Browsing by Subject "Arterial"

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    Equivalence of arterial and venous blood for [11C]CO2-metabolite analysis following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate
    (Elsevier, 2013-04) Ng, Yen; Moberly, Steven P.; Mather, Kieren J.; Brown-Proctor, Clive; Hutchins, Gary D.; Green, Mark A.; Department of Cellular & Integrative Physiology, IU School of Medicine
    PURPOSE: Sampling of arterial blood for metabolite correction is often required to define a true radiotracer input function in quantitative modeling of PET data. However, arterial puncture for blood sampling is often undesirable. To establish whether venous blood could substitute for arterial blood in metabolite analysis for quantitative PET studies with 1-[(11)C]acetate and 1-[(11)C]palmitate, we compared the results of [(11)C]CO2-metabolite analyses performed on simultaneously collected arterial and venous blood samples. METHODS: Paired arterial and venous blood samples were drawn from anesthetized pigs at 1, 3, 6, 8, 10, 15, 20, 25 and 30min after i.v. administration of 1-[(11)C]acetate and 1-[(11)C]palmitate. Blood radioactivity present as [(11)C]CO2 was determined employing a validated 10-min gas-purge method. Briefly, total blood (11)C radioactivity was counted in base-treated [(11)C]-blood samples, and non-[(11)C]CO2 radioactivity was counted after the [(11)C]-blood was acidified using 6N HCl and bubbled with air for 10min to quantitatively remove [(11)C]CO2. RESULTS: An excellent correlation was found between concurrent arterial and venous [(11)C]CO2 levels. For the [(11)C]acetate study, the regression equation derived to estimate the venous [(11)C]CO2 from the arterial values was: y=0.994x+0.004 (r(2)=0.97), and for the [(11)C]palmitate: y=0.964x-0.001 (r(2)=0.9). Over the 1-30min period, the fraction of total blood (11)C present as [(11)C]CO2 rose from 4% to 64% for acetate, and 0% to 24% for palmitate. The rate of [(11)C]CO2 appearance in venous blood appears similar for the pig model and humans following i.v. [(11)C]-acetate administration. CONCLUSION: Venous blood [(11)C]CO2 values appear suitable as substitutes for arterial blood samples in [(11)C]CO2 metabolite analysis after administration of [(11)C]acetate or [(11)C]palmitate ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Quantitative PET studies employing 1-[(11)C]acetate and 1-[(11)C]palmitate can employ venous blood samples for metabolite correction of an image-derived tracer arterial input function, thereby avoiding the risks of direct arterial blood sampling.
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    Transcriptomic Analysis of Survival of Pulmonary Arterial Hypertension Patients
    (2025-05) Gomez Aleman, Adrian; Liu, Yunlong; Schwantes-An , Tae-Hwi Linus; Fadel, William; Reiter, Jill
    Pulmonary arterial hypertension (PAH) is a rare and often fatal condition characterized by obliterative PA remodeling, inflammation, and metabolic reprogramming leading to increased pulmonary vascular resistance (PVR) and right heart failure. To elucidate the genetic causes for disease risk, progression, and outcomes in PAH, many genetic studies, including genome-wide association studies (GWAS), have been conducted. These efforts culminated in identifying both rare and common genetic variants that alter the risk for developing PAH. However, the genetic underpinning of outcomes in PAH remains largely unidentified. To address this crucial gap in developing treatments for PAH, we sought to leverage available data to identify transcriptomic signatures that stratify the hazard for death among patients with PAH, affecting all-cause mortality using the PAH Biobank, which included over 1,000 patients with PAH from diverse genetic ancestry groups. Using available whole-blood RNA-Seq data, we conducted a survival analysis for all-cause mortality or transplant stratified by genetic ancestry groups using the Cox proportional hazards model. RNA-Seq data were quantified using SALMON and normalized using the DESeq2 package in R. Both normalized and tertile gene expression levels were tested for association with survival while adjusting for age at diagnosis, sex, type of PAH, PVR, neutrophils, and the 5 principal components in the survival analysis. A two-stage analysis with EUR as the discovery cohort and AFR and AMR as two independent replication cohorts was performed. A Bonferroni correction was applied to adjust for the number of discovery tests conducted. In total, there were 848 EUR (European genetic ancestry), 81 AFR (African genetic ancestry), and 103 AMR (Admixed American genetic ancestry) participants for analyses. In the discovery cohort, 45,915 genes were tested, and 8 genes were statistically significantly associated with the hazard. Three gene associations (REXO2, FHL2, and CABP4) were replicated (p-value < 0.05 with an exact direction of effect on hazard) in both replication cohorts (AFR, AMR). Using one of the largest cohorts of patients with PAH, we identified three genes that are significantly associated with all-cause mortality across populations. These genes represent potential targets for therapeutic developments as well as for understanding the biological underpinning of progression in PAH.