K. Lance Gould

Frequent Diagnostic Errors in Cardiac PET/CT Due to Misregistration of CT Attenuation and Emission PET Images: A Definitive Analysis of Causes, Consequences, and Corrections

Cardiac PET combined with CT is rapidly expanding despite artifactual defects and false-positive results due to misregistration of PET and CT attenuation correction data—the frequency, cause, and correction of which remain undetermined. Methods: Two hundred fifty-nine consecutive patients underwent diagnostic rest–dipyridamole myocardial perfusion PET/CT using 82Rb, a 16-slice PET/CT scanner, helical CT attenuation correction with breathing and also at end-expiratory breath-hold, and averaged cine CT data during breathing. Misregistration on superimposed PET/CT fusion images was objectively measured in millimeters and correlated with associated quantitative size and severity of PET defects. Misregistration artifacts were defined as PET defects with corresponding misregistration on helical CT-PET fusion images that resolved after correct coregistration using a repeat CT scan, cine CT averaged attenuation during normal breathing, or shifted cine CT data that coregistered with PET data. Results: Misregistration of standard helical CT PET images caused artifactual PET defects in 103 of 259 (40%) patients that were moderate to severe in 59 (23%) (P = 0.0000) and quantitatively normalized on cine or shifted cine CT PET (P = 0.0000). Quantitative misregistration was a powerful predictor of artifact size and severity (P = 0.0000), particularly for transaxial misregistration >6 mm occurring in anterior or lateral areas in 76%, in inferior areas in 16%, and at the apex in 8% of 103 artifactual defects. Conclusion: Misregistration of helical CT attenuation and PET emission images causes artifactual defects with false-positive results in 40% of patients that normalize on cine CT PET using averaged CT attenuation data during normal breathing comparable to normal breathing during PET emission scanning and shifting cine CT images to coregister visually with PET.

Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography

BACKGROUNDnDiffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET.nnnMETHODS AND RESULTSnIn this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis.nnnCONCLUSIONSnIn patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

Does Coronary Flow Trump Coronary Anatomy

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?

Combined intense lifestyle and pharmacologic lipid treatment further reduce coronary events and myocardial perfusion abnormalities compared with usual-care cholesterol-lowering drugs in coronary artery disease ☆

OBJECTIVESnThe purpose of this study was to determine if combined intense lifestyle and pharmacologic lipid treatment reduce myocardial perfusion abnormalities and coronary events in comparison to usual-care cholesterol-lowering drugs and whether perfusion changes predict outcomes.nnnBACKGROUNDnLifestyle and lipid drugs separately benefit patients with coronary artery disease (CAD).nnnMETHODSnA total of 409 patients with CAD, who underwent myocardial perfusion imaging by dipyridamole positron emission tomography at baseline and after 2.6 years, had quantitative size/severity of perfusion defects measured objectively by automated software with follow-up for five additional years for coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction, or cardiac death. Patients were categorized blindly according to prospective, predefined criteria as poor treatment without diet or lipid drugs, or smoking; moderate treatment on American Heart Association diet and lipid-lowering drugs or on strict low-fat diet (<10% of calories) without lipid drugs; and maximal treatment with diet <10% of calories as fat, regular exercise, and lipid active drugs dosed to target goals of low-density lipoproteins <2.3 mmol/l (90 mg/dl), high-density lipoproteins >1.2 mmol/l (45 mg/dl), and triglycerides <1.1 mmol/l (100 mg/dl).nnnRESULTSnOver five years, coronary events occurred in 6.6%, 20.3%, and 30.6% of patients on maximal, moderate, and poor treatment, respectively (p = 0.001). Size/severity of perfusion abnormalities significantly decreased for patients receiving maximal treatment and increased for patients undergoing moderate and poor treatment (p = 0.003 and 0.0001, respectively). Combined intense lifestyle change plus lipid active drugs and severity/change of perfusion abnormalities independently predicted cardiac events.nnnCONCLUSIONSnIntense lifestyle and pharmacologic lipid treatment reduce size/severity of myocardial perfusion abnormalities and cardiac events compared with usual-care cholesterol-lowering drugs. Perfusion changes parallel treatment intensity and predict outcomes.

Integrating noninvasive absolute flow, coronary flow reserve, and ischemic thresholds into a comprehensive map of physiological severity

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.

High Prevalence of Myocardial Perfusion Abnormalities on Positron Emission Tomography in Asymptomatic Persons With a Parent or Sibling With Coronary Artery Disease

Background —We hypothesized that asymptomatic persons with a parent or sibling with coronary artery disease (CAD) have myocardial perfusion defects on positron emission tomography (PET) as markers of early CAD. Methods and Results —After medical and family histories were recorded, 90 subjects underwent rest-dipyridamole cardiac PET perfusion imaging, including 18 index cases (a subject with CAD documented by PET and arteriography), 32 asymptomatic adults without known CAD who had a parent or sibling with CAD among these index cases, 30 asymptomatic subjects with comparable coronary risk factors without CAD or a family history of CAD, and 10 volunteer control subjects with no risk factors and no family history. PET perfusion images were quantified with automated software for size of abnormalities as percent of the cardiac image outside 95% CIs of normal controls and for severity as the lowest quadrant average relative activity. Of asymptomatic subjects with a parent or sibling with CAD (first-degree relatives), 50% had dipyridamole-induced myocardial perfusion defects that involved ≥5% of the cardiac image outside normal 95% CIs with or without other risk factors. The size of perfusion defects was larger in first-degree relatives than in control subjects (11±13% versus 1±1%, P =0.02) and larger than in asymptomatic subjects with comparable risk factors but no family history of CAD (11±13% versus 5±6%, P =0.02). Conclusions —This study documents the presence of quantitative, statistically significant, dipyridamole-induced myocardial perfusion abnormalities on PET in 50% of asymptomatic persons with a parent or sibling with CAD, independent of other risk factors, indicating preclinical coronary atherosclerosis.

Reducing Radiation Dose in Rest–Stress Cardiac PET/CT by Single Poststress Cine CT for Attenuation Correction: Quantitative Validation

Cardiac PET/CT is optimized by cine CT with dedicated shift software for manual correction of attenuation–emission misregistration. Separate rest and stress CT scans incur greater radiation dose to patients than does standard helical PET/CT or “pure” PET using rotating rod attenuation sources. To reduce radiation dose, we tested quantitative accuracy of using a single poststress cine CT attenuation scan for reconstructing rest perfusion images to eliminate resting CT attenuation scans. Methods: A total of 250 consecutive patients underwent diagnostic rest-dipyridamole myocardial perfusion PET/CT with 82Rb and a 16-slice PET/CT scanner using averaged cine CT attenuation data during breathing at rest and stress. After correcting for any attenuation–emission misregistration, we quantitatively compared resting perfusion images reconstructed using rest cine CT attenuation data with the same resting emission data reconstructed with poststress cine CT attenuation data. Automated software quantifying average regional quadrant activity, severity, size, and combined size and severity of perfusion defects was used for this comparison. Results: Resting perfusion images reconstructed using rest cine CT attenuation data were quantitatively comparable to resting images reconstructed with poststress cine CT attenuation data with no clinically significant differences. Twenty-five (10%) of 250 cases required shifting of stress cine CT attenuation data to achieve optimal attenuation–emission coregistration with resting perfusion data. Eliminating rest CT attenuation scans reduced CT radiation dose by 50% below rest-plus-stress cine CT protocols. Conclusion: Resting perfusion images reconstructed using poststress cine CT attenuation data are quantitatively comparable to resting images reconstructed with resting cine CT attenuation data. Eliminating the rest CT scan reduces CT radiation dose by 50%.

Coronary Flow Reserve and Pharmacologic Stress Perfusion Imaging. Beginnings and Evolution

Pharmacologic stress for myocardial perfusion imaging fell out of my first experiment measuring coronary flow during progressive stenosis in 1972, published in 1974 ([1][1]). The arteriogram and flowmeter dramatically showed the 3 fundamental physiological concepts underlying all stress myocardial

Positron emission tomography in coronary artery disease.

Purpose of review Mortality and coronary events are dramatically reduced in coronary artery disease by intense lifestyle and pharmacologic management without further improvement by revascularization procedures, thereby requiring definitive noninvasive diagnostic imaging. Consequently, this review summarizes the evidence supporting cardiac positron emission tomography as a definitive, noninvasive, ‘one-stop’ test for routine management of coronary artery disease that is well validated in the scientific literature and illustrated by clinical cases. Recent findings Substantial evidence documents accuracy of positron emission tomography for identifying early or advanced coronary artery disease, quantifying its severity, risk stratification, deciding on revascularization procedures, following progression or regression and for evaluating coronary endothelial function as the basis for preventive treatment. Recent technology like positron emission tomography-computed tomography, however, requires advanced knowledge, training and attention to technical details to avoid common artifactual results and to provide definitive conclusions illustrated in this review. Summary Cardiac positron emission tomography, done correctly with attention to technical details, provides definitive noninvasive assessment of early or advanced coronary atherosclerosis as the basis for invasive procedures or for lifelong intense risk factor management, demonstrates progression or regression of disease, predicts clinical outcomes and serves as the primary definitive noninvasive guide for managing coronary artery disease.

A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease.

BACKGROUNDnIn coronary artery disease (CAD), statins decrease morbidity and mortality but changes in myocardial perfusion abnormalities remain poorly defined.nnnMETHODSnWe completed a randomized, double blind, placebo controlled, multi-center trial of 145 patients, 43 to 86 years old, with CAD from seven community and academic centers for cardiac positron emission tomography (PET) randomized to 6 months of atorvastatin 80 mg daily (72 patients) or placebo (73 patients). PET scans were obtained at baseline, 6 weeks and 6 months using N-13 ammonia or Rb-82 at rest and after dipyridamole or adenosine stress, submitted to the core PET laboratory in Houston. Change in stress induced perfusion defects from baseline to follow-up PET scans was scored by two independent, double blinded readers and by automated quantitative software.nnnRESULTSnTotal and LDL cholesterol decreased by 37% and 51%, respectively in atorvastatin but not placebo groups (P < .05). The primary endpoint, quantitative severity (lowest mean quadrant activity), showed no significant difference between treatment and placebo. The secondary endpoint, predefined blinded visual change scores, improved significantly after atorvastatin compared to placebo at six months (P = .02). Ad-hoc subgroup analysis showed interaction between quantitative defect size and treatment response with perfusion defects in the upper tertile of size by automated software improving more in atorvastatin than placebo groups (P = .016).nnnCONCLUSIONnThe primary endpoint, quantitative severity of myocardial perfusion abnormalities by PET, did not improve after 6 months of atorvastatin 80 mg daily compared to placebo. The secondary endpoint of predefined blinded visual change scores significantly improved, as did a subgroup in the upper tertile of defect size, compared to placebo.