A fast cardiac gamma camera with dynamic SPECT capabilities: design, system validation and future potential.

PURPOSE: The goal of this study is to present the Discovery NM 530c (DNM), a cardiac SPECT camera, interfacing multi-pinhole collimators with solid-state modules, aiming at slashing acquisition time without jeopardizing quality. DNM resembles PET since it enables 3-D SPECT without detector motion. We further envision how these novel capabilities may help with current and future challenges of cardiac imaging. METHODS: DNM sensitivity, spatial resolution (SR) and energy resolution (ER), count rate response, cardiac uniformity and cardiac defect contrast were measured and compared to a dedicated cardiac, dual-head standard SPECT (S-SPECT) camera. RESULTS: DNM sensitivity was more than threefold higher while SR was notably better. Significantly, SR was the same for (99m)Tc and (201)Tl. ER was improved on DNM and allowed good separation of (99m)Tc and (123)I spectral peaks. Count rate remained linear on DNM up to 612 kcps, while S-SPECT showed severe dead time limitations. Phantom studies revealed comparable uniformity and defect contrast, notwithstanding significantly shorter acquisition time for the DNM. First patient images, including dynamic SPECT, are also presented. CONCLUSION: DNM is raising the bar for expedition and upgrade of practice. It features high sensitivity as well as improved SR, temporal resolution and ER. It enables reduction of acquisition time and fast protocols. Importantly, it is potentially capable of dynamic 3-D acquisition. The new technology is potentially upgradeable and may become a milestone in the evolution of nuclear cardiology as it assumes its key role in molecular imaging of the heart.

Nonpainful remote electrical stimulation alleviates episodic migraine pain.

OBJECTIVE: To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain. METHODS: This is a prospective, double-blinded, randomized, crossover, sham-controlled trial. Migraineurs applied skin electrodes to the upper arm soon after attack onset for 20 minutes, at various pulse widths, and refrained from medications for 2 hours. Patients were asked to use the device for up to 20 attacks. RESULTS: In 71 patients (299 treatments) with evaluable data, 50% pain reduction was obtained for 64% of participants based on best of 200-µs, 150-µs, and 100-µs pulse width stimuli per individual vs 26% for sham stimuli. Greater pain reduction was found for active stimulation vs placebo; for those starting at severe or moderate pain, reduction (1) to mild or no pain occurred in 58% (25/43) of participants (66/134 treatments) for the 200-µs stimulation protocol and 24% (4/17; 8/29 treatments) for placebo (p = 0.02), and (2) to no pain occurred in 30% (13/43) of participants (37/134 treatments) and 6% (1/17; 5/29 treatments), respectively (p = 0.004). Earlier application of the treatment, within 20 minutes of attack onset, yielded better results: 46.7% pain reduction as opposed to 24.9% reduction when started later (p = 0.02). CONCLUSION: Nonpainful remote skin stimulation can significantly reduce migraine pain, especially when applied early in an attack. This is presumably by activating descending inhibition pathways via the conditioned pain modulation effect. This treatment may be proposed as an attractive nonpharmacologic, easy to use, adverse event free, and inexpensive tool to reduce migraine pain. CLINICALTRIALSGOV IDENTIFIER: NCT02453399. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain.

Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl triphenyl phosphonium in dog myocardium.

UNLABELLED: 18F-Labeled p-fluorobenzyl triphenyl phosphonium cation (18F-FBnTP) is a member of a new class of positron-emitting lipophilic cations that may act as myocardial perfusion PET tracers. Here, we characterize the 18F-FBnTP uptake and retention kinetics, in vitro and in vivo, as well as the myocardial and whole-body biodistribution in healthy dogs, using PET. METHODS: Time-dependent accumulation and retention of 18F-FBnTP in myocytes in vitro was studied. Seven anesthetized, mongrel dogs underwent dynamic PET scans of the heart after intravenous administration of 126-240 MBq 18F-FBnTP. In 4 of the 7 dogs, at the completion of a 60-min dynamic scan, whole-body scans (4 bed positions, 5-min emission and 3-min transmission per bed) were acquired. Arterial blood samples were collected at 0, 5, 10, 20, 30, and 60 min after administration, plasma activity was counted, and high-performance liquid chromatographic analyses for metabolites were performed. The extent of defluorination was assessed by measuring 18F-FBnTP bone uptake in mice, compared with 18F-fluoride. RESULTS: The metabolite fraction comprised <5% of total activity in blood at 5 min and gradually increased to 25% at 30 min after injection. In vivo, 18F-FBnTP myocardial concentration reached a plateau level within a few minutes, which was retained throughout the scanning time. In contrast, activity in the blood pool and lungs cleared rapidly (half-life = 19.5 +/- 4.4 and 30.7 +/- 11.6 s, respectively). Liver uptake did not exceed the activity measured in the myocardium. At 60 min, the uptake ratios of left ventricular wall to blood, lung, and liver (mean of 7 dogs) were 16.6, 12.2, and 1.2, respectively. Summation of activity from 5 to 15 min and from 30 to 60 min after injection produced high-quality cardiac images of similar contrast. Circumferential sampling and a polar plot revealed a uniform distribution, near unitary value, throughout the entire myocardium. The mean coefficient of variance, on 30- to 60-min images along the septum-to-anterior wall and the apex-to-base axes was 7.58% +/- 1.04% and 6.11% +/- 0.89% (mean +/- SD; n = 7), respectively, and on 5- to 15-min images was 7.25% +/- 1.43% and 6.12% +/- 1.88%, respectively. 18F-FBnTP whole-body distribution was highly organ specific with the kidney cortex being the major target organ, followed by the heart and the liver. CONCLUSION: 18F-FBnTP is a promising new radionuclide for cardiac imaging using PET with rapid kinetics, uniform myocardial distribution, and favorable organ biodistribution.

Assessment of cardiac single-photon emission computed tomography performance using a scanning linear observer.

PURPOSE: Single-photon emission computed tomography (SPECT) is widely used to detect myocardial ischemia and myocardial infarction. It is important to assess and compare different SPECT system designs in order to achieve the highest detectability of cardiac defects. METHODS: Whitaker et al.'s study ["Estimating random signal parameters from noisy images with nuisance parameters: linear and scanning-linear methods," Opt. Express 16(11), 8150-8173 (2008)] on the scanning linear observer (SLO) shows that the SLO can be used to estimate the location and size of signals. One major advantage of the SLO is that it can be used with projection data rather than with reconstruction data. Thus, this observer model assesses the overall hardware performance independent of any reconstruction algorithm. In addition, the computation time of image quality studies is significantly reduced. In this study, three systems based on the design of the GE cadmium zinc telluride-based dedicated cardiac SPECT camera Discovery 530c were assessed. This design, which is officially named the Alcyone Technology: Discovery NM 530c, was commercialized in August, 2009. The three systems, GE27, GE19, and GE13, contain 27, 19, and 13 detectors, respectively. Clinically, a human heart can be virtually segmented into three coronary artery territories: the left-anterior descending artery, left-circumflex artery, and right coronary artery. One of the most important functions of a cardiac SPECT system is to produce images from which a radiologist can accurately predict in which territory the defect exists [http://www.asnc.org/media/PDFs/PPReporting081511.pdf, Guideline from American Society of Nuclear Cardiology]. A good estimation of the extent of the defect from the projection images is also very helpful for determining the seriousness of the myocardial ischemia. In this study, both the location and extent of defects were estimated by the SLO, and the system performance was assessed by localization receiver operating characteristic (LROC) [P. Khurd and G. Gindi, "Decision strategies maximizing the area under the LROC curve," Proc. SPIE 5749, 150-161 (2005)] or estimation receiver operating characteristic (EROC) [E. Clarkson, "Estimation receiver operating characteristic curve and ideal observers for combined detection/estimation tasks," J. Opt. Soc. Am. A 24, B91-B98 (2007)] curves. RESULTS: The area under the LROC/EROC curve (AULC/AUEC) and the true positive fraction (TPF) at a specific false positive fraction (FPF) can be treated as the figures of merit. For radii estimation with a 1 mm tolerance, the AUEC values of the GE27, GE19, and GE13 systems are 0.8545, 0.8488, and 0.8329, and the TPF at FPF = 5% are 77.1%, 76.46%, and 73.55%, respectively. The assessment of all three systems revealed that the GE19 system yields estimated information and cardiac defect detectability very close to those of the GE27 system while using eight fewer detectors. Thus, 30% of the expensive detector units can be removed with confidence. CONCLUSIONS: As the results show, a combination of the SLO and LROC/EROC curves can determine the configuration that yields the most relevant estimation/detection information. Thus, this is a useful method for assessing cardiac SPECT systems.

Singular Value Decomposition of Pinhole SPECT Systems.

A single photon emission computed tomography (SPECT) imaging system can be modeled by a linear operator H that maps from object space to detector pixels in image space. The singular vectors and singular-value spectra of H provide useful tools for assessing system performance. The number of voxels used to discretize object space and the number of collection angles and pixels used to measure image space make the matrix dimensions H large. As a result, H must be stored sparsely which renders several conventional singular value decomposition (SVD) methods impractical. We used an iterative power methods SVD algorithm (Lanczos) designed to operate on very large sparsely stored matrices to calculate the singular vectors and singular-value spectra for two small animal pinhole SPECT imaging systems: FastSPECT II and M(3)R. The FastSPECT II system consisted of two rings of eight scintillation cameras each. The resulting dimensions of H were 68921 voxels by 97344 detector pixels. The M(3)R system is a four camera system that was reconfigured to measure image space using a single scintillation camera. The resulting dimensions of H were 50864 voxels by 6241 detector pixels. In this paper we present results of the SVD of each system and discuss calculation of the measurement and null space for each system.

Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated (82)rubidium myocardial perfusion PET.

PURPOSE: Myocardial perfusion imaging with (82)Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. METHODS: One hundred ten consecutive patients undergoing (82)Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480-2,220 MBq of (82)Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. RESULTS: Significant reversibility (SDS > or = 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 +/- 13% at rest and 53 +/- 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = -0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = -0.20; p = 0.03) and SSS (r = -0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. CONCLUSIONS: Gated (82)Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on (82)Rb PET.