PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of (18)F would result in better image resolution. Flurpiridaz F 18 is by far the most thoroughly studied in animal models and is the only (18)F-based PET MPI radiotracer currently undergoing clinical evaluation. Preclinical and clinical experience with Flurpiridaz F 18 demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast that was stable over time-important properties of an ideal PET MPI radiotracer. Preclinical data from other (18)F-labeled myocardial perfusion tracers are encouraging.

Unlabelled

Absolute quantitation of myocardial blood flow (MBF) by PET is an established method of analyzing coronary artery disease (CAD) but subject to the various shortcomings of available radiotracers. Flurpiridaz F 18 is a novel PET radiotracer that exhibits properties of an ideal tracer.

Methods

A new absolute perfusion quantitation method with flurpiridaz was developed, taking advantage of the early kinetics and high first-pass extraction by the myocardium of this radiotracer, and the first-in-human measurements of MBF performed in 7 healthy subjects and 8 patients with documented CAD. PET images with time-activity curves were acquired at rest and during adenosine stress.

Results

In healthy subjects, regional MBF between coronary artery territories did not differ significantly, leading to a mean global MBF of 0.73 mL/min/g at rest and 2.53 mL/min/g during stress, with a mean global myocardial flow reserve (MFR) of 3.70. CAD vascular territories with <50% stenosis demonstrated a mean MBF of 0.73 at rest and 2.02 during stress, leading to a mean MFR of 2.97. CAD vascular territories with ≥50% stenosis exhibited a mean MBF of 0.86 at rest and 1.43 during stress, leading to a mean MFR of 1.86. Differences in stress MBF and MFR between normal and CAD territories, as well as between <50% and ≥50% stenosis vascular territories, were significant (P < 0.01).

Conclusion

Absolute quantitation of MBF in humans with the novel PET radiotracer flurpiridaz is feasible over a wide range of cardiac flow in the presence or absence of stress-inducible myocardial ischemia. The significant decrease in stress MBF and ensuing MFR in CAD territories allows a clear distinction between vascular territories exhibiting stress-inducible myocardial ischemia and those with normal perfusion.

Recent advances in epigenomics measurements have resulted in a preponderance of genomic sequencing datasets that require focused analyses to discover mechanisms governing biological processes. In addition, multiple epigenomics experiments are typically performed within the same study, thereby increasing the complexity and difficulty of making meaningful inferences from large datasets. One gap in the sequencing data analysis pipeline is the availability of tools to efficiently browse genomic data for scientists that do not have bioinformatics training. To bridge this gap, we developed genomeSidekick, a graphical user interface written in R that allows researchers to perform bespoke analyses on their transcriptomic and chromatin accessibility or chromatin immunoprecipitation data without the need for command line tools. Importantly, genomeSidekick outputs lists of up- and downregulated genes or chromatin features with differential accessibility or occupancy; visualizes omics data using interactive volcano plots; performs Gene Ontology analyses locally; and queries PubMed for selected gene candidates for further evaluation. Outputs can be saved using the user interface and the code underlying genomeSidekick can be edited for custom analyses. In summary, genomeSidekick brings wet lab scientists and bioinformaticians into a shared fluency with the end goal of driving mechanistic discovery.

Patients with end-stage liver disease (ESLD) who also have underlying coronary artery disease (CAD) may be at increased risk for undergoing hemodynamically challenging orthotopic liver transplantation. Noninvasive single-photon emission computed tomographic (SPECT) imaging is often used to determine whether a patient with ESLD has unsuspected CAD. The objective of this study was to determine the accuracy of SPECT imaging for detection of CAD in patients with ESLD. Patients with ESLD who underwent coronary angiography and SPECT imaging before orthotopic liver transplantation were analyzed retrospectively. The predictive accuracy of clinical risk factors was calculated and compared to the results of SPECT imaging. There were 473 SPECT imaging studies. Adenosine SPECT imaging had a sensitivity of 62%, specificity of 82%, positive predictive value of 30%, and negative predictive value of 95% for diagnosing severe CAD. Regadenoson SPECT imaging had a sensitivity of 35%, specificity of 88%, positive predictive value of 23%, and negative predictive value of 93% for diagnosing severe CAD. The accuracy of a standard risk factor analysis showed no statistical difference in predicting CAD compared with adenosine (sensitivity McNemar's p = 0.48, specificity McNemar's p = 1.00) or regadenoson (sensitivity McNemar's p = 0.77, specificity McNemar's p = 1.00) SPECT studies. In conclusion, the 2 pharmaceutical agents had low sensitivity but high specificity for diagnosing CAD. However, because the sensitivity of the test is low, the chances of missing patients with ESLD with CAD is high, making SPECT imaging an inaccurate screening test. A standard risk factor analysis as a predictor for CAD in patients with ESLD is less expensive, has no radiation exposure, and is as accurate as SPECT imaging.