Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failur

Quantitative first-pass perfusion MRI of the mouse myocardium

In this article, we present a first-pass perfusion imaging protocol to determine quantitative regional perfusion values (in mL min-1 g-1) of the mouse myocardium. Perfusion was quantified using a Fermi-constrained deconvolution of the myocardial tissue response with the arterial input function. A dual-bolus approach was implemented. Experimental evidence is presented for the linearity of signal intensity in the left-ventricular lumen during the prebolus (r = 0.99, P <0.001) and in the myocardium during the full-bolus injection (r = 0.99, P <0.01) as function of Gd(DTPA)2- injection concentration used. The prebolus was used to reconstruct a nonsaturated arterial input function. Regional perfusion values proved repeatable in a cohort of nine healthy C57BL/6 mice. The perfusion values over two measurements with a 1-week interval were 7.3 ± 0.9 and 7.2 ± 0.6 mL min-1 g-1, respectively. No effects of time (P > 0.05) and myocardial region (P > 0.05) were observed. The between-session coefficient of variation was only 6%, whereas the inter-animal coefficient of variation was 11 and 8% for the separate experiments. We expect that the first-pass perfusion method here presented will be useful in preclinical studies of myocardial perfusion deficits and valuable to assess the impact of pro-angiogenic therapy after myocardial infarction. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc

Quantitative first-pass perfusion MRI of the mouse myocardium

In this article, we present a first-pass perfusion imaging protocol to determine quantitative regional perfusion values (in mL min-1 g-1) of the mouse myocardium. Perfusion was quantified using a Fermi-constrained deconvolution of the myocardial tissue response with the arterial input function. A dual-bolus approach was implemented. Experimental evidence is presented for the linearity of signal intensity in the left-ventricular lumen during the prebolus (r = 0.99, P 0.05) and myocardial region (P > 0.05) were observed. The between-session coefficient of variation was only 6%, whereas the inter-animal coefficient of variation was 11 and 8% for the separate experiments. We expect that the first-pass perfusion method here presented will be useful in preclinical studies of myocardial perfusion deficits and valuable to assess the impact of pro-angiogenic therapy after myocardial infarction. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc

Immunogenicity of bivalent omicron (BA.1) booster vaccination after different priming regimens in health-care workers in the Netherlands (SWITCH ON): results from the direct boost group of an open-label, multicentre, randomised controlled trial

BackgroundBivalent mRNA-based COVID-19 vaccines encoding the ancestral and omicron spike (S) protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We aimed to assess the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent omicron (BA.1) vaccines in individuals who were primed with adenovirus-based or mRNA-based vaccines encoding the ancestral spike protein.MethodsWe analysed results of the direct boost group of the SWITCH ON study, an open-label, multicentre, randomised controlled trial. Health-care workers from four academic hospitals in the Netherlands aged 18–65 years who had completed a primary COVID-19 vaccination regimen and received one booster of an mRNA-based vaccine, given no later than 3 months previously, were eligible. Participants were randomly assigned (1:1) using computer software in block sizes of 16 and 24 to receive an omicron BA.1 bivalent booster straight away (direct boost group) or a bivalent omicron BA.5 booster, postponed for 90 days (postponed boost group), stratified by priming regimen. The BNT162b2 OMI BA.1 boost was given to participants younger than 45 years, and the mRNA-1273.214 boost was given to participants 45 years or older, as per Dutch guidelines. The direct boost group, whose results are presented here, were divided into four subgroups for analysis: (1) Ad26.COV2.S (Johnson & Johnson) prime and BNT162b2 OMI BA.1 (BioNTech–Pfizer) boost (Ad/P), (2) mRNA-based prime and BNT162b2 OMI BA.1 boost (mRNA/P), (3) Ad26.COV2.S prime and mRNA-1273.214 (Moderna) boost (Ad/M), and (4) mRNA-based prime and mRNA-1273.214 boost (mRNA/M). The primary outcome was fold change in S protein S1 subunit-specific IgG antibodies before and 28 days after booster vaccination. The primary outcome and safety were assessed in all participants except those who withdrew, had a SARS-CoV-2 breakthrough infection, or had a missing blood sample at day 0 or day 28. This trial is registered with ClinicalTrials.gov, NCT05471440.FindingsBetween Sept 2 and Oct 4, 2022, 219 (50%) of 434 eligible participants were randomly assigned to the direct boost group; 187 participants were included in the primary analyses; exclusions were mainly due to SARS-CoV-2 infection between days 0 and 28. From the 187 included participants, 138 (74%) were female and 49 (26%) were male. 42 (22%) of 187 participants received Ad/P and 44 (24%) mRNA/P (those aged binding antibody concentrations increased 7 days after bivalent booster vaccination and remained stable over 28 days in all four subgroups (geometric mean ratio [GMR] between day 0 and day 28 was 1·15 [95% CI 1·12–1·19] for the Ad/P group, 1·17 [1·14–1·20] for the mRNA/P group, 1·20 [1·17–1·23] for the Ad/M group, and 1·16 [1·13–1·19] for the mRNA/M group). We observed no significant difference in the GMR between the Ad/P and mRNA/P groups (p=0·51). The GMR appeared to be higher in the Ad/M group than in the mRNA/M group, but was not significant (p=0·073). Most side-effects were mild to moderate in severity and resolved within 48 h in most individuals.InterpretationBooster vaccination with mRNA-1273.214 or BNT162b2 OMI BA.1 in adult healthcare workers resulted in a rapid recall of humoral and cellular immune responses independent of the priming regimen. Monitoring of SARS-CoV-2 immunity at the population level, and simultaneously antigenic drift at the virus level, remains crucial to assess the necessity and timing of COVID-19 variant-specific booster vaccinations.Immunogenetics and cellular immunology of bacterial infectious disease