Myocardial edema, interstitial expansion and clinical correlates in takotsubo syndrome: a cardiac magnetic resonance tissue mapping study

Funding Acknowledgements Type of funding sources: None. Background takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by transient systolic dysfunction, widespread myocardial edema and not trivial rate of in-hospital complications. Tissue mapping by cardiac magnetic resonance (CMR) imaging provides measure of myocardial interstitial expansion. Few studies to date comprehensively examined native T1, T2 and extracellular volume (ECV) quantification by CMR in TTS. Purpose to describe T1 and T2 mapping findings by cardiac magnetic resonance (CMR) imaging in a cohort of TTS patients and control subjects. Methods we performed CMR imaging with native T1 and T2 mapping assessment as well as ECV and late gadolinium enhancement (LGE) imaging in n = 14 TTS patients at a median of 4 (3, 7) days after the acute event. Control group consisted of n = 14 healthy individuals with no known prior acute cardiac events. Extracellular-volume (ECV) fraction estimate was derived from native and post-contrast T1 of myocardium and blood pool corrected for hematocrit as reported in literature. All mapping measurements were performed in the interventricular septum from the mid-short-axis view. Results median age of the study population was 72 years, 84% female. Typical apical ballooning was present in 72% of the patients, atypical in 28%, with median left ventricular ejection fraction (LVEF) of 45%; mid interventricular septum was involved in all patients based on the presence of wall motion abnormalities at hospital admission. Median native T1, T2 and ECV were 1078 msec vs 965 msec, 55 msec vs 47 msec and 29% vs 25% in TTS and controls respectively (p < 0.001 for all). A significant direct correlation was found between T2 and both native T1 and ECV in TTS (r = 0.759, p = 0.002 and r = 0.630, p = 0.018 respectively) but not in controls. Moreover, in TTS patients, native T2 inversely correlated with LVEF as assessed at hospital admission (r=-0.563, p = 0.037), whereas non-significant trends were observed between admission LVEF and both native T1 and ECV. No LGE was detected neither in TTS patients nor in controls. Conclusions myocardial edema, as signified by increased T2, is a prominent feature of TTS, likely driving interstitial expansion and increase of native T1 and ECV in the acute phase. Correlation of T2 with LVEF on admission suggests that CMR-based parametric assessment of myocardial edema could contribute to better characterize disease severity in TTS.

Genetic-epigenetic tissue mapping for plasma DNA: applications in prenatal testing, transplantation and oncology

We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.

Continuous Polony Gels for Tissue Mapping with High Resolution and RNA Capture Efficiency

Current technologies for acquiring spatial transcript information from tissue sections rely on either RNA probes or spatial barcodes. The former methods require a priori knowledge for probeset formulation; the latter have yet to achieve single cell resolution and/or transcript capture efficiencies approaching dissociative, single-cell methods. Here, we describe a novel spatial transcriptome assay called polony (or DNA cluster)-indexed library-sequencing (PIXEL-seq). It improves upon other spatial barcoding methods by employing “continuous” polony oligos arrayed across a customized gel surface. In terms of assay performance, PIXEL-seq attains ≤ 1 µm resolution and captures >1,000 unique molecular identifiers/10×10 µm2. In other words, this global, naive platform achieves subcellular spatial transcriptome mapping while maintaining high transcript capture efficiencies.

Genetic-epigenetic tissue mapping for plasma DNA: applications in prenatal testing, transplantation and oncology

We developed Genetic-Epigenetic Tissue Mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung-transplant recipients, we showed that, at 72 hours after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring and cancer screening.