PET radiopharmaceuticals for imaging chemotherapy-induced cardiotoxicity

PURPOSE OF REVIEW: Currently, cardiotoxicity is monitored through echocardiography or multigated acquisition scanning and is defined as 10% or higher LVEF reduction. The latter stage may represent irreversible myocardium injury and limits modification of therapeutic paradigms at earliest stages. To stratify patients for anthracycline-related heart failure, highly sensitive and molecularly specific probes capable of interrogating cardiac damage at the subcellular levels have been sought. RECENT FINDINGS: PET tracers may provide noninvasive assessment of earliest changes within myocardium. These tracers are at nascent stages of development and belong primarily to (a) mitochondrial potential-targeted and (b) general ROS (reactive oxygen species)-targeted radiotracers. Given that electrochemical gradient changes at the mitochondrial membrane represent an upstream, and earliest event before triggering the production of the ROS and caspase activity in a biochemical cascade, the former category might offer interrogation of cardiotoxicity at earliest stages exemplified by PET imaging, usin

CHANDRA reveals galaxy cluster with the most massive nearby cooling core, RXCJ1504.1-0248

A CHANDRA follow-up observation of an X-ray luminous galaxy cluster with a compact appearance, RXCJ1504.1-0248 discovered in our REFLEX Cluster Survey, reveals an object with one of the most prominent cluster cooling cores. With a core radius of ~30 kpc smaller than the cooling radius with ~140 kpc more than 70% of the high X-ray luminosity of Lbol = 4.3 10e45 erg s-1 of this cluster is radiated inside the cooling radius. A simple modeling of the X-ray morphology of the cluster leads to a formal mass deposition rate within the classical cooling flow model of 1500 - 1900 Msun yr-1 (for h=0.7), and 2300 - 3000 Msun yr-1 (for h=0.5). The center of the cluster is marked by a giant elliptical galaxy which is also a known radio source. Thus it is very likely that we observe one of the interaction systems where the central cluster AGN is heating the cooling core region in a self-regulated way to prevent a massive cooling of the gas, similar to several such cases studied in detail in more nearby clusters. The interest raised by this system is then due to the high power recycled in RXCJ1504-0248 over cooling time scales which is about one order of magnitude higher than what occurs in the studied, nearby cooling core clusters. The cluster is also found to be very massive, with a global X-ray temperature of about 10.5 keV and a total mass of about 1.7 10e15 Msun inside 3 Mpc.Comment: accepted for publication in Astrophys. Journal, 10 figure

Identify. Quantify. Predict. Why immunologists should widely use molecular imaging for Coronavirus Disease 2019

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offerin

Standardized radiomics analysis of clinical myocardial perfusion stress SPECT images to identify coronary artery calcification

PURPOSE: Myocardial perfusion (MP) stress single-photon emission computed tomography (SPECT) is an established diagnostic test for patients suspected of coronary artery disease (CAD). Meanwhile, coronary artery calcification (CAC) scoring obtained from diagnostic CT is a highly sensitive test, offering incremental diagnostic information in identifying patients with significant CAD yet normal MP stress SPECT (MPSS) scans. However, after decades of wide utilization of MPSS, CAC is not commonly reimbursed (e.g. by the CMS), nor widely deployed in community settings. We studied the potential of complementary information deduced from the radiomics analysis of normal MPSS scans in predicting the CAC score. METHODS: We collected data from 428 patients with normal (non-ischemic) MPSS ( RESULTS: Unsupervised feature selection significantly reduced 8×487 features to 56. In univariate analysis, no feature survived the false-discovery rate (FDR) to directly correlate with CAC scores. Applying Fisher\u27s method to the multivariate regression results demonstrated combining radiomics with the clinical features to enhance the significance of the prediction model across all cardiac segments. Conclusions: Our standardized and statistically robust multivariate analysis demonstrated significant prediction of the CAC score for all cardiac segments when combining MPSS radiomic features with clinical features, suggesting radiomics analysis can add diagnostic or prognostic value to standard MPSS for wide clinical usage

The Effects of Gas Dynamics, Cooling, Star Formation, and Numerical Resolution in Simulations of Cluster Formation

We present the analysis of a suite of simulations of a Virgo mass galaxy cluster. Undertaken within the framework of standard cold dark matter cosmology, these simulations were performed at differing resolutions and with increasingly complex physical processes, with the goal of identifying the effects of each on the evolution of the cluster. We focus on the cluster at the present epoch and examine properties including the radial distributions of density, temperature, entropy and velocity. We also map `observable' projected properties such as the surface mass density, X-ray surface brightness and SZ signature. We identify significant differences between the simulations, which highlights the need for caution when comparing numerical simulations to observations of galaxy clusters. While resolution affects the inner density profile in dark matter simulations, the addition of a gaseous component, especially one that cools and forms stars, affects the entire cluster. We conclude that both resolution and included physical processes play an important role in simulating the formation and evolution of galaxy clusters. Therefore, physical inferences drawn from simulations that do not include a gaseous component that can cool and form stars present a poor representation of reality. (Abridged)Comment: Accepted for publication in the Astrophysical Journal. Several changes from previous version, including new materia

3C 295, a cluster and its cooling flow at z=0.46

We present ROSAT HRI data of the distant and X-ray luminous (L_x(bol)=2.6^ {+0.4}_{-0.2} 10^{45}erg/sec) cluster of galaxies 3C 295. We fit both a one-dimensional and a two-dimensional isothermal beta-model to the data, the latter one taking into account the effects of the point spread function (PSF). For the error analysis of the parameters of the two-dimensional model we introduce a Monte-Carlo technique. Applying a substructure analysis, by subtracting a cluster model from the data, we find no evidence for a merger, but we see a decrement in emission South-East of the center of the cluster, which might be due to absorption. We confirm previous results by Henry & Henriksen(1986) that 3C 295 hosts a cooling flow. The equations for the simple and idealized cooling flow analysis presented here are solely based on the isothermal beta-model, which fits the data very well, including the center of the cluster. We determine a cooling flow radius of 60-120kpc and mass accretion rates of dot{M}=400-900 Msun/y, depending on the applied model and temperature profile. We also investigate the effects of the ROSAT PSF on our estimate of dot{M}, which tends to lead to a small overestimate of this quantity if not taken into account. This increase of dot{M} (10-25%) can be explained by a shallower gravitational potential inferred by the broader overall profile caused by the PSF, which diminishes the efficiency of mass accretion. We also determine the total mass of the cluster using the hydrostatic approach. At a radius of 2.1 Mpc, we estimate the total mass of the cluster (M{tot}) to be (9.2 +/- 2.7) 10^{14}Msun. For the gas to total mass ratio we get M{gas}/M{tot} =0.17-0.31, in very good agreement with the results for other clusters of galaxies, giving strong evidence for a low density universe.Comment: 26 pages, 7 figures, accepted for publication in Ap

Effect of hormone replacement therapy on vasomotor function of the coronary microcirculation in post-menopausal women with medically treated cardiovascular risk factors

Aims The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on coronary vasomotor function in post-menopausal women (PM) with medically treated cardiovascular risk factors (RFs) in a cross-sectional and a longitudinal follow-up (FU) study. Methods and results Myocardial blood flow (MBF) response to cold pressor testing (CPT) and during pharmacologically induced hyperaemia was measured with positron emission tomography in pre-menopausal women (CON), in PM with HRT and without HRT, and repeated in PM after a mean FU of 24 ± 14 months. When compared with CON at baseline, the endothelium-related change in MBF (ΔMBF) to CPT progressively declined in PM with HRT and without HRT (0.35 ± 0.23 vs. 0.24 ± 0.20 and 0.16 ± 0.12 mL/g/min; P = 0.171 and P = 0.021). In PM without HRT and in those with HRT at baseline but with discontinuation of HRT during FU, the endothelium-related ΔMBF to CPT was significantly less at FU than at baseline (0.05 ± 0.19 vs. 0.16 ± 0.12 and −0.03 ± 0.14 vs. 0.25 ± 0.18 mL/g/min; P = 0.023 and P = 0.001), whereas no significant change was observed in PM with HRT (0.19 ± 0.22 vs. 0.23 ± 0.22 mL/g/min; P = 0.453). Impaired hyperaemic MBFs when compared with CON were not significantly altered from those at baseline exam. Conclusion Long-term administration of oestrogen may contribute to maintain endothelium-dependent coronary function in PM with medically treated cardiovascular RF

Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus

Aims To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU). Methods and results In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima-media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P ≤ 0.036 and r = 0.46, P ≤ 0.055) and with an improvement in endothelium-related ΔMBF to CPT and to adenosine (r = 0.46, P ≤ 0.038 and r = 0.36, P ≤ 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in ΔMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P ≤ 0.001 by one-way analysis of variance). Conclusion In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CA

Improvement in coronary circulatory function in morbidly obese individuals after gastric bypass-induced weight loss: relation to alterations in endocannabinoids and adipocytokines

Aims To investigate the effect of surgical gastric bypass-induced weight loss and related alterations in endocannabinoids (ECs) and adipocytokine plasma levels on coronary circulatory dysfunction in morbidly obese (MOB) individuals. Methods and results Myocardial blood flow (MBF) responses to cold pressor test (CPT) from rest (ΔMBF) and during pharmacologically induced hyperaemia were measured with 13N-ammonia PET/CT in 18 MOB individuals with a body mass index (BMI) > 40 kg/m2 at baseline and after a median follow-up period of 22 months. Gastric bypass intervention decreased BMI from a median of 44.8 (inter-quartile range: 43.3, 48.2) to 30.8 (27.3, 34.7) kg/m2 (P < 0.0001). This decrease in BMI was accompanied by a marked improvement in endothelium-related ΔMBF to CPT and hyperaemic MBFs, respectively [0.34 (0.18, 0.41) from 0.03 (−0.08, 0.15) mL/g/min, P = 0.002; and 2.51 (2.17, 2.64) from 1.53 (1.39, 2.18) mL/g/min, P < 0.001]. There was an inverse correlation between decreases in plasma concentrations of the EC anandamide and improvement in ΔMBF to CPT (r = −0.59, P = 0.009), while increases in adiponectin plasma levels correlated positively with hyperaemic MBFs (r = 0.60, P = 0.050). Conversely, decreases in leptin plasma concentrations were not observed to correlate with the improvement in coronary circulatory function (r = 0.22, P = 0.400, and r = −0.31, P = 0.250). Conclusions Gastric bypass-related reduction of BMI in MOB individuals beneficially affects coronary circulatory dysfunction. The dysbalance between ECs and adipocytokines appears to be an important determinant of coronary circulatory function in obesit