Sang-Geon Cho

Characteristics of anginal patients with high resting myocardial blood flow measured with N-13 ammonia PET/CT.

ObjectivesWe hypothesized that anginal patients with low coronary flow reserve (CFR) could have variable clinical features according to resting myocardial blood flow (MBF). Therefore, we analyzed the clinical and imaging characteristics according to resting MBF in anginal patients. MethodsWe enrolled 70 patients who underwent N-13 ammonia PET–computed tomography (CT) for evaluation of angina. Resting and stress MBF values were obtained and resting MBF was corrected with rate–pressure product to exclude the effect of heart rate and blood pressure on resting MBF. Clinical and imaging characteristics were compared on the basis of MBF and CFR. ResultsAmong patients with CFR less than 2.0, those with high resting MBF (≥1.0 ml/min/g) had significantly fewer number of smokers, were younger, had lower Agatston calcium scores, and had less coronary stenosis compared with those with low resting MBF (<1.0 ml/min/g). In contrast, there was no significant difference in clinical or imaging findings according to resting MBF when compared among all patients or within those with CFR greater than or equal to 2.0. The subgroup analysis of patients with CFR less than 2.0 revealed lower Agatston calcium score and less coronary stenosis in patients with high resting MBF regardless of stress MBF. ConclusionHigh resting MBF is associated with a lower rate of smoking, younger age, less coronary calcium burden, and less coronary stenosis compared with low resting MBF in anginal patients with low CFR. Moreover, in these patients, favorable angiographic features were mainly associated with high resting MBF, irrespective of stress MBF. Therefore, resting MBF should be reviewed to validate the clinical significance of low CFR measured by N-13 ammonia PET/CT especially in anginal patients showing low CFR.

Indirect Radionuclide Coronary Angiography to Evaluate Gradients of Myocardial Blood Flow and Flow Reserve Through Coronary Stenosis Using N-13 Ammonia PET/CT

Although quantitative evaluation of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has been perceived as an attractive advantage of positron emission tomography (PET) over other cardiac imaging technologies, application of the information to specific coronary lesions is a difficult task for nuclear cardiologists. We hypothesized that changes in MBF and MFR over a coronary lesion could be identified by use of a hybrid technology of CT coronary angiography (CTCA) and N-13 ammonia PET. To evaluate this hypothesis, we measured the gradient of MBF and MFR through coronary stenosis in seven patients (M:F=3:4, median age 56 years) with coronary artery disease who underwent N-13 ammonia PET, CTCA, and interventional coronary angiography. Two patients had proximal left anterior descending (LAD) coronary artery disease and five patients had mid to distal LAD disease. Mean global stress and rest MBF were 2.62±0.58 and 1.03±0.19 ml/min/g, respectively. Mean global MFR was 2.6±0.73. Regional stress and rest MBF in the LAD territory were 2.36±0.75 and 0.96±0.21 ml/min/g, respectively. Regional MFR in the LAD territory was 2.55±0.83 ml/min/g. Stress MBF changed dramatically according to the location of coronary stenosis. It dropped acutely in proximal lesions, whereas it diminished gradually in mid to distal lesions. In conclusion, by use of a hybrid technology of CTCA and PET, it was feasible to make a direct correlation of coronary lesions with the gradient of MFR and CFR through coronary stenosis, which indicated the severity of the coronary lesion. We named this technique indirect radionuclide coronary angiography.

Radiation Safety in Nuclear Medicine Procedures

Since the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant in 2011, radiation safety has become an important issue in nuclear medicine. Many structured guidelines or recommendations of various academic societies or international campaigns demonstrate important issues of radiation safety in nuclear medicine procedures. There are ongoing efforts to fulfill the basic principles of radiation protection in daily nuclear medicine practice. This article reviews important principles of radiation protection in nuclear medicine procedures. Useful references, important issues, future perspectives of the optimization of nuclear medicine procedures, and diagnostic reference level are also discussed.

Safer stress tests for myocardial perfusion imaging

In this issue of the Journal of Nuclear Cardiology, Andrikopolou et al. conducted a systematic review of the safety of vasodilatory stress tests using adenosine and regadenoson for myocardial perfusion imaging (MPI). By searching SCOPUS with the predefined keywords, they selected 34 studies which include 22,957 patients. Among 34 studies, adenosine was used in 21 and regadenoson in 15, while both were used in two studies. The estimated incidence of overall and highgrade atrioventricular block (AVB) was 3.81% (95% CI 1.99%-6.19%) and 1.93% (95% CI 0.77%-3.59%), respectively. The incidence of AVB and high-grade AVB in adenosine group was 8.58% (95% CI 5.55%12.21%) and 5.21% (95% CI 2.81%-8.30%), while that in regadenoson group was 0.30% (95% CI 0.04%0.82%) and 0.05% (95% CI\ 0.001%-0.19%), respectively. They concluded that both overall and high-grade AVB are significantly less frequent with regadenoson compared to adenosine. Adenosine is a naturally occurring ligand of four distinct subtypes (A1, A2A, A2B, and A3) of cell membrane G protein-coupled receptors. It produces coronary artery vasodilatation by activating adenylyl cyclase that results in the opening of potassium channels. The opening of these channels in vascular smooth muscle cells hyperpolarizes the cells and inhibits voltage-gated calcium channels and intracellular calcium release, resulting in relaxation. The common actions of adenosine on different types of adenosine receptors are associated with several life-threatening side effects. Actions on the A1 receptor can induce AVB, while actions on A2B and A3 receptors can induce bronchoconstriction especially in patients with asthma or severe chronic obstructive pulmonary disease (COPD). The use of adenosine can be limited in a substantial number of patients as the prevalence of COPD can be found in 30% patients undergoing adenosine MPI. Regadenoson, an A2A selective agonist, is used as a pharmacologic stress vasodilator for MPI. It was approved by theUSFood andDrugAdministration (FDA) on April 10th, 2008, and on September 6th, 2010 by the European Medicine Agency. It has comparable accuracy and non-inferiority to adenosine in regard to detection of perfusion defects by nuclear perfusion imaging. Regadenoson has been used successfully in patients with chronic kidney disease (CKD), COPD, asthma, and liver disease and needed MPI. Remarkably low incidence of bronchoconstriction by regadenoson was reported, which can be explained by the fact that regadenoson selectively binds with the A2A receptors only and does not with the A3 receptors, which induce mast cell activation and smooth muscle constriction of the airways. There are some concerns about the diagnostic efficacy of regadenoson. Gould et al. first described the importance of inducing hyperemia for the diagnosis of coronary artery disease. The vasodilatory reserve is exhausted in stenosed arteries to preserve a baseline perfusion as a compensatory mechanism. The contrast between normal and stenosed arteries can be maximized by the induction of hyperemia Sang-Geon Cho and Zeenat Jabin have equally contributed to this work as co-first authors. Reprint requests: Sang-Geon Cho, MD, Department of Nuclear Medicine, Chonnam National University Hospital, Gwangju, South Korea; mujuk203@hanmail.net J Nucl Cardiol 2019;26:629–32. 1071-3581/

Usefulness of 3-dimensional stereotactic surface projection FDG PET images for the diagnosis of dementia.

34.00 Copyright 2017 American Society of Nuclear Cardiology.

Flow-Based Functional Assessment of Coronary Artery Disease by Myocardial Perfusion Positron Emission Tomography in the Era of Fractional Flow Reserve

Abstract To compare diagnostic performance and confidence of a standard visual reading and combined 3-dimensional stereotactic surface projection (3D-SSP) results to discriminate between Alzheimer disease (AD)/mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). [18F]fluorodeoxyglucose (FDG) PET brain images were obtained from 120 patients (64 AD/MCI, 38 DLB, and 18 FTD) who were clinically confirmed over 2 years follow-up. Three nuclear medicine physicians performed the diagnosis and rated diagnostic confidence twice; once by standard visual methods, and once by adding of 3D-SSP. Diagnostic performance and confidence were compared between the 2 methods. 3D-SSP showed higher sensitivity, specificity, accuracy, positive, and negative predictive values to discriminate different types of dementia compared with the visual method alone, except for AD/MCI specificity and FTD sensitivity. Correction of misdiagnosis after adding 3D-SSP images was greatest for AD/MCI (56%), followed by DLB (13%) and FTD (11%). Diagnostic confidence also increased in DLB (visual: 3.2; 3D-SSP: 4.1; P < 0.001), followed by AD/MCI (visual: 3.1; 3D-SSP: 3.8; P = 0.002) and FTD (visual: 3.5; 3D-SSP: 4.2; P = 0.022). Overall, 154/360 (43%) cases had a corrected misdiagnosis or improved diagnostic confidence for the correct diagnosis. The addition of 3D-SSP images to visual analysis helped to discriminate different types of dementia in FDG PET scans, by correcting misdiagnoses and enhancing diagnostic confidence in the correct diagnosis. Improvement of diagnostic accuracy and confidence by 3D-SSP images might help to determine the cause of dementia and appropriate treatment.

Emerging Tracers for Nuclear Cardiac PET Imaging

Myocardial perfusion positron emission tomography (PET) has long been regarded as a gold standard of myocardial blood flow (MBF) measurement. However, since randomized clinical trials showed the prognostic value of fractional flow reserve (FFR)-guided revascularization, FFR has rapidly become a new gold standard of functionally significant coronary artery disease (CAD). Despite the predominance of FFR in the management of stable CAD, FFR also has limitations. Overcoming hurdles by the lesion-specific MBF measurement by hybrid imaging and novel flow parameter can be a complimentary tool.

Preparation for radioactive iodine therapy is not a risk factor for the development of hyponatremia in thyroid cancer patients.

Myocardial perfusion imaging using positron emission tomography (PET) has several advantages over single photon emission computed tomography (SPECT). The recent advances in SPECT technology have shown promise, but there is still a large need for PET in the clinical management of coronary artery disease (CAD). Especially, absolute quantification of myocardial blood flow (MBF) using PET is extremely important. In spite of considerable advances in the diagnosis of CAD, novel PET radiopharmaceuticals remain necessary for the diagnosis of CAD because clinical use of current cardiac radiotracers is limited by their physical characteristics, such as decay mode, emission energy, and half-life. Thus, the use of a radioisotope that has proper characteristics and a proper half-life to develop myocardial perfusion agents could overcome these limitations. In this review, the current state of cardiac PET and a general overview of novel 18F or 68Ga-labeled radiotracers, including their radiosynthesis, in vivo characterization, and evaluation, are provided. The future perspectives are discussed in terms of their potential usefulness based on new image analysis methods and hybrid imaging.

The tools are ready, are we?

Abstract The aim of this study was to evaluate whether the preparation for radioactive iodine (RAI) therapy by thyroid hormone withdrawal (THW) or a low-iodine diet (LID) can be risk factors for the development of hyponatremia in patients with differentiated thyroid cancer after thyroidectomy. We retrospectively reviewed the medical records and laboratory findings of 326 patients who underwent preparation for RAI therapy after thyroidectomy from 2012 to 2014. Demographic and clinical variables including the method of thyrotropin stimulation and duration of LID were assessed. Serum sodium was measured twice, before operation and before RAI therapy. Hyponatremia was detected in only 3 patients (0.9%) before operation, but in 15 patients (4.6%) before RAI therapy. None of the patients had severe hyponatremia after preparation for RAI therapy. Pre-RAI therapy serum sodium was correlated with the method of thyrotropin stimulation (TWH vs recombinant human thyroid stimulating hormone, P = 0.014) and duration of LID (r = −0.131, P = 0.018); however, the preparation of RAI therapy, THW and LID, did not affect the development of hyponatremia in logistic regression analysis. Preoperative serum sodium was a significant risk factor for hyponatremia during preparation for RAI therapy. Preparation for RAI therapy by THW or LID is not a risk factor for the development of hyponatremia in patients with thyroid cancer. The development of hyponatremia was neither frequent nor severe during preparation for RAI therapy. Physicians should not be greatly concerned about rare life-threatening hyponatremia during preparation for RAI therapy.

Prognostic Significance of Metabolic Tumor Volume Measured by 18 F-FDG PET/CT in Operable Primary Breast Cancer

In this issue of the Journal of Nuclear Cardiology, Lee and colleagues elegantly review the recent advances in the instrumentations for nuclear cardiac imaging. Solid-state radiation detectors incorporating cadmium zinc telluride (CZT) become the detector of choice for dedicated cardiac imaging systems. CZT single-photon emission computed tomography (SPECT) has improved image quality and shortened acquisition time of myocardial perfusion imaging (MPI) thanks to its direct energy conversion mechanism, narrow energy resolution, and pixelated nature of electrical circuit. The measurement of absolute myocardial blood flow (MBF) as well as coronary flow reserve (CFR) using CZT SPECT is now under active investigation and is showing clinical feasibility. Multimodality imaging systems which hybridized SPECT and positron emission tomography (PET) with CT widened clinical application of cardiac imaging studies. Quantitative SPECT/CT provides additive information of coronary calcium burden, attenuation correction for both visual and quantitative assessment of myocardial perfusion, and enables quantification of myocardial blood flow and flow reserve. Cardiac PET is also an active progress. Adoption of silicon photomultipliers (SiPMs) leads to enhancements in image quality and count rates. The application of accurate time-of-flight (TOF) information reduced emission-transmission mismatch artifacts. Information of the extracted coronary arteries from CT angiography allows non-linear motion correction of PET plaque images. Replacement of photomultiplier tubes with semiconductor photosensors such as the avalanche photodiode (APD) and SiPM has made it possible to integrate PET with magnetic resonance (MR). PET/MR system is now clinically available in hybrid as well as parallel camera structure. The recently introduced nuclear cardiac imaging tools are ready to provide more information in better quality than ever before. It is fair to question whether we are ready to apply these tools in clinical fields. There are challenges to overcome before we can use the state-ofthe-art imaging tools.