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To enable patients with rheumatoid arthritis (RA) and their healthcare professionals to choose the optimal treatment, it is crucial to accurately assess the current state of inflammatory activity. The objectives of this study were to (1) investigate the perspective of RA patients on their insight into the current status of their disease, and to (2) investigate the patients’ perspective on the possible added value of a monitoring device based on optical spectral transmission—called the HandScan—that measures the location and severity of joint inflammation. A survey was distributed online among patients with RA in the Netherlands. Four-hundred and eight patients with RA completed the survey. Of these, 298 (73%) felt they have sufficient insight into their current disease status. Most respondents perceived either a large (n = 242; 59%) or small (n = 148; 36%) added value of the HandScan in their monitoring process, mostly because the device provides additional knowledge on the presence of inflammation. This perceived added value was higher for respondents experienced with the device (n = 46; p = .04). Respondents preferred monitoring with the device on every (n = 192; 47%) or most (n = 171; 42%) visits to the outpatient clinic, or even more often than on every visit (n = 17; 4%). Monitoring RA using an optical spectral transmission device is seen by patients as a possibly valuable addition to the monitoring process of inflammatory activity during visits to an outpatient clinic. Their main reason was that the device can increase insight into their current disease status. More insight may support patients in discussing treatment options with their rheumatologist.

Synthetic antimicrobial peptide fragment, 99mTc-Ubiquicidin 29–41, is shown to be sensitive and also specific for imaging bacterial infections. We undertook this study to explore the advantage of using a positron emission agent, 68Ga-DOTA-Ubiquicidin 29–41 (68Ga-DOTA-UBI), for detecting Staph-A infection in an animal model, and also evaluated its ability to distinguish a turpentine-induced sterile inflammation in an animal model. Pure Ga-68 was freshly eluted from a 68Ge/68Ga generator (IGG-100). DOTA-UBI (50 μg) was ra diolabeled with pure Ga-68 (500MBq) by incubating the reaction mixture at pH 4.5 for 10 min, 95°C. Rats were infected with Staph-A at the hind leg joint of rats to form bacterial abscess. Sterile inflammation was induced in the right thigh muscle by injecting 200 μl of 100% turpentine oil. Rats were injected intravenously with 10–15 MBq of tracer, and images were acquired at different time intervals with Siemens (Biograph mCT) positron emission tomography computed tomography scanner. The early images at 6 min postinjection clearly indicated mild uptake of the agent corresponding to the infection site, which increased dramatically at 20, 30, and 60 min postinjection. The target to background ratio (T/B) increased significantly over the same time period of study (1.6, 4.2, and 6.1, respectively). There was a mild uptake of 68Ga-DOTA-UBI at the site corresponding to sterile inflammation at 6 min postinjection, which was rapidly washed off as seen at 25 and 45 min images. The images indicated fast clearance of the agent from liver and soft tissues within 6 min. Control rats showed similar biodistribution of activity. The mild uptake of 68Ga-DOTA-UBI at the corresponding Staph-A infection lesion and very fast kinetics of clearance from the blood pool and soft tissues suggested a very high clinical potential for this agent. The absence of uptake of the agent at sterile inflammation site suggests that the agent may be useful in distinguishing infection from inflammation.

Total-body PET scans will initiate a new era for the PET clinic. The benefits of 40-fold effective sensitivity improvement provide new capabilities to image with lower radiation dose, perform delayed imaging, and achieve improved temporal resolution. These technical features are detailed in the first of this 2-part series. In this part, the clinical impacts of the novel features of total-body PET scans are further explored. Applications of total-body PET scans focus on the real-time interrogation of systemic disease manifestations in a variety of practical clinical contexts. Total-body PET scans make clinical systems biology imaging a reality.

This review discusses nuclear imaging of inflammation using molecular probes beyond fluoro-d-glucose, is structured by cellular targets, and focuses on those tracers that have been successfully applied clinically.

Somatostatin receptor (SSTR)-based imaging and therapy has emerged as well-established modality in neuroendocrine tumors. However, its role in inflammation imaging is still evolving. We present a 48-year-old male with metastatic neuroendocrine tumor who underwent lutetium-177-based somatostatin receptor-based therapy. The post-therapy scan showed a focal tracer uptake in the left calf muscle in addition to the expected tracer uptake at the primary and metastatic sites. Further, cross-sectional imaging and biochemical investigations revealed peripheral vascular disease (PVD). The incidental tracer uptake in the calf on post-therapy scan potentiates the role of somatostatin receptor scintigraphy in identifying macrophage-specific inflammatory reactions.

Positron emission tomography and/or computed tomography (PET/CT) MPI is a powerful imaging modality for the assessment of cardiovascular diseases. It offers several advantages over single-photon emission computed tomography (SPECT) MPI including robust attenuation correction and absolute quantification of radiotracer activity. PET MPI has a large evidence base and is the only clinical tool to evaluate coronary microvascular dysfunction. In addition, the clinical use and evidence base for 2-deoxy-2-[18F]fluoro-D-g1ucose (18F-FDG) cardiac PET imaging for inflammation and metabolism imaging is rising exponentially. In order to gain from the advances of this sophisticated quantitative technique, a high-quality scan is critical. It is important for readers to recognize a poor-quality scan, identify artifacts contributing to the poor image quality, and understand how to correct them prior to reporting the results. In this review, we will discuss some normal variants and pitfalls in cardiac PET/CT radionuclide MPI, myocardial viability, and inflammation imaging.

Imaging techniques have evolved impressively lately, allowing whole new concepts like multimodal imaging, personal medicine, theranostic therapies, and molecular imaging to increase general awareness of possiblities of imaging to medicine field. Here, we have collected the selected (3D) imaging modalities and evaluated the recent findings on preclinical and clinical inflammation imaging. The focus has been on the feasibility of imaging to aid in inflammation precision medicine, and the key challenges and opportunities of the imaging modalities are presented. Some examples of the current usage in clinics/close to clinics have been brought out as an example. This review evaluates the future prospects of the imaging technologies for clinical applications in precision medicine from the pre-clinical development point of view.

As a basic innate immune response to the disordered tissue homeostasis, inflammation is related to the pathogenesis of multiple diseases, including bacterial infections, atherosclerosis, neurodegenerative diseases, and cancers. It is also a pivotal feature of some metabolic disorders such as diabetes and obesity. The visualization of in vivo inflammations can help us to comprehend the pathogenesis of these diseases and develop new solutions to diagnose them. Over the past few decades, a variety of strategies (eg, computed tomography, magnetic resonance imaging [MRI], and ultrasound [US] imaging) have been utilized for visualizing inflammations by imaging the structural changes of inflammatory tissues. Moreover, many recent studies have focused on some probes that can target or localize the inflammatory sites by specific binding to inflammation‐related molecules, being internalized by inflammatory cells, or becoming detectable only under inflammatory conditions. These probes can also be applied to visualize inflammations by MRI, positron emission tomography, single‐photon emission computed tomography, photoacoustic imaging, optical imaging (eg, fluorescence imaging, bioluminescence imaging, and chemiluminescence imaging), contrast‐enhanced US imaging, and the combined use of the abovementioned methods. This review not only summarizes the existing strategies for visualizing inflammations, but also discusses the limitations of the present strategies and the future directions on the development of new strategies for realizing the in vivo inflammation visualization.

Recurrent pericarditis can occur in up to 30% of patients after acute episode of pericarditis and is associated with significantly impaired quality of life and morbidity1. High rate of recurrence remains despite treatment as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, steroids or other immunosuppressants1. If medical therapy fails, in case of symptomatic constrictive hemodynamics, surgical approach-pericardiectomy is indicated. Therefore, imaging modalities have to distinguish between hemodynamic assessment, where echocardiography is first line imaging modality, and inflammation where other cardiac imaging modalities complement echocardiographic findings.

Magnetic particle imaging is an emerging tomographic technique with the potential for simultaneous high-resolution, high-sensitivity, and real-time imaging. Magnetic particle imaging is based on the unique behavior of superparamagnetic iron oxide nanoparticles modeled by the Langevin theory, with the ability to track and quantify nanoparticle concentrations without tissue background noise. It is a promising new imaging technique for multiple applications, including vascular and perfusion imaging, oncology imaging, cell tracking, inflammation imaging, and trauma imaging. In particular, many neuroimaging applications may be enabled and enhanced with magnetic particle imaging. In this review, we will provide an overview of magnetic particle imaging principles and implementation, current applications, promising neuroimaging applications, and practical considerations.

The role of nuclear imaging in the characterization of high-risk atherosclerotic plaque is increasing thanks to its high sensitivity to detect radiopharmaceuticals signal in tissues. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most studied and widely used radiopharmaceutical for the molecular imaging of atherosclerotic plaques with positron emission tomography (PET). [18F]FDG PET is a valuable tool to non-invasively detect, monitor and quantify inflammatory processes occurring in atherosclerotic plaques. The aim of this review is to gather insights provided by [18F]FDG PET to better understand the role of inflammation in the definitions of the vulnerable plaque and the vulnerable patient. Alternatives radiopharmaceuticals targeting inflammation and other potential high-risk plaque related processed are also discussed.

Fluorine-19 (19F) MRI with intravenously applied perfluorocarbons allows the in vivo monitoring of infiltrating immune cells as demonstrated in small animal models at high field. Here, we aimed to transfer this approach to a clinical scanner for detection of inflammatory processes in the heart after acute myocardial infarction (AMI) in a large animal model. Optimization of coil and sequence performance was carried out on phantoms and in vivo at a 3 T Philips Achieva. AMI was induced in Munich mini pigs by 90-min occlusion of the left anterior descending artery. At day 3 after AMI, pigs received a body weight-adjusted intravenous dose of a perfluorooctyl bromide nanoemulsion followed by 1H/19F MRI at day 6 after AMI. A balanced steady-state free precession turbo gradient echo sequence using an ellipsoidal 19F/1H surface coil provided the best signal-to-noise ratio and a superior localization of 19F patterns in vivo. This approach allowed the reliable detection of 19F signals in the injured myocardium within less than 20 min. The 19F signal magnitude correlated significantly with the functional impairment after AMI. This study demonstrates the feasibility of in vivo 19F MR inflammation imaging after AMI at 3 T within a clinically acceptable acquisition time.

Background:Magnetic resonance imaging (MRI) trial outcomes have largely focused on synovitis, bone marrow oedema (BME) and erosions. Tenosynovitis is a common manifestation of rheumatoid arthritis (RA), but is relatively understudied; a combined inflammation score (CIS) summing synovitis, BME and tenosynovitis may be a highly responsive measure. We previously showed the responsiveness of the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and a machine-learning derived automated tool (RAMRIQ) in a randomised controlled trial (RCT) of tofacitinib and methotrexate (MTX) in MTX-naïve patients (pts) with early RA.1Objectives:This post hoc analysis assessed the impact of tofacitinib ± MTX on MRI tenosynovitis and CIS in pts with early RA using semiquantitative and quantitative MRI outcomes.Methods:Study A3921068 (NCT01164579), a 1-year, exploratory, Phase 2, RCT, compared tofacitinib 10 mg twice daily (BID) ± MTX, and MTX monotherapy, in MTX-naïve pts with early RA.1 MRI of unilateral wrist and metacarpophalangeal joints was performed at screening/baseline (BL) and Months (M)1/3/6/12. MRI tenosynovitis and CIS were assessed using RAMRIS and RAMRIQ. Changes from BL (Δ) in RAMRIS and RAMRIQ tenosynovitis and CIS were evaluated at M1/3/6/12. Data were assessed using a mixed-effect model for repeated measures, with treatment arms as factors and BL values as covariates. Using data pooled across treatment arms, Spearman’s rank correlation coefficients were calculated for associations between BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]), and ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12.Results:In total, 109 pts were randomised and treated. ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS were generally significantly greater at M3/6/12 in pts receiving tofacitinib ± MTX vs MTX, while ΔRAMRIQ CIS was also significantly greater at M1 (Figure 1). Compared with RAMRIS, RAMRIQ outcomes were generally more responsive to treatment with tofacitinib ± MTX. Significant correlations were seen between BL RAMRIS and BL RAMRIQ tenosynovitis and BL RAMRIS CIS vs BL DAS28-4(CRP), and between ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (Table 1). In general, stronger correlations were seen between BL DAS28-4(CRP) and BL RAMRIS vs BL RAMRIQ parameters, while correlations were similar between ΔDAS28-4(CRP) at M12 and ΔRAMRIS and ΔRAMRIQ parameters at M12.Table 1.Correlations between a) BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL DAS28-4(CRP) (N=109) and b) ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (N=73) across treatment armsaa)BL DAS28-4(CRP)b)ΔDAS28-4(CRP)BL imaging featureCorrelationp valueΔImaging featureCorrelationp valueRAMRIStenosynovitis0.3660.0001RAMRIStenosynovitis0.531RAMRIS CIS0.399RAMRIS CIS0.554RAMRIQtenosynovitis0.2050.037RAMRIQtenosynovitis0.543RAMRIQ CIS0.1800.062RAMRIQ CIS0.564aData were pooled across the tofacitinib 10 mg BID ± MTX and MTX monotherapy armsSpearman’s rank correlation coefficients and p values were calculated for associations between RAMRIS and RAMRIQ parameters and DAS28-4(CRP); tenosynovitis and CIS were assessed using combined data from metacarpophalangeal and wrist joints; CIS is the sum of synovitis, BME and tenosynovitis valuesΔ, change from BL; N, number of pts with values at BL/timepoint of interestConclusion:Responsiveness of RAMRIS and RAMRIQ tenosynovitis and CIS was demonstrated with significant improvements through M12 in pts receiving tofacitinib 10 mg BID ± MTX vs MTX. Construct validity for RAMRIS and RAMRIQ tenosynovitis and CIS was evident from correlations with DAS28-4(CRP). Further work is needed to validate these novel imaging biomarkers in terms of relative responsiveness and prediction of later structural progression.References:[1]Conaghan et al. Ann Rheum Dis 2016; 75: 1024-1033.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Arnold, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Flexion, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Regeneron, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Consultant of: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Grant/research support from: AbbVie, Centocor, Merck, Orrin Troum Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Horizon, Novartis, Pfizer Inc, Sanofi-Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Pfizer Inc, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Centocor, Corrona, Novartis, Pfizer Inc, Zhiyong Xie Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alan Brett Shareholder of: Stryker Corp, Employee of: Stryker Corp, Mark Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gosford Sawyerr Consultant of: Pfizer Inc, Employee of: Syneos Health, John Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Labeling of macrophages with perfluorocarbon(PFC)-based compounds allows the visualization of inflammatory processes by 19F-magnetic resonance imaging (19F-MRI), due to the absence of endogenous background. Even if PFC-labeling of monocytes/macrophages has been largely investigated and used, information is lacking about the impact of these agents over the polarization towards one of their cell subsets and on the best way to image them. In the present work, a PFC-based nanoemulsion was developed to monitor the course of inflammation in a model of spinal cord injury (SCI), a pathology in which the understanding of immunological events is of utmost importance to select the optimal therapeutic strategies. The effects of PFC over macrophage polarization were studied in vitro, on cultured macrophages, and in vivo, in a mouse SCI model, by testing and comparing various cell tracking protocols, including single and multiple administrations, the use of MRI or Point Resolved Spectroscopy (PRESS), and application of pre-saturation of Kupffer cells. The blood half-life of nanoemulsion was also investigated by 19F Magnetic Resonance Spectroscopy (MRS). In vitro and in vivo results indicate the occurrence of a switch towards the M2 (anti-inflammatory) phenotype, suggesting a possible theranostic function of these nanoparticles. The comparative work presented here allows the reader to select the most appropriate protocol according to the research objectives (quantitative data acquisition, visual monitoring of macrophage recruitment, theranostic purpose, rapid MRI acquisition, etc.). Finally, the method developed here to determine the blood half-life of the PFC nanoemulsion can be extended to other fluorinated compounds.

In nuclear medicine, the detection of inflamed and infected lesions is of growing interest. Extensive efforts have been made to develop radiopharmaceuticals specific for inflammation or for discriminating sterile inflammation from infection. 99mTc is the worldwide most widely used radioisotope for SPECT imaging. The scope of this review article is to give an overview on the development of 99mTc-labelled small molecule radiotracers targeting inflammatory lesions and infections, ranging from their radiopharmacological evaluation to examples of their clinical applications. A systematic overview of 99mTc-citrate, 99mTc-antibiotics and antifungal agents as well as 99mTc-labelled antimicrobial peptides is provided. Additionally, the class of 99mTc-labelled cyclooxygenase-2 inhibitors is discussed, since cyclooxygenases are known to play a key role in inflammatory diseases and also in malignant neoplastic diseases. In a short perspective, newer developments in the field of inflammation imaging covering 99mTc-labelled bacteriophages and chemotactic peptides are highlighted.

The process of inflammation (with or without infection) forms part of essentially every major debilitating disease. Early detection and accurate distinction of inflammation from infection are important to optimize and individualize therapy. Nuclear medicine is ideally suited for the detection of pathologic changes early on and is able to target a magnitude of role players involved in the aforementioned processes. Hybrid modalities such as PET/CT and PET/MRI offer high spatial resolution that combines morphologic and pathophysiological changes and add various quantification possibilities that are preferable in these settings. It follows then that the development of PET radiopharmaceuticals is imperative to make use of these latest advances. Gallium-68 (Ga-68)-based tracers are exceptionally well suited to these indications, considering the year-round availability from a single generator, the relative cost-effectiveness, and relative ease of labeling. Over the past few years, the development of Ga-68-based tracers has understandably exploded with a recent growing interest in infection and inflammation imaging. This review aims to highlight some of the most important and interesting advances made with Ga-68-based PET/CT in the field of infection and inflammation imaging.

The rupture of vulnerable atherosclerotic plaques and subsequent thrombus formation are the major causes of myocardial and cerebral infarction. Accordingly, the detection of vulnerable plaques is important for risk stratification and to provide appropriate treatment. Inflammation imaging using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) has been most extensively studied for detecting vulnerable atherosclerotic plaques. It is of great importance to develop PET/SPECT probes capable of specifically visualizing the biological molecules involved in atherosclerotic plaque formation and/or progression. In this article, we review recent advances in the development of PET/SPECT probes for visualizing atherosclerotic plaques and their application to therapy monitoring, mainly focusing on experimental studies.

Bacterial infections are the main cause of patient morbidity and mortality worldwide. Diagnosis can be difficult and delayed as well as the identification of the etiological pathogen, necessary for a tailored antibiotic therapy. Several non-invasive diagnostic procedures are available, all with pros and cons. Molecular nuclear medicine has highly contributed in this field by proposing several different radiopharmaceuticals (antimicrobial peptides, leukocytes, cytokines, antibiotics, sugars, etc.) but none proved to be highly specific for bacteria, although many agents in development look promising. Indeed, factors including the number and strain of bacteria, the infection site, and the host condition, may affect the specificity of the tested radiopharmaceuticals. At the Third European Congress on Infection/Inflammation Imaging, a round table discussion was dedicated to debate the pros and cons of different radiopharmaceuticals for imaging bacteria with the final goal to find a consensus on the most relevant research steps that should be fulfilled when testing a new probe, based on experience and cumulative published evidence.

International audience; Background: Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke. Contribution: We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects. Conclusion: This review presents the contribution of the collaborative research project under the "TecSan" grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. (C) 2018 Published by Elsevier Masson SAS on behalf of AGBM.

Both the referring clinician and the nuclear medicine specialist must be aware of the main known or potential pitfalls that can occur in infection and inflammation imaging. They must decide in consensus which tracer and which imaging protocol should be used for a specific indication. This article provides an overview of all the pitfalls and limitations of nuclear medicine techniques to image infections and inflammation. Both general pitfalls and pitfalls in specific clinical entities are discussed. (C) 2015 Elsevier Inc. All rights reserved.

Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. The aim of this study was to develop a new radiopharmaceutical for imaging infection. The labeling conditions were optimized, and lyophilized kits were developed for instant preparing. The stability of 99mTc-AMOX in human serum was identified, sterility and pyrogenicity of the radiopharmaceutical were estimated, gamma scintigraphy and in vivo biodistribution with infected rats were investigated. The promising properties of 99mTc-AMOX combined with the development of reliable and instant lyophilized kit afford the opportunity of inflammatory process imaging.

Nuclear medicine techniques have been an integral part of infection and inflammation imaging for decades; in recent years, fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) has taken over many indications. This review provides a comprehensive overview of the current and potential applications for FDG-PET/CT in infectious and inflammatory diseases (ie, systemic infections, bone infections, vascular infection and inflammation, thoracic and abdominal inflammation) and potential novel applications in both infection and inflammation.

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical–subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment.

BACKGROUND: There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells. METHODS: The in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO. RESULTS: Established an in vitro cellular model of endothelial inflammation induced with TNF-α (tumor necrosis factor alpha). Inflammation of endothelial cells was confirmed with both immunocytochemistry and MRI. These results revealed both a temporal and dose dependent expression of the inflammatory markers, P-selectin and VCAM-1, on exposure to TNF-α. CONCLUSION: This study has demonstrated the development of an in vitro model to characterise and detect inflamed endothelial cells by immunocytochemistry and MRI. This will allow the future development of contrast agents and protocols for imaging vascular inflammation in atherosclerosis. This work may form the basis for a translational study to provide clinicians with a novel tool for the in vivo assessment of atherosclerosis.

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA- and 18F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV, 0.88±0.087) and 18F-FDR-Siglec-9 (SUV, 0.77±0.22) showed comparable (P=0.29) imaging of inflammation. In atherosclerotic mice, 18F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6±0.078) similar to previously tested 68Ga-DOTA-Siglec-9 (P=0.35). Human effective dose estimates for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion. Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

The aim of this overview article is to present the current possibilities of radionuclide scintigraphic small intestine imaging. Nuclear medicine has a few methods—scintigraphy with red blood cells labelled by means ofTc99mfor detection of the source of bleeding in the small intestine, Meckel’s diverticulum scintigraphy for detection of the ectopic gastric mucosa, radionuclide somatostatin receptor imaging for carcinoid, and radionuclide inflammation imaging. Video capsule or deep enteroscopy is the method of choice for detection of most lesions in the small intestine. Small intestine scintigraphies are only a complementary imaging method and can be successful, for example, for the detection of the bleeding site in the small intestine, ectopic gastric mucosa, carcinoid and its metastasis, or inflammation. Radionuclide scintigraphic small intestine imaging is an effective imaging modality in the localisation of small intestine lesions for patients in whom other diagnostic tests have failed to locate any lesions or are not available.

Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4–12 hours prior to 18F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients.

Cardiac positron emission tomography is a powerful, quantitative, non-invasive imaging modality, which adds valuable diagnostic and prognostic information to the clinical work-up. Myocardial perfusion and viability imaging are, as a result of continuously growing evidence, established clinical indications that may be cost-effective, due to the high diagnostic accuracy of cardiac positron emission tomography, despite high single-test costs. In the field of inflammation imaging, new indications are entering the clinical arena, which may contribute to a better diagnosis and overall patient care, as for instance in patients with cardiac sarcoidosis, prosthetic valve endocarditis and cardiac device infections. This review will discuss the individual strengths and weaknesses of cardiac positron emission tomography and, hence, the resulting clinical usefulness based on the current evidence for an individualized, patient-centered imaging approach.

The potential value of multiplexed positron emission tomography (PET) tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) for glucose metabolism imaging. These PET tracers included [18F]fluoromethylcholine ([18F]FCH) for choline metabolism imaging, (S-[11C]methyl)-D-cysteine ([11C]DMCYS) for amino acid metabolism imaging, [11C]bis(zinc(II)-dipicolylamine) ([11C]DPA-Zn2+) for apoptosis imaging, 2-(4-N-[11C]-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) for β amyloid binding imaging, and [18F]fluoride (18F−) for bone metabolism imaging. In mice with turpentine-induced inflammation mice, the biodistribution of all the tracers mentioned above at 5, 15, 30, 45, and 60 min postinjection was determined. Also, the time-course curves of the tracer uptake ratios for inflammatory thigh muscle (IM) to normal uninflammatory thigh muscle (NM), IM to blood (BL), IM to brain (BR), and IM to liver (LI) were acquired, respectively. Moreover, PET imaging with the tracers within 60 min postinjection on a clinical PET/CT scanner was also conducted. [18F]FDG and 18F− showed relatively higher uptake ratios for IM to NM, IM to BL, IM to BR, and IM to LI than [18F]FCH, [11C]DPA-Zn2+, [11C]DMCYS and [11C]PIB, which were highly consistent with the results delineated in PET images. The results demonstrate that 18F− seems to be a potential PET tracer for inflammation imaging. [18F]FCH and [11C]DMCYS, with lower accumulation in inflammatory tissue than [18F]FDG, are not good PET tracers for inflammation imaging. As a promising inflammatory tracer, the chemical structure of [11C]DPA-Zn2+ needs to be further optimized.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12574-010-0051-z., Background: Reports on ultrasound inflammation imaging with non-specific targeted microbubbles in the heart have been scarce. We investigated whether inflammation induced by myocardial ischemia-reperfusion in rats could be evaluated by ultrasound inflammation imaging with non-specific targeted microbubbles. Methods: Six rats subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion (ischemia group) and 4 rats subjected to the sham operation (sham group) were used. Ultrasound inflammation imaging was performed 4 h after reperfusion, and non-circulating signal intensity (SI), which reflects the signal derived from microbubbles phagocytosed by neutrophils in inflamed tissue, was calculated by the SI difference between the initial and subsequent imaging both in the LAD and non-LAD areas. The accumulation of neutrophils was confirmed by myeloperoxidase (MPO) staining. Results: Non-circulating SI in the LAD area was significantly greater for the ischemia group than the sham group [5.19 ± 2.19 (ischemia) vs. 0.31 ± 0.13 (sham) dB, p < 0.01]. Non-circulating SI in the LAD area was significantly higher than that in the non-LAD area when compared in the same rat of the ischemia group [5.19 ± 2.19 (LAD) vs. 0.18 ± 0.64 (non-LAD) dB, p < 0.01]. MPO-positive cells were confirmed in the LAD area of the ischemia group. Conclusion: Inflammation induced by myocardial ischemia-reperfusion in rats could be quantitatively assessed by ultrasound inflammation imaging with non-specific targeted microbubbles.

Inflammation is important at many stages of atherosclerotic plaque development. We highlight several imaging modalities that can quantify the degree of plaque inflammation noninvasively. Imaging of this type might allow testing of novel antiatherosclerosis drugs, identification of patients at risk of plaque rupture, and deeper insight into the biology of the disease. The imaging modalities are discussed in relation to their potential use in these areas.

Positron emission tomography (PET) with 18 F fluoro-deoxyglucose (FDG) is now an established functional imaging modality predominantly used in the work-up of several neoplastic diseases. It also has several neurological and cardiac applications in routine clinical practice. However, the radiopharmaceutical, 18 F-FDG, most commonly used for clinical PET studies today is also taken up by inflammatory and infectious cells and it also has a potential role in inflammation imaging in the future. Since this technique provides a map of glucose metabolism in the body, it is extremely important to understand the bio-distribution of FDG in the human body and factors that alter it. Accordingly, the technique used and several patient factors have a significant impact on the quality of images obtained. Hence, it becomes critical to perform this highly sophisticated exam with adequate patient preparation, following an accepted technique and interpret the images with the knowledge of normal and physiologic bio-distribution of FDG in several body organs and tissues. With this objective, this two-series review article will review the current principles and practice of clinical FDG-PET. The first section of this article deals mostly with basic aspects of FDG-PET and PET/CT including properties of FDG, PET instrumentation and technique and normal variants.

Background: Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue (Tc-99m-EDDA/tricine-HYNIC-tyr(3)-octreotide (Tc-99m-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjogren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment.Methods: Eighteen patients with rheumatoid arthritis and secondary Sjogren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-alpha. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of 99mTc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively.Results: All patients showed uptake of Tc-99m-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands.Conclusions: SRS using Tc-99m-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjogren's syndrome. It may also aid therapy decision-making with anti-TNF alpha antibodies in the joints but not in salivary glands.

While depiction and definition of morphological and architectural characteristics of CNS vascular disorders remains the first step of an MR analysis, emerging imaging techniques offer new functional information that might help to characterize rupture risk of CNS vascular disorders. Two main orientations are suggested by recent studies: inflammation of the vessel wall and analysis of physical constraints of blood flow using 4D flow imaging (shear parietal). This paper will focus on radiological application of 4D flow imaging and inflammation imaging, in the characterization of potential prognostic markers of CNS vascular disorders. We will review the basic technical considerations of 4D flow MRA, inflammation imaging and discuss their applications in CNS vascular disorders: aneurysms, arteriovenous malformation, dural arteriovenous fistulas. We will illustrate their potential in the development of individual rupture risk criteria in brain vascular disorders.

Combination of SPECT (single-photon emission computed tomography) with CT (computed tomography) provides the opportunity for a direct correlation of anatomic information and functional data and leads to a better localization and definition of scintigraphic findings. Besides anatomic referencing, the other advantage of CT co-registration is the attenuation correction capabilities of CT. These advantages together result in a higher specificity of imaging and a significant reduction in indeterminate findings. This chapter highlights the potential clinical applications of integrated SPECT/CT in neurology, inflammation imaging, and radiation planning and summarizes future directions for SPECT/CT in these fields.

Positron emission tomography (PET) and combined PET/CT provide powerful metabolic and anatomical information together in a single exam. This article reviews the fundamentals of PET physics, the state of the art and future directions in PET technology, and the current clinical applications of PET. The latter is quite diverse and includes oncology, cardiology, neurology, and infection and inflammation imaging, all with FDG as the tracer. Additionally, novel radiopharmeuticals are under development, many of which are target cellular processes that are more specific than glucose metabolism.

To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque.The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis.With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93).Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system.http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with Na125I by Iodogen method. Animal models were induced in the mice by intramuscular injection ofS. aureus,E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of125I-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found inS. aureusgroup and the lowest was inE. coligroup. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders.

Barium concretions are a rare complication of barium administration resulting from prolonged retention of the barium within the bowel. Indium-111 white blood cell localization studies are a sensitive and specific indicator of inflammation. Indium-111 white blood cell localization was noted

The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99mTc or 111In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform ‘evidence-based biological therapy’ of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up.

Series Editor: Zahi Fayad Molecular Imaging of Cardiovascular Disease ATVB In Focus Articles in this series: •Choudhury RP, Fisher EA. Molecular imaging in atherosclerosis, thrombosis, and vascular inflammation. Arterioscler Thromb Vasc Biol . 2009;29:983–991. •Cormode DP, Skajaa T, Fayad ZA, Mulder WJM. Nanotechnology in medical imaging: probe design and applications. Arterioscler Thromb Vasc Biol . 2009;29:992–1000. •Tang TY, Muller KH, Graves MJ, Li ZY, Walsh SR, Young V, Sadat U, Howarth SPS, Gillard JH. Iron oxide particles for atheroma imaging. Arterioscler Thromb Vasc Biol . 2009;29:1001–1008. •Rudd JHF, Hyafil F, Fayad ZA. Inflammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol . 2009;29:1009–1016. •Jaffer FA, Libby P, Weissleder R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:1017–1024. •Kraitchman DL, Bulte JWM. In vivo imaging of stem cells and beta cells using direct cell labeling and reporter gene methods. Arterioscler Thromb Vasc Biol . 2009;29:1025–1030. •Laufer EM, Winkens MHM, Narula J, Hofstra L. Imaging of cell death in atherosclerosis. Arterioscler Thromb Vasc Biol . 2009;29:1031–1038. Molecular imaging is defined today as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems, and molecular imaging agents are probes …

Determination of the localization of acute, subacute and chronic infectious foci may have important implications for the management of patients. Imaging techniques like ultrasound, CT-scanning or MRI are in most cases unable to discriminate active processes from scar tissue due to a cured infection or after surgery. In contrast, scintigraphic images are not determined morphologically, they are based on physiochemical processes in tissues. In clinical practice not only the presence of an active inflammatory process, but also the localization and the number of foci needs to be determined; scintigraphic imaging is an excellent noninvasive method of whole-body scanning. In clinical practice several radiopharmaceuticals are used to image foci of infection and inflammation. In this chapter the development and the potential of a liposome-based radiopharmaceutical for infection and inflammation imaging is described and compared with conventional radiopharmaceuticals.

In the last 15 years, the indications for inflammation imaging have changed, largely for two reasons; firstly, the number of patients with an increased predisposition to infection, especially immunocompromised patients, has increased, and secondly, developments in interventional radiology have led to an increasing number of soft tissue abscesses being diagnosed and drained by radiologists without referral for a leucocyte scan. The challenge to nuclear medicine, therefore, is now the localisation of pathology in patients referred with fever but no diagnosis, a clinical presentation called, often imprecisely, pyrexia of unknown origin (PUO).