Vincent Finnerty

Comparison of left ventricular contraction homogeneity index using SPECT gated blood pool imaging and planar phase analysis.

BackgroundThere 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.Methods and ResultsSubjects 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°±29.6° and 124.4°±28.7°, 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 (SDΦ) was 28.2° (interquartile range, 17.5°–46.8°) and correlated inversely with CHI (r=−0.61, P<.0001).ConclusionThe 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.

Evaluation of the right ventricle: Comparison of gated blood-pool single photon electron computed tomography and echocardiography with cardiac magnetic resonance

BACKGROUND 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. METHODS Fifty-eight patients underwent CMR, GBPS and TTE for RV assessment, including volumes, RVEF and TTEs 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. RESULTS Nuclear medicine derived volumes quantification showed very good correlations with CMR, for RV end-diastolic (r=0.84 and 0.77, all p<0.001) and end-systolic (r=0.82 and 0.67, all p<0.001) 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). CONCLUSIONS GBPS, both with MHI and QBS software, exhibited significant correlations with CMR for evaluation of the RV (volumes and decreased RVEF estimation). Among TTEs parameters, only FAC and MPI-TDI showed significant correlation with CMR with RVEF ≤ 45%.

Characterization and reproducibility of forearm arterial flow during reactive hyperemia

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.

Molecular Imaging of the Human Pulmonary Vascular Endothelium Using an Adrenomedullin Receptor Ligand

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 99mTc, 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) 99mTc-PulmoBind. SPECT imaging was serially performed, and 99mTc-PulmoBind dosimetric analysis was accomplished. The radiochemical purity of 99mTc-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. 99mTc-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.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 99mTc, 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) 99mTc-PulmoBind. SPECT imaging was serially performed, and 99mTc-PulmoBind dosimetric analysis was accomplished. The radiochemical purity of 99mTc-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. 99mTc-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.

Mobile detection system to evaluate reactive hyperemia using radionuclide plethysmography

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.

Al18F-complexation of DFH17, a NOTA-conjugated adrenomedullin analog, for PET imaging of pulmonary circulation

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.

Cardiopulmonary, biomarkers, and vascular responses to acute hypoxia following cardiac transplantation

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.

MOLECULAR IMAGING OF THE HUMAN PULMONARY VASCULAR ENDOTHELIUM IN PULMONARY HYPERTENSION: THE PULMOBIND SAFETY AND PROOF OF PRINCIPLE TRIAL

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