Accuracy of low-dose rubidium-82 myocardial perfusion imaging for detection of coronary artery disease using 3D PET and normal database interpretation

Background

Our aim was to develop a normal database to be used for quantification of myocardial perfusion and diagnosis of ??obstructive coronary artery disease?? (CAD) using low-dose rubidium-82 three-dimensional (3D) positron emission tomography (PET)-CT.

Methods

From a record of 1,501 patients, 77 were identified as having low-likelihood (LLK) of CAD. Forty LLK patients were used to construct a normal database using 4DM-PET, the remainder used for validation of normalcy. A group of 70 patients with CAD who had invasive coronary angiography and PET-CT were used to evaluate the accuracy of the database for detecting CAD using the sum-stress-score. The effect of clinical exclusion criteria and the inclusion of LLK patients were evaluated.

Results

The normal database for CAD detection had a normalcy rate of 95%. Sensitivity was 100% for detecting patients with either 50% or 70% stenosis. Optimal specificity was 87% for either 50% or 70% stenosis. For localizing disease at 50% stenosis in the left anterior descending, left circumflex, and right coronary artery, sensitivity ranged from 59% to 68%, while specificity was maintained at 87-89%. Similarly, at 70% stenosis, sensitivity ranged from 64% to 79%, and specificity from 87% to 91%.

Conclusions

A normal database containing the relative perfusion scores of patients with LLK of CAD can be used to accurately diagnose obstructive coronary disease using low-dose Rb-82 with 3D PET-CT imaging.     

Adenosine stress rubidium-82 PET/computed tomography in patients with known and suspected coronary artery disease

BACKGROUND: Integrated positron emission tomography/computed tomography (PET/CT) is increasingly being utilized for myocardial perfusion imaging (MPI). However, there is a potential for increased imaging artifact compared with standard PET due to the different temporal resolution of PET and CT. We reviewed the diagnostic accuracy of adenosine stress Rb myocardial perfusion PET/CT to detect obstructive coronary artery disease (CAD) on invasive angiography at our institution. METHODS AND RESULTS: Seventy-five patients were included, 23 (13 men, mean age 55.8+/-11.8 years) with low likelihood of CAD and 52 (28 men, mean age 67.1+/-11.4 years) with intermediate to high pretest probability of disease. Coronary angiography was performed only in the latter 52 patients on average within 17 days of the MPI study. The test characteristics of PET/CT MPI were assessed using a threshold of >or=50 and >or=70% stenosis in one or more major coronary artery on invasive angiography. Dedicated software was used for registration, processing, and interpretation. Consensus interpretation of the tomographic PET slices using a 4-point scale (1=definitely normal, 2=probably normal, 3=probably abnormal, 4=definitely abnormal) was done by two readers blinded to clinical information. RESULTS: All MPI studies in the 23 low likelihood patients were normal. In the remaining 52 patients using a stenosis severity>or=50%, global sensitivity and specificity, negative and positive predictive value for detection of CAD were 86, 100, 57, and 100%. Using a stenosis severity>or=70%, these values changed to 90, 83, 71, and 87%. CONCLUSION: Adenosine stress Rb MPI using PET/CT with manual registration demonstrates diagnostic accuracy comparable with that of traditional PET MPI.     

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.     

Automated quantitative Rb-82 3D PET/CT myocardial perfusion imaging: Normal limits and correlation with invasive coronary angiography

Background

We aimed to characterize normal limits and to determine the diagnostic accuracy for an automated quantification of 3D 82-Rubidium (Rb-82) PET/CT myocardial perfusion imaging (MPI).

Methods

We studied 125 consecutive patients undergoing Rb-82 PET/CT MPI, including patients with suspected coronary artery disease (CAD) and invasive coronary angiography, and 42 patients with a low likelihood (LLk) of CAD. Normal limits for perfusion and function were derived from LLk patients. QPET software was used to quantify perfusion abnormality at rest and stress expressed as total perfusion deficit (TPD).

Results

Relative perfusion databases did not differ in any of the 17 segments between males and females. The areas under the receiver operating characteristic curve for detection of CAD were 0.86 for identification of ??50% and ??70% stenosis. The sensitivity/specificity was 86%/86% for detecting ??50% stenosis and 93%/77% for ??70% stenosis, respectively. In regard to normal limits, mean rest and stress left ventricular ejection fraction (LVEF) were 67%?±?10% and 75%?±?9%, respectively. Mean transient ischemic dilation ratio was 1.06?±?0.14 and mean increase in LVEF with stress was 7.4%?±?6.1% (95th percentile of 0%).

Conclusion

Normal limits have been established for 3D Rb-82 PET/CT analysis with QPET software. Fully automated quantification of myocardial perfusion PET data shows high diagnostic accuracy for detecting obstructive CAD.     

Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity

PURPOSE: The relationship between myocardial blood flow (MBF) and stenosis severity has been determined previously using cyclotron-produced radiotracers such as (15)O-H(2)O and (13)N-ammonia. An attractive alternative to overcome the limitations related to the use of cyclotron might be to use the generator-produced (82)Rb as a flow tracer. The current study was undertaken to investigate the relationship between MBF and coronary vasodilator reserve (CVR) as measured by (82)Rb positron emission tomography (PET) and the percent diameter stenosis as defined by quantitative coronary arteriography. METHODS: We prospectively evaluated 22 individuals: 15 patients (60 +/- 11 years of age) with angiographically documented coronary artery disease (CAD) and seven age-matched (56 +/- 9 years) asymptomatic individuals without risk factors for CAD. Dynamic (82)Rb PET was performed at rest and after dipyridamole vasodilation. MBF, CVR and an index of 'minimal coronary resistance' (MCR) were assessed in each of the three main coronary territories. RESULTS: Rest and stress MBF in regions subtended by vessels with less than 50% diameter stenosis was similar to that of the individuals with no risk factors for CAD. As a result, CVR was also similar in the two groups (1.9, interquartile [IQ] range from 1.7 to 2.7 vs. 2.2, IQ range from 2 to 3.4 respectively, p = 0.09). CVR successfully differentiated coronary lesions with stenosis severity 70% to 89% from those with 50% to 69% stenosis (1, IQ range from 1 to 1.3 vs. 1.7, IQ range from 1.4 to 2), respectively, p = 0.001. In addition, hyperaemic MBF (r (2) = 0.74, p < 0.001), CVR (r (2) = 0.69, p < 0.001) and MCR (r (2) = 0.78, p < 0.001) measurements were inversely and non-linearly correlated to the percent diameter stenosis on angiography. CONCLUSION: MBF and CVR are inversely and non-linearly correlated to stenosis severity. Quantitative (82)Rb PET can be a clinically useful tool for an accurate functional assessment of CAD.     

Integrated PET/CT for the assessment of coronary artery disease: a feasibility study.

An accurate, noninvasive technique for the diagnosis of coronary artery disease (CAD) should provide complementary information on coronary anatomy and pathophysiologic lesion severity. We present, what is to our knowledge, the first clinical evaluation of integrated PET/CT for combined acquisition of coronary anatomy and perfusion. METHODS: On an integrated PET/CT scanner, contrast-enhanced CT angiography (CTA) and rest/adenosine-stress myocardial perfusion scanning with (13)N-ammonia were performed on 25 patients with CAD documented by coronary angiography. Contrast-enhanced CTA was performed with retrospective electrocardiography gating after injection of 150 mL of intravenous contrast medium. Decisions on whether to treat with revascularization (anatomic lesion plus ischemia) or conservatively (no lesion or no ischemia) based on PET/CT were compared with those based on PET plus coronary angiography. RESULTS: Of the 100 coronary artery segments (left main, left anterior descending, left circumflex, and right in 25 patients), 7 (in 5 patients) were considered impossible to evaluate by CT because of rapid vessel movement but were correctly categorized by PET alone. In the remaining 93 segments, the sensitivity and specificity of PET/CT versus PET plus coronary angiography were 90% and 98%, respectively. Positive and negative predictive values were 82% and 99%, and accuracy was 97%. CONCLUSION: The data of this preliminary study suggest that PET/CT allows accurate noninvasive clinical decision making about CAD. Because of its high negative predictive value, PET/CT may play an important role in noninvasive selection of CAD patients for revascularization. Integration of higher-performance multislice spiral CT scanners into PET/CT hybrids will accelerate the clinical implementation of this technique.     

Pathophysiologic correlates of <Superscript>82</Superscript>Rb biodistribution in cardiac PET/CT

Purpose  

PET perfusion imaging with ⁸²Rb is a powerful tool for evaluating coronary artery disease (CAD). Little is known about normal patterns or significance of ⁸²Rb lung distribution in the setting of heart disease. Herein, PET/CT hybrid imaging was used to obtain insights into the frequency and potential radiomorphologic correlates of altered ⁸²Rb distribution.     

腺苷负荷13N-NH3 PET心肌灌注显像结合冠状动脉CTA诊断冠心病

目的 评价腺苷负荷13N-NH3PET心肌灌注显像(MPI)与CT冠状动脉造影(CTA)相结合对提高冠心病(CAD)诊断准确性的临床应用价值.方法 对25例怀疑CAD的患者同时行腺苷负荷13N-NH3MPI及CTA,1个月内行导管法冠状动脉造影(CAG).结果 (1)25例患者共300个冠状动脉节段,CTA显示良好节段为263个,显示率(显示良好节段所占百分比)达87.7%.(2)25例患者CTA、MPI及CTA+MPI诊断CAD的灵敏度、特异性、准确性、阳性预测值及阴性预测值分别为82.1%(23/28),87.5%(14/16)及93.8%(15/16);93.2%(219/235),8/9及9/9;92.O%(242/263),88.0%(22/25)及96.0%(24/25);58.9%(23/29),93.3%(14/15)及100.0%(15/15);97.8%(219/224),8/10及9/10.结论 PET/CT实现了同机腺苷负荷"N-NH3PET心肌灌注显像与CTA相结合,提高了诊断CAD的准确性.     

Does quantification of myocardial flow reserve using rubidium-82 positron emission tomography facilitate detection of multivessel coronary artery disease?

Background

Relative myocardial perfusion imaging (MPI) is the standard imaging approach for the diagnosis and prognostic work-up of coronary artery disease (CAD). However, this technique may underestimate the extent of disease in patients with 3-vessel CAD. Positron emission tomography (PET) is also able to quantify myocardial blood flow. Rubidium-82 (⁸²Rb) is a valid PET tracer alternative in centers that lack a cyclotron. The aim of this study was to assess whether assessment of myocardial flow reserve (MFR) measured with ⁸²Rb PET is an independent predictor of severe obstructive 3-vessel CAD.

Methods

We enrolled a cohort of 120 consecutive patients referred to a dipyridamole ⁸²Rb PET MPI for evaluation of ischemia neither with prior coronary artery bypass graft nor with recent percutaneous coronary intervention that also underwent coronary angiogram within 6?months of the PET study. Patients with and without 3-vessel CAD were compared.

Results

Among patients with severe 3-vessel CAD, MFR was globally reduced (<2) in 88% (22/25). On the adjusted logistic Cox model, MFR was an independent predictor of 3-vessel CAD [.5 unit decrease, HR: 2.1, 95% CI (1.2-3.8); P?=?.015]. The incremental value of ⁸²Rb MFR over the SSS was also shown by comparing the adjusted SSS models with and without ⁸²Rb MFR (P?=?.005).

Conclusion

⁸²Rb MFR is an independent predictor of 3-vessel CAD and provided added value to relative MPI. Clinical integration of this approach should be considered to enhance detection and risk assessment of patients with known or suspected CAD.     

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.     

Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (>or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.     

Mechanisms of progression and regression of coronary artery disease by PET related to treatment intensity and clinical events at long-term follow-up.

Changes in regional myocardial perfusion throughout the entire coronary vascular tree, as opposed to changes in the worst regional perfusion defect, have not been described during long-term regression or progression of coronary artery disease (CAD) or related to clinical outcomes. METHODS: Four-hundred nine patients with CAD undergoing dipyridamole PET at baseline and after 2.6 +/- 1.4 y were followed over 5 more years for coronary events. PET images were objectively quantified by automated software for changes in severity of the (i) baseline worst quadrant, indicating the worst flow-limiting stenosis at baseline PET; (ii) follow-up worst quadrant, indicating the worst stenosis on follow-up PET; and (iii) maximal change quadrant, indicating the largest change of any same quadrant pair from baseline-to-follow-up images. RESULTS: At follow-up PET, new regional perfusion defects were seen in 40% of patients. In 77% of patients, the greatest change was in a quadrant different from the worst baseline defect. The maximal change quadrant improved in 70% of patients on intense lifestyle and pharmacologic lipid treatment, in 48% on moderate treatment, and in 39% on poor treatment (P < 0.0001). Combined quadrant changes integrated throughout the heart independently predicted cardiovascular events at long-term follow-up. In contrast, changes of any single baseline-to-follow-up quadrant pair did not. CONCLUSION: By PET, 77% of patients with CAD had the greatest perfusion changes in areas different from the baseline worst perfusion defect and 40% had new perfusion defects. Changes in perfusion defects throughout the entire coronary vascular tree predicted coronary events, whereas changes in the worst flow-limiting stenosis at baseline or in any one segment of myocardium did not. To our knowledge, these data provide the first direct evidence on mechanisms for disproportionately greater reduction in cardiac events than changes in single stenosis severity with lipid treatment.     

Diagnostic performance of low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT using the 530c CZT camera: Quantitative vs visual analysis

Background

We set out to develop normal databases and prospectively validate abnormality criteria for a low-dose Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera.

Methods

All patients received 6 mCi rest/20 mCi stress doses of Tc-99m tetrofosmin. Rest and stress images were obtained over 7-9 and 5-7 minutes according to the chest size. Low-dose CT of the chest was obtained on a standalone CT scanner. Forty patients with very low likelihood (LLK) of coronary artery disease (CAD) were used to define the normal count distributions. The abnormality criteria were prospectively validated in 55 patients who had coronary angiography and in 40 patients with LLK of CAD.

Results

The results for quantitative non-attenuation-corrected (AC) and AC analysis and visual analysis were as follows: sensitivity of 79%, 85%, and 92% (P = NS) and specificity of 44%, 75%, and 56% (P = NS), respectively. The normalcy rates for quantitative non-AC and AC analyses and visual analysis were 95%, 98%, and 98% (P = NS).

Conclusions

We have developed non-AC and AC normal databases for low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. The per-patient diagnostic performance of quantitative analyses is not significantly different from visual analysis by an experienced reader.     

Economic analysis of clinical positron emission tomography of the heart with rubidium-82

This report describes a cost analysis for clinical positron emission tomography (PET) of the heart using generator produced rubidium-82 (82Rb). Considered sequentially are the clinical problem, current noninvasive radionuclide methods, positron emission tomograph, and the cost of PET per study. Also analyzed are the costs of PET versus thallium imaging in the management of chest pain, for screening asymptomatic men at high risk for coronary artery disease and for evaluating myocardial viability after myocardial infarction or thrombolytic therapy. Noninvasive assessment of coronary artery stenosis and myocardial ischemia/viability in symptomatic or asymptomatic subjects remains a major medical problem because the sensitivity and specificity of thallium imaging are only 70-85% and 50-70%, respectively, in recent studies. Cardiac positron imaging has an accuracy for noninvasive diagnosis of coronary artery disease in symptomatic or asymptomatic patients with a sensitivity and specificity of 95-98%. It can also be used for assessing physiologic stenosis severity, for imaging myocardial infarction and viability, for assessing effects of interventions such as thrombolysis, percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery on myocardial perfusion, metabolism or coronary flow reserve, for assessing collateral function noninvasively in man, and for diagnosing cardiomyopathy not due to coronary artery disease. Although the cost for cardiac PET with 82Rb may be modestly higher than for 201Tl, the greater diagnostic yield of PET results in comparable or lower overall medical management costs than no diagnostic tests/interventions and lower overall costs compared to thallium imaging for evaluating patients with chest pain, asymptomatic high risk males, and patients after acute myocardial infarction/thrombolysis for myocardial viability.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by <Superscript>82</Superscript>Rb PET/CT in the identification of obstructive coronary artery disease

Purpose

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD).

Methods

We analyzed 113 patients with suspected CAD referred to ⁸²Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD.

Results

Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6?±?6.2 vs. 0.6?±?1.3) and lower hyperemic MBF (1.01?±?0.5 vs. 1.75?±?0.6 ml/min/g) and CFR (1.56?±?0.6 vs. 2.38?±?0.7; all p?<?0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p?<?0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365–1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64–1.26) for the CAC/ITPD/CFR model.

Conclusion

Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

     

Diagnostic performance of fusion of myocardial perfusion imaging (MPI) and computed tomography coronary angiography

Background  We evaluated the incremental diagnostic value of fusion images of coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) over MPI alone or MPI and CTA side-by-side to identify obstructive coronary artery disease (CAD > 50% stenosis) using invasive coronary angiography (ICA) as the gold standard. Methods  50 subjects (36 men; 56 ± 11 years old) underwent rest-stress MPI and CTA within 12-26 days of each other. CTAs were performed with multi-detector CT-scanners (31 on 64-slice; and 19 on 16-slice). 37 patients underwent ICA while 13 subjects did not because of low (<5%) pre-test likelihood (LLK) of disease. Three blinded readers scored the images in sequential sessions using (1) MPI alone (2) MPI and CTA side-by-side, (3) fused CTA/MPI images. Results  One or more critical stenoses during ICA were found in 28 patients and non-critical stenoses were found in 9 patients. MPI, side-by-side MPI-CTA, and fused CTA/MPI showed the same normalcy rate (NR:13/13) in LLK subjects. The fusion technique performed better than MPI and MPI and CTA side-by-side for the presence of CAD in any vessel (overall area under the curve (AUC) for fused images: 0.89; P = .005 vs MPI, P = .04 vs side-by-side MPI-CTA) and for localization of CAD to the left anterior descending coronary artery (AUC: 0.82, P < .001 vs MPI; P = .007 vs side-by-side MPI-CTA). There was a non-significant trend for better detection of multi-vessel disease with fusion. Conclusions  Using ICA as the gold standard, fusion imaging provided incremental diagnostic information compared to MPI alone or side-by-side MPI-CTA for the diagnosis of obstructive CAD and for localization of CAD to the left anterior descending coronary artery.     

Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects.

Coronary endothelial dysfunction is an early marker of coronary artery disease (CAD) but its noninvasive assessment is limited. We tested the hypothesis that diffuse patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET, quantified objectively by Markovian homogeneity analysis, or its improvement during dipyridamole stress, is a predictor of even mild stress perfusion abnormalities, consistent with coronary microvascular dysfunction as an early marker of CAD. METHODS: Rest-dipyridamole PET with (82)Rb was performed on 1,034 consecutive subjects for possible CAD or follow-up, for second opinion on revascularization procedures, or for screening because of risk factors and on 50 healthy control subjects. Objective, automated software quantified myocardial PET perfusion images for (i) patchy diffuse perfusion heterogeneity by Markovian homogeneity analysis separately from, independently of, and around significant localized regional perfusion defects; (ii) size and severity of localized regional perfusion defects caused by flow-limiting stenosis; and (iii) the graded base-to-apex longitudinal perfusion gradient due to early diffuse CAD without flow-limiting stenosis. History of vascular risk factors was obtained for all subjects. RESULTS: Resting myocardial perfusion heterogeneity with a homogeneity index outside 1 SD of healthy reference subjects and its improvement with dipyridamole correlated closely with CAD documented by stress-induced regional myocardial perfusion abnormalities outside 1 SD independently of other risk factors by multivariate logistic regression analysis (P < 0.001), by multivariate linear regression analysis (P < 0.001), and by chi(2) analysis (P < 0.001). The relative odds ratios of having stress-induced myocardial perfusion abnormalities for a resting homogeneity index outside 1 SD of healthy reference subjects was highly predictive and substantially greater than for standard risk factors. CONCLUSION: Patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET quantified objectively using Markovian homogeneity analysis, and its improvement after dipyridamole, are powerful independent predictors of even mild stress-induced perfusion abnormalities, more than standard risk factors, consistent with coronary microvascular dysfunction as an early marker of preclinical CAD for potential preventive treatment.     

Noninvasive assessment of coronary collaterals in man by PET perfusion imaging

At present, coronary collateralization cannot be identified or assessed noninvasively in patients. In animal studies, coronary collaterals are associated with coronary steal, defined as a regional fall in perfusion during coronary arteriolar vasodilation. To determine the effect of coronary arteriolar vasodilation on collateral bed perfusion in man, myocardial perfusion imaging was performed before and after pharmacologic coronary vasodilation in patients with coronary artery disease (CAD). Regional myocardial activity of 82Rb or 13N ammonia was measured by positron emission tomography (PET) at rest and with intravenous dipyridamole/handgrip stress in 28 patients with angiographic collaterals and in 25 control patients with similar CAD severity by quantitative arteriography. Regional myocardial activity decreased after dipyridamole, indicating coronary steal, in 25 of 28 patients with angiographic collaterals and in only 4 of 25 control patients without angiographic collaterals. These findings suggest that developed collaterals are associated with myocardial steal in patients with CAD, allowing potential use of PET for non-invasive identification of coronary collateralization.     

82Rb PET myocardial perfusion imaging is superior to 99mTc-labelled agent SPECT in patients with known or suspected coronary artery disease

Purpose

We compared the quality, interpretive confidence and interreader agreement between SPECT and PET myocardial perfusion imaging (MPI) in the same group of patients.

Methods

The study group comprised 27 patients (age 55?±?8.5?years, 12 men) with known or suspected coronary artery disease (CAD) who had undergone gated rest/stress MPI with ^99mTc-labelled agent SPECT (with and without attenuation correction, AC), and subsequent clinical confirmation with ⁸²Rb PET. Three experienced readers blinded to the clinical information interpreted all MPI studies.

Results

Interreader agreement was significantly superior for PET studies than for SPECT studies. Following consensus interpretation, the quality of 22?% of the non-AC SPECT studies, 33?% of the AC SPECT studies and 63?% of the PET studies was assessed as excellent or good (p?=?0.016). Interpretations were definitely normal or abnormal in 7?% of non-AC SPECT studies, 30?% of AC SPECT studies and 85?% of PET studies (p?=?0.046). In 13 patients who had received either invasive coronary angiography or CT angiography with no significant CAD, the true-positive rate for significant CAD was higher for PET, and the true-negative rate was equal for PET and AC SPECT, and lower for non-AC SPECT.

Conclusion

⁸²Rb PET MPI, used as a confirmatory test after SPECT, offers improved image quality, interpretive confidence and interreader agreement.     

Comparison of 99mTc-sestamibi lung/heart ratio, transient ischaemic dilation and perfusion defect size for the identification of severe and extensive coronary artery disease

The ability to identify patients with severe coronary artery disease (CAD) by analysis of perfusion defects is limited. The lung/heart ratio (LHR) and transient ischaemic dilatation (TID) have been used for this purpose in thallium-201 scintigraphy. The value of these parameters in technetium-99m sestamibi single-photon emission tomography (SPET) imaging is controversial. In this study, therefore, we determined TID and LHR in a single-day rest/stress 99mTc-sestamibi SPET perfusion protocol and compared these measurements with perfusion defect size (PDS) and angiographic severity of CAD. Severe CAD was defined as >75% left main coronary stenosis and/or >90% proximal left anterior descending artery stenosis and/or >90% proximal stenosis in the left circumflex and right coronary arteries. LHR was determined from a stress anterior planar image recorded < or =6 min after exercise. TID ratio was derived from automatically calculated left ventricular rest/stress volumes, and PDS was measured based on semi-automated computer software (CEqual). Diagnostic accuracy and predictive values were compared between 22 patients with severe and 98 patients without severe CAD. LHRs showed a higher sensitivity (73%) for the assessment of severe CAD as compared to PDS and TID ratio (41% and 23% respectively, P<0.01), whereas specificity was highest for TID ratio [95%, P<0.01 when compared to PDS (84%) and LHR (82%)]. It is concluded that increased LHR in 99mTc-sestamibi myocardial perfusion imaging seems to yield good diagnostic accuracy in the detection of patients with severe CAD and may be derived from a single-day rest/stress study.