Laterality defect of the heart in non-teleost fish.

Dextrocardia is a rare congenital malformation in humans in which most of the heart mass is positioned in the right hemithorax rather than on the left. The heart itself may be normal and dextrocardia is sometimes diagnosed during non-related explorations. A few reports have documented atypical positions of the cardiac chambers in farmed teleost fish. Here, we report the casual finding of a left-right mirrored heart in an 85 cm long wild-caught spiny dogfish (Squalus acanthias) with several organ malformations. Macroscopic observations showed an outflow tract originating from the left side of the ventricular mass, rather than from the right. Internal inspection revealed the expected structures and a looped cavity. The inner curvature of the loop comprised a large trabeculation, the bulboventricular fold, as expected. The junction between the sinus venosus and the atrium appeared normal, only mirrored. MRI data acquired at 0.7 mm isotropic resolution and subsequent 3D-modeling revealed the atrioventricular canal was to the right of the bulboventricular fold, rather than on the left. Spurred by the finding of dextrocardia in the shark, we revisit our previously published material on farmed Adriatic sturgeon (Acipenser naccarii), a non-teleost bony fish. We found several alevins with inverted (left-loop) hearts, amounting to an approximate incidence of 1%-2%. Additionally, an adult sturgeon measuring 90 cm in length showed abnormal topology of the cardiac chambers, but normal position of the abdominal organs. In conclusion, left-right mirrored hearts, a setting that resembles human dextrocardia, can occur in both farmed and wild non-teleost fish.

Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b1 and b2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2 , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b2 from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Venous Blood Oxygenation Measurements Using TRUST and T2-TRIR MRI During Hypoxic and Hypercapnic Gas Challenges.

BACKGROUND: Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) may serve as biomarkers in several diseases. OEF and CMRO2 can be estimated from venous blood oxygenation (Yv ) levels, which in turn can be calculated from venous blood T2 values (T2b ). T2b can be measured using different MRI sequences, including T2-relaxation-under-spin-tagging (TRUST) and T2-prepared-blood-relaxation-imaging-with-inversion-recovery (T2-TRIR). The latter measures both T2b and T1 (T1b ) but was found previously to overestimate T2b compared to TRUST. It remained unclear, however, if this bias is constant across higher and lower oxygen saturations. PURPOSE: To compare TRUST and T2-TRIR across a range of O2 saturations using hypoxic and hypercapnic gas challenges. STUDY TYPE: Prospective. POPULATION: Twelve healthy volunteers (four female, age 36 ± 10 years). FIELD STRENGTH/SEQUENCE: A 3T; turbo-field echo-planar-imaging (TFEPI), echo-planar-imaging (EPI), and fast-field-echo (FFE). ASSESSMENT: TRUST- and T2-TRIR-derived T2b , Yv , OEF, and CMRO2 were compared across different respiratory challenges. T1b from T2-TRIR was used to estimate Hct (HctTRIR ) and compared with venipuncture (HctVP ). STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, Friedman test, Bland-Altman, and correlation analysis. Bonferroni multiple-comparison correction was performed. Significance level was 0.05. RESULTS: A significant bias was observed between TRUST- and T2-TRIR-derived T2b , Yv , and OEF values (-13 ± 11 msec, -5.3% ± 3.5% and 5.9 ± 4.1%, respectively). For Yv and OEF, this bias was constant across the range of measured values. T1b was significantly lower during severe hypoxia and hypercapnia compared to baseline (1712 ± 86 msec and 1634 ± 79 msec compared to 1757 ± 90 msec). While no significant bias was found between HctVP and HctTRIR (0.02% ± 0.06%, P = 0.20), the correlation between these Hct values was significant but weak (r = 0.19). DATA CONCLUSION: Given the constant bias, TRUST- and T2-TRIR-derived venous T2b values can be used interchangeably to estimate Yv , OEF, and CMRO2 across a broad range of oxygen saturations. Hct from T2-TRIR-derived T1-values only weakly correlated with Hct from venipuncture. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Acceleration of neuromelanin-sensitive MRI sequences in the substantia nigra using standard MRI options.

PURPOSE: Neuromelanin MRI (NM-MRI) is applied as a proxy measurement of dopaminergic functioning of the substantia nigra pars compacta (SN). To increase its clinical applicability, a fast and easily applicable NM-MRI sequence is needed. This study therefore compared accelerated NM-MRI sequences using standard available MRI options with a validated 2D gradient recalled echo NM-MRI sequence with off-resonance magnetization transfer (MT) pulse (2D-MToffRes). METHODS: We used different combinations of compressed sense (CS) acceleration, repetition times (TR), and MT pulse to accelerate the validated 2D-MToffRes. In addition, we compared a recently introduced 3D sequence with the 2D-MToffRes. RESULTS: Our results show that the 2D sequences perform best with good to excellent reliability. Only excellent intraclass correlation coefficients were found for the CS factor 2 sequences. CONCLUSION: We conclude that there are several reliable approaches to accelerate NM-MRI, in particular by using CS.

A unified model for reconstruction and R2* mapping of accelerated 7T data using the quantitative recurrent inference machine.

Quantitative MRI (qMRI) acquired at the ultra-high field of 7 Tesla has been used in visualizing and analyzing subcortical structures. qMRI relies on the acquisition of multiple images with different scan settings, leading to extended scanning times. Data redundancy and prior information from the relaxometry model can be exploited by deep learning to accelerate the imaging process. We propose the quantitative Recurrent Inference Machine (qRIM), with a unified forward model for joint reconstruction and R2*-mapping from sparse data, embedded in a Recurrent Inference Machine (RIM), an iterative inverse problem-solving network. To study the dependency of the proposed extension of the unified forward model to network architecture, we implemented and compared a quantitative End-to-End Variational Network (qE2EVN). Experiments were performed with high-resolution multi-echo gradient echo data of the brain at 7T of a cohort study covering the entire adult life span. The error in reconstructed R2* from undersampled data relative to reference data significantly decreased for the unified model compared to sequential image reconstruction and parameter fitting using the RIM. With increasing acceleration factor, an increasing reduction in the reconstruction error was observed, pointing to a larger benefit for sparser data. Qualitatively, this was following an observed reduction of image blurriness in R2*-maps. In contrast, when using the U-Net as network architecture, a negative bias in R2* in selected regions of interest was observed. Compressed Sensing rendered accurate, but less precise estimates of R2*. The qE2EVN showed slightly inferior reconstruction quality compared to the qRIM but better quality than the U-Net and Compressed Sensing. Subcortical maturation over age measured by a linearly increasing interquartile range of R2* in the striatum was preserved up to an acceleration factor of 9. With the integrated prior of the unified forward model, the proposed qRIM can exploit the redundancy among repeated measurements and shared information between tasks, facilitating relaxometry in accelerated MRI.

Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation.

The ventricular walls of the human heart comprise an outer compact layer and an inner trabecular layer. In the context of an increased pre-test probability, diagnosis left ventricular noncompaction cardiomyopathy is given when the left ventricle is excessively trabeculated in volume (trabecular vol >25% of total LV wall volume) or thickness (trabecular/compact (T/C) >2.3). Here, we investigated whether higher spatial resolution affects the detection of trabeculation and thus the assessment of normal and excessively trabeculated wall morphology. First, we screened left ventricles in 1112 post-natal autopsy hearts. We identified five excessively trabeculated hearts and this low prevalence of excessive trabeculation is in agreement with pathology reports but contrasts the prevalence of approximately 10% of the population found by in vivo non-invasive imaging. Using macroscopy, histology and low- and high-resolution MRI, the five excessively trabeculated hearts were compared with six normal hearts and seven abnormally trabeculated and excessive trabeculation-negative hearts. Some abnormally trabeculated hearts could be considered excessively trabeculated macroscopically because of a trabecular outflow or an excessive number of trabeculations, but they were excessive trabeculation-negative when assessed with MRI-based measurements (T/C <2.3 and vol <25%). The number of detected trabeculations and T/C ratio were positively correlated with higher spatial resolution. Using measurements on high resolution MRI and with histological validation, we could not replicate the correlation between trabeculations of the left and right ventricle that has been previously reported. In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.

Comparative Analysis of Blood T2 Values Measured by T2 -TRIR and TRUST.

BACKGROUND: Venous blood oxygenation (Yv), which can be derived from venous blood T2 (T2 b), combined with oxygen-extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T2 -Prepared-Blood-Relaxation-Imaging-with-Inversion-Recovery (T2 -TRIR) was introduced allowing for simultaneous measurements of blood T2 and T1 (T1 b), potentially improving Yv estimation by overcoming the need to estimate hematocrit. PURPOSE: To optimize and compare T2 -TRIR with T2 -relaxation-under-spin-tagging (TRUST) sequence. STUDY TYPE: Prospective. POPULATION: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old). FIELD STRENGTH/SEQUENCE: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE). ASSESSMENT: T2 b, Yv, and OEF from TRUST and T2 -TRIR were compared and T2 -TRIR-derived T1 b was assessed. Within- and between-session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients. STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, mixed linear model, Bland-Altman analysis and correlation analysis. Sidak multiple-comparison correction was performed. Significance level was 0.05. RESULTS: In controls, T2 b from T2 -TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T2 b values were lower pre- compared to post-ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T2 -TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre- compared to post-ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T2 -TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T2 -TRIR OEF: 25% ± 8% and 18% ± 6%). DATA CONCLUSION: TRUST and T2 -TRIR are reproducible, but T2 -TRIR-derived T2 b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

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.

Fetal Tricuspid Valve Agenesis/Atresia: Testing Predictions of the Embryonic Etiology.

Tricuspid valve agenesis/atresia (TVA) is a congenital cardiac malformation where the tricuspid valve is not formed. It is hypothesized that TVA results from a failure of the normal rightward expansion of the atrioventricular canal (AVC). We tested predictions of this hypothesis by morphometric analyses of the AVC in fetal hearts. We used high-resolution MRI and ultrasonography on a post-mortem fetal heart with TVA and with tricuspid valve stenosis (TVS) to validate the position of measurement landmarks that were to be applied to clinical echocardiograms. This revealed a much deeper right atrioventricular sulcus in TVA than in TVS. Subsequently, serial echocardiograms of in utero fetuses between 12 and 38 weeks of gestation were included (n = 23 TVA, n = 16 TVS, and n = 74 controls) to establish changes in AVC width and ventricular dimensions over time. Ventricular length and width and estimated fetal weight all increased significantly with age, irrespective of diagnosis. Heart rate did not differ between groups. However, in the second trimester, in TVA, the ratio of AVC to ventricular width was significantly lower compared to TVS and controls. This finding supports the hypothesis that TVA is due to a failed rightward expansion of the AVC. Notably, we found in the third trimester that the AVC to ventricular width normalized in TVA fetuses as their mitral valve area was greater than in controls. Hence, TVA associates with a quantifiable under-development of the AVC. This under-development is obscured in the third trimester, likely because of adaptational growth that allows for increased stroke volume of the left ventricle.

Double delay alternating with nutation for tailored excitation facilitates banding-free isotropic high-resolution intracranial vessel wall imaging.

The purpose of this study was to evaluate the use of a double delay alternating with nutation for tailored excitation (D-DANTE)-prepared sequence for banding-free isotropic high-resolution intracranial vessel wall imaging (IC-VWI) and to compare its performance with regular DANTE in terms of signal-to-noise ratio (SNR) as well as cerebrospinal fluid (CSF) and blood suppression efficiency. To this end, a D-DANTE-prepared 3D turbo spin echo sequence was implemented by interleaving two separate DANTE pulse trains with different RF phase-cycling schemes, but keeping all other DANTE parameters unchanged, including the total number of pulses and total preparation time. This achieved a reduction of the banding distance compared with regular DANTE enabling banding-free imaging up to higher resolutions. Bloch simulations assuming static vessel wall and flowing CSF spins were performed to compare DANTE and D-DANTE in terms of SNR and vessel wall/CSF contrast. Similar image quality measures were assessed from measurements on 13 healthy middle-aged volunteers. Both simulation and in vivo results showed that D-DANTE had only slightly lower vessel wall/CSF and vessel wall/blood contrast-to-noise ratio values compared with regular DANTE, which originated from a 10%-15% reduction in vessel wall SNR but not from reduced CSF or blood suppression efficiency. As anticipated, IC-VWI acquisitions showed that D-DANTE can successfully remove banding artifacts compared with regular DANTE with equal scan time or DANTE preparation length. Moreover, application was demonstrated in a patient with an intracranial aneurysm, indicating improved robustness to slow flow artifacts compared with clinically available 3D turbo spin echo scans. In conclusion, D-DANTE provides banding artifact-free IC-VWI up to higher isotropic resolutions compared with regular DANTE. This allows for a more flexible choice of DANTE preparation parameters in high-resolution IC-VWI protocols.

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.

The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function.

Tetracycline antibiotics act by inhibiting bacterial protein translation. Given the bacterial ancestry of mitochondria, we tested the hypothesis that doxycycline-which belongs to the tetracycline class-reduces mitochondrial function, and results in cardiac contractile dysfunction in cultured H9C2 cardiomyoblasts, adult rat cardiomyocytes, in Drosophila and in mice. Ampicillin and carbenicillin were used as control antibiotics since these do not interfere with mitochondrial translation. In line with its specific inhibitory effect on mitochondrial translation, doxycycline caused a mitonuclear protein imbalance in doxycycline-treated H9C2 cells, reduced maximal mitochondrial respiration, particularly with complex I substrates, and mitochondria appeared fragmented. Flux measurements using stable isotope tracers showed a shift away from OXPHOS towards glycolysis after doxycycline exposure. Cardiac contractility measurements in adult cardiomyocytes and Drosophila melanogaster hearts showed an increased diastolic calcium concentration, and a higher arrhythmicity index. Systolic and diastolic dysfunction were observed after exposure to doxycycline. Mice treated with doxycycline showed mitochondrial complex I dysfunction, reduced OXPHOS capacity and impaired diastolic function. Doxycycline exacerbated diastolic dysfunction and reduced ejection fraction in a diabetes mouse model vulnerable for metabolic derangements. We therefore conclude that doxycycline impairs mitochondrial function and causes cardiac dysfunction.

An iterative sparse deconvolution method for simultaneous multicolor 19 F-MRI of multiple contrast agents.

PURPOSE: 19 F-MRI is gaining widespread interest for cell tracking and quantification of immune and inflammatory cells in vivo. Different fluorinated compounds can be discriminated based on their characteristic MR spectra, allowing in vivo imaging of multiple 19 F compounds simultaneously, so-called multicolor 19 F-MRI. We introduce a method for multicolor 19 F-MRI using an iterative sparse deconvolution method to separate different 19 F compounds and remove chemical shift artifacts arising from multiple resonances. METHODS: The method employs cycling of the readout gradient direction to alternate the spatial orientation of the off-resonance chemical shift artifacts, which are subsequently removed by iterative sparse deconvolution. Noise robustness and separation was investigated by numerical simulations. Mixtures of fluorinated oils (PFCE and PFOB) were measured on a 7T MR scanner to identify the relation between 19 F signal intensity and compound concentration. The method was validated in a mouse model after intramuscular injection of fluorine probes, as well as after intravascular injection. RESULTS: Numerical simulations show efficient separation of 19 F compounds, even at low signal-to-noise ratio. Reliable chemical shift artifact removal and separation of PFCE and PFOB signals was achieved in phantoms and in vivo. Signal intensities correlated excellently to the relative 19 F compound concentrations (r-2 = 0.966/0.990 for PFOB/PFCE). CONCLUSIONS: The method requires minimal sequence adaptation and is therefore easily implemented on different MRI systems. Simulations, phantom experiments, and in-vivo measurements in mice showed effective separation and removal of chemical shift artifacts below noise level. We foresee applicability for simultaneous in-vivo imaging of 19 F-containing fluorine probes or for detection of 19 F-labeled cell populations.

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.

Emerging Magnetic Resonance Imaging Techniques for Atherosclerosis Imaging.

Atherosclerosis is a prevalent disease affecting a large portion of the population at one point in their lives. There is an unmet need for noninvasive diagnostics to identify and characterize at-risk plaque phenotypes noninvasively and in vivo, to improve the stratification of patients with cardiovascular disease, and for treatment evaluation. Magnetic resonance imaging is uniquely positioned to address these diagnostic needs. However, currently available magnetic resonance imaging methods for vessel wall imaging lack sufficient discriminative and predictive power to guide the individual patient needs. To address this challenge, physicists are pushing the boundaries of magnetic resonance atherosclerosis imaging to increase image resolution, provide improved quantitative evaluation of plaque constituents, and obtain readouts of disease activity such as inflammation. Here, we review some of these important developments, with specific focus on emerging applications using high-field magnetic resonance imaging, the use of quantitative relaxation parameter mapping for improved plaque characterization, and novel 19F magnetic resonance imaging technology to image plaque inflammation.

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.

Three-dimensional diffusion imaging with spiral encoded navigators from stimulated echoes (3D-DISPENSE).

PURPOSE: To introduce a new method for motion-insensitive 3D multishot diffusion imaging using 3D spiral-encoded navigators from stimulated echoes (3D-DISPENSE). METHODS: The 3D-DISPENSE sequence contains a 3D stack-of-spiral navigator generated between the diffusion preparation and the turbo spin-echo image acquisition from the twin pathway of a stimulated echo. Unlike normal navigator methods, 3D-DISPENSE separates the navigator acquisition from the imaging readout without compromising the image SNR. Phase information from the navigators was included in an iterative image reconstruction algorithm to correct for intershot phase incoherence caused by motion. RESULTS: In a phantom experiment, 3D-DISPENSE correctly estimated deliberately introduced phase errors. In a moving phantom, motion-induced artifacts in the DWI were greatly mitigated by 3D-DISPENSE. The ADC after 3D-DISPENSE correction was identical to the reference. In a brain diffusion tensor experiment, phase-incoherence artifacts from breathing, cardiac, and subject motion were removed almost perfectly in all view angles, resulting in distortion-free DWI and color-coded fractional anisotropy maps with 1.5-mm isotropic resolution and nearly full brain coverage. CONCLUSION: Three-dimensional DISPENSE corrects motion-induced phase-incoherence artifacts in 3D multishot diffusion imaging and produces high-quality 3D DWI and DTI.

Rapid T1 quantification from high resolution 3D data with model-based reconstruction.

PURPOSE: Magnetic resonance imaging protocols for the assessment of quantitative information suffer from long acquisition times since multiple measurements in a parametric dimension are required. To facilitate the clinical applicability, accelerating the acquisition is of high importance. To this end, we propose a model-based optimization framework in conjunction with undersampling 3D radial stack-of-stars data. THEORY AND METHODS: High resolution 3D T1 maps are generated from subsampled data by employing model-based reconstruction combined with a regularization functional, coupling information from the spatial and parametric dimension, to exploit redundancies in the acquired parameter encodings and across parameter maps. To cope with the resulting non-linear, non-differentiable optimization problem, we propose a solution strategy based on the iteratively regularized Gauss-Newton method. The importance of 3D-spectral regularization is demonstrated by a comparison to 2D-spectral regularized results. The algorithm is validated for the variable flip angle (VFA) and inversion recovery Look-Locker (IRLL) method on numerical simulated data, MRI phantoms, and in vivo data. RESULTS: Evaluation of the proposed method using numerical simulations and phantom scans shows excellent quantitative agreement and image quality. T1 maps from accelerated 3D in vivo measurements, e.g. 1.8 s/slice with the VFA method, are in high accordance with fully sampled reference reconstructions. CONCLUSIONS: The proposed algorithm is able to recover T1 maps with an isotropic resolution of 1 mm3 from highly undersampled radial data by exploiting structural similarities in the imaging volume and across parameter maps.

Insufficient slow-flow suppression mimicking aneurysm wall enhancement in magnetic resonance vessel wall imaging: a phantom study.

OBJECTIVE: MR vessel wall imaging (VWI) is increasingly performed in clinical settings to support treatment decision-making regarding intracranial aneurysms. Aneurysm wall enhancement after contrast agent injection is expected to be related to aneurysm instability and rupture status. However, the authors hypothesize that slow-flow artifacts mimic aneurysm wall enhancement. Therefore, in this phantom study they assess the effect of slow flow on wall-like enhancement by using different MR VWI techniques. METHODS: The authors developed an MR-compatible aneurysm phantom model, which was connected to a pump to enable pulsatile inflow conditions. For VWI, 3D turbo spin echo sequences-both with and without motion-sensitized driven equilibrium (MSDE) and delay alternating with nutation for tailored excitation (DANTE) preparation pulses-were performed using a 3-T MR scanner. VWI was acquired both before and after Gd contrast agent administration by using two different pulsatile inflow conditions (2.5 ml/sec peak flow at 77 and 48 beats per minute). The intraluminal signal intensity along the aneurysm wall was analyzed to assess the performance of slow-flow suppression. RESULTS: The authors observed wall-like enhancement after contrast agent injection, especially in low pump rate settings. Preparation pulses, in particular the DANTE technique, improved the performance of slow-flow suppression. CONCLUSIONS: Near-wall slow flow mimics wall enhancement in VWI protocols. Therefore, VWI should be carefully interpreted. Preparation pulses improve slow-flow suppression, and therefore the authors encourage further development and clinical implementation of these techniques.

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.