Early Versus Standard Late Image Acquisition in Adenosine Myocardial Perfusion Imaging

INTRODUCTION

Myocardial ischemia most frequently occurs due to the presence of atherosclerotic disease in one or more epicardial coronary arteries, resulting in a localized decrease in myocardial blood flow and insufficient perfusion of the myocardium nourished by the affected coronary artery.^[1]

Nuclear imaging techniques involve Gated single-photon emission computed tomography (GSPECT), Myocardial Perfusion Imaging (MPI), performed using dual dual-head/triple-head conventional gamma camera or a dedicated cardiac Cadmium Zinc Telluride (CZT) gamma camera following the radiopharmaceutical injection. It has been used to diagnose and determine prognosis in coronary artery disease (CAD).^[2,3] Technetium-99m (^99mTc)-Tetrofosmin has gained attention for its ability to produce clear images, and its biokinetics closely resemble those of ^99mTc-sestamibi. It is a positively charged (cationic) diphosphine radiopharmaceutical with high myocardial uptake, exhibiting a first-pass extraction efficiency of around 50%. Tetrofosmin demonstrates excellent retention with minimal redistribution, binding predominantly to cytoplasmic mitochondria. Hepatic uptake of ^99mTc-Tetrofosmin is minimal, and clearance from the liver postexercise is rapid. The choice of MPI protocol, whether a 1-day or 2-day protocol, is flexible.^[2]

In individuals diagnosed with significant coronary artery disease, stress testing often reveals a disparity between myocardial supply and demand. This imbalance leads to abnormalities in myocardial perfusion, followed by irregularities in segmental contractility, a process reliant on energy, resulting in temporary stunning of the cardiac muscle cells. While this occurrence is frequently associated with physical exercise or the administration of dobutamine, vasodilator (adenosine) stress testing can also trigger myocardial ischemia, a phenomenon commonly referred to as the steal phenomenon.^[4] Transient postischemic left ventricle (LV) dysfunction due to myocardial stunning in patients with ischemic heart disease can be missed by conventional GSPECT acquisitions, as current American Society of Nuclear Cardiology imaging guidelines for ^99mTc-tetrofosminsuggest minimum delays of 10–15 min for exercise, 30–45 min for rest, and 45 min for pharmacological stress.^[5]

Compared with other ^99mTc-labeled myocardial perfusion scan agents, ^99mTc-tetrofosmin shows rapid accumulation in the myocardium and relatively rapid clearance from background organs. Because of its minimal redistribution and therefore lack of significant changes in myocardial tracer distribution over time, there is a rationale for imaging as early as 5–15 min after tracer injection.

Therefore, if the time delay between tracer injection and imaging is reduced, there will be more chances to detect poststress stunning in ischemic myocardium (the shorter the time delay between stress injection and imaging, the maximum is the chance to detect ischemic wall motion abnormality).^[4,6] This information is of importance to demonstrate, for example, postischemic stunning, or to evaluate the LV stress adaptation by means of ejection fraction and volumes measurements, as well as transient ischemic dilatation of the left ventricle, which are all markers indicative of severe CAD and can be used as prognostic factors that are the main parameters for prognostic assessment.

MATERIAL AND METHODS

A total of 100 patients with suspected or known ischemic heart disease who were referred to our nuclear medicine department for pharmacological stress MPI study, underwent MPI rest-stress same-day protocol on a dedicated solid-state CZT detector cardiac SPECT camera (Discovery NM 530c; GE Healthcare, Haifa, Israel) imaging. This involved the administration of 185 MBq of ^99mTc-Tetrofosmin. Resting-CZT images were acquired 1 h later for 8 min. Patient underwent pharmacological stress with adenosine infusion over 4 min at a rate of 140 μg/kg/min. At 2 min, 740 MBq^99mTc-Tetrofosmin was injected intravenously, and poststress CZT images were acquired after 15 min (early stress-T15) and 45 min (standard late stress-T45) later for 5 min. Image acquisition times and injected tracer doses were already validated in similar patients’ populations with the same camera and calculated in order to obtain a number of counts generally acquired by the same CZT camera after a standard tracer injection.^[7] Patients were imaged in the supine position with arms placed over their heads without any detector or collimator motion. All images were acquired with a 32 × 32 matrix and a 20% energy window centered at the 140 keV photopeak of ^99mTc (pixel width 4 mm). Acquisition of list mode files was performed, and images were reconstructed on a standard workstation (Xeleris II; GE Healthcare, Haifa, Israel) using a dedicated iterative algorithm with 50 iterations. A Butterworth postprocessing filter (frequency 0.37, order 7) was applied to the reconstructed slices. Reconstruction of images was performed without scatter or attenuation correction.

In our study, the poststress images were taken twice, 15 and 45 min after stress, while a single rest study was conducted. However, due to separate processing of the rest-early stress images and rest-delayed stress images, different values for the rest scan were obtained despite it being acquired only once.

RESULTS

We have taken a total of 100 patients (n = 100) in our study.

The mean age of the patient’s population was 63.34 ± 11.32 years. Median age of the population was 65. Out of 100, 75% were males, while 25% were females. There was a statistically significant difference between the ischemic and nonischemic groups in terms of the distribution of Gender (χ² = 5.058, P = 0.025).

In our study, we found that 43% were diabetic, 39% were dyslipidemic, 12% were smokers, 28% had a family history of CAD, and 72% were hypertensive. A clinical history of coronary artery disease was present in 47% patients, previous revascularization with percutaneous coronary angioplasty or coronary artery bypass graft in 44% and 42% had symptoms of angina pain. Among these parameters, we found a statistically significant difference between the ischemic and nonischemic groups in terms of distribution of diabetes (χ² = 8.965, P = 0.003) [Table 1].

Image quality

Change in image quality over time– subjective semi-quantitative grading At T15 (early) imaging– Image quality was graded as excellent in 64% of the participants and good in 30% while 6% participants had fair image quality. At T45 (standard late) imaging– Image quality was graded as excellent in 90% of the participants and good in 9% while 1% participants had fair image quality. No studies were uninterpretable due to poor image quality. 22 (22.0%) patients moved from the category Grade 1 to the category Grade 0. 4 (4.0%) patients moved from the category Grade 2 to the category Grade 0. 1 (1.0%) patient moved from the category Grade 2 to the category Grade 1. The overall change in Quality was statistically significant (Stuart– Maxwell test: χ2 = 26.228, P ≤ 0.001).

Assessment of heart/lung ratio over time The mean Heart/Lung Ratio increased from a minimum of 3.02 at the T15 imaging to a maximum of 3.16 at the T45 imaging (P ≤ 0.001) [Table 2].

We found the prevalence of ischemia in 39% of our patients with the SDS ≥4 on either T15 or T45 imaging. Six patients were classified differently using the two acquisition times; five of them had a higher SDS in T15 imaging, and one had a higher SDS in T45 imaging. There was a statistically significant difference between T15 and T45 groups in terms of distribution of ischemia (χ² = 76.266, P ≤ 0.001) [Table 3 and Fig 1 and 2].

Table 2: Assessment of change in heart/lung ratio over time

Timepoint	Heart/lung ratio			Wilcoxon test
	Mean±SD	Median (IQR)	Range	V	P
T15	3.02±0.62	2.99 (0.72)	1.85-4.55	1115.0	<0.001
T45	3.16±0.66	3.03 (0.89)	1.67-5.56
Absolute change	0.14±0.40	0.12 (0.34)	-0.78-2.22
Percentage change	5.4%±13.3	3.7% (11.3)	-18%-67%

SD: Standard Deviation, IQR: Interquartile range, V represents the sum of the ranks assigned to the positive differences between matched pairs, p<0.001: Significant

Table 3: Ischemia status at T15 and T45 imaging

Ischemia (T45)	Ischemia (T15)			Chi-squared test
	Yes, n (%)	No, n (%)	Total, n (%)	X2	P
Yes	33 (86.8)	1 (1.6)	34 (34.0)	76.266	<0.001
No	5 (13.2)	61 (98.4)	66 (66.0)
Total	38 (100.0)	62 (100.0)	100 (100.0)

(P ≤ 0.001): Significant

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Fig 1:

A 77-year-old female, known case of hypertension, DM, Dyslipidemia, coronary artery disease (CAD) (post angioplasty to Right Coronary Artery), presented with intermittent chest pain at rest for 15 days. (a) Early post stress images showed mild hypoperfusion in the apex, apical septum, apical inferolateral and basal septum (blue arrows). (b) Delayed post stress images show mild hypoperfusion in the apex and apical septum (yellow arrows). Resting images show improvement in the perfusion defects. Overall, early stress images showed more perfusion defects as compared to standard delayed stress images

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Fig 2:

A 50-year-old male, known case of coronary artery disease post angioplasty to Left Anterior Descending, asymptomatic. (a) Early post stress images show severe hypoperfusion in the apex, apical anterior wall, apical anteroseptum and moderate hypoperfusion in the mid septum. There is mild-to-moderate hypoperfusion in the entire inferior wall (blue arrows). (b) Delayed standard stress images showed severe hypoperfusion in the apex, apical anterior wall, apical anteroseptum, and moderate hypoperfusion in the mid septum and mild hypoperfusion in the entire inferior wall (yellow arrows). Resting images showed partial improvement in the perfusion defects. Early stress images showed more severe hypoperfusion in the inferior wall as compared to standard delayed stress images

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There was no statistically significant difference for the perfusion scores SSS and SDS at T15 and T45 imaging. No statistically significant differences were noted between T15 and T45 imaging individually for ischemic and nonischemic groups.

For the ischemic group, although the P values for both SSS (0.054) and SDS (0.106) are slightly above the conventional threshold of 0.05, they suggest a trend towards significance, indicating a possible change in perfusion scores between T15 and T45, however, not strong enough to reach statistical significance. In the nonischemic group, no statistically significant changes in perfusion scores between T15 and T45 were noted.

DISCUSSION

Philippe et al.,^[9] in their study, they imaged 194 patients with tetrofosmin early poststress and at 30 min poststress. They found similar image quality at early poststress SPECT (GPS) (excellent/good in 93.9%) and at 30 min poststress (GS30) SPECT (excellent/good in 96.6%).

A similar study was conducted by Katsikis et al.^[10] using a 1-day stress-rest protocol involving 78 patients who underwent either exercise or adenosine stress. Imaging was performed with tetrofosmin at early (15 min) and late (45 min) time points following stress and rest tracer injection. They found that 93% of patients in the early imaging group achieved optimal or good image quality, as compared to 98% in the late imaging group.

In the study by Philippe et al.,^[9] Single-frame anterior projections were used to acquire the counts in the heart and lung. Statistically significant differences in the heart-to-lung ratios between 99mTc-tetrofosmin early and 30 min poststress with ratios increasing with increased imaging time, was reported. Heart/lung ratio: GPS-2.72 and GS30-2.92.

Giorgetti et al.,^[11] assessed 120 patients at two imaging delay times (15 min and 45 min). They reported no statistically significant differences in counts of the heart, lungs, liver, and subdiaphragmatic area between the two times after 99 mTc-tetrofosmininjection.

LIMITATIONS

• Alterations in wall motion or thickening were not assessed in our study, with the main concentration on variations in LVEF

• Additionally, we do not have outcome data to evaluate the comparative prognostic significance of changes in LVEF between early and standard late imaging sessions.

CONCLUSION

• We recommend that early imaging offers a potential advantage over standard late imaging by providing a more accurate assessment of myocardial stunning, facilitated by a reduced interval between the pharmacological stress test and SPECT acquisition. Our results support that early imaging maintains good image quality; however, if initial image quality is suboptimal, we advise considering delayed acquisition to ensure comprehensive evaluation and confirmation of findings

• Additionally, early imaging is anticipated to improve patient adherence and enhance the cost-effectiveness of services.