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13N-ammonia and 18F-flurpiridaz require longer delays between rest and stress studies to allow for decay, lowering clinical throughput. In this study, we investigated the impact of residual subtraction on MBF and MFR estimates, as well as its effects on diagnostic accuracy. We retrospectively analyzed 63 patients who underwent a dynamic ammonia rest/stress study and 231 patients from the flurpiridaz 301 trial. Residual subtraction was performed by subtracting the mean pre-injection activity in each sampled region from that region’s time activity curve. Corrected and uncorrected MBF and MFR were analyzed. Diagnostic accuracy was compared to quantitative coronary angiograms (QCA) for the flurpiridaz population. With delays between injections above 3 half-lives, and a doubled stress dose, residual activity did not meaningfully increase ammonia MBF (

As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification. Fifty-nine rest/stress dynamic 82Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations. TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions. Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution.

PET myocardial flow reserve (MFR) has established diagnostic and prognostic value. Technological advances have now enabled SPECT MFR quantification. We investigated whether SPECT MFR precision is sufficient for clinical categorization of patients. Validation studies vs invasive flow measurements and PET MFR were reviewed to determine global SPECT MFR thresholds. Studies vs PET and a SPECT MFR repeatability study were used to establish imprecision in SPECT MFR measurements as the standard deviation of the difference between SPECT and PET MFR, or test-retest SPECT MFR. Simulations were used to evaluate the impact of SPECT MFR imprecision on confidence of clinically relevant categorization. Based on validation studies, the typical PET MFR categories were used for SPECT MFR classification ( 2.0). Imprecision vs PET MFR ranged from 0.556 to 0.829, and test-retest imprecision was 0.781-0.878. Simulations showed correct classification of up to only 34% of patients when 1.5 ≤ true MFR ≤ 2.0. Categorization with high confidence (> 80%) was only achieved for extreme MFR values ( 2.5), with correct classification in only 15% of patients in a typical lab with MFR of 1.8 ± 0.5. Current SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.

In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling. During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67). Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

Clinical measurement of myocardial blood flow (MBF) has emerged as an important component of routine PET-CT assessment of myocardial perfusion in patients with known or suspected coronary artery disease. Although multiple society guidelines recommend patient-specific dosing, there is a lack of studies evaluating the efficacy of patient-specific dosing for quantitative MBF accuracy. Two patient-specific dosing protocols (weight- and BMI-adjusted) were retrospectively evaluated in 435 consecutive clinical patients referred for PET myocardial perfusion assessment. MBF was estimated at rest and after regadenoson-induced hyperemia. The effect of dosing protocol on dose reduction, PET scanner saturation, relative perfusion, and image quality was compared. The effect of PET saturation on the accuracy of MBF and myocardial flow reserve (MFR) in remote myocardium was assessed with multivariable linear regression. BMI-adjusted dosing was associated with lower administered 82Rb activities (1036.0 ± 274 vs. 1147 ± 274 MBq, p = 0.003) and lower PET scanner saturation incidence (28 vs. 38%, p = 0.006) and severity (median saturation severity index 0.219 ± 0.33 vs. 0.397 ± 0.59%, p = 0.018) compared to weight-adjusted dosing. PET saturation that occurred with either dosing protocol was moderate and resulted in modest remote MBF and MFR biases ranging from 2 to 9% after adjusting for patient age, sex, BMI, rate-pressure product, and LV ejection fraction. No adverse effects of BMI dose adjustment were observed in relative perfusion assessment or image quality. Patient-specific dosing according to BMI is an effective method for guideline-directed dose reduction while maintaining image quality and accuracy for routine MBF and MFR quantification.

Myocardial flow reserve (MFR) measurement provides incremental diagnostic and prognostic information. The objective of the current study was to investigate the application of a simplified model for the estimation of MFR using only the stress/rest myocardial activity ratio (MAR) in patients undergoing rest–stress cardiac PET MPI. Rest and dipyridamole stress dynamic PET imaging was performed in consecutive patients using 82Rb or 13NH3 (n = 250 each). Reference standard MFR was quantified using a standard one-tissue compartment model. Stress/rest myocardial activity ratio (MAR) was calculated using the LV-mean activity from 2 to 6 minutes post-injection. Simplified estimates of MFR (MFREST) were then calculated using an inverse power function. For 13NH3, there was good correlation between MFR and MFREST values (R = 0.63), with similar results for 82Rb (R = 0.73). There was no bias in the MFREST values with either tracer. The overall diagnostic performance of MFREST for detection of MFR

Quantitative analysis has been applied extensively to image processing and interpretation in nuclear cardiology to improve disease diagnosis and risk stratification. This is Part 2 of a two-part continuing medical education article, which will review the potential clinical role for emerging quantitative analysis tools. The article will describe advanced methods for quantifying dyssynchrony, ventricular function and perfusion, and hybrid imaging analysis. This article discusses evolving methods to measure myocardial blood flow with positron emission tomography and single-photon emission computed tomography. Novel quantitative assessments of myocardial viability, microcalcification and in patients with cardiac sarcoidosis and cardiac amyloidosis will also be described. Lastly, we will review the potential role for artificial intelligence to improve image analysis, disease diagnosis, and risk prediction. The potential clinical role for all these novel techniques will be highlighted as well as methods to optimize their implementation. (J Nucl Cardiol 2020).

Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant® and Corridor4DM®; (2) evaluate test–retest repeatability of regional denervation scores. N = 190 dynamic [11C]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF ≤ 35%). N = 12 scans were excluded due to non-diagnostic quality. N = 178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test–retest scans from N = 20 patients with stable heart failure were utilized for test–retest analysis. Denervation scores were defined as extent × severity of relative uptake defects in LV regions with

Qualification and interpretation standards are essential for establishing 99mTc-SPECT MPI accuracy vs. alternative modalities. Rest–stress 99mTc-SPECT phantom scans were acquired on 35 cameras. LV defects were quantified with summed stress (SSS) and difference scores (SDS) at 2 core labs. SDS ≥ 2 in the right coronary artery (RCA) was the qualifying standard. Twenty rest (R)–stress (S) patient images were acquired on qualified cameras and interpreted by core labs. Global scoring differences > 3 between labs or discordant clinical interpretations underwent review. Scoring, interpretation, image quality, and diagnostic parameter agreement were assessed. Phantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90. Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine 99mTc-SPECT MPI accuracy.

Type II-P supernov\ae~(SNe), the most common core-collapse SNe type, result from the explosions of red supergiant stars. Their detection in the radio domain testifies of the presence of relativistic electrons, and shows that they are potentially efficient energetic particle accelerators. If hadrons can also be accelerated, these energetic particles are expected to interact with the surrounding medium to produce a gamma-ray signal even in the multi--TeV range. The intensity of this signal depends on various factors, but an essential one is the density of the circumstellar medium. Such a signal should however be limited by electron-positron pair production arising from the interaction of the gamma-ray photons with optical photons emitted by the supernova photosphere, which can potentially degrade the gamma-ray signal by over ten orders of magnitude in the first days/weeks following the explosion. We calculate the gamma-gamma opacity from a detailed modelling of the time evolution of the forward shock and supernova photosphere, taking a full account of the non-isotropy of the photon interactions. We discuss the time-dependent gamma-ray TeV emission from type II-P SNe as a function of the stellar progenitor radius and mass-loss rate, as well as the explosion energy and mass of the ejected material. We evaluate the detectability of the SNe with the next generation of Cherenkov telescopes. We find that, while most extragalactic events may be undetectable, type II-P SNe exploding in our Galaxy or in the Magellanic Clouds should be detected by gamma-ray observatories such as the upcoming Cherenkov Telescope Array., Comment: 9 pages, 8 figures, Accepted for publication in MNRAS

Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [11C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF). Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VT), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values

Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is widely used for coronary artery disease (CAD) evaluation. Although attenuation correction is recommended to diminish image artifacts and improve diagnostic accuracy, approximately 3/4ths of clinical MPI worldwide remains non-attenuation-corrected (NAC). In this work, we propose a novel deep learning (DL) algorithm to provide "virtual" DL attenuation-corrected (DLAC) perfusion polar maps solely from NAC data without concurrent computed tomography (CT) imaging or additional scans.SPECT MPI studies (N = 11,532) with paired NAC and CTAC images were retrospectively identified. A convolutional neural network-based DL algorithm was developed and trained on half of the population to predict DLAC polar maps from NAC polar maps. Total perfusion deficit (TPD) was evaluated for all polar maps. TPDs from NAC and DLAC polar maps were compared to CTAC TPDs in linear regression analysis. Moreover, receiver-operating characteristic analysis was performed on NAC, CTAC, and DLAC TPDs to predict obstructive CAD as diagnosed from invasive coronary angiography.DLAC TPDs exhibited significantly improved linear correlation (p 0.001) with CTAC (RThe proposed DL algorithm provided attenuation correction comparable to CTAC without the need for additional scans. Compared to conventional NAC perfusion imaging, DLAC significantly improved diagnostic accuracy.

We retrospectively analyzed 63 patients who underwent a dynamic ammonia rest/stress study and 231 patients from the flurpiridaz 301 trial. Residual subtraction was performed by subtracting the mean pre-injection activity in each sampled region from that region's time activity curve. Corrected and uncorrected MBF and MFR were analyzed. Diagnostic accuracy was compared to quantitative coronary angiograms (QCA) for the flurpiridaz population.With delays between injections above 3 half-lives, and a doubled stress dose, residual activity did not meaningfully increase ammonia MBF ( 5%). For shorter injection delays, stress MBF was overestimated by 13.6% ± 5.0% (P .001). Residual activity had a large effect on flurpiridaz stress MBF, overestimating it by 37.9% ± 23.2% (P .001). Comparison to QCA showed a significant improvement in AUC with residual subtraction (from 0.748 to 0.831, P = .001). MFR yielded similar results.Accounting for residual activity has a marked impact on stress MBF and MFR and improves diagnostic accuracy relative to QCA.

In addition to acquired photon counts, image noise depends on the image reconstruction algorithm. This work develops patient-specific activity or acquisition time protocols to standardize the average noise in a reconstructed image for different patients, cameras, and reconstruction algorithms. Image noise was calculated for images from 43 patients acquired on both a conventional and a multiple-pinhole cardiac SPECT camera. Functions were found to relate image noise to radiotracer activity, scan time, and body mass and were validated by normalizing the image noise in a test set of 58 patients. There was a 3.6-fold difference in photon sensitivity between the two cameras but a 16-fold difference in activity-scan time was necessary to match the noise levels. Image noise doubled from 45 to 128 kg for the conventional camera (12.8 minutes) and tripled for the multiple-pinhole camera (5 minutes) for 350 MBq (9.5 mCi) 99mTc-tetrofosmin. It was 16.3% and 6.1% respectively for an average sized patient. A linear scaling of activity with respect to the patient weight normalizes image noise but the scaling factors depend on the choice of camera and image reconstruction parameters. Therefore, equivalent numbers of acquired photon counts are not sufficient to guarantee equivalent image noise.

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.

PET myocardial flow reserve (MFR) has established diagnostic and prognostic value. Technological advances have now enabled SPECT MFR quantification. We investigated whether SPECT MFR precision is sufficient for clinical categorization of patients.Validation studies vs invasive flow measurements and PET MFR were reviewed to determine global SPECT MFR thresholds. Studies vs PET and a SPECT MFR repeatability study were used to establish imprecision in SPECT MFR measurements as the standard deviation of the difference between SPECT and PET MFR, or test-retest SPECT MFR. Simulations were used to evaluate the impact of SPECT MFR imprecision on confidence of clinically relevant categorization.Based on validation studies, the typical PET MFR categories were used for SPECT MFR classification (lt; 1.5, 1.5-2.0,gt; 2.0). Imprecision vs PET MFR ranged from 0.556 to 0.829, and test-retest imprecision was 0.781-0.878. Simulations showed correct classification of up to only 34% of patients when 1.5 ≤ true MFR ≤ 2.0. Categorization with high confidence (gt; 80%) was only achieved for extreme MFR values (lt; 1.0 orgt; 2.5), with correct classification in only 15% of patients in a typical lab with MFR of 1.8 ± 0.5.Current SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.背景: PET 心肌血流储备 (Myocardial Flow Reserve, MFR)诊断和预后价值已经明确。SPECT MFR 的量化随着技术的进步也已实现。我们探讨 SPECT MFR 精度能否满足对患者进行临床分类。 方法: 回顾有创血流测量和PET-MFR对比的研究来确定SPECT的整体MFR阈值。PET和SPECT-MFR重复性研究用于确定SPECT-MFR测量的不精确性, 并以此作为SPECT和PET-MFR之间或SPECT-MFR的重测差异的标准差。模拟用来评估SPECT MFR的不精确性对临床相关分类可信度的影响。 结果: 在验证研究中, SPECT-MFR分类采用典型PET-MFR分类 (lt; 1.5, 1.5-2.0,gt; 2.0)。对比PET-MFR, 不精确度的比值范围为0.556∼0.829, 重测不精确度为0.781∼0.878。模拟显示, 当 1.5≤真实 MFR≤2.0时, 正确分类的患者只有 34%。 在MFR值为1.8±0.5的典型实验模拟中, 只有15%的患者进行了正确的分类, 只有极端的MFR值 (lt; 1.0或gt;2.5) 才能实现高置信度分类 (gt;80%)。 结论: 目前SPECT估计得出的MFR缺乏精确性, 用于临床风险分层尚需要进一步优化。.L’évaluation de la réserve du flot myocardique (RFM) en TEP possède une valeur diagnostique et pronostique reconnue. Des avancées technologiques permettent maintenant une quantification de la RFM à l’aide de la SPECT. MéTHODOLOGIE: Des études de validation versus des mesures de flot invasives et de la RFM en TEP ont été analysées afin de déterminer les seuils globaux de la RFM en SPECT. Les études TEP et de répétabilité de la RFM en SPECT ont été utilisées afin d’établir le degré d’imprécision sur les mesures de la RFM en SPECT comme déviation standard de la différence entre la RFM évaluée en SPECT et en TEP, ou évaluation – réévaluation de la RFM en SPECT. Des simulations ont été utilisées afin d’évaluer l’impact de l’imprécision de la RFM en SPECT sur la confiance de catégorisation clinique. RéSULTATS: Basées sur les études de validation, les catégories de RFM en TEP typiques ont été utilisées pour la classification de la RFM en SPECT (lt; 1.5, 1.5–2.0,gt; 2.0). L’imprécision versus RFM en TEP variait de 0.556 à 0.829 et l’imprécision de l’évaluation-réévaluation était de 0.781–0.878. Les simulations ont démontré une classification correcte jusqu’à seulement 34% des patients lorsque la RFM vraie se situait entre 1.5 et 2.0. Une catégorisation avec un haut degré de confiance (gt; 80%) a été effectuée seulement pour les valeurs extrêmes de RFM (lt; 1.0 ougt; 2.5) avec une classification correcte chez uniquement 15% des patients vus dans un laboratoire typique avec une RFM de 1.8 ± 0.5.Les estimations de la RFM à partir des SPECT actuels manquent de précision et nécessitent davantage d’optimisation pour la stratification du risque clinique.la reserva de flujo miocárdico (RFM) por PET tiene un valor diagnóstico y pronóstico bien establecido. Los avances tecnológicos ahora han permitido la cuantificación RFM por SPECT. Investigamos si la precisión de la RFM por SPECT es suficiente para la categorización clínica de pacientes. MéTODOS: se revisaron los estudios de validación versus mediciones invasivas de flujo y RFM por PET para determinar los puntos de cohorte globales de la RFM por SPECT. Estudios versus PET y un estudio de repetibilidad de la RFM por SPECT fueron usados para establecer la imprecisión de las mediciones de RFM por SPECT como la desviación estándar de la diferencia entre la RFM por SPECT y PET, o estudio-repetir estudio de la RFM por SPECT. Se utilizaron simulaciones para evaluar el impacto de la imprecisión en la confianza de la categorización clínicamente relevante por la RFM por SPECT.basado en estudios de validación, las típicas categorías de la RFM por PET se utilizaron para la clasificación de la RFM por SPECT (lt; 1.5, 1.5–2.0,gt; 2.0). La imprecisión frente a la RFM por PET osciló entre 0.556 y 0.829, y la imprecisión de estudio-repetir estudio fue de 0.781–0.878. Las simulaciones mostraron una correcta clasificación de hasta solo el 34% de los pacientes cuando 1.5 ≤ RFM real ≤ 2.0. La categorización con alta confianza (gt; 80%) solo se logró para valores extremos de RFM (lt; 1.0 ogt; 2.5), con clasificación correcta en solo el 15% de los pacientes en un laboratorio típico con RFM de 1.8 ± 0.5.las estimaciones actuales de MFR derivadas de SPECT carecen de precisión y requieren una mayor optimización para la estratificación del riesgo clínico.

As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification.Fifty-nine rest/stress dynamicsup82/supRb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations.TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions.Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution.

In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NHDuring 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NHQuantification of HED distribution volume and NH

Successful succession planning necessitates use of innovative strategies to encourage and support knowledge recovery and transfer. This quality improvement project evaluated the impact of a critical reflective inquiry workshop on experienced nurses' insights into practice. Nurses assessed written clinical narratives using the Critical Reflective Inquiry Assessment Tool before and after the workshop. Guided reflection led by nursing professional development practitioners fostered insight into practice, which is an essential step in supporting knowledge transfer to novice nurses.

Carbon and oxygen burning reactions, in particular, $^{12}$C+$^{12}$C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-$\gamma$ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for $^{12}$C+$^{12}$C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed., Comment: accepted for publication in Phys. Rev. Lett

Aims. Colliding wind binary systems have long been suspected to be high-energy (HE; 100 MeV < E < 100 GeV) {\gamma}-ray emitters. {\eta} Car is the most prominent member of this object class and is confirmed to emit phase-locked HE {\gamma} rays from hundreds of MeV to ~100 GeV energies. This work aims to search for and characterise the very-high-energy (VHE; E >100 GeV) {\gamma}-ray emission from {\eta} Car around the last periastron passage in 2014 with the ground-based High Energy Stereoscopic System (H.E.S.S.). Methods. The region around {\eta} Car was observed with H.E.S.S. between orbital phase p = 0.78 - 1.10, with a closer sampling at p {\approx} 0.95 and p {\approx} 1.10 (assuming a period of 2023 days). Optimised hardware settings as well as adjustments to the data reduction, reconstruction, and signal selection were needed to suppress and take into account the strong, extended, and inhomogeneous night sky background (NSB) in the {\eta} Car field of view. Tailored run-wise Monte-Carlo simulations (RWS) were required to accurately treat the additional noise from NSB photons in the instrument response functions. Results. H.E.S.S. detected VHE {\gamma}-ray emission from the direction of {\eta} Car shortly before and after the minimum in the X-ray light-curve close to periastron. Using the point spread function provided by RWS, the reconstructed signal is point-like and the spectrum is best described by a power law. The overall flux and spectral index in VHE {\gamma} rays agree within statistical and systematic errors before and after periastron. The {\gamma}-ray spectrum extends up to at least ~400 GeV. This implies a maximum magnetic field in a leptonic scenario in the emission region of 0.5 Gauss. No indication for phase-locked flux variations is detected in the H.E.S.S. data., Comment: 9 pages, 4 figures, 3 tables, in press with A&A

Active-target detectors have the potential to address the difficulties associated with the low intensities of radioactive beams. We have developed an active-target detector, the Notre Dame Cube (ND-Cube), to perform experiments with radioactive beams produced at $\mathit{TwinSol}$ and to aid in the development of active-target techniques. Various aspects of the ND-Cube and its design were characterized. The ND-Cube was commissioned with a $^{7}$Li beam for measuring $^{40}$Ar + $^{7}$Li fusion reaction cross sections and investigating $^{7}$Li($\alpha$,$\alpha$)$^{7}$Li scattering events. The ND-Cube will be used to study a range of reactions using light radioactive ions produced at low energy., Comment: 13 pages, 12 figures

BACKGROUND: Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to: 1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant® and Corridor4DM®; 2) evaluate test-retest repeatability of regional denervation scores. METHODS: N=190 dynamic [(11)C]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF≤35%). N=12 scans were excluded due to non-diagnostic quality. N=178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test-retest scans from n=20 patients with stable heart failure were utilized for test-retest analysis. Denervation scores were defined as extent×severity of relative uptake defects in LV regions with

Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism. Dynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients’ clinical data used FlowQuant® to evaluate test–retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland–Altman coefficient-of-repeatability (CR). Test–retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test–retest repeatability values (22%-54%, P

Recent studies have reported the usefulness of 18F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18F-FDG PET/CT images. 18F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion: The interobserver agreement of cardiac 18F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary preparation seemed to improve interobserver agreement.

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Purpose. Myocardial blood flow (MBF) quantification with Rb82 positron emission tomography (PET) is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic Rb82 PET, from which MBF was quantified using 1-tissue-compartment kinetic model variants: (1) blood-pool versus uptake region sampled input function (Blood/Uptake-ROI), (2) dual spillover correction (SOC-On/Off), (3) right blood correction (RBC-On/Off), (4) arterial blood transit delay (Delay-On/Off), and (5) distribution volume (DV) constraint (Global/Regional-DV). Repeatability of MBF, stress/rest myocardial flow reserve (MFR), and stress/rest MBF difference (ΔMBF) was assessed using nonparametric reproducibility coefficients (RPCnp = 1.45 × interquartile range). Results. MBF using SOC-On, RVBC-Off, Blood-ROI, Global-DV, and Delay-Off was most repeatable for combined rest and stress: RPCnp = 0.21 mL/min/g (15.8%). Corresponding MFR and ΔMBF RPCnp were 0.42 (20.2%) and 0.24 mL/min/g (23.5%). MBF repeatability improved with SOC-On at stress (p<0.001) and tended to improve with RBC-Off at both rest and stress (p<0.08). DV and ROI did not significantly influence repeatability. The Delay-On model was overdetermined and did not reliably converge. Conclusion. MBF and MFR test-retest repeatability were the best with dual spillover correction, left atrium blood input function, and global DV.

Background: The induction of matrix metalloproteinases (MMPs) and reduction in tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) injury post-myocardial infarction (MI) and subsequent left ventricular remodeling. We developed a hybrid dual isotope single-photon emission computed tomography/computed tomography approach for noninvasive evaluation of regional myocardial MMP activation with 99m Tc-RP805 and dynamic 201 Tl for determination of myocardial blood flow, to quantify the effects of intracoronary delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. Methods: Studies were performed in control pigs (n=5) and pigs following 90-minute balloon occlusion–induced ischemia/reperfusion (I/R) of left anterior descending artery (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual isotope imaging was performed with 99m Tc-RP805 and 201 Tl along with contrast cineCT to assess left ventricular function. Results: The ischemic to nonischemic ratio of 99m Tc-RP805 was significantly increased following I/R in saline group (4.03±1.40), and this ratio was significantly reduced with rTIMP-3 treatment (2.22±0.57; P =0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment group was associated with an improvement in relative MI region myocardial blood flow compared with the MI-saline group and improved myocardial strain in the MI region. Conclusions: We have established a novel hybrid single-photon emission computed tomography/computed tomography imaging approach for the quantitative assessment of regional MMP activation, myocardial blood flow, and cardiac function post-I/R that can be used to evaluate therapeutic interventions such as intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases of post-MI remodeling.

Qualification and interpretation standards are essential for establishingRest-stressPhantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90.Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine

Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (VIntra- and inter-observer correlations of both VQuantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex V

The effects of chronic adolescent fluoxetine (FLX, Prozac®) exposure on adult cognition are largely unknown. We used a serial multiple choice (SMC) task to characterize the effects of adolescent FLX exposure on rat serial pattern learning in adulthood. Male rats were exposed to either 1.0, 2.0, or 4.0 mg/kg/day FLX for five consecutive days each week for five weeks during adolescence, followed by a 35-day drug-free period. As adults, the rats were trained in a task that required them to learn a highly structured sequential pattern of responses in an octagonal chamber for water reinforcement. In a transfer phase, the terminal element of the pattern was replaced by a violation element that was inconsistent with previously learned pattern structure. Results indicated that adolescent FLX exposure caused differential learning deficits for different types of elements in the serial pattern. Adolescent exposure to 1.0 or 4.0 mg/kg/day FLX, but not 2.0 mg/kg/day FLX, impaired chunk-boundary element learning, which is known to be mediated by stimulus-response (S-R) learning. All three doses of FLX impaired violation element learning, which is known to be mediated by multiple-cue learning. FLX did not impair within-chunk element learning, which is known to be mediated by rule-learning mechanisms. The results indicate that adolescent FLX exposure produced multiple cognitive impairments that were detectable in adulthood long after drug exposure ended.

Reduced left ventricular (LV) function is associated with increased myocardial oxygen consumption rate (MVO2) and altered sympathetic activity, the role of which is not well described in right ventricular (RV) dysfunction. 33 patients with left heart failure were assessed for RV function/size using echocardiography. Positron emission tomography (PET) was used to measure 11C-acetate clearance rate (kmono), 11C-hydroxyephedrine (11C-HED) standardized uptake value (SUV), and retention rate. RV MVO2 was estimated from kmono. 11C-HED SUV and retention indicated sympathetic neuronal function. A composite clinical endpoint was defined as unplanned cardiac hospitalization within 5 years. Patients with (n = 10) or without (n = 23) RV dysfunction were comparable in terms of sex (male: 70.0 vs 69.5%), LV ejection fraction (39.6 ± 9.0 vs 38.6 ± 9.4%), and systemic hypertension (70.0 vs 78.3%). RV dysfunction patients were older (70.9 ± 13.5 vs 59.4 ± 11.5 years; P = .03) and had a higher prevalence of pulmonary hypertension (60.0% vs 13.0%; P = .01). RV dysfunction was associated with increased RV MVO2 (.106 ± .042 vs .068 ± .031 mL/min/g; P = .02) and decreased 11C-HED SUV and retention (6.05 ± .53 vs 7.40 ± 1.39 g/mL (P

Measurements have been performed with scintillation crystals of LaBr3:Ce coupled to an array of Silicon Photomultipliers (SiPMs) in a 3 T magnetic field. The SiPMs were read out by digital data acquisition systems, including the GET electronics system. Inside of the B-field, energy resolution values of 3.82% FWHM at 661.7 keV are reported for a 1.5′′ cubic LaBr3:Ce crystal coupled to a 6 × 6 array of 6 × 6 mm2 SiPMs. No measurable degradation in energy resolution due to the presence of the strong magnetic field was observed.

Introduction Alors que le traitement de la maladie de Kaposi (MK) iatrogenique et epidemique est relativement bien codifie, reposant avant tout sur une restauration des fonctions immunitaires, le traitement optimal de la MK classique/endemique reste a definir. Les patients avec atteinte cutanee etendue ou viscerale sont traites generalement par interferon ou chimiotherapie, mais la tolerance peut etre mediocre chez des sujets souvent âges, et les remissions a long terme sont rares. Les anti-PD1 ont fait preuve d’une efficacite spectaculaire dans de nombreux cancers dont le carcinome de Merkel, une tumeur viro-induite comme la MK, notamment mediee par l’immunogenicite des antigenes associes au virus. Compte tenu de l’implication du virus HHV8 dans la MK et de la bonne tolerance des anti-PD1 chez les sujets âges, les anti-PD1 apparaissent comme une option therapeutique interessante. Materiel et methodes Nous avons conduit un essai de phase 2 multicentrique incluant les patients atteints de MK classique/endemique avec atteinte cutanee etendue, evolutive, avec indication a un traitement systemique. Les patients etaient traites par pembrolizumab 200 mg/3 semaines IV pendant 6 mois. La reponse tumorale etait evaluee par une mesure clinique des lesions cibles (nombre, taille, infiltration, couleur) suivant les criteres ACTG pour definir la meilleure reponse dans les 6 mois (critere principal). Une probabilite de reponse > 30 % suivant le plan de Simon en 2 etapes permettait de conclure a l’efficacite. Resultats Dix-sept patients ont ete inclus (47 % et 53 % de MK classique et endemique), dont 6 avec une atteinte ganglionnaire associee. Une majorite (12, 71 %) avait deja recu de la chimiotherapie. Avec une mediane de suivi de 25 semaines, 2 patients etaient en reponse complete, 10 en reponse partielle, et 5 en stabilite comme meilleure reponse. Onze patients ont eu ≥ 1 effet secondaire lie au traitement dont 1 de grade 3 (œdeme aigu pulmonaire, OAP). Deux patients ont arrete prematurement pour toxicite (un OAP grade 3 sans myocardite et une pancreatite aigue grade 2, traites symptomatiquement, reversibles). Sur les biopsies initiales, l’absence d’expression de PDL1 sur les cellules tumorales et immunes etait associee a la non reponse au pembrolizumab. Le score de divergence entre alleles du HLA de classe 1 a ete mesure chez chaque patient, et etait significativement plus faible chez les 5 patients non repondeurs (p = 0,031). Discussion Dans ce premier essai clinique evaluant l’efficacite d’un anti-PD1 dans la MK classique/endemique, le pembrolizumab etait efficace (taux de reponse de 71 %) et la tolerance acceptable. Si confirmes, ces resultats suggerent que les anti-PD1 pourraient rapidement devenir un traitement systemique de premier plan dans cette indication.

Quantification of myocardial blood flow (MBF) and stress/rest flow reserve is used increasingly to diagnose multi-vessel coronary artery disease and micro-vascular disease with PET imaging. However, variability in the measurements may limit physician confidence to direct revascularization therapies based on specific threshold values. This study evaluated the effects of rubidium-82 (82Rb) tracer injection profile using a constant-activity-rate (CA) vs a constant-flow-rate (CF) infusion to improve test–retest repeatability of MBF measurements. 22 participants underwent single-session 82Rb dynamic PET imaging during rest and dipyridamole stress using one of 2 test–retest infusion protocols: CA–CA (n = 12) or CA–CF (n = 10). MBF was quantified using a single-tissue-compartment model (1TCM) and a simplified retention model (SRM). Non-parametric test–retest repeatability coefficients (RPCnp) were compared between groups. Myocardium-to-blood contrast and signal-to-noise ratios of the late uptake images (2 to 6 minutes) were also compared to evaluate standard myocardial perfusion image (MPI) quality. MBF values in the CA–CA group were more repeatable (smaller RPCnp) than the CA–CF group using the 1TCM at rest alone, rest and stress combined, and stress/rest reserve (21% vs 36%, 16% vs 19%, and 20% vs 27%, P