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

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

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

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

Prerequisites for Clinical Implementation of Whole-Heart 4D-Flow MRI: A Delphi Analysis.

Whole-heart 4D-flow MRI is a valuable tool for advanced visualization and quantification of blood flow in cardiovascular imaging. Despite advantages over 2D-phase-contrast flow, clinical implementation remains only partially exploited due to many hurdles in all steps, from image acquisition, reconstruction, postprocessing and analysis, clinical embedment, reporting, legislation, and regulation to data storage. The intent of this manuscript was 1) to evaluate the extent of clinical implementation of whole-heart 4D-flow MRI, 2) to identify hurdles hampering clinical implementation, and 3) to reach consensus on requirements for clinical implementation of whole-heart 4D-flow MRI. This study is based on Delphi analysis. This study involves a panel of 18 experts in the field on whole-heart 4D-flow MRI. The experience with and opinions of experts (mean 13 years of experience, interquartile range 6) in the field were aggregated. This study showed that among experts in the cardiovascular field, whole-heart 4D-flow MRI is currently used for both clinical and research purposes. Overall, the panelists agreed that major hurdles currently hamper implementation and utilization. The sequence-specific hurdles identified were long scan time and lack of standardization. Further hurdles included cumbersome and time-consuming segmentation and postprocessing. The study concludes that implementation of whole-heart 4D-flow MRI in clinical routine is feasible, but the implementation process is complex and requires a dedicated, multidisciplinary team. A predefined plan, including risk assessment and technique validation, is essential. The reported consensus statements may guide further tool development and facilitate broader implementation and clinical use. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 5.

Whole-Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo-Spiral Sampling and EPI Readout.

BACKGROUND: Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. HYPOTHESIS: Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. STUDY TYPE: Prospective. POPULATION: Twelve healthy subjects and eight patients with valvular regurgitation. FIELD STRENGTH/SEQUENCE: 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. ASSESSMENT: Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. STATISTICAL TESTS: We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. RESULTS: PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. CONCLUSION: PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Retrospective Camera-Based Respiratory Gating in Clinical Whole-Heart 4D Flow MRI.

BACKGROUND: Respiratory gating is generally recommended in 4D flow MRI of the heart to avoid blurring and motion artifacts. Recently, a novel automated contact-less camera-based respiratory motion sensor has been introduced. PURPOSE: To compare camera-based respiratory gating (CAM) with liver-lung-navigator-based gating (NAV) and no gating (NO) for whole-heart 4D flow MRI. STUDY TYPE: Retrospective. SUBJECTS: Thirty two patients with a spectrum of cardiovascular diseases. FIELD STRENGTH/SEQUENCE: A 3T, 3D-cine spoiled-gradient-echo-T1-weighted-sequence with flow-encoding in three spatial directions. ASSESSMENT: Respiratory phases were derived and compared against each other by cross-correlation. Three radiologists/cardiologist scored images reconstructed with camera-based, navigator-based, and no respiratory gating with a 4-point Likert scale (qualitative analysis). Quantitative image quality analysis, in form of signal-to-noise ratio (SNR) and liver-lung-edge (LLE) for sharpness and quantitative flow analysis of the valves were performed semi-automatically. STATISTICAL TESTS: One-way repeated measured analysis of variance (ANOVA) with Wilks's lambda testing and follow-up pairwise comparisons. Significance level of P ≤ 0.05. Krippendorff's-alpha-test for inter-rater reliability. RESULTS: The respiratory signal analysis revealed that CAM and NAV phases were highly correlated (C = 0.93 ± 0.09, P < 0.01). Image scoring showed poor inter-rater reliability and no significant differences were observed (P ≥ 0.16). The image quality comparison showed that NAV and CAM were superior to NO with higher SNR (P = 0.02) and smaller LLE (P < 0.01). The quantitative flow analysis showed significant differences between the three respiratory-gated reconstructions in the tricuspid and pulmonary valves (P ≤ 0.05), but not in the mitral and aortic valves (P > 0.05). Pairwise comparisons showed that reconstructions without respiratory gating were different in flow measurements to either CAM or NAV or both, but no differences were found between CAM and NAV reconstructions. DATA CONCLUSION: Camera-based respiratory gating performed as well as conventional liver-lung-navigator-based respiratory gating. Quantitative image quality analysis showed that both techniques were equivalent and superior to no-gating-reconstructions. Quantitative flow analysis revealed local flow differences (tricuspid/pulmonary valves) in images of no-gating-reconstructions, but no differences were found between images reconstructed with camera-based and navigator-based respiratory gating. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Pseudo-spiral sampling and compressed sensing reconstruction provides flexibility of temporal resolution in accelerated aortic 4D flow MRI: A comparison with k-t principal component analysis.

INTRODUCTION: Time-resolved three-dimensional phase contrast MRI (4D flow) of aortic blood flow requires acceleration to reduce scan time. Two established techniques for highly accelerated 4D flow MRI are k-t principal component analysis (k-t PCA) and compressed sensing (CS), which employ either regular or random k-space undersampling. The goal of this study was to gain insights into the quantitative differences between k-t PCA- and CS-derived aortic blood flow, especially for high temporal resolution CS 4D flow MRI. METHODS: The scan protocol consisted of both k-t PCA and CS accelerated 4D flow MRI, as well as a 2D flow reference scan through the ascending aorta acquired in 15 subjects. 4D flow scans were accelerated with factor R = 8. For CS accelerated scans, we used a pseudo-spiral Cartesian sampling scheme, which could additionally be reconstructed at higher temporal resolution, resulting in R = 13. 4D flow data were compared with the 2D flow scan in terms of flow, peak flow and stroke volume. A 3D peak systolic voxel-wise velocity and wall shear stress (WSS) comparison between k-t PCA and CS 4D flow was also performed. RESULTS: The mean difference in flow/peak flow/stroke volume between the 2D flow scan and the 4D flow CS with R = 8 and R = 13 was 4.2%/9.1%/3.0% and 5.3%/7.1%/1.9%, respectively, whereas for k-t PCA with R = 8 the difference was 9.7%/25.8%/10.4%. In the voxel-by-voxel 4D flow comparison we found 13.6% and 3.5% lower velocity and WSS values of k-t PCA compared with CS with R = 8, and 15.9% and 5.5% lower velocity and WSS values of k-t PCA compared with CS with R = 13. CONCLUSION: Pseudo-spiral accelerated 4D flow acquisitions in combination with CS reconstruction provides a flexible choice of temporal resolution. We showed that our proposed strategy achieves better agreement in flow values with 2D reference scans compared with using k-t PCA accelerated acquisitions.

Highly accelerated 4D flow cardiovascular magnetic resonance using a pseudo-spiral Cartesian acquisition and compressed sensing reconstruction for carotid flow and wall shear stress.

BACKGROUND: 4D flow cardiovascular magnetic resonance (CMR) enables visualization of complex blood flow and quantification of biomarkers for vessel wall disease, such as wall shear stress (WSS). Because of the inherently long acquisition times, many efforts have been made to accelerate 4D flow acquisitions, however, no detailed analysis has been made on the effect of Cartesian compressed sensing accelerated 4D flow CMR at different undersampling rates on quantitative flow parameters and WSS. METHODS: We implemented a retrospectively triggered 4D flow CMR acquisition with pseudo-spiral Cartesian k-space filling, which results in incoherent undersampling of k-t space. Additionally, this strategy leads to small jumps in k-space thereby minimizing eddy current related artifacts. The pseudo-spirals were rotated in a tiny golden-angle fashion, which provides optimal incoherence and a variable density sampling pattern with a fully sampled center. We evaluated this 4D flow protocol in a carotid flow phantom with accelerations of R = 2-20, as well as in carotids of 7 healthy subjects (27 ± 2 years, 4 male) for R = 10-30. Fully sampled 2D flow CMR served as a flow reference. Arteries were manually segmented and registered to enable voxel-wise comparisons of both velocity and WSS using a Bland-Altman analysis. RESULTS: Magnitude images, velocity images, and pathline reconstructions from phantom and in vivo scans were similar for all accelerations. For the phantom data, mean differences at peak systole for the entire vessel volume in comparison to R = 2 ranged from - 2.3 to - 5.3% (WSS) and - 2.4 to - 2.2% (velocity) for acceleration factors R = 4-20. For the in vivo data, mean differences for the entire vessel volume at peak systole in comparison to R = 10 were - 9.9, - 13.4, and - 16.9% (WSS) and - 8.4, - 10.8, and - 14.0% (velocity), for R = 20, 25, and 30, respectively. Compared to single slice 2D flow CMR acquisitions, peak systolic flow rates of the phantom showed no differences, whereas peak systolic flow rates in the carotid artery in vivo became increasingly underestimated with increasing acceleration. CONCLUSION: Acquisition of 4D flow CMR of the carotid arteries can be highly accelerated by pseudo-spiral k-space sampling and compressed sensing reconstruction, with consistent data quality facilitating velocity pathline reconstructions, as well as quantitative flow rate and WSS estimations. At an acceleration factor of R = 20 the underestimation of peak velocity and peak WSS was acceptable (< 10%) in comparison to an R = 10 accelerated 4D flow CMR reference scan. Peak flow rates were underestimated in comparison with 2D flow CMR and decreased systematically with higher acceleration factors.

Accelerated 4D phase contrast MRI in skeletal muscle contraction.

PURPOSE: 3D time-resolved (4D) phase contrast MRI can be used to study muscle contraction. However, 3D coverage with sufficient spatiotemporal resolution can only be achieved by interleaved acquisitions during many repetitions of the motion task, resulting in long scan times. The aim of this study was to develop a compressed sensing accelerated 4D phase contrast MRI technique for quantification of velocities and strain rate of the muscles in the lower leg during active plantarflexion/dorsiflexion. METHODS: Nine healthy volunteers were scanned during active dorsiflexion/plantarflexion task. For each volunteer, we acquired a reference scan, as well as 4 different accelerated scans (k-space undersampling factors: 3.14X, 4.09X, 4.89X, and 6.41X) obtained using Cartesian Poisson disk undersampling schemes. The data was reconstructed using a compressed sensing pipeline. For each scan, velocity and strain rate values were quantified in the gastrocnemius lateralis, gastrocnemius medialis, tibialis anterior, and soleus. RESULTS: No significant differences in velocity values were observed as a function acceleration factor in the investigated muscles. The strain rate calculation resulted in one positive (s+ ) and one negative (s- ) eigenvalue, whereas the third eigenvalue (s3 ) was consistently 0 for all the acquisitions. No significant differences were observed for the strain rate eigenvalues as a function of acceleration factor. CONCLUSIONS: Data undersampling combined with compressed sensing reconstruction allowed obtainment of time-resolved phase contrast acquisitions with 3D coverage and quantitative information comparable to the reference scan. The 3D sensitivity of the method can help in understanding the connection between muscle architecture and muscle function in future studies.

Abnormal aortic hemodynamics are associated with risk factors for aortic complications in patients with marfan syndrome.

Background: It is difficult to assess the risk for aortic dissection beyond the aortic root in patients with Marfan syndrome (MFS). To aid risk assessment in these patients, we investigated aortic flow and wall shear stress (WSS) by 4D flow magnetic resonance imaging (MRI) in patients with MFS and compared the results with healthy volunteers. We hypothesized that MFS patients with a high-risk profile for aortic dissection would show abnormal hemodynamics in aortic regions associated with aortic dissection. Methods: MFS patients (n = 55) and healthy subjects (n = 25), matched for age and sex, prospectively underwent 4D flow MRI. 4D flow maps were constructed to detect elevated (defined as higher than the three-dimensional 95 % confidence interval) and deviant directed (defined as vector angle differences higher than 120°) WSS in MFS patients as compared to the controls. Univariate and multivariate associations with risk factors for aortic dissection in MFS patients were assessed. Results: The maximum incidence for elevated WSS was 20 % (CI 9 %-31 %) and found in the ascending aorta. The maximum for deviant directed WSS was 39 % (CI 26 %-52 %) and found in the inner descending aorta. Significantly more male patients had deviant directed WSS in the inner proximal descending aorta (63 % vs 24 %, p = 0.014). Multivariate analysis showed that deviant directed WSS was associated with male sex (p = 0.019), and a haplo-insufficient FBN1 mutation type (p = 0.040). In 60 % of MFS patients with a previous aortic root replacement surgery, abnormal hemodynamics were found in the ascending aorta. No significant differences between hemodynamics were found in the descending aorta between operated and non-operated patients. Conclusion: Deviant directed WSS in the proximal descending aorta is associated with known risk factors for aortic dissection in MFS patients, namely male sex and a haploinsufficient FBN1 mutation type.

Coronary Flow Assessment Using Accelerated 4D Flow MRI With Respiratory Motion Correction.

Magnetic resonance imaging (MRI) can potentially be used for non-invasive screening of patients with stable angina pectoris to identify probable obstructive coronary artery disease. MRI-based coronary blood flow quantification has to date only been performed in a 2D fashion, limiting its clinical applicability. In this study, we propose a framework for coronary blood flow quantification using accelerated 4D flow MRI with respiratory motion correction and compressed sensing image reconstruction. We investigate its feasibility and repeatability in healthy subjects at rest. Fourteen healthy subjects received 8 times-accelerated 4D flow MRI covering the left coronary artery (LCA) with an isotropic spatial resolution of 1.0 mm3. Respiratory motion correction was performed based on 1) lung-liver navigator signal, 2) real-time monitoring of foot-head motion of the liver and LCA by a separate acquisition, and 3) rigid image registration to correct for anterior-posterior motion. Time-averaged diastolic LCA flow was determined, as well as time-averaged diastolic maximal velocity (VMAX) and diastolic peak velocity (VPEAK). 2D flow MRI scans of the LCA were acquired for reference. Scan-rescan repeatability and agreement between 4D flow MRI and 2D flow MRI were assessed in terms of concordance correlation coefficient (CCC) and coefficient of variation (CV). The protocol resulted in good visibility of the LCA in 11 out of 14 subjects (six female, five male, aged 28 ± 4 years). The other 3 subjects were excluded from analysis. Time-averaged diastolic LCA flow measured by 4D flow MRI was 1.30 ± 0.39 ml/s and demonstrated good scan-rescan repeatability (CCC/CV = 0.79/20.4%). Time-averaged diastolic VMAX (17.2 ± 3.0 cm/s) and diastolic VPEAK (24.4 ± 6.5 cm/s) demonstrated moderate repeatability (CCC/CV = 0.52/19.0% and 0.68/23.0%, respectively). 4D flow- and 2D flow-based diastolic LCA flow agreed well (CCC/CV = 0.75/20.1%). Agreement between 4D flow MRI and 2D flow MRI was moderate for both diastolic VMAX and VPEAK (CCC/CV = 0.68/20.3% and 0.53/27.0%, respectively). In conclusion, the proposed framework of accelerated 4D flow MRI equipped with respiratory motion correction and compressed sensing image reconstruction enables repeatable diastolic LCA flow quantification that agrees well with 2D flow MRI.