Advances in Radiopharmaceutical Sciences for Vascular Inflammation Imaging: Focus on Clinical Applications.

Biomedical imaging technologies offer identification of several anatomic and molecular features of disease pathogenesis. Molecular imaging techniques to assess cellular processes in vivo have been useful in advancing our understanding of several vascular inflammatory diseases. For the non-invasive molecular imaging of vascular inflammation, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is currently the most widely used radiopharmaceutical for molecular imaging of vascular inflammatory diseases such as atherosclerosis and large-vessel vasculitis. The combination of [18F]FDG and positron emission tomography (PET) imaging has become a powerful tool to identify and monitor non-invasively inflammatory activities over time but suffers from several limitations including a lack of specificity and avid background in different localizations. The use of novel radiotracers may help to better understand the underlying pathophysiological processes and overcome some limitations of [18F]FDG PET for the imaging of vascular inflammation. This review examines how [18F]FDG PET has given us deeper insight into the role of inflammation in different vascular pathologies progression and discusses perspectives for alternative radiopharmaceuticals that could provide a more specific and simple identification of pathologies where vascular inflammation is implicated. Use of these novel PET tracers could lead to a better understanding of underlying disease mechanisms and help inform the identification and stratification of patients for newly emerging immune-modulatory therapies. Future research is needed to realize the true clinical translational value of PET imaging in vascular inflammatory diseases.

Radionuclide Imaging for Neuroscience: Current Opinion and Future Directions.

This meeting report summarizes a Consultants Meeting that was held at International Atomic Energy Agency headquarters in Vienna to provide an update on radionuclide imaging for neuroscience applications.

Impact of International Atomic Energy Agency support to the development of nuclear cardiology in low-and-middle-income countries: Case of Latin America and the Caribbean.

Cardiovascular diseases (CVDs) are the leading cause of death in Latin America and the Caribbean (LAC) region as well as worldwide. Lifestyle, nutritional habits and the upsurge of obesity have contributed to the increase in the prevalence of CVDs in the region. The role of nuclear cardiology in the management of patients with CVDs is well established. Particularly, myocardial perfusion imaging is widely used in LAC countries and has been increasingly integrated into the healthcare systems in the region for the diagnosis of coronary artery disease, risk stratification and to guide patient management. In its role to support countries around the world to address their health needs through the peaceful applications of nuclear techniques, the International Atomic Energy Agency (IAEA) has provided assistance to the LAC region for the establishment and strengthening of the nuclear cardiology practice. To that extent, the IAEA provides support in building capacities of multidisciplinary teams of professionals, the provision of medical equipment and the promotion of communication and exchange of knowledge among the different stakeholders. In addition, the IAEA encourages the participation of nuclear medicine centers in international multi-center research studies. In this paper, we present some of the projects through which the IAEA has supported the LAC region, including regional technical cooperation projects and coordinated research projects related to cardiology within the current multimodality approach to cardiac imaging.

Trends in Use of Medical Imaging in US Health Care Systems and in Ontario, Canada, 2000-2016.

Importance: Medical imaging increased rapidly from 2000 to 2006, but trends in recent years have not been analyzed. Objective: To evaluate recent trends in medical imaging. Design, Setting, and Participants: Retrospective cohort study of patterns of medical imaging between 2000 and 2016 among 16 million to 21 million patients enrolled annually in 7 US integrated and mixed-model insurance health care systems and for individuals receiving care in Ontario, Canada. Exposures: Calendar year and country (United States vs Canada). Main Outcomes and Measures: Use of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine imaging. Annual and relative imaging rates by imaging modality, country, and age (children [<18 years], adults [18-64 years], and older adults [≥65 years]). Results: Overall, 135 774 532 imaging examinations were included; 5 439 874 (4%) in children, 89 635 312 (66%) in adults, and 40 699 346 (30%) in older adults. Among adults and older adults, imaging rates were significantly higher in 2016 vs 2000 for all imaging modalities other than nuclear medicine. For example, among older adults, CT imaging rates were 428 per 1000 person-years in 2016 vs 204 per 1000 in 2000 in US health care systems and 409 per 1000 vs 161 per 1000 in Ontario; for MRI, 139 per 1000 vs 62 per 1000 in the United States and 89 per 1000 vs 13 per 1000 in Ontario; and for ultrasound, 495 per 1000 vs 324 per 1000 in the United States and 580 per 1000 vs 332 per 1000 in Ontario. Annual growth in imaging rates among US adults and older adults slowed over time for CT (from an 11.6% annual percentage increase among adults and 9.5% among older adults in 2000-2006 to 3.7% among adults in 2013-2016 and 5.2% among older adults in 2014-2016) and for MRI (from 11.4% in 2000-2004 in adults and 11.3% in 2000-2005 in older adults to 1.3% in 2007-2016 in adults and 2.2% in 2005-2016 in older adults). Patterns in Ontario were similar. Among children, annual growth for CT stabilized or declined (United States: from 10.1% in 2000-2005 to 0.8% in 2013-2016; Ontario: from 3.3% in 2000-2006 to -5.3% in 2006-2016), but patterns for MRI were similar to adults. Changes in annual growth in ultrasound were smaller among adults and children in the United States and Ontario compared with CT and MRI. Nuclear medicine imaging declined in adults and children after 2006. Conclusions and Relevance: From 2000 to 2016 in 7 US integrated and mixed-model health care systems and in Ontario, rates of CT and MRI use continued to increase among adults, but at a slower pace in more recent years. In children, imaging rates continued to increase except for CT, which stabilized or declined in more recent periods. Whether the observed imaging utilization was appropriate or was associated with improved patient outcomes is unknown.

Preoperative Cardiac Stress Testing in the Southern California Vascular Outcomes Improvement Collaborative.

BACKGROUND: The objective of this study was to examine the use of preoperative cardiac stress testing (PCST) in the Southern California Vascular Outcomes Improvement Collaborative (So Cal VOICe). METHODS: A retrospective review was performed on data in all modules of the So Cal VOICe from September 2012 through May 2016. PCST was defined as stress echocardiogram or nuclear stress test. A new postoperative myocardial infarction (MI) was defined as troponin elevation and/or electrocardiogram/imaging changes with or without ischemic symptoms. Only elective cases in patients with asymptomatic cardiac status were included in the study. RESULTS: During the study period, 3,063 procedures meeting the inclusion criteria were performed in 7 registries: carotid endarterectomy (CEA), carotid artery stent, thoracic endovascular aneurysm repair, infrainguinal bypass (Infra), endovascular aneurysm repair (EVAR), suprainguinal bypass (Supra), and open abdominal aortic aneurysm repair (OAAA). PCST varied across registries from 17% in PVI to 62% in OAAA. PCST in CEA varied across 9 institutions from 10% to 79%. PCST in EVAR varied across 7 institutions from 14% to 83%. PCST in Infra varied across 4 institutions from 10% to 57%. Of the 12 patients across all registries who had a new MI, 6 had PCST, one of which was abnormal. CONCLUSIONS: The incidence of PCST varies widely across registries and institutions in the So Cal VOICe. Despite the wide variation, the incidence of new postoperative MI is exceptionally low. Further studies should evaluate the cost-effectiveness of the PCST practices and future quality improvement efforts should focus on standardization of indications for PCST.

A quick glance at selected topics in this issue.

"A quick glance at selected topics in this issue" aims to highlight few randomly selected articles and provide a quick review to the readers.

Highlights lecture EANM 2015: the search for nuclear medicine's superheroes.

The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1).

Rationale for the use of radiolabelled peptides in diagnosis and therapy.

Nuclear medicine techniques are becoming more important in imaging oncological and infectious diseases. For metabolic imaging of these diseases, antibody and peptide imaging are currently used. In recent years peptide imaging has become important, therefore the rationale for the use of peptide imaging is described in this article. Criteria for a successful peptide tracer are a high target specificity, a high binding affinity, a long metabolic stability and a high target-to-background ratio. Tracer internalization is also beneficial. For oncological imaging, many tracers are available, most originating from regulatory peptides, but penetrating peptides are also being developed. Peptides for imaging inflammatory and infectious diseases include regulatory peptides, antimicrobial peptides and others. In conclusion, for the imaging of oncological, imflammatory and infectious diseases, many promising peptides are being developed. The ideal peptide probe is characterized by rapid and specific target localization and binding with a high tumour-to-background ratio.

Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive, and disabling disease, but the diagnosis is often missed and markedly delayed. An early diagnosis is important to establish a treatment to reduce disability and modify the natural course of disease. The aim of this study was to investigate the diagnostic (DD) and therapeutic (TD) delay according to the decade of diagnosis. The DD and TD correlation with radiological severity score and the new imaging techniques used in diagnosis (magnetic resonance [MRI], computerised tomography, scintigraphy for sacroiliac joints) were also investigated. METHODS: 135 AS patients (45 female and 90 male, 36.5±10.2 years old at diagnosis) with disease onset between 1950 and 2008, were investigated; the time from onset to diagnosis (DD) and treatment (TD), the New York and ASAS criteria fulfilment, the New York sacroiliac radiological score, bamboo spine presence at first visit and the new imaging technique used at diagnosis were recorded and their correlations were analysed. RESULTS: The New York and ASAS criteria were met at the first visit, by 87% and 96%, respectively. The delay from onset of symptoms to diagnosis and treatment was 9±8 and 12±11 years, respectively, but decreased significantly between different decades (p<0.001). The severity of sacroiliitis (mean 2±1; 17/135, 12.5% - IV grade sacroiliitis at diagnosis) and bamboo spine (3.7% at diagnosis) correlated with DD and TD (p<0.001). Sacroiliac MRI use at diagnosis significantly decreased both DD and TD (p>0.001 and p<0.05, respectively). CONCLUSIONS: DD and TD were correlated to radiological severity; they progressively decreased over 6 decades.

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology.

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. ¹²³I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) ¹²³I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. ¹²³I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds.

Clinical applications in molecular imaging.

Molecular imaging is aimed at the noninvasive in vivo characterization and measurement of processes at a cellular and molecular level with clinical imaging methods. Contrast agents are constructed to target markers that are specific either for certain diseases or for functional states of specialized tissues. Efforts are currently focused mainly on processes involved in angiogenesis, inflammation, and apoptosis. Cell tracking is performed for diagnostic purposes as well as for monitoring of novel cell therapies. Visualization of these processes would provide more precise information about disease expansion as well as treatment response, and could lead to a more individualized therapy for patients. Many attempts have shown promising results in preclinical studies; however, translation into the clinic remains a challenge. This applies especially to paediatrics because of more stringent safety concerns and the low prevalence of individual diseases. The most promising modalities for clinical translation are nuclear medicine methods (positron emission tomography [PET] and single photon emission CT [SPECT]) due to their high sensitivity, which allows concentrations below biological activity. However, special dose consideration is required for any application of ionizing radiation especially in children. While very little has been published on molecular imaging in a paediatric patient population beyond fluorodeoxyglucose (FDG)-PET and metaiodobenzylguanidine (MIBG) tracers, this review will attempt to discuss approaches that we believe have promise for paediatric imaging. These will include agents that already reached clinical trials as well as preclinical developments with high potential for clinical application.

Advancing molecular imaging: a chairman's perspective on how radiology can meet the challenge.

To date, most molecular imaging techniques applied clinically have offered relatively general information about the metabolism and physiology of diseased cells and tissues. However, due to recent scientific and technological advances, much more specifically targeted molecular imaging probes (e.g., reporter gene probes, whole cell-tracking probes, and probes for localizing specific biomolecules) are now being used in preclinical research and, in some cases, translated to the clinical setting. As a result, the imaging community is poised to help lead a revolution in personalized, molecularly targeted medicine. This article considers the importance of molecular imaging for advancing research and clinical care both within individual institutions and across the medical field. It outlines specific steps that leaders in academic radiology can take to hasten progress in molecular imaging and explains why they must have the courage to reach across traditional interdisciplinary boundaries and advocate for major investments in equipment, education, and personnel.

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives.

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue.

Responsible Radionuclide Cancer Care.

The landscape of nuclear oncology is rapidly changing. The advent of molecular radionuclide theranostics, multidisciplinary tumor board decision making, artificial intelligence and radiomics interpretation of diagnostic imaging, evolution of pharmacogenomics prediction of tumor response, and regulatory requirements for prospective individual dosimetry are just some of the elements which are broadening the essence of physician responsibility. The burgeoning knowledge base essential for mastering the emergent technologies, and their profound effect on moral philosophic aspects of provision of cancer care, are challenging. The new relationship of the theranostic nuclear physician with respect to shared care of the individual patient, particularly with regard to transparency, accountability, and responsibility for targeted radionuclide diagnosis and therapy of cancer, will be explored in this update.

Scope of Practice of US Interventional Cardiologists from an Analysis of Medicare Billing Data.

The contemporary scope of practice of interventional cardiologists (ICs) in the United States and recent trends are unknown. Using Medicare claims from 2013 to 2017, we categorized ICs into 4 practice categories (only percutaneous coronary intervention [PCI], PCI with noninvasive imaging, PCI with specialized interventions [peripheral/structural], and all 3 services) and evaluated associations with region, hospital bed size and teaching status, gender, and graduation year. Of 6,083 ICs in 2017, 10.9% performed only PCI, 68.3% PCI with noninvasive imaging, 5.7% PCI with specialized interventions, and 15.1% all 3 services. A higher proportion of Northeast ICs (vs South ICs) were performing only PCI (24.8% vs 7.3%) and PCI with specialized interventions (12% vs 3.4%), but lower PCI and noninvasive imaging (53.8% vs 71.7%) and all 3 services (9.3% and 17.6%). Regarding ICs at larger hospitals (bed size >575 vs <218), a higher proportion was performing only PCI (23.8% vs 5.2%) or PCI with specialized interventions (13.5% vs 1.7%) and lower proportion was performing PCI with noninvasive imaging (48.8% vs 78%), similar to teaching hospitals. Female ICs (vs male ICs) more frequently performed only PCI (18.9% vs 10.6%) and less frequently all 3 services (8.3% vs 15.4%). A lower proportion of recent graduates (2001 to 2016) performed only PCI (9.8% vs 13.8%) and PCI with noninvasive imaging (66.3% vs 72.6%) but a higher proportion performed all 3 services (18% vs 8.4%) than earlier graduates (1959 to 1984). From 2013 to 2017, only PCI and PCI with noninvasive imaging decreased, whereas PCI and specialized interventions and all 3 services increased (all p <0.001). In conclusion, there is marked heterogeneity in practice responsibilities among ICs, which has implications for training and competency assessments.