Design, Synthesis, and Preclinical Evaluation of a High-Affinity F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post-myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics.

Myocardial glucose suppression may interfere with the detection of inflammatory cells with FDG-PET as suggested in a canine model of myocardial infarction.

Background: After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin.

Changes in myocardial blood flow in a canine model of left sided breast cancer radiotherapy.

Background: Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured.

PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT.

Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease.

Background: The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function.

Simultaneous measurements of myocardial glucose metabolism and extracellular volumes with hybrid PET/MRI using concurrent injections of Gd-DTPA and [F]FDG.

Background: The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impact of glucose suppression using heparin on ECV.

Methods: Five healthy canine subjects were imaged to compare three different protocols for injecting Gd-DTPA and FDG: bolus alone, CI alone, bolus followed by CI. Suppression of myocardial glucose uptake was induced using a continuous infusion of 20% lipid at a rate of 0.

Tracking the progress of inflammation with PET/MRI in a canine model of myocardial infarction.

Background: Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined constant infusion of F-FDG and Gd-DTPA to quantitate inflammation and extracellular volume (ECV) from 3 to 40 days after myocardial infarction.

Hybrid PET/MR imaging in myocardial inflammation post-myocardial infarction.

Hybrid PET/MR imaging is an emerging imaging modality combining positron emission tomography (PET) and magnetic resonance imaging (MRI) in the same system. Since the introduction of clinical PET/MRI in 2011, it has had some impact (e.g.

Cubic-Spline Interpolation for Sparse-View CT Image Reconstruction With Filtered Backprojection in Dynamic Myocardial Perfusion Imaging.

We investigated a projection interpolation method for reconstructing dynamic contrast-enhanced (DCE) heart images from undersampled x-ray projections with filtered backprojecton (FBP). This method may facilitate the application of sparse-view dynamic acquisition for ultralow-dose quantitative computed tomography (CT) myocardial perfusion (MP) imaging. We conducted CT perfusion studies on 5 pigs with a standard full-view acquisition protocol (984 projections).

Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation.

Currently, the early preclinical detection of left ventricular dysfunction is difficult because biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics.

Same day comparison of PET/CT and PET/MR in patients with cardiac sarcoidosis.

Background: Inflammatory cardiac disorders, in particular, sarcoidosis, play an important role in left ventricular dysfunction, conduction abnormalities, and arrhythmias. In this study, we compared the imaging characteristics and diagnostic information obtained when patients were imaged sequentially with PET/CT and then with hybrid PET/MRI on the same day following a single F-FDG injection.

Methods: Ten patients with known or suspected sarcoidosis underwent imaging in sequence of (a) Tc-MIBI, (b) F-FDG with PET/CT, and (c) F-FDG with 3T PET/MRI.

Sensitivity and specificity of chest imaging for sarcoidosis screening in patients with cardiac presentations.

Background: Patients with sarcoidosis can present with cardiac symptoms as the first manifestation of disease in any organ. In these patients, the use of chest imaging modalities may serve as an initial screening tool towards the diagnosis of sarcoidosis through identification of pulmonary/mediastinal involvement; however, the use of chest imaging for this purpose has not been well studied. We assessed the utility of different chest imaging modalities for initial screening for cardiac sarcoidosis (CS).

[F]FDG cardiac PET imaging in a canine model of radiation-induced cardiovascular disease associated with breast cancer radiotherapy.

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [F]fluorodeoxyglucose PET to assess changes in myocardial inflammation.

Functional CT assessment of extravascular contrast distribution volume and myocardial perfusion in acute myocardial infarction.

Purpose: In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection.

Methods: In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ± 3 day post ischemic insult.

Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view dynamic acquisition and image reconstruction: A feasibility study.

Purpose: We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections.

Methods: DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view).

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Unlabelled: Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging.

Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart quantitative myocardial perfusion imaging.

Purpose: The authors investigated the performance of a recently introduced 160-mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging of the whole heart. This platform is equipped with a gantry capable of rotating at 280 ms per full cycle, a second generation of adaptive statistical iterative reconstruction (ASiR-V) to correct for image noise arising from low tube voltage potential/tube current dynamic scanning, and image reconstruction algorithms to tackle beam-hardening, cone-beam, and partial-scan effects.

Methods: Phantom studies were performed to investigate the effectiveness of image noise and artifact reduction with a GE Healthcare Revolution CT system for three acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140 kVp/25 mAs.

Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

Unlabelled: Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

Unlabelled: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation.

Methods: Cardiac phantom qualifying scans were obtained at 7 recruiting centers.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial.

Background: Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging.

Methods/design: This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial.

Transcatheter aortic valve implantation in a patient with severe aortic insufficiency and minimal aortic annular calcification.

Severe aortic insufficiency with minimal aortic annular calcification has been considered a relative contraindication to transcatheter aortic valve implantation (TAVI) because of a lack of calcium for fluoroscopic visualization and radial stent fixation. We report a patient with severe aortic insufficiency after previous coronary artery bypass and aortic valve repair who underwent successful TAVI. Intraoperative transesophageal echocardiography was critical to guide valve implantation and previous surgical pledgets were used to seat an oversized TAVI prosthesis within the aortic annulus.