Interpretation of SPECT wall motion with deep learning.

OBJECTIVES: We sought to develop a novel deep learning (DL) workflow to interpret single-photon emission computed tomography (SPECT) wall motion. BACKGROUND: Wall motion assessment with SPECT is limited by image temporal and spatial resolution. Visual interpretation of wall motion can be subjective and prone to error. Artificial intelligence (AI) may improve accuracy of wall motion assessment. METHODS: A total of 1038 patients undergoing rest electrocardiogram (ECG)-gated SPECT and echocardiography were included. Using echocardiography as truth, a DL-model (DL-model 1) was trained to predict the probability of abnormal wall motion. Of the 1038 patients, 317 were used to train a DL-model (DL-model 2) to assess regional wall motion. A 10-fold cross-validation was adopted. Diagnostic performance of DL was compared with human readers and quantitative parameters. RESULTS: The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of DL model (AUC: .82 [95% CI: .79-.85]; ACC: .88) were higher than human (AUC: .77 [95% CI: .73-.81]; ACC: .82; P < .001) and quantitative parameter (AUC: .74 [95% CI: .66-.81]; ACC: .78; P < .05). The net reclassification index (NRI) was 7.7%. The AUC and accuracy of DL model for per-segment and per-vessel territory diagnosis were also higher than human reader. The DL model generated results within 30 seconds with operable guided user interface (GUI) and therefore could provide preliminary interpretation. CONCLUSIONS: DL can be used to improve interpretation of rest SPECT wall motion as compared with current human readers and quantitative parameter diagnosis.

Exponential dosing to standardize myocardial perfusion image quality with rubidium-82 PET.

BACKGROUND: 82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional functions of body weight on the standardization of myocardial perfusion image (MPI) quality. METHODS: Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg-2 exponential and 9 MBq·kg-1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight. RESULTS: Average (min-max) patient body weight was 81 ± 18 kg (46-137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P < 0.05). Exponential dosing eliminated the weight-dependent decreases in these image quality metrics that were observed in the proportional dosing group. CONCLUSION: 82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.

Measuring SPECT myocardial blood flow at the University of Ottawa Heart Institute.

The introduction of new cardiac SPECT cameras has made it practical to do dynamic SPECT imaging and opened the door to performing myocardial blood flow (MBF) imaging with SPECT. In this paper, we describe in detail our approach to dynamic SPECT MBF imaging using a multi-pinhole cardiac SPECT camera and commercially available kinetic analysis software. We use a 1-day rest/stress protocol with 370 MBq injected at rest and 1,000 MBq at stress with a 1- to 2-hour interval between rest and stress imaging. The tracer is injected mechanically over 30 seconds using a syringe pump. Projection data are acquired in listmode for a duration of 11 minutes and then reframed into a dynamic series. Each image is reconstructed independently using vendor-supplied software. The dynamic images are corrected for residual activity and manually corrected for motion using rigid-body translation. The uptake rate constant, K1, is calculated using a 1-tissue-compartment kinetic model and converted to MBF using a previously determined extraction fraction correction.

Reduced acquisition times for measurement of myocardial blood flow with 99mTc-tetrofosmin and solid-state detector SPECT.

BACKGROUND: Measurement of myocardial blood flow (MBF) is feasible using SPECT imaging but the acquisition requires more time than usual. Our study assessed the impact of reducing acquisition times on the accuracy and repeatability of the uptake rate constant (K1). METHODS: Twenty-nine patients underwent two rest/stress studies with Tc-99m-tetrofosmin 18 ± 13 days apart, using a one-day rest/stress dynamic SPECT imaging protocol with a solid-state cardiac camera. A 5-minute static image was acquired prior to tracer injection for subtraction of residual activity, followed immediately by 11-minute of list-mode data collection. Static image acquisition times of 0.5, 1, and 3 minutes and dynamic imaging times of 5, 7, and 9 minutes were simulated by truncating list-mode data. Images were reconstructed with/without attenuation correction and with/without motion correction. Kinetic parameters were calculated using a 1-tissue-compartment model. RESULTS: K1 increased with reduced dynamic but not static imaging time (P < 0.001). The increase in K1 for a 9-minute scan was small (4.7 ± 5.3%) compared with full-length studies. The repeatability of K1 did not change significantly (13 ± 12%, P > 0.17). CONCLUSIONS: A shortened imaging protocol of 3-minute (rest) or 30-second (stress) static image acquisition and 9 minutes of dynamic image acquisition altered K1 by less than 5% compared to a previously validated 11-minute acquisition.

Noise heterogeneity in attenuation-corrected cardiac SPECT images increases perfusion value uncertainty near the base of the heart.

BACKGROUND: Dedicated cardiac SPECT cameras which employ multi-pinhole detectors have variable photon sensitivity within the camera's field-of-view such that a lower number of photon counts is typically detected from the base of the heart than from the apex. Consequently, the noise in a reconstructed image is expected to be higher at the base than at the apex of the heart. METHODS: Patient emission images were resampled to create statistical replicates which were reconstructed with and without attenuation correction. Noise images were computed using one standard deviation of the replicated images. These were evaluated for 93 patients with normal study results, each imaged with both a dual-headed parallel-hole camera and a multi-pinhole camera. Statistics for a normal database (NDB) of images from the 93 patients were also calculated. RESULTS: Image noise (1.7-fold) and NDB uncertainty (1.3-fold) increase significantly from the apex-to-the base of the heart in attenuation-corrected multi-pinhole SPECT images. The differences for non-attenuation-corrected images or those acquired with a parallel-hole camera were not significant. CONCLUSIONS: For best interpretation of attenuation-corrected images acquired with multi-pinhole cameras, knowledge of NDB uncertainty gradients should be taken into consideration.

Patient-specific SPECT imaging protocols to standardize image noise.

BACKGROUND: In addition to acquired photon counts, image noise depends on the image reconstruction algorithm. This work develops patient-specific activity or acquisition time protocols to standardize the average noise in a reconstructed image for different patients, cameras, and reconstruction algorithms. METHODS: Image noise was calculated for images from 43 patients acquired on both a conventional and a multiple-pinhole cardiac SPECT camera. Functions were found to relate image noise to radiotracer activity, scan time, and body mass and were validated by normalizing the image noise in a test set of 58 patients. RESULTS: There was a 3.6-fold difference in photon sensitivity between the two cameras but a 16-fold difference in activity-scan time was necessary to match the noise levels. Image noise doubled from 45 to 128 kg for the conventional camera (12.8 minutes) and tripled for the multiple-pinhole camera (5 minutes) for 350 MBq (9.5 mCi) 99mTc-tetrofosmin. It was 16.3% and 6.1% respectively for an average sized patient. CONCLUSIONS: A linear scaling of activity with respect to the patient weight normalizes image noise but the scaling factors depend on the choice of camera and image reconstruction parameters. Therefore, equivalent numbers of acquired photon counts are not sufficient to guarantee equivalent image noise.

Acquisition, Processing, and Interpretation of PET 18F-FDG Viability and Inflammation Studies.

PURPOSE OF REVIEW: This article reviews the acquisition protocols and image interpretation for 18F-fluorodeoxyglucose (18F-FDG) imaging with positron emission tomography (PET) applied to the evaluation of myocardial viability and inflammation. RECENT FINDINGS: Cardiac PET with 18F-FDG provides essential information for the assessment of myocardial viability and inflammation and is usually combined with PET perfusion imaging using 82Rb or 13N-ammonia. Viable myocardium maintains glucose metabolism which can be detected via the uptake of 18F-FDG by PET imaging. The patient is prepared for viability imaging by shifting the metabolism of the heart to maximize the uptake of glucose and hence of 18F-FDG. Comparison of the 18F-FDG and myocardial perfusion images allows distinction between regions of the myocardium that are hibernating and thus may recover function with intervention, from those that are infarcted. Increased glucose utilization in the inflammatory cells also makes 18F-FDG a useful imaging technique in conditions such as cardiac sarcoidosis. Here, suppression of normal myocardial uptake is essential for accurate image interpretation. 18F-FDG PET broadens the scope of information potentially available through a cardiac PET study. With careful patient preparation, it provides valuable insights into myocardial viability and inflammatory processes such as sarcoidosis.

Correction to: Patient-specific SPECT imaging protocols to standardize image noise.

The originally published version of this article contained typographical errors in the units of photon sensitivity. The units of counts · MBq-1 · min-1 and kcounts · mCi-1 · min-1 were mistakenly recorded as counts · MBq · min and kcounts · mCi · min respectively. The original article has been corrected.

Single CT for attenuation correction of rest/stress cardiac SPECT perfusion imaging.

Common practice is to use separate CT scans acquired during rest and stress for attenuation correction of SPECT myocardial perfusion imaging (MPI). We evaluated using a single CT scan to correct both rest and stress SPECT scans. Studies from 154 patients were reprocessed using one CT acquired at stress to correct both rest and stress scans (1CT) and compared to correction of each scan with its own CT (2CT). Two expert readers independently read the images and determined summed stress (SSS), rest (SRS), and difference (SDS) scores. The correlation in SRS between 2CT and 1CT was r ≥ 0.88. The concordance in SDS was ≥0.84 (kappa ≥ 0.62). The mean SDS difference between 2CT and 1CT for the averaged observer was not significantly different from zero (p > 0.31). 1CT images had a small but significant increase in SRS and an increase in SDS variability. However, the mean SDS difference was similar to the mean inter-observer SDS difference for the 2CT approach (-0.08 vs -0.23, p = 0.46) and had less uncertainty (1.02 vs 2.05, p < 0.001). Thus, the differences between 1CT and 2CT are unlikely to be clinically significant, and the 1CT approach is feasible for SPECT MPI.

Contemporary Cardiac SPECT Imaging-Innovations and Best Practices: An Information Statement from the American Society of Nuclear Cardiology.

This information statement from the American Society of Nuclear Cardiology highlights advances in cardiac SPECT imaging and supports the incorporation of new technology and techniques in laboratories performing nuclear cardiology procedures. The document focuses on the application of the latest imaging protocols and the utilization of newer hardware and software options to perform high quality, state-of-the-art SPECT nuclear cardiology procedures. Recommendations for best practices of cardiac SPECT imaging are discussed, highlighting what imaging laboratories should be doing as the standard of care in 2018 to achieve optimal results (based on the ASNC 2018 SPECT guideline [Dorbala et al., J Nucl Cardiol. 2018. https://doi.org/10.1007/s12350-018-1283-y ]).

Instrumentation in molecular imaging.

In vivo molecular imaging is a challenging task and no single type of imaging system provides an ideal solution. Nuclear medicine techniques like SPECT and PET provide excellent sensitivity but have poor spatial resolution. Optical imaging has excellent sensitivity and spatial resolution, but light photons interact strongly with tissues and so only small animals and targets near the surface can be accurately visualized. CT and MRI have exquisite spatial resolution, but greatly reduced sensitivity. To overcome the limitations of individual modalities, molecular imaging systems often combine individual cameras together, for example, merging nuclear medicine cameras with CT or MRI to allow the visualization of molecular processes with both high sensitivity and high spatial resolution.

"Same-patient processing" for multiple cardiac SPECT studies. 2. Improving quantification repeatability.

OBJECTIVES: This paper investigates the ability of grouped quantification (an expression of the same-patient processing approach, or SPP) to improve repeatability of measurements in patients with multiple SPECT studies, and evaluates its performance compared to standard quantification in a population of 100 patients undergoing rest, stress, gated rest, and gated stress SPECT MPI. All acquisitions were performed twice, back-to-back, for a total of 800 image datasets (8 per patient). METHODS: Each dataset was automatically processed (a) independently, using standard quantitative software, and (b) as a group, together with the other 7 datasets belonging to the same patient, using an SPP-modified version of the software that registered the images to one another using a downhill simplex algorithm for the search of optimal translation, rotation, and scaling parameters. RESULTS: Overall, grouped quantification resulted in significantly lower differences between repeated measurements of stress ungated volumes (1.40 ± 2.76 mL vs 3.33 ± 5.06 mL, P < .05), end-diastolic volumes (1.78 ± 2.78 vs 3.49 ± 5.35 mL, P < .05), end-systolic volumes (1.17 ± 1.96 vs 2.44 ± 3.35 mL, P < .05), and LVEFs (-0.45 ± 2.29% vs -1.16 ± 3.30%, P < .05). Additionally, grouped quantification produced better repeatability (lower repeatability coefficients) for stress and rest ungated volumes (5.4 vs 9.9 and 5.2 vs 13.1, respectively), stress TPD (2.6 vs 3.6), stress and rest end-diastolic volumes (5.5 vs 10.5 and 7.2 vs 14.7, respectively), stress and rest end-systolic volumes (3.8 vs 6.6 and 5.3 vs 10.3, respectively), stress and rest LVEFs (4.5 vs 6.5 and 4.7 vs 8.2, respectively), and rest total motion deficit (5.6 vs 9.6). CONCLUSION: It is possible to improve the repeatability of quantitative measurements of parameters of myocardial perfusion and function derived from SPECT MPI studies of a same patient by group processing of image datasets belonging to that patient. This application of the same-patient processing approach is an extension of the "paired processing" technique already described by our group, and can be performed in automated fashion through incorporation in the quantitative algorithm.

Characterization of the four isomers of (123)I-CMICE-013: a potential SPECT myocardial perfusion imaging agent.

UNLABELLED: Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) is widely used in the assessment of coronary artery disease (CAD). We have developed (123)I-CMICE-013 based on rotenone, a mitochondrial complex I (MC-1) inhibitor, as a promising new MPI agent. Our synthesis results in a mixture of four species of (123)I-CMICE-013 A, B, C, D. In this study, we separated the four species and evaluated their biodistribution and imaging properties. The cold analogs (127)I-CMICE-013 A, B, C, D were isolated and characterized and their chemical structures proposed. METHODS: (123)I-CMICE-013 was synthesized by radiolabeling rotenone with Na(123)I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60°C for 45min, and the four species were separated by RP-HPLC. The cold analogs (127)I-CMICE-013 A, B, C and D were isolated with a similar procedure and characterized by NMR and mass spectrometry. Biodistribution and microSPECT imaging studies were carried out on normal rats. RESULTS: We propose the mechanism of the rotenone iodination and the structures of the four species. First, I(+) forms an intermediate three-membered ring with 6' and 7' carbons. Second, the lone electron pair of the water molecule attacks the 6' or 7'-carbon, following by the formation of 6'-OH, and 7'-I bonds as in major products C and D, or 6'-I and 7'-OH bonds as in minor products A and B. The weaker 6'-I bond in the intermediate prompts the nucleophilic attachment of water at the favorable 6'-carbon to generate C and D. MicroSPECT images of (123)I-CMICE-013 A, B, C, D in rats showed clear visualization of myocardium and little interference from lung and liver. The imaging time activity curves and biodistribution data showed complex profiles for the four isomers, which is not expected from the structure activity relationship theory. CONCLUSION: (123/127)I-CMICE-013 A and B are constitutional isomers with C and D, while A and C are diastereomers of B and D, respectively. Overall, the biological characteristics of the four species are not correlated perfectly with their molecular structures.

Myocardial blood flow quantification with SPECT.

INTRODUCTION: The addition of absolute myocardial blood flow (MBF) data improves the diagnostic and prognostic accuracy of relative perfusion imaging with nuclear medicine. Cardiac-specific gamma cameras allow measurement of MBF with SPECT. METHODS: This paper reviews the evidence supporting the use of SPECT to measure myocardial blood flow (MBF). Studies have evaluated SPECT MBF in large animal models and compared it in humans with invasive angiographic measurements and against the clinical standard of PET MBF. The repeatability of SPECT MBF has been determined in both single-site and multi-center trials. RESULTS: SPECT MBF has excellent correlation with microspheres in an animal model, with the number of stenoses and fractional flow reserve, and with PET-derived MBF. The inter-user coefficient of variability is ∼20% while the COV of test-retest MBF is ∼30%. SPECT MBF improves the sensitivity and specificity of the detection of multi-vessel disease over relative perfusion imaging and provides incremental value in predicting adverse cardiac events. CONCLUSION: SPECT MBF is a promising technique for providing clinically valuable information in the assessment of coronary artery disease.