Improved diagnostic accuracy for coronary artery disease detection with quantitative 3D 82Rb PET myocardial perfusion imaging.

PURPOSE: To establish requirements for normal databases for quantitative rubidium-82 (82Rb) PET MPI analysis with contemporary 3D PET/CT technology and reconstruction methods for maximizing diagnostic accuracy of total perfusion deficit (TPD), a combined metric of defect extent and severity, versus invasive coronary angiography. METHODS: In total, 1571 patients with 82Rb PET/CT MPI on a 3D scanner and stress static images reconstructed with and without time-of-flight (TOF) modeling were identified. An additional eighty low pre-test probability of disease (PTP) patients reported as normal were used to form separate sex-stratified and sex-independent iterative and TOF normal databases. 3D normal databases were applied to matched patient reconstructions to quantify TPD. Per-patient and per-vessel performance of 3D versus 2D PET normal databases was assessed with receiver operator characteristic curve analysis. Diagnostic accuracy was evaluated at optimal thresholds established from PTP patients. Results were compared against logistic regression modeling of TPD adjusted for clinical variables, and standard clinical interpretation. RESULTS: TPD diagnostic accuracy was significantly higher using 3D PET normal databases (per-patient: 80.1% for 3D databases, versus 74.9% and 77.7% for 2D database applied to iterative and TOF images respectively, p < 0.05). Differences in male and female normal distributions for 3D attenuation-corrected reconstructions were not clinically meaningful; therefore, sex-independent databases were used. Logistic regression modeling including TPD demonstrated improved performance over clinical reads. CONCLUSIONS: Normal databases tailored to 3D PET images provide significantly improved diagnostic accuracy for PET MPI evaluation with automated quantitative TPD. Clinical application of these techniques should be considered to support accurate image interpretation.

Multi-center, multi-vendor validation of deep learning-based attenuation correction in SPECT MPI: data from the international flurpiridaz-301 trial.

PURPOSE: Although SPECT myocardial perfusion imaging (MPI) is susceptible to artifacts from soft tissue attenuation, most scans are performed without attenuation correction. Deep learning-based attenuation corrected (DLAC) polar maps improved diagnostic accuracy for detection of coronary artery disease (CAD) beyond non-attenuation-corrected (NAC) polar maps in a large single center study. However, the generalizability of this approach to other institutions with different scanner models and protocols is uncertain. In this study, we evaluated the diagnostic performance of DLAC compared to NAC for detection of CAD as defined by invasive coronary angiography (ICA) in a large multi-center trial. METHODS: During the phase 3 flurpiridaz multi-center diagnostic clinical trial, conducted over 74 international sites, patients with known or suspected CAD who were referred for a clinically indicated ICA were enrolled. Using receiver operating characteristic (ROC) analysis, we evaluated the detectability of obstructive CAD, defined by quantitative coronary angiography by a core laboratory, using total perfusion deficit (TPD) as an integrated measure of defect extent and severity on DLAC polar maps compared to NAC polar maps. This was also compared against the visual scoring of three expert core lab readers. RESULTS: Out of 755 patients, 722 (69% male) had evaluable SPECT and ICA for this study. ROC analysis demonstrated significant improvement in detecting per-patient obstructive CAD with DLAC over NAC with area under the curve (AUC) of 0.752 (95% CI: 0.711-0.792) for DLAC compared to 0.717 (0.675-0.759) for NAC (p value = 0.016). Compared to the consensus of expert readers AUC = 0.743 (0.701-0.784), DLAC was comparable (p value = 0.913), whereas NAC underperformed (p value = 0.051). CONCLUSION: DL-based attenuation correction improves diagnostic performance of SPECT MPI for detecting CAD in data from a large multi-center clinical trial regardless of SPECT camera model or protocol. TRIAL REGISTRATION: A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients With CAD, ClinicalTrials.gov Identifier: NCT01347710, registered on 4 May 2011. https://clinicaltrials.gov/ct2/show/study/NCT01347710.

Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion.

BACKGROUND AND AIMS: Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. METHODS: This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. RESULTS: In total, 6867 patients were included with a median follow-up of 3.4 years [1st-3rd quartiles, 1.9-5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37-2.97]) and global MFR (HR 2.29, 95%C.I. [2.08-2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46-1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03-1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183-0.310]). CONCLUSIONS: The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.

Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease.

PURPOSE: Distinguishing obstructive epicardial coronary artery disease (CAD) from microvascular dysfunction and diffuse atherosclerosis would be of immense benefit clinically. However, quantitative measures of absolute myocardial blood flow (MBF) integrate the effects of focal epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. In this study, MFR and relative perfusion quantification were combined to create integrated MFR (iMFR) which was evaluated using data from a large clinical registry and an international multi-center trial and validated against invasive coronary angiography (ICA). METHODS: This study included 1,044 clinical patients referred for 82Rb rest/stress positron emission tomography myocardial perfusion imaging and ICA, along with 231 patients from the Flurpiridaz 301 trial (clinicaltrials.gov NCT01347710). MFR and relative perfusion quantification were combined to create an iMFR map. The incremental value of iMFR was evaluated for diagnosis of obstructive stenosis, adjusted for patient demographics and pre-test probability of CAD. Models for high-risk anatomy (left main or three-vessel disease) were also constructed. RESULTS: iMFR parameters of focally impaired perfusion resulted in best fitting diagnostic models. Receiver-operating characteristic analysis showed a slight improvement compared to standard quantitative perfusion approaches (AUC 0.824 vs. 0.809). Focally impaired perfusion was also associated with high-risk CAD anatomy (OR 1.40 for extent, and OR 2.40 for decreasing mean MFR). Diffusely impaired perfusion was associated with lower likelihood of obstructive CAD, and, in the absence of transient ischemic dilation (TID), with lower likelihood of high-risk CAD anatomy. CONCLUSIONS: Focally impaired perfusion extent derived from iMFR assessment is a powerful incremental predictor of obstructive CAD while diffusely impaired perfusion extent can help rule out obstructive and high-risk CAD in the absence of TID.

Measuring myocardial blood flow using dynamic myocardial perfusion SPECT: artifacts and pitfalls.

Dynamic acquisition allows absolute quantification of myocardial perfusion and flow reserve, offering an alternative to overcome the potential limits of relative quantification, especially in patients with balanced multivessel coronary artery disease. SPECT myocardial perfusion is widely available, at lower cost than PET. Dynamic cardiac SPECT is now feasible and has the potential to be the next step of comprehensive perfusion imaging. In order to help nuclear cardiologists potentially interested in using dynamic perfusion SPECT, we sought to review the different steps of acquisition, processing, and reporting of dynamic SPECT studies in order to enlighten the potentially critical pitfalls and artifacts. Both patient-related and technical artifacts are discussed. Key parameters of the acquisition include pharmacological stress, radiopharmaceuticals, and injection device. When it comes to image processing, attention must be paid to image-derived input function, patient motion, and extra-cardiac activity. This review also mentions compartment models, cameras, and attenuation correction. Finally, published data enlighten some facets of dynamic cardiac SPECT while several issues remain. Harmonizing acquisition and quality control procedures will likely improve its performance and clinical strength.

"Virtual" attenuation correction: improving stress myocardial perfusion SPECT imaging using deep learning.

PURPOSE: Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) is widely used for coronary artery disease (CAD) evaluation. Although attenuation correction is recommended to diminish image artifacts and improve diagnostic accuracy, approximately 3/4ths of clinical MPI worldwide remains non-attenuation-corrected (NAC). In this work, we propose a novel deep learning (DL) algorithm to provide "virtual" DL attenuation-corrected (DLAC) perfusion polar maps solely from NAC data without concurrent computed tomography (CT) imaging or additional scans. METHODS: SPECT MPI studies (N = 11,532) with paired NAC and CTAC images were retrospectively identified. A convolutional neural network-based DL algorithm was developed and trained on half of the population to predict DLAC polar maps from NAC polar maps. Total perfusion deficit (TPD) was evaluated for all polar maps. TPDs from NAC and DLAC polar maps were compared to CTAC TPDs in linear regression analysis. Moreover, receiver-operating characteristic analysis was performed on NAC, CTAC, and DLAC TPDs to predict obstructive CAD as diagnosed from invasive coronary angiography. RESULTS: DLAC TPDs exhibited significantly improved linear correlation (p < 0.001) with CTAC (R2 = 0.85) compared to NAC vs. CTAC (R2 = 0.68). The diagnostic performance of TPD was also improved with DLAC compared to NAC with an area under the curve (AUC) of 0.827 vs. 0.780 (p = 0.012) with no statistically significant difference between AUC for CTAC and DLAC. At 88% sensitivity, specificity was improved by 18.9% for DLAC and 25.6% for CTAC. CONCLUSIONS: The proposed DL algorithm provided attenuation correction comparable to CTAC without the need for additional scans. Compared to conventional NAC perfusion imaging, DLAC significantly improved diagnostic accuracy.

Effect of iterations and time of flight on normal distributions of 82Rb PET relative perfusion and myocardial blood flow.

BACKGROUND: As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification. METHODS: Fifty-nine rest/stress dynamic 82Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations. RESULTS: TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions. CONCLUSION: Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution.

Myocardial flow reserve estimation with contemporary CZT-SPECT and 99mTc-tracers lacks precision for routine clinical application.

BACKGROUND: PET myocardial flow reserve (MFR) has established diagnostic and prognostic value. Technological advances have now enabled SPECT MFR quantification. We investigated whether SPECT MFR precision is sufficient for clinical categorization of patients. METHODS: Validation studies vs invasive flow measurements and PET MFR were reviewed to determine global SPECT MFR thresholds. Studies vs PET and a SPECT MFR repeatability study were used to establish imprecision in SPECT MFR measurements as the standard deviation of the difference between SPECT and PET MFR, or test-retest SPECT MFR. Simulations were used to evaluate the impact of SPECT MFR imprecision on confidence of clinically relevant categorization. RESULTS: Based on validation studies, the typical PET MFR categories were used for SPECT MFR classification (< 1.5, 1.5-2.0, > 2.0). Imprecision vs PET MFR ranged from 0.556 to 0.829, and test-retest imprecision was 0.781-0.878. Simulations showed correct classification of up to only 34% of patients when 1.5 ≤ true MFR ≤ 2.0. Categorization with high confidence (> 80%) was only achieved for extreme MFR values (< 1.0 or > 2.5), with correct classification in only 15% of patients in a typical lab with MFR of 1.8 ± 0.5. CONCLUSIONS: Current SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.

The prognostic value of positron emission tomography in the evaluation of suspected cardiac sarcoidosis.

OBJECTIVES: To assess the prognostic value of positron emission tomography (PET) imaging in patients undergoing evaluation for known or suspected cardiac sarcoidosis (CS) while not on active immunotherapy. BACKGROUND: Previous studies have attempted to identify the value of PET imaging to aid in risk stratification of patients with CS, however, most cohorts have included patients currently on immunosuppression, which may confound scan results by suppressing positive findings. METHODS: We retrospectively analyzed 197 patients not on immunosuppression who underwent 18F-fluorodeoxyglucose (FDG) PET scans for evaluation of known or suspected CS. The primary endpoint of the study was time to ventricular arrhythmia (VT/VF), or death. Candidate predictors were identified by univariable Cox proportional hazards regression. Independent predictors were identified by performing multivariable Cox regression with stepwise forward selection. RESULTS: Median follow-up time was 531 [IQR 309, 748] days. 41 patients met the primary endpoint. After stepwise forward selection, left ventricular ejection fraction (LVEF) (HR 0.98, 95% CI 0.96-0.99, P = 0.02), history of VT/VF (HR 4.19, 95% CI 2.15-8.17, P < 0.001), and summed rest score (SRS) (HR 1.06, 95% CI 1.02-1.12, P = 0.01) were predictive of the primary endpoint. Quantitative and qualitative measures of FDG uptake on PET were not predictive of clinical events. CONCLUSIONS: Among untreated patients who underwent PET scans to evaluate known or suspected CS, LVEF, history of VT/VF, and SRS were associated with adverse clinical outcomes.

Left ventricular mass on positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important clinical finding that is independently associated with mortality and cardiovascular events. We aimed to assess the interstudy variability of LV mass quantitation between PET and CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. LV mass on PET was compared against LV mass on CMR using several statistical measures of agreement. RESULTS: A total of 105 patients (mean age 60 ± 14 years, 67.6% male) were included. The median (interquartile range, IQR) duration between CMR and PET was 47 (11-154) days. The median (IQR) LV mass values were 168.0 g (126.0-202.0) on CMR and 174.0 g (150.0-212.0) with PET (absolute mean difference 29.42 ± 25.3). There was a good correlation (Spearman ρ = 0.81, P < 0.001; Intraclass Correlation Coefficient 0.78, 95% CI 0.70-0.85, P < 0.001) with moderate limits of agreement (95% limits of agreement - 63.78 to 83.7.) Results were consistent, albeit with moderate correlation, in subgroups of patients with LVH, in patients with myocardial infarction, in patients with LV ejection fraction < 50%, and those with limited image quality. LV mass on PET tended to be underestimated at high values compared to CMR. CONCLUSION: We demonstrate good correlation and reproducibility of LV mass quantitation by PET against the reference standard of CMR across a wide range of normal and diseased hearts with a tendency of PET to underestimate mass at higher mass values.

Impact of residual subtraction on myocardial blood flow and reserve estimates from rapid dynamic PET protocols.

BACKGROUND: 13N-ammonia and 18F-flurpiridaz require longer delays between rest and stress studies to allow for decay, lowering clinical throughput. In this study, we investigated the impact of residual subtraction on MBF and MFR estimates, as well as its effects on diagnostic accuracy. METHODS: We retrospectively analyzed 63 patients who underwent a dynamic ammonia rest/stress study and 231 patients from the flurpiridaz 301 trial. Residual subtraction was performed by subtracting the mean pre-injection activity in each sampled region from that region's time activity curve. Corrected and uncorrected MBF and MFR were analyzed. Diagnostic accuracy was compared to quantitative coronary angiograms (QCA) for the flurpiridaz population. RESULTS: With delays between injections above 3 half-lives, and a doubled stress dose, residual activity did not meaningfully increase ammonia MBF (< 5%). For shorter injection delays, stress MBF was overestimated by 13.6% ± 5.0% (P < .001). Residual activity had a large effect on flurpiridaz stress MBF, overestimating it by 37.9% ± 23.2% (P < .001). Comparison to QCA showed a significant improvement in AUC with residual subtraction (from 0.748 to 0.831, P = .001). MFR yielded similar results. CONCLUSIONS: Accounting for residual activity has a marked impact on stress MBF and MFR and improves diagnostic accuracy relative to QCA.

Effects of two patient-specific dosing protocols on measurement of myocardial blood flow with 3D 82Rb cardiac PET.

PURPOSE: Clinical measurement of myocardial blood flow (MBF) has emerged as an important component of routine PET-CT assessment of myocardial perfusion in patients with known or suspected coronary artery disease. Although multiple society guidelines recommend patient-specific dosing, there is a lack of studies evaluating the efficacy of patient-specific dosing for quantitative MBF accuracy. METHODS: Two patient-specific dosing protocols (weight- and BMI-adjusted) were retrospectively evaluated in 435 consecutive clinical patients referred for PET myocardial perfusion assessment. MBF was estimated at rest and after regadenoson-induced hyperemia. The effect of dosing protocol on dose reduction, PET scanner saturation, relative perfusion, and image quality was compared. The effect of PET saturation on the accuracy of MBF and myocardial flow reserve (MFR) in remote myocardium was assessed with multivariable linear regression. RESULTS: BMI-adjusted dosing was associated with lower administered 82Rb activities (1036.0 ± 274 vs. 1147 ± 274 MBq, p = 0.003) and lower PET scanner saturation incidence (28 vs. 38%, p = 0.006) and severity (median saturation severity index 0.219 ± 0.33 vs. 0.397 ± 0.59%, p = 0.018) compared to weight-adjusted dosing. PET saturation that occurred with either dosing protocol was moderate and resulted in modest remote MBF and MFR biases ranging from 2 to 9% after adjusting for patient age, sex, BMI, rate-pressure product, and LV ejection fraction. No adverse effects of BMI dose adjustment were observed in relative perfusion assessment or image quality. CONCLUSIONS: Patient-specific dosing according to BMI is an effective method for guideline-directed dose reduction while maintaining image quality and accuracy for routine MBF and MFR quantification.

Added value of myocardial blood flow using 18F-flurpiridaz PET to diagnose coronary artery disease: The flurpiridaz 301 trial.

BACKGROUND: 18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. METHODS: We retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. RESULTS: Stress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P < 0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P < 0.05). In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. CONCLUSIONS: Clinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.

Initial clinical experience of N13-ammonia myocardial perfusion PET/CT using a compact superconducting production system.

BACKGROUND: Although N13-ammonia has favorable properties among FDA approved radiotracers, complexity of implementation has limited its use. We describe the initial patient experience of N13-ammonia PET imaging using a compact N13-ammonia production system. METHODS: N13 was produced using the ION-12SC, a 12MeV, 10uA superconducting minimally shielded cyclotron, and reduced to N13-ammonia in an automated multi-use purification unit. Patients were power injected with 9.3 ± 1.1 mCi (344.1 ± 40.7 MBq) of N13-ammonia for rest imaging, and 18.8 ± 0.9 mCi (695.6 ± 33.3 MBq) of N13-ammonia was injected at peak hyperemia for stress testing. Images were interpreted for relative perfusion, left ventricular volumes/function, blood flow quantification, and scored for image quality. RESULTS: In total 97 patients underwent 98 N13-ammonia PET scans (32 rest only/65 rest-stress/1 stress only). Image quality was 91.8% good or excellent. None were poor/non-diagnostic. Study durations were acceptable. Tracer related radiation dosimetry to patients was 0.7 ± 0.1 mSv (rest only), and 2.1 ± 0.1 mSv (rest-stress). CONCLUSION: Clinical N13-ammonia production by the Ionetix ION-12SC delivers high quality myocardial PET perfusion images in a rapid protocol.

Reducing motion-correction-induced variability in 82rubidium myocardial blood-flow quantification.

BACKGROUND: Clinical use of myocardial blood flow (MBF) and flow reserve (MFR) is increasing. Motion correction is necessary to obtain accurate results but can introduce variability when performed manually. We sought to reduce that variability with an automated motion-correction algorithm. METHODS: A blinded randomized controlled trial of two technologists was performed on the motion correction of 100 dynamic 82Rb patient studies comparing manual motion correction with manual review and adjustment of automated motion correction. Inter-rater variability between technologists for MBF and MFR was the primary outcome with comparison made by analysis of the limits of agreement. Processing time was the secondary outcome. RESULTS: Limits of agreements between the two technologists decreased significantly for both MBF and MFR, going from [- 0.22, 0.22] mL/min/g and [- 0.31, 0.36] to [- 0.12, 0.15] mL/min/g and [- 0.15, 0.18], respectively (both P < .002). In addition, the average time spent on motion correcting decreased by 1 min per study from 5:21 to 4:21 min (P = .001). CONCLUSIONS: In this randomized controlled trial, the use of automated motion correction significantly decreased inter-user variability and reduced processing time.

Automated dynamic motion correction using normalized gradient fields for 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Patient motion can lead to misalignment of left ventricular (LV) volumes-of-interest (VOIs) and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to develop an image-based 3D-automated motion-correction algorithm that corrects the full dynamic sequence for translational motion, especially in the early blood phase frames (~ first minute) where the injected tracer activity is transitioning from the blood pool to the myocardium and where conventional image registration algorithms have had limited success. METHODS: We studied 225 consecutive patients who underwent dynamic rest/stress rubidium-82 chloride (82Rb) PET imaging. Dynamic image series consisting of 30 frames were reconstructed with frame durations ranging from 5 to 80 seconds. An automated algorithm localized the RV and LV blood pools in space and time and then registered each frame to a tissue reference image volume using normalized gradient fields with a modification of a signed distance function. The computed shifts and their global and regional flow estimates were compared to those of reference shifts that were assessed by three physician readers. RESULTS: The automated motion-correction shifts were within 5 mm of the manual motion-correction shifts across the entire sequence. The automated and manual motion-correction global MBF values had excellent linear agreement (R = 0.99, y = 0.97x + 0.06). Uncorrected flows outside of the limits of agreement with the manual motion-corrected flows were brought into agreement in 90% of the cases for global MBF and in 87% of the cases for global MFR. The limits of agreement for stress MBF were also reduced twofold globally and by fourfold in the RCA territory. CONCLUSIONS: An image-based, automated motion-correction algorithm for dynamic PET across the entire dynamic sequence using normalized gradient fields matched the results of manual motion correction in reducing bias and variance in MBF and MFR, particularly in the RCA territory.

Blood pool and tissue phase patient motion effects on 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Patient motion can lead to misalignment of left ventricular volumes of interest and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to identify the prevalence of patient motion in both blood and tissue phases and analyze the effects of this motion on MBF and MFR estimates. METHODS: We selected 225 consecutive patients that underwent dynamic stress/rest rubidium-82 chloride (82Rb) PET imaging. Dynamic image series were iteratively reconstructed with 5- to 10-second frame durations over the first 2 minutes for the blood phase and 10 to 80 seconds for the tissue phase. Motion shifts were assessed by 3 physician readers from the dynamic series and analyzed for frequency, magnitude, time, and direction of motion. The effects of this motion isolated in time, direction, and magnitude on global and regional MBF and MFR estimates were evaluated. Flow estimates derived from the motion corrected images were used as the error references. RESULTS: Mild to moderate motion (5-15 mm) was most prominent in the blood phase in 63% and 44% of the stress and rest studies, respectively. This motion was observed with frequencies of 75% in the septal and inferior directions for stress and 44% in the septal direction for rest. Images with blood phase isolated motion had mean global MBF and MFR errors of 2%-5%. Isolating blood phase motion in the inferior direction resulted in mean MBF and MFR errors of 29%-44% in the RCA territory. Flow errors due to tissue phase isolated motion were within 1%. CONCLUSIONS: Patient motion was most prevalent in the blood phase and MBF and MFR errors increased most substantially with motion in the inferior direction. Motion correction focused on these motions is needed to reduce MBF and MFR errors.

The utility of 82Rb PET for myocardial viability assessment: Comparison with perfusion-metabolism 82Rb-18F-FDG PET.

BACKGROUND: 82Rb kinetics may distinguish scar from viable but dysfunctional (hibernating) myocardium. We sought to define the relationship between 82Rb kinetics and myocardial viability compared with conventional 82Rb and 18F-fluorodeoxyglucose (FDG) perfusion-metabolism PET imaging. METHODS: Consecutive patients (N = 120) referred for evaluation of myocardial viability prior to revascularization and normal volunteers (N = 37) were reviewed. Dynamic 82Rb 3D PET data were acquired at rest. 18F-FDG 3D PET data were acquired after metabolic preparation using a standardized hyperinsulinemic-euglycemic clamp. 82Rb kinetic parameters K1, k2, and partition coefficient (KP) were estimated by compartmental modeling RESULTS: Segmental 82Rb k2 and KP differed significantly between scarred and hibernating segments identified by Rb-FDG perfusion-metabolism (k2, 0.42 ± 0.25 vs. 0.22 ± 0.09 min-1; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). As compared to Rb-FDG analysis, segmental Rb KP had a c-index, sensitivity and specificity of 0.809, 76% and 84%, respectively, for distinguishing hibernating and scarred segments. Segmental k2 performed similarly, but with lower specificity (75%, P < .001) CONCLUSIONS: In this pilot study, 82Rb kinetic parameters k2 and KP, which are readily estimated using a compartmental model commonly used for myocardial blood flow, reliably differentiated hibernating myocardium and scar. Further study is necessary to evaluate their clinical utility for predicting benefit after revascularization.