DESIGN AND VALIDATION OF A NOVEL 3D-PRINTED RETROGRADE INTRARENAL SURGERY TRAINER.

OBJECTIVES: To report on the design of a novel 3D-printed retrograde intrarenal surgery (RIRS) benchtop trainer and detail its validation against real-life experiences. METHODS: Digital Imaging and Communications in Medicine (DICOM) files of two patients with normal computed tomography of the kidney and bladder were converted into stereolithography files to create 3D triangular mesh models. These images were further refined using Autodesk Meshmixer. These 3D models were fabricated through additive manufacturing, a process commonly known as 3D printing and assembled in a polypropylene case. After development, the model was validated by 40 experienced who were asked to rate the components of the simulation using a nine-point questionnaire. RESULTS: The model's value in understanding the principles of RIRS and simulating contextual anatomy had mean scores of 9.43 (standard deviation [SD] = 0.74) and 9.21 (SD = 1.03), respectively. Mean scores for specific steps in RIRS were 8.07 (SD 1.47) for cannulating the ureteric orifice, 8.61 (SD 1.24) for inserting the ureteric access sheath, 9.29 (SD 0.97) for performing a renoscopy and evaluating all the calyces, 9.46 (SD 0.87) for laser lithotripsy, and 9.17 (SD 0.94) for manual stone retrieval. Participants scored the model with a mean score of 9.04 (SD 0.87) regarding realism and a mean score of 9.18 (SD 0.89) when evaluating its ability to enhance a trainee's confidence in RIRS. CONCLUSIONS: The model performed well for all components of RIRS. This model allows high fidelity of the simulation, and is cost-effective, portable, durable, reusable, and compatible with standard ureteroscopes.

Results of the Dutch scalp cooling registry in 7424 patients: analysis of determinants for scalp cooling efficacy.

BACKGROUND: Chemotherapy-induced alopecia is a common consequence of cancer treatment with a high psychological impact on patients and can be prevented by scalp cooling (SC). With this multi-center patient series, we examined the results for multiple currently used chemotherapy regimens to offer an audit into the real-world determinants of SC efficacy. MATERIALS AND METHODS: The Dutch Scalp Cooling Registry collected data on 7424 scalp-cooled patients in 68 Dutch hospitals. Nurses and patients completed questionnaires on patient characteristics, chemotherapy, and SC protocol. Patient-reported primary outcomes at the start of the final SC session included head cover (HC) (eg, wig/scarf) use (yes/no) as a surrogate for patient satisfaction with SC and WHO score for alopecia (0 = no hair loss up to 3 = total alopecia) as a measure of scalp cooling success. Exhaustive logistic regression analysis stratified by chemotherapy regimen was implemented to examine characteristics and interactions associated with the SC result. RESULTS: Overall, over half of patients (n = 4191, 56%) did not wear a HC and 53% (n = 3784/7183) reported minimal hair loss (WHO score 0/1) at the start of their final treatment. Outcomes were drug and dose dependent. Besides the chemotherapy regimen, this study did not identify any patient characteristic or lifestyle factor as a generic determinant influencing SC success. For non-gender specific cancers, gender played no statistically significant role in HC use nor WHO score. CONCLUSIONS: Scalp cooling is effective for the majority of patients. The robust model for evaluating the drug and dose-specific determinants of SC efficacy revealed no indications for changes in daily practice, suggesting factors currently being overlooked. As no correlation was identified between the determinants explaining HC use and WHO score outcomes, new methods for evaluation are warranted.

The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes.

BACKGROUND: Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. METHODS: In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). RESULTS: There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (ß = 0.133, p < 0.001; ß = 0.017, p < 0.001) and insulin resistance (ß = 0.095, p = 0.024; ß = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. CONCLUSION: 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.

A comparison of ultrafast and conventional spectral Doppler ultrasound to measure cerebral blood flow velocity during inguinal hernia repair in infants.

BACKGROUND: Ultrafast cerebral Doppler ultrasound enables simultaneous quantification and visualization of cerebral blood flow velocity. The aim of this study is to compare the use of conventional and ultrafast spectral Doppler during anesthesia and their potential to show the effect of anesthesiologic procedures on cerebral blood flow velocities, in relation to blood pressure and cerebral oxygenation in infants undergoing inguinal hernia repair. METHODS: A single-center prospective observational cohort study in infants up to six months of age. We evaluated conventional and ultrafast spectral Doppler cerebral ultrasound measurements in terms of number of successful measurements during the induction of anesthesia, after sevoflurane induction, administration of caudal analgesia, a fluid bolus and emergence of anesthesia. Cerebral blood flow velocity was quantified in pial arteries using conventional spectral Doppler and in the cerebral cortex using ultrafast Doppler by peak systolic velocity, end diastolic velocity and resistivity index. RESULTS: Twenty infants were included with useable conventional spectral Doppler images in 72/100 measurements and ultrafast Doppler images in 51/100 measurements. Intraoperatively, the success rates were 53/60 (88.3%) and 41/60 (68.3%), respectively. Cerebral blood flow velocity increased after emergence for both conventional (end diastolic velocity, from 2.01 to 2.75 cm/s, p < 0.001) and ultrafast spectral Doppler (end diastolic velocity, from 0.59 to 0.94 cm/s), whereas cerebral oxygenation showed a reverse pattern with a decrease after the emergence of the infant (85% to 68%, p < 0.001). CONCLUSION: It is possible to quantify cortical blood flow velocity during general anesthesia using conventional and ultrafast spectral Doppler cerebral ultrasound. Cerebral blood flow velocity and blood pressure decreased, while regional cerebral oxygenation increased during general anesthesia. Ultrafast spectral Doppler ultrasound offers novel insights into perfusion within the cerebral cortex, unattainable through conventional spectral ultrasound. Yet, ultrafast Doppler is curtailed by a lower success rate and a more rigorous learning curve compared to conventional method.

An Ultrasound Matrix Transducer for High-Frame-Rate 3-D Intra-cardiac Echocardiography.

OBJECTIVE: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography. METHODS: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified. RESULTS: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm. CONCLUSION: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart.

Automatic Max-Likelihood Envelope Detection Algorithm for Quantitative High-Frame-Rate Ultrasound for Neonatal Brain Monitoring.

OBJECTIVE: Post-operative brain injury in neonates may result from disturbed cerebral perfusion, but accurate peri-operative monitoring is lacking. High-frame-rate (HFR) cerebral ultrasound could visualize and quantify flow in all detectable vessels using spectral Doppler; however, automated quantification in small vessels is challenging because of low signal amplitude. We have developed an automatic envelope detection algorithm for HFR pulsed wave spectral Doppler signals, enabling neonatal brain quantitative parameter maps during and after surgery. METHODS: HFR ultrasound data from high-risk neonatal surgeries were recorded with a custom HFR mode (frame rate = 1000 Hz) on a Zonare ZS3 system. A pulsed wave Doppler spectrogram was calculated for each pixel containing blood flow in the image, and spectral peak velocity was tracked using a max-likelihood estimation algorithm of signal and noise regions in the spectrogram, where the most likely cross-over point marks the blood flow velocity. The resulting peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) were compared with other detection schemes, manual tracking and RIs from regular pulsed wave Doppler measurements in 10 neonates. RESULTS: Envelope detection was successful in both high- and low-quality arterial and venous flow spectrograms. Our technique had the lowest root mean square error for EDV, PSV and RI (0.46 cm/s, 0.53 cm/s and 0.15, respectively) when compared with manual tracking. There was good agreement between the clinical pulsed wave Doppler RI and HFR measurement with a mean difference of 0.07. CONCLUSION: The max-likelihood algorithm is a promising approach to accurate, automated cerebral blood flow monitoring with HFR imaging in neonates.

4D Flow Patterns and Relative Pressure Distribution in a Left Ventricle Model by Shake-the-Box and Proper Orthogonal Decomposition Analysis.

PURPOSE: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. METHODS: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. RESULTS: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. CONCLUSIONS: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.

Continuous shear wave measurements for dynamic cardiac stiffness evaluation in pigs.

Ultrasound-based shear wave elastography is a promising technique to non-invasively assess the dynamic stiffness variations of the heart. The technique is based on tracking the propagation of acoustically induced shear waves in the myocardium of which the propagation speed is linked to tissue stiffness. This measurement is repeated multiple times across the cardiac cycle to assess the natural variations in wave propagation speed. The interpretation of these measurements remains however complex, as factors such as loading and contractility affect wave propagation. We therefore applied transthoracic shear wave elastography in 13 pigs to investigate the dependencies of wave speed on pressure-volume derived indices of loading, myocardial stiffness, and contractility, while altering loading and inducing myocardial ischemia/reperfusion injury. Our results show that diastolic wave speed correlates to a pressure-volume derived index of operational myocardial stiffness (R = 0.75, p < 0.001), suggesting that both loading and intrinsic properties can affect diastolic wave speed. Additionally, the wave speed ratio, i.e. the ratio of systolic and diastolic speed, correlates to a pressure-volume derived index of contractility, i.e. preload-recruitable stroke work (R = 0.67, p < 0.001). Measuring wave speed ratio might thus provide a non-invasive index of contractility during ischemia/reperfusion injury.

Validation of the smartphone-based dietary assessment tool "Traqq" for assessing actual dietary intake by repeated 2-h recalls in adults: comparison with 24-h recalls and urinary biomarkers.

BACKGROUND: Conventional dietary assessment methods are affected by measurement errors. We developed a smartphone-based 2-h recall (2hR) methodology to reduce participant burden and memory-related bias. OBJECTIVE: Assessing the validity of the 2hR method against traditional 24-h recalls (24hRs) and objective biomarkers. METHODS: Dietary intake was assessed in 215 Dutch adults on 6 randomly selected nonconsecutive days (i.e., 3 2hR-days and 3 24hRs) during a 4-wk period. Sixty-three participants provided 4 24-h urine samples, to assess urinary nitrogen and potassium concentrations. RESULTS: Intake estimates of energy (2052±503 kcal vs. 1976±483 kcal) and nutrients (e.g., protein: 78±23 g vs. 71±19 g; fat: 84±30 g vs. 79±26 g; carbohydrates: 220±60 g vs. 216±60 g) were slightly higher with 2hR-days than with 24hRs. Comparing self-reported protein and potassium intake to urinary nitrogen and potassium concentrations indicated a slightly higher accuracy of 2hR-days than 24hRs (protein: -14% vs. -18%; potassium: -11% vs. -16%). Correlation coefficients between methods ranged from 0.41 to 0.75 for energy and macronutrients and from 0.41 to 0.62 for micronutrients. Generally, regularly consumed food groups showed small differences in intake (<10%) and good correlations (>0.60). Intake of energy, nutrients, and food groups showed similar reproducibility (intraclass correlation coefficient) for 2hR-days and 24hRs. CONCLUSIONS: Comparing 2hR-days with 24hRs showed a relatively similar group-level bias for energy, most nutrients, and food groups. Differences were mostly due to higher intake estimates by 2hR-days. Biomarker comparisons showed less underestimation by 2hR-days as compared with 24hRs, suggesting that 2hR-days are a valid approach to assess the intake of energy, nutrients, and food groups. This trial was registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) registry as ABR. No. NL69065.081.19.

Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial.

Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health. Women and men with MIR or LIR (n = 242, body mass index [BMI] 25-40 kg/m2, 40-75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA). PhenoDiet group B showed no significant improvements in the primary outcome disposition index, but greater improvements in insulin sensitivity, glucose homeostasis, serum triacylglycerol, and C-reactive protein compared with PhenoDiet group A were observed. We demonstrate that modulating macronutrient composition within the dietary guidelines based on tissue-specific insulin resistance (IR) phenotype enhances cardiometabolic health improvements. Clinicaltrials.gov registration: NCT03708419, CCMO registration NL63768.068.17.

A Tiled Ultrasound Matrix Transducer for Volumetric Imaging of the Carotid Artery.

High frame rate three-dimensional (3D) ultrasound imaging would offer excellent possibilities for the accurate assessment of carotid artery diseases. This calls for a matrix transducer with a large aperture and a vast number of elements. Such a matrix transducer should be interfaced with an application-specific integrated circuit (ASIC) for channel reduction. However, the fabrication of such a transducer integrated with one very large ASIC is very challenging and expensive. In this study, we develop a prototype matrix transducer mounted on top of multiple identical ASICs in a tiled configuration. The matrix was designed to have 7680 piezoelectric elements with a pitch of 300 µm × 150 µm integrated with an array of 8 × 1 tiled ASICs. The performance of the prototype is characterized by a series of measurements. The transducer exhibits a uniform behavior with the majority of the elements working within the -6 dB sensitivity range. In transmit, the individual elements show a center frequency of 7.5 MHz, a -6 dB bandwidth of 45%, and a transmit efficiency of 30 Pa/V at 200 mm. In receive, the dynamic range is 81 dB, and the minimum detectable pressure is 60 Pa per element. To demonstrate the imaging capabilities, we acquired 3D images using a commercial wire phantom.

High-frame-rate contrast-enhanced ultrasound particle image velocimetry in patients with a stented superficial femoral artery: a feasibility study.

BACKGROUND: Local blood flow affects vascular disease and outcomes of endovascular treatment, but quantifying it is challenging, especially inside stents. We assessed the feasibility of blood flow quantification in native and stented femoral arteries, using high-frame-rate (HFR) contrast-enhanced ultrasound (CEUS) particle image velocimetry (PIV), also known as echoPIV. METHODS: Twenty-one patients with peripheral arterial disease, recently treated with a stent in the femoral artery, were included. HFR CEUS measurements were performed in the native femoral artery and at the inflow and outflow of the stent. Two-dimensional blood flow was quantified through PIV analysis. EchoPIV recordings were visually assessed by five observers and categorised as optimal, partial, or unfeasible. To evaluate image quality and tracking performance, contrast-to-tissue ratio (CTR) and vector correlation were calculated, respectively. RESULTS: Fifty-eight locations were measured and blood flow quantification was established in 49 of them (84%). Results were optimal for 17/58 recordings (29%) and partial for 32 recordings (55%) due to loss of correlation (5/32; 16%), short vessel segment (8/32; 25%), loss of contrast (14/32; 44%), and/or shadows (18/32; 56%). In the remaining 9/58 measurements (16%) no meaningful flow information was visualised. Overall, CTR and vector correlation were lower during diastole. CTR and vector correlation were not different between stented and native vessel segments, except for a higher native CTR at the inflow during systole (p = 0.037). CONCLUSIONS: Blood flow quantification is feasible in untreated and stented femoral arteries using echoPIV. Limitations remain, however, none of them related to the presence of the stent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04934501 (retrospectively registered).

Imaging Scheme for 3-D High-Frame-Rate Intracardiac Echography: A Simulation Study.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is normally treated by RF ablation. Intracardiac echography (ICE) is widely employed during RF ablation procedures to guide the electrophysiologist in navigating the ablation catheter, although only 2-D probes are currently clinically used. A 3-D ICE catheter would not only improve visualization of the atrium and ablation catheter, but it might also provide the 3-D mapping of the electromechanical wave (EW) propagation pattern, which represents the mechanical response of cardiac tissue to electrical activity. The detection of this EW needs 3-D high-frame-rate imaging, which is generally only realizable in tradeoff with channel count and image quality. In this simulation-based study, we propose a high volume rate imaging scheme for a 3-D ICE probe design that employs 1-D micro-beamforming in the elevation direction. Such a probe can achieve a high frame rate while reducing the channel count sufficiently for realization in a 10-Fr catheter. To suppress the grating-lobe (GL) artifacts associated with micro-beamforming in the elevation direction, a limited number of fan-shaped beams with a wide azimuthal and narrow elevational opening angle are sequentially steered to insonify slices of the region of interest. An angular weighted averaging of reconstructed subvolumes further reduces the GL artifacts. We optimize the transmit beam divergence and central frequency based on the required image quality for EW imaging (EWI). Numerical simulation results show that a set of seven fan-shaped transmission beams can provide a frame rate of 1000 Hz and a sufficient spatial resolution to visualize the EW propagation on a large 3-D surface.

Blood Flow Quantification with High-Frame-Rate, Contrast-Enhanced Ultrasound Velocimetry in Stented Aortoiliac Arteries: In Vivo Feasibility.

Local flow patterns influence stent patency, while blood flow quantification in stents is challenging. The aim of this study was to investigate the feasibility of 2-D blood flow quantification using high-frame-rate, contrast-enhanced ultrasound (HFR-CEUS) and particle image velocimetry (PIV), or echoPIV, in patients with aortoiliac stents. HFR-CEUS measurements were performed at 129 locations in 62 patients. Two-dimensional blood flow velocity fields were obtained using echoPIV. Visual inspection was performed by five observers to evaluate feasibility. The contrast-to-background ratio and average vector correlation were calculated and compared between stented and native vessel segments. Flow quantification with echoPIV was feasible in 128 of 129 locations (99%), with optimal quantification in 40 of 129 locations (31%). Partial quantification was achieved in 88 of 129 locations (68%), where one or multiple limiting issues occurred (not related to the stent) including loss of correlation during systole (57/129), short vessel segments (20/129), loss of contrast during diastole (20/129) and shadow regions (20/129). The contrast-to-background ratio and vector correlation were lower downstream in the imaged blood vessel, independent of the location of the stent. In conclusion, echoPIV was feasible in stents placed in the aortoiliac region, and the stents did not adversely affect flow tracking.

Left ventricular high frame rate echo-particle image velocimetry: clinical application and comparison with conventional imaging.

BACKGROUND: Echo-Particle Image Velocimetry (echoPIV) tracks speckle patterns from ultrasound contrast agent(UCA), being less angle-sensitive than colour Doppler. High frame rate (HFR) echoPIV enables tracking of high velocity flow in the left ventricle (LV). We aimed to demonstrate the potential clinical use of HFR echoPIV and investigate the feasibility and accuracy in patients. METHODS: Nineteen patients admitted for heart failure were included. HFR contrast images were acquired from an apical long axis view (ALAX), using a fully-programmable ultrasound system. A clinical UCA was continuously infused with a dedicated pump. Additionally, echocardiographic images were obtained using a clinical system, including LV contrast-enhanced images and pulsed-wave (PW) Doppler of the LV inflow and outflow in ALAX. 11 patients underwent CMR and 4 cardiac CT as clinically indicated. These CMR and CT images were used as reference. In 10 patients with good echoPIV tracking and reference imaging, the intracavitary flow was compared between echoPIV, conventional and UCA echocardiography. RESULTS: EchoPIV tracking quality was good in 12/19 (63%), moderate in 2/19 (10%) and poor in 5/19 (26%) subjects. EchoPIV could determine inflow velocity in 17/19 (89%), and outflow in 14/19 (74%) patients. The correlation of echoPIV and PW Doppler was good for the inflow (R2 = 0.77 to PW peak; R2 = 0.80 PW mean velocity) and moderate for the outflow (R2 = 0.54 to PW peak; R2 = 0.44 to PW mean velocity), with a tendency for echoPIV to underestimate PW velocities. In selected patients, echoPIV was able in a single acquisition to demonstrate flow patterns which required multiple interrogations with classical echocardiography. Those flow patterns could also be linked to anatomical abnormalities as seen in CMR or CT. CONCLUSION: HFR echoPIV tracks multidirectional and complex flow patterns which are unapparent with conventional echocardiography, while having comparable feasibility. EchoPIV tends to underestimate flow velocities as compared to PW Doppler. It has the potential to provide in one acquisition all the functional information obtained by conventional imaging, overcoming the angle dependency of Doppler and low frame rate of classical contrast imaging.

Echo planar imaging-induced errors in intracardiac 4D flow MRI quantification.

PURPOSE: To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). METHODS: Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume. RESULTS: In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow. CONCLUSIONS: Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers.

Healthy aging and muscle function are positively associated with NAD+ abundance in humans.

Skeletal muscle is greatly affected by aging, resulting in a loss of metabolic and physical function. However, the underlying molecular processes and how (lack of) physical activity is involved in age-related metabolic decline in muscle function in humans is largely unknown. Here, we compared, in a cross-sectional study, the muscle metabolome from young to older adults, whereby the older adults were exercise trained, had normal physical activity levels or were physically impaired. Nicotinamide adenine dinucleotide (NAD+) was one of the most prominent metabolites that was lower in older adults, in line with preclinical models. This lower level was even more pronounced in impaired older individuals, and conversely, exercise-trained older individuals had NAD+ levels that were more similar to those found in younger individuals. NAD+ abundance positively correlated with average number of steps per day and mitochondrial and muscle functioning. Our work suggests that a clear association exists between NAD+ and health status in human aging.

Evaluation of intraventricular flow by multimodality imaging: a review and meta-analysis.

BACKGROUND: The aim of this systematic review was to evaluate current inter-modality agreement of noninvasive clinical intraventricular flow (IVF) assessment with 3 emerging imaging modalities: echocardiographic particle image velocimetry (EPIV), vector flow mapping (VFM), and 4-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR). METHODS: We performed a systematic literature review in the databases EMBASE, Medline OVID and Cochrane Central for identification of studies evaluating left ventricular (LV) flow patterns using one of these flow visualization modalities. Of the 2224 initially retrieved records, 10 EPIV, 23 VFM, and 25 4D flow CMR studies were included in the final analysis. RESULTS: Vortex parameters were more extensively studied with EPIV, while LV energetics and LV transport mechanics were mainly studied with 4D flow CMR, and LV energy loss and vortex circulation were implemented by VFM studies. Pooled normative values are provided for these parameters. The meta- analysis for the values of two vortex morphology parameters, vortex length and vortex depth, failed to reveal a significant change between heart failure patients and healthy controls. CONCLUSION: Agreement between the different modalities studying intraventricular flow is low and different methods of measurement and reporting were used among studies. A multimodality framework with a standardized set of flow parameters is necessary for implementation of noninvasive flow visualization in daily clinical practice. The full potential of noninvasive flow visualization in addition to diagnostics could also include guiding medical or interventional treatment.

US Velocimetry in Participants with Aortoiliac Occlusive Disease.

Background The accurate quantification of blood flow in aortoiliac arteries is challenging but clinically relevant because local flow patterns can influence atherosclerotic disease. Purpose To investigate the feasibility and clinical application of two-dimensional blood flow quantification using high-frame-rate contrast-enhanced US (HFR-CEUS) and particle image velocimetry (PIV), or US velocimetry, in participants with aortoiliac stenosis. Materials and Methods In this prospective study, participants with a recently diagnosed aortoiliac stenosis underwent HFR-CEUS measurements of the pre- and poststenotic vessel segments (August 2018 to July 2019). Two-dimensional quantification of blood flow was achieved by performing PIV analysis, which was based on pairwise cross-correlation of the HFR-CEUS images. Visual inspection of the entire data set was performed by five observers to evaluate the ability of the technique to enable adequate visualization of blood flow. The contrast-to-background ratio and average vector correlation were calculated. In two participants who showed flow disturbances, the flow complexity and vorticity were calculated. Results Thirty-five participants (median age, 67 years; age range, 56-84 years; 22 men) were included. Visual scoring showed that flow quantification was achieved in 41 of 42 locations. In 25 locations, one or multiple issues occurred that limited optimal flow quantification, including loss of correlation during systole (n = 12), shadow regions (n = 8), a short vessel segment in the image plane (n = 7), and loss of contrast during diastole (n = 5). In the remaining 16 locations, optimal quantification was achieved. The contrast-to-background ratio was higher during systole than during diastole (11.0 ± 2.9 vs 6.9 ± 3.4, respectively; P < .001), whereas the vector correlation was lower (0.58 ± 0.21 vs 0.47 ± 0.13; P < .001). The flow complexity and vorticity were high in regions with disturbed flow. Conclusion Blood flow quantification with US velocimetry is feasible in patients with an aortoiliac stenosis, but several challenges must be overcome before implementation into clinical practice. Clinical trial registration no. NTR6980 © RSNA, 2021 Online supplemental material is available for this article.