Aortic valve stenosis-multimodality assessment with PET/CT and PET/MRI

Aortic valve disease is the most common form of heart valve disease in developed countries and a growing healthcare burden with an ageing population. Transthoracic and transoesophageal echocardiography remains central to the diagnosis and surveillance of patients with aortic stenosis, providing gold standard assessments of valve haemodynamics and myocardial performance. However, other multimodality imaging techniques are being explored for the assessment of aortic stenosis, including combined PET/CT and PET/MR. Both approaches provide unique information with respect to disease activity in the valve alongside more conventional anatomic assessments of the valve and myocardium in this condition. This review investigates the emerging use of PET/CT and PET/MR to assess patients with aortic stenosis, examining how the complementary data provided by each modality may be used for research applications and potentially in future clinical practice

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications

Nuclear medicine in the assessment and prevention of cancer therapy-related cardiotoxicity: prospects and proposal of use by the European Association of Nuclear Medicine (EANM)

Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity

PET Cell Tracking Using 18F-FLT is Not Limited by Local Reuptake of Free Radiotracer

Assessing the retention of cell therapies following implantation is vital and often achieved by labelling cells with 2'-[(18)F]-fluoro-2'-deoxy-D-glucose ((18)F-FDG). However, this approach is limited by local retention of cell-effluxed radiotracer. Here, in a preclinical model of critical limb ischemia, we assessed a novel method of cell tracking using 3'-deoxy-3'-L-[(18)F]-fluorothymidine ((18)F-FLT); a clinically available radiotracer which we hypothesise will result in minimal local radiotracer reuptake and allow a more accurate estimation of cell retention. Human endothelial cells (HUVECs) were incubated with (18)F-FDG or (18)F-FLT and cell characteristics were evaluated. Dynamic positron emission tomography (PET) images were acquired post-injection of free (18)F-FDG/(18)F-FLT or (18)F-FDG/(18)F-FLT-labelled HUVECs, following the surgical induction of mouse hind-limb ischemia. In vitro, radiotracer incorporation and efflux was similar with no effect on cell viability, function or proliferation under optimised conditions (5 MBq/mL, 60 min). Injection of free radiotracer demonstrated a faster clearance of (18)F-FLT from the injection site vs. (18)F-FDG (p ≤ 0.001), indicating local cellular uptake. Using (18)F-FLT-labelling, estimation of HUVEC retention within the engraftment site 4 hr post-administration was 24.5 ± 3.2%. PET cell tracking using (18)F-FLT labelling is an improved approach vs. (18)F-FDG as it is not susceptible to local host cell reuptake, resulting in a more accurate estimation of cell retention

Hybrid PET- and MR-driven attenuation correction for enhanced ¹⁸F-NaF and ¹⁸F-FDG quantification in cardiovascular PET/MR imaging

Background: The standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from ¹⁸F-Sodium Fluoride (¹⁸F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for ¹⁸F-NaF and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) PET/MR cardiovascular imaging. Methods: We introduce 5-class Ki/MR-AC for (i) ¹⁸F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) ¹⁸F-FDG-only data, with a streamlined simultaneous administration of ¹⁸F-FDG and ¹⁸F-NaF at 4:1 ratio (R4:1), or (iii) for ¹⁸F-FDG-only or both ¹⁸F-FDG and ¹⁸F-NaF dual-tracer data, by administering ¹⁸F-NaF 90 minutes after an equal ¹⁸F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD). Results: In rabbits, we observed similar (< 1.2% mean difference) vertebral bone ¹⁸F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (¹⁸F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher ¹⁸F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean ¹⁸F-FDG:¹⁸F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (¹⁸F-FDG) and 15.5% (¹⁸F-NaF) at carotid bifurcations and 21.6% (¹⁸F-FDG) and 22.5% (¹⁸F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication. Conclusions: Ki-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance ¹⁸F-NaF and ¹⁸F-FDG contrast and quantification in bone tissues and carotid walls

Imaging pheochromocytoma in small animals: Preclinical models to improve diagnosis and treatment.

Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats