Reducing acquisition time may improve patient throughput, increase camera efficiency, and reduce costs; reducing acquisition time also increases image noise. Newly available software controls the effects of noise by maximum a posteriori reconstruction while maintaining resolution with resolution-recovery methods. This study compares half-time (HT) gated myocardial SPECT images processed with ordered-subset expectation maximization with resolution recovery (OSEM-RR) (with and without CT-based attenuation correction [AC]) with full-time (FT) images obtained with a standard clinical protocol and reconstructed with filtered backprojection (FBP) and OSEM (with and without AC). Methods: A total of 212 patients (mean age, 57 y; age range, 27-86 y) underwent 1-d rest/stress 99m Tc-tetrofosmin gated SPECT. FT (12.5 min, both rest and stress) and HT (rest, 7.5 min; stress, 6.0 min) images were acquired with low-dose CT for AC in 112 patients. HT acquisitions were processed with OSEM-RR (with and without AC) using software, and FT acquisitions were processed with FBP and OSEM (with and without AC). In another 100 patients, test-retest repeatability was assessed using 2 sets of FT images (FBP reconstruction) that were acquired one immediately after the other. Radiologists unaware of the acquisition and reconstruction protocols visually assessed all reconstructed images for summed stress, summed rest, and summed difference scores and regional wall motion using a 17-segment model. Automated analysis on gated SPECT was used to determine left ventricular volumes, ejection fraction, and dilation (end-diastolic volume, end-systolic volume, left ventricular ejection fraction, and transient ischemic dilation [TID]). A clinical diagnosis was also determined. Results: All measurements resulted in significant correlations (P , 0.01) between the HT and FT images. The only significant difference in mean values was for OSEM-RR plus AC; this method led to an increase in TID by 4% over FT imaging. The concordance in the clinical diagnosis for HT versus FT was 106 to 112 (k 5 0.88) for no AC and 102 to 106 (k 5 0.91) for AC, similar to the repeatability of FT versus FT (98/100, k 5 0.95). Conclusion: HT images processed with the new algorithm provided a clinical diagnosis in concordance with that from FT images in 95% (no AC) to 96% (AC) of cases. This concordance is similar to the test-retest repeatability of FT imaging.
Background: Measurement of myocardial blood flow (MBF) with single photon emission computed tomography (SPECT) is feasible using cardiac cameras with solid-state detectors. SPECT MBF has been shown to be accurate when compared with positron emission tomography MBF measured in the same patients. However, the value of a test result applied to an individual patient depends strongly on the precision or repeatability of the test. The purpose of our study is to measure the precision of SPECT MBF measurements using 99m Tc-tetrofosmin and a solid-state cardiac camera. Methods: SPECT MBF was measured in 30 patients and repeated at a mean interval of 18 days. MBF was evaluated from images with and without attenuation correction based on a separately acquired CT scan. The dynamic images were processed independently by 2 operators using in-house kinetic analysis software that applied a 1-tissue-compartment model. The K1 rate constant was converted to MBF using previously determined extraction fraction corrections. Correction for patient body motion was applied manually. Results: The average coefficient of variation (COV) in the differences between the 2 MBF measurements was between 28% and 31%. The interobserver COV was between 11% and 15%. Myocardial flow reserve is the ratio of MBF measured at stress and rest, and the COV is correspondingly higher. The COV for the difference in repeated myocardial flow reserve was 33% to 38%, whereas the interobserver COV was 13% to 22%. Conclusions: The COV for the difference in SPECT MBF measurements obtained on separate days is 28% to 31%. The corresponding COV for myocardial flow reserve is 33% to 38%.
Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.
A noninvasive and repeatable method for assessing mouse myocardial glucose uptake with 18 F-FDG PET and Patlak kinetic analysis was systematically assessed using the vena cava imagederived blood input function (IDIF). Methods: Contrast CT and computer modeling was used to determine the vena cava recovery coefficient. Vena cava IDIF (n 5 7) was compared with the left ventricular cavity IDIF, with blood and liver activity measured ex vivo at 60 min. The test-retest repeatability (n 5 9) of Patlak influx constant K i at 10-40 min was assessed quantitatively using BlandAltman analysis. Myocardial glucose uptake rates (rMGU) using the vena cava IDIF were calculated at baseline (n 5 8), after induction of type 1 diabetes (streptozotocin [50 mg/kg] intraperitoneally, 5 d), and after acute insulin stimulation (0.08 mU/kg of body weight intraperitoneally). These changes were analyzed with a standardized uptake value calculation at 20 and 40 min after injection to correlate to the Patlak time interval. Results: The proximal mouse vena cava diameter was 2.54 6 0.30 mm. The estimated recovery coefficient, calculated using nonlinear image reconstruction, decreased from 0.76 initially (time 0 to peak activity) to 0.61 for the duration of the scan. There was a 17% difference in the image-derived vena cava blood activity at 60 min, compared with the ex vivo blood activity measured in the g-counter. The coefficient of variability for Patlak K i values between mice was found to be 23% with the proposed method, compared with 51% when using the left ventricular cavity IDIF (P , 0.05). No significant bias in K i was found between repeated scans with a coefficient of repeatability of 0.16 mL/min/g. Calculated rMGU values were reduced by 60% in type 1 diabetic mice from baseline scans (P , 0.03, ANOVA), with a subsequent increase of 40% to a level not significantly different from baseline after acute insulin treatment. These results were confirmed with a standardized uptake value measured at 20 and 40 min. Conclusion: The mouse vena cava IDIF provides repeatable assessment of the blood time-activity curve for Patlak kinetic modeling of rMGU. An expected significant reduction in myocardial glucose uptake was demonstrated in a type 1 diabetic mouse model, with significant recovery after acute insulin treatment, using a mouse vena cava IDIF approach.
Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biologic agent, OV has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in preclinical models and in clinical trials. To give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral-based platforms with 2 specific gene reporters. Methods: We incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSSR2) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo. Results: Early and high-level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allowed a higher functional expression of the protein and much stronger 123 I or 99 Tc uptake. In vivo, the hNIS-containing virus infected and amplified in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allowed for the imaging of viral infection and tumor regression. Similarly, hSSR2-containing OV vaccinia infected and lysed cancer cells. Conclusion: When tumor-bearing mice were given hNIS-and hSSR2-containing OV, 99 Tc and 111 In signals coalesced at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.
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