Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

Regional contributions to left ventricular stroke volume determined by cardiac magnetic resonance imaging in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) restores ventricular synchrony and induces left ventricular (LV) reverse remodeling in patients with heart failure (HF) and dyssynchrony. However, 30% of treated patients are non-responders despite all efforts. Cardiac magnetic resonance imaging (CMR) can be used to quantify regional contributions to stroke volume (SV) as potential CRT predictors. The aim of this study was to determine if LV longitudinal (SVlong%), lateral (SVlat%), and septal (SVsept%) contributions to SV differ from healthy controls and investigate if these parameters can predict CRT response. METHODS: Sixty-five patients (19 women, 67 ± 9 years) with symptomatic HF (LVEF ≤ 35%) and broadened QRS (≥ 120 ms) underwent CMR. SVlong% was calculated as the volume encompassed by the atrioventricular plane displacement (AVPD) from end diastole (ED) to end systole (ES) divided by total SV. SVlat%, and SVsept% were calculated as the volume encompassed by radial contraction from ED to ES. Twenty age- and sex-matched healthy volunteers were used as controls. The regional measures were compared to outcome response defined as ≥ 15% decrease in echocardiographic LV end-systolic volume (LVESV) from pre- to 6-months post CRT (delta, Δ). RESULTS: AVPD and SVlong% were lower in patients compared to controls (8.3 ± 3.2 mm vs 15.3 ± 1.6 mm, P < 0.001; and 53 ± 18% vs 64 ± 8%, P < 0.01). SVsept% was lower (0 ± 15% vs 10 ± 4%, P < 0.01) with a higher SVlat% in the patient group (42 ± 16% vs 29 ± 7%, P < 0.01). There were no differences between responders and non-responders in neither SVlong% (P = 0.87), SVlat% (P = 0.09), nor SVsept% (P = 0.65). In patients with septal net motion towards the right ventricle (n = 28) ΔLVESV was - 18 ± 22% and with septal net motion towards the LV (n = 37) ΔLVESV was - 19 ± 23% (P = 0.96). CONCLUSIONS: Longitudinal function, expressed as AVPD and longitudinal contribution to SV, is decreased in patients with HF scheduled for CRT. A larger lateral contribution to SV compensates for the abnormal septal systolic net movement. However, LV reverse remodeling could not be predicted by these regional contributors to SV.

Measuring extracellular volume fraction by MRI: First verification of values given by clinical sequences.

PURPOSE: To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1-mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers. METHODS: Between May 2016 and March 2017, 8 volunteers (25 ± 4 years, 3 female) and 8 pigs (4 female) underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method. RESULTS: In pigs, ECV in normal myocardium was not different between radioisotope (average ± standard deviation; 19 ± 2%) and SASHA (21 ± 2%; P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope (P ≤ 0.001 for all). ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA (22 ± 3%; P = 0.022 and P = 0.033). No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs (0.08% and 0.07%/min; P = 0.004 and P = 0.013) and by MOLLI5s(3s)3s for volunteers (0.07%/min; P = 0.032) but did not increase as measured by SASHA. CONCLUSION: Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI-sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence.

Analysis of three-chamber view conventional and tagged cine MRI in patients with suspected hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the potential value of adding a tagged three-chamber (3Ch) cine to clinical hypertrophic cardiomyopathy (HCM) magnetic resonance imaging (MRI) protocols, including to help distinguish HCM patients with regionally impaired cardiac function. METHODS: Forty-eight HCM patients, five patients with "septal knuckle" (SK), and 20 healthy volunteers underwent MRI at 1.5T; a tagged 3Ch cine was added to the protocol. Regional strain, myocardial wall thickness, and mitral valve leaflet lengths were measured in the 3Ch view. RESULTS: In HCM, we found a reduced tangential strain with decreased diastolic relaxation in both hypertrophied (p = 0.003) and remote segments (p = 0.035). Strain in the basal septum correlated with the length of the coaptation zone + residual leaflet (r = 0.48, p < 0.001). In the basal free wall, patients with SK had faster relaxation compared to HCM patients with septal hypertrophy. DISCUSSION: The 3Ch tagged MRI sequence provides useful information for the examination of suspected HCM patients, with minimal additional time cost. Local wall function is closely associated with morphological changes of the mitral apparatus measured in the same plane and may provide insights into mechanisms of obstruction. The additional strain information may be helpful when analyzing local myocardial wall motion patterns in the presence of SK.

Validation and reproducibility of cardiovascular 4D-flow MRI from two vendors using 2 × 2 parallel imaging acceleration in pulsatile flow phantom and in vivo with and without respiratory gating.

BACKGROUND: 4D-flow magnetic resonance imaging (MRI) is increasingly used. PURPOSE: To validate 4D-flow sequences in phantom and in vivo, comparing volume flow and kinetic energy (KE) head-to-head, with and without respiratory gating. MATERIAL AND METHODS: Achieva dStream (Philips Healthcare) and MAGNETOM Aera (Siemens Healthcare) 1.5-T scanners were used. Phantom validation measured pulsatile, three-dimensional flow with 4D-flow MRI and laser particle imaging velocimetry (PIV) as reference standard. Ten healthy participants underwent three cardiac MRI examinations each, consisting of cine-imaging, 2D-flow (aorta, pulmonary artery), and 2 × 2 accelerated 4D-flow with (Resp+) and without (Resp-) respiratory gating. Examinations were acquired consecutively on both scanners and one examination repeated within two weeks. Volume flow in the great vessels was compared between 2D- and 4D-flow. KE were calculated for all time phases and voxels in the left ventricle. RESULTS: Phantom results showed high accuracy and precision for both scanners. In vivo, higher accuracy and precision ( P < 0.001) was found for volume flow for the Aera prototype with Resp+ (-3.7 ± 10.4 mL, r = 0.89) compared to the Achieva product sequence (-17.8 ± 18.6 mL, r = 0.56). 4D-flow Resp- on Aera had somewhat larger bias (-9.3 ± 9.6 mL, r = 0.90) compared to Resp+ ( P = 0.005). KE measurements showed larger differences between scanners on the same day compared to the same scanner at different days. CONCLUSION: Sequence-specific in vivo validation of 4D-flow is needed before clinical use. 4D-flow with the Aera prototype sequence with a clinically acceptable acquisition time (<10 min) showed acceptable bias in healthy controls to be considered for clinical use. Intra-individual KE comparisons should use the same sequence.

Importance of standardizing timing of hematocrit measurement when using cardiovascular magnetic resonance to calculate myocardial extracellular volume (ECV) based on pre- and post-contrast T1 mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can be used to calculate myocardial extracellular volume fraction (ECV) by relating the longitudinal relaxation rate in blood and myocardium before and after contrast-injection to hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which could affect the calculations of ECV. The aim of this study was to test the hypothesis that there is a significant increase in calculated ECV values if the Hct is sampled after the CMR examination in supine position compared to when the patient arrives at the MR department. METHODS: Forty-three consecutive patients including various pathologies as well as normal findings were included in the study. Venous blood samples were drawn upon arrival to the MR department and directly after the examination with the patient remaining in supine position. A Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid-ventricular short-axis images before and after contrast injection from which motion-corrected T1 maps were derived and ECV was calculated. RESULTS: Hematocrit decreased from 44.0 ± 3.7% before to 40.6 ± 4.0% after the CMR examination (p < 0.001). This resulted in a change in calculated ECV from 24.7 ± 3.8% before to 26.2 ± 4.2% after the CMR examination (p < 0.001). All patients decreased in Hct after the CMR examination compared to before except for two patients whose Hct remained the same. CONCLUSION: Variability in CMR-derived myocardial ECV can be reduced by standardizing the timing of Hct measurement relative to the CMR examination. Thus, a standardized acquisition of blood sample for Hct after the CMR examination, when the patient is still in supine position, would increase the precision of ECV measurements.

Decreased global myocardial perfusion at adenosine stress as a potential new biomarker for microvascular disease in systemic sclerosis: a magnetic resonance study.

BACKGROUND: Patients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine if patients with SSc have lower global myocardial perfusion (MP) at rest or during adenosine stress, compared to healthy controls, quantified with CMR. METHODS: Nineteen SSc patients (17 females, 61 ± 10 years) and 22 controls (10 females, 62 ± 11 years) underwent CMR. Twelve patients had limited cutaneous SSc and 7 patients had diffuse cutaneous SSc. One patient had pulmonary arterial hypertension (PAH). MP was quantified using coronary sinus flow (CSF) measurements at rest and during adenosine stress, divided by left ventricular mass (LVM). RESULTS: There was no difference in MP at rest between patients and controls (1.1 ± 0.5 vs. 1.1 ± 0.3 ml/min/g, P = 0.85) whereas SSc patients showed statistically significantly lower MP during adenosine stress (3.1 ± 0.9 vs. 4.2 ± 1.3 ml/min/g, P = 0.008). Three out of the 19 SSc patients showed fibrosis in the right ventricle insertion points despite absence of PAH. None had signs of myocardial infarction. CONCLUSIONS: Patients with SSc have decreased MP during adenosine stress compared to healthy controls. Thus hypoperfusion at stress may be a sensitive marker of cardiac disease in SSc patients possibly signifying microvascular myocardial disease.

Experimental validation of contrast-enhanced SSFP cine CMR for quantification of myocardium at risk in acute myocardial infarction.

BACKGROUND: Accurate assessment of myocardium at risk (MaR) after acute myocardial infarction (AMI) is necessary when assessing myocardial salvage. Contrast-enhanced steady-state free precession (CE-SSFP) is a recently developed cardiovascular magnetic resonance (CMR) method for assessment of MaR up to 1 week after AMI. Our aim was to validate CE-SSFP for determination of MaR in an experimental porcine model using myocardial perfusion single-photon emission computed tomography (MPS) as a reference standard and to test the stability of MaR-quantification over time after injecting gadolinium-based contrast. METHODS: Eleven pigs were subjected to either 35 or 40 min occlusion of the left anterior descending artery followed by six hours of reperfusion. A technetium-based perfusion tracer was administered intravenously ten minutes before reperfusion. In-vivo and ex-vivo CE-SSFP CMR was performed followed by ex-vivo MPS imaging. MaR was expressed as % of left ventricular mass (LVM). RESULTS: There was good agreement between MaR by ex-vivo CMR and MaR by MPS (bias: 1 ± 3% LVM, r 2 = 0.92, p < 0.001), between ex-vivo and in-vivo CMR (bias 0 ± 2% LVM, r 2 = 0.94, p < 0.001) and between in-vivo CMR and MPS (bias -2 ± 3% LVM, r 2 = 0.87, p < 0.001. No change in MaR was seen over the first 30 min after contrast injection (p = 0.95). CONCLUSIONS: Contrast-enhanced SSFP cine CMR can be used to measure MaR, both in vivo and ex vivo, in a porcine model with good accuracy and precision over the first 30 min after contrast injection. This offers the option to use the less complex ex-vivo imaging when determining myocardial salvage in experimental studies.

Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure.

PURPOSE: To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure. MATERIALS AND METHODS: 4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow ). The volume mixed into the vortex-ring was quantified as VVmix-in = VV-VVinflow . The mixing ratio was defined as MXR = VVmix-in /VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in /ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV). RESULTS: PLIF validation of MXR showed fair agreement (R(2) = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P < 0.001), while VVmix-in /ESV and VV/DV were lower in patients (10 ± 6% vs. 18 ± 12%, P < 0.01 and 25 ± 8% vs. 50 ± 6%, P < 0.0001). CONCLUSION: Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386-1397.

Left ventricular fluid kinetic energy time curves in heart failure from cardiovascular magnetic resonance 4D flow data.

BACKGROUND: Measurement of intracardiac kinetic energy (KE) provides new insights into cardiac hemodynamics and may improve assessment and understanding of heart failure. We therefore aimed to investigate left ventricular (LV) KE time curves in patients with heart failure and in controls. METHODS: Patients with heart failure (n = 29, NYHA class I-IV) and controls (n = 12) underwent cardiovascular magnetic resonance (CMR) including 4D flow. The vortex-ring boundary was computed using Lagrangian coherent structures. The LV endocardium and vortex-ring were manually delineated and KE was calculated as ½mv(2) of the blood within the whole LV and the vortex ring, respectively. RESULTS: The systolic average KE was higher in patients compared to controls (2.2 ± 1.4 mJ vs 1.6 ± 0.6 mJ, p = 0.048), but lower when indexing to EDV (6.3 ± 2.2 µJ/ml vs 8.0 ± 2.1 µJ/ml, p = 0.025). No difference was seen in diastolic average KE (3.2 ± 2.3 mJ vs 2.0 ± 0.8 mJ, p = 0.13) even when indexing to EDV (9.0 ± 4.4 µJ/ml vs 10.2 ± 3.3 µJ/ml, p = 0.41). In patients, a smaller fraction of diastolic average KE was observed inside the vortex ring compared to controls (72 ± 6% vs 54 ± 9%, p < 0.0001). Three distinctive KE time curves were seen in patients which were markedly different from findings in controls, and with a moderate agreement between KE time curve patterns and degree of diastolic dysfunction (Cohen's kappa = 0.49), but unrelated to NYHA classification (p = 0.12), or 6-minute walk test (p = 0.72). CONCLUSION: Patients with heart failure exhibit higher systolic average KE compared to controls, suggesting altered intracardiac blood flow. The different KE time curves seen in patients may represent a conceptually new approach for heart failure classification.

Whole-heart four-dimensional flow can be acquired with preserved quality without respiratory gating, facilitating clinical use: a head-to-head comparison.

BACKGROUND: Respiratory gating is often used in 4D-flow acquisition to reduce motion artifacts. However, gating increases scan time. The aim of this study was to investigate if respiratory gating can be excluded from 4D flow acquisitions without affecting quantitative intracardiac parameters. METHODS: Eight volunteers underwent CMR at 1.5 T with a 5-channel coil (5ch). Imaging included 2D flow measurements and whole-heart 4D flow with and without respiratory gating (Resp(+), Resp(-)). Stroke volume (SV), particle-trace volumes, kinetic energy, and vortex-ring volume were obtained from 4D flow-data. These parameters were compared between 5ch Resp(+) and 5ch Resp(-). In addition, 20 patients with heart failure were scanned using a 32-channel coil (32ch), and particle-trace volumes were compared to planimetric SV. Paired comparisons were performed using Wilcoxon's test and correlation analysis using Pearson r. Agreement was assessed as bias±SD. RESULTS: Stroke volume from 4D flow was lower compared to 2D flow both with and without respiratory gating (5ch Resp(+) 88±18 vs 97±24.0, p=0.001; 5ch Resp(-) 86±16 vs 97.1±22.7, p<0.01). There was a good correlation between Resp(+) and Resp(-) for particle-trace derived volumes (R2=0.82, 0.2±9.4 ml), mean kinetic energy (R2=0.86, 0.07±0.21 mJ), peak kinetic energy (R2=0.88, 0.14±0.77 mJ), and vortex-ring volume (R2=0.70, -2.5±9.4 ml). Furthermore, good correlation was found between particle-trace volume and planimetric SV in patients for 32ch Resp(-) (R2=0.62, -4.2±17.6 ml) and in healthy volunteers for 5ch Resp(+) (R2=0.89, -11±7 ml), and 5ch Resp(-) (R2=0.93, -7.5±5.4 ml), Average scan duration for Resp(-) was shorter compared to Resp(+) (27±9 min vs 61±19 min, p<0.05). CONCLUSIONS: Whole-heart 4D flow can be acquired with preserved quantitative results without respiratory gating, facilitating clinical use.

Cardiac MRI of characteristic motion findings in right bundle branch block.

While there have been many descriptions of characteristic motion findings in left bundle branch block (LBBB), there are few published descriptions of such findings in right bundle branch block (RBBB). The purpose of this study was to assess the frequency of particular regional motion findings in cardiac magnetic resonance imaging (CMR) studies of patients with RBBB, compared with normal subjects. We focused on three distinctive motion patterns that can be seen in RBBB during early systole: delayed apex-ward motion of the RV base, "reverse septal flash", and "basal bulge". The presence and relative magnitude of these findings were independently scored by four experienced observers, in 3-chamber and 4-chamber CMR cines, for both normal subjects and patients with RBBB. These motion patterns were found to be strongly associated with the presence of RBBB. While only moderately sensitive, they were quite specific for RBBB, when present. In particular, with ROC analysis, a combined feature set of the findings in the 4-chamber view had an area under the curve of 0.81.This previously undescribed set of RBBB-associated early-systolic regional motion features (delayed apex-ward motion of the RV base, "reverse septal flash", and "basal bulge") is strongly suggestive of RBBB when present, particularly in the 4-chamber view. Although here evaluated with CMR, it is also likely to be associated with RBBB when seen with other cardiac imaging modalities.

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 (DLCO) (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 DLCO, 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.

Infarct quantification using 3D inversion recovery and 2D phase sensitive inversion recovery; validation in patients and ex vivo.

BACKGROUND: Cardiovascular-MR (CMR) is the gold standard for quantifying myocardial infarction using late gadolinium enhancement (LGE) technique. Both 2D- and 3D-LGE-sequences are used in clinical practise and in clinical and experimental studies for infarct quantification. Therefore the aim of this study was to investigate if image acquisitions with 2D- and 3D-LGE show the same infarct size in patients and ex vivo. METHODS: Twenty-six patients with previous myocardial infarction who underwent a CMR scan were included. Images were acquired 10-20 minutes after an injection of 0.2 mmol/kg gadolinium-based contrast agent. Two LGE-sequences, 3D-inversion recovery (IR) and 2D-phase-sensitive (PS) IR, were used in all patients to quantify infarction size. Furthermore, six pigs with reperfused infarction in the left anterior descending artery (40 minutes occlusion and 4 hours of reperfusion) were scanned with 2D- and 3D-LGE ex vivo. A high resolution T1-sequence was used as reference for the infarct quantification ex vivo. Spearman's rank-order correlation, Wilcoxon matched pairs test and bias according to Bland-Altman was used for comparison of infarct size with different LGE-sequences. RESULTS: There was no significant difference between the 2D- and 3D-LGE sequence in left ventricular mass (LVM) (2D: 115 ± 25 g; 3D: 117 ± 24 g: p = 0.35). Infarct size in vivo using 2D- and 3D-LGE showed high correlation and low bias for both LGE-sequences both in absolute volume of infarct (r = 0.97, bias 0.47 ± 2.1 ml) and infarct size as part of LVM (r = 0.94, bias 0.16 ± 2.0%). The 2D- and 3D-LGE-sequences ex vivo correlated well (r = 0.93, bias 0.67 ± 2.4%) for infarct size as part of the LVM. The IR LGE-sequences overestimated infarct size as part of the LVM ex vivo compared to the high resolution T1-sequence (bias 6.7 ± 3.0%, 7.3 ± 2.7% for 2D-PSIR and 3D-IR respectively, p < 0.05 for both). CONCLUSIONS: Infarct quantification with 2D- and 3D-LGE gives similar results in vivo with a very low bias. IR LGE-sequences optimized for in vivo use yield an overestimation of infarct size when used ex vivo.

SequenceMorph: A Unified Unsupervised Learning Framework for Motion Tracking on Cardiac Image Sequences.

Modern medical imaging techniques, such as ultrasound (US) and cardiac magnetic resonance (MR) imaging, have enabled the evaluation of myocardial deformation directly from an image sequence. While many traditional cardiac motion tracking methods have been developed for the automated estimation of the myocardial wall deformation, they are not widely used in clinical diagnosis, due to their lack of accuracy and efficiency. In this paper, we propose a novel deep learning-based fully unsupervised method, SequenceMorph, for in vivo motion tracking in cardiac image sequences. In our method, we introduce the concept of motion decomposition and recomposition. We first estimate the inter-frame (INF) motion field between any two consecutive frames, by a bi-directional generative diffeomorphic registration neural network. Using this result, we then estimate the Lagrangian motion field between the reference frame and any other frame, through a differentiable composition layer. Our framework can be extended to incorporate another registration network, to further reduce the accumulated errors introduced in the INF motion tracking step, and to refine the Lagrangian motion estimation. By utilizing temporal information to perform reasonable estimations of spatio-temporal motion fields, this novel method provides a useful solution for image sequence motion tracking. Our method has been applied to US (echocardiographic) and cardiac MR (untagged and tagged cine) image sequences; the results show that SequenceMorph is significantly superior to conventional motion tracking methods, in terms of the cardiac motion tracking accuracy and inference efficiency.

Optimal timing of hypothermia in relation to myocardial reperfusion.

Two previous clinical trials investigating hypothermia as an adjunct therapy for myocardial infarction have failed. Recently a pilot study has demonstrated a significant reduction in infarct size. The aims of this study were to elucidate the effects of hypothermia on reperfusion injury and to investigate the optimal hypothermia protocol for a future clinical trial. Pigs (40-50 kg) were anesthetized and a normal pig temperature of 38°C was established utilizing an endovascular temperature modulating catheter. The pigs were randomized to a combination hypothermia group (1,000 ml of 4°C saline solution and endovascular cooling, n = 8), or to normothermic controls (n = 8). A PCI balloon was then inflated in the LAD for 40 min (control) or 45 min with hypothermia induced during the last 5 min. Furthermore, hypothermia induced by cold saline alone (n = 8), and prolonged combination hypothermia during reperfusion (n = 7) were also examined. Infarct size and area at risk were determined ex vivo after 4 h of reperfusion using gadolinium-enhanced MRI and Tc-99-tetrofosmin SPECT, respectively. All pigs in the combination hypothermia group were cooled to <35°C within 5 min. Combination hypothermia reduced IS/AAR by 18% compared with normothermic controls despite 5 min longer ischemic time (61 ± 5 vs. 74 ± 4%, p = 0.03). Cold saline did not reduce IS/AAR. Prolonging hypothermia treatment after onset of reperfusion by an additional 45 min over that used in a previous paper did not confer any additional benefit. The cardioprotective effects of hypothermia treatment are due to an attenuation of myocardial injury during both ischemia and reperfusion. The results suggest that a hypothermia protocol using a cold saline infusion and endovascular cooling enables hypothermia to be induced in a clinical setting without delaying reperfusion therapy.

Quantification and visualization of cardiovascular 4D velocity mapping accelerated with parallel imaging or k-t BLAST: head to head comparison and validation at 1.5 T and 3 T.

BACKGROUND: Three-dimensional time-resolved (4D) phase-contrast (PC) CMR can visualize and quantify cardiovascular flow but is hampered by long acquisition times. Acceleration with SENSE or k-t BLAST are two possibilities but results on validation are lacking, especially at 3 T. The aim of this study was therefore to validate quantitative in vivo cardiac 4D-acquisitions accelerated with parallel imaging and k-t BLAST at 1.5 T and 3 T with 2D-flow as the reference and to investigate if field strengths and type of acceleration have major effects on intracardiac flow visualization. METHODS: The local ethical committee approved the study. 13 healthy volunteers were scanned at both 1.5 T and 3 T in random order with 2D-flow of the aorta and main pulmonary artery and two 4D-flow sequences of the heart accelerated with SENSE and k-t BLAST respectively. 2D-image planes were reconstructed at the aortic and pulmonary outflow. Flow curves were calculated and peak flows and stroke volumes (SV) compared to the results from 2D-flow acquisitions. Intra-cardiac flow was visualized using particle tracing and image quality based on the flow patterns of the particles was graded using a four-point scale. RESULTS: Good accuracy of SV quantification was found using 3 T 4D-SENSE (r2 = 0.86, -0.7 ± 7.6%) and although a larger bias was found on 1.5 T (r2 = 0.71, -3.6 ± 14.8%), the difference was not significant (p = 0.46). Accuracy of 4D k-t BLAST for SV was lower (p < 0.01) on 1.5 T (r2 = 0.65, -15.6 ± 13.7%) compared to 3 T (r2 = 0.64, -4.6 ± 10.0%). Peak flow was lower with 4D-SENSE at both 3 T and 1.5 T compared to 2D-flow (p < 0.01) and even lower with 4D k-t BLAST at both scanners (p < 0.01). Intracardiac flow visualization did not differ between 1.5 T and 3 T (p = 0.09) or between 4D-SENSE or 4D k-t BLAST (p = 0.85). CONCLUSIONS: The present study showed that quantitative 4D flow accelerated with SENSE has good accuracy at 3 T and compares favourably to 1.5 T. 4D flow accelerated with k-t BLAST underestimate flow velocities and thereby yield too high bias for intra-cardiac quantitative in vivo use at the present time. For intra-cardiac 4D-flow visualization, however, 1.5 T and 3 T as well as SENSE or k-t BLAST can be used with similar quality.

ST-segment dynamics during reperfusion period and the size of myocardial injury in experimental myocardial infarction.

BACKGROUND: Exacerbation of ST elevation associated with reperfusion has been reported in patients with myocardial infarction. However, the cause of the "reperfusion peak" and relation of its magnitude to the size of myocardial damage has not been explored. The aim of our study was to assess the correlation between the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct size (IS). METHODS: Infarction was induced in 15 pigs by a 40-minute-long balloon inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was given intravenously after 20 minutes of occlusion, and ex vivo single photon emission computed tomography was performed to assess MaR. Maximal ST elevation in a single lead and maximal sum of ST deviations in 12 leads were measured before, during, and after occlusion from continuous 12-lead electrocardiographic monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes before explantation of the heart. Final IS was estimated using ex vivo cardiac magnetic resonance imaging. RESULTS: All pigs developed an anteroseptal infarct with MaR = 42% ± 9% and IS = 26% ± 7% of left ventricle. In all pigs, reperfusion was accompanied by transitory exacerbation of ST elevation that measured 1300 ± 500 µV as maximum in a single lead compared with 570 ± 220 µV at the end of occlusion (P < .001). The transitory exacerbation of ST elevation exceeded the maximal ST elevation during occlusion (920 ± 420 µV, P < .05). The ST elevation resolved by the end of the reperfusion period (90 ± 30 µV, P < .001). Exacerbation of ST elevation after reperfusion correlated with the final IS (r = 0.64, P = .025 for maximal ST elevation in a single lead and r = 0.80, P = .002 for sum of ST deviations) but not with MaR (r = 0.43, P = .17 for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST deviations). The maximal ST elevation in a single lead and the sum of ST deviations during occlusion did not correlate with either MaR or final IS. CONCLUSION: In the experiment, exacerbation of ST elevation is common during restoration of blood flow in the occluded coronary artery. The magnitude of the exacerbation of ST elevation after reperfusion in experimentally induced myocardial infarction in pigs is associated with infarct size but not with MaR.

Pulmonary blood volume variation decreases after myocardial infarction in pigs: a quantitative and noninvasive MR imaging measure of heart failure.

PURPOSE: To prospectively evaluate the usefulness of magnetic resonance (MR) imaging for estimating pulmonary blood volume (PBV) and the variation in PBV throughout the cardiac cycle in experimental heart failure. MATERIALS AND METHODS: The animal care committee approved this prospective study. Seven pigs were studied before and after myocardial infarction. PBV measurement was validated in a phantom and calculated as the product of cardiac output determined with velocity-encoded MR imaging and the pulmonary transit time for an intravenous bolus of contrast material to pass through the pulmonary circulation. The difference in arterial and venous pulmonary flow during the cardiac cycle was integrated for calculation of the PBV variation (expressed as percentage of stroke volume). Differences were evaluated with the Wilcoxon test. RESULTS: Calculated and direct phantom measurements of PBV differed by a mean of 4% +/- 3 (standard deviation) (R(2) = 0.97, P < .001). Infarction induced a decrease in left ventricular stroke volume (44 mL +/- 6 vs 27 mL +/- 7; P = .02), ejection fraction (55% +/- 5 vs 41% +/- 4; P = .02), and PBV variation (61% +/- 12 vs 43% +/- 15; P = .04) but not PBV (225 mL +/- 23 vs 211 mL +/- 42; P = .50). The mean pulmonary artery pressure increased after infarction (19 mm Hg +/- 6 vs 27 mm Hg +/- 4; P = .04). CONCLUSION: Following infarction, the PBV variation but not PBV decreased. PBV variation was the noninvasive measure exhibiting the greatest percentage of change following infarction. MR imaging can be used to assess the variation of the PBV during the cardiac cycle as a marker of heart failure.

Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model.

BACKGROUND: Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. METHODS: In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. RESULTS: ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. CONCLUSIONS: ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.