Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET

Purpose. Myocardial blood flow (MBF) quantification with R b 82 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 R b 82 PET, from which MBF was quantified usin

QUANTITATIVE NUCLEAR MEDICINE IMAGING USING ADVANCED IMAGE RECONSTRUCTION AND RADIOMICS

Our aim is to help put nuclear medicine at the forefront of quantitation on the path to the realization of personalized medicine. We propose and evaluate (Part I) advanced image reconstruction and (Part II) robust radiomics (large-scale data-oriented study of radiological images). The goal is to attain significantly improved diagnostic, prognostic and treatment-response assessment capabilities. Part I presents a new paradigm in point-spread function (PSF)-modeling, a partial volume correction method in PET imaging where resolution-degrading phenomena are modeled within the reconstruction framework. PSF-modeling improves resolution and enhances contrast, but significantly alters noise properties and induces edge-overshoots. Past efforts involve a dichotomy of PSF vs. no-PSF modeling; by contrast, we focus on a wide-spectrum of PSF models, including under- and over-estimation of the true PSF, for the potential of enhanced quantitation in standardized uptake values (SUVs). We show for the standard range of iterations employed in clinic (not excessive), edge enhancement due to overestimation actually lower SUV bias in small regions, while inter-voxel correlations suppress image roughness and enhance uniformity. An overestimated PSF yields improved contrast and limited edge-overshoot effects at lower iterations, enabling enhanced SUV quantitation. Overall, our framework provides an effective venue for quantitative task-based optimization. Part II proposes robust and reproducible radiomics methods. Radiomics workflows are complex, generating hundreds of features, which can lead to high variability and overfitting, and ultimately hampering performance. We developed and released a Standardized Environment for Radiomics Analysis (SERA) solution to enable robust radiomics analyses. We conduct studies on two unique imaging datasets – renal cell carcinoma SPECT and prostate cancer PET – identifying robust and reproducible radiomic features. In addition, we evaluate a novel hypothesis that radiomic features extracted from clinically normal (non-ischemic) myocardial perfusion SPECT (MPS) can predict coronary artery calcification (CAC; as extracted from CT). This has important implications, since CAC assessment is not commonly-performed nor reimbursed in wide community settings. SERA-derived radiomic features were utilized in a multi-step feature selection framework, followed by the application of machine learning to radiomic features. Our results show the potential to predict CAC from normal MPS, suggesting added usage and value for routine standard MPS

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET

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

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes

Radiobiology Textbook:Space Radiobiology

The study of the biologic effects of space radiation is considered a “hot topic,” with increased interest in the past years. In this chapter, the unique characteristics of the space radiation environment will be covered, from their history, characterization, and biological effects to the research that has been and is being conducted in the field. After a short introduction, you will learn the origin and characterization of the different types of space radiation and the use of mathematical models for the prediction of the radiation doses during different mission scenarios and estimate the biological risks due to this exposure. Following this, the acute, chronic, and late effects of radiation exposure in the human body are discussed before going into the detailed biomolecular changes affecting cells and tissues, and in which ways they differ from other types of radiation exposure. The next sections of this chapter are dedicated to the vast research that has been developed through the years concerning space radiation biology, from small animals to plant models and 3D cell cultures, the use of extremophiles in the study of radiation resistance mechanisms to the importance of ground-based irradiation facilities to simulate and study the space environment