The utility of PET imaging in depression.

This educational review article aims to discuss growing evidence from PET studies in the diagnosis and treatment of depression. PET has been used in depression to explore the neurotransmitters involved, the alterations in neuroreceptors, non-neuroreceptor targets (e.g., microglia and astrocytes), the severity and duration of the disease, the pharmacodynamics of various antidepressants, and neurobiological mechanisms of non-pharmacological therapies like psychotherapy, electroconvulsive therapy, and deep brain stimulation therapy, by showing changes in brain metabolism and receptor and non-receptor targets. Studies have revealed alterations in neurotransmitter systems such as serotonin, dopamine, GABA, and glutamate, which are linked to the pathophysiology of depression. Overall, PET imaging has furthered the neurobiological understanding of depression. Despite these advancements, PET findings have not yet led to significant changes in evidence-based practices. Addressing the reasons behind inconsistencies in PET imaging results, conducting large sample size studies with a more standardized methodological approach, and investigating further the genetic and neurobiological aspects of depression may better leverage PET imaging in future studies.

[18F]FDG PET/CT for identifying the causes of fever of unknown origin (FUO).

Fever of unknown origin (FUO) continues to be a challenging diagnosis in clinical medicine. It has more than 200 known causes, including infections, autoimmune diseases, neoplasia, and other miscellaneous disorders. Despite the development of a wide range of diagnostic tools, a specific diagnostic algorithm for FUO is not yet available. However, [18F]FDG PET/CT, which yields information on cellular metabolism, in addition to details of organ anatomy, has been shown to be successful in the FUO investigation. This study highlights the uses of [18F]FDG PET/CT in diagnosing various causes of FUO. [18F]FDG PET/CT has been increasingly used to detect septic infections, sterile inflammatory processes, and malignancies, occupying a significant portion of the known causes of FUO. It has led to a more definitive identification of the etiology of FUO and accurate clinical management. However, more in-depth studies are crucial to understanding if [18F]FDG PET/CT can be used in the work-up of FUO.

Role of PET/CT in diagnosing and monitoring disease activity in rheumatoid arthritis: a review.

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA.

Imaging of Rotator Cuff Calcific Tendinopathy Using 18 F-NaF and 18 F-FDG PET/CT.

ABSTRACT: Calcific tendinopathy is a common condition of the shoulder caused by the inflammation and deposition of hydroxyapatite crystals in the rotator cuff tendons. PET tracers capturing the molecular changes associated with the crystal deposition of calcific tendinopathy remain underinvestigated. In this report, we present calcified tendinopathy of the infraspinatus tendon demonstrating both 18 F-NaF and 18 F-FDG focal uptake in a 61-year-old woman.

Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications.

We review the rationale, methodology, and clinical utility of quantitative [18F] sodium fluoride ([18F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (Ki, also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [18F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [18F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique.

Simultaneous Uptake of 18 F-NaF and 18 F-FDG by Bladder and Prostate Calculi.

ABSTRACT: Calcification and formation of calculi in the genitourinary system such as the bladder, kidney, and prostate are common processes of aging. Despite being in different parts of the body, these calculi can share risk factors; for instance, bladder and prostate calculi are seen in older men with benign prostatic hyperplasia. There have been increasing reports of detection of calculi using PET tracers such as 18 F-NaF and 18 F-FDG, suggesting their role for detection of extraosseous calcification. In this report, we present simultaneous detection of bladder and prostate calculi with both 18 F-NaF and 18 F-FDG avidity in a 74-year-old man with multiple myeloma.

Novel technique of detecting inflammatory and osseous changes in the glenohumeral joint associated with patient age and weight using FDG- and NaF-PET imaging.

OBJECTIVE: The glenohumeral (GH) joint is a classic ball-and-socket joint of the shoulder subject to various pathologies including osteoarthritis (OA). Degenerative changes of the OA evident on traditional imaging are proceeded by molecular changes, which if detected early could enhance disease prevention and treatment. In this study, we use 18F-FluoroDeoxyGlucose (FDG) and 18F-sodium-fluoride (NaF)-PET/CT to investigate the effects limb laterality, age, and BMI on the inflammation and bone turnover of the GH shoulder joint. METHODS: FDG and NaF-PET/CT scans of 41 females (mean age of 43.9 ± 14.2 years) and 45 males (mean age of 44.5 ± 13.8 years) were analyzed with a semi-quantitative technique based on predefined region of interest. RESULTS: There was greater FDG uptake in the left side of the GH joint compared to the right in both females (left: 0.79 ± 0.17, right: 0.71 ± 0.2; P < 0.0001) and males (left: 0.76 ± 0.19, right: 0.57 ± 0.18; P < 0.0001). We also observed a strong positive association between BMI and FDG uptakes in females (left: P < 0.0001, r = 0.71, right: P < 0.0001, r = 0.58) and males (left: P < 0.0001, r = 0.56, right: P < 0.0001, r = 0.64). Association between BMI and NaF uptake were found in males as well (left: P = 0.004, r = 0.42, right: P = 0.02, r = 0.35). CONCLUSION: Our study demonstrates the varying effect of limb laterality and BMI on FDG and NaF uptake at the GH joint. Adoption of molecular imaging will require future studies that correlate tracer uptake with relevant medical and illness history as well as degenerative change evident on traditional imaging.

Update on Positron Emission Tomography/Magnetic Resonance Imaging: Cancer and Inflammation Imaging in the Clinic.

Hybrid PET/MRI is highly valuable, having made significant strides in overcoming technical challenges and offering unique advantages such as reduced radiation, precise data coregistration, and motion correction. Growing evidence highlights the value of PET/MRI in broad clinical aspects, including inflammatory and oncological imaging in adults, pregnant women, and pediatrics, potentially surpassing PET/CT. This newly integrated solution may be preferred over PET/CT in many clinical conditions. However, further technological advancements are required to facilitate its broader adoption as a routine diagnostic modality.

Neurological and Psychiatric Manifestations of Long COVID-19 and Their [18F]FDG PET Findings: A Review.

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

18F-FDG and 18F-NaF PET/CT Global Assessment of Large Joint Inflammation and Bone Turnover in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) involves chronic inflammation of synovial joints, causing pain, stiffness, and limited mobility. 18F-sodium fluoride (NaF) is a PET tracer whose uptake reflects bone turnover, while 18F-fludeoxyglucose (FDG) shows glucose metabolism and can serve as a marker for inflammation. The aim of this study is to determine the feasibility of calculating the FDG and NaF mean standardized uptake value (SUVmean) in the knee joint, hip joint, and sacroiliac (SI) joint of RA patients and to determine their association with patient characteristics. Prospective FDG-PET/CT as well as NaF-PET/CT imaging was performed on 18 RA patients. The global SUVmean was calculated on FDG-PET/CT and NaF-PET/CT images using a semiautomated CT-based method of segmentation. FDG and NaF uptake were found to be significantly correlated in the knee (r = 0.77, p < 0.001), but not in the hip and SI joints. In the knee, both NaF SUVmean and FDG SUVmean were significantly correlated with body weight, BMI, leptin, and sclerostin levels (p < 0.05). NaF SUVmean was significantly positively correlated with BMI and leptin for both the hip and SI joints (p < 0.05). No significant correlation was observed between either PET parameter and age, height, erythrocyte sedimentation rate (ESR), and interleukins 1 and 6 (IL-1 and IL-6); however, FDG was correlated with inflammatory markers such as C-reactive protein (CRP) and patient global visual analogue scale (VAS-PtGlobal) in some joints. In this study, both FDG and NaF uptake were quantified in large joints of patients with RA using CT segmentation. NaF and FDG SUVmean were correlated with clinical variables related to body weight and adiposity, suggesting that degenerative joint disease may play a larger role in influencing the uptake of these tracers in large joints than RA disease activity. FDG and its correlation with markers of inflammation such as CRP and VAS-PtGlobal suggests that this tracer may serve as a more specific marker for RA disease activity than NaF. Larger prospective and longitudinal data are necessary to gain a better understanding of the roles of FDG and NaF in evaluating RA joint activity in these joints.

Stroke and molecular imaging: a focus on FDG-PET.

Stroke is the leading cause of disability worldwide, the second most common cause of dementia and the third leading cause of death. Though the etiology of stroke has been explored extensively, there remains open questions in the scientific and clinical study of stroke. Traditional imaging techniques, such as magnetic resonance imaging and computed tomography, have been applied extensively and remain mainstays in clinical practice. Nevertheless, positron emission tomography has proven to be a powerful molecular imaging tool in exploring the scientific aspects of neurological disease, and stroke remains an area of great interest. This review article examines the role of positron emission tomography in the study of stroke including its contributions to elaborating related pathophysiology and delving into possible clinical applications.

The value of FDG-PET/CT imaging in the assessment, monitoring, and management of COVID-19.

The pathogenesis of Coronavirus Disease 2019 (COVID-19) involves cytokine-driven recruitment and accumulation of inflammatory cells at sites of infection. These activated neutrophils, monocytes, and effector T cells are highly glycolytic and thus appear as [18]F-labeled fluorodeoxyglucose (FDG) avid sites on positron emission tomography (PET) imaging. FDG-PET-computed tomography (FDG-PET/CT) is a highly sensitive modality for the detection, monitoring, and assessing response related to COVID-19 disease activity that holds significant clinical relevance. To date, concerns over cost, access, and undue radiation exposure have limited the use of FDG-PET/CT in COVID-19 to a small number of individuals where PET-based interventions were already indicated. In this review, we summarize the existing literature on the use of FDG-PET in the detection and monitoring of COVID-19 with particular focus on several areas of clinical relevance that warrant future research: (1) incidental early detection of subclinical COVID-19 in patients who have undergone FDG-PET for other underlying diseases, (2) standardized quantitative assessment of COVID-19 disease burden at specific points in time, and (3) analysis of FDG-PET/CT data leading to better characterization of COVID-19 pathogenesis. Employing FDG-PET/CT for these purposes may allow for the earliest detection of COVID-19-associated venous thromboembolism (VTE), standardized monitoring of disease progression and response to treatment, and better characterization of the acute and chronic complications of this disease.

The role of 18F-FDG PET/CT in primary cutaneous lymphoma: an educational review.

INTRODUCTION: Primary cutaneous lymphoma (PCL) is a cutaneous non-Hodgkin's lymphoma that originates in the skin and lacks extracutaneous spread upon initial diagnosis. The clinical management of secondary cutaneous lymphomas is different from that of PCLs, and earlier detection is associated with better prognosis. Accurate staging is necessary to determine the extent of disease and to choose the appropriate treatment. The aim of this review is to investigate the current and potential roles of 18F- fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the diagnosis, staging, and monitoring of PCLs. METHODS: A focused review of the scientific literature was performed using inclusion criteria to filter results pertaining to human clinical studies performed between 2015 and 2021 that analyzed cutaneous PCL lesions on 18F PET/CT imaging. RESULTS & CONCLUSION: A review of 9 clinical studies published after 2015 concluded that 18F-FDG PET/CT is highly sensitive and specific for aggressive PCLs and proved valuable for identifying extracutaneous disease. These studies found 18F-FDG PET/CT highly useful for guiding lymph node biopsy and that imaging results influenced therapeutic decision in many cases. These studies also predominantly concluded that 18F-FDG PET/CT is more sensitive than computed tomography (CT) alone for detection of subcutaneous PCL lesions. Routine revision of nonattenuation-corrected (NAC) PET images may improve the sensitivity of 18F-FDG PET/CT for detection of indolent cutaneous lesions and may expand the potential uses of 18F-FDG PET/CT in the clinic. Furthermore, calculating a global disease score from 18F-FDG PET/CT at every follow-up visit may simplify assessment of disease progression in the early clinical stages, as well as predict the prognosis of disease in patients with PCL.

Is Imaging Bacteria with PET a Realistic Option or an Illusion?

The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

The Utility of 18 F-NaF-Positron Emission Tomography/Computed Tomography in Measuring the Metabolic Activity of the Aging Spine : Implications for Osteoporosis.

STUDY DESIGN: Cross-sectional; observational. OBJECTIVES: To determine whether sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) can be used to monitor decreased bone turnover with aging in the spine. BACKGROUND: Osteoporosis is characterized by structural changes in the bone such as decreased bone mineral density leading to an increased risk for fractures. An imaging modality capable of identifying molecular changes that precede these structural changes could be critical for the early diagnosis and monitoring of osteoporosis and other metabolic bone disorders. MATERIALS AND METHODS: The potential of 18 F-sodium fluoride (NaF)-PET/CT in detecting changes in bone turnover associated with aging was examined in the lumbar spine of 88 healthy volunteers (43 females, 45 males; mean age 44.6 yr). Regions of interest equal to the trabecular body of the L1 to L4 vertebrae were used to calculate the mean standardized uptake value (SUVmean) and average Hounsfield unit (HU) values. Receiver-operating characteristic curve analysis with an area under the curve using the Wilson/Brown method was generated to assess the value of NaF uptake (SUVmean) in predicting osteoporosis as defined by HU-threshold values. To determine the correlation among global SUVmean, mean HU values, and age, the Spearman correlation test was performed on images acquired at 90 minutes postinjection. RESULTS: There was a significant negative correlation between NaF SUVmean and age in females ( P < 0.0001, r = -0.59), and a weaker, but also significant correlation in males ( P = 0.03, r = -0.32). In females only, there was a significant correlation between NaF uptake and age at all acquisition time points. Measured NaF uptake increased by 10% to 15% with acquisition time in both sexes, from 45 to 90 minutes and from 90 to 180 minutes. CONCLUSIONS: NaF-PET/CT detects decreased vertebral bone turnover with aging, particularly in females. Measured NaF uptake increased with PET acquisition time after tracer injection, which must be considered in follow-up studies monitoring disease development and treatment effects.

A prospective 18 F-fluorodeoxyglucose positron emission tomography/computed tomography study of the neurometabolic effects in cocaine use and HIV infection.

OBJECTIVES: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in cocaine users with HIV infection. DESIGN: Sixty-three participants were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV-) individuals. Each group was further split into cocaine users (CO+) and non-cocaine users (CO-). Of the HIV+, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18 F-FDG-PET and low dose CT scans were performed on all participants. METHODS: Brain glucose metabolism was evaluated by 18 F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 min after injection. ROVER software was used for image analysis and regions of interest masks were applied via an adaptive threshold system. ANOVA tests and t -tests were performed to assess the respective differences between the four groups. RESULTS: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV-/CO- group (group D) showed the highest; the HIV+/CO- and HIV-/CO+ groups (groups B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum. CONCLUSION: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18 F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18 F-FDG uptake.

NaF-PET Imaging of Atherosclerosis Burden.

The method of 18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) of atherosclerosis was introduced 12 years ago. This approach is particularly interesting because it demonstrates microcalcification as an incipient sign of atherosclerosis before the development of arterial wall macrocalcification detectable by CT. However, this method has not yet found its place in the clinical routine. The more exact association between NaF uptake and future arterial calcification is not fully understood, and it remains unclear to what extent NaF-PET may replace or significantly improve clinical cardiovascular risk scoring. The first 10 years of publications in the field were characterized by heterogeneity at multiple levels, and it is not clear how the method may contribute to triage and management of patients with atherosclerosis, including monitoring effects of anti-atherosclerosis intervention. The present review summarizes findings from the recent 2¾ years including the ability of NaF-PET imaging to assess disease progress and evaluate response to treatment. Despite valuable new information, pertinent questions remain unanswered, not least due to a pronounced lack of standardization within the field and of well-designed long-term studies illuminating the natural history of atherosclerosis and effects of intervention.

Atherosclerosis Imaging: Positron Emission Tomography.

Assessment of molecular changes by PET has introduced a new paradigm in atherosclerosis imaging, which has traditionally relied on anatomic changes visualized by conventional angiography or computed tomography. The use of 18F-fluorodeoxyglucose (FDG) to identify atherosclerotic changes in the vessel wall was first described more than 2 decades ago. Since then, PET tracers targeting macrophage activity, neoangiogenesis, smooth muscle activity, and other aspects of atherogenic changes have been proposed. The evolving roles of PET tracers including frontrunners FDG and 18F-sodium fluoride, which show arterial wall inflammation and microcalcification, respectively, are discussed.

Monitoring the Progression of a Calcifying Uterine Leiomyoma: Detection Using 18 F-NaF-PET/CT.

ABSTRACT: Uterine leiomyomas (fibroids) are common and benign hormone-dependent tumors of the uterus, often coinciding with atypical menstrual bleeding, urinary incontinence, and lower abdominal pain. The PET tracer 18 F-NaF has been used to study metastatic and benign bone disorders, but its potential use in investigating the molecular alterations of extraosseous tissues and tumors has not been fully investigated. In this report, we present a calcifying uterine leiomyoma incidentally detected on 18 F-NaF PET/CT scans in a postmenopausal 61-year-old woman and follow-up image 2 years after, highlighting the potential of 18 F-NaF in monitoring both the molecular and structural progression of uterine leiomyomas.

Feasibility of Global Assessment of Bone Metastases in Prostate Cancer with 18F-Sodium Fluoride-PET/Computed Tomography.

18F-sodium fluoride (NaF) PET/computed tomography (CT) allows detection of bone metastases in patients with prostate cancer (PCa). The aim of this study was to test the feasibility of assessing global metastatic bone disease in patients with PCa by using a threshold-based PET segmentation technique. This retrospective analysis was performed in 32 patients with PCa with known bone metastases who underwent NaF-PET/CT imaging. An adaptive contrast-oriented thresholding technique was used to segment NaF avid lesions. The mean metabolic volumetric product (MVPmean), partial volume-corrected MVPmean (cMVPmean), and metabolically active volume (MAV) were calculated. Lesional values were summed within each patient to obtain the global PET disease burden. Pearson correlation analysis was used to assess the associations between global NaF-PET/CT metrics and clinical biomarkers of metastatic disease activity. Global MVPmean, cMVPmean, and MAV were significantly correlated with alkaline phosphatase (ALP) levels (p < 0.05). No correlation was observed between global NaF-PET/CT measures and prostate-specific antigen (PSA) levels. Global assessment is a feasible method to quantify metastatic bone disease activity in patients with PCa. Convergent validity was supported by demonstrating a significant correlation between NaF-PET/CT parameters and blood ALP levels.