Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Quantitative myocardial perfusion positron emission tomography and caffeine revisited with new insights on major adverse cardiovascular events and coronary flow capacity.

AIMS: To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). METHODS AND RESULTS: Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). CONCLUSION: Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.

Fulminant Vascular and Cardiac Toxicity Associated with Tyrosine Kinase Inhibitor Sorafenib.

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

Influence of Contrast Media Dose and Osmolality on the Diagnostic Performance of Contrast Fractional Flow Reserve.

BACKGROUND: Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance. METHODS AND RESULTS: cFFR, instantaneous wave-free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR≤0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (P<0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity. CONCLUSIONS: The overall accuracy of cFFR is greater than instantaneous wave-free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02184117.

Optimal Adenosine Stress for Maximum Stress Perfusion, Coronary Flow Reserve, and Pixel Distribution of Coronary Flow Capacity by Kolmogorov-Smirnov Analysis.

BACKGROUND: Different adenosine stress imaging protocols have not been systemically validated for absolute myocardial perfusion and coronary flow reserve (CFR) by positron emission tomography, where submaximal stress precludes assessing physiological severity of coronary artery disease. METHODS AND RESULTS: In 127 volunteers, serial rest-stress positron emission tomography scans using rubidium-82 with various adenosine infusion protocols identified (1) the protocol with maximum stress perfusion and CFR, (2) test-retest precision in same subject, (3) stress perfusion and CFR after adenosine compared with dipyridamole, (4) heterogeneity of coronary flow capacity combining stress perfusion and CFR, and (5) potential relevance for patients with risk factors or coronary artery disease. The adenosine 6-minute infusion with rubidium-82 injection at 3 minutes caused CFR that was significantly 15.7% higher than the 4-minute adenosine infusion with rubidium-82 injection at 2 minutes and significantly more homogeneous by Kolmogorov-Smirnov analysis for histograms of 1344 pixel range of perfusion in paired positron emission tomographies. In a coronary artery disease cohort separate from volunteers of this study, compared with the 3/6-minute protocol, the 2/4-minute adenosine protocol would potentially have changed 332 of 1732 (19%) positron emission tomographies at low-risk physiological severity CFR ≥2.3 to CFR <2.0, thereby implying high-risk quantitative severity potentially appropriate for interventions but because of suboptimal stress of the 2/4 protocol in some patients. CONCLUSIONS: The 6-minute adenosine infusion with rubidium-82 activation at 3 minutes produced CFR that averaged 15.7% higher than that in the 2/4-minute protocol, thereby potentially providing essential information for personalized management in some patients.

The Influence of Lesion Location on the Diagnostic Accuracy of Adenosine-Free Coronary Pressure Wire Measurements.

OBJECTIVES: This work compares the diagnostic performance of adenosine-free coronary pressure wire indices based on lesion location. BACKGROUND: Several adenosine-free coronary pressure wire indices have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that lesion location and the mass of perfused myocardium may affect diagnostic performance. METHODS: A total of 763 patients were prospectively enrolled from 12 institutions. Fractional flow reserve (FFR) and contrast-based FFR (cFFR) were obtained during adenosine-induced maximal hyperemia and contrast-induced submaximal hyperemia respectively, whereas the instantaneous wave-free ratio (iFR) and distal pressure/aortic pressure (Pd/Pa) were obtained at rest. Using an FFR of ≤0.80 as a reference standard, the diagnostic accuracy of each index was compared based on lesion location (left main or proximal left anterior descending artery [LM/pLAD] compared with other lesion locations). RESULTS: The median FFR, cFFR, iFR, and Pd/Pa were 0.81 (interquartile range [IQR]: 0.74 to 0.87), 0.86 (IQR: 0.79 to 0.91), 0.90 (IQR: 0.85 to 0.94), and 0.92 (IQR: 0.88 to 0.95), respectively. The cFFR, iFR, and Pd/Pa were less accurate in LM/pLAD compared with other lesion locations (cFFR: 80.3% vs. 87.8%; iFR: 73.3% vs. 81.8%; Pd/Pa: 71.4% vs. 81.1%, respectively). By receiver-operating characteristics curve analysis, cFFR provided better diagnostic accuracy than resting indices regardless of lesion location (p ≤0.0001 vs. iFR and Pd/Pa for both groups). CONCLUSIONS: The cFFR, iFR, and Pd/Pa are less accurate in LM/pLAD compared with other lesion locations, likely related to the larger amount of myocardium supplied by LM/pLAD. Nevertheless, cFFR provides the best diagnostic accuracy among the adenosine-free indices, regardless of lesion location.

Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment.

OBJECTIVES: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). BACKGROUND: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. METHODS: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. RESULTS: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. CONCLUSIONS: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.

Quantitative Coronary Physiology for Clinical Management: the Imaging Standard.

Pressure derived FFR and coronary flow capacity by PET define a physiologic severity-risk-benefit continuum wherein probability of benefit from revascularization over risk of the procedure and risk of residual global diffuse disease guides personalized, informed, evidenced based, interventional decisions. For the many variations in PET or MRI protocols for quantifying myocardial perfusion to define physiologic severity, the simple standard performance test combining measurement accuracy and clinical coronary pathophysiology to assure correct clinical decisions is the capacity to measure (i) rest perfusion of 0.2 cm(3)/min/gm in transmural scar in at least five patients to test low perfusion accuracy (ii) regional and global CFR of 4.0 or stress perfusion of 2.9 cm(3)/min/gm on two sequential rest-stress PET perfusion studies in the same subject with ±15 % variability for at least 15 young healthy volunteers with no risk factors, no smoking, no obesity, and no measureable blood caffeine levels.

Repeatability of Fractional Flow Reserve Despite Variations in Systemic and Coronary Hemodynamics.

OBJECTIVES: This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion. BACKGROUND: Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate. METHODS: We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 µg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the "smart minimum" FFR using a novel algorithm, which was compared with human core laboratory analysis. RESULTS: A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: "classic" (sigmoid) in 57%, "humped" (sigmoid with superimposed bumps of varying height) in 39%, and "unusual" (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the "smart minimum" FFR demonstrated excellent repeatability (bias -0.001, SD 0.018, paired p = 0.93, r(2) = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE). CONCLUSIONS: Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR - when chosen appropriately - proved to be a highly reproducible value. Therefore, operators can confidently select the "smart minimum" FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis.

An Analysis of 3 Common CardioGen-82 82Rb Infusion System Injection Methods and Their Impact on Clinical Volume and Image Counts.

UNLABELLED: In the wake of the Food and Drug Administration (FDA) recall, many clinics have had to reduce their examination volumes to meet the new generator volume usage requirements. This review tests 3 common infusion methods and how they affect patient dose, generator volume usage, image counts, and generator volume limits. METHODS: Three common configurations of the (82)Rb infusion system settings--standard 50-mL, volume-limiting, and bolus methods--were tested to determine how they affect patient dose, generator volume, and image counts. Each injection configuration was tested daily for the duration of 3 consecutive generators by injection into separate vials. Each injection configuration was also infused into a beaker and imaged to determine the impact of image counts for each method. The total estimated volumes for multiple examination and quality assurance clinical situations were simulated to observe the use of each method relative to the new FDA volume alert and expiration limits. RESULTS: Vial tests confirmed that the bolus method used the least amount of volume per infusion and stayed the most consistent throughout the life of the generator. The bolus method also produced a lower patient dose after approximately 10 d of use. The beaker tests in the scanner showed that the standard 50-mL method produced the greatest number of total counts for the flow and uptake images. On the basis of the estimated total volume simulations, the bolus method allowed for the most examinations over the life of the generator while staying within the new FDA limits. CONCLUSION: All 3 methods for augmenting the (82)Rb infusion system produced different outcomes for patient dose, image counts, and total generator volume use. The standard 50-mL method ensured the maximum amount of counts available for imaging throughout the life of the generator. The bolus method provided a consistent and predictable amount of volume use. The volume-limiting method fell somewhere in the middle of volume predictability and count preservation.

Regadenoson versus dipyridamole hyperemia for cardiac PET imaging.

OBJECTIVES: The goal of this study was to compare regadenoson and dipyridamole hyperemia for quantitative myocardial perfusion imaging. BACKGROUND: Regadenoson is commonly used for stress perfusion imaging. However, no study in nuclear cardiology has employed a paired design to compare quantitative hyperemic flow from regadenoson to more traditional agents such as dipyridamole. Additionally, the timing of regadenoson bolus relative to tracer administration can be expected to affect quantitative flow. METHODS: Subjects underwent 2 rest/stress cardiac positron emission tomography scans using an Rb-82 generator. Each scan employed dipyridamole and a second drug in random sequence, either regadenoson according to 5 timing sequences or repeated dipyridamole. A validated retention model quantified absolute flow and coronary flow reserve. RESULTS: A total of 176 pairs compared regadenoson (126 pairs, split unevenly among 5 timing sequences) or repeated dipyridamole (50 pairs). The cohort largely had few symptoms, only risk factors, and nearly normal relative uptake images, with 8% typical angina or dyspnea, 20% manifest coronary artery disease, and a minimum quadrant average of 80% (interquartile range: 76% to 83%) on dipyridamole scans. Hyperemic flow varied among regadenoson timing sequences but showed consistently lower stress flow and coronary flow reserve compared with dipyridamole. A timing sequence most similar to the regadenoson package insert achieved about 80% of dipyridamole hyperemia, whereas further delaying radiotracer injection reached approximately 90% of dipyridamole hyperemia. Because of the small numbers of pairs for each regadenoson timing protocol and a paucity of moderate or large perfusion defects, we did not observe a difference in relative uptake. CONCLUSIONS: With the standard timing protocol from the package insert, regadenoson achieved only 80% of dipyridamole hyperemia quantitatively imaged by cardiac positron emission tomography using Rb-82. A nonstandard protocol using a more delayed radionuclide injection after the regadenoson bolus improved its effect to 90% of dipyridamole hyperemia.

Circulating and urinary adrenal corticosterone, progesterone, and estradiol in response to acute stress in female mice (Mus musculus).

In studies of stress, it can be difficult to obtain blood rapidly enough to avoid confounding steroid measures. Noninvasive urinary steroid measures may provide an alternative insofar as they reflect systemic steroids. In Experiment 1, we profiled urinary corticosterone, progesterone, and estradiol in ovariectomized female mice following 1 h on an elevated platform. This increased urinary corticosterone for 3 h and progesterone for 4 h. In Experiment 2, blood and urine samples were obtained at 0-6 h following stressor offset. Females showed increased serum corticosterone and progesterone immediately after stressor offset. Urinary corticosterone was increased at both 0 and 2 h post-stress, while an increase in progesterone 2-6 h after stressor offset was not significant. Estradiol was not influenced by this mild stressor. In Experiment 3, mice were exposed to a more severe 1 h stressor, a rat across a wire-mesh grid. In serum, both corticosterone and progesterone were elevated immediately after stressor offset and returned to baseline within 2 h. In urine, this severe stressor elevated corticosterone immediately and 2 h after stressor offset, and in progesterone 2 h after stressor offset. Estradiol in serum was not dynamic, but it was significantly elevated in urine 4 h after stressor offset. Urinary measures generally reflected systemic measures; however, with a different time course resulting in a longer return to baseline. We suggest that the relative value of serum or urinary steroid measures in mice depends upon the experimental design, and that estradiol may only respond when the stressor is severe.

Does the instantaneous wave-free ratio approximate the fractional flow reserve?

OBJECTIVES: This study sought to examine the clinical performance of and theoretical basis for the instantaneous wave-free ratio (iFR) approximation to the fractional flow reserve (FFR). BACKGROUND: Recent work has proposed iFR as a vasodilation-free alternative to FFR for making mechanical revascularization decisions. Its fundamental basis is the assumption that diastolic resting myocardial resistance equals mean hyperemic resistance. METHODS: Pressure-only and combined pressure-flow clinical data from several centers were studied both empirically and by using pressure-flow physiology. A Monte Carlo simulation was performed by repeatedly selecting random parameters as if drawing from a cohort of hypothetical patients, using the reported ranges of these physiologic variables. RESULTS: We aggregated observations of 1,129 patients, including 120 with combined pressure-flow data. Separately, we performed 1,000 Monte Carlo simulations. Clinical data showed that iFR was +0.09 higher than FFR on average, with ±0.17 limits of agreement. Diastolic resting resistance was 2.5 ± 1.0 times higher than mean hyperemic resistance in patients. Without invoking wave mechanics, classic pressure-flow physiology explained clinical observations well, with a coefficient of determination of >0.9. Nearly identical scatter of iFR versus FFR was seen between simulation and patient observations, thereby supporting our model. CONCLUSIONS: iFR provides both a biased estimate of FFR, on average, and an uncertain estimate of FFR in individual cases. Diastolic resting myocardial resistance does not equal mean hyperemic resistance, thereby contravening the most basic condition on which iFR depends. Fundamental relationships of coronary pressure and flow explain the iFR approximation without invoking wave mechanics.

Defining peri-prosthetic infection: do we have a workable gold standard?

Peri-prosthetic infection remains a leading cause of revision surgery. Recent publications from the American Musculoskeletal Infection Society have sought to establish a definition of peri-prosthetic infection based on clinical findings and laboratory investigations. The limitations of their approach are discussed and an alternative definition is proposed, which it is felt may better reflect the uncertainties encountered in clinical practice.

Reducing radiation dose in rest-stress cardiac PET/CT by single poststress cine CT for attenuation correction: quantitative validation.

UNLABELLED: 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 (82)Rb 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%.

Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: a comparison with 15O-labeled water-measured blood flow.

UNLABELLED: PET molecular imaging of 15O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18F-FDG could be used to measure regional blood flow in tumors in the absence of 15O-water. METHODS: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10 mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired, consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15-min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. RESULTS: Blood flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2 regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction relative to 15O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18F-FDG blood flow analysis in tumor diagnosis. CONCLUSION: These results suggest that the first-pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18F-FDG compared with 15O-water.

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.

BACKGROUND: In coronary artery disease (CAD), statins decrease morbidity and mortality but changes in myocardial perfusion abnormalities remain poorly defined. METHODS: We 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. RESULTS: Total 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). CONCLUSION: The 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.