the overall compartmental contrast. Test-retest reproducibility was variable, ranging from poor to excellent across parameters and compartments. In conclusion, unfertilized chicken eggs may represent a stable and structurally heterogeneous biological phantom for MRE with consistent compartmental differentiation. The consistent contrast between yolk and egg white across different thermal states highlights their potential as a simplified two-compartment model for elastography-based imaging and methodological development.

Within Avemetatarsalia, postcranial skeletal pneumaticity (PSP) occurs in pterosaurs, as well as theropod (including extant Aves) and sauropod dinosaurs. However, the evolutionary origins of PSP in the latter clade remain largely unknown, with few studies assessing species closely related to, but outside, the sauropod radiation, that is, early-branching sauropodomorphs. Furthermore, most proposed identifications of PSP in early-branching sauropodomorphs relate to external indicators of internal pneumaticity, for example, the presence of vertebral subfossae. To address this deficit, we CT scanned representative elements from the vertebral columns of the early-branching sauropodomorphs Thecodontosaurus antiquus, Pantydraco caducus, Ruehleia bedheimensis and Plateosaurus longiceps, all from the Late Triassic of Europe. These new data were compared with the small number of early-branching sauropodomorphs with published vertebral CT scan data, namely the Late Triassic Brazilian species, Buriolestes schultzi, Pampadromaeus barberenai and Macrocollum itaquii. Based on the sampled vertebrae, PSP is absent in Buriolestes, Pampadromaeus, Pantydraco and probably Thecodontosaurus. It is possible that the neural arches of the posterior cervical vertebrae of Thecodontosaurus possess PSP, but this can only be interpreted from broken transverse cross-sections and not CT scans. The posterior cervical vertebrae of Ruehleia possess PSP in the neural arches; however, their corresponding centra, along with the centra and neural arches of the anterior-middle dorsal vertebrae, are apneumatic. Plateosaurus possesses PSP in the neural arches of the middle cervical vertebrae through to the middle dorsal vertebrae, whereas the presacral centra are apneumatic. Where present, pneumatic internal chambers are neither exclusively camerate nor camellate, nor do they align with the 'protocamerate' bone structure previously described in the posterior cervical and anterior dorsal vertebrae of Macrocollum. From external indicators, PSP might be present in the sacral neural arches of Ruehleia and Plateosaurus but is absent in the caudal vertebrae. However, our results reveal that PSP cannot be unambiguously determined from external indicators; subfossae do not always communicate with internal chambers; and internal chambers sometimes communicate with undivided fossae. PSP in early-branching sauropodomorphs probably evolved first in the neural arches of the posterior cervical vertebrae, expanding anteriorly and posteriorly along the vertebral column. Furthermore, the distribution of PSP in Late Triassic early-branching sauropodomorphs does not appear to be correlated with body size. Finally, our results lend support to the idea that pterosauromorphs, theropods and sauropodomorphs evolved PSP in the Late Triassic independently of each other.

Introduction:Assessment of intervertebral disc (IVD) degeneration on conventional magnetic resonance imaging (MRI) is limited by large inter-reader variability and lack of stratification in clinical trials and their assessment of treatment responses. Therefore, we aimed to introduce and diagnostically validate multifrequency magnetic resonance elastography (MRE) with tomoelastography processing for the assessment of lumbar IVD degeneration in healthy volunteers and patients with low back pain. Methods:In this prospective single-center study, 60 participants (30 volunteers without low back pain and 30 patients with low back pain, 41 ± 17 years, body mass index 23.9 ± 3.7 kg/m2, 25 women) underwent multifrequency MRE using vibration frequencies from 40 to 70 Hz using a custom-built MRE setup in a 3T MRI scanner (Magnetom Skyra, software version XA30, Siemens Healthineers, Erlangen, Germany). Maps of shear wave speed (SWS in m/s) and loss angle (φ in rad), representing stiffness and viscous properties, respectively, were generated using tomoelastography data processing. The Pfirrmann score was used as reference standard to assess lumbar IVD degeneration on sagittal T2-weighted images. Inter-reader agreement (3 readers) and repeatability were assessed using the intraclass correlation coefficient (ICC). Results:Area under the receiver operating characteristic curve (AUC) analysis showed good diagnostic performance for detecting IVD degeneration (Pfirrmann score I/II/III/IV/V with n = 7/18/9/18/9, respectively) based on SWS (AUC: ≥II: 0.83, ≥III: 0.91, ≥IV: 0.96, V: 0.97) and φ (AUC: ≥II: 0.88, ≥III: 0.93, ≥IV: 0.98, V: 0.95). Good and excellent inter-reader agreements were found for Pfirrmann score (ICC = 0.87), SWS (ICC = 0.87), and φ (ICC = 0.92), respectively. Good repeatability was demonstrated for SWS (ICC = 0.88) and φ (ICC = 0.88). Discussion:Multifrequency MRE with tomoelastography processing allows effective IVD assessment and shows promise as a quantitative clinical imaging modality for assessing IVD degeneration.

Background and Aim Metabolic dysfunction-associated steatohepatitis (MASH) is an increasingly prevalent condition worldwide, associated with biomechanical liver changes and detectable by magnetic resonance elastography (MRE). This study explored the pathophysiological features and their biomechanical manifestations at different stages of MASH in a mouse dietary model. Methods Using MRE on a clinical 3 Tesla MRI scanner, we measured liver stiffness, viscosity, fat fraction and water diffusion in 45 male mice. These values were correlated with histopathology and proteomics analyses to further characterize the liver microstructural and metabolic changes during MASH progression. Results We found in a high-fat, low amino-acid model that early MASH was marked by fat accumulation and increasing inflammatory activity, while later stages showed a reduction in fat despite persistent inflammation. These changes in microstructure were associated with biomechanical adaptations, including a progressive decrease in hepatic viscosity and the water diffusion. Notably, viscosity was inversely correlated with lobular inflammation, cell adhesion, antioxidant activity, and metabolic adaptations such as enhanced ketone body synthesis. These findings, which precede the onset of fibrosis and tissue stiffening, show that tissue viscosity is highly sensitive to early microstructural and metabolic alterations in MASH. Conclusion Steatosis and inflammation significantly alter liver biophysical properties, particularly viscosity, in a mouse dietary model of MASH, even in the absence of fibrosis. These findings suggest that viscosity is a potential early and clinically translatable biomarker for the development and progression of MASH. ### Competing Interest Statement The authors have declared no competing interest. * ACAC : Acetoacetate ADC : Apparent diffusion coefficient BHB : Beta-hydroybutyrate CDAHFD : L-amino acid-defined · high-fat diet DWI : Diffusion weighted imaging FA : Fatty acid k-MDEV : Wave-number-based multifrequency dual elasto-visco inversion MRE : Magnetic resonance elastography PR : Penetration rate SWS : Shear wave speed TAG : Triaglycerol VLDL : very-low-density lipoprotein Deutsche Forschungsgemeinschaft, BIOQIC, SFB1340, Matrix in Vision, FOR6528 grant No. 534075507, GRK2260 German Federal Ministry of Education and Research (BMBF), DEEP-HCC, grant 26 No. 031L0315G

Acquired generalized lipodystrophy (AGL) is a rare metabolic disorder frequently associated with autoimmunity. Its etiology is incompletely understood and the impact of adipose tissue loss on autoimmunity and intestinal inflammation in AGL remains unclear. Using mass cytometry and single-cell RNA sequencing, we observed an oligoclonal expansion of T cells in the periphery and inflamed intestine in a patient with AGL and Crohns disease (AGLCD). To explore if loss of adipose tissue triggers lymphoproliferation, we studied lipodystrophic mice as a model for AGL. Unexpectedly, lipodystrophic mice did not show T-cell expansion, were protected from colitis and displayed a defect in the development of pro-inflammatory T cells, which could be reversed by allogeneic fat transplantations, indicating that clonal T-cell expansion is not primarily caused by lipodystrophy. Instead, gene sequencing revealed a T cell-intrinsic de-novo NRAS mutation, pointing towards somatic mosaicism as a driver of clonal T-cell expansion and systemic autoimmunity in AGLCD. ### Competing Interest Statement B.S. received grant support by Pfizer, served as consultant for Abbvie, BMS, Boehringer, Endpoint Health, Falk, Galapagos, Gilead, Janssen, Johnson & Johnson, Landos, Lilly, MSD, Pfizer, Takeda (BS served as representative of the Charité) and received speaker's fees from Abbvie, AlfaSigma, BMS, CED Service GmbH, Falk, Ferring, Galapagos, Janssen, Lilly, Pfizer, Takeda (BS served as representative of the Charité). C.W. received grant support by Pfizer, served as consultant for Pfizer and received speaker's fees from Falk, Ferring, Janssen. The other authors declare to not have any competing interests. ### Funding Statement This work was funded by the German Research Foundation (We 5303/3‐2 to CW, SFB‐TRR 241 (project-ID 375876048) B01 to BS and CW, A09 to AS and CW, A03 to CB and Z02 to BS, CRU 5023 (project-ID: 50474582), CRC 1449-B04 (project-ID: 431232613); CRC 1340-B06 (project-ID 372486779), SI749/14-1 (project-ID: 418055832) all to BS. CW and JZ received funding by the Clinician Scientist Program of the Berlin Institute of Health. CW received funding by the Fritz-Thyssen Foundation (10.19.2.028MN). Prargfl/fl mice were a kind gift of Prof. Dr. Ulrich Kintscher, Charite, Berlin. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study was approved by the institutional review board of Charite - Universitatsmedizin Berlin (Approval number EA1/200/17). Written informed consent was obtained from all healthy volunteers and patients as approved by the institutional review board of Charite - Universitatsmedizin Berlin. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Patient data supporting the human findings of this study are available from the corresponding authors upon reasonable request. scRNA-seq and mouse bulk seq data for this project will be uploaded to the NCBI database upon acceptance of this paper.

BACKGROUND AND OBJECTIVE:Prostate cancer (PCa) screening using prostate-specific antigen (PSA) thresholding and systematic biopsies reduces advanced disease presentations and cancer-specific mortality, but also leads to overdiagnosis. Magnetic resonance imaging (MRI) integration may maintain screening benefits, while reducing overdiagnosis and unnecessary biopsies. This review analyses the benefit-harm balance when MRI is integrated as first-line and second-stage (after PSA >3 ng/ml) test in PCa screening. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a PROSPERO-registered systematic review (CRD420251006926). Literature searches identified five first-line and four second-stage MRI screening studies. We assessed MRI strategies (first-line/second-stage and risk thresholds), biopsy avoidance, and biopsy methods (targeted/systematic) for histological outcomes (grade group [GG] ≥2/GG 1 cancer detection and benign biopsies). Benefit-to-harm ratios of >1 suggest a positive net benefit. KEY FINDINGS AND LIMITATIONS:First-line MRI screening detects twice as many men with GG ≥2 cancer as second-stage MRI screening but has more MRI-negative men (range, 66-89% vs 56-61%). Second-stage MRI significantly reduced biopsy rates (range, 42-79%) compared with systematic biopsy rates in all PSA-positive men. Subsequently, GG ≥2/GG 1 cancer detection ratios increased in MRI-positive men undergoing targeted and systematic biopsies (range, 1.9-6.2) and targeted biopsies alone (range, 1.8-7.0), compared with systematic biopsies alone (range, 0.8-1.4). First-line and second-stage MRI screening allowed biopsy avoidance in three to 55 and two to 15 men, respectively, for each benign diagnosis. All benefit-to-harm ratios showed positive net benefits (>1). Heterogeneity in the study protocols limits generalisability. CONCLUSIONS AND CLINICAL IMPLICATIONS:Targeted biopsies in second-stage MRI screening optimise clinically significant PCa detection, while reducing the number of biopsies. First-line MRI screening requires further assessments of its feasibility. PCa screening quality assurance requires standardised MRI interpretations and biopsy protocols.

Prostate MRI has evolved to a diagnostic imaging test that is crucial in the pathway of patients with suspected prostate cancer. The technical acquisition and the interpretation of prostate MRI have been accurately standardised in the PI-RADS recommendations, which have laid the foundation for the widespread implementation of prostate MRI. While the sensitivity and negative predictive value for prostate cancer detection are high, specificity and positive predictive value remain moderate. There is also substantial variation in the diagnostic performance of prostate MRI in the literature and this is a result of several factors including different levels of expertise and different image quality.

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium.

PURPOSE:To study the potential of viscoelastic parameters such as liver stiffness, loss tangent (marker of viscous properties) and viscoelastic dispersion to detect hepatic inflammation by in-vivo and ex-vivo MR elastography (MRE) at low and high vibration frequencies. METHODS:15 patients scheduled for liver tumor resection surgery were prospectively enrolled in this IRB-approved study and underwent multifrequency in-vivo MRE (30-60Hz) at 1.5-T prior to surgery. Immediately after liver resection, tumor-free tissue specimens were examined with ex-vivo MRE (0.8-2.8 kHz) at 0.5-T and histopathologic analysis including NAFLD activity score (NAS) and inflammation score (I-score) as sum of histological sub-features of inflammation. RESULTS:In-vivo, in regions where tissue samples were obtained, the loss tangent correlated with the I-score (R = 0.728; p = 0.002) and c-dispersion (stiffness dispersion over frequency) correlated with lobular inflammation (R = -0.559; p = 0.030). In a subgroup of patients without prior chemotherapy, c-dispersion correlated with I-score also in the whole liver (R = -0.682; p = 0.043). ROC analysis of the loss tangent for predicting the I-score showed a high AUC for I ≥ 1 (0.944; p = 0.021), I ≥ 2 (0.804; p = 0.049) and I ≥ 3 (0.944; p = 0.021). Ex-vivo MRE was not sensitive to inflammation, whereas strong correlations were observed between fibrosis and stiffness (R = 0.589; p = 0.021), penetration rate (R = 0.589; p = 0.021), loss tangent (R = -0.629; p = 0.012), and viscoelastic model parameters (spring-pot powerlaw exponent, R = -0.528; p = 0.043; spring-pot shear modulus, R = 0.589; p = 0.021). CONCLUSION:Our results suggest that c-dispersion of the liver is sensitive to inflammation when measured in-vivo in the low dynamic range (30-60Hz), while at higher frequencies (0.8-2.8 kHz) viscoelastic parameters are dominated by fibrosis.

Importance:The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown. Objective:To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring. Design, Setting, and Participants:This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023. Exposures:Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months. Main Outcomes and Measures:The total proportion of men avoiding PB and those with csPCa. Results:A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa. Conclusions and Relevance:In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.

The present minireview aims to provide a context for imagination of the timespan for bone infection evolution from the origin of cellular bone tissue to modern orthopedic surgery. From a phylogenetic osteomyelitis-bracketing perspective, and due to the time of osteocyte origin, bacteria might have been able to infect the skeleton for approximately 400 million years. Thereby, bone infections happened simultaneously with central expansions of the immune system and development of terrestrial bone structure. This co-evolution might aid in explaining the many immune evasion strategies seen in the field of bone infections. Bone infection patients with long disease-free periods followed by sudden recurrence and anamnesis of long-term and low-grade infections indicate that bacteria can perform silent parasitism within bone tissue (parasitism; one organism lives on another organism, the host, causing it harm and is structurally adapted to it). The silence seems to be disturbed by immunosuppression and the present minireview shows that a compromised immune system has been associated with bone infection development across all species in the phylogenetic tree. Orthopedic surgery, including arthroplasty and osteosynthesis, favor introduction of bacteria and prosthesis/implant related infections are thus anthropogenic infections (anthropogenic; resulting from the influence of human beings on nature). In that light it is important to remember that the skeleton and immune system have not evolved for millions of years to protect titanium alloys and other metals, commonly used for orthopedic devices from bacterial invasion. Therefore, these relatively new orthopedic infection types must be seen as distinct with unique implant/prosthesis related pathophysiology and immunology.