Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if COPD patients have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography(PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-year period. We compared 77 COPD patients with 44 healthy kidney donors (controls). Cardiac output (Q̇) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. Q̇ was similar at rest (COPD: 3649 ± 120 mL vs. control: 3891 ± 160 mL, p=0.368) but lower in COPD patients compared to controls during adenosine infusion (COPD: 5432 ± 124 mL vs. control: 6185 ± 161 mL, p < 0.050). MBTT was shorter in COPD patients compared to controls at rest (COPD: 8.7 ± 0.28 seconds vs. control: 11.4 ± 0.37 seconds, p < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 seconds vs. control: 10.2 ± 0.37 seconds, p < 0.014). PBV was lower in COPD patients, even after adjustment for body surface area, sex, and age at rest (COPD: 530 (29) mL vs. 708 (38) mL, p < 0.001) and during adenosine infusion (COPD: 826 (29) mL vs. 1044 (38) mL, p<0.001). In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.

Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria.

Diabetes affects the kidneys, and the presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advances in noninvasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of subclinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (18F-sodium fluoride positron emission tomography/computed tomography [PET/CT], plaque inflammation [64Cu-DOTATATE PET/CT], and myocardial flow reserve [82Rb PET/CT]). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g]), and 30 had normoalbuminuria (UACR <30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particular, higher levels of microcalcifications and impaired myocardial microvascular function; however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome.

Myocardial creep and cardiorespiratory motion correction improves diagnostic accuracy of Rubidium-82 cardiac positron emission tomography.

AIM: To evaluate the feasibility of retrospectively detecting and correcting periodical (cardiac and respiratory motion) and non-periodical shifts of the myocardial position (myocardial creep) using only the acquired Rubidium-82 positron emission tomography raw (listmode) data. METHODS: This study comprised 25 healthy participants (median age = 23 years) who underwent repeat rest/adenosine stress Rubidium-82 myocardial perfusion imaging (MPI) and 53 patients (median age = 64 years) considered for revascularization who underwent a single MPI session. All subjects were evaluated for myocardial creep during MPI by assessing the myocardial position every 200 ms. A proposed motion correction protocol, including corrections for cardiorespiratory and creep motion (3xMC), was compared to a guideline-recommended protocol (StandardRecon). For the volunteers, we report test-retest repeatability using standard error of measurements (SEM). For the patient cohort, we evaluated the area under the receiver operating curve (AUC) for both stress and ischemic total perfusion deficits (sTPD and iTPD, respectively) using myocardial ischemia defined as fractional flow reserve values < 0.8 in the relevant coronary segment as the gold standard. RESULTS: Test-retest repeatability was significantly improved following corrections for myocardial creep (SEM; sTPD: StandardRecon = 2.2, 3xMC = 1.8; iTPD: StandardRecon = 1.6, 3xMC = 1.2). AUC analysis of the ROC curves revealed significant improvements for iTPD measurements following 3xMC [sTPD: StandardRecon = 0.88, 3xMC = 0.92 (P = .21); iTPD: StandardRecon = 0.88, 3xMC = 0.95 (P = .039)]. CONCLUSION: 3xMC has the potential to improve the diagnostic accuracy of myocardial MPI obtained from positron emission tomography. Therefore, its use should be considered both in clinical routine and large-scale multicenter studies.

Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia.

BACKGROUND: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. METHODS: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient. RESULTS: Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia.

Fully Automated, Fast Motion Correction of Dynamic Whole-Body and Total-Body PET/CT Imaging Studies.

We introduce the Fast Algorithm for Motion Correction (FALCON) software, which allows correction of both rigid and nonlinear motion artifacts in dynamic whole-body (WB) images, irrespective of the PET/CT system or the tracer. Methods: Motion was corrected using affine alignment followed by a diffeomorphic approach to account for nonrigid deformations. In both steps, images were registered using multiscale image alignment. Moreover, the frames suited to successful motion correction were automatically estimated by calculating the initial normalized cross-correlation metric between the reference frame and the other moving frames. To evaluate motion correction performance, WB dynamic image sequences from 3 different PET/CT systems (Biograph mCT, Biograph Vision 600, and uEXPLORER) using 6 different tracers (18F-FDG, 18F-fluciclovine, 68Ga-PSMA, 68Ga-DOTATATE, 11C-Pittsburgh compound B, and 82Rb) were considered. Motion correction accuracy was assessed using 4 different measures: change in volume mismatch between individual WB image volumes to assess gross body motion, change in displacement of a large organ (liver dome) within the torso due to respiration, change in intensity in small tumor nodules due to motion blur, and constancy of activity concentration levels. Results: Motion correction decreased gross body motion artifacts and reduced volume mismatch across dynamic frames by about 50%. Moreover, large-organ motion correction was assessed on the basis of correction of liver dome motion, which was removed entirely in about 70% of all cases. Motion correction also improved tumor intensity, resulting in an average increase in tumor SUVs by 15%. Large deformations seen in gated cardiac 82Rb images were managed without leading to anomalous distortions or substantial intensity changes in the resulting images. Finally, the constancy of activity concentration levels was reasonably preserved (<2% change) in large organs before and after motion correction. Conclusion: FALCON allows fast and accurate correction of rigid and nonrigid WB motion artifacts while being insensitive to scanner hardware or tracer distribution, making it applicable to a wide range of PET imaging scenarios.

Performance of 8- vs 16 ECG-gated reconstructions in assessing myocardial function using Rubidium-82 myocardial perfusion imaging: Findings in a young, healthy population.

BACKGROUND: Current imaging guidelines recommend using at least 16 ECG gates when performing MUGA and cardiac SPECT to assess left ventricular ejection fraction (LVEF). However, for Rubidium-82 (82Rb) PET, 8 ECG-gated reconstructions have been a mainstay. This study investigated the implications of quantitative assessments when employing 16 gate, instead of 8 gate, reconstructions for 82Rb myocardial perfusion imaging (MPI). METHODS: The study comprised 25 healthy volunteers (median age 23 years) who underwent repeat MPI sessions employing 82Rb PET/CT. We report LVEF, its reserve (stress LVEF - rest LVEF), and their repeatability measures (RMS method) obtained for 8- and 16 ECG-gated reconstructions. RESULTS: Similar LVEF and LVEF reserve estimates were found for the 8- and 16-gated reconstructions ([%] LVEF (8/16 gates): rest = 61 ± 6/64 ± 6, stress = 68 ± 7/71 ± 6, LVEF reserve (8/16 gates): 8 ± 3/6 ± 4, and all P ≥ 0.13). Similar test-retest repeatability measures were observed for rest and stress LVEF and their reserves [LVEF (8/16 gates); Rest = 4.5/4.6 (P = 0.81), Stress = 3.5/3.2 (P = 0.33), LVEF reserve = 46.7/49.3 (P = 0.13)]. CONCLUSION: In healthy subjects, 8 and 16 ECG gates can be used interchangeably if only volumetric assessments are desired. However, if filling and emptying rates are of interest, a minimum of 16 ECG gates should be employed.

Phantom Study on the Robustness of MR Radiomics Features: Comparing the Applicability of 3D Printed and Biological Phantoms.

The objectives of our study were to (a) evaluate the feasibility of using 3D printed phantoms in magnetic resonance imaging (MR) in assessing the robustness and repeatability of radiomic parameters and (b) to compare the results obtained from the 3D printed phantoms to metrics obtained in biological phantoms. To this end, three different 3D phantoms were printed: a Hilbert cube (5 × 5 × 5 cm3) and two cubic quick response (QR) code phantoms (a large phantom (large QR) (5 × 5 × 4 cm3) and a small phantom (small QR) (4 × 4 × 3 cm3)). All 3D printed and biological phantoms (kiwis, tomatoes, and onions) were scanned thrice on clinical 1.5 T and 3 T MR with 1 mm and 2 mm isotropic resolution. Subsequent analyses included analyses of several radiomics indices (RI), their repeatability and reliability were calculated using the coefficient of variation (CV), the relative percentage difference (RPD), and the interclass coefficient (ICC) parameters. Additionally, the readability of QR codes obtained from the MR images was examined with several mobile phones and algorithms. The best repeatability (CV ≤ 10%) is reported for the acquisition protocols with the highest spatial resolution. In general, the repeatability and reliability of RI were better in data obtained at 1.5 T (CV = 1.9) than at 3 T (CV = 2.11). Furthermore, we report good agreements between results obtained for the 3D phantoms and biological phantoms. Finally, analyses of the read-out rate of the QR code revealed better texture analyses for images with a spatial resolution of 1 mm than 2 mm. In conclusion, 3D printing techniques offer a unique solution to create textures for analyzing the reliability of radiomic data from MR scans.

Anatomical validation of automatic respiratory motion correction for coronary 18F-sodium fluoride positron emission tomography by expert measurements from four-dimensional computed tomography.

BACKGROUND: Respiratory motion correction is of importance in studies of coronary plaques employing 18 F-NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test-retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four-dimensional cine-computed tomography (CT) by an expert observer. PURPOSE: To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of 18 F-NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine-CT images. METHODS: This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using 18 F-sodium fluoride (18 F-NaF). All patients underwent a 5-s cine-CT (4D-CT), a coronary CT angiography (CTA), and 18 F-NaF PET. The 4D-CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non-contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D-CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t-tests. Signal-to-noise ratios (SNR) are reported for the single-phase images (end-expiratory phase) and for the motion-corrected image-series (employing the motion vector fields extracted during the diffeomorphic registrations). RESULTS: In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 ± 1.5 mm, PET = 2.4 ± 3.2 mm; Y direction: 4D CT = 2.3 ± 1.9 mm, PET = 0.7 ± 2.9 mm, 3D motion: 4D CT = 6.6 ± 3.1 mm, PET = 5.7 ± 2.6 mm, all p ≥ 0.05). Significant differences in respiratory motion were observed in the systems' Z direction: 4D CT = 4.9 ± 3.4 mm, PET = 2.3 ± 3.2 mm, p = 0.04. Significantly improved SNR is reported for the motion corrected images compared to the end-expiratory phase images (end-expiratory phase = 6.8±4.8, motion corrected = 12.2±4.5, p = 0.001). CONCLUSION: Similar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images.

Optimization of the left ventricle ejection fraction estimate obtained during cardiac adenosine stress 82Rubidium-PET scanning: impact of different reconstruction protocols.

BACKGROUND: Left ventricular ejection fraction (LVEF) estimation using adenosine stress myocardial perfusion imaging (MPI) can be challenging. The short half-life of adenosine and the guideline-recommended adenosine infusion stop during Rubidium-82 acquisition protocol may affect the accuracy and repeatability of the LVEF measures. METHODS: This study comprised 25 healthy volunteers (median age 23 years) who underwent repeat myocardial perfusion imaging (MPI) sessions employing Rubidium-82 PET/CT. A guideline-recommended reconstruction protocol was used for both rest and adenosine stress MPI (150-360 s post-radiotracer injection, standardrecon). For the stress MPI protocol, two additional reconstruction protocols were considered; one was employing 60 seconds data (150-210 seconds, shortfixed) and the other a dynamic frame window based on the bolus arrival of Rubidium-82 in the heart until 210 seconds (x-210 seconds, shortindividual). We report rest and stress LVEF, the LVEF reserve, and the LVEF reserve repeatability. RESULTS: Differences in the LVEF assessments were observed between the guideline recommended and alternative reconstruction protocol (LVEF stress MPI: standardrecon = 68 ± 7%, shortfixed = 71 ± 7% (P = .08), shortindividual = 72 ± 7% (P = .04)), and the LVEF reserve was reduced for the guideline-recommended protocol (standardrecon = 7.8 ± 3.5, shortfixed = 10.1 ± 3.7, shortindividual = 10.5 ± 3.6, all P < .001). The best repeatability measures were obtained for the shortindividual protocol (repeatability: standardrecon = 45.3%, shortfixed = 41.2%, shortindividual = 31.7%). CONCLUSION: We recommend using the shortindividual reconstruction protocol for improved LVEF repeatability and reserve assessment. Alternatively, in centers with limited technical support we recommend the use of the shortfixed protocol.

Image-derived and physiological markers to predict adequate adenosine-induced hyperemic response in Rubidium-82 myocardial perfusion imaging.

AIMS: This study aimed to investigate the potential of different markers to identify adequate stressing in subjects with and without caffeine intake prior to Rubidium-82 myocardial imaging. METHODS AND RESULTS: This study comprised 40 healthy subjects who underwent four serial Rubidium-82 rest/adenosine stress MPI; two with 0mg caffeine consumption (baseline MPIs) and two with controlled consumption of caffeine (arm 1: 100 and 300mg, or arm 2: 200 and 400mg). We report the sensitivity and specificity of seven markers ability to predict adequate adenosine-induced hyperemic response: (1) the splenic response ratio (SRR); (2) splenic stress-to-rest intensity ratios (SIR); (3) changes in heart rate (ΔHR); (4) percentwise change in heart rate (Δ%HR); (5) changes in the rate pressure product (ΔRPP); (6) changes in the systolic blood pressure (ΔSBP); and (7) changes in the cardiovascular resistance (ΔCVR). Adequate stressing was determined as stress myocardial blood flow > 3ml/g/min and a corresponding myocardial flow reserve >68% of the individual maximum myocardial flow reserve obtained in the baseline MPIs. RESULTS: 129 MPI sessions (obtained in 39 subjects) were considered for this study. The following sensitivities were obtained: SSR = 72.7%, SIR = 63.6%, ΔHR = 45.5%, Δ%HR = 77.3%, ΔRPP = 54.5%, ΔSBP = 47.7%, and ΔCVR =40.9%, while the specificities were SSR = 80.9%, SIR = 85.0%, ΔHR = 90.4%, Δ%HR = 81.6%, ΔRPP=81.1%, ΔSBP = 86.4%, and ΔCVR =90.4%. CONCLUSION: The image-derived and physiological markers all provide acceptable sensitivities and specificities when patients follow the caffeine pausation before MPI. However, their use warrants great care when caffeine consumption cannot be ruled out.

Aortic valve imaging using 18F-sodium fluoride: impact of triple motion correction.

BACKGROUND: Current 18F-NaF assessments of aortic valve microcalcification using 18F-NaF PET/CT are based on evaluations of end-diastolic or cardiac motion-corrected (ECG-MC) images, which are affected by both patient and respiratory motion. We aimed to test the impact of employing a triple motion correction technique (3 × MC), including cardiorespiratory and gross patient motion, on quantitative and qualitative measurements. MATERIALS AND METHODS: Fourteen patients with aortic stenosis underwent two repeat 30-min PET aortic valve scans within (29 ± 24) days. We considered three different image reconstruction protocols; an end-diastolic reconstruction protocol (standard) utilizing 25% of the acquired data, an ECG-gated (four ECG gates) reconstruction (ECG-MC), and a triple motion-corrected (3 × MC) dataset which corrects for both cardiorespiratory and patient motion. All datasets were compared to aortic valve calcification scores (AVCS), using the Agatston method, obtained from CT scans using correlation plots. We report SUVmax values measured in the aortic valve and maximum target-to-background ratios (TBRmax) values after correcting for blood pool activity. RESULTS: Compared to standard and ECG-MC reconstructions, increases in both SUVmax and TBRmax were observed following 3 × MC (SUVmax: Standard = 2.8 ± 0.7, ECG-MC = 2.6 ± 0.6, and 3 × MC = 3.3 ± 0.9; TBRmax: Standard = 2.7 ± 0.7, ECG-MC = 2.5 ± 0.6, and 3 × MC = 3.3 ± 1.2, all p values ≤ 0.05). 3 × MC had improved correlations (R2 value) to the AVCS when compared to the standard methods (SUVmax: Standard = 0.10, ECG-MC = 0.10, and 3 × MC = 0.20; TBRmax: Standard = 0.20, ECG-MC = 0.28, and 3 × MC = 0.46). CONCLUSION: 3 × MC improves the correlation between the AVCS and SUVmax and TBRmax and should be considered in PET studies of aortic valves using 18F-NaF.

Observer repeatability and interscan reproducibility of 18F-sodium fluoride coronary microcalcification activity.

BACKGROUND: We aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA). METHODS: Patients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level. RESULTS: In 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary18F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively. CONCLUSIONS: CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.

Respiration-averaged CT versus standard CT attenuation map for correction of 18F-sodium fluoride uptake in coronary atherosclerotic lesions on hybrid PET/CT.

BACKGROUND: To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of 18F-sodium fluoride (18F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). METHODS: This study comprised 23 patients who underwent 18F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBRMAX) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. RESULTS: In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBRMAX (median [Interquartile range]): CTAC = 1.65 [1.23 to 2.38], RACTAC = 1.63 [1.23 to 2.33], p = 0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC = 0.10 [0 to 1.0], RACTAC = 0.15 [0 to 1.03], p = 0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary 18F-NaF uptake on PET/CT.

Assessment of left and right ventricular functional parameters using dynamic dual-tracer [13N]NH3 and [18F]FDG PET/MRI.

BACKGROUND: Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan. METHODS: In 22 patients with coronary heart disease (69 ± 9 years) dynamic [13N]NH3 (NH3) and [18F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference. RESULTS: RVFPEF and LVFPEF from FDG and NH3 as well as RVEF and LVEF from MRI were (28 ± 11%, 32 ± 15%), (32 ± 11%, 41 ± 14%) and (42 ± 16%, 45 ± 19%), respectively. LVESV, LVEDV and LVEF from EP FDG and NH3 in 8 and 16 gates were [71 (15 to 213 mL), 98 (16 to 241 mL), 32 ± 17%] and [50 (17 to 206 mL), 93 (13 to 219 mL), 36 ± 17%] as well as [60 (19 to 360 mL), 109 (56 to 384 mL), 41 ± 22%] and [54 (16 to 371 mL), 116 (57 to 431 mL), 46 ± 24%], respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH3 were (85 ± 63 mL, 138 ± 63 mL, 47 ± 19%) and (79 ± 56 mL, 137 ± 63 mL, 47 ± 20%), respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI (R = .51, P = .01; R = .64, P = .001), respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH3 in 16 gates (all R > .7, P = .000). Similarly, all LV parameters from LP FDG and NH3 correlated good to strongly positive with MRI (all R > .7, and P < .001), except EDV from NH3 weakly correlated to EDV of MRI (R = .54, P < .05). Generally, Bland-Altman plots showed good agreements between PET and MRI. CONCLUSIONS: Deriving LV and RV functional values from various phases of dynamic NH3 and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations.

Sex Differences and Caffeine Impact in Adenosine-Induced Hyperemia.

Caffeine consumption before adenosine stress myocardial perfusion imaging (MPI) is known to affect the hemodynamic response and, thus, reduce the stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) assessments. However, it is not clear if any sex-specific differences in the hemodynamic response after caffeine consumption exist. This study aimed to evaluate if such differences exist and, if so, their impact on MBF and MFR assessments. Methods: This study comprised 40 healthy volunteers (19 women). All volunteers underwent 4 serial rest/stress MPI sessions using 82Rb; 2 sessions were acquired without controlled caffeine consumption, and 2 sessions after oral ingestion of either 100 and 300 mg of caffeine or 200 and 400 mg of caffeine. For the caffeine imaging sessions, caffeine was ingested orally 1 h before the MPI scan. Results: Increase in plasma caffeine concentration (PCC) (mg/L) after consumption of caffeine was larger in women (MPI session without caffeine vs. MPI session with caffeine: women = 0.3 ± 0.2 vs. 5.4 ± 5.1, men = 0.1 ± 0.2 vs. 2.7 ± 2.6, both P < 0.001). Caffeine consumption led to reduced stress MBF and MFR assessments for men whereas no changes were reported for women (women [PCC < 1 mg/L vs. PCC ≥ 1 mg/L]: stress MBF = 3.3 ± 0.6 vs. 3.0 ± 0.8 mL/g/min, P = 0.07; MFR = 3.7 ± 0.6 vs. 3.5 ± 1.0, P = 0.35; men [PCC < 1 mg/L vs. PCC ≥ 1 mg/L]: stress MBF = 2.7 ± 0.7 vs. 2.1 ± 1.0 mL/g/min, P = 0.005; MFR = 3.8 ± 1.0 vs. 3.1 ± 1.4, P = 0.018). Significant differences in the stress MBF were observed for the 2 sexes (both P ≤ 0.001), whereas similar MFR was reported (both P ≥ 0.12). Conclusion: Associations between increases in PCC and reductions in stress MBF and MFR were observed for men, whereas women did not have the same hemodynamic response. Stress MBF was affected at lower PCCs in men than women.

Advances in Quantitative Analysis of 18F-Sodium Fluoride Coronary Imaging.

18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has emerged as a promising noninvasive imaging tool for the assessment of active calcification processes in coronary artery disease. 18F-NaF uptake colocalizes to high-risk and ruptured atherosclerotic plaques. Most recently, 18F-NaF coronary uptake was shown to be a robust and independent predictor of myocardial infarction in patients with advanced coronary artery disease. In this review, we provide an overview of the advances in coronary 18F-NaF imaging. In particular, we discuss the recently developed and validated motion correction techniques which address heart contractions, tidal breathing, and patient repositioning during the prolonged PET acquisitions. Additionally, we discuss a novel quantification approach-the coronary microcalcification activity (which has been inspired by the widely employed method in oncology total active tumor volume measurement). This new method provides a single number encompassing 18F-NaF activity within the entire coronary vasculature rather than just information regarding a single area of most intense tracer uptake.

Simulation of Low-Dose Protocols for Myocardial Perfusion 82Rb Imaging.

Quantification of myocardial perfusion and myocardial blood flow using 82Rb PET is increasingly used for assessment of coronary artery disease. Current guidelines suggest injections of 1,100-1,500 MBq for both stress and rest. Reducing the injected dose avoids PET system saturation in first-pass flow images and reduces radiation exposure, but the impact on myocardial perfusion quantification of static perfusion images is not fully understood. In this study, we aimed to evaluate the feasibility of performing myocardial perfusion scans using either a half-dose (HfD) or quarter-dose (QD) protocol using reconstructions from acquired full-dose (FD) scans. Methods: This study comprised 171 patients who underwent rest/stress 82Rb PET with a 3-dimensional 4-ring PET/CT scanner using a FD protocol and invasive coronary angiography within 6 mo of the PET emission scan. HfD and QD reconstructions were obtained using the prescribed percentage of events from the FD list-mode files. The total perfusion deficit was quantified for rest (rTPD), stress (sTPD), and ischemia (ITPD = sTPD - rTPD). Diagnostic accuracy for obstructive coronary artery disease, defined as at least 70% stenosis in any of the 3 major coronary arteries, was compared with area under the receiver-operating-characteristic curve (AUC). Results: Patients with a median body mass index of 28.0 (interquartile range, 23.9-31.7) were injected with doses of 1,165 ± 189 MBq of 82Rb. For sTPD, FD and HfD protocols had similar AUCs (FD, 0.807; HfD, 0.802; P = 0.108), whereas QD had a reduced AUC (0.786, P = 0.037). There was no difference in the AUC obtained for ITPD among the 3 protocols (FD, 0.831; HfD, 0.835; QD, 0.831; all P ≥ 0.805). Conclusion: HfD imaging does not affect the quantitative diagnostic accuracy of 82Rb PET on 3-dimensional PET/CT systems and could be used clinically.

No changes in myocardial perfusion following radiation therapy of left-sided breast cancer: A positron emission tomography study.

BACKGROUND: Adjuvant radiation therapy (RT) for breast cancer has improved overall survival. However, incidental exposure of the heart has been linked to development of radiation-induced heart disease. The aim of this study was, in a cohort of asymptomatic post-irradiation breast cancer patients, to investigate changes in myocardial blood flow (MBF) and presence of perfusion defects in myocardial perfusion positron-emission-tomography (PET) in the irradiated myocardium. METHODS AND RESULTS: Twenty patients treated with RT for left-sided breast cancer underwent 13N-ammonia myocardial perfusion PET 7(± 2) years after breath adapted RT to a total dose of 48 Gy given in 24 fractions. No differences in rest or stress MBF were noted between the irradiated and non-irradiated myocardium (1.29 (± 0.29) vs 1.33 (± 0.29) mL/g/min, ns; 2.74 (± 0.59) vs 2.78 (± 0.66) mL/g/min, ns, respectively). One patient demonstrated a myocardial perfusion defect localized in the irradiated anterior wall myocardium. CONCLUSION: Although limited by a small sample size, early signs of cardiac injury detected by NH3 myocardial perfusion PET was at least not frequent in our cohort of patients treated with a modern RT technique for left-sided breast cancer, even 7 years after treatment. The findings however, may not rule out subsequent development of myocardial injury.