Effects of resveratrol on aortic growth in patients with Marfan syndrome: a single-arm open-label multicentre trial.

BACKGROUND: Resveratrol, a dietary supplement that intervenes in cellular metabolism, has been shown to reduce aortic growth rate in a mouse model of Marfan syndrome (MFS), a condition associated in humans with life-threatening aortic complications, often preceded by aortic dilatation. The primary objective of this study was to investigate the effects of resveratrol on aortic growth rate in patients with MFS . METHODS: In this investigator-initiated, single-arm open-label multicentre trial, we analysed resveratrol treatment in adults aged 18-50 years with MFS. The primary endpoint was the change in estimated annual aortic growth at five predefined levels in the thoracic aorta after 1 year of resveratrol treatment, evaluated using a linear mixed model. Aortic diameters were measured by cardiac MRI at three time points to analyse the annual aortic expansion rate before and after initiation of treatment. Additionally, annual aortic growth was compared with growth in a previously conducted losartan randomised clinical trial. RESULTS: 898 patients were screened of which 19% (168/898) patients met the inclusion criteria.36% (61/168) patients signed informed consent and 93% (57/61) aged 37±9 years, of which 28 males (49%) were included in the final analysis of the study. 46% (26/57) had undergone aortic root replacement prior to the study. Aortic root diameters remained stable after 1.2±0.3 years of resveratrol administration. A trend towards a decrease in estimated growth rate (mm/year) was observed in the aortic root (from 0.39±0.06 to -0.13±0.23, p=0.072), ascending aorta (from 0.40±0.05 to -0.01±0.18, p=0.072) and distal descending aorta (from 0.32±0.04 to 0.01±0.14, p=0.072). CONCLUSION: Resveratrol treatment for 1 year may stabilise the aortic growth rate in adult patients with MFS. However, a subsequent randomised clinical trial with a longer follow-up duration and a larger study cohort is needed to establish an actual long-term beneficial effect of this dietary supplement in patients with MFS. TRIAL REGISTRATION NUMBER: NL66127.018.18.

Assessing Aortic Motion with Automated 3D Cine Balanced SSFP MRI Segmentation.

PURPOSE: To apply free-running three-dimensional (3D) cine balanced steady state free precession (bSSFP) CMR framework in combination with AI segmentations to quantify time-resolved aortic displacement, diameter and diameter change. METHODS: In this prospective study, we implemented a free-running 3D cine bSSFP sequence with scan time of about 4minutes facilitated by pseudo-spiral Cartesian undersampling and compressed-sensing reconstruction. Automated segmentation of all cardiac timeframes was applied through the use of nnU-Net. Dynamic 3D motion maps were created for three repeated scans per volunteer, leading to the detailed quantification of motion, as well as the measurement and change in diameter of the ascending aorta. RESULTS: A total of 14 adult healthy volunteers (median age, 28 years (IQR: 26.0-31.3), 6 female) were included. Automated segmentation compared to manual segmentation of the aorta test set showed a Dice score of 0.93 ± 0.02. The median (interquartile range) over all volunteers for the largest maximum and mean ascending aorta (AAo) displacement in the first scan was 13.0 (4.4) mm and 5.6 (2.4) mm, respectively. Peak mean diameter in the AAo was 25.9 (2.2) mm and peak mean diameter change was 1.4 (0.5) mm. The maximum individual variability over the three repeated scans of maximum and mean AAo displacement was 3.9 (1.6) mm and 2.2 (0.8) mm, respectively. The maximum individual variability of mean diameter and diameter change were 1.2 (0.5) mm and 0.9 (0.4) mm. CONCLUSION: A free-running 3D cine bSSFP CMR scan with a scan time of four minutes combined with an automated nnU-net segmentation consistently captured the aorta's cardiac motion-related 4D displacement, diameter, and diameter change.

Clinical implications of different methods to assess left atrial remodeling: A comparative study between echocardiography and cardiac magnetic resonance imaging for left atrial volume index quantification.

BACKGROUND: Left atrial volume index (LAVI) serves as a crucial marker for assessing left atrial (LA) remodeling, particularly in patients with mitral valve regurgitation (MR). Recent guidelines recommend a LAVI exceeding 60 mL/m2 as Class IIa recommendation for mitral valve repair surgery in asymptomatic MR patients with preserved left ventricular function. Traditionally, echocardiography is the standard for assessing LAVI in MR patients. However, cardiac magnetic resonance imaging (CMR) is increasingly recognized for its more precise measurements of cardiac dimensions and volumes. But still, literature remains scarce on comparing the efficacy of both modalities in assessing LAVI measurements. METHODS: This retrospective study included 168 MR patients undergoing both echocardiography and CMR assessments within a six-month period. LAVI measurements were compared using Pearson correlation and Bland-Altman plots. Patients were stratified based on MR grades, and clinical implications were assessed. RESULTS: Mean LAVI differed significantly between echocardiography and CMR (47.1 ± 20.8 mL/m2 versus 70 ± 20.3 mL/m2, p < 0.001, respectively). CMR consistently yielded higher LAVI measurements compared to echocardiography, with a mean difference of approximately 20 mL/m2. CMR measurements resulted in an increased incidence of patients meeting the class IIa LAVI criterion (LAVI >60 mL/m2) by 37%. Variations in LAVI did not differ across MR grades. CONCLUSION: Echocardiography systematically underestimates LAVI compared to CMR in MR patients. While current guidelines rely on echocardiography, CMR's precision suggests the need for CMR-specific LAVI cutoff values to guide clinical management effectively. Establishing such values could refine patient stratification and timing of surgery, potentially improving clinical outcomes for MR patients.

Optimizing pseudo-spiral sampling for abdominal DCE MRI using a digital anthropomorphic phantom.

PURPOSE: For reliable DCE MRI parameter estimation, k-space undersampling is essential to meet resolution, coverage, and signal-to-noise requirements. Pseudo-spiral (PS) sampling achieves this by sampling k-space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k-space sampling patterns for abdomin al DCE MRI. METHODS: The optimal PS k-space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient. RESULTS: The best PS reconstruction was found to be PS-diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient. CONCLUSION: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient.

Accelerated IVIM-corrected DTI in acute hamstring injury: towards a clinically feasible acquisition time.

BACKGROUND: Intravoxel incoherent motion (IVIM)-corrected diffusion tensor imaging (DTI) potentially enhances return-to-play (RTP) prediction after hamstring injuries. However, the long scan times hamper clinical implementation. We assessed accelerated IVIM-corrected DTI approaches in acute hamstring injuries and explore the sensitivity of the perfusion fraction (f) to acute muscle damage. METHODS: Athletes with acute hamstring injury received DTI scans of both thighs < 7 days after injury and at RTP. For a subset, DTI scans were repeated with multiband (MB) acceleration. Data from standard and MB-accelerated scans were fitted with standard and accelerated IVIM-corrected DTI approach using high b-values only. Segmentations of the injury and contralateral healthy muscles were contoured. The fitting methods as well as the standard and MB-accelerated scan were compared using linear regression analysis. For sensitivity to injury, Δ(injured minus healthy) DTI parameters between the methods and the differences between injured and healthy muscles were compared (Wilcoxon signed-rank test). RESULTS: The baseline dataset consisted of 109 athletes (16 with MB acceleration); 64 of them received an RTP scan (8 with MB acceleration). Linear regression of the standard and high-b DTI fitting showed excellent agreement. With both fitting methods, standard and MB-accelerated scans were comparable. Δ(injured minus healthy) was similar between standard and accelerated methods. For all methods, all IVIM-DTI parameters except f were significantly different between injured and healthy muscles. CONCLUSIONS: High-b DTI fitting with MB acceleration reduced the scan time from 11:08 to 3:40 min:s while maintaining sensitivity to hamstring injuries; f was not different between healthy and injured muscles. RELEVANCE STATEMENT: The accelerated IVIM-corrected DTI protocol, using fewer b-values and MB acceleration, reduced the scan time to under 4 min without affecting the sensitivity of the quantitative outcome parameters to hamstring injuries. This allows for routine clinical monitoring of hamstring injuries, which could directly benefit injury treatment and monitoring. KEY POINTS: • Combining high-b DTI-fitting and multiband-acceleration dramatically reduced by two thirds the scan time. • The accelerated IVIM-corrected DTI approaches maintained the sensitivity to hamstring injuries. • The IVIM-derived perfusion fraction was not sensitive to hamstring injuries.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

Purpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation.

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia associated with impaired cerebral hemodynamics and oxygen metabolism. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for patients with SCD. Whereas normalization of hemoglobin levels and hemolysis markers has been reported after HSCT, its effects on cerebral perfusion and oxygenation in adult SCD patients remain largely unexplored. This study investigated the effects of HSCT on cerebral blood flow (CBF), oxygen delivery, cerebrovascular reserve (CVR), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ) in 17 adult SCD patients (mean age: 25.0 ± 8.0, 6 females) before and after HSCT and 10 healthy ethnicity-matched controls (mean age: 28.0 ± 8.8, 6 females) using MRI. For the CVR assessment, perfusion scans were performed before and after acetazolamide as a vasodilatory stimulus. Following HSCT, gray and white matter (GM and WM) CBF decreased (p < .01), while GM and WM CVR increased (p < .01) compared with the baseline measures. OEF and CMRO2 also increased towards levels in healthy controls (p < .01). The normalization of cerebral perfusion and oxygen metabolism corresponded with a significant increase in hemoglobin levels and decreases in reticulocytes, total bilirubin, and LDH as markers of hemolysis (p < .01). This study shows that HSCT results in the normalization of cerebral perfusion and oxygen metabolism, even in adult patients with SCD. Future follow-up MRI scans will determine whether the observed normalization of cerebral hemodynamics and oxygen metabolism prevents new silent cerebral infarcts.

MR Elastography of the Pancreas: Bowel Preparation and Repeatability Assessment in Pancreatic Cancer Patients and Healthy Controls.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. PURPOSE: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. STUDY TYPE: Prospective. POPULATION: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age-/sex-matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. FIELD STRENGTH/SEQUENCE: 3-T, spin-echo echo-planar-imaging, turbo spin-echo, and fast field echo gradient-echo. ASSESSMENT: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal-to-noise ratio (SNR) was compared between all regimens. MRE repeatability (test-retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions-of-interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. STATISTICAL TESTS: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland-Altman analysis, (un)paired t-test, Mann-Whitney U-test, and Wilcoxon signed-rank test. P-value<0.05 was considered statistically significant. RESULTS: Preparation regimens did not significantly influence MRE-SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy-nontumor (P = 0.094). DATA CONCLUSION: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue-tumor and tumor-nontumor. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

The role of gadolinium-based contrast agents in magnetic resonance imaging structured reporting and data systems (RADS).

Among the 28 reporting and data systems (RADS) available in the literature, we identified 15 RADS that can be used in Magnetic Resonance Imaging (MRI). Performing examinations without using gadolinium-based contrast agents (GBCA) has benefits, but GBCA administration is often required to achieve an early and accurate diagnosis. The aim of the present review is to summarize the current role of GBCA in MRI RADS. This overview suggests that GBCA are today required in most of the current RADS and are expected to be used in most MRIs performed in patients with cancer. Dynamic contrast enhancement is required for correct scores calculation in PI-RADS and VI-RADS, although scientific evidence may lead in the future to avoid the GBCA administration in these two RADS. In Bone-RADS, contrast enhancement can be required to classify an aggressive lesion. In RADS scoring on whole body-MRI datasets (MET-RADS-P, MY-RADS and ONCO-RADS), in NS-RADS and in Node-RADS, GBCA administration is optional thanks to the intrinsic high contrast resolution of MRI. Future studies are needed to evaluate the impact of the high T1 relaxivity GBCA on the assignment of RADS scores.

Muscle fiber strain rates in the lower leg during ankle dorsi-/plantarflexion exercise.

Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water-fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water-fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles.

Single Breath-Hold MR Elastography for Fast Biomechanical Probing of Pancreatic Stiffness.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position-based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath-hold acquisition. PURPOSE: To develop and test a single breath-hold three-dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS-MRE). STUDY TYPE: Prospective. POPULATION: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male). FIELD STRENGTH/SEQUENCE: 3-T, GRE Ristretto MRE. ASSESSMENT: First, optimization of multi breath-hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave-phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS-MRE were compared against (I) 2D and (II) 3D four breath-hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS-MRE in a subgroup of healthy volunteers (N = 15). STATISTICAL TESTS: Tests include repeated measures analysis of variance (ANOVA), Bland-Altman analysis, and coefficients of variation (CoVs). A P-value <.05 was considered statistically significant. RESULTS: Optimization of the four breath-hold acquisitions resulted in 40 Hz vibration frequency, five wave-phases, and echo time (TE) = 6.9 msec as the preferred method (4BH-MRE). CS-MRE quantitative results did not differ from 4BH-MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH-MRE or CS-MRE. The limits of agreement for SWS were [-0.09, 0.10] m/second and the within-subject CoV was 4.8% for CS-MRE. DATA CONCLUSION: CS-MRE might allow a single breath-hold MRE acquisition with comparable SWS and phase angle as 4BH-MRE, and it may still enable to differentiate between HV and PDAC. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

A 3-slice cardiac quantitative native and post-contrast T1 and T2 MRI protocol requiring only four BHs using a 72-channel receive array coil.

Introduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel-imaging approach with a 72-channel receive-array to reduce BHs and demonstrate this in healthy subjects and hypertrophic cardiomyopathy (HCM) patients. Methods: A T1/T2 phantom was scanned at 3 T using a 16-channel and a novel 72-channel coil to assess the impact of different coils and acceleration factors on relaxation times. 16-18 healthy participants (8 female, age 28.4 ± 5.1 years) and 3 HCM patients (3 male, age 55.3 ± 4.2 years) underwent cardiac-MRI with the 72-channel coil, using a Modified Look-Locker scan with a shared inversion pulse across 3 slices and a Gradient-Spin-Echo scan. Acceleration was done by sensitivity encoding (SENSE) with accelerations 2, 4, and 6. LV T1 and T2 values were analyzed globally, per slice, and in 16 segments, with SENSE = 2 as the reference. Results: The phantom scans revealed no bias between coils and acceleration factors for T1 or T2, except for T2 with SENSE = 2, which resulted in a bias of 8.0 ± 6.7 ms (p < 0.001) between coils. SENSE = 4 and 6 enabled T1 mapping of three slices in a single BH, and T2 mapping of three slices within two BHs. In healthy subjects, T1 and T2 values varied. We found an average overestimation of T1 in 3 slices of 25 ± 87 ms for SENSE = 4 and 30 ± 103 ms using SENSE = 6, as compared to SENSE = 2. Acceleration resulted in decreased signal-to-noise; however, visually insignificant and without increased incidence of SENSE-artifacts. T2 was overestimated by 2.1 ± 5.0 ms for SENSE = 4 and 6.4 ± 9.7 ms using SENSE = 6, as compared to SENSE = 2. Native and post-contrast T1 measurements with SENSE = 4 and ECV quantification in HCM patients was successful. Conclusion: The 72-channel receiver-array coil with SENSE = 4 and 6, enabled LV-tissue characterization in three slices. Pre- and post-contrast T1 maps were obtained in a single BH, while T2 required two BHs.

Intestinal acetate and butyrate availability is associated with glucose metabolism in healthy individuals.

Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions.

Effects of mobile phone electromagnetic fields on brain waves in healthy volunteers.

The interaction between biological tissue and electromagnetic fields (EMF) is a topic of increasing interest due to the rising prevalence of background EMF in the past decades. Previous studies have attempted to measure the effects of EMF on brainwaves using EEG recordings, but are typically hampered by experimental and environmental factors. In this study, we present a framework for measuring the impact of EMF on EEG while controlling for these factors. A Bayesian statistical approach is employed to provide robust statistical evidence of the observed EMF effects. This study included 32 healthy participants in a double-blinded crossover counterbalanced design. EEG recordings were taken from 63 electrodes across 6 brain regions. Participants underwent a measurement protocol comprising two 18-min sessions with alternating blocks of eyes open (EO) and eyes closed (EC) conditions. Group 1 (n = 16) had EMF during the first session and sham during the second session; group 2 (n = 16) had the opposite. Power spectral density plots were generated for all sessions and brain regions. The Bayesian analysis provided statistical evidence for the presence of an EMF effect in the alpha band power density in the EO condition. This measurement protocol holds potential for future research on the impact of novel transmission protocols.

Four-Dimensional Flow MRI-Derived Hemodynamics in Abdominal Aortic Aneurysms: Reproducibility and Associations With Diameter, Intraluminal Thrombus Volume, and Vorticity.

BACKGROUND: Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four-dimensional (4D) flow MRI-derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable. PURPOSE: To assess the reproducibility of 4D flow MRI-derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth. STUDY TYPE: Prospective single-arm study. POPULATION: A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm. FIELD STRENGTH/SEQUENCE: A 3.0 T/Free-breathing 4D flow MRI phase-contrast acquisition with retrospective ECG-gating. ASSESSMENT: Patients underwent two consecutive 4D flow MRI scans 1-week apart. Aortic volumes were segmented from time-averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate. STATISTICAL TESTS: For reproducibility assessment, Bland-Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant. RESULTS: Test-retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity (R = 0.75) and inversely correlated with mean lumen diameter (R = -0.73). No significant associations were found between 4D flow MRI-derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22). DATA CONCLUSION: A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Progressive Changes in Cerebral Apparent Diffusion Values in Fabry Disease: A 5-Year Follow-up MRI Study.

BACKGROUND AND PURPOSE: White matter lesions are commonly found in patients with Fabry disease. Existing studies have shown elevated diffusivity in healthy-appearing brain regions that are commonly associated with white matter lesions, suggesting that DWI could help detect white matter lesions at an earlier stage This study explores whether diffusivity changes precede white matter lesion formation in a cohort of patients with Fabry disease undergoing yearly MR imaging examinations during a 5-year period. MATERIALS AND METHODS: T1-weighted anatomic, FLAIR, and DWI scans of 48 patients with Fabry disease (23 women; median age, 44 years; range, 15-69 years) were retrospectively included. White matter lesions and tissue probability maps were segmented and, together with ADC maps, were transformed into standard space. ADC values were determined within lesions before and after detection on FLAIR images and compared with normal-appearing white matter ADC. By means of linear mixed-effects modeling, changes in ADC and ΔADC (relative to normal-appearing white matter) across time were investigated. RESULTS: ADC was significantly higher within white matter lesions compared with normal-appearing white matter (P < .01), even before detection on FLAIR images. ADC and ΔADC were significantly affected by sex, showing higher values in men (60.1 [95% CI, 23.8-96.3] ×10-6mm2/s and 35.1 [95% CI, 6.0-64.2] ×10-6mm2/s), respectively. ΔADC increased faster in men compared with women (0.99 [95% CI, 0.27-1.71] ×10-6mm2/s/month). ΔADC increased with time even when only considering data from before detection (0.57 [95% CI, 0.01-1.14] ×10-6mm2/s/month). CONCLUSIONS: Our results indicate that in Fabry disease, changes in diffusion precede the formation of white matter lesions and that microstructural changes progress faster in men compared with women. These findings suggest that DWI may be of predictive value for white matter lesion formation in Fabry disease.

Viscoelastic properties of small bowel mesentery at MR elastography in Crohn's disease: a prospective cross-sectional exploratory study.

BACKGROUND: Creeping fat is a pathological feature of small bowel Crohn's disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD. METHODS: Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients' mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann-Whitney U-test). Within CD patients, the affected and "presumably" unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland-Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters. RESULTS: SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p < 0.010). No differences were found within CD between affected and presumably unaffected mesentery. Repeatability of SWS showed 95% limits of agreement of (-0.09, 0.13 m/s) and within-subject CoV of 5.3%. CONCLUSION: MRE may have the potential to measure fibrotic disease involvement of the mesentery in CD, possibly guiding clinical decision-making with respect to extended mesenteric resection. TRIAL REGISTRATION: Dutch trial register, NL9105 , registered 7 December 2020. RELEVANCE STATEMENT: MRE may have the potential to measure the amount of mesenteric fibrosis of the affected mesenteric fat in active Crohn's disease, giving more insight into disease progression and could potentially play a role in clinical decision-making for extended mesenteric resection. KEY POINTS: • MRE of the mesentery in patients with active CD is feasible. • Fluidity and stiffness of the mesentery increase in active CD, while stiffness correlates with the histopathological amount of mesenteric fibrosis. • MRE provides biomarkers to quantify mesenteric disease activity in active CD.

Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross-over trial.

AIMS: Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. METHODS AND RESULTS: The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2 ); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI -2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of -6 [95% CI -18, 7] m vs. -5 [95% CI -22, 22] m, respectively, P = 0.93), N-terminal pro-B-type natriuretic peptide (5 (-156, 166) ng/L vs. -13 (-172, 147) ng/L, P = 0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. CONCLUSIONS: Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

Sex Steroids Regulate Liver Fat Content and Body Fat Distribution in Both Men and Women: A Study in Transgender Persons.

CONTEXT: Liver fat content and visceral fat volume are associated with insulin resistance and cardiovascular disease and are higher in men than in women. OBJECTIVE: To determine the effect of estradiol and testosterone treatment on liver fat and visceral fat in transgender persons. DESIGN: Open-label intervention study (SHAMVA) with a 1-year follow-up. SETTING: Gender clinic in a hospital. PATIENTS: 8 trans women and 18 trans men receiving hormone treatment. INTERVENTIONS: Trans women received an antiandrogen and after 6 weeks estradiol was added. Trans men were randomized to receive triptorelin, testosterone, and anastrozole for 12 weeks or triptorelin and testosterone for 12 weeks, followed by only testosterone until week 52. MAIN OUTCOME MEASURES: Liver fat content, visceral and abdominal subcutaneous fat volume, measured by magnetic resonance spectrometry or imaging at baseline, 6, 8, 18, and 58 weeks in transwomen or at baseline; at 6 and 12 weeks in trans men with anastrozole; and at 52 weeks in trans men without anastrozole. RESULTS: In trans women, liver fat content decreased by 1.55% (-2.99 to -0.12) after 58 weeks, compared to week 6. Visceral fat did not change. In trans men with anastrozole, the liver fat content and visceral fat volume did not change. In trans men without anastrozole, after 52 weeks, liver fat content increased by 0.83% (0.14 to 1.52) and visceral fat volume increased by 34% (16 to 51). CONCLUSIONS: Sex hormones regulate liver fat content and visceral fat in men and women.

The role and implications of left atrial fibrosis in surgical mitral valve repair as assessed by CMR: the ALIVE study design and rationale.

Background: Patients with mitral regurgitation (MR) commonly suffer from left atrial (LA) remodeling. LA fibrosis is considered to be a key player in the LA remodeling process, as observed in atrial fibrillation (AF) patients. Literature on the presence and extent of LA fibrosis in MR patients however, is scarce and its clinical implications remain unknown. Therefore, the ALIVE trial was designed to investigate the presence of LA remodeling including LA fibrosis in MR patients prior to and after mitral valve repair (MVR) surgery. Methods: The ALIVE trial is a single center, prospective pilot study investigating LA fibrosis in patients suffering from MR in the absence of AF (identifier NCT05345730). In total, 20 participants will undergo a CMR scan including 3D late gadolinium enhancement (LGE) imaging 2 week prior to MVR surgery and at 3 months follow-up. The primary objective of the ALIVE trial is to assess the extent and geometric distribution of LA fibrosis in MR patients and to determine effects of MVR surgery on reversed atrial remodelling. Implications: This study will provide novel insights into the pathophysiological mechanism of fibrotic and volumetric atrial (reversed) remodeling in MR patients undergoing MVR surgery. Our results may contribute to improved clinical decision making and patient-specific treatment strategies in patients suffering from MR.