An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.

Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery to the nervous system, are widely used in neuroscience research, and are the basis of FDA-approved neuron-targeting gene therapies. Here we find that an innate immune response to the AAV genome reduces dendritic length and complexity and disrupts synaptic transmission in mouse somatosensory cortex. Dendritic loss is apparent 3 weeks after injection of experimentally relevant viral titers, is not restricted to a particular capsid serotype, transgene, promoter, or production facility, and cannot be explained by responses to surgery or transgene expression. AAV-associated dendritic loss is accompanied by a decrease in the frequency and amplitude of miniature excitatory postsynaptic currents and an increase in the proportion of GluA2-lacking, calcium-permeable AMPA receptors. The AAV genome is rich in unmethylated CpG DNA, which is recognized by the innate immunoreceptor Toll-like receptor 9 (TLR9), and acutely blocking TLR9 preserves dendritic complexity and AMPA receptor subunit composition in AAV-injected mice. These results reveal unexpected impacts of an immune response to the AAV genome on neuronal structure and function and identify approaches to improve the safety and efficacy of AAV-mediated gene delivery in the nervous system.

Identification of impactful imaging biomarker: Clinical applications for breast and prostate carcinoma. / Ermittlung aussagekräftiger Bildgebungsbiomarker: Klinische Anwendungen bei Mamma- und Prostatakarzinomen.

BACKGROUND: Imaging biomarkers are quantitative parameters from imaging modalities, which are collected noninvasively, allow conclusions about physiological and pathophysiological processes, and may consist of single (monoparametric) or multiple parameters (bi- or multiparametric). METHOD: This review aims to present the state of the art for the quantification of multimodal and multiparametric imaging biomarkers. Here, the use of biomarkers using artificial intelligence will be addressed and the clinical application of imaging biomarkers in breast and prostate cancers will be explained. For the preparation of the review article, an extensive literature search was performed based on Pubmed, Web of Science and Google Scholar. The results were evaluated and discussed for consistency and generality. RESULTS AND CONCLUSION: Different imaging biomarkers (multiparametric) are quantified based on the use of complementary imaging modalities (multimodal) from radiology, nuclear medicine, or hybrid imaging. From these techniques, parameters are determined at the morphological (e. g., size), functional (e. g., vascularization or diffusion), metabolic (e. g., glucose metabolism), or molecular (e. g., expression of prostate specific membrane antigen, PSMA) level. The integration and weighting of imaging biomarkers are increasingly being performed with artificial intelligence, using machine learning algorithms. In this way, the clinical application of imaging biomarkers is increasing, as illustrated by the diagnosis of breast and prostate cancers. KEY POINTS: · Imaging biomarkers are quantitative parameters to detect physiological and pathophysiological processes.. · Imaging biomarkers from multimodality and multiparametric imaging are integrated using artificial intelligence algorithms.. · Quantitative imaging parameters are a fundamental component of diagnostics for all tumor entities, such as for mammary and prostate carcinomas.. CITATION FORMAT: · Bäuerle T, Dietzel M, Pinker K et al. Identification of impactful imaging biomarker: Clinical applications for breast and prostate carcinoma. Fortschr Röntgenstr 2024; 196: 354 - 362.

Cerebellar contributions to a brainwide network for flexible behavior in mice.

The cerebellum regulates nonmotor behavior, but the routes of influence are not well characterized. Here we report a necessary role for the posterior cerebellum in guiding a reversal learning task through a network of diencephalic and neocortical structures, and in flexibility of free behavior. After chemogenetic inhibition of lobule VI vermis or hemispheric crus I Purkinje cells, mice could learn a water Y-maze but were impaired in ability to reverse their initial choice. To map targets of perturbation, we imaged c-Fos activation in cleared whole brains using light-sheet microscopy. Reversal learning activated diencephalic and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (including thalamus and habenula) and crus I (including hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. To identify functional networks, we used correlated variation in c-Fos activation within each group. Lobule VI inactivation weakened within-thalamus correlations, while crus I inactivation divided neocortical activity into sensorimotor and associative subnetworks. In both groups, high-throughput automated analysis of whole-body movement revealed deficiencies in across-day behavioral habituation to an open-field environment. Taken together, these experiments reveal brainwide systems for cerebellar influence that affect multiple flexible responses.

Automated high-throughput mouse transsynaptic viral tracing using iDISCO+ tissue clearing, light-sheet microscopy, and BrainPipe.

Transsynaptic viral tracing requires tissue sectioning, manual cell counting, and anatomical assignment, all of which are time intensive. We describe a protocol for BrainPipe, a scalable software for automated anatomical alignment and object counting in light-sheet microscopy volumes. BrainPipe can be generalized to new counting tasks by using a new atlas and training a neural network for object detection. Combining viral tracing, iDISCO+ tissue clearing, and BrainPipe facilitates mapping of cerebellar connectivity to the rest of the murine brain. For complete details on the use and execution of this protocol, please refer to Pisano et al. (2021).

A Flexible Platform for Monitoring Cerebellum-Dependent Sensory Associative Learning.

Climbing fiber inputs to Purkinje cells provide instructive signals critical for cerebellum-dependent associative learning. Studying these signals in head-fixed mice facilitates the use of imaging, electrophysiological, and optogenetic methods. Here, a low-cost behavioral platform (~$1000) was developed that allows tracking of associative learning in head-fixed mice that locomote freely on a running wheel. The platform incorporates two common associative learning paradigms: eyeblink conditioning and delayed tactile startle conditioning. Behavior is tracked using a camera and the wheel movement by a detector. We describe the components and setup and provide a detailed protocol for training and data analysis. This platform allows the incorporation of optogenetic stimulation and fluorescence imaging. The design allows a single host computer to control multiple platforms for training multiple animals simultaneously.

Osteoblastic Swedish mutant APP expedites brain deficits by inducing endoplasmic reticulum stress-driven senescence.

Patients with Alzheimer's disease (AD) often have osteoporosis or osteopenia. However, their direct link and relationship remain largely unclear. Previous studies have detected osteoporotic deficits in young adult Tg2576 and TgAPPsweOCN mice, which express APPswe (Swedish mutant) ubiquitously and selectively in osteoblast (OB)-lineage cells. This raises the question, whether osteoblastic APPswe contributes to AD development. Here, we provide evidence that TgAPPsweOCN mice also exhibit AD-relevant brain pathologies and behavior phenotypes. Some brain pathologies include age-dependent and regional-selective increases in glial activation and pro-inflammatory cytokines, which are accompanied by behavioral phenotypes such as anxiety, depression, and altered learning and memory. Further cellular studies suggest that APPswe, but not APPwt or APPlon (London mutant), in OB-lineage cells induces endoplasmic reticulum-stress driven senescence, driving systemic and cortex inflammation as well as behavioral changes in 6-month-old TgAPPsweOCN mice. These results therefore reveal an unrecognized function of osteoblastic APPswe to brain axis in AD development.

Reducing adverse events associated with the glucagon stimulation test for the assessment of growth hormone deficiency in adults with a high prevalence of pituitary hormone deficiencies.

DESIGN: A retrospective review of the adverse events (AEs) in 78 patients during the glucagon stimulation test (GST) for the assessment of growth hormone deficiency (GHD) before and after protocol amendments which aimed to reduce AEs in a group of patients with a high prevalence of pituitary hormone deficiencies. PATIENTS: Based on our observations of frequent AEs during the standard GST protocol in an initial 25 patients (cohort 1), a modified protocol was introduced to include the routine administration of 20 mg of hydrocortisone pre-GST in a subsequent 53 patients (cohort 2). Post hoc analysis of the effect of glucocorticoid dosing pre-GST on AEs was examined in those receiving <20 mg hydrocortisone (group A, n = 19) vs ≥20 mg hydrocortisone (group B, n = 59). MEASUREMENTS: AEs including hypotension, hypoglycaemia and nausea/vomiting. RESULTS: Of the 78 patients undergoing the GST, 79% had ≥2 hormone deficiencies. Rates of AEs were 41% vs 30% for hypotension, 60% vs 28% for hypoglycaemia (p < .05) and 20% vs 13% for nausea/vomiting in cohort 1 compared with cohort 2, respectively. Post hoc analysis revealed lower rates of AEs in those receiving ≥20 mg hydrocortisone (group B) compared to those receiving <20 mg due to a reduction in hypoglycaemic events (82% vs 26%, p < .001) and hypotension (50% vs 27%, p = .05). Similar numbers of patients in group A and group B met criteria for GHD. CONCLUSIONS: In patients with a high prevalence of pituitary deficiencies, a modified GST protocol of additional stress dose glucocorticoid attenuated the frequency of AEs without appearing to compromise the performance of the GST.

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging.

This methodical work describes the measurement and calculation of pulmonary blood volume in mice based on two imaging techniques namely by using magnetic particle imaging (MPI) and cardiac magnetic resonance imaging (MRI). Besides its feasibility aspects that may influence quantitative analysis are studied. Eight FVB mice underwent cardiac MRI to determine stroke volumes and anatomic MRI as morphological reference for functional MPI data. Arrival time analyses of boli of 1 µl of 1 M superparamagnetic tracer were performed by MPI. Pulmonary transit time of the bolus was determined by measurements in the right and left ventricles. Pulmonary blood volume was calculated out of stroke volume, pulmonary transit time and RR-interval length including a maximal error analysis. Cardiac stroke volume was 31.7 µl ± 2.3 µl with an ejection fraction of 71% ± 6%. A sharp contrast bolus profile was observed by MPI allowing subdividing the first pass into three distinct phases: tracer arrival in the right ventricle, pulmonary vasculature, and left ventricle. The bolus full width at half maximum was 578 ms ± 144 ms in the right ventricle and 1042 ms ± 150 ms in the left ventricle. Analysis of pulmonary transit time revealed 745 ms ± 81 ms. Mean RR-interval length was 133 ms ± 12 ms. Pulmonary blood volume resulted in 177 µl ± 27 µl with a mean maximal error limit of 27 µl. Non-invasive assessment of the pulmonary blood volume in mice was feasible. This technique can be of specific value for evaluation of pulmonary hemodynamics in mouse models of cardiac dysfunction or pulmonary disease. Pulmonary blood volume can complement cardiac functional parameters as a further hemodynamic parameter.

Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype.

BACKGROUND: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment. METHODS: We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n = 3-8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E-/-); (ii) heterogeneous (E-/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS). RESULTS: We included 314 tumor spots from 69 patients (76.8% male, median age 66, liver cirrhosis/fibrosis 75.8%). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/- and E-/- patients (TTR 5 vs. 19 months, p = 0.022; RFS 5 vs. 14 vs. 21 months, p = 0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (> 400 ng/ml, p = 0.031). CONCLUSIONS: Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.

Thickened Drinks and Oral Nutritional Supplements as Potential Reservoirs of Oral Microorganisms: Microbial Assays In Vitro.

Oral hygiene is difficult to achieve for frail older adults. Aging, chronic diseases, polypharmacy, mouth-washes, and crushed drugs can contribute to uncontrolled proliferation and microbial deposits in the mouth. Looking for avoidable risk factors, in vitro microbial survival or proliferation in thickened drinks and oral nutritional supplements (ONS) was investigated. The safest thickened drinks were ready-to-use products containing preservatives. Escherichia coli, Staphylococcus aureus, and Candida albicans proliferated in dairy ONS at room temperature. C. albicans also proliferated in juices. Oral anerobic bacteria were recovered from part eaten ONS. Thickened drinks and ONS could contribute to microbial proliferation, especially with patients who have swallowing alterations or cognitive troubles, who may keep these solutions longer than necessary in their mouth. These products can also constitute microbial reservoirs in the environment of frail older adults. It is important for health care workers and family members to respect hand hygiene and refrigeration procedures. [Research in Gerontological Nursing, xx(x), xx-xx.].

Bone health in chronic kidney disease-mineral and bone disorder: a clinical case seminar and update.

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates.

Lipolysis Triggers a Systemic Insulin Response Essential for Efficient Energy Replenishment of Activated Brown Adipose Tissue in Mice.

The coordination of the organ-specific responses regulating systemic energy distribution to replenish lipid stores in acutely activated brown adipose tissue (BAT) remains elusive. Here, we show that short-term cold exposure or acute ß3-adrenergic receptor (ß3AR) stimulation results in secretion of the anabolic hormone insulin. This process is diminished in adipocyte-specific Atgl-/- mice, indicating that lipolysis in white adipose tissue (WAT) promotes insulin secretion. Inhibition of pancreatic ß cells abolished uptake of lipids delivered by triglyceride-rich lipoproteins into activated BAT. Both increased lipid uptake into BAT and whole-body energy expenditure in response to ß3AR stimulation were blunted in mice treated with the insulin receptor antagonist S961 or lacking the insulin receptor in brown adipocytes. In conclusion, we introduce the concept that acute cold and ß3AR stimulation trigger a systemic response involving WAT, ß cells, and BAT, which is essential for insulin-dependent fuel uptake and adaptive thermogenesis.

Evaluating size-dependent relaxivity of PEGylated-USPIOs to develop gadolinium-free T1 contrast agents for vascular imaging.

Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles provide a safer alternative to gadolinium-based contrast agents (GBCAs) in T1-weighted MR imaging. MRI contrast behavior of USPIOs depends on their magnetic properties, which in turn depend on their physicochemical composition. Identifying and tailoring USPIO structural characteristics that influence proton relaxation in MRI is crucial to developing effective gadolinium-free T1 contrast agents. Here, we present a systematic empirical evaluation of the relationship between USPIO size and MRI relaxivity (r1 and r2 values). Monodisperse USPIO cores, with precisely controlled core diameter (dC ) were synthesized via the thermal decomposition of iron(III)-oleate precursor. USPIOs with dC = 6.34, 7.58, 8.58, and 9.50nm, were dispersed in aqueous phase via ligand exchange with silane or dopamine-modified polyethylene glycol (PEG) polymers. Relaxivity characterization in a 1.5 T clinical MRI scanner showed the r2 /r1 ratio increased linearly with USPIO core diameter (R2 = 0.95), but varied little with both hydrodynamic diameter (dH ) and PEG molecular weight. One sample, DOPA-6-20 (6.34nm USPIO cores coated with 20 kDa dopamine-modified PEG), provided the lowest r2 /r1 value (3.44) and thus promise as a potential T1 contrast agent. In a preliminary study, we evaluated DOPA-6-20 for in vivo angiography imaging in a mouse with a 7 T scanner and observed strong T1-weighted enhancement of the mouse blood pool. Key anatomical features in the vascular network were visible even 5 min after intravenous administration. Using empirical data, we have presented the basis of a structure-property relationship that can help develop optimized USPIO-based T1 contrast agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2440-2447, 2018.

Magnetic particle imaging for in vivo blood flow velocity measurements in mice.

Magnetic particle imaging (MPI) is a new imaging technology. It is a potential candidate to be used for angiographic purposes, to study perfusion and cell migration. The aim of this work was to measure velocities of the flowing blood in the inferior vena cava of mice, using MPI, and to evaluate it in comparison with magnetic resonance imaging (MRI). A phantom mimicking the flow within the inferior vena cava with velocities of up to 21 cm s-1 was used for the evaluation of the applied analysis techniques. Time-density and distance-density analyses for bolus tracking were performed to calculate flow velocities. These findings were compared with the calibrated velocities set by a flow pump, and it can be concluded that velocities of up to 21 cm s-1 can be measured by MPI. A time-density analysis using an arrival time estimation algorithm showed the best agreement with the preset velocities. In vivo measurements were performed in healthy FVB mice (n = 10). MRI experiments were performed using phase contrast (PC) for velocity mapping. For MPI measurements, a standardized injection of a superparamagnetic iron oxide tracer was applied. In vivo MPI data were evaluated by a time-density analysis and compared to PC MRI. A Bland-Altman analysis revealed good agreement between the in vivo velocities acquired by MRI of 4.0 ± 1.5 cm s-1 and those measured by MPI of 4.8 ± 1.1 cm s-1. Magnetic particle imaging is a new tool with which to measure and quantify flow velocities. It is fast, radiation-free, and produces 3D images. It therefore offers the potential for vascular imaging.

Quantitative and qualitative estimation of atherosclerotic plaque burden in vivo at 7T MRI using Gadospin F in comparison to en face preparation evaluated in ApoE KO mice.

BACKGROUND: The aim of the study was to quantify atherosclerotic plaque burden by volumetric assessment and T1 relaxivity measurement at 7T MRI using Gadospin F (GDF) in comparison to en face based measurements. METHODS AND RESULTS: 9-weeks old ApoE-/- (n = 5 for each group) and wildtype mice (n = 5) were set on high fat diet (HFD). Progression group received MRI at 9, 13, 17 and 21 weeks after HFD initiation. Regression group was reswitched to chow diet (CD) after 13 weeks HFD and monitored with MRI for 12 weeks. MRI was performed before and two hours after iv injection of GDF (100 µmol/kg) at 7T (Clinscan, Bruker) acquiring a 3D inversion recovery gradient echo sequence and T1 Mapping using Saturation Recovery sequences. Subsequently, aortas were prepared for en face analysis using confocal microscopy. Total plaque volume (TPV) and T1 relaxivity were estimated using ImageJ (V. 1.44p, NIH, USA). 2D and 3D en face analysis showed a strong and exponential increase of plaque burden over time, while plaque burden in regression group was less pronounced. Correspondent in vivo MRI measurements revealed a more linear increase of TPV and T1 relaxivity for regression group. A significant correlation was observed between 2D and 3D en face analysis (r = 0.79; p<0.001) as well as between 2D / 3D en face analysis and MRI (r = 0.79; p<0.001; r = 0.85; p<0.001) and delta R1 (r = 0.79; p<0.001; r = 0.69; p<0.01). CONCLUSION: GDF-enhanced in vivo MRI is a powerful non-invasive imaging technique in mice allowing for reliable estimation of atherosclerotic plaque burden, monitoring of disease progression and regression in preclinical studies.

Hepatic shear wave elastography in children under free-breathing and breath-hold conditions.

OBJECTIVES: To compare hepatic 2D shear wave elastography (2D SWE) in children between free-breathing and breath-hold conditions, in terms of measurement agreement and time expenditure. METHODS: A cohort of 57 children (12.7±4.3 years) who underwent standardized 2D SWE between May and October 2015 were retrospectively evaluated. Liver elastograms were obtained under free-breathing and breath-hold conditions and time expenditure was measured. Median stiffness, interquartile range (IQR), and IQR/median ratio were calculated based on 12, six, and three elastograms. Results were compared using Pearson correlation coefficient, intraclass correlation coefficient (ICC), Bland-Altman analysis, and Student's t. RESULTS: Median liver stiffness under free-breathing and breath-hold conditions correlated strongly (7.22±4.5kPa vs. 7.21±4.11kPa; r=0.97, P<0.001). Time to acquire 12 elastograms with free-breathing was lower than that with breath-holding (79.3±32.5sec vs. 143.7±51.8sec, P<0.001). Results for median liver stiffness based of 12, six, and three elastograms demonstrated very high agreement for free-breathing (ICC 0.993) and for breath-hold conditions (ICC 0.994). CONCLUSIONS: Hepatic 2D SWE performed with free-breathing yields results similar to the breath-hold condition. With a substantially lower time requirement, which can be further reduced by lowering the number of elastograms, the free-breathing technique may be suitable for infants and less cooperative children not capable of breath-holding. KEY POINTS: • Hepatic 2D SWE performed with free-breathing yields results similar to breath-hold condition. • Benefit of the free-breathing approach is the substantially lower time requirement. • Lowering the number of elastograms can further reduce time expenditure. • Free-breathing 2D SWE is suitable in children with suspected liver disease.

In vitro and in vivo comparison of a tailored magnetic particle imaging blood pool tracer with Resovist.

Optimizing tracers for individual imaging techniques is an active field of research. The purpose of this study was to perform in vitro and in vivo magnetic particle imaging (MPI) measurements using a new monodisperse and size-optimized tracer, LS-008, and to compare it with the performance of Resovist, the standard MPI tracer. Magnetic particle spectroscopy (MPS) and in vitro MPI measurements were performed in concerns of concentration and amount of tracer in a phantom. In vivo studies were carried out in healthy FVB mice. The first group (n = 3) received 60 µl LS-008 (87 mM) and the second (n = 3) diluted Resovist of the same concentration and volume. Tracer injections were performed with a syringe pump during a dynamic MPI scan. For anatomic referencing MRI was applied beforehand of the MPI measurements. Summing up MPS examinations and in vitro MPI experiments, LS-008 showed better sensitivity and spatial resolution than Resovist. In vivo both tracers can visualize the propagation of the bolus through the inferior vena cava. MPI with LS-008 did show less temporal fluctuation artifacts and the pulsation of blood due to respiratory and cardiac cycle was detectable. With LS-008 the aorta was distinguishable from the caval vein while with Resovist this failed. A liver vessel and a vessel structure leading cranially could only be observed with LS-008 and not with Resovist. Beside these structural advantages both tracers showed very different blood half-life. For LS-008 we found 88 min. Resovist did show a fast liver accumulation and a half-life of 13 min. Only with LS-008 the perfusion fraction in liver and kidney was measureable. MPI for angiography can be significantly improved by applying more effective tracers. LS-008 shows a clear improvement concerning the delineation while resolving a larger number of vessels in comparison to Resovist. Therefore, in aspects of quality and quantity LS-008 is clearly favorable for angiographic and perfusion studies.

Doppler Ultrasound Triggering for Cardiovascular MRI at 3T in a Healthy Volunteer Study.

PURPOSE: Electrocardiogram (ECG) triggering for cardiac magnetic resonance (CMR) may be influenced by electromagnetic interferences with increasing magnetic field strength. The aim of this study was to evaluate the performance of Doppler ultrasound (DUS) as an alternative trigger technique for CMR in comparison to ECG and pulse oximetry (POX) at 3T and using different sequence types. METHODS: Balanced turbo field echo two-dimensional (2D) short axis cine CMR and 2D phase-contrast angiography of the ascending aorta was performed in 11 healthy volunteers at 3T using ECG, DUS, and POX for cardiac triggering. DUS and POX triggering were compared to the reference standard of ECG in terms of trigger quality (trigger detection and temporal variability), image quality [endocardial blurring (EB)], and functional measurements [left ventricular (LV) volumetry and aortic blood flow velocimetry]. RESULTS: Trigger signal detection and temporal variability did not differ significantly between ECG/DUS (I = 0.6) and ECG/POX (P = 0.4). Averaged EB was similar for ECG, DUS, and POX (pECG/DUS = 0.4, pECG/POX = 0.9). Diastolic EB was significantly decreased for DUS in comparison to ECG (P = 0.02) and POX (P = 0.04). The LV function assessment and aortic blood flow were not significantly different. CONCLUSION: This study demonstrated the feasibility of DUS for gating human CMR at 3T. The magnetohydrodynamic effect did not significantly disturb ECG triggering in this small healthy volunteer study. DUS showed a significant improvement in diastolic EB but could not be identified as a superior trigger method. The potential benefit of DUS has to be evaluated in a larger clinical patient population.