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JAMA The Journal of the American Medical Association 01/2013; 309(3):234-5. · 30.03 Impact Factor
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JACC. Cardiovascular imaging 11/2012; 5(11):1184-5. · 14.29 Impact Factor
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Journal of Nuclear Cardiology 10/2012; · 2.67 Impact Factor
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Journal of Nuclear Cardiology 10/2012; · 2.67 Impact Factor
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ABSTRACT: Noninvasive, absolute myocardial perfusion and coronary flow reserve (CFR) can be imaged by many techniques. However, such data must be interpreted for clinical application regardless of its source. Currently, no guide exists for physiological integration. Therefore, we propose 2-dimensional scatter plots of stress flow and CFR with superimposed thresholds for normal flow, reduced flow without ischemia, definite ischemia, and transmural infarction to allow for automatic and objective classification. Application of this schema to 1,500 studies demonstrates that flow capacity relates inversely to risk factors and atherosclerotic burden. Interpreting stress flow to make clinical decisions requires rest flow or CFR for broad application to all patients. Although relative uptake images alone are adequate for some patients, it can either under- or over-estimate flow capacity in many persons. Our standardized framework could prompt future studies leading to a trial of revascularization guided by absolute flow measurements.
JACC. Cardiovascular imaging 04/2012; 5(4):430-40. · 14.29 Impact Factor
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JACC. Cardiovascular imaging 02/2012; 5(2):190-2. · 14.29 Impact Factor
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ABSTRACT: The purpose of this study was to determine whether observed discordance between coronary flow reserve (CFR) and fractional flow reserve (FFR) is due to methodology or reflects basic coronary pathophysiology.
Despite the clinical importance of coronary physiological assessment, relationships between its 2 most common tools, CFR and FFR, remain poorly defined.
The worst CFR and stress relative uptake were recorded from 1,500 sequential cardiac positron emission tomography cases from our center. From the literature, we assembled all combined, invasive CFR-FFR measurements, including a subset before and after angioplasty. Both datasets were compared with a fluid dynamic model of the coronary circulation predicting relationships between CFR and FFR for variable diffuse and focal narrowing.
A modest but significant linear relationship exists between CFR and FFR both invasively (r = 0.34, p < 0.001) and using positron emission tomography (r = 0.36, p < 0.001). Most clinical patients undergoing CFR or FFR measurements have diffusely reduced CFR consistent with diffuse atherosclerosis or small-vessel disease. The theoretical model predicts linear relationships between CFR and FFR for progressive stenosis with slopes dependent on diffuse narrowing, matching observed data. Reported changes in CFR and FFR with angioplasty agree with model predictions of removing focal stenosis but leaving diffuse disease. Although CFR-FFR concordance is common, discordance is due to dominant or absent diffuse versus focal disease, reflecting basic pathophysiology.
CFR is linearly related to FFR for progressive stenosis superimposed on diffuse narrowing. The relative contributions of focal and diffuse disease define the slope and values along the linear CFR and FFR relationship. Discordant CFR and FFR values reflect divergent extremes of focal and diffuse disease, not failure of either tool. With such discordance observed by invasive and noninvasive techniques and also fitting fluid dynamic predictions, it reflects clinically relevant basic coronary pathophysiology, not methodology.
JACC. Cardiovascular imaging 02/2012; 5(2):193-202. · 14.29 Impact Factor
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Journal of Nuclear Medicine 11/2011; 52(11):1835; author reply 1835-6. · 6.38 Impact Factor
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ABSTRACT: This study aimed to determine the quantitative low-flow threshold for stress-induced perfusion defects with severe angina and/or significant ST-segment depression during dipyridamole hyperemia.
Vasodilator stress reveals differences in regional perfusion without ischemia in most patients. However, in patients with a perfusion defect, angina, and/or significant ST-segment depression during dipyridamole stress, quantitative absolute myocardial perfusion and coronary flow reserve (CFR) at the exact moment of definite ischemia have not been established. Defining these low-flow thresholds of angina or ST-segment changes may offer insight into physiological disease severity in patients with atherosclerosis.
Patients underwent rest-dipyridamole stress positron emission tomography (PET) with absolute flow quantification in ml/min/g. Definite ischemia was defined as a new or worse perfusion defect during dipyridamole stress with significant ST-segment depression and/or severe angina requiring pharmacological treatment. Indeterminate clinical features required only 1 of these 3 abnormalities. The comparison group included patients without prior myocardial infarction, or angina or electrocardiographic changes after dipyridamole.
In 1,674 sequential PET studies, we identified 194 (12%) with definite ischemia, 840 (50%) studies with no ischemia, and 301 (18%) that were clinically indeterminate. A vasodilator stress perfusion cutoff of 0.91 ml/min/g optimally separated definite from no ischemia with an area under the receiver-operator characteristic curve (AUC) of 0.98 and a CFR cutoff of 1.74 with an AUC = 0.91, reflecting excellent discrimination at the exact moment of definite ischemia.
Thresholds of low myocardial vasodilator stress perfusion in ml/min/g and CFR sharply separate patients with angina or ST-segment change from those without these manifestations of ischemia during dipyridamole stress with excellent discrimination. Stress flow below 0.91 ml/min/g in dipyridamole-induced PET perfusion defects causes significant ST-segment depression and/or severe angina. However, when the worst vasodilator stress flow exceeds 1.12 ml/min/g, these manifestations of ischemia occur rarely.
JACC. Cardiovascular imaging 09/2011; 4(9):990-8. · 14.29 Impact Factor
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Journal of Nuclear Cardiology 08/2011; 18(6):1115. · 2.67 Impact Factor
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08/2011; 4(8):932-3. · 1.07 Impact Factor
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ABSTRACT: We sought to quantify ranges of normal myocardial perfusion and flow reserve in young, asymptomatic volunteers after systematic historical and laboratory screening for unexpected factors affecting coronary flow.
Noninvasive cardiac positron emission tomography (PET) quantifies absolute flow and coronary flow reserve (CFR), thereby defining physiological severity of coronary artery disease for clinical studies or management. Defining "normal" coronary flow is a necessary prerequisite to its broad clinical application.
Volunteers aged 20 to 40 years of age without cardiac disease or other conditions underwent rest-dipyridamole stress cardiac PET with absolute quantitative flow measurements using Rb-82 in paired studies at least 7 days apart for reproducibility. The presence of coronary calcium, detectable blood nicotine or caffeine, dyslipidemia, and an extended family history of early clinical atherosclerosis were objectively and systematically examined for grouping subjects as true normal or not normal.
We enrolled 125 volunteers, 107 (86%) underwent 2 PET scans. Fifty-six (45%) were classified as true normal, whereas 69 (55%) were classified as not normal. True normals had higher high-density lipoprotein and less PET scan heterogeneity. Hemodynamic responses to dipyridamole stress were similar. Rest flow was the same in both groups (0.72 ± 0.17 ml/min/g vs. 0.69 ± 0.14 ml/min/g, p = 0.164). However, stress flow (2.89 ± 0.50 ml/min/g vs. 2.63 ± 0.61 ml/min/g, p = 0.005) and CFR (4.17 ± 0.80 vs. 3.91 ± 0.86, p = 0.047) were higher in true normals. Paired studies were performed a median of 22 days (interquartile range: 15 to 39) apart. Reproducibility was improved in the true normal group.
One-half of young, asymptomatic volunteers from the community harbor unexpected factors that mildly but systematically reduce stress flow, CFR, and reproducibility. This study establishes normal ranges and reproducibility for flow and CFR as the basis for clinical applications.
JACC. Cardiovascular imaging 04/2011; 4(4):402-12. · 14.29 Impact Factor
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ABSTRACT: Quantitative myocardial PET perfusion imaging requires partial volume corrections.
Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections.
For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18.
Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.
Journal of Nuclear Cardiology 12/2010; 18(2):247-58. · 2.67 Impact Factor
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ABSTRACT: fluid dynamic analysis predicts a new concept in coronary physiology that we call "branch steal," whereby stenosis proximal and distal to arterial branching interact with the nonstenotic branch between stenosis that shunts or "steals" flow away from the distal stenotic artery during reactive hyperemia, tested experimentally.
in 21 large hounds under surgical anesthesia, proximal and distal left circumflex and obtuse marginal coronary arteries were instrumented with electromagnetic flowmeters, proximal and distal machined Teflon screw-down stenosers with round concentric closing and distal silk-in-tubing sleeve occluders. Baseline reactive hyperemia was recorded after 15-second occlusions of both arteries at baseline and for progressive distal stenosis during each step of progressive proximal stenosis. At each combination of stenosis, a coronary arteriogram was obtained using left Judkins catheters and Philips cine calibrated with modulated transfer function to ± 0.1 mm accuracy for fluid dynamic analysis of arterial stenosis-branching anatomy. In 324 experiments of parent-child stenosis combinations of the left circumflex artery with an intervening obtuse marginal branch, coronary flow reserve (CFR) calculated by the fluid dynamic model accounting for stenosis-branch interactions and "branch steal" correlated with CFR directly measured by flowmeter (linear regression, CFRartgm=0.18+0.7×CFRflowmtr with Pearson r=0.73). Quantitative arteriography and positron emission tomography perfusion imaging confirmed the concept in clinical examples.
functional severity of anatomically fixed stenosis is not constant, specific, or independent of other stenosis in branching coronary arteries but requires analysis as an integrated component of the entire branching coronary artery tree to guide revascularizations.
Circulation Cardiovascular Imaging 11/2010; 3(6):701-9. · 5.94 Impact Factor
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ABSTRACT: Positron emission tomography-computed tomography (PET-CT) uses CT attenuation correction but suffers from misregistration artifacts. However, the quantitative accuracy of helical versus cine CT in the same patient after optimized coregistration by shifting both CT data as needed for each patient is unknown. We studied 293 patients undergoing cardiac perfusion PET-CT using helical CT attenuation correction for comparison to cine CT. Objective, quantitative criteria identified perfusion abnormalities that were associated visually with PET-CT misregistration. Custom software shifted CT data to optimize coregistration with quantitative artifact improvement. The majority (58.1%) of cases with both helical and shifted helical CT data (n = 93) had artifacts that improved or resolved by software shifting helical CT data. Translation of shifted helical CT was greatest in the x-direction (8.8 ± 3.3 mm) and less in the y- and z-directions (approximately 3.5 mm). The magnitude of differences in quantitative end points was greatest for helical (p = .0001, n = 177 studies), less for shifted helical but significant (p = .0001, n = 93 studies), and least for cine (not significant, n = 161 studies) CT compared to optimal attenuation correction for each patient. Frequent artifacts owing to attenuation-emission misregistration are substantially corrected by software shifting helical CT scans to achieve proper coregistration that, however, remains on average significantly inferior to cine CT attenuation quantitatively.
Molecular Imaging 10/2010; 9(5):256-67. · 3.18 Impact Factor
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ABSTRACT: The optimum strategy to treat patients with coronary artery disease (CAD) has been under debate. New data show that revascularization guided by fractional flow measurements leads to better outcomes than revascularization guided by arteriography. we call for a paradigm shift in CAD care, with coronary flow measurements by PET as key to diagnosis and clinical decision-making.
Nature Reviews Cardiology 09/2010; 7(9):482-4. · 8.83 Impact Factor
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ABSTRACT: Nuclear cardiology utilizes radioactive tracers to image primarily physiology as opposed to anatomy. Its two key imaging techniques,
single photon emission computed tomography (SPECT) and positron emission tomography (PET), offer tradeoffs in terms of availability,
cost, artifacts, quantification, and complexity. This chapter discusses the physiologic signals of interest in nuclear cardiology,
from their acquisition to processing to reproducibility and noise.
12/2009: pages 219-250;
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K Lance Gould
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ABSTRACT: Coronary function versus anatomy, flow versus stenosis: which optimizes coronary artery disease (CAD) management? In patients, coronary flow is poorly related to stenosis severity, and revascularization fails to improve mortality over medical treatment in randomized trials. Yet percutaneous intervention (PCI) guided by fractional flow reserve reduces coronary events more than PCI guided by arteriographic stenosis. These paradoxes are explained by the poor relation between coronary flow reserve (CFR) and stenosis severity due to diffuse CAD, with surprising clinical implications. Should the concept of anatomically "critical" coronary stenosis be replaced by the concept of "critical" CFR reduction for managing CAD?
JACC. Cardiovascular imaging 09/2009; 2(8):1009-23. · 14.29 Impact Factor
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K Lance Gould
JACC. Cardiovascular imaging 06/2009; 2(5):664-9. · 14.29 Impact Factor
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04/2009: pages 13-36;
