Mathieu Rubeaux

Motion Correction of 18F-NaF PET for Imaging Coronary Atherosclerotic Plaques

Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has recently been shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using 18F-NaF PET. We aimed to determine whether a motion correction technique applied to gated 18F-NaF PET images could enhance image quality and improve uptake estimates. Methods: Seventeen patients with myocardial infarction (n = 7) or stable angina (n = 10) underwent 18F-NaF PET and prospective coronary CT angiography. PET data were reconstructed in 4 different ways: the first was 1 gated bin (end-diastolic phase with 25% of the counts), the second was 4 gated bins (consecutive 25% segments), the third was 10 gated bins (consecutive 10% segments), and the fourth was ungated. Subsequently, with data from either 4 or 10 bins, gated PET images were registered using a local, nonlinear motion correction method guided by the extracted coronary arteries from CT angiography. Global noise levels and target-to-background ratios (TBR) defined on manually delineated coronary plaque lesions were compared to assess image quality and uptake estimates. Results: Compared with the reference standard of using only 1 bin of PET data, motion correction using 10 bins of PET data reduced image noise by 46% (P < 0.0001). TBR in positive lesions for 10-bin motion-corrected data was 11% higher than for 1-bin data (1.98 [interquartile range, 1.70–2.37] vs. 1.78 [1.58–2.16], P = 0.0027) and 33% higher than for ungated data (1.98 [1.70–2.37] vs. 1.49 [1.39–1.88], P < 0.0001). Conclusion: Motion correction of gated 18F-NaF PET/coronary CT angiography is feasible, reduces image noise, and increases TBR. This improvement may allow more reliable identification of vulnerable coronary artery plaques using 18F-NaF PET.

Dual-Gated Motion-Frozen Cardiac PET with Flurpiridaz F 18

A novel PET radiotracer, Flurpiridaz F 18, has undergone phase II clinical trial evaluation as a high-resolution PET cardiac perfusion imaging agent. In a subgroup of patients imaged with this agent, we assessed the feasibility and benefit of simultaneous correction of respiratory and cardiac motion. Methods: In 16 patients, PET imaging was performed on a 4-ring scanner in dual cardiac and respiratory gating mode. Four sets of data were reconstructed with high-definition reconstruction (HD•PET): ungated and 8-bin electrocardiography-gated images using 5-min acquisition, optimal respiratory gating (ORG)—as developed for oncologic imaging—using a narrow range of breathing amplitude around end-expiration level with 35% of the counts in a 7-min acquisition, and 4-bin respiration-gated and 8-bin electrocardiography-gated images (32 bins in total) using the 7-min acquisition (dual-gating, using all data). Motion-frozen (MF) registration algorithms were applied to electrocardiography-gated and dual-gated data, creating cardiac-MF and dual-MF images. We computed wall thickness, wall/cavity contrast, and contrast-to-noise ratio for standard, ORG, cardiac-MF, and dual-MF images to assess image quality. Results: The wall/cavity contrast was similar for ungated (9.3 ± 2.9) and ORG (9.5 ± 3.2) images and improved for cardiac-MF (10.8 ± 3.6) and dual-MF images (14.8 ± 8.0) (P < 0.05). The contrast-to-noise ratio was 22.2 ± 9.1 with ungated, 24.7 ± 12.2 with ORG, 35.5 ± 12.8 with cardiac-MF, and 42.1 ± 13.2 with dual-MF images (all P < 0.05). The wall thickness was significantly decreased (P < 0.05) with dual-MF (11.6 ± 1.9 mm) compared with ungated (13.9 ± 2.8 mm), ORG (13.1 ± 2.9 mm), and cardiac-MF images (12.1 ± 2.7 mm). Conclusion: Dual (respiratory/cardiac)-gated perfusion imaging with Flurpiridaz F 18 is feasible and improves image resolution, contrast, and contrast-to-noise ratio when MF registration methods are applied.

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high-efficiency SPECT.

BackgroundEjection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT.MethodsFifty patients (mean age 69 years) undergoing regadenoson same-day rest (8-11 mCi)/stress (32-42 mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started 1 minute after sequential intravenous regadenoson .4 mg and Tc-99m injections, and was composed of five 2 minutes supine gated acquisitions followed by two 4 minutes supine and upright images. Ischemic total perfusion deficit (ITPD) ≥5 % was considered as significant ischemia.ResultsSignificantly lower mean EF reserve was obtained in the 5th and 9th minute after regadenoson bolus in patients with significant ischemia vs patients without (5th minute: −4.2 ± 4.6% vs 1.3 ± 6.6%, P = .006; 9th minute: −2.7 ± 4.8% vs 2.0 ± 6.6%, P = .03).ConclusionsNegative EF reserve obtained between 5th and 9th minutes of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of transient ischemic functional changes with Tc-99m HE-SPECT.Spanish AbstractAntecedentesSe ha encontrado que la reserva de la Fracción de Eyección (FE) en la tomografía de emisión de positrones cardiaca (PET, positron emission tomography por sus siglas en ingles) es una herramienta útil adicional en la identificación de pacientes con enfermedad arterial coronaria de alto riesgo. Nuestro objetivo fue evaluar la reserva de la FE obtenida por SPECT de alta eficiencia (AE) con Tecnecio-99m (Tc-99m) sestamibi.MétodosCincuenta pacientes (edad promedio 69 años) a quienes se les realizo un SPECT de AE con Tc‐99m sincronizado con el electrocardiograma en un solo día reposo (8-11mCi)/estrés 32-42mCi) con regadenoson fueron incluidos La adquisición de las imágenes de estrés se inicio un minuto después de la administración secuencial intravenosa de regadenoson .4mg y Tc-99m, compuesta de 5 adquisiciones sincronizadas con el electrocardiograma de 2 minutos cada una en supino seguidas de dos adquisiciones de 4 minutos cada una en supino y sentado. Un defecto total de perfusión isquémico (DTPI) ≥5% fue considerado como isquemia significativa.ResultadosEl promedio obtenido de la Reserva de la FE fue significativamente menor en los minutos 5to y 9no posterior al bolo de regadenoson en pacientes con isquemia significativa comparados con pacientes sin isquemia (5to minuto: −4.2 ± 4.6% vs 1.3 ± 6.6%, p= 0.006; 9no minuto: −2.7 ± 4.8% vs 2.0 ± 6.6%, p = 0.03).ConclusionesUna Reserva de la FE negativa obtenida en los minutos 5to y 9no del estrés con regadenoson demostró una mejor concordancia con la presencia de isquemia significativa y podría ser un herramienta promisoria para la detección de cambios funcionales isquémicos transitorios con un estudio SPECT de AE con Tc-99m.Chinese Abstract背景对于心脏PET显像, 射血分数 (EF) 储备 已成为评判高风险冠心病的有效辅助手段。本文旨在评价采用Tc-99m甲氧基异丁基异睛显影剂和高能SPECT测定EF储备的可行性。方法入选55行类伽腺苷一日法静息 (8-11mCi) /负荷 (32-42mCi) 门控高能SPECT显像的患者, 平均年龄为69岁。在连续静脉注射类伽腺苷 (0.4mg) 和Tc-99m一分钟后开始负荷图像的采集。负荷图像包括5个2分钟的仰卧位门控采集和后续2个分别为仰卧位和直立位的4分钟门控采集。总灌注缺损≧5%为显著缺血。结果注射类伽腺苷后, 显著缺血患者的平均EF储备在第5和第9分钟时较无缺血患者显著降低 (第5分钟: −4.2 ± 4.6% vs. 1.3 ± 6.6%, p = 0.006; 第9分钟: −2.7 ± 4.8% vs. 2.0 ± 6.6%, p=0.03)。结论在类伽腺苷负荷时, 第5至9分钟测得的EF储备负值与显著缺血的一致性最佳, 这很可能成为Tc-99m高能SPECT检测一过性心肌缺血伴随的心功能改变的有效手段。

Automatic Valve Plane Localization in Myocardial Perfusion SPECT/CT by Machine Learning: Anatomical and Clinical Validation

Precise definition of the mitral valve plane (VP) during segmentation of the left ventricle for SPECT myocardial perfusion imaging (MPI) quantification often requires manual adjustment, which affects the quantification of perfusion. We developed a machine learning approach using support vector machines (SVM) for automatic VP placement. Methods: A total of 392 consecutive patients undergoing 99mTc-tetrofosmin stress (5 min; mean ± SD, 350 ± 54 MBq) and rest (5 min; 1,024 ± 153 MBq) fast SPECT MPI attenuation corrected (AC) by CT and same-day coronary CT angiography were studied; included in the 392 patients were 48 patients who underwent invasive coronary angiography and had no known coronary artery disease. The left ventricle was segmented with standard clinical software (quantitative perfusion SPECT) by 2 experts, adjusting the VP if needed. Two-class SVM models were computed from the expert placements with 10-fold cross validation to separate the patients used for training and those used for validation. SVM probability estimates were used to compute the best VP position. Automatic VP localizations on AC and non-AC images were compared with expert placement on coronary CT angiography. Stress and rest total perfusion deficits and detection of per-vessel obstructive stenosis by invasive coronary angiography were also compared. Results: Bland–Altman 95% confidence intervals (CIs) for VP localization by SVM and experts for AC stress images (bias, 1; 95% CI, −5 to 7 mm) and AC rest images (bias, 1; 95% CI, −7 to 10 mm) were narrower than interexpert 95% CIs for AC stress images (bias, 0; 95% CI, −8 to 8 mm) and AC rest images (bias, 0; 95% CI, −10 to 10 mm) (P < 0.01). Bland–Altman 95% CIs for VP localization by SVM and experts for non-AC stress images (bias, 1; 95% CI, −4 to 6 mm) and non-AC rest images (bias, 2; 95% CI, −7 to 10 mm) were similar to interexpert 95% CIs for non-AC stress images (bias, 0; 95% CI, −6 to 5 mm) and non-AC rest images (bias, −1; 95% CI, −9 to 7 mm) (P was not significant [NS]). For regional detection of obstructive stenosis, ischemic total perfusion deficit areas under the receiver operating characteristic curve for the 2 experts (AUC, 0.79 [95% CI, 0.7–0.87]; AUC, 0.81 [95% CI, 0.73–0.89]) and the SVM (0.82 [0.74–0.9]) for AC data were the same (P = NS) and were higher than those for the unadjusted VP (0.63 [0.53–0.73]) (P < 0.01). Similarly, for non-AC data, areas under the receiver operating characteristic curve for the experts (AUC, 0.77 [95% CI, 0.69–0.89]; AUC, 0.8 [95% CI, 0.72–0.88]) and the SVM (0.79 [0.71–0.87]) were the same (P = NS) and were higher than those for the unadjusted VP (0.65 [0.56–0.75]) (P < 0.01). Conclusion: Machine learning with SVM allows automatic and accurate VP localization, decreasing user dependence in SPECT MPI quantification.

Normal Databases for the Relative Quantification of Myocardial Perfusion

Purpose of ReviewMyocardial perfusion imaging (MPI) with SPECT is performed clinically worldwide to detect and monitor coronary artery disease (CAD). MPI allows an objective quantification of myocardial perfusion at stress and rest. This established technique relies on normal databases to compare patient scans against reference normal limits. In this review, we aim to introduce the process of MPI quantification with normal databases and describe the associated perfusion quantitative measures that are used.Recent FindingsNew equipment and new software reconstruction algorithms have been introduced, which require the development of new normal limits. The appearance and regional count variations of normal MPI scans may differ between these new scanners and standard Anger cameras. Therefore, these new systems may require the determination of new normal limits to achieve optimal accuracy in relative myocardial perfusion quantification. Accurate diagnostic and prognostic results rivaling those obtained by expert readers can be obtained by this widely used technique.SummaryThroughout this review, we emphasize the importance of the normal databases and the need for specific databases relative to distinct imaging procedures. Use of appropriate normal limits allows optimal quantification of MPI by taking into account subtle image differences due to the hardware and software used, and the population studied.

Enhancing Cardiac PET by Motion Correction Techniques

Purpose of ReviewCardiac positron emission tomography (PET) images often contain errors due to cardiac, respiratory, and patient motion during relatively long image acquisition. Advanced motion compensation techniques may improve PET spatial resolution, eliminate potential artifacts, and ultimately improve the research and clinical capabilities of PET.Recent FindingsCombined cardiac and respiratory gating has only recently been implemented in clinical PET systems. Considering that the gated image bins contain much lower counts than the original PET data, they need to be summed after correcting for motion, forming motion-corrected, high-count image volume. Furthermore, automated image registration techniques can be used to correct for motion between CT attenuation scan and PET acquisition.SummaryWhile motion correction methods are not yet widely used in clinical practice, approaches including dual-gated non-rigid motion correction and the incorporation of motion correction information into the reconstruction process have the potential to markedly improve cardiac PET imaging.

Motion-corrected imaging of the aortic valve with (18)F-NaF PET/CT and PET/MR: a feasibility study

We investigated whether motion correction of gated 18F-fluoride PET/CT and PET/MRI of the aortic valve could improve PET quantitation and image quality. Methods: A diffeomorphic, mass-preserving, anatomy-guided registration algorithm was used to align the PET images from 4 cardiac gates, preserving all counts, and apply them to the PET/MRI and PET/CT data of 6 patients with aortic stenosis. Measured signal-to-noise ratios (SNRs) and target-to-background ratios (TBRs) were compared with the standard method of using only the diastolic gate. Results: High-intensity aortic valve 18F-fluoride uptake was observed in all patients. After motion correction, SNR and TBR increased compared with the median diastolic gate (SNR, 51.61 vs. 21.0; TBR, 2.85 vs. 2.22) and the median summed data (SNR, 51.61 vs. 34.10; TBR, 2.85 vs. 1.95) (P = 0.028 for all). Furthermore, noise decreased from 0.105 (median, diastolic) to 0.042 (median, motion-corrected) (P = 0.028). Conclusion: Motion correction of hybrid 18F-fluoride PET markedly improves SNR, resulting in improved image quality.

Molecular Imaging of Vulnerable Coronary Plaque: A Pathophysiologic Perspective

Atherothrombotic events in coronary arteries are most often due to rupture of unstable plaque resulting in myocardial infarction. Radiolabeled molecular imaging tracers directed toward cellular targets that are unique to unstable plaque can serve as a powerful tool for identifying high-risk patients and for assessing the potential of new therapeutic approaches. Two commonly available radiopharmaceuticals—18F-FDG and 18F-NaF—have been used in clinical research for imaging coronary artery plaque, and ongoing clinical studies are testing whether there is an association between 18F-NaF uptake and future atherothrombotic events. Other, less available, tracers that target macrophages, endothelial cells, and apoptotic cells have also been tested in small groups of patients. Adoption of molecular imaging of coronary plaque into clinical practice will depend on overcoming major hurdles, ultimately including evidence that the detection of unstable plaque can change patient management and improve outcomes.

Quantification with normal limits: New cameras and low-dose imaging

SPECT myocardial perfusion imaging (MPI) widely utilizes relative quantification of myocardial perfusion. This is accomplished by local comparisons of test patients to other scans of normal patients in most current quantitative SPECT MPI methods. These comparisons allow identification of local areas of hypoperfusion, typically in polar map coordinates. The set of normal patients is usually referred to as ‘‘normal database’’ or ‘‘normal limits’’ (when a collection of databases is considered, for example stress and rest databases). Relative quantification of myocardial perfusion with normal databases is a powerful clinical tool which has been documented to rival expert physicians’ reading. Therefore, the recommendations regarding the appropriate use of such normal databases should be of great interest to all nuclear cardiology clinicians.

Demons versus Level-Set motion registration for coronary 18F-sodium fluoride PET

Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically plausible. Therefore, level-set technique will likely require additional post-processing steps. On the other hand, the observed TBR increases were the highest for the level-set technique. Further investigations of the optimal registration technique of this novel coronary PET imaging technique are warranted.