Rubidium-82 PET/CT in COVID-19

A 56-year-old man presented to the emergency department with shortness of breath during the COVID-19 pandemic. Chest computed tomography angiography (CTa) showed bilateral peripheral ground-glass opacifications classified as CO-RADS 5, but no pulmonary embolism. To analyze the possibility of CTa-undetectable pulmonary microthrombi and to rule out cardiac perfusion abnormalities, we decided to perform a rubidium-82 (⁸²Rb) PET/CT. ⁸²Rb PET/CT imaging in this patient yielded uptake in the pulmonary areas of ground-glass opacification and showed corresponding findings between ⁸²Rb PET/CT and CTa imaging without any signs of microthrombi despite the elevated d-dimer. Even in the areas of profound groundglass opacifications, the increased ⁸²Rb uptake indicates that perfusion is adequate to acquire ⁸²Rb uptake in the pulmonary cells. ⁸²Rb PET/CT is a promising imaging technique and might extend the diagnostic potential of conventional nuclear and radiological imaging in detecting pulmonary microthrombi or other minor perfusion defects.     

Rubidium-82 kinetics after coronary occlusion: temporal relation of net myocardial accumulation and viability in open-chested dogs

Serial assessment of perfusion and viability during myocardial infarction has not been feasible, in part, because of the long half-lives of available tracers. Rubidium-82 (82Rb) is a generator-produced, positron-emitting potassium analog with a short half-life (75 sec) that permits repeated studies. To determine the temporal relation of net myocardial 82Rb accumulation to loss of viability during prolonged ischemia, a 2-3 mCi bolus of 82Rb was given to 46 open-chested dogs while regional myocardial time-activity curves were obtained with beta probes at baseline, and serially after coronary occlusion lasting 1-6 hr. Hearts were then stained with triphenyl tetrazolium chloride (TTC) to assess the viability of the epicardium under the probe to a depth corresponding to the range of positrons. Irreversible injury occurred in two out of 16 experiments at 1 hr and ten out of 15 experiments at 3 hr and also at 6 hr (p less than 0.05 vs. 1 hr). In viable myocardial samples, rubidium extraction increased with low flow as compared with nonischemic controls for all time periods but was unchanged (failed to increase) in nonviable tissue. Net 82Rb accumulation decreased during 1 to 6 hr of occlusion in irreversibly injured samples (0.28 +/- 0.19 to 0.16 +/- 0.07, p less than 0.05) but remained unchanged in myocardial tissue subsequently shown to be viable. For myocardial samples that were nonviable at 3 and 6 hr, changes in net accumulation of tracer became abnormal only after 6 hr of occlusion. The mechanisms primarily responsible for the decrease in net accumulation of 82Rb at 6 hr appeared to be leakage of tracer after first pass. Therefore, failure to increase extraction at low flows may be an early indicator of cell death, whereas membrane leakage occurs several hours after loss of viability.     

Normal values and prospective validation of transient ischaemic dilation index in 82Rb PET myocardial perfusion imaging

BACKGROUND: The use of Rb positron emission tomography (PET) for the diagnosis of coronary artery disease (CAD) has increased in recent years but the role of some of the traditional parameters used in SPECT for the diagnosis of CAD, such as transient ischaemic dilation index (TID) of the left ventricle, have not been validated in PET studies. METHODS AND RESULTS: We studied 95 patients who had undergone rest/pharmacological stress Rb PET scans. Thirty of these patients (18 female and 12 male) who had less than 5% likelihood of CAD (LLK) based on sequential Bayesian analysis, were used to determine the normal limits of TID index in this protocol. The remaining 65 patients (33 female and 32 male) underwent coronary angiography within 15 days of the cardiac PET scan. This second group of patients was used to validate the TID normal limits determined in the first group. In LLK patients mean TID index was 1.01+/-0.07 and there were no significant differences between genders. The TID index upper normal limit was 1.15 and was calculated as mean+2 SD. Using this cut-off point, TID index had high specificity and PPV in the diagnosis of single vessel CAD (100% and 100% respectively) and multiple vessel CAD (93% and 85%, respectively). CONCLUSION: Our results indicate that elevated TID index is a specific, although not sensitive marker of single and multiple vessel CAD in pharmacologically stressed Rb PET myocardial perfusion studies.     

Right and left ventricular uptake with Rb-82 PET myocardial perfusion imaging: Markers of left main or 3 vessel disease

Background

Relative myocardial perfusion imaging may underestimate severity of coronary disease (CAD), particularly in cases of balanced ischemia. Can quantification of peak left (LV) and right (RV) ventricular Rb-82 uptake measurements identify patients with left main or 3 vessel disease?

Methods

Patients (N = 169) who underwent Rb-82 PET MPI and coronary angiography were categorized as having no significant coronary stenosis (n = 60), 1 or 2 vessel disease (n = 81), or left main disease/3 vessel disease (n = 28), based on angiography. Maximal LV and RV ventricular myocardial Rb-82 uptake was measured during stress and rest.

Results

Failure to augment LV uptake by ≥ 8500 Bq/cc at stress, predicted left main or 3 vessel disease with a sensitivity of 93% and specificity of 61% (area under curve = 0.83). A ≥10% increase in RV: LV uptake ratios with stress over rest was 93% specific (area under curve = 0.74) for left main or 3 vessel disease. These indices incrementally predicted left main or 3 vessel disease compared to models including age, gender, cardiac risk factors, and summed stress and difference scores.

Conclusion

Quantifying maximal rest and stress LV and RV uptake with PET myocardial perfusion imaging may independently and incrementally identify patients with left main or 3 vessel disease.

     

Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis

Purpose

Absolute quantification of myocardial blood flow expands the diagnostic potential of PET for assessment of coronary artery disease. ⁸²Rb has significantly contributed to increasing utilization of PET; however, clinical studies are still mostly analysed qualitatively. The aim of this study was to reevaluate the feasibility of ⁸²Rb for flow quantification, using hybrid PET-CT in an animal model of coronary stenosis.

Methods

Nine dogs were prepared with experimental coronary artery stenosis. Dynamic PET was performed for 8 min after ⁸²Rb(1480–1850 MBq) injection during adenosine-induced vasodilation. Microspheres were injected simultaneously for reference flow measurements. CT angiography was used to determine the myocardial regions related to the stenotic vessel. Two methods for flow calculation were employed: a two-compartment model including a spill-over term, and a simplified retention index.

Results

The two-compartment model data were in good agreement with microsphere flow (y?=?0.84x + 0.20; r?=?0.92, p<0.0001), although there was variability in the physiological flow range <3 ml/g per minute (y?=?0.54x + 0.53; r =?0.53, p?=?0.042). Results from the retention index also correlated well with microsphere flow (y?=?0.47x + 0.52; r?=?0.75, p?=?0.0004). Error increased with higher flow, but the correlation was good in the physiological range (y?=?0.62x + 0.29; r?=?0.84, p?=?0.0001).

Conclusion

Using current state-of-the-art PET-CT systems, quantification of myocardial blood flow is feasible with ⁸²Rb. A simplified approach based on tracer retention is practicable in the physiological flow range. These results encourage further testing of the robustness and usefulness in the clinical context of cardiac hybrid imaging.     

Patterns of papillary muscle ischemia in myocardial PET

PURPOSE: Conventional nuclear medicine equipment lacks sufficient spatial resolution to reliably visualize the papillary muscles (PM). Positron emission tomography (PET), however, can adequately visualize these structures using various positron emitters. METHODS AND PATIENTS: We present various patterns of PM observed on myocardial PET imaging in 4 patients. These patterns demonstrate different pathologic conditions such as PM ischemia of varying severity, as well as hibernation, using both N-13 NH3 and F-18 FDG as perfusion and metabolic agents, respectively. These patterns of infarction, stress-induced myocardial ischemia, or hibernation can be identified in one or both PM using PET scanning. Normal PM visualization on chest F-18 FDG PET images is also presented. CONCLUSION: This report illustrates the potential ability of myocardial PET as a noninvasive modality to study the perfusion and metabolic abnormalities of the PM.     

Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT

Objective  

To compare the diagnostic accuracy of Rb-82 myocardial perfusion three-dimensional (3D) PET with and without prompt-gamma compensation (PGC).     

Comparison of 2-dimensional and 3-dimensional 82Rb myocardial perfusion PET imaging.

We compared 2-dimensional (2D) and 3-dimensional (3D) (82)Rb PET imaging in 3 different experiments: in a realistic heart-thorax phantom, in a uniformity-resolution phantom, and in 14 healthy volunteers. METHODS: A nonuniform heart-thorax phantom was filled with 111 MBq of (82)Rb injected into the left ventricular (LV) wall. In the LV wall of the cardiac phantom, 3 inserts-1, 2, and 3 cm in diameter-were placed to simulate infarcts. A standard rest cardiac PET imaging protocol in 2D and 3D modes was used. Following the same protocol, a uniformity-resolution phantom with uniformly distributed activity of 1,998 MBq and 740 MBq of (82)Rb in water was used to obtain 2D PET images and 3D PET images, respectively. All 2D volunteer studies were performed by injecting 2,220 MBq of (82)Rb intravenously. For half the volunteers, 3D studies were performed with a high dose (HD) (2,220 MBq) of (82)Rb; for the remainder of the 3D studies, a low dose (LD) (740 MBq) of (82)Rb was used. In the 2D and LD 3D studies, there was a delay of 2 min and 3 min, respectively, followed by a 6-min acquisition. In the HD 3D volunteer studies, there was a delay of 5 min followed by a 6-min acquisition. Circumferential profiles of the short-axis slices and the contrast of the inserts were used to evaluate the cardiac phantom PET images. The transaxial slices from the uniformity-resolution phantom were evaluated by visual inspection and by measuring uniformity. The human studies were evaluated by measuring the contrast between LV wall and LV cavity, using linear profiles and visual analysis. RESULTS: In the cardiac phantom study, circumferential profiles for the 2D and 3D images were similar. The contrast values for the 1-, 2-, and 3-cm inserts in the 2D study were 0.19 +/- 0.03, 0.34 +/- 0.05, and 0.61 +/- 0.03, respectively. The respective contrast values in the 3D study were 0.15 +/- 0.02, 0.36 +/- 0.04, and 0.52 +/- 0.05. In the uniformity-resolution phantom study, the coefficients of variation, calculated for a representative uniform slice, were 5.3% and 7.6% for the 2D and 3D studies, respectively. For the 7 volunteers on whom HD 3D was used, the mean 2D contrast was 0.33 +/- 0.08 and the mean HD 3D contrast was 0.35 +/- 0.08 (P = not statistically significant). For the other 7 volunteers, on whom LD 3D was used, the mean 2D contrast was 0.39 +/- 0.06 and the mean LD 3D contrast was 0.39 +/- 0.10 (P = not statistically significant). In the tomographic slices, the 2D and 3D images and polar plots were similar. CONCLUSION: When obtained with a PET system having a high counting-rate performance, 2D and 3D (82)Rb PET cardiac images are comparable. LD 3D imaging can make (82)Rb PET cardiac imaging more affordable.     

Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

The use of myocardial perfusion (82)Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. METHODS: A sex-independent normal database and criteria for abnormality for rest-stress (82)Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age +/- SD, 63.3 +/- 13.3 y; 145 males: mean age +/- SD, 63.9 +/- 12.8 y) who underwent a rest-adenosine stress (82)Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. RESULTS: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis > or =50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (> or =50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (< or =50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). CONCLUSION: The quantitative (82)Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.     

Time course of regional myocardial glucose metabolism after transient ischemia assessed by positron emission tomography]

The purpose of this study was to examine the significance of glucose metabolism in ischemic canine myocardium after reperfusion. Transient ischemia was induced by 90 or 180 minutes occlusion of the left anterior descending coronary artery. Twelve hours and 4 weeks after reperfusion, myocardial blood flow (MBF) and glucose metabolism were assessed (with H2(15)O and 18F-FDG, respectively) by positron emission tomography (PET) under the fasting state, and the metabolic findings were compared with the histologic examination. Glucose metabolism in ischemic regions was inversely related to the amount of tissue necrosis 12 hours and 4 weeks after reperfusion (r = -0.89 and r = -0.82, respectively). The perfusion-metabolism mismatch pattern was seen in the area with less than 10 percent necrosis 12 hours after reperfusion, but this pattern disappeared after 4 weeks. The area with 10 to 50 percent necrosis showed the mismatch pattern until 4 weeks after reperfusion, and in the area with more than 50 percent necrosis, perfusion-metabolism concordantly decreased. Thus, metabolic index assessed early after reperfusion by PET identified myocardial viability, and the perfusion-metabolism mismatch pattern sustained in relation to the degree of ischemic injury. Since some regions estimated to be irreversible by PET were viable by the histologic examination, PET study might underestimate the myocardial viability.     

Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging

Background

Rubidium-82 (⁸²Rb) PET imaging has been proposed for routine myocardial blood flow (MBF) quantification. However, few studies have investigated the test-retest repeatability of this method. The aim of this study was to optimize same-day repeatability of rest MBF imaging with a highly automated analysis program (FlowQuant) using image-derived input functions and dual spillover corrections (SOC).

Methods

Test-retest repeatability of resting left-ventricle (LV) MBF was measured in patients (n?=?27) with suspected coronary artery disease (CAD) and healthy volunteers (n?=?9). The effects of scan-time, reconstruction, and quantification methods were assessed with correlation and Bland-Altman repeatability coefficients.

Results

Factors affecting rest MBF included gender, suspected CAD, and SOC (P?<?.001). Significant test-retest correlations were found using all analysis methods tested (r?>?0.79). The best repeatability coefficient for same-day MBF was 0.20?mL/minute/g using a 6-minute scan-time, iterative reconstruction, SOC, resting rate-pressure-product (RPP) adjustment, and left atrium input function. This protocol was significantly less variable than standard protocols using filtered back-projection reconstruction, longer scan-time, no SOC, or LV input function.

Conclusion

Absolute MBF can be measured with good repeatability using FlowQuant analysis of ⁸²Rb PET scans with a 6-minute scan time, iterative reconstruction, dual SOC, RPP-adjustment, and an image-derived input function in the left atrium cavity.     

Detection of serial changes in absolute myocardial perfusion with 82Rb PET.

Serial changes in myocardial perfusion may represent an important marker of disease progression or regression or the effects of therapy for patients with coronary artery disease (CAD). Quantitative methods have not been developed for the assessment of serial changes in perfusion. The objective of this study was to use receiver operator characteristic (ROC) analysis to determine the sensitivity and specificity of direct paired comparisons (DPCs) to detect changes in absolute myocardial perfusion measured with 82Rb PET. METHODS: Repeated dynamic 82Rb PET scans were obtained on 8 dogs at rest and during hyperemia induced with dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used to verify perfusion changes. Polar maps of absolute 82Rb retention and associated SD were estimated from the dynamic images. Paired comparisons were then performed using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress differences were used to assess specificity and reproducibility, and stress-rest differences were used to assess sensitivity. RESULTS: 82Rb retention differences of 20% over baseline were detected with 85%-90% sensitivity and specificity, using the optimal DPC probability value and image smoothness. The average 82Rb retention differences correlated well with microspheres (r = 0.74; P = 0.001). Reproducibility of the mean retention values was 4.7% +/- 2.1%. As reproducibility varies, the DPC probability value can be adjusted to maintain specificity. These ROC results are directly applicable to other image modalities that produce measurements with similar SEs (3.7% +/- 0.9%). CONCLUSION: The developed method of DPCs is sensitive and specific for the detection of changes in absolute myocardial perfusion measured with 82Rb PET.