Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling. Genet Med 19 4, 386–395.

Purpose: In this work, we integrated the pilot tone (PT) navigation system into a reconstruction framework for respiratory and cardiac motion‐resolved 5D flow. We tested the hypotheses that PT would provide equivalent respiratory curves, cardiac triggers, and corresponding flow measurements to a previously established self‐gating (SG) technique while being independent from changes to the acquisition parameters.Methods: Fifteen volunteers and 9 patients were scanned with a free‐running 5D flow sequence, with PT integrated. Respiratory curves and cardiac triggers from PT and SG were compared across all subjects. Flow measurements from 5D flow reconstructions using both PT and SG were compared to each other and to a reference electrocardiogram‐gated and respiratory triggered 4D flow acquisition. Radial trajectories with variable readouts per interleave were also tested in 1 subject to compare cardiac trigger quality between PT and SG.Results: The correlation between PT and SG respiratory curves were 0.95 ± 0.06 for volunteers and 0.95 ± 0.04 for patients. Heartbeat duration measurements in volunteers and patients showed a bias to electrocardiogram measurements of, respectively, 0.16 ± 64.94 ms and 0.01 ± 39.29 ms for PT versus electrocardiogram and of 0.24 ± 63.68 ms and 0.09 ± 32.79 ms for SG versus electrocardiogram. No significant differences were reported for the flow measurements between 5D flow PT and from 5D flow SG. A decrease in the cardiac triggering quality of SG was observed for increasing readouts per interleave, whereas PT quality remained constant.Conclusion: PT has been successfully integrated in 5D flow MRI and has shown equivalent results to the previously described 5D flow SG technique, while being completely acquisition‐independent.

Purpose: To validate a respiratory motion correction method called focused navigation (fNAV) for free‐running radial whole‐heart 4D flow MRI.Methods: Using fNAV, respiratory signals derived from radial readouts are converted into three orthogonal displacements, which are then used to correct respiratory motion in 4D flow datasets. Hundred 4D flow acquisitions were simulated with non‐rigid respiratory motion and used for validation. The difference between generated and fNAV displacement coefficients was calculated. Vessel area and flow measurements from 4D flow reconstructions with (fNAV) and without (uncorrected) motion correction were compared to the motion‐free ground‐truth. In 25 patients, the same measurements were compared between fNAV 4D flow, 2D flow, navigator‐gated Cartesian 4D flow, and uncorrected 4D flow datasets.Results: For simulated data, the average difference between generated and fNAV displacement coefficients was 0.04 0.32 mm and 0.31 0.35 mm in the x and y directions, respectively. In the z direction, this difference was region‐dependent (0.02 0.51 mm up to 5.85 3.41 mm). For all measurements (vessel area, net volume, and peak flow), the average difference from ground truth was higher for uncorrected 4D flow datasets (0.32 0.11 cm², 11.1 3.5 mL, and 22.3 6.0 mL/s) than for fNAV 4D flow datasets (0.10 0.03 cm², 2.6 0.7 mL, and 5.1 .9 mL/s, p < 0.05). In vivo, average vessel area measurements were 4.92 2.95 cm², 5.06 2.64 cm², 4.87 2.57 cm², 4.87 2.69 cm², for 2D flow and fNAV, navigator‐gated and uncorrected 4D flow datasets, respectively. In the ascending aorta, all 4D flow datasets except for the fNAV reconstruction had significantly different vessel area measurements from 2D flow. Overall, 2D flow datasets demonstrated the strongest correlation to fNAV 4D flow for both net volume (r² = 0.92) and peak flow (r² = 0.94), followed by navigator‐gated 4D flow (r² = 0.83 and r² = 0.86, respectively), and uncorrected 4D flow (r² = 0.69 and r² = 0.86, respectively).Conclusion: fNAV corrected respiratory motion in vitro and in vivo, resulting in fNAV 4D flow measurements that are comparable to those derived from 2D flow and navigator‐gated Cartesian 4D flow datasets, with improvements over those from uncorrected 4D flow.

Purpose: To compare two blind source separation (BSS) techniques to principal component analysis and the electrocardiogram for the identification of cardiac triggers in self‐gated free‐running 5D whole‐heart MRI. To ascertain the precision and robustness of the techniques, they were compared in three different noise and contrast regimes.Methods: The repeated superior–inferior (SI) projections of a 3D radial trajectory were used to extract the physiological signals in three cardiac MRI cohorts: (1) 9 healthy volunteers without contrast agent injection at 1.5T, (2) 30 ferumoxytol‐injected congenital heart disease patients at 1.5T, and (3) 12 gadobutrol‐injected patients with suspected coronary artery disease at 3T. Self‐gated cardiac triggers were extracted with the three algorithms (principal component analysis [PCA], second‐order blind identification [SOBI], and independent component analysis [ICA]) and the difference with the electrocardiogram triggers was calculated. PCA and SOBI triggers were retained for image reconstruction. The image sharpness was ascertained on whole‐heart 5D images obtained with PCA and SOBI and compared among the three cohorts.Results: SOBI resulted in smaller trigger differences in Cohorts 1 and 3 compared to PCA (p < 0.01) and in all cohorts compared to ICA (p < 0.04). In Cohorts 1 and 3, the sharpness increased significantly in the reconstructed images when using SOBI instead of PCA (p < 0.03), but not in Cohort 2 (p = 0.4).Conclusion: We have shown that SOBI results in more precisely extracted self‐gated triggers than PCA and ICA. The validation across three diverse cohorts demonstrates the robustness of the method against acquisition variability.

Coarctation of the aorta (CoA) is often treated percutaneously. The aim of this study was to describe the immediate results of percutaneous management of native aortic coarctation (NaCoA) and recoarctation of the aorta (ReCoA) at our institution. We identified all patients with NaCoA or ReCoA who underwent percutaneous dilatation by either balloon angioplasty (BAP) or endovascular stent implantation (ESI) between 2011 and 2017. Success was defined as a residual peak-to-peak gradient (PPG) <20 mmHg or a ≥50% reduction in the gradient if the pre-intervention PPG was <20 mmHg. 63 patients (median age 6.8 years, interquartile range [IQR] 0.4-14.2) were identified. Among 11 patients with NaCoA, 7 underwent BAP and 4 had ESI, and among 52 patients with ReCoA, 42 underwent BAP and 10 had ESI. In patients with NaCoA, BAP was successful in 71%, with median PPG decreasing from 32 mmHg (IQR 25-46) to 17 mmHg (IQR 4-23) (p = .02), and ESI was successful in 100%, with median PPG decreasing from 20 mmHg (IQR 14.5-40) to 2 mmHg (IQR 0-6) (p < .01). In patients with ReCoA, BAP was successful in 69%, with median PPG decreasing from 20 mmHg (IQR 16-31.3) to 9 mmHg (IQR 0-14.3) (p < .001), and ESI was successful in 100%, with median PPG decreasing from 18 mmHg (IQR 11.5-22.8) to 0 mmHg (IQR 0-3.5) (p < .01). ESI was more successful than BAP (p = .01). There was only one complication. Percutaneous management of CoA is safe and effective in both NaCoA and ReCoA. Stent implantation is more effective than BAP.

CMR has not seen widespread adoption beyond large urban academic centers. The reasons for this limited uptake include the cost, time-intensive nature and special expertise of CMR. Self-navigated 5D, x-y-z-cardiac-respiratory, free-funning whole-heart CMR using self-navigation (5D CMR) implemented on a low-field clinical scanner may help bridge this gap for bi-ventricular function assessment and left atrium volume index measurement. Whole-heart 3D radial phyllotaxis bSSFP data were collected in 10 healthy adult subjects. Self-navigation was used to extract respiratory and cardiac motion signals and to generate motion-resolved 5D CMR datasets. The right- and left-ventricular ejection fraction (RVEF and LVEF), left atrial volume index (LAVI), contrast ratio, sharpness, perceived image quality, and total scan durations were ascertained and compared to those obtained with the reference 2D cine images. 5D CMR allowed for time-efficient and concordant measurements when compared to the 2D reference method. The 5D CMR images resulted in lower CR on 5D CMR images (3.3 ± 2.9) than on 2D cines (4.7 ± 1.2), and similarly lower perceived image quality (1.8 ± 0.8 for 5D CMR and 3.6 ± 0.9 for the 2D cines). However, the LVEF measurements were similar with no statistically significant differences (Mean: 58 ± 5% for 5D CMR and 59 ± 5% for 2D cine, p = 0.49) and the LoA were low (-2.81% to 3.81%). For the RVEF, the measurements were also in good agreement when RVEF was measured on the axial views (60 ± 3% for 5D CMR and 60 ± 4% for 2D cine, p = 0.85) and the LoA were also low (-2.87% to 3.07%). 5D CMR without the need for ECG, breath-holding, navigators, or complex scan planning enables a highly simplified and time-efficient assessment of bi-ventricular cardiac function on a 0.55T clinical system in 7:50min.