Accelerated free breathing ECG triggered contrast enhanced pulmonary vein magnetic resonance angiography using compressed sensing

Background

To investigate the feasibility of accelerated electrocardiogram (ECG)-triggered contrast enhanced pulmonary vein magnetic resonance angiography (CE-PV MRA) with isotropic spatial resolution using compressed sensing (CS).

Methods

Nineteen patients (59 ± 13 y, 11 M) referred for MR were scanned using the proposed accelerated free breathing ECG-triggered 3D CE-PV MRA sequence (FOV = 340 × 340 × 110 mm³, spatial resolution = 1.5 × 1.5 × 1.5 mm³, acquisition window = 140 ms at mid diastole and CS acceleration factor = 5) and a conventional first-pass breath-hold non ECG-triggered 3D CE-PV MRA sequence. CS data were reconstructed offline using low-dimensional-structure self-learning and thresholding reconstruction (LOST) CS reconstruction. Quantitative analysis of PV sharpness and subjective qualitative analysis of overall image quality were performed using a 4-point scale (1: poor; 4: excellent).

Results

Quantitative PV sharpness was increased using the proposed approach (0.73 ± 0.09 vs. 0.51 ± 0.07 for the conventional CE-PV MRA protocol, p < 0.001). There were no significant differences in the subjective image quality scores between the techniques (3.32 ± 0.94 vs. 3.53 ± 0.77 using the proposed technique).

Conclusions

CS-accelerated free-breathing ECG-triggered CE-PV MRA allows evaluation of PV anatomy with improved sharpness compared to conventional non-ECG gated first-pass CE-PV MRA. This technique may be a valuable alternative for patients in which the first pass CE-PV MRA fails due to inaccurate first pass timing or inability of the patient to perform a 20–25 seconds breath-hold.     

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core

Background

Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR.

Methods

Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR.

Results

For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 – 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 – 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm³ vs. 53.4 ± 56.3 mm³, p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm³ vs. 111.3 ± 122.7 mm³, p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001).

Conclusion

MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.     

Feasibility study of electrocardiographic and respiratory gated,gadolinium enhanced magnetic resonance angiography of pulmonary veins and the impact of heart rate and rhythm on study quality

Background

We aimed to assess the feasibility of 3 dimensional (3D) respiratory and ECG gated, gadolinium enhanced magnetic resonance angiography (MRA) on a 3 Tesla (3 T) scanner for imaging pulmonary veins (PV) and left atrium (LA). The impact of heart rate (HR) and rhythm irregularity associated with atrial fibrillation (AF) on image and segmentation qualities were also assessed.

Methods

101 consecutive patients underwent respiratory and ECG gated (ventricular end systolic window) MRA for pre AF ablation imaging. Image quality (assessed by PV delineation) was scored as 1 = not visualized, 2 = poor, 3 = good and 4 = excellent. Segmentation quality was scored on a similar 4 point scale. Signal to noise ratios (SNRs) were calculated for the LA, LA appendage (LAA), and PV. Contrast to noise ratios (CNRs) were calculated between myocardium and LA, LAA and PV, respectively. Associations between HR/rhythm and quality metrics were assessed.

Results

35 of 101 (34.7%) patients were in AF at time of MRA. 100 (99%) patients had diagnostic studies, and 91 (90.1%) were of good or excellent quality. Overall, mean ± standard deviation (SD) image quality score was 3.40 ± 0.69. Inter observer agreement for image quality scores was substantial, (kappa = 0.68; 95% confidence interval (CI): 0.46, 0.90). Neither HR adjusting for rhythm [odds ratio (OR) = 1.03, 95% CI = 0.98,1.09; p = 0.22] nor rhythm adjusting for HR [OR = 1.25, 95% CI = 0.20, 7.69; p = 0.81] demonstrated association with image quality. Similarly, SNRs and CNRs were largely independent of HR after adjusting for rhythm. Segmentation quality scores were good or excellent for 77.3% of patients: mean ± SD score = 2.91 ± 0.63, and scores did not significantly differ by baseline rhythm (p = 0.78).

Conclusions

3D respiratory and ECG gated, gadolinium enhanced MRA of the PVs and LA on a 3 T system is feasible during ventricular end systole, achieving high image quality and high quality image segmentation when imported into electroanatomic mapping systems. Quality is independent of HR and heart rhythm for this free breathing, radiation free, alternative strategy to current MRA or CT based approaches, for pre AF ablation imaging of PVs and LA.     

Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity,cumulative dose and remodeling

Background

The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.

Methods

Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO₂). CMR measured ventricular function, mass, T₁ and T₂ values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T₁ values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.

Results

Patients had normal LVEF (59 ± 7%) but peak VO₂ was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO₂(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO₂ or cumulative dose.

Conclusions

Myocardial T₁ and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.     

Reproducibility of rest and exercise stress contrast-enhanced calf perfusion magnetic resonance imaging in peripheral arterial disease

Background

The purpose was to determine the reproducibility and utility of rest, exercise, and perfusion reserve (PR) measures by contrast-enhanced (CE) calf perfusion magnetic resonance imaging (MRI) of the calf in normal subjects (NL) and patients with peripheral arterial disease (PAD).

Methods

Eleven PAD patients with claudication (ankle-brachial index 0.67 ±0.14) and 16 age-matched NL underwent symptom-limited CE-MRI using a pedal ergometer. Tissue perfusion and arterial input were measured at rest and peak exercise after injection of 0.1 mM/kg of gadolinium-diethylnetriamine pentaacetic acid (Gd-DTPA). Tissue function (TF) and arterial input function (AIF) measurements were made from the slope of time-intensity curves in muscle and artery, respectively, and normalized to proton density signal to correct for coil inhomogeneity. Perfusion index (PI) = TF/AIF. Perfusion reserve (PR) = exercise TF/ rest TF. Intraclass correlation coefficient (ICC) was calculated from 11 NL and 10 PAD with repeated MRI on a different day.

Results

Resting TF was low in NL and PAD (mean ± SD 0.25 ± 0.18 vs 0.35 ± 0.71, p = 0.59) but reproducible (ICC 0.76). Exercise TF was higher in NL than PAD (5.5 ± 3.2 vs. 3.4 ± 1.6, p = 0.04). Perfusion reserve was similar between groups and highly variable (28.6 ± 19.8 vs. 42.6 ± 41.0, p = 0.26). Exercise TF and PI were reproducible measures (ICC 0.63 and 0.60, respectively).

Conclusion

Although rest measures are reproducible, they are quite low, do not distinguish NL from PAD, and lead to variability in perfusion reserve measures. Exercise TF and PI are the most reproducible MRI perfusion measures in PAD for use in clinical trials.     

Normal values of aortic dimensions,distensibility, and pulse wave velocity in children and young adults: a cross-sectional study

Background

Aortic enlargement and impaired bioelasticity are of interest in several cardiac and non-cardiac diseases as they can lead to cardiovascular complications. Cardiovascular magnetic resonance (CMR) is increasingly accepted as a noninvasive tool in cardiovascular evaluation. Assessment of aortic anatomy and bioelasticity, namely aortic distensibility and pulse wave velocity (PWV), by CMR is accurate and reproducible and could help to identify anatomical and bioelastic abnormalities of the aorta. However, normal CMR values for healthy children and young adults are lacking.

Methods

Seventy-one heart-healthy subjects (age 16.4 ± 7.6 years, range 2.3 - 28.3 years) were examined using a 3.0 Tesla CMR scanner. Aortic cross-sectional areas and aortic distensibility were measured at four positions of the ascending and descending thoracic aorta. PWV was assessed from aortic blood flow velocity measurements in a aortic segment between the ascending aorta and the proximal descending aorta. The Lambda-Mu-Sigma (LMS) method was used to obtain percentile curves for aortic cross-sectional areas, aortic distensibility and PWV according to age.

Results

Aortic areas, PWV and aortic distensibility (aortic cross-sectional areas: r = 0.8 to 0.9, p < 0.001; PWV: r = 0.25 to 0.32, p = 0.047 to 0.009; aortic distensibility r = -0.43 to -0.62, p < 0.001) correlated with height, weight, body surface area, and age. There were no significant sex differences.

Conclusions

This study provides percentile curves for cross-sectional areas, distensibility and pulse wave velocity of the thoracic aorta in children and young adolescents between their 3^rd and 29^th year of life. These data may serve as a reference for the detection of pathological changes of the aorta in cardiovascular disease.     

Characterization and quantification of dynamic eccentric regurgitation of the left atrioventricular valve after atrioventricular septal defect correction with 4D Flow cardiovascular magnetic resonance and retrospective valve tracking

Background

To characterize and directly quantify regurgitant jets of left atrioventricular valve (LAVV) in patients with corrected atrioventricular septal defect (AVSD) by four-dimensional (4D)Flow Cardiovascular Magnetic Resonance (CMR), streamline visualization and retrospective valve tracking.

Methods

Medical ethical committee approval and informed consent from all patients or their parents were obtained. In 32 corrected AVSD patients (age 26 ± 12 years), echocardiography and whole-heart 4DFlow CMR were performed. Using streamline visualization on 2- and 4-chamber views, the angle between regurgitation and annulus was followed throughout systole. On through-plane velocity-encoded images reformatted perpendicular to the regurgitation jet the cross-sectional jet circularity index was assessed and regurgitant volume and fraction were calculated. Correlation and agreement between different techniques was performed with Pearson’s r and Spearman’s rho correlation and Bland-Altman analysis.

Results

In 8 patients, multiple regurgitant jets over the LAVV were identified. Median variation in regurgitant jet angle within patients was 36°(IQR 18–64°) on the 2-chamber and 30°(IQR 20–40°) on the 4-chamber. Regurgitant jets had a circularity index of 0.61 ± 0.16. Quantification of the regurgitation volume was feasible with 4DFlow CMR with excellent correlation between LAVV effective forward flow and aortic flow (r = 0.97, p < 0.001) for internal validation and moderate correlation with planimetry derived regurgitant volume (r = 0.65, p < 0.001) and echocardiographic grading (rho = 0.51, p = 0.003).

Conclusions

4DFlow CMR with streamline visualization revealed multiple, dynamic and eccentric regurgitant jets with non-circular cross-sectional shape in patients after AVSD correction. 4DFlow with retrospective valve tracking allows direct and accurate quantification of the regurgitation of these complex jets.     

Monocenter feasibility study of the MRI compatibility of the Evia pacemaker in combination with Safio S pacemaker lead

Background

The purpose of this study was to evaluate the feasibility of the magnetic resonance (MR) conditional pacemaker (PM) system (Evia SR-T and DR-T with Safio S leads) under MR conditions.

Methods

Patients with standard PM indications and Evia PM were eligible for enrollment in this single center prospective non-randomized pilot study. Patients underwent MR of the brain and lower lumbar spine at 1.5 Tesla. Atrial (RA) und ventricular (RV) lead parameters (sensing, pacing threshold [PTH], pacing impedance) were assessed immediately before (baseline follow-up [FU]) and immediately after MRI (1^st FU), after 1 month (2^nd FU) and 3 months (3^rd FU). The effect of MR on serious adverse device effect (SADE) free-rate, on atrial and ventricular sensing (AS/VS; mV) and atrial (RA) and ventricular (RV) pacing thresholds (PTH; V/0.4 ms) were investigated between baseline and 2^nd FU. Continuous variables are expressed as mean ± SD and were compared using paired Student’s t-test. A p < 0.05 was considered significant.

Results

Thirty-one patients were enrolled. One patient had to be excluded because of an enrollment violation. Therefore, data of 30 patients (female 12 [40%], age 73 ± 12 years, dual chamber PM 15 [50%]) were included in this analysis. No MR related SADE occurred. Lead measurements were not statistically different between the baseline FU and the 2^nd FU (AS/VS at baseline 3.2 ± 2.1/15.0 ± 6.0, at 2^nd FU 3.2 ± 2.1/14.9 ± 6.5; p = ns. RA-PTH/RV-PTH at baseline 0.68 ± 0.18/0.78 ± 0.22, at 2^nd FU 0.71 ± 0.24/0.78 ± 0.22; p = ns). The presence of the permanent pacemakers led to MR imaging artifacts on diffusion weighted sequences of the brain, but did not affect other sequences (e.g. FLAIR and T2 weighted spin-echo images).

Conclusion

The use of the MR conditional Evia PM in a MR environment under predefined conditions is feasible. No MR related SADEs nor clinically relevant changes in device functions occurred.     

Fast assessment of long axis strain with standard cardiovascular magnetic resonance: a validation study of a novel parameter with reference values

Background

Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR.

Methods

40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula.

Results

LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches.LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI (67 ± 8 s vs. 180 ± 14 s, p < 0.0001). Additionally, LAS-epi/mid performed significantly better than MAPSE (Delta AUC = 0.09; p < 0.005) and the ejection fraction (Delta AUC = 0.11; p = 0.0002).Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was −17.1 ± 2.3 %. Mean values for men were significantly lower compared to women (−16.5 ± 2.2 vs. -17.9 ± 2.1 %; p < 0.0001), while LAS decreased with age.

Conclusions

LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain.     

Systemic-to-pulmonary collateral flow in patients with palliated univentricular heart physiology: measurement using cardiovascular magnetic resonance 4D velocity acquisition

Background

Systemic-to-pulmonary collateral flow (SPCF) may constitute a risk factor for increased morbidity and mortality in patients with single-ventricle physiology (SV). However, clinical research is limited by the complexity of multi-vessel two-dimensional (2D) cardiovascular magnetic resonance (CMR) flow measurements. We sought to validate four-dimensional (4D) velocity acquisition sequence for concise quantification of SPCF and flow distribution in patients with SV.

Methods

29 patients with SV physiology prospectively underwent CMR (1.5 T) (n = 14 bidirectional cavopulmonary connection [BCPC], age 2.9 ± 1.3 years; and n = 15 Fontan, 14.4 ± 5.9 years) and 20 healthy volunteers (age, 28.7 ± 13.1 years) served as controls. A single whole-heart 4D velocity acquisition and five 2D flow acquisitions were performed in the aorta, superior/inferior caval veins, right/left pulmonary arteries to serve as gold-standard. The five 2D velocity acquisition measurements were compared with 4D velocity acquisition for validation of individual vessel flow quantification and time efficiency. The SPCF was calculated by evaluating the disparity between systemic (aortic minus caval vein flows) and pulmonary flows (arterial and venour return). The pulmonary right to left and the systemic lower to upper body flow distribution were also calculated.

Results

The comparison between 4D velocity and 2D flow acquisitions showed good Bland-Altman agreement for all individual vessels (mean bias, 0.05±0.24 l/min/m²), calculated SPCF (−0.02±0.18 l/min/m²) and significantly shorter 4D velocity acquisition-time (12:34 min/17:28 min,p < 0.01). 4D velocity acquisition in patients versus controls revealed (1) good agreement between systemic versus pulmonary estimator for SPFC; (2) significant SPCF in patients (BCPC 0.79±0.45 l/min/m²; Fontan 0.62±0.82 l/min/m²) and not in controls (0.01 + 0.16 l/min/m²), (3) inverse relation of right/left pulmonary artery perfusion and right/left SPCF (Pearson = −0.47,p = 0.01) and (4) upper to lower body flow distribution trend related to the weight (r = 0.742, p < 0.001) similar to the controls.

Conclusions

4D velocity acquisition is reliable, operator-independent and more time-efficient than 2D flow acquisition to quantify SPCF. There is considerable SPCF in BCPC and Fontan patients. SPCF was more pronounced towards the respective lung with less pulmonary arterial flow suggesting more collateral flow where less anterograde branch pulmonary artery perfusion.     

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome

Background

Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS.

Methods

Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index.

Results

The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 11.4 ml/kg/m2, (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02).

Conclusions

ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation.     

Evaluation of diastolic function by three-dimensional volume tracking of the mitral annulus with cardiovascular magnetic resonance: comparison with tissue Doppler imaging

Background

Measurement of mitral annulus (MA) dynamics is an important component of the evaluation of left ventricular (LV) diastolic function; MA velocities are commonly measured using tissue Doppler imaging (TDI). This study aimed to examine the clinical potential of a semi-automated cardiovascular magnetic resonance (CMR) technique for quantifying global LV diastolic function, using 3D volume tracking of the MA with conventional cine-CMR images.

Methods

124 consecutive patients with normal ejection fraction underwent both clinically indicated transthoracic echocardiography (TTE) and CMR within 2 months. Interpolated 3D reconstruction of the MA over time was performed with semi-automated atrioventricular junction (AVJ) tracking in long-axis cine-CMR images, producing an MA sweep volume over the cardiac cycle. CMR-based diastolic function was evaluated, using the following parameters: peak volume sweep rates in early diastole (PSR_E) and atrial systole (PSR_A), PSR_E/PSR_A ratio, deceleration time of sweep volume (DT_SV), and 50% diastolic sweep volume recovery time (DSVRT₅₀); these were compared with TTE diastolic measurements.

Results

Patients with TTE-based diastolic dysfunction (n = 62) showed significantly different normalized MA sweep volume profiles compared to those with TTE-based normal diastolic function (n = 62), including a lower PSR_E (5.25 ± 1.38 s⁻¹ vs. 7.72 ± 1.7 s⁻¹), a higher PSR_A (6.56 ± 1.99 s⁻¹ vs. 4.67 ± 1.38 s⁻¹), a lower PSR_E/PSR_A ratio (0.9 ± 0.44 vs. 1.82 ± 0.69), a longer DT_SV (144 ± 55 ms vs. 96 ± 37 ms), and a longer DSVRT₅₀ (25.0 ± 11.0% vs. 15.6 ± 4.0%) (all p < 0.05). CMR diastolic parameters were independent predictors of TTE-based diastolic dysfunction after adjusting for left ventricular hypertrophy, hypertension, and coronary artery disease. Good correlations were observed between CMR PSR_E/PSR_A and early-to-late diastolic annular velocity ratios (e′/a′) measured by TDI (r = 0.756 to 0.828, p < 0.001).

Conclusions

3D MA sweep volumes generated by semi-automated AVJ tracking in routinely acquired CMR images yielded diastolic parameters that were effective in identifying patients with diastolic dysfunction when correlated with TTE-based variables.     

Reduced circulating endothelial progenitor cells in reversible cerebral vasoconstriction syndrome

Background

The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) remains elusive. Endothelial dysfunction might play a role, but direct evidence is lacking. This study aimed to explore whether patients with RCVS have a reduced level of circulating circulating endothelial progenitor cells (EPCs) to repair the dysfunctional endothelial vasomotor control.

Methods

We prospectively recruited 24 patients with RCVS within one month of disease onset and 24 healthy age- and sex-matched controls. Flow cytometry was used to quantify the numbers of circulating EPCs, defined as KDR⁺CD133⁺, CD34⁺CD133⁺, and CD34⁺KDR⁺ double-positive mononuclear cells. The Lindegaard index, an index of vasoconstriction, was calculated by measuring the mean flow velocity of middle cerebral arteries and distal extracranial internal carotid arteries via color-coded sonography on the same day as blood drawing. A Lindegaard index of 2 was chosen as the cutoff value for significant vasoconstriction of middle cerebral arteries based on our previous study.

Results

Patients with RCVS had a reduced number of CD34⁺KDR⁺ cells (0.009 ± 0.006% vs. 0.014 ± 0.010%, p = 0.031) but not KDR⁺CD133⁺ cells or CD34⁺CD133⁺ EPCs, in comparison with controls. The number of CD34⁺KDR⁺ cells was inversely correlated with the Lindegaard index (rs = -0.418, p = 0.047). Of note, compared to controls, patients with a Lindegaard index > 2 (n = 13) had a reduced number of CD34⁺KDR⁺ cells (0.007 ± 0.005% vs. 0.014 ± 0.010%, p = 0.010), but those with a Lindegaard index ≤ 2 did not.

Conclusions

Patients with RCVS had reduced circulating CD34⁺KDR⁺ EPCs, which were correlated with the severity of vasoconstriction. Endothelial dysfunction might contribute to the pathogenesis of RCVS.     

Pulmonary blood volume indexed to lung volume is reduced in newly diagnosed systemic sclerosis compared to normals – a prospective clinical cardiovascular magnetic resonance study addressing pulmonary vascular changes

Background

Pulmonary involvement, manifested as pulmonary arterial hypertension or pulmonary fibrosis, is the most common cause of death in systemic sclerosis (SSc). We aimed to explore the feasibility of detecting early pulmonary involvement in SSc using recently developed non-invasive quantitative measures of pulmonary physiology using cardiovascular magnetic resonance (CMR).

Methods

Twenty-seven SSc patients (9 men, 57 ± 13 years) and 10 healthy controls (3 men, 54 ± 9 years) underwent CMR to determine the pulmonary blood volume (PBV) and the PBV variation (PBVV) throughout the cardiac cycle. Patients underwent Doppler echocardiography, high-resolution computed tomography (HRCT), and pulmonary function testing by spirometry. Comparisons were performed using the unpaired t-test and linear regression analysis was performed with Pearson’s correlation coefficient (r).

Results

Compared to healthy controls, the PBV indexed to lung volume (PBVI) was lower in patients (16 ± 4 vs 20 ± 5%, p < 0.05). There was no difference in PBV (466 ± 87 vs 471 ± 122 mL, p = 0.91) or PBVV/stroke volume (45 ± 10 vs 40 ± 6%, p = 0.09). There were no significant correlations between PBVI and pulmonary artery pressure estimated by Doppler (p = 0.08) the lung’s diffusion capacity for carbon monoxide (DL_CO) (p = 0.09), vital capacity (p = 0.45), or pulmonary fibrosis by HRCT (p = 0.74).

Conclusions

This study is the first to measure the PBV in humans using CMR. Compared to healthy controls, newly diagnosed SSc patients have a reduced amount of blood in the pulmonary vasculature (PBVI) but unchanged pulmonary vascular distensibility (PBVV/stroke volume). PBVI is unrelated to DL_CO, pulmonary artery pressure, vital capacity, and the presence of pulmonary fibrosis. PBVI may be a novel parameter reflecting vascular lung involvement in early-stage SSc, and these findings may be consistent with pathophysiological changes of the pulmonary vasculature.     

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

Background

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.

Methods

In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.

Results

Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m²; female > 78 g/m²). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).

Conclusion

In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.     

Cardiac output and cardiac index measured with cardiovascular magnetic resonance in healthy subjects,elite athletes and patients with congestive heart failure

Background

Cardiovascular Magnetic Resonance (CMR) enables non-invasive quantification of cardiac output (CO) and thereby cardiac index (CI, CO indexed to body surface area). The aim of this study was to establish if CI decreases with age and compare the values to CI for athletes and for patients with congestive heart failure (CHF).

Methods

CI was measured in 144 healthy volunteers (39 ± 16 years, range 21–81 years, 68 females), in 60 athletes (29 ± 6 years, 30 females) and in 157 CHF patients with ejection fraction (EF) below 40% (60 ± 13 years, 33 females). CI was calculated using aortic flow by velocity-encoded CMR and is presented as mean ± SD. Flow was validated in vitro using a flow phantom and in 25 subjects with aorta and pulmonary flow measurements.

Results

There was a slight decrease of CI with age in healthy subjects (8 ml/min/m² per year, r² = 0.07, p = 0.001). CI in males (3.2 ± 0.5 l/min/m²) and females (3.1 ± 0.4 l/min/m²) did not differ (p = 0.64). The mean ± SD of CI in healthy subjects in the age range of 20–29 was 3.3 ± 0.4 l/min/m², in 30–39 years 3.3 ± 0.5 l/min/m², in 40–49 years 3.1 ± 0.5 l/min/m², 50–59 years 3.0 ± 0.4 l/min/m² and >60 years 3.0 ± 0.4 l/min/m². There was no difference in CI between athletes and age-controlled healthy subjects but HR was lower and indexed SV higher in athletes. CI in CHF patients (2.3 ± 0.6 l/min/m²) was lower compared to the healthy population (p < 0.001). There was a weak correlation between CI and EF in CHF patients (r² = 0.07, p < 0.001) but CI did not differ between patients with NYHA-classes I-II compared to III-IV (n = 97, p = 0.16) or patients with or without hospitalization in the previous year (n = 100, p = 0.72). In vitro phantom validation showed low bias (−0.8 ± 19.8 ml/s) and in vivo validation in 25 subjects also showed low bias (0.26 ± 0.61 l/min, QP/QS 1.04 ± 0.09) between pulmonary and aortic flow.

Conclusions

CI decreases in healthy subjects with age but does not differ between males and females. We found no difference in CI between athletes and healthy subjects at rest but CI was lower in patients with congestive heart failure. The presented values can be used as reference values for flow velocity mapping CMR.     

Comparison of cardiovascular magnetic resonance characteristics and clinical consequences in children and adolescents with isolated left ventricular non-compaction with and without late gadolinium enhancement

Background

Although cardiovascular magnetic resonance (CMR) is showing increasingly diagnostic potential in left ventricular non-compaction (LVNC), relatively little research relevant to CMR is conducted in children with LVNC. This study was performed to characterize and compare CMR features and clinical outcomes in children with LVNC with and without late gadolinium enhancement (LGE).

Methods

A cohort of 40 consecutive children (age, 13.7 ± 3.3 years; 29 boys and 11 girls) with isolated LVNC underwent a baseline CMR scan with subsequent clinical follow-up. Short-axis cine images were used to calculate left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), myocardial mass, ratio of non-compacted-to-compacted myocardial thickness (NC/C ratio), and number of non-compacted segments. The LGE images were analyzed to assess visually presence and patterns of LGE. The primary end point was a composite of cardiac death and heart transplantation.

Results

The LGE was present in 10 (25 %) children, and 46 (27 %) segments were involved, including 23 non-compacted segments and 23 normal segments. Compared with LGE- cohort, LGE+ cohort had significantly lower LVEF (23.8 ± 10.7 % vs. 42.9 ± 16.7 %, p < 0.001) and greater LVEDV (169.2 ± 65.1 vs. 118.2 ± 48.9 mL/m², p = 0.010), LVESV (131.3 ± 55.5 vs. 73.3 ± 46.7 mL/m², p = 0.002), and sphericity indices (0.75 ± 0.19 vs. 0.60 ± 0.20, p = 0.045). There were no differences in terms of number and distribution of non-compacted segments, NC/C ratio, and myocardial mass index between LGE+ and LGE- cohort. In the LGE+ cohort, adverse events occurred in 6 patients compared to 2 events in the LGE- cohort. Kaplan-Meier analysis showed a significant difference in outcome between LGE+ and LGE- cohort for cardiac death and heart transplantation (p = 0.011).

Conclusions

The LGE was present in up to one-fourth of children with LVNC, and the LGE+ children exhibited a more maladaptive LV remodeling and a higher incidence of cardiovascular death and heart transplantation.     

Quantitative CMR markers of impaired vascular reactivity associated with age and peripheral artery disease

Background

The aim of this study was to develop and evaluate an integrated CMR method incorporating dynamic oximetry, blood flow and pulse-wave velocimetry to assess vascular reactivity in patients with peripheral artery disease (PAD) and healthy controls.

Methods and results

The study population consisted of young healthy subjects (YH, 30 ± 7 yrs, N = 19),PAD (71 ± 9 yrs, N = 38), and older healthy controls (OHC, 68 ± 9 yrs, N = 43). Peripheral vascular reactivity was evaluated with two methods, time-resolved quantification of blood flow velocity and oxygenation level in the femoral artery and vein, respectively, performed simultaneously both at rest and hyperemia. Aortic stiffness was assessed via pulse-wave velocity. Oximetric data showed that compared to OHC, the time-course of the hemoglobin oxygen saturation in PAD patients had longer washout time (28.6 ± 1.2 vs 16.9 ± 1.1 s, p < 0.0001), reduced upslope (0.60 ± 0.1 vs 1.3 ± 0.08 HbO₂/sec, p < 0.0001) and lower overshoot (8 ± 1.4 vs 14 ± 1.2 HbO₂, p = 0.0064). PAD patients also had longer-lasting antegrade femoral artery flow during hyperemia (51 ± 2.1 vs 24 ± 1.8 s, p < 0.0001), and reduced peak-to-baseline flow rate (3.1 ± 0.5 vs 7.4 ± 0.4, p < 0.0001). Further, the pulsatility at rest was reduced (0.75 ± 0.32 vs 5.2 ± 0.3, p < 0.0001), and aortic PWV was elevated (10.2 ± 0.4 vs 8.1 ± 0.4 m/s, p = 0.0048).

Conclusion

The proposed CMR protocol quantifies multiple aspects of vascular reactivity and represents an initial step toward development of a potential tool for evaluating interventions, extrapolating clinical outcomes and predicting functional endpoints based on quantitative parameters.     

In-vivo T1 cardiovascular magnetic resonance study of diffuse myocardial fibrosis in hypertrophic cardiomyopathy

Background

In hypertrophic cardiomyopathy (HCM), autopsy studies revealed both increased focal and diffuse deposition of collagen fibers. Late gadolinium enhancement imaging (LGE) detects focal fibrosis, but is unable to depict interstitial fibrosis. We hypothesized that with T1 mapping, which is employed to determine the myocardial extracellular volume fraction (ECV), can detect diffuse interstitial fibrosis in HCM patients.

Methods

T1 mapping with a modified Look-Locker Inversion Recovery (MOLLI) pulse sequence was used to calculate ECV in manifest HCM (n = 16) patients and in healthy controls (n = 14). ECV was determined in areas where focal fibrosis was excluded with LGE.

Results

The total group of HCM patients showed no significant changes in mean ECV values with respect to controls (0.26 ± 0.03 vs 0.26 ± 0.02, p = 0.83). Besides, ECV in LGE positive HCM patients was comparable with LGE negative HCM patients (0.27 ± 0.03 vs 0.25 ± 0.03, p = 0.12).

Conclusions

This study showed that HCM patients have a similar ECV (e.g. interstitial fibrosis) in myocardium without LGE as healthy controls. Therefore, the additional clinical value of T1 mapping in HCM seems limited, but future larger studies are needed to establish the clinical and prognostic potential of this new technique within HCM.     

Evaluation of left ventricular diastolic function by fractional area change using cine cardiovascular magnetic resonance: a feasibility study

Background

Evaluation of left ventricular (LV) diastolic function is essential for the management of heart failure. We verified whether LV diastolic function could be evaluated by measuring the fractional area change (FAC) using cine cardiovascular magnetic resonance (CMR).

Methods

We collected clinical data from 59 patients who underwent echocardiography and cine CMR. Normal, impaired relaxation, pseudonormal, and restrictive LV filling were observed in 15, 28, 11, and 5 patients, respectively. We calculated FAC during the first 30% of diastole (diastolic-index%) in the short-axis view, by tracing the contours on only three MR cine images.

Results

The diastolic index was significantly lower (p < 0.0001) in patients with impaired relaxation (32.4 ± 7.5), pseudonormal filling (25.4 ± 5.6), and restrictive filling (9.5 ± 1.5) compared to those with normal diastolic function (67.7 ± 10.8), and the index decreased significantly with worsening of diastolic dysfunction. The diastolic index correlated positively with early diastolic mitral annular velocity measured by tissue Doppler imaging (r = 0.75, p < 0.0001), respectively.

Conclusions

Measurement of FAC can be useful for the evaluation of LV diastolic function using cine CMR.