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Positron emission tomography (PET) offers an incredible wealth of diverse research applications in vascular disease, providing a depth of molecular, functional, structural, and spatial information. Despite this, vascular PET imaging has not yet assumed the same clinical use as vascular ultrasound, CT, and MR imaging which provides information about late-onset, structural tissue changes. The current clinical utility of PET relies heavily on visual inspection and suboptimal parameters such as SUVmax; emerging applications have begun to harness the tool of whole-body PET to better understand the disease. Even still, without automation, this is a time-consuming and variable process. This review summarizes PET applications in vascular disorders, highlights emerging AI methods, and discusses the unlocked potential of AI in the clinical space.

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets., National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01 AR070148]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319, U01 AR51874 04]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; Office of Rare Diseases Research of the National Center for Advancing Translational Sciences; Imperial College, National Institute for Health Research, Biomedical Research Centre; Wellcome TrustWellcome TrustEuropean Commission [WT107881]; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_00002/4], This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health grant R01 AR070148 to A.H.S. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences. J.C.M., A.P.K., and R.M.M. acknowledge support from the Imperial College, National Institute for Health Research, Biomedical Research Centre. C.W. and G.R. acknowledge support from The Wellcome Trust (WT107881) and the Medical Research Council (MC_UU_00002/4). This work was supported by the use of study data downloaded from the dbGaP website, under dbGaP: phs000272.v1.p1, phs000431.v2.p1, phs000583.v1.p1, and phs000444.v1.p1.

Takayasu's arteritis (TAK) is a clinically heterogenous disease. Patterns of clinical presentation in TAK at diagnosis have not been well described, and a "triphasic pattern" of constitutional symptoms evolving into vascular inflammation and fibrosis has been reported but never systematically evaluated.Patients with TAK were prospectively recruited from the National Institutes of Health (NIH) and the Vasculitis Clinical Research Consortium (VCRC). Based on clinical presentation at diagnosis, patients were divided into five categories: (1) constitutional symptoms alone, (2) carotidynia, (3) other vascular-associated symptoms, (4) major ischemic event, or (5) asymptomatic. Associated clinical characteristics were evaluated in each category. Preceding symptoms were also assessed to determine the presence of a triphasic disease pattern.A total of 275 patients with TAK were included (VCRC=208; NIH=67). Similar heterogeneity of clinical presentation was identified in each cohort: constitutional symptoms (8%), carotidynia (13-15%), other vascular symptoms (43-47%), major ischemic event (28-30%), and asymptomatic (2-6%). An increased relative proportion of males was seen in patients who presented with constitutional symptoms or were asymptomatic at diagnosis (p0.01). Patients who presented with constitutional symptoms and major ischemic events were youngest at diagnosis. Patients in the asymptomatic group were oldest at diagnosis and often were not treated (p0.01). Relapse was most frequent in patients who presented with carotidynia (p0.01). A minority of patients (19%) who presented with a major ischemic event reported a triphasic pattern of disease.There are diverse clinical presentations at diagnosis in TAK. Patients do not necessarily progress sequentially through phases of disease.

OBJECTIVES: To determine the impact of imaging acquisition time on interpretation of disease activity on (18)F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time. METHODS: Patients with giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two sequential PET scans at one and two-hour time points. Images were interpreted for active vasculitis by subjective assessment, qualitative assessment, and semi-quantitative assessment. Agreement was assessed by percent agreement, Cohen’s kappa, and McNemar’s test. Multivariable logistic regression identified associations between PET activity and clinical variables. RESULTS: 79 patients (GCA=44, TAK=35) contributed 168 paired one and two-hour PET studies. A total of 94 out of 168 scans (56%) were interpreted as active at the one-hour time point, and 129 scans (77%) were interpreted as active at the two-hour time point (p

OBJECTIVE: Calcification of the coronary arteries, aorta, and branch vessels can occur in both large-vessel vasculitis (LVV) and atherosclerosis. The study objective was to determine the location and amount of vascular calcification in patients with LVV versus hyperlipidemia (HLD) and to identify risk factors associated with vascular calcification in LVV. METHODS: Patients with giant cell arteritis (GCA), Takayasu’s arteritis (TAK), and HLD underwent non-contrast computed tomography of the aorta and branch vessels. Vascular calcification in 14 specific arterial territories (4 segments of the aorta, 9 branch arteries, and the coronary arteries) was quantified throughout the large arteries by a cumulative Agatston score. Multivariate linear regression analyses were used to identify associations between traditional and disease-specific risk factors and total Agatston score. RESULTS: A total of 88 subjects, including GCA (n=29); TAK (n=22); and HLD (n=37), participated.Prevalence of vascular calcification in the aorta and branch vessels significantly differed in the coronary arteries (HLD=67%, GCA=35%, TAK=9%, p

Takayasu arteritis is a large-vessel vasculitis that often results in pulselessness due to fibrotic stenoses. Whereas minor calcification is sometimes seen with Takayasu arteritis, it rarely causes stenosis. Extensive calcification resulting in malperfusion is exceedingly rare and has been attributed to disorders in calcium trafficking in a chronic inflammatory state. We report an unusual case of rapidly progressive and extensive aortic calcification in the setting of Takayasu arteritis.

Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 to October 2010. A PubMed database search of the medical literature was performed for articles published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49-year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a postrecovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV.

The idiopathic vasculitides are a group of rare, systemic diseases involving inflammation of arteries and other tissue with resulting organ- and life-threatening disease courses. The different forms of idiopathic vasculitis are typically classified based upon the predominant size of the arteries affected in each condition, including small vessel vasculitis [e.g. granulomatosis with polyangiitis (GPA, Wegener’s)]; medium vessel vasculitis [e.g. polyarteritis nodosa (PAN)]; and large vessel vasculitis [e.g. giant cell arteritis (GCA)]. Although patients with each type of vasculitis manage disease-specific aspects of illness, there are substantial disease and treatment burdens common to patients with vasculitis. For each type of idiopathic vasculitis, the disease course is often chronic, relapse is common and unpredictable, organ and tissue damage can accrue over time, new symptoms can occur late into the disease course, and treatment is often associated with toxicity and serious side effects. Illness perceptions, also called illness representations, are the organized beliefs that patients have about their illness. Based upon Leventhal’s Self Regulatory Model (1), it is theorized that patients consistently structure illness perceptions into common and measurable dimensions. Such dimensions include: beliefs about the symptoms that belong to the disease; the perception of the course the disease has and will have; beliefs on the impact of the illness on functioning and emotional well-being; beliefs on the degree of personal and treatment-based controllability of the disease; and the overall understanding of the condition. Illness perceptions have been found to be important determinants of health-related behavior and have been associated with important outcomes, such as treatment adherence and functional recovery, across a spectrum of diseases (2). Despite the substantial burdens of disease and treatment patients with vasculitis incur, illness perceptions have not been comprehensively assessed in systemic vasculitis. Understanding illness perceptions of patients with diverse forms of vasculitis may provide insight into the similarities and differences in the cognitive representations of disease and, as seen in other chronic diseases, may help explain important health-related behaviors and outcomes. Fatigue is a highly prevalent and an increasingly-recognized important manifestation of vasculitis, yet the mechanisms underlying fatigue are poorly understood. One study reported a finding of fatigue with a significant effect on life in approximately half of patients with vasculitis (3). In another study, fatigue was the most commonly reported symptom in a cohort of patients with vasculitis and was a principal contributor to impaired quality of life (4). As seen in other chronic diseases (5), fatigue is not well correlated with disease duration or with physician-derived measures of disease activity in vasculitis (3), suggesting that fatigue may be driven by psycho-social measures in response to disease. Further, illness perceptions may be associated with fatigue in vasculitis as has been demonstrated in other diseases (6). Interestingly, fatigue is considered one of the most important disease burdens by patients with vasculitis and is often rated as more burdensome than most manifestations of vasculitis that are associated with organ damage (7). This finding highlights potential different “models of illness” between patients with vasculitis and health professionals and suggests the importance of understanding illness from patients’ perspectives. The objectives of this study were 1) to compare illness perceptions of patients with a variety of forms of vasculitis; 2) to determine clinical and demographic variables associated with “negative illness perceptions” for vasculitis, defined as less-desirable perceptions about illness; and 3) to assess the association between illness perceptions and fatigue in vasculitis.