10-year experience of utilizing a stress-first SPECT myocardial perfusion imaging.

BACKGROUND: Despite its potential benefits, the utilization of stress-only protocol in clinical practice has been limited. We report utilizing stress-first single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: We assessed 12,472 patients who were referred for SPECT-MPI between 2013 and 2020. The temporal changes in frequency of stress-only imaging were assessed according to risk factors, mode of stress, prior coronary artery disease (CAD) history, left ventricular function, and symptom status. The clinical endpoint was all-cause mortality. RESULTS: In our lab, stress/rest SPECT-MPI in place of rest/stress SPECT-MPI was first introduced in November 2011 and was performed more commonly than rest/stress imaging after 2013. Stress-only SPECT-MPI scanning has been performed in 30-34% of our SPECT-MPI studies since 2013 (i.e.. 31.7% in 2013 and 33.6% in 2020). During the study period, we routinely used two-position imaging (additional prone or upright imaging) to reduce attenuation and motion artifact and introduced SPECT/CT scanner in 2018. The rate of stress-only study remained consistent before and after implementing the SPECT/CT scanner. The frequency of stress-only imaging was 43% among patients without a history of prior CAD and 19% among those with a prior CAD history. Among patients undergoing treadmill exercise, the frequency of stress-only imaging was 48%, while 32% among patients undergoing pharmacologic stress test. In multivariate Cox analysis, there was no significant difference in mortality risk between stress-only and stress/rest protocols in patients with normal SPECT-MPI results (p = 0.271). CONCLUSION: Implementation of a stress-first imaging protocol has consistently resulted in safe cancellation of 30% of rest SPECT-MPI studies.

Automated Motion Correction for Myocardial Blood Flow Measurements and Diagnostic Performance of 82Rb PET Myocardial Perfusion Imaging.

Motion correction (MC) affects myocardial blood flow (MBF) measurements in 82Rb PET myocardial perfusion imaging (MPI); however, frame-by-frame manual MC of dynamic frames is time-consuming. This study aims to develop an automated MC algorithm for time-activity curves used in compartmental modeling and compare the predictive value of MBF with and without automated MC for significant coronary artery disease (CAD). Methods: In total, 565 patients who underwent PET-MPI were considered. Patients without angiographic findings were split into training (n = 112) and validation (n = 112) groups. The automated MC algorithm used simplex iterative optimization of a count-based cost function and was developed using the training group. MBF measurements with automated MC were compared with those with manual MC in the validation group. In a separate cohort, 341 patients who underwent PET-MPI and invasive coronary angiography were enrolled in the angiographic group. The predictive performance in patients with significant CAD (≥70% stenosis) was compared between MBF measurements with and without automated MC. Results: In the validation group (n = 112), MBF measurements with automated and manual MC showed strong correlations (r = 0.98 for stress MBF and r = 0.99 for rest MBF). The automatic MC took less time than the manual MC (<12 s vs. 10 min per case). In the angiographic group (n = 341), MBF measurements with automated MC decreased significantly compared with those without (stress MBF, 2.16 vs. 2.26 mL/g/min; rest MBF, 1.12 vs. 1.14 mL/g/min; MFR, 2.02 vs. 2.10; all P < 0.05). The area under the curve (AUC) for the detection of significant CAD by stress MBF with automated MC was higher than that without (AUC, 95% CI, 0.76 [0.71-0.80] vs. 0.73 [0.68-0.78]; P < 0.05). The addition of stress MBF with automated MC to the model with ischemic total perfusion deficit showed higher diagnostic performance for detection of significant CAD (AUC, 95% CI, 0.82 [0.77-0.86] vs. 0.78 [0.74-0.83]; P = 0.022), but the addition of stress MBF without MC to the model with ischemic total perfusion deficit did not reach significance (AUC, 95% CI, 0.81 [0.76-0.85] vs. 0.78 [0.74-0.83]; P = 0.067). Conclusion: Automated MC on 82Rb PET-MPI can be performed rapidly with excellent agreement with experienced operators. Stress MBF with automated MC showed significantly higher diagnostic performance than without MC.

Reproducibility of quantitative coronary calcium scoring from PET/CT attenuation maps: comparison to ECG-gated CT scans.

PURPOSE: We sought to evaluate inter-scan and inter-reader agreement of coronary calcium (CAC) scores obtained from dedicated, ECG-gated CAC scans (standard CAC scan) and ultra-low-dose, ungated computed tomography attenuation correction (CTAC) scans obtained routinely during cardiac PET/CT imaging. METHODS: From 2928 consecutive patients who underwent same-day 82Rb cardiac PET/CT and gated CAC scan in the same hybrid PET/CT scanning session, we have randomly selected 200 cases with no history of revascularization. Standard CAC scans and ungated CTAC scans were scored by two readers using quantitative clinical software. We assessed the agreement between readers and between two scan protocols in 5 CAC categories (0, 1-10, 11-100, 101-400, and > 400) using Cohen's Kappa and concordance. RESULTS: Median age of patients was 70 (inter-quartile range: 63-77), and 46% were male. The inter-scan concordance index and Cohen's Kappa for readers 1 and 2 were 0.69; 0.75 (0.69, 0.81) and 0.72; 0.8 (0.75, 0.85) respectively. The inter-reader concordance index and Cohen's Kappa (95% confidence interval [CI]) was higher for standard CAC scans: 0.9 and 0.92 (0.89, 0.96), respectively, vs. for CTAC scans: 0.83 and 0.85 (0.79, 0.9) for CTAC scans (p = 0.02 for difference in Kappa). Most discordant readings between two protocols occurred for scans with low extent of calcification (CAC score < 100). CONCLUSION: CAC can be quantitatively assessed on PET CTAC maps with good agreement with standard scans, however with limited sensitivity for small lesions. CAC scoring of CTAC can be performed routinely without modification of PET protocol and added radiation dose.

Predictive Model for 82Rb Generator Bolus Times as a Function of Generator Lifetime.

82Rb cardiac PET is largely used to study myocardial perfusion with function and to calculate myocardial blood flow (MBF) and coronary flow reserve or myocardial flow reserve. Although the dosing activity of 82Rb is determined by the patient weight, the infusion volume and activity concentration varies with the age of the 82Rb generator. We sought to predict the needed bolus volume of 82Rb to help evaluate the accuracy of MBF findings. Methods: Data were collected from deidentified tickets of an 82Rb generator, including the instantaneous eluted activity flow rate. The times to reach 4 activity levels-740, 1,110, 1,480, and 1,665 MBq (20, 30, 40, and 45 mCi, respectively)-were also calculated. The activity flow rate for the largest bolus was fitted to determine the functional form. The time to reach each bolus level was fitted as a function of the generator age, and 95% CIs were created. Results: The activity flow rate was fitted with a growth-saturation model, allowing a calculation of bolus volume. The amplitude of the fit was observed to also be influenced by the time since the last elution and possibly other clinical factors. Elution times to reach the 4 activity levels were plotted versus generator age. The linearized data were fitted, and 95% CIs were created symmetrically around the fit. The 95% CI band allowed a prediction of elution time to achieve each bolus size for future generators, as a function only of generator age. Conclusion: A predictive model was created for elution times from this brand of 82Rb generator as a function of generator age. The value of this model is in determining whether the necessary amount of activity can be extracted from a generator before reaching one of the backup infusion settings, such as volume limits per administration, given a generator age. Some sites may also control the bolus duration for better MBF calculations, since predicting the time for the injection to complete may determine whether MBF and coronary flow reserve calculations are meaningful.

Coronary artery calcium scoring at lower tube voltages - Dose determination and scoring mechanism.

PURPOSE: Population dose has been a concern with coronary artery calcium scoring CT since it is performed in adults with borderline risk. Lower tube voltage acquisitions are appealing but there are no agreed schemes for reduced dose determination. Moreover, conventional scoring cannot be used without changing the multiple Agatston thresholds. METHODS: By applying consistent calcium contrast-to-noise ratio to two anthropomorphic heart phantoms (medium and large) with 3-cm hydroxyapatite (HA) inserts, scanned using a dual-source CT, the relationship was derived between the volume CT dose index (CTDIvol) at lower tube voltages and the baseline CTDIvol at 120 kVp. The baseline CTDIvol was obtained using the noise thresholds from the images acquired at 120 kVp. To preserve the conventional Agatston thresholds, down-scaling with the found factors was applied to images acquired at lower voltages with a dynamic heart module and 1.2-5 mm inserts (50-400 mg/cc) on the coronary tracks. Scores were evaluated on the scaled images by six readers. RESULTS: The CTDIvol at lower voltages was related to the baseline CTDIvol following a power form of the voltage (index 1.246), regardless of the phantom size. The baseline CTDIvol was 1.5 and 4.5 mGy, for the medium and large phantoms, respectively. Correspondingly, the reduced CTDIvol at 100-70 kVp were 1.28-0.76 mGy, and 3.57-2.32 mGy. The downscaling factors were 0.88-0.63. The calcium scores at lower voltages were found within 12 % of the ground-truths. CONCLUSION: A vendor-independent approach was established to obtain the reduced dose and correct coronary calcium scores at lower tube voltages.

Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT myocardial imaging in patients with suspected cardiac amyloidosis.

INTRODUCTION: Assessment of myocardial uptake of Tc-99m-pyrophosphate (Tc-99m PYP) is pivotal in distinguishing transthyretin-associated cardiac amyloidosis (ATTR) from light chain amyloid (AL). It is often difficult to differentiate myocardial uptake from blood pool radioactivity with planar imaging or SPECT. We studied whether simultaneous dual-isotope Tc-99m PYP/Tl-201 SPECT improves assessment of Tc-99m PYP uptake compared to single-isotope SPECT. METHODS: Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT was acquired in 112 patients studied for possible cardiac amyloidosis. Visual interpretation was performed by two observers on single-isotope followed by dual-isotope SPECT. Heart-to-contralateral lung ratio (H/CL) of myocardial counts quantified by single-isotope and dual-isotope SPECT was compared between ATTR, AL, and no amyloidosis groups. RESULTS: In 112 patients (39 ATTR and 26 AL patients, and 47 no amyloidosis), a lower proportion of no amyloidosis and AL patients were classified visually as equivocal with dual-isotope SPECT compared to single-isotope SPECT (2% vs 19%, P = 0.02 and 8% vs 35%, P = 0.04, respectively). H/CL measurements with single-isotope and dual-isotope were lower in AL and no amyloidosis patients vs ATTR patients (P < 0.05). Interobserver agreement of visual assessment was improved with dual-isotope SPECT (P = 0.03). AUCs for detection of ATTR by visual assessment and H/CL quantification were higher with dual-isotope (0.94 and 0.95, respectively) compared to single-isotope SPECT (0.84, P = 0.001 and 0.92, P = 0.02). CONCLUSION: Tc-99m PYP/Tl-201 SPECT improves visual differentiation of ATTR and AL amyloidosis compared to single-isotope SPECT. Visual assessment and H/CL quantitation with dual-isotope SPECT provide similar discrimination between patients with ATTR and AL amyloidosis.

Prognostic value of quantitative high-speed myocardial perfusion imaging.

BACKGROUND: We studied the prognostic value of fully automated quantitative analysis software applied to new solid-state, high-speed (HS) SPECT-myocardial perfusion imaging (MPI). METHODS: 1,613 consecutive patients undergoing exercise or adenosine HS-MPI were followed for 2.6 ± 0.5 years for all-cause mortality (ACM). Automated quantitative software was used to compute stress total perfusion deficit (sTPD) and was compared to semi-quantitative visual analysis. MPI was characterized as 0% (normal), 1%-4% (minimal perfusion defect), 5%-10% (mildly abnormal), and >10% (moderately/severely abnormal). RESULTS: During follow-up, 79 patients died (4.9%). Annualized ACM increased with progressively increasing sTPD; 0% (0.87%), 1%-4% (1.94%), 5%-10% (3.10%), and >10% (5.33%) (log-rank P < .0001). While similar overall findings were observed with visual analysis, only sTPD demonstrated increased risk in patients with minimal perfusion defects. In multivariable analysis, sTPD > 10% was a mortality predictor (HR 3.03, 95% CI 1.30-7.09, P = .01). Adjusted mortality rate was substantial in adenosine MPI, but low in exercise MPI (9.0% vs 1.0%, P < .0001). CONCLUSIONS: By quantitative analysis, ACM increases with increasing perfusion abnormality among patients undergoing stress HS-MPI. These findings confirm previous results obtained with visual analysis using conventional Anger camera imaging systems.

Transient ischemic dilation for coronary artery disease in quantitative analysis of same-day sestamibi myocardial perfusion SPECT.

BACKGROUND: Transient ischemic dilation (TID) of the left ventricle in myocardial perfusion SPECT (MPS) has been shown to be a clinically useful marker of severe coronary artery disease (CAD). However, TID has not been evaluated for 99mTc-sestamibi rest/stress protocols (Mibi-Mibi). We aimed to develop normal limits and evaluate diagnostic power of TID ratio for Mibi-Mibi scans. METHODS: TID ratios were automatically derived from static rest/stress MPS (TID) and gated rest/stress MPS from the end-diastolic phase (TID(ed)) in 547 patients who underwent Mibi-Mibi scans [215 patients with correlating coronary angiography and 332 patients with low likelihood (LLk) of CAD]. Scans were classified as severe (≥ 70% stenosis in proximal left anterior descending (pLAD) artery or left main (LM), or ≥ 90% in ≥ 2 vessels), mild to moderate (≥ 90% stenosis in 1 vessel or ≥ 70%-90% in ≥ 1 vessel except pLAD or LM), and normal (<70% stenosis or LLk group). Another classification based on the angiographic Duke prognostic CAD index (DI) was also applied: DI ≥ 50, 30 ≤ DI < 50 and DI < 30 or LLk group. RESULTS: The upper normal limits were 1.19 for TID and 1.23 for TID(ed) as established in 259 LLk patients. Both ratios increased with disease severity (P < .0001). Incidence of abnormal TID increased from 2% in normal patients to >36% in patients with severe CAD. Similarly, when DI was used to classify disease severity, the average ratios showed significant increasing trend with DI increase (P < .003); incidence of abnormal TID also increased with increasing DI. The incidence of abnormal TID in the group with high perfusion scores significantly increased compared to the group with low perfusion scores (stress total perfusion deficit, TPD < 3%) (P < .0001). The sensitivity for detecting severe CAD improved for TID when added to mild to moderate perfusion abnormality (3% ≤ TPD < 10%): 71% vs 64%, P < .05; and trended to improve for TID(ed)/TID(es): 69% vs 64%, P = .08, while the accuracy remained consistent if abnormal TID was considered as a marker in addition to stress TPD. Similar results were obtained when DI was used for the definition of severe CAD (sensitivity: 76% vs 66%, P < .05 when TID was combined with stress TPD). CONCLUSION: TID ratios obtained from gated or ungated Mibi-Mibi MPS and are useful markers of severe CAD.

Prognostic value of automated vs visual analysis for adenosine stress myocardial perfusion SPECT in patients without prior coronary artery disease: a case-control study.

PURPOSE: We aimed to evaluate the prognostic value of automated quantitative hypoperfusion parameters derived from adenosine stress myocardial perfusion SPECT (MPS) for predicting sudden or cardiac death (CD) in case-controlled patients with suspected coronary artery disease (CAD). METHODS: We considered patients with available adenosine stress Tc-99m sestamibi MPS scans and follow-up information. 81 CD patients from a registry of 428 patients documented by the National Death Index were directly matched in a retrospective case-control design to patients without CD by key clinical parameters (age by deciles, gender, no early revascularization, pre-test likelihood categories, diabetes, and chest pain symptoms). Multivariable analysis of stress MPS total perfusion deficit (STPD) and major clinical confounders were used as predictors of CD. Visual 17-segment summed stress segmental scores (VSSS) obtained by an expert reader, were compared to STPD. RESULTS: CD patients had higher stress hypoperfusion measures compared to controls [STPD: 7.0% vs 3.6% (P < .05), VSSS: 5.3 vs 2.1 (P < .05)]. By univariate analysis, STPD and VSSS have similar predictive power (the areas under receiver operator characteristics curves: STPD = 0.64, VSSS = 0.63; Kaplan-Meier models: χ(2) = 7.59, P = .0059 for STPD and χ(2) = 11.10, P = .0009 for VSSS). The multiple Cox proportional hazards regression models with continuous perfusion measures showed that STPD had similar power to normalized VSSS as a predictor for CD (χ(2) = 4.92; P = .027) vs (χ(2) = 8.90; P = .003). CONCLUSIONS: Quantitative analysis is comparable to expert visual scoring in predicting CD in a case-controlled study.

Usefulness of rapid low-dose/high-dose 1-day 99mTc-sestamibi ECG-gated myocardial perfusion single-photon emission computed tomography.

BACKGROUND: The clinical usefulness of a rapid rest low-dose/stress high-dose (dose ratio =1:5) (99m)Tc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT) protocol for the detection of coronary artery disease was evaluated. METHODS AND RESULTS: In 89 patients, rest images were obtained immediately after the injection of (99m)Tc-sestamibi (256.1+/-28.4 MBq) followed by drinking water (400 ml). Exercise or vasodilator stress test was performed immediately after the completion of rest imaging with the injection of (99m)Tc-sestamibi (1312.3 +/-167.6 MBq). Prior to the post-stress imaging, patients were asked again to drink water (400 ml) in order to eliminate subdiaphragmatic tracer activity. The myocardial count ratio (stress/rest) of (99m)Tc-sestamibi was calculated. Image quality was scored using a 4-point scale system (4= excellent, 3= good, 2= poor, 1= unacceptable). Coronary angiography was performed in 56 patients within 1 month of the SPECT scan. All patients successfully performed the protocol and total examination time was 108+/-7 min. The myocardial count ratio of (99m)Tc-sestamibi was always greater than 6. The image quality was satisfactory both at rest (3.4+/-0.9) and after stress (3.9+/-0.2). The sensitivity and specificity to detect coronary artery stenosis >50% was 84% and 97%, respectively. CONCLUSIONS: This rapid one-day (99m)Tc-sestamibi protocol provides adequate image quality and diagnostic accuracy for detecting coronary artery disease.