Splanchnic vessel blood flow assessment can describe physiology or pathophysiology and also has clinical relevance for patients with altered abdominal blood flow, vascular neuropathy, or atherosclerotic conditions. Reliable and practicable methods for this assessment are needed. We assessed the reproducibility of non-invasive phase-contrast MRI (PC-MRI) for measuring splanchnic blood flow and its feasibility for detecting postprandial blood flow changes. We included measurements from two groups of healthy individuals (Group A: n = 10; C: n = 10) and a group of patients with type 2 diabetes (B: n = 10) from randomized, single-blind, placebo-controlled studies, and assessed blood flow with 2D PC sequences (3 Tesla Siemens Biograph MRI and 3 Tesla Philips Achieva). Blood flow was measured in the arteria mesenterica superior, truncus coeliacus, arteria hepatica (Group A only), and vena portae hepatis over multiple days, with repeated scans each day to assess variability and reproducibility. To confirm detection of postprandial changes, nine repeated measurements were acquired during ingestion of 75-g oral glucose tolerance test compared to water ingestion. Reproducibility was assessed by coefficient of variation (CoV) and limits of agreement with the mean (LoAM) using an extended Bland-Altman analysis. Blood flow in arteria mesenterica superior, truncus coeliacus, and vena portae hepatis demonstrated low intrasubject within session CoV (7%-22%) and intrasubject between session CoV (16%-26%). Blood flow in arteria hepatica had poorer CoV for both within sessions (12%) and between sessions (32%). Glucose ingestion induced a blood flow peak increase of 88% ± 52% in arteria mesenterica superior and 68% ± 36% in vena portae hepatis, both robustly detected, while no change was observed in the arteria hepatica or truncus coeliacus. In conclusion, PC-MRI is a reproducible and feasible technique for measuring blood flow in arteria mesenterica superior, truncus coeliacus, and vena portae hepatis with the ability to detect postprandial changes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05391581, NCT06426823, NCT06774807.

In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. Ten participants with type 2 diabetes (age 20–80 years, BMI 20–35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57

Abstract Background: Bioelectrical impedance analysis (BIA) is considered a portable alternative to Dual-energy X-ray absorptiometry (DXA) when assessing deficient muscle mass, a major concern for older adults associated with increased risks of falls, fractures, disability, and mortality. However, several studies have demonstrated that BIA overestimates muscle mass in the older population and that estimates of muscle mass may depend on the BIA and DXA devices utilized. This study aims to describe the concordance between lean mass assessed by DXA and BIA across the adult population. Methods: This study is based on data from the Copenhagen Sarcopenia Study, a cross-sectional study of 1127 healthy participants aged 22-92 years with complete measurements of lean mass from both DXA (iDXA, GE Lunar) and BIA (Inbody 770). Relative appendicular lean mass (ALM) was calculated by normalizing ALM to height2 to account for allometric differences in body size. Results: For the total cohort, linear regression models showed a strong correlation between BIA and DXA for ALM (R2 = 0.92) and relative ALM (R2 = 0.83). A small, yet consistent, bias of relative ALM values was observed where BIA measures were on average 0.25±0.50 kg/m2 higher compared to measurements by DXA. The bias was consistent across age groups with a mean difference in relative ALM of 0.24±0.50 kg/m2, and 0.26±0.49 kg/m2 for younger participants, and older participants, respectively. Conclusion: BIA is a reliable alternative to DXA for assessing muscle mass, in both younger, and older adults. The findings indicate that with simple correction models for ALM and relative ALM, BIA can be a practical and accessible tool in clinical settings where DXA is unavailable. These models make BIA particularly useful for diagnosing sarcopenia, allowing for early detection and management regardless of age. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### 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: All participants provided written informed consent, and the study was approved by the Ethical Committee of the Capital Region and Frederiksberg (H-3-2013-124) and conducted in accordance with the Declaration of Helsinki II. 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 All data produced in the present work are contained in the manuscript

Gastrointestinal hormones are essential for nutrient handling and regulation of glucose metabolism and may affect postprandial blood redistribution. In a randomized cross-over design in 10 healthy men, the involvement of glucose-dependent insulinotropic polypeptide (GIP) in splanchnic blood flow regulation was investigated using an infusion of GIP receptor antagonist (GIPR-An) GIP(3-30)NH2 during ingestion of oral glucose (75 g). In five separate sessions, we investigated GIP(1-42), GIPR-An with and without oral glucose, oral glucose alone, and a control saline infusion. Blood flow was assessed by phase contrast MRI, hepatic oxygen consumption by T2*, and plasma glucose, insulin, C-peptide, glucagon, GIP, GIPR-An, glucagon-like peptide 2, and bone metabolism markers by frequent blood sampling during all sessions. We found GIP(1-42) to stimulate blood flow in the superior mesenteric artery by ∼10% in the fasting state. Oral glucose alone increased mean blood flow in the superior mesenteric artery by ∼70% and portal vein by ∼40% of baseline. During oral glucose ingestion with concurrent infusion of GIPR-An, blood flow in the superior mesenteric artery was ∼22% lower. The hormone infusions did not affect blood flow in the hepatic artery and the celiac artery. Infusion of GIPR-An during oral glucose ingestion resulted in lower insulin secretion and higher levels of carboxy-terminal collagen crosslinks (bone resorption biomarker) compared with saline infusion, whereas glucagon levels were unaffected by both the injection of GIP and the GIPR-An infusions. We conclude that endogenous GIP increases splanchnic blood flow and contributes to postprandial intestinal hyperemia in healthy men. ARTICLE HIGHLIGHTS:Administration of the gut hormone glucose-dependent insulinotropic polypeptide (GIP) increases splanchnic blood flow. We investigated the role of endogenous GIP in splanchnic blood flow regulation using a receptor antagonist in humans. Oral glucose ingestion increased blood flow in the superior mesenteric artery by ∼70%, and the increase was significantly lower during concurrent infusion of the GIP receptor antagonist. Thus, endogenous GIP contributed ∼22% of the postprandial increase in superior mesenteric artery blood flow. We have identified a novel physiological aspect of vascular biology related to the GIP receptor in humans. Treatments targeting the GIP receptors are likely to affect splanchnic blood flow.

Objective: The objective of this study was to investigate subchondral bone turnover at rest and after acute loading using Fluorine-18-labeled sodium fluoride (Na[18F]F) Positron Emission Tomography (PET), in patients with unilateral PFP. Design: Twenty-seven patients with unilateral PFP were recruited from the Institute of Sports Medicine Copenhagen. Participants underwent Na[18F]F-PET imaging before and after a bout of single-leg squats. Bone turnover measures, including mean and maximal standardized uptake value (SUVmean and SUVmax), rate of bone perfusion (K1), rate of tracer uptake into bone (Ki), and extraction fraction of tracer absorbed into bone mineral were assessed for patella and trochlea. Results: At rest, the painful knees showed lower SUVmax, K1, and Ki compared to the pain-free knees in the superficial part of the patella. No significant differences were found in the profound part of the patella or trochlea at rest. Following knee loading, the acute increases in SUVmean, SUVmax, Ki and blood flow were reduced in the superficial patella of the painful knees compared to the pain-free knees. In the trochlea, painful knees showed larger increases in SUVmean and Ki in the lateral part, whereas the medial part showed greater increases in K1, Ki, and a larger decrease in extraction fraction after loading. Conclusion: Patella displayed decreased bone metabolism at rest and reduced response to loading in the painful versus pain-free knees. Trochlea in the painful knees showed significantly larger increases in subchondral bone metabolism following knee loading compared to the pain-free knees. These novel findings highlight potential differences in bone turnover between the patellar and trochlear regions.

Low serum testosterone concentrations have been associated with low muscle mass and strength in older men. However, the existing literature is inconclusive. To investigate the differences in the relationship between total and calculated free serum testosterone and muscle status, in young vs. old men. Body mass index (BMI), fat percentage, appendicular lean mass (ALM), percentage ALM (ALM

Background Osteoporosis is a common, underdiagnosed condition causing increased risk of fracture. While dual-energy X-ray absorptiometry (DXA) is the diagnostic standard, this may not be successfully targeted to individuals at the highest risk. This study presents an extensive nationwide dataset characterizing DXA-scanning practices in Denmark. Methodology In this study, we identified all Danish residents from the birth cohort 1900-1960, with a first DXA scan between 2010-2022 to form the Nationwide Osteoporosis Cohort Trials Environment (NOCTE) dataset. These individuals were matched 1:5 to a non-scanned reference population by birth year, sex, and region of residence. Individual data were linked to national registers for comprehensive sociodemographic and clinical information. Results The final cohort included 263,651 individuals who underwent DXA scanning. At their first scan, 33% of women and 17% of men had osteoporosis. Compared to the matched reference, the scanned cohort had similar socioeconomic profiles but substantially different clinical profiles. Scanned individuals had a much higher prevalence of prior major osteoporotic fractures, prior systemic glucocorticoid exposure, and overall comorbidity burden. Conclusion Referral for DXA in Denmark is driven by clinical risk rather than socioeconomic status, reflecting an equitable resource allocation. However, a significant diagnostic gap persists, as many high-risk individuals with prior fractures did not receive a DXA. The NOCTE cohort is a new, powerful resource for developing strategies to help close this gap.

The objectives of this study were to examine how extremity lymphatic collector contraction frequency is influenced by gender, age, and methodological variations in indocyanine green (ICG) injection using near infrared fluorescence (NIRF) imaging in healthy adults. Ten women (19-46 years) and eight men (18-59 years) were examined with 30-min NIRF videos recorded at different time points 0-150 min after injection of ICG. Variations in ICG volume (0.1 mL vs. 0.3 mL), -concentration (1 mg/mL vs. 2.5 mg/mL), -injection site (hand vs. foot), -route of administration (subcutaneous vs. intradermal) were applied to all subjects. The primary outcome was mean contraction frequency with maximum contraction frequency and number of visualised extremity lymphatic collectors as secondary outcomes. The median of mean contraction frequencies for females and males were 0.42 min-1 (IQR 0,19 min-1) and 0.25 min-1 (IQR 0,15 min-1), respectively (p = 0.022). The median of maximum contraction frequencies for females and males were 0.70 min-1 (IQR 0,26 min-1) and 0.34 min-1 (IQR 0,15 min-1), respectively (p = 0.015). Neither age, method variations nor imaging delay had any significant effect on contraction frequencies. Number of visualised collectors increased slightly during 150 min (p = 0.02). Mean and maximum contraction frequencies were significantly higher in women compared to men. This is a novel finding that warrants verification in future studies. Contraction frequency measured with 30-min NIRF imaging using an ICG volume as little as 0.1 mL and a concentration of 1 mg/mL is seemingly robust and readily available. This method is recommendable for perturbation studies of lymphatic collector function and pathophysiology.

INTRODUCTION Quantitative MRI and [¹⁸F]NaF PET enable assessment of cartilage composition, bone shape, and subchondral bone metabolism in knee OA. Current workflows rely on manual segmentation that is time-consuming and subject to inter- and intra-reader variability. Furthermore, computing quantitative metrics requires considerable time and expertise. An open-source, automated, deep learning (DL) pipeline with standardized biomarker extraction has the potential to enhance reproducibility and make large-scale analysis accessible to clinical research communities, including non-technical users. OBJECTIVE Develop and validate an automated DL-based pipeline for comprehensive MRI-based segmentation and quantitative analysis of multiple knee tissues from multi-modal MR and PET images. METHODS We developed and open-sourced a comprehensive segmentation and analysis pipeline. A 2D U-Net was trained to segment 9 tissues using a dataset of 347 DESS and qDESS images: 3 bones (femur, tibia, patella), 4 cartilage regions (femoral, medial and lateral tibial, patellar), and 2 menisci (medial and lateral). Subchondral bone masks and femoral cartilage subregions were fitted automatically. Quantitative imaging biomarkers were computed as follows: cartilage T2 was computed analytically from qDESS scans; cartilage thickness was computed as the 3D Euclidean thickness of cartilage overlying the bone surface; meniscal volume was calculated as the product of voxel count and voxel volume; OA bone shape (BScore) was derived using a neural shape model; PET-derived subchondral bone metabolism was computed as regional SUVmean/max, and kinetic modeling via Hawkin’s method was used to extract KiNLR (bone mineralization rate) and K1 (perfusion to subchondral bone). To evaluate the pipeline, 20 unilateral qDESS and [¹⁸F]NaF PET knee scans (10 symptomatic OA, 10 controls) were analyzed by the automated pipeline, and two manual annotators. Manual and automated segmentations were compared using the Dice Similarity Coefficient (DSC) and average symmetric surface distance (ASSD). Biomarkers were compared using ICC and normalized mean RMSE (NRMSE). RESULTS All automated segmentations had good to excellent overlap measured using DSC (bone: 0.95-0.98; cartilage: 0.84-0.91; menisci: 0.85-0.89) and small surface errors (bone: 0.13-0.32 mm; cartilage: 0.11-0.21 mm; menisci: 0.17-0.30 mm). Notably, automated segmentations had better DSC and ASSD than the inter-rater comparison (Fig. 2). With the exception of cartilage thickness and patellar cartilage whole T2 values, all quantitative metrics showed excellent agreement with ICC >0.96 and NRMSE <0.1, comparable to inter-rater comparison. Bone metrics (BScore, SUV, PET kinetics) had ICC >0.96. Cartilage metrics had more variability, with the best reproducibility for whole cartilage T2 (ICC 0.89-0.98, NRMSE 0.01-0.04), then superficial T2 (ICC 0.93-0.99, NRMSE 0.01-0.05), and finally deep T2 (ICC 0.7-0.97, NRMSE 0.01-0.06). Cartilage thickness showed the worst reproducibility but still was comparable to inter-rater measures. Meniscus volume also shows high concordance (ICC 0.93-0.97; NRMSE 0.05-0.10). Overall, we found that most of the metrics derived from automated segmentations are comparable to those derived from manual segmentations. CONCLUSION Our open-source, AI-driven pipeline delivers rapid, accurate segmentation and quantitative analysis of multimodal knee MRI and PET data. Next steps include support for other MR sequences, multi-site validation, and 3D Slicer integration to facilitate translation. This resource provides a foundation for reproducible and scalable imaging biomarker analysis in OA research and clinical trials.

The accurate estimation of the tracer arterial blood concentration is crucial for reliable quantitative kinetic analysis in PET. In the current work, we demonstrate the automatic extraction of an image-derived input function (IDIF) from a CT AI-based aorta segmentation subsequently resliced to a dynamic PET series acquired on a Siemens Vision Quadra long-axial field of view scanner in 10 human subjects scanned with [15O]H2O. We demonstrate that the extracted IDIF is quantitative and in excellent agreement with a delay- and dispersion-corrected sampled arterial input function (AIF). Perfusion maps in the brain are calculated and compared from the IDIF and AIF, respectively, showed a high degree of correlation. The results demonstrate the possibility of defining a quantitatively correct IDIF compared with AIFs from the new-generation high-sensitivity and high-time-resolution long-axial field-of-view PET/CT scanners.

BACKGROUND AND HYPOTHESIS:The kidneys may be susceptible to ectopic fat and its lipotoxic effects, disposing them to chronic kidney disease (CKD) in type 2 diabetes (T2D). We investigated whether the kidney parenchyma fat content and kidney sinus fat volume would be higher in persons with T2D and CKD. METHODS:Cross-sectional study including 29 controls, 27 persons with T2D and no CKD, and 48 persons with T2D and early CKD (urine albumin creatinine ratio (UACR) ≥ 30 mg/g). Kidney parenchyma fat content and kidney sinus fat volume were assessed using magnetic resonance spectroscopy and Dixon scans respectively. RESULTS:In the control, T2D without CKD and T2D with CKD groups, respectively, median [1st - 3rd quartile] UACR was 5 [4 - 6], 6 [5 - 10] and 95 [43 - 278] mg/g. and mean ± standard deviation estimated glomerular filtration rate was 89 ± 11, 94 ± 11 and 77 ± 22 ml/min/1.73m2. Kidney parenchyma fat content was, respectively, 1.0 [0.5-2.4], 0.7 [0.2-1.2], 1.0 [0.3-2.0] % (p = 0.26). Kidney sinus fat volume was 2.8 [1.6-7.6], 8.0 [4.7-11.3], 10.3 [5.7-14.0] ml (p < 0.01). Around 90 % of T2D participants received a sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. CONCLUSIONS:In a setting of modern, multifactorial T2D management, kidney parenchyma fat content, evaluated with magnetic resonance spectroscopy, was similar among healthy controls and persons with T2D irrespective of CKD status. Still, kidney sinus fat volume was higher in the presence of T2D and higher still with CKD.

Academic performance (AP) is a strong predictor of long-term professional and social success. In recent years, physical fitness (PF) has been associated with AP in school age students. However, data related to a possible association between AP and PF in college students are scarce. PURPOSE: To verify the relationship between PF components with AP in college students. METHODS: Cross-section pilot study conducted with 69 college students (n = 40 Female age: 29 ± 9, n = 29 male age: 23 ± 3). Body composition (bioelectrical impedance), cardiorespiratory fitness (Queens’ college step test), flexibility (sit and reach test), muscular strength (handgrip test) and endurance (push-up test) were assessed according to ACSM’s guidelines. AP was obtained throughout the student’s official GPA. RESULTS: In females, the results revealed a negative correlation between AP with BMI (r = -.328; p = 0.05), and a positive correlation with flexibility (r = .341; p = 0.04), muscular endurance (r = .355; p = 0.03), when adjusted by age. No correlations were observed for male participants. CONCLUSION: Physical fitness is correlated with academic performance in female college students, but not in male students. If future studies confirm these results, strategies aiming to increase fitness levels among college students may be implemented as a way to improve students’ academic success.

Chronic kidney disease (CKD) is a major population disease. In diabetes as well as hypertension, kidney disease is one of the most serious complications. Recent research has demonstrated that chronic hypoxia is a key actor in the pathogenesis of CKD. In this review, we focus on how functional magnetic resonance imaging (fMRI) techniques can shed light on pathogenetic mechanisms and monitor new treatments aimed at preventing or ameliorating the disease. Multiparametric MRI techniques can measure changes in renal artery flow, tissue perfusion, and oxygenation repetitively over short time periods, enabling high time resolution. Furthermore, renal fibrosis can be quantified noninvasively by MRI diffusion tensor imaging, and techniques are upcoming to measure renal oxygen consumption. These techniques are all radiation and contrast-free.We briefly present data, demonstrating that fMRI techniques can play a major role in future research in CKD, and possibly also in daily clinical practice.

Molecular information derived from dynamic [ 18 F]NaF PET imaging holds promise to study bone remodeling in bone and joint disorders. The porosity index (PI), based on ultra-short echo-time (uTE) MRI, has been proposed to study bone porosity in clinically valuable acquisition times. We explored the association between bone metabolic and porosity information in the tibial tuberosity in a cohort of 10 subjects with knee OA using hybrid PET-MRI imaging. We found a moderate negative correlation between the metabolic bone remodeling (K i ) and the porosity index. These promising results may highlight a new tool to unveil unknown pathways in musculoskeletal disease pathophysiology.

IntroductionAccurately estimating bone perfusion and metabolism using [18F]NaF kinetics from shorter scan times could help address concerns related to patient comfort, motion, and throughput for PET scans. We examined the impact of changing the PET scan duration on the accuracy of [18F]NaF kinetic parameters in the knee.MethodsBoth knees of twenty participants with and without osteoarthritis were scanned using a hybrid PET-MRI system (53 ± 13 years, BMI 25.9 ± 4.2 kg/m2, 13 female). Seventeen participants were scanned for 54 ± 2 min, and an additional three participants were scanned for 75 min. Patlak Ki and Hawkins kinetic parameters (Ki, K1, extraction fraction) were assessed using 50- or 75-minutes of scan data as well as for scan durations that were retrospectively shortened. The error of the kinetic uptake parameters was calculated in bone regions throughout the knee.ResultsThe mean error of Patlak Ki, Hawkins Ki, K1, and extraction fraction was less than 10% for scan durations exceeding 30 min and decreased with increasing scan duration.ConclusionsThe length of dynamic data acquisition can be reduced to as short as 30 min while retaining accuracy within the limits of reproducibility of Hawkins kinetic uptake parameters.

Aim: To investigate the effects of ezetimibe on the urine albumin creatinine ratio (UACR) and kidney parenchyma fat content (kidney-PF) in individuals with type 2 diabetes (T2D) and early chronic kidney disease. Materials and Methods: A randomized, double-blind, placebo-controlled study of ezetimibe 10 mg once daily for 16 weeks in individuals with T2D and a UACR of 30 mg/g or higher was conducted. Kidney-PF was assessed with magnetic resonance spectroscopy. Geometric mean changes from baseline were derived from linear regressions. Results: A total of 49 participants were randomized to ezetimibe (n = 25) or placebo (n = 24). Overall, mean +/- standard deviation age was 67 +/- 7 years, body mass index was 31 +/- 4 kg/m(2) and the proportion of men was 84%. The mean estimated glomerular filtration rate was 76 +/- 22 mL/min/1.73m(2) and median (first-third quartile) UACR was 95 (41-297) mg/g. Median kidney-PF was 1.0% (0.3%-2.1%). Compared with placebo, ezetimibe did not significantly reduce UACR (mean [95% confidence interval] change: -3% [-28%-31%]) or kidney-PF (mean change: -38% [-66%14%]). In participants with baseline kidney-PF above the median, ezetimibe reduced kidney-PF significantly (mean change: -60% [-84% - -3%]) compared with placebo, while the reduction in UACR was not significant (mean change: -28% [-54%-15%]). Conclusions: Ezetimibe did not reduce the UACR or kidney-PF on top of modern T2D management. However, kidney-PF was reduced with ezetimibe in participants with high baseline kidney-PF.