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Pyrophosphate (PYP) scintigraphy provides high diagnostic accuracy for the detection of transthyretin (ATTR) cardiac amyloidosis (CA). There has recently been emerging interest in using 18F-sodium fluoride (NaF) for this application, yet its sensitivity has never been directly compared to that of PYP, the current molecular gold standard Twelve subjects with ATTR-CA and 5 controls referred for PYP-SPECT were prospectively enrolled. 18F-NaF PET/CT scans were performed at 1 and 3 hours. Qualitative and quantitative analyses of the images were performed, and the sensitivity of 18F-NaF PET/CT and PYP-SPECT were compared Visual interpretation of NaF PET/CT yielded a sensitivity of 0.25 (95% CI 0.089 to 0.53) for the detection of ATTR-CA, which is significantly inferior to that of PYP-SPECT/CT (100%, P = .016). Visual interpretation at 3 hours yielded a similar sensitivity of 0.30 (95% CI 0.11 to 0.60, P = 1.00). There were no false-positive NaF PET studies. Mean target-to-background ratio (TBRmean) at 1h did not differ significantly (P = .21) in ATTR-CA subjects (0.83 ± 0.15) compared to controls (0.72 ± 0.15). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.69 ± 0.16 (95% CI 0.37 to 1.00, P = .23). With qualitative and quantitative analyses, sensitivity of NaF PET/CT is significantly inferior to that of PYP-SPECT for the diagnosis of ATTR-CA

Evaluate the impact of 82-Rubidium positron emission tomography (PET) myocardial perfusion imaging (MPI) availability on patient management presenting at the emergency department (ED) with chest pain (CP).This is a single-center retrospective study of clinical databases. Patients presenting with CP with a non-definitive suspicion of acute coronary syndrome (ACS) at the ED between April 2016 and February 2020 were divided into 2 groups based on PET availability. The proportion of invasive coronary angiography (ICA) without significant coronary artery disease (CAD), length of stay (LoS), and additional downstream testing were evaluated.There were 21,242 ED visits for CP without definitive ACS: 5,492 when PET is not available and 15,750 when PET is available. When PET is available, proportion of patients undergoing a MPI study was greater (20.7% vs 17.6%, P0.0001), proportion of ICA without significant CAD was similar (18.5% vs 21.4%, P=0.24), and median ED LoS was shorter (16.6 vs 18.1 hours, P=0.03). Patients undergoing SPECT MPI had significantly more downstream testing (8.9% vs 6.4%, P=0.003) and a higher rate of coronary angiogram without significant CAD (21.2% vs 14.2%, P=0.09) compared to those who underwent PET MPI.Availability of PET MPI was associated with an increased number of MPI referral from the ED, similar rates of ICA without significant CAD, decreased LoS, and fewer downstream testing.Evaluar el impacto de la tomografía por emisión de positrones (PET) con 82-Rubidio y la disponibilidad de imágenes de perfusión miocárdica (MPI) en el manejo de los pacientes que se presentan en el servicio de urgencias (ED) con dolor torácico (CP). MéTODOS: Este es un estudio retrospectivo de bases de datos clínicas de un solo centro. Pacientes que presentaron CP con sospecha no definitiva de síndrome coronario agudo (ACS) en el ED entre abril de 2016 y febrero de 2020, se dividieron en 2 grupos según la disponibilidad de PET. Se evaluó la proporción de angiografía coronaria invasiva (ICA) sin enfermedad arterial coronaria (CAD) significativa, la duración de la estancia (LoS) y las pruebas posteriores adicionales.Hubo 21,242 visitas al ED por CP sin ACS definitivo: 5,492 cuando no se dispone de PET y 15.750 cuando se dispone de PET. Cuando se dispone de PET, la proporción de pacientes sometidos a estudio de MPI fue mayor (20.7% vs 17.6%, p=0.03). Los pacientes que se sometieron a SPECT MPI tuvieron significativamente más pruebas posteriores (8.9 % frente a 6.4 %, p = 0.003) y una tasa más alta de angiografía coronaria sin CAD significativa (21.2 % frente a 14.2 %, p = 0.09) en comparación con los que se sometieron a PET MPI. CONCLUSIóN: La disponibilidad de PET MPI se asoció con un mayor número de referencias de MPI desde el ED, tasas similares de ICA sin CAD significativa, disminución de LoS y menos pruebas posteriores.

Qualification and interpretation standards are essential for establishing 99mTc-SPECT MPI accuracy vs. alternative modalities. Rest–stress 99mTc-SPECT phantom scans were acquired on 35 cameras. LV defects were quantified with summed stress (SSS) and difference scores (SDS) at 2 core labs. SDS ≥ 2 in the right coronary artery (RCA) was the qualifying standard. Twenty rest (R)–stress (S) patient images were acquired on qualified cameras and interpreted by core labs. Global scoring differences > 3 between labs or discordant clinical interpretations underwent review. Scoring, interpretation, image quality, and diagnostic parameter agreement were assessed. Phantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90. Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine 99mTc-SPECT MPI accuracy.

Background We examined the use of [18F]FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). Methods PET/CT images in patients with suspected NVE were retrospectively reviewed independently by two experienced physicians blinded to all clinical information. The gold standard consisted of surgical findings, when available, or the modified Duke criteria. Results Fifty four subjects were included, 31 (57%) with a diagnosis of NVE. [18F]FDG-PET/CT correctly identified 21/31 (67.7%) subjects, yielding a sensitivity and specificity of 68% (95% CI 49-83%) and 100% (95% CI 85-100%), respectively. The sensitivity and specificity of the modified Duke criteria were 48% and 74%, respectively. Positive and negative predictive values of PET were 100% (95% CI 84-100%) and 70% (95% CI 51-84%), respectively. Modifying the Duke criteria to include [18F]FDG-PET positivity as a major criterion increased sensitivity to 77% without affecting specificity and led to the correct reclassification of 8/18 (44.4%) subjects from Possible IE to Definite IE. Conclusion The addition of a positive [18F]FDG-PET/CT as a major criterion in the modified Duke Criteria improved performance of the criteria for the diagnosis of NVE, particularly in those subjects with Possible IE.

Pyrophosphate (PYP) scintigraphy provides high diagnostic accuracy for the detection of transthyretin (ATTR) cardiac amyloidosis (CA). There has recently been emerging interest in using 18F-sodium fluoride (NaF) for this application, yet its sensitivity has never been directly compared to that of PYP, the current molecular gold standard METHODS: Twelve subjects with ATTR-CA and 5 controls referred for PYP-SPECT were prospectively enrolled. 18F-NaF PET/CT scans were performed at 1 and 3 hours. Qualitative and quantitative analyses of the images were performed, and the sensitivity of 18F-NaF PET/CT and PYP-SPECT were compared RESULTS: Visual interpretation of NaF PET/CT yielded a sensitivity of 0.25 (95% CI 0.089 to 0.53) for the detection of ATTR-CA, which is significantly inferior to that of PYP-SPECT/CT (100%, P = .016). Visual interpretation at 3 hours yielded a similar sensitivity of 0.30 (95% CI 0.11 to 0.60, P = 1.00). There were no false-positive NaF PET studies. Mean target-to-background ratio (TBRmean) at 1h did not differ significantly (P = .21) in ATTR-CA subjects (0.83 ± 0.15) compared to controls (0.72 ± 0.15). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.69 ± 0.16 (95% CI 0.37 to 1.00, P = .23).With qualitative and quantitative analyses, sensitivity of NaF PET/CT is significantly inferior to that of PYP-SPECT for the diagnosis of ATTR-CA.

International audience; INTRODUCTION: Adrenomedullin receptors are highly expressed in human alveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [18F]AlF, for PET imaging of pulmonary microcirculation.METHODS: Highly concentrated [18F](AlF)2+ (15 μL) was produced from purified fluorine-18 in NaCl 0.9%. Various complexation experiments were carried out at Al-to-NOTA molar ratios ranging from 1:1 to 1:40 to assess optimal radiolabeling conditions before using the peptide. DFH17 peptide (2 mM, pH 4) was radiolabeled with [18F](AlF)2+ for 15 min at 100 °C in a total volume of 60 μL. As part of the radiolabeling process, parameters such as fluorine-18 activity (~37 and 1480 MBq), concentration of AlCl3 (0.75, 2, 3, 6 or 10 mM) and the effects of hydrophilic organic solvent (aqueous vs ethanol 50%) were studied. The final formulation was tested for purity, identity and stability in saline. Initial in vivo evaluation of [18F]AlF-DFH17 was performed in normal rats by PET/CT.RESULTS: The scaled-up production of [18F]AlF-DFH17 was performed in high radiochemical and chemical purities in an overall radiochemical yield of 22-38% (at end-of-synthesis) within 60 min. The final formulation was stable in saline at different radioactive concentrations for 8 h. PET evaluation in rats revealed high lung-to-background ratios and no defluorination in vivo up to 1 h post-injection.CONCLUSION: The novel radioconjugate [18F]AlF-DFH17 appears to be a promising PET ligand for pulmonary microcirculation imaging.

Circulating adrenomedullin (AM) levels are elevated in several cardiovascular diseases, including pulmonary vascular diseases causing pulmonary hypertension. To date the perfusion agent (99m)Tc-albumin macroaggregates (MAA) is the only approved radiopharmaceutical used for imaging of pulmonary circulation. Unlike (99m)Tc-MAA, imaging the AM receptors involves a molecular process dependent on the density of the receptors and the affinity of specific radioligands. The AM receptors are abundantly distributed in lung capillaries and its integrity provides protection in the development of pulmonary vascular diseases. This review summarizes the development and characterization of radioligands for in vivo imaging of AM receptors as an early predictor of the onset of a pulmonary vascular disease.

PURPOSE: FDG-PET/CT has the potential to play an important role in the diagnosis of sternal wound infections (SWI). The purpose of this study was to analyze the diagnostic accuracy of FDG-PET/CT for SWI in patients following sternotomy. METHODS: We performed a single-center, retrospective analysis of patients who had undergone median sternotomy and FDG-PET/CT imaging. The gold standard consisted of positive bacterial culture and/or the presence of purulent material at surgery. Qualitative patterns of sternal FDG uptake, SUV(max), and associated CT findings were determined, and an imaging scoring system was developed. The diagnostic performances were studied in both the recent (≤ 6 months between sternotomy and imaging) and remote surgery phase (> 6 months). RESULTS: A total of 40 subjects were identified with 11 confirmed SWI cases. Consensus interpretation was associated with a sensitivity of 91% and specificity of 97%. Combination of uptake patterns yielded an AUC of 0.96 while use of SUVmax yielded an AUC of 0.82. CONCLUSIONS: Results suggest that FDG-PET/CT may be useful for the diagnosis of SWI with optimal diagnostic accuracy achieved by identifying specific patterns of uptake. SUV(max) can be helpful in assessing subjects with remote surgery, but its use is limited in the context of recent surgery. Further studies are required to confirm these results.

Qualification and interpretation standards are essential for establishingRest-stressPhantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90.Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine

Purpose The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Methods Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi 99mTc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. Results PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∼50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. Conclusions In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using 99mTc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and direct comparisons to lung perfusion agents such as labeled macro-aggregates of albumin are needed. Clinical trial ClinicalTrials.gov, NCT02216279 Electronic supplementary material The online version of this article (doi:10.1007/s00259-017-3655-y) contains supplementary material, which is available to authorized users.

Conventional nuclear imaging with bone-seeking radiopharmaceuticals has been shown to be a sensitive test for the detection of transthyretin cardiac amyloidosis (ATTR); however, to date, few data exist on the utility ofMyocardial perfusion imaging and cardiacAverage TBRWhile

Adrenomedullin receptors are highly expressed in human alveolar capillaries and provide a molecular target for imaging the integrity of pulmonary microcirculation. In this work, we aimed to develop a NOTA-derivatized adrenomedullin analog (DFH17), radiolabeled with [Highly concentrated [The scaled-up production of [The novel radioconjugate [

Myocardial perfusion imaging (MPI) with positron emission tomography allows accurate measurements of myocardial blood flow (MBF). Stress MBF thresholds have been proposed to provide diagnostic and prognostic information in different pathology. Most studies relying on dipyridamole use a 5-minute infusion protocol, while current guidelines recommend a 4-minute infusion. The purpose of this study is to compare the effects of different dipyridamole infusion times on stress MBF. The charts of 2,207 patients who underwent rubidium-82 MPI were retrospectively reviewed and 147 subjects with low likelihood of significant coronary artery disease (CAD) defined as calcium score = 0, body mass index

IQ-SPECT has been shown to significantly reduce acquisition time and administered dose while preserving image quality in myocardial perfusion imaging. Whether IQ-SPECT provides accurate left ventricular ejection fractions (LVEF) with gated blood pool SPECT (GBPS) remains unknown. Sixty patients underwent IQ-SPECT GBPS and planar imaging. Among those patients, 11 underwent both cMRI and GBPS. GBPS LVEF, LVEDV, and LVESV were calculated using 2 validated software; QBS (Cedars-Sinai Medical Center, Los Angeles, USA) and MHI (Montreal Heart Institute, Montreal, Canada). LVEF, LVEDV, and LVESV obtained with the different modalities were compared. Average planar LVEF was 48 ± 11% (mean ± SD), average LVEDV was 177 ± 59 mL (range 63 to 342 mL), and average LVESV was 96 ± 46 mL (range 16 to 234 mL). GBPS LVEF and their correlation coefficient with planar LVEF were 40 ± 12% (r = 0.70) and 44 ± 12% (r = 0.83) with QBS and MHI, respectively. Correlation coefficient between cMRI and planar LVEF was 0.65 and were 0.69 and 0.52 between cMRI and GBPS using QBS and MHI, respectively. LVEF calculated with GBPS using IQ-SPECT correlates with planar measurements. Correlation is best using the MHI method and variation is independent of LVEDV.

The evaluation of the right ventricle (RV) is a challenge; as a result six transthoracic echocardiography (TTE) parameters have been suggested. While gated blood-pool single photon electron computed tomography (GBPS) is a promising technique, there is currently no completely automated and validated processing software available clinically. Consequently, cardiac magnetic resonance (CMR) imaging remains the gold standard for RV assessment. We aimed to compare RV evaluation by GBPS and TTE to CMR.Fifty-eight patients underwent CMR, GBPS and TTE for RV assessment, including volumes, RVEF and TTE's indices of RV function (fractional area change (FAC), RV myocardial performance index by pulsed wave Doppler (MPI-PWD) and tissue Doppler (MPI-TDI) and tricuspid annular plane systolic excursion (TAPSE) by M-Mode and tissue Doppler (TAPSE-TDI)). GBPS was performed using both a commercial (QBS) and the Montreal Heart Institute (MHI) proprietary software.Nuclear medicine derived volumes quantification showed very good correlations with CMR, for RV end-diastolic (r=0.84 and 0.77, all p0.001) and end-systolic (r=0.82 and 0.67, all p0.001) volumes by MHI and QBS software respectively. RVEF showed a significant correlation with CMR in patients with RVEF ≤ 45% (r=0.54, p=0.029 and r=0.55, p=0.028, by MHI and QBS respectively). Among TTE parameters, only FAC and MPI-TDI were significantly correlated with CMR-RVEF, mainly for RVEF ≤ 45% (r=0.63, p=0.011 and r=0.58, p=0.046).GBPS, both with MHI and QBS software, exhibited significant correlations with CMR for evaluation of the RV (volumes and decreased RVEF estimation). Among TTE's parameters, only FAC and MPI-TDI showed significant correlation with CMR with RVEF ≤ 45%.

Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty-six CTx recipients and 17 age-matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O2 , 20-minutes hypoxia (11.5% O2 ), and following a 10-minute exposure to 11.5% O2 using 30% of peak power output were completed. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), suppression of tumorigenicity 2 (ST2) were measured at baseline and at peak stress. Endothelial peripheral function was assessed using near-infrared spectroscopy. Compared with HC, CTx presented a lesser O2 desaturation both at rest (-19.4 ± 6.8 [CTx] vs -24.2 ± 6.0% O2 [HC], P < 0.05) and following exercise (-23.2 ± 4.9 [CTx] vs -26.2 ± 4.7% O2 [HC], P < 0.05). CTx patients exhibited a significant decrease in peak oxygen uptake. IL-6 and VEGF levels were significantly higher in CTx recipients in basal conditions but did not change in response to acute stress. CTx patients exhibit a favorable ventilatory and overall response to hypoxic stress. These data provide further insights on the good adaptability of CTx to exposure to high altitude.

We evaluated the accuracy of planar radionuclide angiography and different count-based and space-based electrocardiogram (ECG)-gated blood-pool single-photon emission computed tomography (GBPS) algorithms for assessment of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) compared with the gold standard of cardiac magnetic resonance imaging (cMRI). The goal is to assess the accuracy of a recently developed GBPS algorithm.Subjects had planar, GBPS, and cMRI sequentially. Datasets were processed by QBS software (Cedar-Sinai) and by MHI software (Montreal Heart Institute). Space-based approaches were used to compute LVEDV, LVESV, and LVEF. Count-based techniques were also used to assess LVEF. All results were compared to cMRI. Fifty-five patients (85% male; mean age 63 +/- 9 years) completed the study. LVEFs and their correlations to cMRI values were 43 +/- 12% (r = .82), 39 +/- 14% (r = .82), and 39 +/- 13% for MHI(space), QBS(space), and cMRI methodologies, respectively. LVEF by count-based methods also demonstrated good correlation to LVEF provided by cMRI (42 +/- 13%, r = .88 for MHI(count) and 46 +/- 15%, r = .84 for QBS(count)). Strong correlations were obtained for LVEDV (r = .96 for MHI and r = .92 for QBS) and for LVESV (.97 for MHI and r = .94 for QBS).All Gated blood-pool SPECT algorithms had significant variation in estimating LVEF. Nevertheless our software provides good estimates of LV volumes and LVEF. Such software may, therefore, be applied to assess LV morphology and function.

Pulmonary perfusion is not spatially homogeneously distributed, and its variations could be of diagnostic value in lung vascular disease. PulmoBind is a ligand of the adrenomedullin receptor densely expressed in endothelial cells of lung capillaries. The aim of this study was to evaluate spatial distribution of human lung perfusion by using this novel molecular tracer of the pulmonary vascular endothelium. Normal humans (n = 19) enrolled into the PulmoBind phase I trial were studied (Clinicaltrials.gov. NCT01539889 ). They were injected with 99mTc-PulmoBind for SPECT imaging. Results were compared with 99mTc-PulmoBind in quadruped mammals (dogs, n = 5). Imaging was performed in the supine position and distribution of activity was determined as a function of cumulative voxels along the different anatomical planes. PulmoBind uptake in humans was 58 ± 1 % (mean ± SEM) of the injected dose. Dorsal activity was 18.1 ± 2.1 % greater than ventral, and caudal activity was 25.7 ± 1.6 % greater than cranial. Lateral activity was only mildly higher than medial by 7.0 ± 1.0 %. In supine dogs, similar but higher PulmoBind gradients were present: dorsal 28.6 ± 2.5 %, caudal 34.1 ± 5.0 % and lateral 18.1 ± 2.0 %. The perfused pulmonary circulation of supine humans, assessed by an adrenomedullin receptor ligand, is not homogeneously distributed with more prominent distribution in dorsal and caudal regions. It is qualitatively similar to a supine quadruped mammal confirming the presence of a microcirculatory gravitational perfusion gradient detectable with this tracer. Future studies are needed to determine if this novel endothelial cell tracer could be used to detect physiologic and pathologic variations of lung perfusion such as in pulmonary hypertension. ClinicalTrial.gov, NCT01539889

We validated a novel mobile detection system to evaluate reactive hyperemia using the radionuclide plethysmography technique. Twenty-six subjects underwent simultaneously radionuclide plethysmography with strain gauge plethysmography. Strain gauge and radionuclide methods showed excellent reproducibility with intraclass correlation coefficients of 0.96 and 0.89 respectively. There was also a good correlation of flows between the two methods during reactive hyperemia (r = 0.87). We conclude that radionuclide plethysmography using this mobile detection system is a non-invasive alternative to assess forearm blood flow and its dynamic variations during reactive hyperemia.

We developed a new segmentation algorithm based on the invariance of the Laplacian (IL) to compute volumes and ejection fractions and compared these results with planar analysis and gradients by use of a standard algorithm (QBS).Planar and single photon emission computed tomography blood pool acquisition was performed in 202 patients. Planar left ventricular ejection fraction (LVEF) was used as the gold standard, and single photon emission computed tomography images were processed by both 3-dimensional (3D) methods. Correlations between each 3D algorithm and planar methodology were as follows: r = 0.77 for QBS and r = 0.84 for IL. Mean LVEFs were 32.72% +/- 13.05% for the planar method, 32.32% +/- 15.98% for QBS, and 31.93% +/- 13.44% for IL (P = .16). Bland-Altman analysis closely demonstrated negligible systematic bias for both 3D methods. Standard errors of bias were comparable between methods (9.36% for QBS and 7.44% for IL, P = .48). Linear regression of the Bland-Altman bias revealed a slope significantly different from 0 for the QBS method (0.22 +/- 0.048, P.0001) but not for IL (-0.032 +/- 0.0044, P = .47).The new segmentation algorithm provides comparable results to QBS and planar analysis. However, with QBS, the difference in LVEF was correlated with the magnitude of LVEF, which was not found with the new algorithm.

This phase I study (NCT01539889) evaluated the safety, efficacy, and dosing of PulmoBind for molecular imaging of pulmonary circulation. PulmoBind is a ligand of the adrenomedullin receptor abundantly distributed in lung capillaries. Labeled with 99m Tc, it allows single-photon emission computed tomographic (SPECT) imaging of lung perfusion. In preclinical studies, PulmoBind scans enabled detection of lung perfusion defects and quantification of microcirculatory occlusion caused by pulmonary hypertension. Healthy humans ( N = 20) were included into escalating groups of 5 mCi ( n = 5), 10 mCi ( n = 5), or 15 mCi ( n = 10) 99m Tc-PulmoBind. SPECT imaging was serially performed, and 99m Tc-PulmoBind dosimetric analysis was accomplished. The radiochemical purity of 99m Tc-PulmoBind was greater than 95%. There were no safety concerns at the three dosages studied. Imaging revealed predominant and prolonged lung uptake with a mean peak extraction of 58% ± 7%. PulmoBind was well tolerated, with no clinically significant adverse event related to the study drug. The highest dose of 15 mCi provided a favorable dosimetric profile and excellent imaging. The postural lung perfusion gradient was detectable. 99m Tc-PulmoBind is safe and provides good quality lung perfusion imaging. The safety/efficacy of this agent can be tested in disorders of pulmonary circulation such as pulmonary arterial hypertension.

Precise identification of left ventricular (LV) systolic mechanical dyssynchrony may be useful in optimizing the response to cardiac resynchronization therapy in heart failure (HF) patients. However, LV dyssynchrony is mostly measured at rest; patients often suffer from the HF symptoms during exercise.Our objective was to examine the impacts of stress on LV synchronism with phase analysis of gated SPECT myocardial perfusion imaging (GMPS) within a normal animal cohort.Stress was induced with different levels of dobutamine infusion in six healthy canine subjects. Hemodynamic properties were assessed by LV pressure measurements. Also, LV mechanical synchronism (coordination of LV septal and lateral wall at the time of contraction) was determined by phase analysis of GMPS using commercially available QGS software and in-house MHI4MPI software, with the thickening- and displacement-based method. Synchrony indexes in MHI4MPI included the septal-to-lateral delay and homogeneity index, derived from each of the two methods. Also, bandwidth, SD, and entropy (synchrony indexes) of the QGS software were assessed.LVEF increased from 36.7% ± 8.7% at rest to 53.67% ± 12.34% at 20 μg · kg(-1) · minute(-1) (P.001). Also, cardiac output increased from 3.67 ± 1.0 L · minute(-1) at rest to 8.4 ± 2.6 L · minute(-1) at 10 μg · kg(-1) · minute(-1) (P.001). The same trend was observed for dP/dt max which increased from 1,247 ± 382.7 at rest to 5,062 ± 1,800 mm Hg · s(-1) at 10 μg · kg(-1) · minute(-1) (P.01). Entropy decreased from 55.2% ± 8% at baseline to 43.5% ± 8.5% at 5 and 43.0% ± 3.7% at 10 μg · kg(-1) · minute(-1) dobutamine (P.01). Thickening homogeneity index showed a difference from 91.7% ± 5.53% at rest to 98.2% ± 0.75% at 20 μg · kg(-1) · minute(-1) (P.05).Dobutamine stimulation could amplify the ventricular synchronism, and the thickening-based approach is more accurate than wall displacement for assessment of mechanical dyssynchrony in GMPS.

In cardiac resynchronization therapy, many devices need to be optimized to take into account the magnitude and characteristics of patients' ventricular mechanical dyssynchrony. The optimization process is mostly performed at rest; however, mechanical resynchronization might be more important under stress, while patients need to improve their cardiac efficiency. The objective of this study was to observe if levels of cardiac stress could modify the ventricular contraction synchronism. Cardiac stress was induced with dobutamine infusion in eight healthy canine subjects. Hemodynamic and ventricular synchronism assessments were performed by left ventricular pressure measurements and radionuclide tomographic-gated blood pools. Cardiac output increased from 2.8 ± 1.0 at rest to 5.7 ± 2.2 L min(-1) at 20 µg kg(-1) min(-1), while the ventricular performance (dP/dtmax) increased from 1588 ± 374 to 8004 ± 710 mmHg s(-1). At baseline, the interventricular delay (in degrees) was -6.3 ± 2.6°, the left ventricle contraction preceding the right. The delay significantly increased to -21.6 ± 3.1° with dobutamine stress (p < 0.0001). On assessment of the left intraventricular synchrony, septal-to-lateral delay was -6.9 ± 5.1° at baseline which revealed a preceded contraction of the left lateral wall from the septum. Cardiac stress produced a significant modulation (p = 0.01), with an inversion of the contraction pattern, the septum contraction preceding the lateral wall contraction by 15.5 ± 5.6° at maximum dobutamine infusion; a significant linear trend (p < 0.001) was found between cardiac stress levels and septal-to-lateral delays. Cardiac activity levels modified the ventricular synchronism supporting the fact that optimizations of cardiac resynchronization devices could be improved by taking cardiac stress into account.

The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. To evaluate the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular

Cardiac resynchronization therapy may improve survival and quality of life in patients suffering from heart failure with left ventricular (LV) contraction dyssynchrony. While several studies have investigated electrical or mechanical determinants of synchronous contraction, few have focused on activation contraction coupling at a macroscopic level. The objective of the study was to characterize LV electromechanical behavior and response to pacing in a heart failure model. We analyzed data from 3D electroanatomic non-contact mapping and blood pool SPECT for 12 dogs with right ventricular (RV) tachycardia pacing-induced dilated cardiomyopathy. Surfaces generated by the two modalities were registered. Electrical signals were analyzed, and endocardial wall displacement curves were portrayed. Rapid pacing decreased the mean LV ejection fraction (LVEF) to 20.9 % and prolonged the QRS duration to 79 ± 10 ms (normal range: 40–50 ms). QRS duration remained unchanged with biventricular pacing (88.5 ms), while single site pacing further prolonged the QRS duration (113.3 ms for RV pacing and 111.6 ms for LV pacing). No trend was observed in LV systolic function. Activation duration time was significantly increased with all pacing modes compared to baseline. Finally, electromechanical delay, as defined by the delay between electrical activation and mechanical response, was increased by single site pacing (172.9 ms for RV pacing and 174.6 ms for LV pacing) but not by biventricular pacing (162.4 ms). Combined temporal and spatial coregistration electroanatomic maps and baseline gated blood pool SPECT imaging allowed us to quantify activation duration time, electromechanical delay, and LVEF for different pacing modes. Even if pacing modes did not significantly modify LVEF or activation duration, they produced alterations in electromechanical delay, with biventricular pacing significantly decreasing the electromechanical delay as measured by surface tracings and endocardial non-contact mapping.

Peripheral arterial flow has been assessed for a variety of indications including characterization of endothelial function during reactive hyperemia. However, quantification of this blood flow as a surrogate remains an imperfect reflection of endothelial function. We sought to better characterize hyperemic reaction to (1) elucidate the influence of the endothelial function and (2) assess the reproducibility of our modeling over time. Sixteen normal subjects underwent simultaneous forearm reactive hyperemia testing with a near-infrared system at baseline, baseline +24 h and baseline +27 h. Baseline flow was measured to 3.6 +/- 0.2 ml dl(-1) min(-1), and was highly reproducible 24 and 27 h later. With reactive hyperemia, the blood flow increased to 20.5 +/- 4.6 ml dl(-1) min(-1). Arterial blood flow curves during reactive hyperemia displayed a bimodal pattern, with the second peak occurring 59.1 +/- 10.6 s after the onset of hyperemia. We believe that this latest peak represents the contribution of endothelial factors to the hyperemic reaction. Modeling of hyperemic curves led to the introduction of a reproducible new parameter (etafactor) that reflects the normalized contribution of this second peak. In conclusion, forearm arterial flow during reactive hyperemia revealed a bimodal distribution where functional interpretation allowed distinction of the two components. Basal flow measurements and results of this modeling were reproducible 24 and 27 h later.

There is growing interest in developing a practical technique to accurately assess ventricular synchrony. We describe a novel 3-dimensional (3D) gated blood pool single photon emission computed tomography (SPECT) approach, from which a contraction homogeneity index (CHI) is derived and compared with planar phase analyses.Subjects underwent planar and SPECT blood pool acquisition. Planar images were processed for left ventricular ejection fraction computation and phase values. SPECT images were processed by our novel algorithm, with which CHI was computed. Overall, 235 patients (79% male; mean age, 62 +/- 11 years) completed the study. Left ventricular ejection fractions were similar by planar (33.5% +/- 13.5%) and 3D (34.7% +/- 12.7%) methods (r = 0.83, P.0001). Mean phase angles for planar and tomographic methods were 126.3 degrees +/- 29.6 degrees and 124.4 degrees +/- 28.7 degrees , respectively (r = 0.53, P.0001). Phase and amplitude signals were incorporated in the CHI, which was non-normally distributed with a median of 73.8% (interquartile range, 58.7%-84.9%). This index minimized the negative impact of dyskinetic wall segments with limited regional motion. The planar heterogeneity index (SDPhi) was 28.2 degrees (interquartile range, 17.5 degrees -46.8 degrees ) and correlated inversely with CHI (r = -0.61, P.0001).The novel 3D dispersion index CHI accounts for both phase delay of a dyssynchronous segment and its magnitude of contraction and is moderately correlated with planar phase analyses. Its potential in cardiac resynchronization therapy remains to be exploited.