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Inorganic resins enable the increased purification efficiency of 82 Sr from rubidium targets for use in PET imaging isotope production

The 82 Sr/ 82 Rb generator system has found use in positron emission tomography (PET) imaging of myocardial perfusion. 82 Sr is produced by proton irradiation of Rb metal/RbCl salt followed by chemical separation. Inorganic ion-exchangers were synthesized by hydrothermal methods and evaluated for the purification of accelerator-produced 82Sr from a RbCl target and co-produced impurities like 75 Se, Fe, Cr, and Ni. A process consisting of removal of bulk RbCl using sodium nonatitanate (SNT), then removal of remaining tracers of Rb and Se using poorly crystalline silicotitanate (pCST) is suitable for 82 Sr separation and achieves higher purity of 82 Sr vs. commonly used organic resins.

43 PARTICLE ACCELERATORS↗

Nuclear Data Sheets for A=82☆

The evaluators present in this publication spectroscopic data and level schemes from radioactive decay and nuclear reactions studies for all isobars, Z=28(Ni) to Z=42(Mo), with mass number A=82. For {sup 82}Ni not much is known other than its identification. Most of the new data, i.e., after the last NDS (2003Tu03), are based on compilations included in XUNDL. Contributions of the various compilers in XUNDL are gratefully acknowledged.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Automatic determination of cardiovascular risk by CT attenuation correction maps in Rb-82 PET/CT

Background: We investigated fully automatic coronary artery calcium (CAC) scoring and cardiovascular disease (CVD) risk categorization from CT attenuation correction (CTAC) acquired at rest and stress during cardiac PET/CT and compared it with manual annotations in CTAC and with dedicated calcium scoring CT (CSCT). Methods and Results: We included 133 consecutive patients undergoing myocardial perfusion {sup 82}Rb PET/CT with the acquisition of low-dose CTAC at rest and stress. Additionally, a dedicated CSCT was performed for all patients. Manual CAC annotations in CTAC and CSCT provided the reference standard. In CTAC, CAC was scored automatically using a previously developed machine learning algorithm. Patients were assigned to a CVD risk category based on their Agatston score (0, 1-10, 11-100, 101-400, >400). Agreement in CVD risk categorization between manual and automatic scoring in CTAC at rest and stress resulted in Cohen’s linearly weighted κ of 0.85 and 0.89, respectively. The agreement between CSCT and CTAC at rest resulted in κ of 0.82 and 0.74, using manual and automatic scoring, respectively. For CTAC at stress, these were 0.79 and 0.70, respectively. Conclusion: Automatic CAC scoring from CTAC PET/CT may allow routine CVD risk assessment from the CTAC component of PET/CT without any additional radiation dose or scan time.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Coronary vascular age: An alternate means for predicting stress-induced myocardial ischemia in patients with suspected coronary artery disease

Background: Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year’s scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD). Methods: A total of 717 subjects referred to CAC scoring and {sup 82}Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1). Results: Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P < .001) in patients with ischemia compared to those without. At incremental analysis, the global Chi square increased from 41.26 to 68.77 (P < .001) when chronological age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P < .001). Adding chronological age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients. Conclusions: In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-F-I-56: High-Precision Gamma-Ray Analysis of Medical Isotopes

Purpose: Advanced, time-resolved, Compton-suppressed gamma-ray spectroscopy with germanium detectors is implemented for assaying medical isotopes to study the radioactive decay process leading to a more accurate appraisal of the received dose and treatment planning. Lowell’s Array for Radiological Assay (LARA), a detector array that is comprised of six Compton-suppressed high-purity germanium detectors, is currently under development at UMass-Lowell which combines Compton-suppression and time-and-angle correlations to allow for highly efficient and highly sensitive measurements. Methods: Two isotopes produced Brookhaven Linac Isotope Producer (BLIP) were investigated. {sup 82}Sr which is the parent isotope for producing {sup 82}Rb is often used in cardiac PET. {sup 82}Sr gamma-ray spectrum is dominated by the 511keV photons from positron annihilation which prevent precise measurement of co-produced contaminant isotopes. A second project was to investigate the production of platinum isotopes. Natural platinum was bombarded with protons from 53MeV to 200MeV. The resulting spectrum was complicated due to the large number of stable platinum isotopes in the target, the variety of open reaction channels (p,xn), (p,pxn), (p,axn). Results: By using face-to-face NaI(Tl) counters 90-degrees to the Compton-suppressed germaniums to detect the 511keV photons, a much cleaner and more sensitive measurement of {sup 85}Sr and other contaminants was obtained. For the platinum target, we identified the production of {sup 188–189–191–195}Pt, {sup 191–192–193–194–195–196}Au and {sup 186–188–189–190–192–194–189–190–192–194}Ir. For example, at the lower energies (53 and 65MeV), we measured {sup 191}Pt production cross-sections of 144mb and 157mb. Considerable care was needed in following the process of dissolving and diluting the samples to get consistent results. The new LARA array will help us better ascertain the absolute efficiency of the counting system and more reliable production cross-sections. Conclusion: Modern HPGe spectroscopic techniques provide enhanced sensitivity, promising precise quantification of the quality of radioisotopes used in medical physics. Using new decay information may have non-trivial impact on treatment planning and dose-assessment.

07 ISOTOPE AND RADIATION SOURCES↗

Limitations of Rb-82 weight-adjusted dosing accuracy at low doses

Introduction: Weight-adjusted dosing is important to maintain accurate quantification for dynamic cardiac three-dimensional positron emission tomography (PET). However, the manufacturer of the only Food and Drug Administration approved rubidium-82 (Rb-82) generator (CardioGen-82, Bracco Diagnostics, Inc.) recommends recalibration after each change in dose which is inefficient in a busy clinical PET lab. The objective of this study was to evaluate the accuracy of Rb-82 dosing without this recalibration. Methods: After daily calibration to either 30 mCi (1110 MBq) or 12 mCi (444 MBq), Rb-82 doses between 6 and 45 mCi (222-1665 MBq) were eluted and measured on an external dose calibrator. This was repeated for four generators at weeks 1, 2, or 4 of the generator cycle. The measurements were compared with values reported by the infusion system. Results: For requested doses less than 30 mCi, the measured dose was consistently lower than the requested dose, ranging from −3.2 mCi at 25 mCi to −5.5 mCi at 10 mCi. The error exceeded 10% for doses less than or equal to 26 mCi for the 30 mCi calibration. Residual activity in the infusion system dead volume accounted for the discrepancy between requested and delivered doses for calibration to 30 mCi but not 12 mCi. Conclusions: The CardioGen-82 infusion system is capable of accurate weight-adjusted doses without recalibration for Rb-82 doses as low as 26 mCi when calibrated to 30 mCi. For doses less than 26 mCi, the generator-reported residual activity within the infusion system can be used to correct the delivered dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Clinical performance of Rb-82 myocardial perfusion PET and Tc-99m-based SPECT in patients with extreme obesity

Background: We evaluated the performance of stress imaging with technetium-99m-labeled tetrofosmin single-photon emission computed tomography (SPECT) and rubidium-82 positron emission tomography (PET) in patients with extreme obesity, defined as body mass index ≥40 kg/m{sup 2}. Methods: We identified patients with extreme obesity who underwent angiography in our center and either stress SPECT or PET within the previous six months. Cohorts of patients with extreme obesity and a <5% pretest likelihood of CAD who underwent SPECT (N = 25) or PET (N = 25) were also included. Results: In total, 108 patients who underwent SPECT (N = 57) or PET (N = 51) were identified. Scan interpretation was classified as definitely normal or abnormal in 83.3% of PET and 60.5% of SPECT scans, respectively (P < .01). PET demonstrated higher diagnostic accuracy and normalcy rate. PET was found to have higher specificity for the pooled cohort. Similar findings were observed using stenosis cut-offs of ≥50% and ≥70%. Conclusions: In patients with extreme obesity, PET enabled more definitive scan interpretation with less artifact compared to SPECT. PET provided higher diagnostic accuracy and specificity in the detection of obstructive coronary artery disease.

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Relationship of non-invasive quantification of myocardial blood flow to arrhythmic events in patients with implantable cardiac defibrillators

Background: Ischemia contributes to arrhythmogenesis though its role is incompletely understood. Abnormal myocardial perfusion measured by PET imaging may predict ventricular arrhythmias (VAs) in a high-risk population. Methods: Patients with implantable cardiac defibrillators who had undergone rubidium-82 cardiac PET imaging were identified. Patients were stratified by median MBF and MFR values for analysis. The Cox proportional hazards model was used to assess the impact of myocardial perfusion on survival free of VT independent of critical covariates. Results: A total of 159 patients (124 (78%) males, median age 65.9 years, IQR [56.76-72.63]) were followed for 1.43 years IQR [0.83-2.21]. VA occurred in 29 patients (23.7%). After adjustment for ejection fraction, age, and sex, impaired stress MBF was associated with an increased risk of VA (adjusted HR per ml/min/g 1.52, 95% CI (1.01-2.31), P = 0.04). Summed rest and stress scores were not predictive of VA. Among patients with severe LV dysfunction, stress MBF remained an independent predictor of VA (adjusted HR per 1 ml/min/g HR 1.69, 95% CI (1.03-11.36), P = 0.03), while residual EF, summed rest, and summed stress scores were not (P > 0.05). Conclusions: Impaired stress myocardial blood flow was associated with less survival free of ventricular arrhythmias.

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Comparison of maximal Rubidium-82 activities for myocardial blood flow quantification between digital and conventional PET systems

Background: PET-based myocardial blood flow (MBF) quantification can be inaccurate when using high tracer activities. Our aim was to derive the maximal Rubidium-82 activity for MBF assessment using a new digital PET system and compare the results with conventional analog systems. Methods: 1.8 GBq Rubidium-82 was injected into the cardiac insert of an anthropomorphic torso phantom. Data were acquired for 10 min using an Ingenuity TF (Philips Healthcare), Discovery 690 (D690, GE Healthcare), and digital PET prototype system (Philips Healthcare). The dynamic ranges, defined as the maximal measured activity in the reconstructed images deviating < 10% from the true present activity, were determined in all scans. Results: The dynamic ranges were 312 MBq for Ingenuity TF, 650 MBq for D690, and 654 MBq for digital PET prototype. Conclusions: The maximal Rb-82 activity for MBF assessment using digital PET prototype is higher than that for its analog counterpart (Ingenuity TF), but seems comparable to the D690.

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Impact of regadenoson-induced myocardial creep on dynamic Rubidium-82 PET myocardial blood flow quantification

Background: Repositioning of the heart during myocardial perfusion imaging (MPI) using Rubidium-82 (Rb-82) PET may occur when using regadenoson. Our aim was to determine the prevalence and the effect of correcting for this myocardial creep on myocardial blood flow (MBF) quantification. Methods: We retrospectively included 119 consecutive patients who underwent dynamic rest- and regadenoson-induced stress MPI using Rb-82 PET. The presence of myocardial creep was visually assessed in the dynamic stress PET series by identifying differences between the automatically drawn myocardium contour and the activity. Uncorrected and corrected stress MBFs were compared for the three vascular territories (LAD, LCX, and RCA) and for the whole myocardium. Results: Myocardial creep was observed in 52% of the patients during stress. Mean MBF values decreased after correction in the RCA from 4.0 to 2.7 mL/min/g (P < 0.001), in the whole myocardium from 2.7 to 2.6 mL/min/g (P = 0.01), and increased in the LAD from 2.5 to 2.6 mL/min/g (P = 0.03) and remained comparable in the LCX (P = 0.3). Conclusions: Myocardial creep is a frequent phenomenon when performing regadenoson-induced stress Rb-82 PET and has a significant impact on MBF values, especially in the RCA territory. As this may hamper diagnostic accuracy, myocardial creep correction seems necessary for reliable quantification. [French] French Abstract: Contexte: Un repositionnement du cœur lors de l’imagerie de perfusion myocardique (MPI) à l’aide de la TEP au rubidium-82 (RB-82) peut survenir lors de l’utilisation du regadenoson. Notre objectif était de déterminer la prévalence et l’effet de la correction du fluage sur la quantification du débit sanguin myocardique (DSM). Méthodes: dans cette étude rétrospective, nous avons inclus 119 patients consécutifs ayant beneficié d’un examen au repos suivi d’un stress pharamacologique au régadénoson en utilisant le RB-82. La présence de fluage myocardique a été évaluée visuellement sur les images TEP de stress dynamique en utilisant les différences entre les contours automatiques et les images myocardiques. Les DSM de stress non corrigés et corrigés ont été comparés pour les trois territoires vasculaires (coronaire gauche-CG, la circonflexe-CX, et coronaire droite-CD) et pour l’ensemble du myocarde. Résultats: le fluage myocardique a été observé chez 52% des patients sur les examens de stress. Les valeurs moyennes de DSM ont diminué après correction dans le territoire de la CD de 4,0 à 2,7 mL/min/g (p < 0,001), dans le myocarde entier de 2,7 à 2,6 mL/min/g (p = 0,01) et augmenté dans le territoire de la CG de 2,5 à 2,6 mL/min/g (p = 0,03) et est resté comparable dans le territoire de la CX (p = 0,3). Conclusions: le fluage myocardique est un phénomène fréquent lors de l’exécution du stress phramacologique au régadénoson à l’aide du RB-82. Il a un impact significatif sur les valeurs de DSM, en particulier dans le territoire de la CD. La correction du fluage myocardique semble donc nécessaire pour une quantification fiable des flux coronariens. [Spanish] Spanish Abstract: Antecedentes: El movimiento del corazón durante la imagen de perfusión miocárdica usando Rubidio-82 (Rb-82) PET puede ocurrir cuando se usa regadenosón. Nuestro enfoque fue determinar la prevalencia y efecto de la corrección de este Artefacto de movimiento en la cuantificación del flujo sanguíneo miocárdico. Métodos: Se incluyeron de forma retrospectiva 119 pacientes que se realizaron estudio dinámico en reposo y estudio de perfusión miocárdica en estrés inducido por regadenosón usando Rb-82 PET. La presencia de el artefacto de movimiento fue evaluado visualmente en el estudio en serie de PET dinámico en estrés identificando las diferencias entre el contorno miocárdico dibujado automáticamente y la actividad. La perfusión miocárdica en estrés corregida y sin corregir se compararon para los tres territorios vasculares (Descendente Anterior, Circunfleja, Coronaria Derecha) y para todo el miocardio. Resultados: El artefacto de movimiento miocárdico se observo en un 52% de los pacientes durante el estrés. El promedio de los valores de flujo sanguíneo miocárdico disminuyen después de la corrección en la arteria coronaria derecha de 4.0 a 2.7 ml/min/g (p < 0.001), en todo el miocardio de 2.7 a 2.6 mL/min/g (p = 0.01) y un aumento en la arteria descendente anterior de 2.5 a 2.6 mL/min/g (p = 0.03) y se mantuvo comparable en la arteria circunfleja (p = 0.3). Conclusiones: El artefacto de movimiento miocárdico es un fenómeno frecuente cuando se realiza la prueba de estrés inducido con regadenosón Rb-82 PET y tiene un impacto significativo en los valores de flujo sanguíneo miocárdico, principalmente en el territorio de la coronaria derecha. Esto puede disminuir la precisión diagnostica, la corección del artefacto de movimiento es necesario para una cuantificación confiable. [Chinese] Chinese Abstract: 背景: 铷-82 (Rb-82) PET心肌灌注成像 (MPI) 过程在使用类伽腺苷时可能会发生心脏重定位。我们的目的是确定心肌蠕动 (myocardial creep) 校正对心肌血流灌注定量的影响及其普遍性。 方法: 我们连续回顾了119 名使用 Rb-82 PET 进行动态的静息与类伽腺苷负荷MPI的患者。通过识别自动绘制的心肌轮廓和心肌活动之间的差异, 在动态负荷 PET 检查中肉眼评估心肌蠕动的存在。分别在已校正和未校正的负荷 MBF上, 对三个血管区域 (LAD, LCX, RCA) 和整个心肌灌注情况进行比较。 结果: 负荷检查中, 52% 的患者观察到心肌蠕动。 RCA 校正后平均MBF值从4.0降至 2.7 mL / min / g (p <0.001), 整个心肌从 2.7降至 2.6 mL / min / g (p = 0.01) , LAD 从 2.5 升至 2.6mL / min / g (p = 0.03) 并且在LCX中保持不变 (p = 0.3) 。 结论: 类伽腺苷负荷 Rb-82 PET 检查中, 心肌蠕动是一种常见的现象, 并且对 MBF 值有显著影响, 特别在 RCA 区域。这可能妨碍诊断准确性, 因此心肌蠕动校正是准确定量的必要条件。.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

How to detect and correct myocardial creep in myocardial perfusion imaging using Rubidium-82 PET?

Reliability of myocardial blood flow (MBF) quantification in myocardial perfusion imaging (MPI) using PET can majorly be affected by the occurrence of myocardial creep when using pharmacologically induced stress. In this paper, we provide instructions on how to detect and correct for myocardial creep. For example, in each time frame of the PET images the myocardium contour and the observed activity have to be compared to check for misalignments. In addition, we provide an overview of the functionality of commonly used software packages to perform this quality control step as not all software packages currently provide this functionality. Furthermore, important clinical considerations to obtain accurate MBF measurements are given.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

No need for frame-wise attenuation correction in dynamic Rubidium-82 PET for myocardial blood flow quantification

Background: Regadenoson-induced stress causes a repositioning of the heart, myocardial creep, in half of the patients undergoing Rubidium-82 (Rb-82) positron emission tomography (PET). As a result, misalignment of dynamic PET and computer tomography (CT) may occur, possibly affecting CT-based attenuation correction (AC) and thereby PET-based myocardial blood flow (MBF) quantification. Our aim was to determine the need for frame-wise PET-CT AC to obtain reliable MBF measurements. Methods: 31 Out of 64 consecutive patients had myocardial creep during regadenoson-induced stress Rb-82 PET-CT and were included. Prior to PET image reconstruction, we applied two AC methods; single PET-CT alignment and frame-wise alignment in which PET time-frames with myocardial creep were individually co-registered with CT. The PET-CT misalignment was then quantified and MBFs for the three vascular territories and whole myocardium were calculated and compared between both methods. Results: The magnitude of misalignment due to myocardial creep was 13.8 ± 4.5 mm in caudal-cranial direction, 1.8 ± 2.1 mm in medial-lateral and 2.5 ± 1.8 mm in anterior-posterior direction. Frame-wise PET-CT registration did not result in different MBF measurements (P ≥ .07) and the magnitude of misalignment and MBF differences did not correlate (P ≥ .58). Conclusion: There is no need for frame-wise AC in dynamic Rb-82 PET for MBF quantification. Single alignment seems sufficient in patients with myocardial creep.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Correction to: No need for frame-wise attenuation correction in dynamic Rubidium-82 PET for myocardial blood flow quantification

Due to the typesetter not carrying out the author’s corrections at proof stage, there are two errors in the published article: where “mL × min × g” appears, it should be “mL/min/g”. One error is in the Figure 3 caption, and one error is in the second sentence under the heading “MBF Quantification”. The original article has been corrected.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Rubidium-82 PET imaging is feasible in a rat myocardial infarction model

Background: Small-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET perfusion imaging is feasible with Rubidium-82 ({sup 82}Rb) in a small-animal scanner using a rat myocardial infarct model. Methods: 18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. {sup 82}Rb-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI. Results: Follow-up global {sup 82}Rb-uptake correlated significantly with infarct size (infarct group: r = −0.81, P < 0.001 and reperfusion group: r = −0.61, P = 0.04). Only {sup 82}Rb-uptake in the infarct group correlated with LVEF. At follow-up, a higher segmental {sup 82}Rb-uptake in the infarct group was associated with better wall motion (β = 0.034, CI [0.028;0.039], P < 0.001, R{sup 2} = 0.30), and inversely associated with scar transmurality (β = −2.4 [−2.6; −2.2], P < 0.001, R{sup 2} = 0.59). The associations were similar for the reperfusion group. Conclusion: {sup 82}Rb-PET is feasible in small animal scanners despite the long positron range and enables fast and time-efficient myocardial perfusion imaging in rat models.

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Early risk stratification using Rubidium-82 positron emission tomography in STEMI patients

Background: Assessment of infarct size after myocardial infarction is predictive of subsequent morphological changes and clinical outcome. This study aimed to assess subacute post-intervention Rubidium-82 ({sup 82}Rb)-PET imaging in predicting left ventricle ejection fraction, regional wall motion, and final infarct size by CMR at 3-months after STEMI. Methods: STEMI patients undergoing percutaneous coronary intervention were included prospectively. Rest-only {sup 82}Rb-PET perfusion imaging was performed at median 36 hours [IQR: 22 to 50] after the treatment. The extent of hypoperfusion and absolute blood flow (mL·min·g) were estimated on a global and a 17-segment model with dedicated software. At 3-months follow-up patients completed the CMR functional and late gadolinium enhancement imaging. Results: 42 patients were included, but only 35 had follow-up CMR and constituted the study population. Absolute blood flow was significantly lower in the infarct-related territory compared to remote myocardium, P < .005. Extent of hypoperfusion correlated with final infarct size, r = 0.58, P < .001, while blood flow correlated with ejection fraction, r = 0.41, P < .05. In linear mixed models, higher subacute absolute blood flow (β = 4.6, confidence interval [3.5; 5.2], P < .001, R{sup 2} = 0.67) was associated with greater wall motion. Segmental extent of subacute hypoperfusion (β = 0.43 [0.38; 0.49], P < .001, R{sup 2} = 0.58) was associated with the degree of late gadolinium enhancement at 3-months. Conclusions: Subacute rest-only {sup 82}Rb-PET is feasible following STEMI and seems predictive of myocardial function and infarct size at 3-months.

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