Genetic Determined Iron Starvation Signature in Friedreich's Ataxia.

BACKGROUND: Early studies in cellular models suggested an iron accumulation in Friedreich's ataxia (FA), yet findings from patients are lacking. OBJECTIVES: The objective is to characterize systemic iron metabolism, body iron storages, and intracellular iron regulation in FA patients. METHODS: In FA patients and matched healthy controls, we assessed serum iron parameters, regulatory hormones as well as the expression of regulatory proteins and iron distribution in peripheral blood mononuclear cells (PBMCs). We applied magnetic resonance imaging with R2*-relaxometry to quantify iron storages in the liver, spleen, and pancreas. Across all evaluations, we assessed the influence of the genetic severity as expressed by the length of the shorter GAA-expansion (GAA1). RESULTS: We recruited 40 FA patients (19 women). Compared to controls, FA patients displayed lower serum iron and transferrin saturation. Serum ferritin, hepcidin, mean corpuscular hemoglobin and mean corpuscular volume in FA inversely correlated with the GAA1-repeat length, indicating iron deficiency and restricted availability for erythropoiesis with increasing genetic severity. R2*-relaxometry revealed a reduction of splenic and hepatic iron stores in FA. Liver and spleen R2* values inversely correlated with the GAA1-repeat length. FA PBMCs displayed downregulation of ferritin and upregulation of transferrin receptor and divalent metal transporter-1 mRNA, particularly in patients with >500 GAA1-repeats. In FA PBMCs, intracellular iron was not increased, but shifted toward mitochondria. CONCLUSIONS: We provide evidence for a previously unrecognized iron starvation signature at systemic and cellular levels in FA patients, which is related to the underlying genetic severity. These findings challenge the use of systemic iron lowering therapies in FA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Functional aortic valve area differs significantly between sexes: A phase-contrast cardiac MRI study in patients with severe aortic stenosis.

Background: Aortic stenosis (AS) is one of the most prevalent valvular heart-diseases in Europe. Currently, diagnosis and classification are not sex-sensitive; however, due to a distinctly different natural history of AS, further investigations of sex-differences in AS-patients are needed. Thus, this study aimed to detect sex-differences in severe AS, especially concerning flow-patterns, via phase-contrast cardiac magnetic resonance imaging (PC-CMR). Methods: Forty-four severe AS-patients (20 women, 45 % vs. 24 men, 55 %) with a median age of 72 years underwent transthoracic echocardiography (TTE), cardiac catheterization (CC) and CMR. Aortic valve area (AVA) and stroke volume (SV) were determined in all modalities, with CMR yielding geometrical AVA via cine-planimetry and functional AVA via PC-CMR, the latter being also used to examine flow-properties. Results: Geometrical AVA showed no sex-differences (0.91 cm2, IQR: 0.61-1.14 vs. 0.94 cm2, IQR: 0.77-1.22, p = 0.322). However, functional AVA differed significantly between sexes in all three modalities (TTE: p = 0.044; CC/PC-CMR: p < 0.001). In men, no significant intermethodical biases in functional AVA-measurements between modalities were found (p = 0.278); yet, in women the particular measurements differed significantly (p < 0.001). Momentary flowrate showed sex-differences depending on momentary opening-degree (at 50 %, 75 % and 90 % of peak-AVA, all p < 0.001), with men showing higher flowrates with increasing opening-area. In women, flowrate did not differ between 75 % and 90 % of peak-AVA (p = 0.191). Conclusions: In severe AS-patients, functional AVA showed marked sex-differences in all modalities, whilst geometrical AVA did not differ. Inter-methodical biases were negligible in men, but not in women. Lastly, significant sex-differences in flow-patterns fit in with the different pathogenesis of AS.

Cardiac Magnetic Resonance Imaging Versus Computed Tomography to Guide Transcatheter Aortic Valve Replacement: A Randomized, Open-Label, Noninferiority Trial.

BACKGROUND: Computed tomography (CT) is recommended for guiding transcatheter aortic valve replacement (TAVR). However, a sizable proportion of TAVR candidates have chronic kidney disease, in whom the use of iodinated contrast media is a limitation. Cardiac magnetic resonance imaging (CMR) is a promising alternative, but randomized data comparing the effectiveness of CMR-guided versus CT-guided TAVR are lacking. METHODS: An investigator-initiated, prospective, randomized, open-label, noninferiority trial was conducted at 2 Austrian heart centers. Patients evaluated for TAVR according to the inclusion criteria (severe symptomatic aortic stenosis) and exclusion criteria (contraindication to CMR, CT, or TAVR, a life expectancy <1 year, or chronic kidney disease level 4 or 5) were randomized (1:1) to undergo CMR or CT guiding. The primary outcome was defined according to the Valve Academic Research Consortium-2 definition of implantation success at discharge, including absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance. Noninferiority was assessed using a hybrid modified intention-to-treat/per-protocol approach on the basis of an absolute risk difference margin of 9%. RESULTS: Between September 11, 2017, and December 16, 2022, 380 candidates for TAVR were randomized to CMR-guided (191 patients) or CT-guided (189 patients) TAVR planning. Of these, 138 patients (72.3%) in the CMR-guided group and 129 patients (68.3%) in the CT-guided group eventually underwent TAVR (modified intention-to-treat cohort). Of these 267, 19 patients had protocol deviations, resulting in a per-protocol cohort of 248 patients (121 CMR-guided, 127 CT-guided). In the modified intention-to-treat cohort, implantation success was achieved in 129 patients (93.5%) in the CMR group and in 117 patients (90.7%) in the CT group (between-group difference, 2.8% [90% CI, -2.7% to 8.2%]; P<0.01 for noninferiority). In the per-protocol cohort (n=248), the between-group difference was 2.0% (90% CI, -3.8% to 7.8%; P<0.01 for noninferiority). CONCLUSIONS: CMR-guided TAVR was noninferior to CT-guided TAVR in terms of device implantation success. CMR can therefore be considered as an alternative for TAVR planning. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03831087.

Impact of Dual-Energy Computed Tomography (DECT) Postprocessing Protocols on Detection of Monosodium Urate (MSU) Deposits in Foot Tendons of Cadavers.

OBJECTIVE: To evaluate two different dual-energy computed tomography (DECT) post-processing protocols for the detection of MSU deposits in foot tendons of cadavers with verification by polarizing light microscopy as the gold standard. MATERIAL AND METHODS: A total of 40 embalmed cadavers (15 male; 25 female; median age, 82 years; mean, 80 years; range, 52-99; SD ± 10.9) underwent DECT to assess MSU deposits in foot tendons. Two postprocessing DECT protocols with different Hounsfield unit (HU) thresholds, 150/500 (=established) versus 120/500 (=modified). HU were applied to dual source acquisition with 80 kV for tube A and 140 kV for tube B. Six fresh cadavers (4 male; 2 female; median age, 78; mean, 78.5; range 61-95) were examined by DECT. Tendon dissection of 2/6 fresh cadavers with positive DECT 120 and negative DECT 150 studies were used to verify MSU deposits by polarizing light microscopy. RESULTS: The tibialis anterior tendon was found positive in 57.5%/100% (DECT 150/120), the peroneus tendon in 35%/100%, the achilles tendon in 25%/90%, the flexor halluces longus tendon in 10%/100%, and the tibialis posterior tendon in 12.5%/97.5%. DECT 120 resulted in increased tendon MSU deposit detection, when DECT 150 was negative, with an overall agreement between DECT 150 and DECT 120 of 80% (p = 0.013). Polarizing light microscope confirmed MSU deposits detected only by DECT 120 in the tibialis anterior, the achilles, the flexor halluces longus, and the peroneal tendons. CONCLUSION: The DECT 120 protocol showed a higher sensitivity when compared to DECT 150.

Evaluation of Classic and Quantitative Imaging Features in the Differentiation of Benign and Atypical Lipomatous Soft Tissue Tumors Using a Standardized Multiparametric MRI Protocol: A Prospective Single-Centre Study in 45 Patients.

BACKGROUND: Discrimination between benign and atypical lipomatous tumors (ALT) is important due to potential local complications and recurrence of ALT but can be difficult due to the often-similar imaging appearance. Using a standardized MRI protocol, this study aimed to rank established and quantitative MRI features by diagnostic value in the differentiation of benign and atypical lipomatous tumors and to develop a robust scoring system. METHODS: Patients with clinical or sonographic suspicion of a lipomatous tumor were prospectively and consecutively enrolled from 2015 to 2019 after ethic review board approval. Histology was confirmed for all ALT and 85% of the benign cases. Twenty-one demographic and morphologic and twenty-three quantitative features were extracted from a standardized MRI protocol (T1/T2-proton-density-weighting, turbo-inversion recovery magnitude, T2* multi-echo gradient-echo imaging, qDIXON-Vibe fat-quantification, T1 relaxometry, T1 mapping, diffusion-weighted and post-contrast sequences). A ranking of these features was generated through a Bayes network analysis with gain-ratio feature evaluation. RESULTS: Forty-five patients were included in the analysis (mean age, 61.2 ± 14.2 years, 27 women [60.0%]). The highest-ranked ALT predictors were septation thickness (gain ratio merit [GRM] 0.623 ± 0.025, p = 0.0055), intra- and peritumoral STIR signal discrepancy (GRM 0.458 ± 0.046, p < 0.0001), orthogonal diameter (GRM 0.554 ± 0.188, p = 0.0013), contrast enhancement (GRM 0.235 ± 0.015, p = 0.0010) and maximum diameter (GRM 0.221 ± 0.075, p = 0.0009). The quantitative features did not provide a significant discriminatory value. The highest-ranked predictors were used to generate a five-tiered score for the identification of ALTs (correct classification rate 95.7% at a cut-off of three positive items, sensitivity 100.0%, specificity 94.9%, likelihood ratio 19.5). CONCLUSIONS: Several single MRI features have a substantial diagnostic value in the identification of ALT, yet a multiparametric approach by a simple combination algorithm may support radiologists in the identification of lipomatous tumors in need for further histological assessment.

Tissue iron distribution in patients with anemia of inflammation: Results of a pilot study.

Anemia of inflammation (AI) is frequently present in subjects with inflammatory disorders, primarily caused by inflammation-driven iron retention in macrophages. So far, only limited data on qualitative and quantitative estimates of tissue iron retention in AI patients exist. We performed a prospective cohort study analyzing splenic, hepatic, pancreatic, and cardiac iron content with MRI-based R2*-relaxometry in AI patients, including subjects with concomitant true iron deficiency (AI+IDA) hospitalized between 05/2020-01/2022. Control groups were individuals without inflammation. Spleen R2* values in AI patients with ferritin ≤200 µg/L (AI+IDA) were comparable with those found in controls. In AI patients with ferritin >200 µg/L, spleen (47.6 s-1 vs. 19.3 s-1 , p < .001) and pancreatic R2* values (32.5 s-1 vs. 24.9 s-1 , p = .011) were significantly higher compared with controls, while liver and heart R2*-values did not differ. Higher spleen R2* values were associated with higher ferritin, hepcidin, CRP, and IL-6 concentrations. Spleen R2* values normalized in AI patients after recovery (23.6 s-1 vs. 47.6 s-1 , p = .008), while no changes were found in patients with baseline AI+IDA. This is the first study investigating tissue iron distribution in patients with inflammatory anemia and AI with concomitant true iron deficiency. The results support the findings in animal models demonstrating iron retention in macrophages, which are primarily accumulating in the spleen under inflammatory conditions. MRI-related iron measurement may help to better characterize actual iron needs and to define better biomarker thresholds in the diagnosis of true ID in patients with AI. It may qualify as a useful diagnostic method to estimate the need for iron supplementation and to guide therapy.

1.5-T MR relaxometry in quantifying splenic and pancreatic iron: retrospective comparison of a commercial 3D-Dixon sequence and an established 2D multi-gradient echo sequence.

OBJECTIVES: To compare the quantitative measurement of splenic and pancreatic iron content using a commercial 3D-Dixon sequence (qDixon) versus an established fat-saturated R2* relaxometry method (ME-GRE). METHODS: We analyzed splenic and pancreatic iron levels in 143 MR examinations (1.5 T) using the qDixon and a ME-GRE sequence (108 patients: 65 males, 43 females, mean age 61.31 years). Splenic and pancreatic R2* values were compared between both methods using Bland-Altman plots, concordance correlation coefficients (CCC), and linear regression analyses. Iron overload (R2* > 50 1/s) was defined for both organs and compared using contingency tables, overall agreement, and Gwet's AC1 coefficient. RESULTS: Of all analyzable examinations, the median splenic R2* using the qDixon sequence was 25.75 1/s (range: 5.6-433) and for the ME-GRE sequence 35.35 1/s (range: 10.9-400.8) respectively. Concerning the pancreas, a median R2* of 29.93 1/s (range: 14-111.45) for the qDixon and 31.25 1/s (range: 14-97) for the ME-GRE sequence was found. Bland-Altman analysis showed a mean R2* difference of 2.12 1/s with a CCC of 0.934 for the spleen and of 0.29 1/s with a CCC of 0.714 for the pancreas. Linear regression for the spleen/pancreas resulted in a correlation coefficient of 0.94 (p < 0.001)/0.725 (p < 0.001). Concerning iron overload, the proportion of overall agreement between the two methods was 91.43% for the spleen and 93.18% for the pancreas. CONCLUSIONS: Our data show good concordance between R2* values obtained with a commercial qDixon sequence and a validated ME-GRE relaxometry method. The 3D-qDixon sequence, originally intended for liver assessment, seems to be a reliable tool for non-invasive evaluation of iron content also in the spleen and the pancreas. KEY POINTS: • A 3D chemical shift imaging sequence and 2D multi-gradient echo sequence show good conformity quantifying splenic and pancreatic R2* values. • The 3D chemical shift imaging sequence allows a reliable analysis also of splenic and pancreatic iron status. • In addition to the liver, the analysis of the spleen and pancreas is often helpful for further differential diagnostic clarification and patient guidance regarding the iron status.

Slice positioning in phase-contrast MRI impacts aortic stenosis assessment.

AIMS: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS). METHODS AND RESULTS: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm2, 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm2, 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm2, 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm2, p < 0.001), respectively. CONCLUSION: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP.

Morphological and Tissue Characterization with 3D Reconstruction of a 350-Year-Old Austrian Ardea purpurea Glacier Mummy.

Glaciers are dwindling archives, releasing animal mummies preserved in the ice for centuries due to climate changes. As preservation varies, residual soft tissues may differently expand the biological information content of such mummies. DNA studies have proven the possibility of extracting and analyzing DNA preserved in skeletal residuals and sediments for hundreds or thousands of years. Paleoradiology is the method of choice as a non-destructive tool for analyzing mummies, including micro-computed tomography (micro-CT) and magnetic resonance imaging (MRI). Together with radiocarbon dating, histo-anatomical analyses, and DNA sequencing, these techniques were employed to identify a 350-year-old Austrian Ardea purpurea glacier mummy from the Ötztal Alps. Combining these techniques proved to be a robust methodological concept for collecting inaccessible information regarding the structural organization of the mummy. The variety of methodological approaches resulted in a distinct picture of the morphological patterns of the glacier animal mummy. The BLAST search in GenBank resulted in a 100% and 98.7% match in the cytb gene sequence with two entries of the species Purple heron (Ardea purpurea; Accession number KJ941160.1 and KJ190948.1) and a 98% match with the same species for the 16 s sequence (KJ190948.1), which was confirmed by the anatomic characteristics deduced from micro-CT and MRI.

Time-Synchronized MRI-Assessment of Respiratory Apparatus Subsystems-A Feasibility Study.

The thorax (TH), the thoracic diaphragm (TD), and the abdominal wall (AW) are three sub-systems of the respiratory apparatus whose displacement motion has been well studied with the use of magnetic resonance imaging (MRI). Another sub-system, which has however received less research attention with respect to breathing, is the pelvic floor (PF). In particular, there is no study that has investigated the displacement of all four sub-systems simultaneously. Addressing this issue, it was the purpose of this feasibility study to establish a data acquisition paradigm for time-synchronous quantitative analysis of dynamic MRI data from these four major contributors to respiration and phonation (TH, TD, AW, and PF). Three healthy females were asked to breathe in and out forcefully while being recorded in a 1.5-Tesla whole body MR-scanner. Spanning a sequence of 15.12 seconds, 40 MRI data frames were acquired. Each data frame contained two slices, simultaneously documenting the mid-sagittal (TH, TD, PF) and transversal (AW) planes. The displacement motion of the four anatomical structures of interest was documented using kymographic analysis, resulting in time-varying calibrated structure displacement data. After computing the fundamental frequency of the cyclical breathing motion, the phase offsets of the TH, PF, and AW with respect to the TD were computed. Data analysis revealed three fundamentally different displacement patterns. Total structure displacement was in the range of 0.94 cm (TH) to 4.27 cm (TD). Phase delays of up to 90∘ (i.e., a quarter of a breathing cycle) between different structures were found. Motion offsets in the range of -28.30∘ to 14.90∘ were computed for the PF with respect to the TD. The diversity of results in only three investigated participants suggests a variety of possible breathing strategies, warranting further research.

Cardiac exercise imaging using a 3-tesla magnetic resonance-conditional pedal ergometer: Preliminary results in healthy volunteers and patients with known or suspected coronary artery disease.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR METHODS: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. RESULTS: Median subjective image quality of real-time cine at rest was 1 (interquartile range [IQR] 1-2) and 2 (IQR 2-2.5) for post-exercise real-time cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62-73] to 111 [104-143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m2, respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution postexercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. CONCLUSIONS: Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis.

AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in the treatment of type 2 diabetes, heart failure and chronic kidney disease. Their role in the prevention of diet-induced metabolic deteriorations, such as obesity, insulin resistance and fatty liver disease, has not been defined yet. In this study we set out to test whether empagliflozin prevents weight gain and metabolic dysfunction in a mouse model of diet-induced obesity and insulin resistance. METHODS: C57Bl/6 mice were fed a western-type diet supplemented with empagliflozin (WDE) or without empagliflozin (WD) for 10 weeks. A standard control diet (CD) without or with empagliflozin (CDE) was used to control for diet-specific effects. Metabolic phenotyping included assessment of body weight, food and water intake, body composition, hepatic energy metabolism, skeletal muscle mitochondria and measurement of insulin sensitivity using hyperinsulinaemic-euglycaemic clamps. RESULTS: Mice fed the WD were overweight, hyperglycaemic, hyperinsulinaemic and insulin resistant after 10 weeks. Supplementation of the WD with empagliflozin prevented these metabolic alterations. While water intake was significantly increased by empagliflozin supplementation, food intake was similar in WDE- and WD-fed mice. Adipose tissue depots measured by MRI were significantly smaller in WDE-fed mice than in WD-fed mice. Additionally, empagliflozin supplementation prevented significant steatosis found in WD-fed mice. Accordingly, hepatic insulin signalling was deteriorated in WD-fed mice but not in WDE-fed mice. Empagliflozin supplementation positively affected size and morphology of mitochondria in skeletal muscle in both CD- and WD-fed mice. CONCLUSIONS/INTERPRETATION: Empagliflozin protects mice from diet-induced weight gain, insulin resistance and hepatic steatosis in a preventative setting and improves muscle mitochondrial morphology independent of the type of diet.

Prognostic value of pulmonary transit time by cardiac magnetic resonance imaging in ST-elevation myocardial infarction.

OBJECTIVES: To investigate the prognostic value of pulmonary transit time (pTT) determined by cardiac magnetic resonance (CMR) after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: Comprehensive CMR examinations were performed in 207 patients 3 days and 4 months after reperfused STEMI. Functional parameters and infarct characteristics were assessed. PTT was defined as the interval between peaks of gadolinium contrast time-intensity curves in the right and left ventricles in first-pass perfusion imaging. Cox regression models were calculated to assess the association between pTT and the occurrence of major adverse cardiac events (MACE), defined as a composite of death, re-infarction, and congestive heart failure. RESULTS: PTT was 8.6 s at baseline and 7.8 s at the 4-month CMR. In Cox regression, baseline pTT (hazard ratio [HR]: 1.58; 95% CI: 1.12 to 2.22; p = 0.009) remained significantly associated with MACE occurrence after adjustment for left ventricular ejection fraction (LVEF) and cardiac index. The association of pTT and MACE remained significant also after adjusting for infarct size and microvascular obstruction size. In Kaplan-Meier analysis, pTT ≥ 9.6 s was associated with MACE (p < 0.001). Addition of pTT to LVEF resulted in a categorical net reclassification improvement of 0.73 (95% CI: 0.27 to 1.20; p = 0.002) and integrated discrimination improvement of 0.07 (95% CI: 0.02 to 0.13; p = 0.007). CONCLUSIONS: After reperfused STEMI, CMR-derived pTT was associated with hard clinical events with prognostic information independent of and incremental to infarct size and LV systolic function. KEY POINTS: • Pulmonary transit time is the duration it takes the heart to pump blood from the right chambers across lung vessels to the left chambers. • This prospective single-centre study showed inferior outcome in patients with prolonged pulmonary transit time after myocardial infarction. • Pulmonary transit time assessed by magnetic resonance imaging added incremental information to established prognostic markers.

Cardiac magnetic resonance imaging versus computed tomography to guide transcatheter aortic valve replacement: study protocol for a randomized trial (TAVR-CMR).

BACKGROUND: The standard procedure for the planning of transcatheter aortic valve replacement (TAVR) is the combination of echocardiography, coronary angiography, and cardiovascular computed tomography (TAVR-CT) for the exact determination of the aortic valve dimensions, valve size, and implantation route. However, up to 80% of the patients undergoing TAVR suffer from chronic renal insufficiency. Alternatives to reduce the need for iodinated contrast agents are desirable. Cardiac magnetic resonance (CMR) imaging recently has emerged as such an alternative. Therefore, we aim to investigate, for the first time, the non-inferiority of TAVR-CMR to TAVR-CT regarding efficacy and safety end-points. METHODS: This is a prospective, randomized, open-label trial. It is planned to include 250 patients with symptomatic severe aortic stenosis scheduled for TAVR based on a local heart-team decision. Patients will be randomized in a 1:1 fashion to receive a predefined TAVR-CMR protocol or to receive a standard TAVR-CT protocol within 2 weeks after inclusion. Follow-up will be performed at hospital discharge after TAVR and after 1 and 2 years. The primary efficacy outcome is device implantation success at discharge. The secondary endpoints are a combined safety endpoint and a combined clinical efficacy endpoint at baseline and at 1 and 2 years, as well as a comparison of imaging procedure related variables. Endpoint definitions are based on the updated 2012 VARC-2 consensus document. DISCUSSION: TAVR-CMR might be an alternative to TAVR-CT for planning a TAVR procedure. If proven to be effective and safe, a broader application of TAVR-CMR might reduce the incidence of acute kidney injury after TAVR and thus improve outcomes. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT03831087). The results will be disseminated at scientific meetings and publication in peer-reviewed journals.

Breathing, (S)Training and the Pelvic Floor-A Basic Concept.

BACKGROUND: The current scientific literature is inconsistent regarding the potential beneficial or deleterious effects of high-intensity physical activities on the pelvic floor (PF) in women. So far, it has not been established with certainty whether disparate breathing mechanisms may exert short- or long-term influence on the PF function in this context, although based on the established physiological interrelationship of breathing with PF activation, this seems plausible. OBJECTIVE: To propose a basic concept of the influence of different breathing patterns on the PF during strenuous physical efforts. Methodical approaches: Review of the recent literature, basic knowledge of classical western medicine regarding the principles of muscle physiology and the biomechanics of breathing, additional schematic illustrations, and magnetic resonance imaging (MRI) data corroborate the proposed concept and exemplify the consequences of strenuous efforts on the PF in relation to respective breathing phases. CONCLUSION: The pelvic floor muscles (PFMs) physiologically act as expiratory muscles in synergy with the anterolateral abdominal muscles, contracting during expiration and relaxing during inspiration. Obviously, a strenuous physical effort requires an expiratory motor synergy with the PFM and abdominal muscles in a co-contracted status to train the PFM and protect the PF against high intra-abdominal pressure (IAP). Holding breath in an inspiratory pattern during exertion stresses the PF because the high IAP impinges on the relaxed, hence insufficiently protected, PFMs. It seems conceivable that such disadvantageous breathing, if performed regularly and repeatedly, may ultimately cause PF dysfunction. At any rate, future research needs to take into account the respective breathing cycles during measurements and interventions addressing PFM function.

Revisiting brain iron deficiency in restless legs syndrome using magnetic resonance imaging.

STUDY OBJECTIVES: Studies on brain iron content in restless legs syndrome (RLS) using magnetic resonance imaging (MRI) are heterogeneous. In this study, we sought to leverage the availability of a large dataset including a range of iron-sensitive MRI techniques to reassess the association between brain iron content and RLS with added statistical power and to compare these results to previous studies. METHODS: The relaxation rates R2, R2', and R2* and quantitative susceptibility are MRI parameters strongly correlated to iron content. In general, these parameters are sensitive to magnetic field variations caused by iron particles. These parameters were quantified within iron-rich brain regions using a fully automatized approach in a cohort of 72 RLS patients and individually age and gender-matched healthy controls identified from an existing dataset acquired at the Sleep Laboratory of the Department of Neurology, Medical University of Innsbruck. 3 T-MRI measures were corrected for age and volume of the segmented brain nuclei and results were compared with previous findings in a meta-analysis. RESULTS: In our cohort, RLS patients had increased R2* signal in the caudate and increased quantitative susceptibility signal in the putamen and the red nucleus compared to controls, suggesting increased iron content in these areas. The meta-analysis revealed no significant pooled effect across all brain regions. Furthermore, potential publication bias was identified for the substantia nigra. CONCLUSIONS: Normal and increased iron content of subcortical brain areas detected in this study is not in line with the hypothesis of reduced brain iron storage, but favors CSF investigations and post mortem studies indicating alteration of brain iron mobilization and homeostasis in RLS.

Dimensions and forms of artefacts in 1.5 T and 3 T MRI caused by cochlear implants.

Cochlear implantation is a standard treatment option due to expanding indications. Cranial magnetic resonance imaging (cMRI) has become a widespread diagnostic tool. Therefore, an increased number of cochlear implant (CI) users are undergoing cMRI scans. This study aimed to investigate the issue of the CI magnet impacting MRI quality and artifacts. 1.5 T and 3 T MRI scans with 4 defined sequences (T2-TSE, T2-TIRM, T1-3D-MPRAGE, and TDI) were performed on a phantom with a CI (SYNCHRONY System by MED-EL Austria) in place. The resulting MRI artifacts were retrospectively compared to MRI artifacts observed in patients with a CI. All images were transferred to AMIRA and visualized by manual segmentation. Usable image quality was achieved in three sequences (T2-TSE, T2-TIRM and T1-mprage). Observed artifacts differed in shape and size depending on the sequence. Maximum diameters of signal void areas ranged from 58 × 108 × 98 mm to 127 × 123 × 153 mm. Image distortions were larger. MRI artifacts caused by the SYNCHRONY system are asymmetric with varying shape, depending on the sequence. The phantom artefacts are similar to those in CI users. Considering the observed asymmetry, the hypothesis of varying implantation locations resulting in varying positions of the signal void area needs to be further investigated.

A novel approach to determine aortic valve area with phase-contrast cardiovascular magnetic resonance.

BACKGROUND: Transthoracic echocardiography (TTE) is the diagnostic routine standard for assessing aortic stenosis (AS). However, its inaccuracies in determining stroke volume (SV) and aortic valve area (AVA) call for a more precise and dependable method. Phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) is a promising tool to push these boundaries. Thus, the aim of this study was to validate a novel approach based on PC-CMR against the gold-standard of invasive determination of AVA in AS compared to TTE. METHODS: A total of 50 patients with moderate or severe AS underwent TTE, cardiac catheterization and CMR. AVA via PC-CMR was determined by plotting momentary flow across the valve against flow-velocity. SV by CMR was measured directly via PC-CMR and volumetrically using cine-images. Invasive SV and AVA were determined via Fick-principle and Gorlin-formula, respectively. TTE yielded SV and AVA using continuity equation. Gradients were calculated via the modified Bernoulli-equation. RESULTS: SV by PC-CMR (85 ± 31 ml) correlated strongly (r: 0.73, p < 0.001) with cine-CMR (85 ± 19 ml) without significant bias (lower and upper limits of agreement (LLoA and ULoA): - 41 ml and 44 ml, p = 0.83). In PC-CMR, mean pressure gradient correlated significantly with invasive determination (r: 0.36, p = 0.011). Mean AVA, as determined by PC-CMR during systole (0.78 ± 0.25 cm2), correlated moderately (r: 0.54, p < 0.001) with invasive AVA (0.70 ± 0.23 cm2), resulting in a small bias of 0.08 cm2 (LLoA and ULoA: - 0.36 cm2 and 0.55 cm2, p = 0.017). Inter-methodically, AVA by TTE (0.81 ± 0.23 cm2) compared to invasive determination showed similar correlations (r: 0.58, p < 0.001 with a bias of 0.11 cm2, LLoA and ULoA: - 0.30 and 0.52, p < 0.001) to PC-CMR. Intra- and interobserver reproducibility were excellent for AVA (intraclass-correlation-coefficients of 0.939 and 0.827, respectively). CONCLUSIONS: Our novel approach using continuous determination of flow-volumes and velocities with PC-CMR enables simple AVA measurement with no bias to invasive assessment. This approach highlights non-invasive AS grading through CMR, especially when TTE findings are inconclusive.

MRI of middle ear cholesteatoma: The importance of observer reliance from diffusion sequences.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging(DWI) in MRI has been developed as an important tool for the detection of cholesteatoma. Various DWI sequences are available. This study aims to evaluate the importance of the observer's reliance level for the detection of cholesteatoma. METHODS: Forty patients meeting the following criteria were included in the study: (1) chronic otitis media, (2) preoperative MRI including various DWI sequences, and (3) middle-ear surgery. The MRI protocol contained the following sequences: (1) axial and (2) coronal echoplanar imaging (EPI) readout-segmented (RESOLVE) DWI with Trace acquisition and (3) coronal non-EPI half-Fourier acquired single-shot turbo spin-echo (HASTE) DWI. Cholesteatoma diagnosis was based on standard diagnostic criteria for cholesteatoma with DWI. Additionally, the radiologists were asked to grade personal reliance on their diagnosis using a Likert-type scale from 1 = very insecure to 5 = very secure. RESULTS: Axial and coronal RESOLVE DWI showed a sensitivity of 77.3% and a specificity of 72.2%, respectively. The mean reliance was 3.9 for axial and 3.8 for coronal images. HASTE DWI had a sensitivity/specificity of 81.8%/66.7% with the highest reliance of all evaluated sequences (4.4). Cases with a reliance level of 5 showed a sensitivity/specificity of 100% in all sequences. A reliance level of 5 was given in the axial and coronal RESOLVE DWI in 32.5% of cases and in the HASTE DWI in 57.5%. CONCLUSION: The evaluated DWI sequences showed comparable results. The reliance level significantly improved the predictor of cholesteatoma disease with MRI techniques.

MR elastography in patients with suspected diffuse liver disease at 1.5T: Intraindividual comparison of gradient-recalled echo versus spin-echo echo-planar imaging sequences and investigation of potential confounding factors.

PURPOSE: To compare liver stiffness (LS) in patients with suspected diffuse liver disease between gradient-recalled-echo magnetic resonance elastography (GRE-MRE) and different spin-echo echo-planar imaging (SE-EPI-MRE) sequences and to investigate confounding factors including fat, iron, age, and sex. METHOD: LS was measured at 1.5T using GRE-MRE, SE-EPI-MRE and short-TE-SE-EPI-MRE (hiSE-EPI-MRE) sequences and compared using Bland-Altman-plots together with concordance correlation coefficients (CCC). Success gradings were evaluated considering possible confounding factors. RESULTS: 305 patients (225 male, 80 females, mean age 51.12 years) were included. 109/305 showed hepatic iron overload, 183 hepatic steatosis. The mean difference (bias) in stiffness values between GRE-MRE and SE-EPI-MRE/hiSE-EPI-MRE was 0.15/0.2 kPa (LOA: -0.72,0.41 kPa/-0.94,0.55 kPa), between SE-EPI-MRE and hiSE-EPI-MRE 0.04 kPa (LOA: -0.62,0.53 kPa). The CCC for agreement between stiffness values for GRE-MRE and SE-EPI-MRE was 0.94 (0.92-0.95), 0.89 (0.86-0.91) for hiSE-EPI-MRE and GRE-MRE and 0.94 (0.92-0.95) for SE-EPI-MRE and hiSE-EPI-MRE. Using GRE-MRE, 72/305 showed unusable results whereby all these patients had high iron levels (mean R2*=209.7 1/s). For SE-EPI-MRE and hiSE-EPI-MRE only 10/305 and 8/305 were inconclusive respectively, corresponding to a significantly higher iron load (mean R2*= 549.2 1/s for SE-EPI-MRE and 570.7 1/s for hiSE-EPI-MRE). Concerning fat, age or sex no significant influence on success was observed for all sequences. CONCLUSIONS: Good agreement of LS values was observed between GRE-MRE and SE-EPI-MRE sequences. The number of successful exams, however, was considerably lower for GRE-MRE, mainly due to iron content. Study reference number: AN5093.