Emerging Trends and Future Perspective of Novel Cardiac SPECT Technology
In response to concerns about overuse and increasing radiation exposure of myocardial perfusion imaging, nuclear medicine societies have declared statements aimed at lowering its radiation dose and costs. Simultaneously, two vendors have launched novel SPECT scanners with solid-state semiconductor detectors. Discovery NM 530c and D-SPECT utilize the same cadmium zinc telluride (CZT) detectors with a different combination of high-sensitivity multi-pinhole or parallel-hole collimator which focuses on the heart. The physical performance of those is dramatically higher than that of conventional Anger cameras; however, 2 CZT cameras are inherently different.
Although 99mTc-labeled myocardial perfusion tracers might not be ideal agents, estimation of absolute myocardial blood flow or myocardial flow reserve (MFR) using dynamic CZT SPECT is a challenging subject and attracts a great deal of interest in the field. Thus, novel software which allows automatic calculation of MFR index with dynamic CZT SPECT is currently under development and validated in our institution. This technology will hold promise if the several issues can be solved through future studies.
KeywordsCadmium zinc telluride Cardiac SPECT Coronary flow reserve Effective dose Dynamic imaging
The overall utilization for stress myocardial perfusion imaging (MPI) reached its height in 2006 with over 10 million studies and Medicare payment over 1 billion dollars . The National Council on Radiation Protection and Measurements reported that since the early 1980s, a six-fold increase in radiation exposure to the US population from medical procedures  emphasizes that more than 10 % of the entire radiation burden was related to MPI . In response to these concerns, professional societies have declared statements aimed at lowering its radiation dose and costs [4, 5].
Simultaneously, vendors have developed dedicated cardiac SPECT scanners with solid-state semiconductor detectors in order to do something about radiation dose and long imaging time. Two vendors have introduced novel scanners: Discovery NM 530c, (D530c); GE Healthcare and D-SPECT; and Spectrum Dynamics utilizing the same cadmium zinc telluride (CZT) detectors, with a different combination of high-sensitivity multi-pinhole or parallel-hole collimators which focuses on the myocardium [6, 7]. More than 300 of such cardiac CZT SPECT scanners are currently available in the world, and the number is increasing by more than 100 per year.
Firstly, we focus on the latest advances in MPI procedures which ought to be able to maximize the value of SPECT cameras with CZT detectors. Secondly, we try to develop a novel software for calculating the myocardial flow reserve (MFR) index using these cameras and to validate its utility for screening patients with multi-vessel coronary artery disease (CAD).
14.2 Materials and Methods
Initially, we conducted a comparative study using 99mTc line-source phantoms with and without photon scattering caused by water in the cylinder . D530c had a more than two-fold spatial resolution than did the conventional Anger camera with a dual detector (Infinia; GE Healthcare). We also found that a D530c has better energy resolution compared to Infinia, which is as narrow as 5 %. Therefore, energy window width could be narrowed enough to be feasible for performing dual radioisotope simultaneous SPECT with 99mTc-tetrofosmin and 123I-BMIPP .
The software allows the automatic edge detection of volume of interest for the blood pool in the left ventricle and the myocardium. Global time-activity curves were fitted to a one-tissue two-compartment kinetic model (2-com), a Patlak plot analysis (PPA), and a dose uptake ratio of MPI (DUR) with input function. K1 and K2 were calculated for the stress and rest images. MFR index was calculated as follows: MFR index = K1 stress/K1 at rest.
The validation study included 64 consecutive pts who underwent CZT SPECT and invasive coronary angiography within 2 weeks (35 males, 67 ± 10 years old). 15 pts had single-vessel CAD, and 22 pts had multi-vessel CAD (10 had two-vessel and 12 had three-vessel CAD) and 27 pts with no significant coronary stenosis less than 70 %.
14.3 Results and Discussion
14.3.1 Reduction in Injection Dose of Radiopharmaceuticals
The introduction of CZT cameras has opened the possibility of reducing radiation dose of SPECT MPI. Oddstig et al.  reported that they performed a 1-day 99mTc-tetrofosmin stress-rest protocol using D530c in 150 patients who were divided into three subgroups (50 patients in each group) with 4, 3, and 2.5 MBq/kg body weight of administered activity in the stress MPI, respectively. The total effective dose (stress and rest) decreased from 9.3 mSv in the 4 MBq/kg group to 5.8 mSv in the 2.5 MBq/kg group. The image acquisition times for 2.5 MBq/kg were 8 and 5 min (stress and rest, respectively) compared to 15 min for each when using conventional SPECT. The average image quality for the stress and the rest showed no statistically significant difference among the 4, 3, and 2.5 MBq/kg groups.
Starting the MPS protocol with examination at stress and analyzing the stress images before deciding of the need for rest examination (i.e., to say “stress-only protocol”) reduce the effective dose [13, 14]. The effective dose was no more than 1.4 mSv for a patient receiving 2.5 MBq/kg, who underwent the stress-only protocol. The total effective radiation dose ranged 3 to 6 mSv with the stress-rest protocol in our institution. If applied, stress-only protocol would be performed with the effective dose averaging 1 mSv. Novel CZT technology can considerably decrease the effective dose for MPI with preserved high image quality.
Moreover, the high sensitivity of D530c allows for a shorter acquisition time; actually, 5 min is sufficient for QGS in the clinical setting. Although CZT detectors are higher in cost, they have been shown to provide an eight- to ten-fold increase in sensitivity, coupled with a two-fold improvement in spatial resolution, and higher energy resolution enabling a significant reduction in imaging time and dose of isotopes and a dual radionuclide simultaneous SPECT with 99mTc and 123I [6, 7].
Imbert et al. also conducted analyses of phantom and human SPECT images, comparing the D530c and D-SPECT CZT cameras with Anger cameras, and reported that the physical performance of CZT cameras is dramatically higher than that of Anger cameras; however, 2 CZT cameras are inherently different. Spatial resolution and contrast-to-noise ratio are better with the Discovery NM 530c, whereas detection sensitivity is markedly higher with the D-SPECT .
14.3.2 Attempts to Estimate Coronary Flow Reserve Using CZT SPECT
At present, coronary flow reserve (CFR) has been mostly replaced by FFR primarily due to its technical simplicity in the catheterization lab. In contrast, in the noninvasive field, PET-derived CFR is an emerging index used for improving both the diagnosis and risk stratification in patients with suspected CAD. And with the increased use, reliable evidences have been suggested that CFR is a powerful independent predictor of cardiac events and mortality [16, 17, 18, 19].
In parallel to the work on these PET studies, some studies have continuously reported that using first-pass planar scintigraphy in humans [20, 21, 22, 23, 24] or dynamic SPECT in animals  provides evidences that the estimates of CFR can be also derived from conventional SPECT MPI. Although fair agreements have been noted between CFR estimated by SPECT and PET or intracoronary Doppler flow studies, they also highlighted the limitations of conventional gamma camera for the dynamic data collection during rapidly changing radiotracer concentrations .
The CZT cameras provide higher temporal and spatial resolution. Dynamic SPECT imaging during the first pass of a tracer was attained with the use of these cameras. From the list data, time-activity curves (TAC) would be generated for the left ventricular cavity (input function) and for myocardial tissue (output function) during stress and rest. Ben-Haim et al.  firstly reported the feasibility of dynamic 99mTc-MIBI SPECT and quantitation of global and regional CFRs using the D-SPECT. They calculated CFR index as the ratio of the stress and rest K1 values. Global CFR index was higher in patients with normal MPI than in patients with abnormal MPI. The CFR index was lower in territories supplied by stenotic coronary arteries than in non-stenotic arteries.
Most recently, Wells et al. applied the D530c to a study with a pig model for quantitation of absolute myocardial blood flow (MBF) using common perfusion tracers as 99mTc-MIBI, 99mTc-tetrofosmin, and thallium-201 . Dynamic images were reconstructed with CT-based attenuation correction and energy window-based scatter correction and then processed with kinetic analysis using a 1-tissue 2-com model to obtain the uptake rate constant K1 as a function of microsphere MBF. Converting K1 back to MBF using the measured extraction fractions produced accurate values and good correlations with microsphere MBF. They have demonstrated that dynamic SPECT by the CZT camera may be feasible to estimate absolute MBF.
14.3.3 Advantages and Disadvantages of the Measurement of CFR with SPECT
At the current moment, PET plays a major role in accurate estimation of MBF or CFR. However, it has limited value for routine clinical studies because of its higher cost and more complicated procedures, including the production of short-half-lived positron tracers by in-house cyclotrons. Therefore, the advantage of SPECT-measured technique utilizing common technetium-99 m perfusion tracers is that it would increase the utility of CFR measurement in the clinical setting with a much smaller financial cost.
On the other hand, the disadvantage of quantifying CFR with SPECT may be the underestimation of the CFR value, compared to that with PET. The reasons for this underestimation could be mainly due to the limited extraction of technetium-99 m perfusion tracers at high flow rates, at which the extraction of the tracer becomes limited by membrane transport .
We need to explore patient-centered, radiation exposure-controlled, and appropriately designed protocols which do not sacrifice image quality or diagnostic accuracy of the new modality. Although 99mTc-labeled radiotracers might not be ideal flow agents, estimation of absolute MBF or CFR using dynamic CZT SPECT is challenging and of great interest. This technology will hold great promise if the several issues can be solved through future studies.
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