Improved Diagnostic Accuracy for Polymyalgia Rheumatica using FDG-PET/CT with Clinical Diagnosis or 2012 ACR/EULAR Classification Criteria.

PURPOSE: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR. METHODS: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively. RESULTS: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score. CONCLUSION: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.

Multimodality imaging to assess diagnosis and evaluate complications of large vesselarteritis.

Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischemia, and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for the diagnosis and identification of vascular complications in the field of large vessel vasculitis.

Salivary gland 18F-FDG-PET/CT uptake patterns in Sjögren's syndrome and giant cell arteritis patients.

OBJECTIVES: Wide variety in salivary gland 18F-FDG-uptake is observed in the general population. A general consensus about the usefulness of 18F-FDG-PET/CT to detect salivary gland inflammatory conditions, such as in primary Sjögren's syndrome (pSS), is not yet clear. This study aimed to investigate whether there are differences in uptake of 18F-FDG in salivary glands among two autoimmune groups [pSS, giant cell arteritis (GCA)] and a non-autoimmune group (lung cancer). METHODS: PSS patients aged ≥50 years who underwent 18F-FDG-PET/CT were included and age-matched with GCA patients and a non-autoimmune control group (lung cancer patients). Scans were visually evaluated and quantitative analysis was performed by measuring standardised uptake values (SUV) within salivary glands and lacrimal glands. For GCA patients, arteries in the vicinity of the parotid and submandibular gland were assessed for positivity. RESULTS: PSS patients did not show increased 18F-FDG-uptake in the parotid or submandibular gland, compared to the other two groups. For the tubarial gland, significantly higher SUVmax was found in the pSS patient group. Interestingly, GCA patients had significantly higher SUVmax in the submandibular gland than the other two groups. Visual 18F-FDG-positivity of cranial arteries related to the parotid and submandibular glands was associated with significantly higher SUVmax in salivary glands of GCA patients. CONCLUSIONS: Although 18F-FDG-uptake was not increased in parotid and submandibular glands of pSS patients, increased 18F-FDG-uptake in tubarial glands of pSS patients might indicate a role for these glands in pSS. Furthermore, parotid and submandibular glands may be affected by local vasculitis in GCA.

Plasma Pyruvate Kinase M2 as a marker of vascular inflammation in giant cell arteritis.

OBJECTIVES: GCA is a large vessel vasculitis in which metabolically active immune cells play an important role. GCA diagnosis is based on CRP/ESR and temporal artery biopsies (TABs), in combination with 18F-fluorodeoxyglucose ([18F]FDG)-PET/CT relying on enhanced glucose uptake by glycolytic macrophages. Here, we studied circulating Pyruvate Kinase M2 (PKM2), a glycolytic enzyme, as a possible systemic marker of vessel wall inflammation in GCA. METHODS: Immunohistochemical detection of PKM2 was performed on inflamed (n = 12) and non-inflamed (n = 4) TABs from GCA patients and non-GCA (n = 9) patients. Dimeric PKM2 levels were assessed in plasma of GCA patients (n = 44), age-matched healthy controls (n = 41), metastatic melanoma patients (n = 7) and infection controls (n = 11). CRP, ESR and macrophage markers calprotectin and YKL-40 were correlated with plasma PKM2 levels. To detect the cellular source of plasma PKM2 in tissue, double IF staining was performed on inflamed GCA TABs. [18F]FDG-PET scans of 23 GCA patients were analysed and maximum standard uptake values and target to background ratios were calculated. RESULTS: PKM2 is abundantly expressed in TABs of GCA patients. Dimeric PKM2 plasma levels were elevated in GCA and correlated with CRP, ESR, calprotectin and YKL-40 levels. Elevated plasma PKM2 levels were downmodulated by glucocorticoid treatment. PKM2 was detected in both macrophages and T cells at the site of vascular inflammation. Circulating PKM2 levels correlated with average target to background ratios PET scores. CONCLUSION: Elevated plasma PKM2 levels reflect active vessel inflammation in GCA and may assist in disease diagnosis and in disease monitoring.

Altered Plasma Levels and Tissue Expression of Fibroblast Activation Protein Alpha in Giant Cell Arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease that promotes both inflammation and fibrosis. Here, we investigated the plasma levels and vascular expression of FAP in GCA. METHODS: Plasma FAP levels were measured with enzyme-linked immunosorbent assay in treatment-naive patients with GCA (n = 60) and polymyalgia rheumatica (PMR) (n = 63) compared with age- and sex-matched healthy controls (HCs) (n = 42) and during follow-up, including treatment-free remission (TFR). Inflamed temporal artery biopsies (TABs) of patients with GCA (n = 9), noninflamed TABs (n = 14), and aorta samples from GCA-related (n = 9) and atherosclerosis-related aneurysm (n = 11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts (CD90), macrophages (CD68/CD206/folate receptor beta), vascular smooth muscle cells (desmin), myofibroblasts (α-smooth muscle actin), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). RESULTS: Baseline plasma FAP levels were significantly lower in patients with GCA compared with patients with PMR and HCs and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months on remission in patients with GCA and gradually increased to the level of HCs in TFR. FAP expression was increased in inflamed TABs and aorta of patients with GCA compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Some of the FAP+ fibroblasts expressed IL-6 and MMP-9. CONCLUSION: FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as a target for imaging and therapeutic intervention.

Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends.

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides.

Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.

BACKGROUND: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive. PURPOSE: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease. METHODS: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[18F]FDG and Na[18F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. RESULTS: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively). CONCLUSIONS: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring.

Role of 18F-FDG PET/CT in Large Vessel Vasculitis and Polymyalgia Rheumatica.

Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels, including large vessel vasculitis (LVV) and medium-sized vessel vasculitis such as giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA frequently overlaps with polymyalgia rheumatica (PMR), a rheumatic inflammatory condition affecting bursae, tendons or tendon sheaths, and joints. 18F-FDG PET/CT plays an important role in the diagnostic work-up of GCA, PMR, and TAK and is increasingly used to monitor treatment response. This continuing education article provides up-to-date guidance on the role of 18F-FDG PET/CT in patients with LVV, medium-sized vessel vasculitis, and PMR. It provides a general introduction on the clinical presentation and challenges in the diagnostic work-up of LVV and medium-sized vessel vasculitis, with a focus on the 2 major LVV subtypes: GCA, including PMR, and TAK. Next, practice points to perform and interpret the results of 18F-FDG PET/CT are described in line with the published procedure recommendations. Furthermore, the diagnostic performance and its role for treatment monitoring are discussed, taking into account recent international recommendations for the use of imaging in LVV and medium-sized vessel vasculitis in clinical practice. This is illustrated by several clinically representative PET/CT scan examples. Lastly, knowledge of limitations and pitfalls is essential to understand the role of 18F-FDG PET/CT in LVV, medium-sized vessel vasculitis, and PMR. Challenges and opportunities, as well as future research and conclusions, are highlighted. Learning objectives provide up-to-date guidance for the role of 18F-FDG PET/CT in patients with suspected LVV, medium-sized vessel vasculitis, and PMR.

Comparing Diagnostic Performance of Short and Long [18F]FDG-PET Acquisition Times in Giant Cell Arteritis.

(1) Background: In giant cell arteritis (GCA), the assessment of cranial arteries using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) combined with low-dose computed tomography (CT) may be challenging due to low image quality. This study aimed to investigate the effect of prolonged acquisition time on the diagnostic performance of [18F]FDG PET/CT in GCA. (2) Methods: Patients with suspected GCA underwent [18F]FDG-PET imaging with a short acquisition time (SAT) and long acquisition time (LAT). Two nuclear medicine physicians (NMPs) reported the presence or absence of GCA according to the overall image impression (gestalt) and total vascular score (TVS) of the cranial arteries. Inter-observer agreement and intra-observer agreement were assessed. (3) Results: In total, 38 patients were included, of whom 20 were diagnosed with GCA and 18 were without it. Sensitivity and specificity for GCA on SAT scans were 80% and 72%, respectively, for the first NMP, and 55% and 89% for the second NMP. On the LAT scans, these values were 65% and 83%, and 75% and 83%, respectively. When using the TVS, LAT scans showed especially increased specificity (94% for both NMPs). Observer agreement was higher on the LAT scans compared with that on the SAT scan. (4) Conclusions: LAT combined with the use of the TVS may decrease the number of false-positive assessments of [18F]FDG PET/CT. Additionally, LAT and TVS may increase both inter and intra-observer agreement.

The clinical value of quantitative cardiovascular molecular imaging: a step towards precision medicine.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and have an increasing impact on society. Precision medicine, in which optimal care is identified for an individual or a group of individuals rather than for the average population, might provide significant health benefits for this patient group and decrease CVD morbidity and mortality. Molecular imaging provides the opportunity to assess biological processes in individuals in addition to anatomical context provided by other imaging modalities and could prove to be essential in the implementation of precision medicine in CVD. New developments in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) systems, combined with rapid innovations in promising and specific radiopharmaceuticals, provide an impressive improvement of diagnostic accuracy and therapy evaluation. This may result in improved health outcomes in CVD patients, thereby reducing societal impact. Furthermore, recent technical advances have led to new possibilities for accurate image quantification, dynamic imaging, and quantification of radiotracer kinetics. This potentially allows for better evaluation of disease activity over time and treatment response monitoring. However, the clinical implementation of these new methods has been slow. This review describes the recent advances in molecular imaging and the clinical value of quantitative PET and SPECT in various fields in cardiovascular molecular imaging, such as atherosclerosis, myocardial perfusion and ischemia, infiltrative cardiomyopathies, systemic vascular diseases, and infectious cardiovascular diseases. Moreover, the challenges that need to be overcome to achieve clinical translation are addressed, and future directions are provided.

Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40-60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR.

A Case of Clinical Uncertainty Solved: Giant Cell Arteritis with Polymyalgia Rheumatica Swiftly Diagnosed with Long Axial Field of View PET.

The clinical presentation of giant cell arteritis (GCA) is often nonspecific. Differentiating GCA from infectious, malignant, or other autoimmune pathology based on signs, symptoms, and laboratory parameters may therefore be difficult. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging is an established tool in the diagnostic workup of GCA. An advantage of 18F-FDG-PET/CT is its ability to assist in the differential diagnosis by being able to demonstrate infection, inflammation, and malignancy when used in conjunction with clinical and laboratory data. Downsides to the use of 18F-FDG-PET/CT include its relatively low spatial resolution, associated radiation exposure, and the relatively long duration of imaging, causing limited availability and patient inconvenience. The advent of long axial field-of-view (LAFOV) PET/CT systems allows for PET imaging at a reduced imaging time or reduced tracer dose while maintaining high image quality. Here, we provide the first reported case of a patient with GCA and polymyalgia rheumatica (PMR) diagnosed using LAFOV PET/CT imaging. The patient presented in this case report had already been experiencing nonspecific symptoms for several years for which no cause was found. Lab investigations showed increased inflammatory parameters as well as persistent anemia. 18F-FDG LAFOV PET/CT attained high-quality images with clear signs of GCA and PMR even at 1 min of scan duration.

18F-BMS986192 PET Imaging of PD-L1 in Metastatic Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors: A Pilot Study.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) frequently induces tumor response in metastatic melanoma patients. However, tumor response often takes months and may be heterogeneous. Consequently, additional local treatment for nonresponsive metastases may be needed, especially in the case of brain metastases. Noninvasive imaging may allow the characterization of (brain) metastases to predict response. This pilot study uses 18F-BMS986192 PET for PD-L1 expression to explore the variability in metastatic tracer uptake and its relation to tumor response, with a special focus on brain metastases. Methods: Metastatic melanoma patients underwent whole-body 18F-BMS986192 PET/CT scanning before and 6 wk after starting ICI therapy. 18F-BMS986192 uptake was measured in healthy tissues, organs, and tumor lesions. Tumor response was evaluated at 12 wk using CT of the thorax/abdomen and MRI of the brain. RECIST, version 1.1, was used to define therapy response per patient. Response per lesion was measured by the percentage change in lesion diameter. Toxicity was assessed according to Common Terminology Criteria for Adverse Events, version 4.0. Results: Baseline 18F-BMS986192 PET/CT was performed in 8 patients, with follow-up scans in 4 patients. The highest tracer uptake was observed in the spleen, bone marrow, kidneys, and liver. Tracer uptake in tumor lesions was heterogeneous. In total, 42 tumor lesions were identified at baseline, with most lesions in the lungs (n = 21) and brain (n = 14). Tracer uptake was similar between tumor locations. 18F-BMS986192 uptake in lesions at baseline, corrected for blood-pool activity, was negatively correlated with the change lesion diameter at response evaluation (r = -0.49, P = 0.005), both in intra- and extracerebral lesions. Receiver-operating-characteristic analysis demonstrated that 18F-BMS986192 uptake can discriminate between responding and nonresponding lesions with an area under the curve of 0.82. At the follow-up scan, an increased 18F-BMS986192 uptake compared with baseline scan was correlated with an increased lesion diameter at response evaluation. In the follow-up 18F-BMS986192 PET scan of 2 patients, ICI-related toxicity (thyroiditis and colitis) was detected. Conclusion: In this pilot study, 18F-BMS986192 PET showed heterogeneous uptake in intra- and extracerebral metastatic lesions in melanoma patients. Baseline 18F-BMS986192 uptake was able to predict an ICI treatment-induced reduction in lesion volume, whereas the follow-up PET scan allowed the detection of treatment-induced toxicity.

Limitations and Pitfalls of FDG-PET/CT in Infection and Inflammation.

White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted.

A Review on the Value of Imaging in Differentiating between Large Vessel Vasculitis and Atherosclerosis.

Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk assessment, and tailored treatment at a patient level. This paper reviews the current evidence of ultrasound (US), 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) to distinguish LVV from atherosclerosis. In this review, we identified a total of eight studies comparing LVV patients to atherosclerosis patients using imaging-four US studies, two FDG-PET studies, and two CT studies. The included studies mostly applied different methodologies and outcome parameters to investigate vessel wall inflammation. This review reports the currently available evidence and provides recommendations on further methodological standardization methods and future directions for research.

Toward Reliable Uptake Metrics in Large Vessel Vasculitis Studies.

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = -0.25 to -0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.

Visual and semiquantitative assessment of cranial artery inflammation with FDG-PET/CT in giant cell arteritis.

BACKGROUND AND AIM: Assessing cranial artery inflammation plays an important role in the diagnosis of cranial giant cell arteritis (C-GCA). However, current diagnostic tests are limited. The use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging is an established tool for assessing large vessel inflammation but is currently not used for assessment of the cranial arteries. This study aimed to evaluate the accuracy of FDG-PET/CT in the diagnosis of biopsy proven C-GCA and its relation to clinical presentation. METHODS: This retrospective case control study included temporal artery biopsy (TAB) positive C-GCA patients and age- and sex-matched controls. FDG-PET/CT scans were performed according to EANM/EARL guidelines, visually assessed by an experienced nuclear medicine physician, and semiquantitatively assessed using the maximum standardised uptake value (SUVmax). The visual and semiquantitative assessments were performed on the temporal arteries, maxillary arteries, vertebral arteries, and occipital arteries. Clinical signs and symptoms were scored for comparison. RESULTS: A total of 24 C-GCA patients and 24 controls were included in the study. Visual analysis revealed an 83% sensitivity and a 75% specificity. Receiver operating characteristic (ROC) analysis of the semiquantitative assessment revealed a 79% sensitivity and a 92% specificity when measuring SUVmax in the cranial arteries. Visual and semiquantitative assessments showed moderate agreement (Fleiss kappa 0.55). There was a positive correlation between the number of cranial symptoms and the SUVmax in the vertebral artery. CONCLUSION: FDG-PET/CT can reliably diagnose C-GCA by assessing cranial artery inflammation using SUVmax. Extending the use of FDG-PET/CT to include assessment of the cranial arteries may improve its diagnostic value in GCA and provide a suitable alternative to TAB. Moderate agreement between visual and semiquantitative assessment methods suggest diagnostic accuracy may be improved by further standardisation.