Mikael Kanski

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.

BackgroundThree-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.MethodsThe 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.ResultsGood 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).ConclusionsThe 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.

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

BackgroundPolymorphonuclear 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.MethodsIn 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.ResultsADC-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.ConclusionsADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

Contrast-Enhanced CMR Overestimates Early Myocardial Infarct Size: Mechanistic Insights Using ECV Measurements on Day 1 and Day 7.

OBJECTIVES This study aimed to investigate whether an overestimation of infarct size on cardiac magnetic resonance (CMR) versus triphenyltetrazolium chloride (TTC) exists acutely and whether it remains after 7 days in an experimental pig model and to elucidate possible mechanisms. BACKGROUND Overestimation of infarct size (IS) on late gadolinium enhancement CMR early after acute myocardial infarction has been debated. METHODS Pigs were subjected to 40 min of left anterior descending artery occlusion and 6 h (n = 9) or 7 days (n = 9) reperfusion. IS by in vivo and ex vivo CMR was compared with TTC staining. Extracellular volume (ECV) was obtained from biopsies using technetium 99m diethylenetriamine pentaacetic acid (99mTc-DTPA) and light microscopy. TTC slices were rescanned on CMR enabling slice-by-slice comparison. RESULTS IS did not differ between in vivo and ex vivo CMR (p = 0.77). IS was overestimated by 27.3% with ex vivo CMR compared with TTC (p = 0.008) acutely with no significant difference at 7 days (p = 0.39). Slice-by-slice comparison showed similar results. A significant decrease in ECV was seen in biopsies of myocardium at risk (MaR) close to the infarct (sometimes referred to as the peri-infarction zone) over 7 days (48.3 ± 4.4% vs. 29.2 ± 2.4%; p = 0.0025). The ECV differed between biopsies of MaR close to the infarct and the rest of the salvaged MaR acutely (48.3 ± 4.4% vs. 32.4 ± 3.2%; p = 0.013) but not at 7 days (29.2 ± 2.4% vs 25.7 ± 1.4%; p = 0.23). CONCLUSIONS CMR overestimates IS compared with TTC acutely but not at 7 days. This difference may be explained by higher ECV in MaR closest to the infarct acutely that decreases during 7 days to the same level as the rest of the salvaged MaR. The increased ECV in the MaR closest to the infarct day 1 could be due to severe edema or an admixture of infarcted and salvaged myocardium (partial volume) or both. Nonetheless, this could not be reproduced at 7 days. These results have implications for timing of magnetic resonance infarct imaging early after acute myocardial infarction.

Original ResearchContrast-Enhanced CMR Overestimates Early Myocardial Infarct Size: Mechanistic Insights Using ECV Measurements on Day 1 and Day 7

OBJECTIVES This study aimed to investigate whether an overestimation of infarct size on cardiac magnetic resonance (CMR) versus triphenyltetrazolium chloride (TTC) exists acutely and whether it remains after 7 days in an experimental pig model and to elucidate possible mechanisms. BACKGROUND Overestimation of infarct size (IS) on late gadolinium enhancement CMR early after acute myocardial infarction has been debated. METHODS Pigs were subjected to 40 min of left anterior descending artery occlusion and 6 h (n = 9) or 7 days (n = 9) reperfusion. IS by in vivo and ex vivo CMR was compared with TTC staining. Extracellular volume (ECV) was obtained from biopsies using technetium 99m diethylenetriamine pentaacetic acid (99mTc-DTPA) and light microscopy. TTC slices were rescanned on CMR enabling slice-by-slice comparison. RESULTS IS did not differ between in vivo and ex vivo CMR (p = 0.77). IS was overestimated by 27.3% with ex vivo CMR compared with TTC (p = 0.008) acutely with no significant difference at 7 days (p = 0.39). Slice-by-slice comparison showed similar results. A significant decrease in ECV was seen in biopsies of myocardium at risk (MaR) close to the infarct (sometimes referred to as the peri-infarction zone) over 7 days (48.3 ± 4.4% vs. 29.2 ± 2.4%; p = 0.0025). The ECV differed between biopsies of MaR close to the infarct and the rest of the salvaged MaR acutely (48.3 ± 4.4% vs. 32.4 ± 3.2%; p = 0.013) but not at 7 days (29.2 ± 2.4% vs 25.7 ± 1.4%; p = 0.23). CONCLUSIONS CMR overestimates IS compared with TTC acutely but not at 7 days. This difference may be explained by higher ECV in MaR closest to the infarct acutely that decreases during 7 days to the same level as the rest of the salvaged MaR. The increased ECV in the MaR closest to the infarct day 1 could be due to severe edema or an admixture of infarcted and salvaged myocardium (partial volume) or both. Nonetheless, this could not be reproduced at 7 days. These results have implications for timing of magnetic resonance infarct imaging early after acute myocardial infarction.

Apyrase treatment of myocardial infarction according to a clinically applicable protocol fails to reduce myocardial injury in a porcine model

BackgroundEctonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.MethodsA percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI.ResultsNo differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.ConclusionApyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.

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.

Myocardium at risk can be determined by ex vivo T2-weighted magnetic resonance imaging even in the presence of gadolinium: comparison to myocardial perfusion single photon emission computed tomography

AIMS Determination of the myocardium at risk (MaR) and final infarct size by cardiac magnetic resonance imaging (CMR) enables calculation of salvaged myocardium in acute infarction. T2-weighted imaging is performed prior to the administration of gadolinium, since gadolinium affects T2 tissue properties. This is, however, difficult in an ex vivo model since gadolinium must be administered for determination of infarct size by CMR. We aimed to test the ability of ex vivo T2-weighted imaging to assess MaR using myocardial perfusion single photon emission computed tomography (SPECT) as reference and to investigate whether MaR could be assessed by ex vivo T2-weighted imaging after injection of gadolinium. Materials and methods In 18 domestic pigs, the left anterior descending artery was occluded for either 30 or 40 min, followed by 4 h of reperfusion. After explantation of the hearts, myocardial perfusion SPECT and T2-weighted imaging were performed for determination of MaR, either with or without gadolinium. Infarct size was determined by T1-weighted imaging and by triphenyl tetrazolium chloride (TTC) staining. RESULTS T2-weighted imaging agreed with myocardial perfusion SPECT, both with and without gadolinium (r(2)= 0.70, P < 0.01) with a bias of 2.6 ± 5.1% (P = 0.04). Infarct size was 15.4 ± 5.3 and 22.1 ± 5.6% with TTC and T1-weighted imaging, respectively (P = 0.008) in nine pigs who had both infarct measures. CONCLUSION T2-weighted CMR imaging can be used to determine MaR in an ex vivo experimental model, both with and without the presence of gadolinium. Thus, CMR alone can be used to assess 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.

Vortex ring mixing in the left ventricle of the human heart.

Background During rapid filling of the left ventricle, a vortex ring forms downstream from the mitral valve. Previous experiments in water tanks have shown that vortex ring formation is an optimized method for fluid transport. The rotation of the vortex ring leads to mixing of the inflowing blood and blood that was already in the ventricle (Figure 1). In water tanks, the amount of mixing decreases with increasing vortex formation ratio (VFR), a dimensionless parameter relating inflowing volume to the annulus diameter (Figure 2). However, the flow and anatomy of the left ventricle is more complex which may affect this established relationship. Therefore, we aimed to investigate if the relationship between VFR and mixing ratio demonstrated in water tank experiments holds in the human heart.

Diastolic vortex ring formation in the human left ventricle: quantitative analysis using Lagrangian coherent structures and 4D cardiovascular magnetic resonance velocity mapping

Summary We show that 4D magnetic resonance velocity mapping and Lagrangian Coherent Structures can be used to quantify vortex ring volume in the human left ventricle. Background The vortex ring formed in the left ventricle (LV) of the human heart during early diastolic inflow (corresponding to the Doppler E-wave) contains information about the normal and pathophysiologic aspects of diastole. Previous studies suggest that the volume of the vortex ring is an important characteristic of vortex ring formation. However, due to lack of quantitative methods, vortex ring volume has not previously been studied in the human left ventricle. The study of Lagrangian Coherent Structures (LCS) is a new flow analysis method, which for the first time enables a description of vortex ring shape and the quantification of vortex ring volume. LCS have not previously been used to quantify diastolic vortex volume in humans. Therefore, the purpose of this study was to investigate if LCS and three-dimensional, time-resolved, three-directional phase contrast magnetic resonance velocity mapping (4D PC-MR) can be used to describe vortex ring shape and quantify vortex ring volume in the human LV. Methods