Right and left ventricle native T1 mapping in systolic phase in patients with congenital heart disease

Background T1 mapping is emerging as a powerful tool in cardiac magnetic resonance (CMR) to evaluate diffuse fibrosis. However, right ventricular (RV) T1 mapping proves difficult due to the limited wall thickness in diastolic phase. Several studies focused on systolic T1 mapping, albeit only on the left ventricle (LV). Purpose To estimate intra- and inter-observer variability of native T1 (nT1) mapping of the RV, and its correlations with biventricular and pulmonary function in patients with congenital heart disease (CHD). Material and Methods In this retrospective, observational, cross-sectional study we evaluated 36 patients with CHD, having undergone CMR on a 1.5-T scanner. LV and RV functional evaluations were performed. A native modified look-locker inversion recovery short-axis sequence was acquired in the systolic phase. Intra- and inter-reader reproducibility were reported as complement to 100% of the ratio between coefficient of reproducibility and mean. Spearman rho and Mann-Whitney U-test were used to compare distributions. Results Intra- and inter-reader reproducibility was 84% and 82%, respectively. Median nT1 was 1022 ms (interquartile range [IQR] 1108-972) for the RV and 947 ms (IQR 986-914) for the LV. Median RV-nT1 was 1016 ms (IQR 1090-1016) in patients with EDVI <= 100 mL/m(2) and 1100 ms (IQR 1113-1100) in patients with EDVI >100 mL/m(2) (P = 0.049). A significant negative correlation was found between RV ejection fraction and RV-nT1 (rho = -0.284, P = 0.046). Conclusion Systolic RV-nT1 showed a high reproducibility and a negative correlation with RV ejection fraction, potentially reflecting an adaptation of the RV myocardium to pulmonary valve/conduit (dys)-function

Variability and homogeneity of cardiovascular magnetic resonance myocardial T2-mapping in volunteers compared to patients with edema

BACKGROUND: The aim of the study was to test the reproducibility and variability of myocardial T2 mapping in relation to sequence type and spatial orientation in a large group of healthy volunteers. For control T2 mapping was also applied in patients with true edema. Cardiovascular magnetic resonance (CMR) T2-mapping has potential for the detection and quantification of myocardial edema. Clinical experience is limited so far. The variability and potential pitfalls in broad application are unknown. METHODS: Healthy volunteers (n = 73, 35 +/- 13 years) and patients with edema (n = 28, 55 +/- 17 years) underwent CMR at 1.5 T. Steady state free precession (SSFP) cine loops and T2-weighted spin echo images were obtained. In patients, additionally late gadolinium enhancement images were acquired. We obtained T2 maps in midventricular short axis (SAX) and four-chamber view (4CV) based on images with T2 preparation times of 0, 24, 55 ms and compared fast low angle shot (FLASH) and SSFP readout. 10 volunteers were scanned twice on separate days. Two observers analysed segmental and global T2 per slice. RESULTS: In volunteers global myocardial T2 systematically differed depending on image orientation and sequence (FLASH 52 +/- 5 vs. SSFP 55 +/- 5 ms in SAX and 57 +/- 6 vs. 59 +/- 6 ms in 4CV; p /= 70 ms. Mean intraobserver variability was 1.07 +/- 1.03 ms (r = 0.94); interobserver variability was 1.6 +/- 1.5 ms (r = 0.87). The coefficient of variation for repeated scans was 7.6% for SAX and 6.6% for 4CV. Mapping revealed focally increased T2 (73 +/- 9 vs. 51 +/- 3 ms in remote myocardium; p < 0.0001) in all patients with edema. CONCLUSIONS: Myocardial T2 mapping is technically feasible and highly reproducible. It can detect focal edema und differentiate it from normal myocardium. Increased T2 was found in some volunteers most likely due to partial volume and residual motion

Aortic valve stenotic area calculation from phase contrast cardiovascular magnetic resonance: the importance of short echo time

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) can potentially quantify aortic valve area (AVA) in aortic stenosis (AS) using a single-slice phase contrast (PC) acquisition at valve level: AVA = aortic flow/aortic velocity-time integral (VTI). However, CMR has been shown to underestimate aortic flow in turbulent high velocity jets, due to intra-voxel dephasing. This study investigated the effect of decreasing intra-voxel dephasing by reducing the echo time (TE) on AVA estimates in patients with AS.</p> <p>Method</p> <p>15 patients with moderate or severe AS, were studied with three different TEs (2.8 ms/2.0 ms/1.5 ms), in the main pulmonary artery (MPA), left ventricular outflow tract (LVOT) and 0 cm/1 cm/2.5 cm above the aortic valve (AoV). PC estimates of stroke volume (SV) were compared with CMR left ventricular SV measurements and PC peak velocity, VTI and AVA were compared with Doppler echocardiography. CMR estimates of AVA obtained by direct planimetry from cine acquisitions were also compared with the echoAVA.</p> <p>Results</p> <p>With a TE of 2.8 ms, the mean PC SV was similar to the ventricular SV at the MPA, LVOT and AoV_{0 cm}(by Bland-Altman analysis bias ± 1.96 SD, 1.3 ± 20.2 mL/-6.8 ± 21.9 mL/6.5 ± 50.7 mL respectively), but was significantly lower at AoV₁and AoV_2.5(-29.3 ± 31.2 mL/-21.1 ± 35.7 mL). PC peak velocity and VTI underestimated Doppler echo estimates by approximately 10% with only moderate agreement. Shortening the TE from 2.8 to 1.5 msec improved the agreement between ventricular SV and PC SV at AoV_{0 cm}(6.5 ± 50.7 mL vs 1.5 ± 37.9 mL respectively) but did not satisfactorily improve the PC SV estimate at AoV_{1 cm}and AoV_{2.5 cm}. Agreement of CMR AVA with echoAVA was improved at TE 1.5 ms (0.00 ± 0.39 cm²) versus TE 2.8 (0.11 ± 0.81 cm²). The CMR method which agreed best with echoAVA was direct planimetry (-0.03 cm²± 0.24 cm²).</p> <p>Conclusion</p> <p>Agreement of CMR AVA at the aortic valve level with echo AVA improves with a reduced TE of 1.5 ms. However, flow measurements in the aorta (AoV 1 and 2.5) are underestimated and 95% limits of agreement remain large. Further improvements or novel, more robust techniques are needed in the CMR PC technique in the assessment of AS severity in patients with moderate to severe aortic stenosis.</p

Hyperbranched PEG-based multi-NHS polymer and bioconjugation with BSA

Star-shaped poly(ethylene glycol)-N-hydroxysuccinimide (star- PEG-NHS) has shown great promise in a variety of biomedical applications owing to its non-toxicity, innate non-immunogenic properties and versatile, multifunctional end groups. However, its complex and sophisticated synthetic methods, as well as high costs, have significantly impeded its wide application. Here, we report the design and synthesis of a hyperbranched PEG-based polymer with multiple NHS functional groups (>12). The hyper- branched PEG-based multi-NHS polymer can react easily with a protein (bovine serum albumin, BSA) to form a PEG-protein hydro- gel that displays great potential for biomedical applications

Myocardial T(1) and T(2) mapping at 3 T: reference values, influencing factors and implications

BACKGROUND: Myocardial T1 and T2 mapping using cardiovascular magnetic resonance (CMR) are promising to improve tissue characterization and early disease detection. This study aimed at analyzing the feasibility of T1 and T2 mapping at 3 T and providing reference values. METHODS: Sixty healthy volunteers (30 males/females, each 20 from 20--39 years, 40--59 years, 60--80 years) underwent left-ventricular T1 and T2 mapping in 3 short-axis slices at 3 T. For T2 mapping, 3 single-shot steady-state free precession (SSFP) images with different T2 preparation times were acquired. For T1 mapping, modified Look-Locker inversion recovery technique with 11 single shot SSFP images was used before and after injection of gadolinium contrast. T1 and T2 relaxation times were quantified for each slice and each myocardial segment. RESULTS: Mean T2 and T1 (pre-/post-contrast) times were: 44.1 ms/1157.1 ms/427.3 ms (base), 45.1 ms/1158.7 ms/411.2 ms (middle), 46.9 ms/1180.6 ms/399.7 ms (apex). T2 and pre-contrast T1 increased from base to apex, post-contrast T1 decreased. Relevant inter-subject variability was apparent (scatter factor 1.08/1.05/1.11 for T2/pre-contrast T1/post-contrast T1). T2 and post-contrast T1 were influenced by heart rate (p < 0.0001, p = 0.0020), pre-contrast T1 by age (p < 0.0001). Inter- and intra-observer agreement of T2 (r = 0.95; r = 0.95) and T1 (r = 0.91; r = 0.93) were high. T2 maps: 97.7% of all segments were diagnostic and 2.3% were excluded (susceptibility artifact). T1 maps (pre-/post-contrast): 91.6%/93.9% were diagnostic, 8.4%/6.1% were excluded (predominantly susceptibility artifact 7.7%/3.2%). CONCLUSIONS: Myocardial T2 and T1 reference values for the specific CMR setting are provided. The diagnostic impact of the high inter-subject variability of T2 and T1 relaxation times requires further investigation

Current T(1) and T(2) mapping techniques applied with simple thresholds cannot discriminate acute from chronic myocadial infarction on an individual patient basis: a pilot study

BACKGROUND: Studying T1- and T2-mapping for discrimination of acute from chronic myocardial infarction (AMI, CMI). METHODS: Eight patients with AMI underwent CMR at 3 T acutely and after >3 months. Imaging techniques included: T2-weighted imaging, late enhancement (LGE), T2-mapping, native and post-contrast T1-mapping. Myocardial T2- and T1-relaxation times were determined for every voxel. Abnormal voxels as defined by having T2- and T1-values beyond a predefined threshold (T2 > 50 ms, native T1 > 1250 ms and post-contrast T1 delete acute infarction; unfortunately this is not possible in your web interface) acute infarction only in half of the subjects. Abnormal T2-values were also present in subjects with CMI, thereby matching the chronically infarcted territory in some. Abnormal native T1 times were present in voxels with AMI in 5/8 subjects, but also remote from the infarcted territory in four. In CMI, abnormal native T1 values corresponded with infarcted voxels, but were also abnormal remote from the infarcted territory. Voxels with abnormal post-contrast T1-relaxation times agreed well with LGE in AMI and CMI. CONCLUSIONS: In this pilot-study, T2- and T1-mapping with simple thresholds did not facilitate the discrimination of AMI and CMI

In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care