Quantitative Myocardial Perfusion Imaging Assessment by SPECT/CT

Coronary artery disease is a major cause of morbidity and mortality worldwide and requires accurate diagnostic and functional assessment to guide patient management. Non-invasive myocardial perfusion imaging plays a central role in the evaluation of ischemia and risk stratification. Single-photon emission computed tomography (SPECT) is widely used for this purpose due to its availability, established clinical utility, and integration into routine cardiology practice.

Recent technological advancements have led to the development of cadmium-zinc-telluride (CZT) SPECT cameras, which offer significant improvements over conventional systems. These improvements include higher sensitivity, better spatial resolution, and faster acquisition times, allowing more efficient imaging workflows and enhanced patient comfort. Despite these advances, conventional SPECT imaging is primarily based on relative perfusion assessment and does not routinely provide absolute quantification of myocardial blood flow.

Positron emission tomography (PET) myocardial perfusion imaging is currently considered the reference standard for the non-invasive quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR). This technique enables absolute measurement of myocardial perfusion under rest and stress conditions and provides important diagnostic and prognostic information. However, the widespread use of PET is limited by several factors, including high costs, the need for dedicated infrastructure, and limited availability of radiotracers such as Rubidium-82. As a result, access to PET imaging remains restricted in many clinical settings.

In this context, there is a growing interest in developing alternative approaches that could provide quantitative functional information using more accessible imaging modalities. CZT-SPECT imaging has the potential to enable absolute quantification of myocardial tracer uptake expressed as standardized uptake values (SUV). This approach may allow the calculation of a stress-to-rest uptake ratio, which could serve as an indirect marker of myocardial perfusion reserve and potentially approximate the information provided by MFR measured with PET.

The present study is designed as a prospective, single-center, pilot, study conducted at the University Hospital of Orléans. The primary objective is to assess the feasibility of obtaining quantitative SUV measurements using CZT-SPECT and to compare the resulting stress-to-rest SUV ratios with MFR values derived from PET imaging in the same patients. This comparison aims to evaluate the potential of CZT-SPECT as a surrogate method for functional myocardial assessment.

Eligible participants include adult patients under cardiology follow-up who are referred for diagnostic coronary angiography or coronary computed tomography angiography as part of their standard clinical care. Patients will be informed about the study during their cardiology consultation and will be invited to participate on a voluntary basis. Written informed consent will be obtained prior to inclusion. All enrolled participants will undergo the same study procedures without randomization or group allocation. Patients eligible for inclusion are those identified during routine clinical care, either following coronary computed tomography angiography or invasive coronary angiography, presenting with moderate coronary stenosis (typically between 50% and 70%) for which further functional evaluation is indicated to guide clinical management. Patients with severe coronary disease requiring immediate revascularization are not eligible for participation.

The imaging protocol has been designed to align with routine clinical practice while enabling direct comparison between PET and SPECT-derived measurements. On Day 0 (J0), participants will undergo a PET myocardial perfusion study using Rubidium-82. This examination includes both rest and pharmacological stress phases using a coronary vasodilator agent, allowing the measurement of MBF and the calculation of MFR.

During PET imaging, participants will receive a concomitant injection of 99mTc-tetrofosmin under the same pharmacological stress conditions to ensure comparable hemodynamic states. A stress CZT-SPECT/CT acquisition will then be performed after the PET acquisition under the same pharmacological stress conditions, enabled by the short half-life of the PET radiotracer (Rubidium-82). This sequential approach avoids the need for repeated pharmacological stress, minimizes variability between imaging modalities and allows direct comparison of functional parameters obtained during similar physiological conditions.

Within seven days after the initial visit (J0), participants will undergo a second CZT-SPECT/CT acquisition at rest (second visit = J1). This delayed rest imaging allows measurement of baseline myocardial tracer uptake. Quantitative image analysis will be performed to derive SUV values for both stress and rest acquisitions. From these measurements, a stress-to-rest SUV ratio will be calculated for each participant.

As a single-group study, all participants serve as their own controls, allowing within-subject comparison between PET-derived myocardial flow reserve and SPECT-derived SUV ratios. The study aims to assess feasibility and generate preliminary data to support future larger-scale investigations.

The study will evaluate feasibility endpoints, including the ability to perform standardized quantitative acquisitions, the success rate of SUV calculation, and the quality of the imaging data obtained. In addition, exploratory analyses will assess the relationship between SUV ratios derived from CZT-SPECT and MFR values obtained from PET. These analyses will provide preliminary information on the potential agreement and clinical relevance of this approach.

The results of this study are intended to generate preliminary evidence to support the design of a subsequent larger-scale clinical trial. The long-term objective is to determine whether CZT-SPECT imaging with SUV quantification could represent a simplified, faster, and more widely available alternative to PET myocardial perfusion imaging for the assessment of myocardial function and coronary physiology in routine clinical practice.

Inclusion criteria

• Participant has provided informed consent to participate in the study.
• Age ≥ 18 years.
• Patients referred for functional cardiac imaging assessment (SPECT or PET) following diagnostic coronary CT angiography (CCTA) or invasive coronary angiography demonstrating either:

• moderate coronary atherosclerosis without significant coronary stenosis (<50% stenosis), or
• coronary lesions for which functional cardiac imaging assessment or medical therapy is indicated.

Exclusion criteria

• Severe coronary artery disease requiring prompt revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), including left main coronary artery stenosis >50% or other severe coronary lesions with FFR <0.80.
• History of coronary revascularization (PCI, coronary stenting, or CABG).
• Left ventricular ejection fraction (LVEF) <35%.
• Contraindication to pharmacological stress testing for cardiac PET/SPECT, including severe hypotension, second- or third-degree atrioventricular block, or recent myocardial infarction.
• Protected adult under legal guardianship or curatorship.
• Individual under judicial protection measures.
• Individual deprived of liberty.
• Individual not affiliated with a health insurance
• Pregnant or breastfeeding woman.