Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.

BACKGROUND: Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging. METHOD AND RESULTS: Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUVmax 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUVmean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUVmean uptake, the latter with a very strong correlation with remote uptake (R2 = .74, P < .01). CONCLUSION: Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.

ANTECEDENTES: Proteína de activación de fibroblastos (FAP) como marcador específico de fibroblastos maduros activados se puede visualizar mediante tomografía por emisión de positrones (PET) usando inhibidores de Ga-68-FAP (FAPI). El FAPI marcado con galio 68 se usa cada vez más en la estatificación de varios tipos de cáncer.Además, se han reportado los primeros casos de abordajes teranósticos. En este trabajo describimos el fenómeno de la captación de FAPI miocárdica en pacientes que recibieron Ga-68 FAPI PET para estatificación tumoral. MéTODO Y RESULTADOS: Los exámenes de PET Ga-68 FAPI para estadificación de cáncer se analizaron retrospectivamente con respecto a la captación del marcador cardíaco. Los valores de absorción estandarizados (SUV) se correlacionaron con covariables clínicas en un modelo de regresión univariante. Del 09/2018 al 11/2019 con una n = 32 pacientes fueron sometidos a PET FAPI en nuestra institución. Seis de 32 pacientes (18.8%) demostraron un aumento de acumulación del marcador localizado en el miocardio, con la captación remota de FAPI siendo significativamente mayor en pacientes con aumento de la captación vs sin captación focalizada de miocardio (SUVmax 2.2 ± 0.6 vs. 1.5 ± 0.4, p <0.05 y SUV mean 1.6 ± 0.4 vs. 1.2 ± 0.3, p <0.05, respectivamente). La regresión univariante demostró una correlación significativa de la enfermedad de la arteria coronaria (CAD), la edad y la fracción de eyección ventricular izquierda (FEVI) con absorción SUV remota, esta última con una muy fuerte correlación con la captación remota (R² = 0.74, p <0.01). CONCLUSIóN: Nuestro estudio indica una asociación de CAD, edad y FEVI con la captación de FAPI. Se necesitan más estudios para evaluar si la activación de fibroblastos se puede medir de manera confiable y se puede usar para la estratificación de riesgo con respecto a la detección temprana o la progresión de la CAD y la remodelación ventricular izquierda.

CONTEXTE: La protéine d'activation des fibroblastes (FAP) activés et matures peut être visualisée par tomographie à émission de positons (TEP) à l'aide d'inhibiteurs de l'activation des fibroblastes (FAPI). FAPI marqué au gallium 68 est de plus en plus utilisé dans la stratification de divers cancers. De plus, les premiers exemples d'approches théranostiques ont été rapportés. Dans ce travail nous décrivons la captation myocardique de FAPI chez les patients qui bénéficié d'une TEP au Ga-68 FAPI pour stratification tumorale. MéTHODE ET RéSULTATS: Les examens TEP Ga-68 FAPI pour la stratification oncologique ont été analysés rétrospectivement pour l'absorption du traceur au niveau cardiaque. Les valeurs d'absorption normalisées (SUV) font été corrélées aux variables cliniques selon un modèle de régression univarié. A partir de septembre 2018 jusqu'en novembre 2019, 32 patients ont bénéficié d'une TEP FAPI dans notre établissement. Six de nos 32 patients (18,8%) ont démontré une augmentation focale de captation du tracer au niveau myocardique. Les foyers systémiques se sont révélés significativement plus élevé chez les patients avec foyers myocardiques localisés (SUV max 2,2 ± 0,6 vs 1,5 ± 0,4, p <0,05 et SUV mean 1,6 ± 0,4 vs 1,2 ± 0,3, p <0,05, respectivement). Nous avons observé une corrélation significative entre la maladie coronarienne, l'âge, la fraction d'éjection du ventricule gauche et la présence de foyer myocardiques FAPI (R² = 0,74, p <0,01) CONCLUSION: Notre étude indique une association entre la maladie cardiovasculaire coronarienne, l'âge et la FEVG et la captation myocardique de FAPI. Des études additionnelles sont nécessaires pour déterminer si l'activation des fibroblastes peut être mesurée de manière fiable et utilisée pour la détection et la progression de la maladie coronarienne et le remodelage du ventricule gauche.

Signatures of a magnetic field-induced unconventional nematic liquid in the frustrated and anisotropic spin-chain cuprate LiCuSbO4.

Modern theories of quantum magnetism predict exotic multipolar states in weakly interacting strongly frustrated spin-1/2 Heisenberg chains with ferromagnetic nearest neighbor (NN) inchain exchange in high magnetic fields. Experimentally these states remained elusive so far. Here we report strong indications of a magnetic field-induced nematic liquid arising above a field of ~13 T in the edge-sharing chain cuprate LiSbCuO4 ≡ LiCuSbO4. This interpretation is based on the observation of a field induced spin-gap in the measurements of the 7Li NMR spin relaxation rate T 1-1 as well as a contrasting field-dependent power-law behavior of T 1-1 vs. T and is further supported by static magnetization and ESR data. An underlying theoretical microscopic approach favoring a nematic scenario is based essentially on the NN XYZ exchange anisotropy within a model for frustrated spin-1/2 chains and is investigated by the DMRG technique. The employed exchange parameters are justified qualitatively by electronic structure calculations for LiCuSbO4.

Unconventional charge order in a co-doped high-Tc superconductor.

Charge-stripe order has recently been established as an important aspect of cuprate high-Tc superconductors. However, owing to the complex interplay between competing phases and the influence of disorder, it is unclear how it emerges from the parent high-temperature state. Here we report on the discovery of an unconventional ordered phase between charge-stripe order and (pseudogapped) metal in the cuprate La1.8-xEu0.2SrxCuO4. We use three complementary experiments-nuclear quadrupole resonance, nonlinear conductivity and specific heat-to demonstrate that the order appears through a sharp phase transition and exists in a dome-shaped region of the phase diagram. Our results imply that the new phase is a state, which preserves translational symmetry: a charge nematic. We thus resolve the process of charge-stripe development in cuprates, show that this nematic phase is distinct from high-temperature pseudogap and establish a link with other strongly correlated electronic materials with prominent nematic order.

Two distinct superconducting phases in LiFeAs.

A non-trivial temperature evolution of superconductivity including a temperature-induced phase transition between two superconducting phases or even a time-reversal symmetry breaking order parameter is in principle expected in multiband superconductors such as iron-pnictides. Here we present scanning tunnelling spectroscopy data of LiFeAs which reveal two distinct superconducting phases: at = 18 K a partial superconducting gap opens, evidenced by subtle, yet clear features in the tunnelling spectra, i.e. particle-hole symmetric coherence peak and dip-hump structures. At Tc = 16 K, these features substantiate dramatically and become characteristic of full superconductivity. Remarkably, the distance between the dip-hump structures and the coherence peaks remains practically constant in the whole temperature regimeT ≤ . This rules out the connection of the dip-hump structures to an antiferromagnetic spin resonance.

NMR Evidence for Inhomogeneous Nematic Fluctuations in BaFe_{2}(As_{1-x}P_{x})_{2}.

We present evidence for nuclear spin-lattice relaxation driven by glassy nematic fluctuations in isovalent P-doped BaFe_{2}As_{2} single crystals. Both the ^{75}As and ^{31}P sites exhibit a stretched-exponential relaxation similar to the electron-doped systems. By comparing the hyperfine fields and the relaxation rates at these sites we find that the As relaxation cannot be explained solely in terms of magnetic spin fluctuations. We demonstrate that nematic fluctuations couple to the As nuclear quadrupolar moment and can explain the excess relaxation. These results suggest that glassy nematic dynamics are a common phenomenon in the iron-based superconductors.

Anomalous superconducting state in LiFeAs implied by the 75As Knight shift measurement.

(75)As NMR investigation of a single crystal of superconducting LiFeAs is presented. The Knight shift and the in situ ac susceptibility measurements as a function of temperature and external field are indicative of two superconducting (SC) transition temperatures, each of which is associated with its own upper critical field. Strikingly, the Knight shift maintains its normal state value over a temperature range in the SC state before it drops abruptly, being consistent with spin-singlet pairing. Together with our previous NMR study, the anomalous SC state featuring the constant Knight shift is attributed to the extremely sensitive SC properties of LiFeAs, probably stemming from its proximity to a critical instability.

Inelastic neutron-scattering measurements of incommensurate magnetic excitations on superconducting LiFeAs single crystals.

Magnetic correlations in superconducting LiFeAs were studied by elastic and by inelastic neutron-scattering experiments. There is no indication for static magnetic ordering, but inelastic correlations appear at the incommensurate wave vector (0.5±Î´,0.5-/+δ,0) with δ~0.07 slightly shifted from the commensurate ordering observed in other FeAs-based compounds. The incommensurate magnetic excitations respond to the opening of the superconducting gap by a transfer of spectral weight.

Spin gap in the zigzag spin-1/2 chain cuprate Sr(0.9)Ca(0.1)CuO(2).

We report a comparative study of (63)Cu nuclear magnetic resonance spin lattice relaxation rates T(1)(-1) on undoped SrCuO(2) and Ca-doped Sr(0.9)Ca(0.1)CuO(2) spin chain compounds. A temperature independent T(1)(-1) is observed for SrCuO(2) as expected for an S=1/2 Heisenberg chain. Surprisingly, we observe an exponential decrease of T(1)(-1) for T<90 K in the Ca-doped sample evidencing the opening of a spin gap. The data analysis within the J(1)-J(2) Heisenberg model employing density-matrix renormalization group calculations suggests an impurity driven small alternation of the J(2)-exchange coupling as a possible cause of the spin gap.

Nanoscale electronic order in iron pnictides.

The charge distribution in RFeAsO1-xFx (R=La,Sm) iron pnictides is probed using As nuclear quadrupole resonance. Whereas undoped and optimally doped or overdoped compounds feature a single charge environment, two charge environments are detected in the underdoped region. Spin-lattice relaxation measurements show their coexistence at the nanoscale. Together with the quantitative variations of the spectra with doping, they point to a local electronic order in the iron layers, where low- and high-doping-like regions would coexist. Implications for the interplay of static magnetism and superconductivity are discussed.

75As NMR studies of superconducting LaFeAsO0.9F0.1.

We have performed 75As nuclear magnetic resonance measurements on aligned powders of the new LaFeAsO0.9F0.1 superconductor. In the normal state, we find a strong temperature dependence of the spin shift and Korringa behavior of the spin lattice relaxation rate. In the superconducting state, we find evidence for line nodes in the superconducting gap and spin-singlet pairing. Our measurements reveal a strong anisotropy of the spin lattice relaxation rate, which suggests that superconducting vortices contribute to the relaxation rate when the field is parallel to the c axis but not for the perpendicular direction.

Nuclear-magnetic-resonance evidence for charge inhomogeneity in stripe ordered La(1.8-x)Eu0.2Sr(x)CuO4.

We report 17O nuclear-magnetic-resonance (NMR) results in the stripe ordered La(1.8-x)Eu0.2Sr(x)CuO4 system. Below a temperature T(q) approximately 80 K, the local electric field gradient and the absolute intensity of the NMR signal of the planar O site exhibit a dramatic decrease. We interpret these results as microscopic evidence for a spatially inhomogeneous charge distribution, where the NMR signal from O sites in the domain walls of the spin density modulation are wiped out due to large hyperfine fields, and the remaining signal arises from the intervening Mott insulating regions.

Traffic exposure and allergic sensitization against latex in children.

BACKGROUND: Latex antigens have been found in urban air samples and in debris deposited near freeways. OBJECTIVE: We investigated whether exposure to road traffic in a large city is associated with allergic sensitization against latex in children. METHODS: A population-based sample of 2505 children aged 5 to 11 years was examined in a cross-sectional study in the city of Dresden, Germany. Specific IgE levels against latex and a panel of common aeroallergens (timothy grass, rye, birch, mugwort, Cladosporium herbarum, Dermatophagoides pteronyssinus, cat dander, and dog dander) was determined by using a fluorescence immunoassay (CAP Pharmacia). Traffic exposure was assessed by (1) parental self-report on traffic frequency and truck traffic in the street of residence, (2) traffic counts, and (3) measurements of benzene at 182 points on a 1-km(2) grid for 1 year, which were used to estimate the children's individual exposure at the home address. RESULTS: Eight hundred fifty-four (34.1%) of the children were sensitized against any of the allergens, and 150 (6.0%) had specific IgE (>0.35 kU/L) against latex. The prevalence of latex sensitization was not positively associated with self-reported traffic exposure, traffic counts in the street of residence (adjusted prevalence odds ratio for >5000 vs < or =5000 cars/d, 0.7; 95% confidence interval, 0.4-1.3), or benzene exposure (adjusted prevalence odds ratio for an increase of 1 microg/m(3) air, 0.8; 95% confidence interval, 0.7-1.05). CONCLUSION: The data suggest that exposure to road traffic is not associated with allergic sensitization to latex in children.

Inner city air pollution and respiratory health and atopy in children.

The impact of inner city air pollution on the development of respiratory and atopic diseases in childhood is still unclear. In a cross sectional study in Dresden, Germany, 5,421 children in two age groups (5-7 yrs and 9-11 yrs) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. The prevalences of wheezing and cough as well as doctor diagnosed asthma and bronchitis were assessed by parental questionnaires. Children also underwent skin-prick testing, venipuncture for the measurement of serum immunoglobulin (Ig)E, lung function testing and a bronchial challenge test (4.5% saline) to assess airway hyperresponsiveness. Exposure was assessed on an individual basis by relating mean annual air pollution levels (SO2, NO2, CO, benzene, and O3) which had been measured on a 1 km2 grid, to the home and school address of each study subject. After adjusting for potential confounding factors an increase in the exposure to benzene of 1 microg x m3 air was associated with an increased prevalence of morning cough (adjusted odds ratio (aOR)): 1.15; 1.04-1.27) and bronchitis (aOR: 1.11; 1.03-1.19). Similar associations were observed for NO2 and CO. In turn, the prevalences of atopic sensitization, symptoms of atopic diseases and bronchial hyperresponsiveness were not positively associated with exposure to any of these pollutants. It is concluded that in this study a moderate increase in exposure to traffic-related air pollution was associated with an increased prevalence of cough and bronchitis, but not with atopic conditions in children.