Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography.

The aim of this study was to assess coronary artery and aortic calcification in healthy controls, angina pectoris patients, and prostate cancer patients using 18F-sodium fluoride PET/computed tomography (NaF-PET/CT). A retrospective analysis compared 33 prostate cancer patients with 33 healthy subjects and 33 patients with angina pectoris. Increased target-to-background ratio (TBR) of the coronary arteries, ascending aorta, aortic arch, and descending aorta was observed in cancer patients compared to healthy controls but not compared to angina pectoris patients. These results demonstrate the feasibility of assessing vascular microcalcification with NaF-PET/CT, with significant differences in uptake according to comorbidities.

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

Utility of FDG-PET/CT in clinical psoriasis grading: the PET-PASI scoring system.

Psoriatic skin lesions are metabolically active, which makes them candidates for imaging with 18-F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The aim of our study was to correlate FDG-PET findings with Psoriasis Area and Severity Index (PASI) scores, the most widely-used grading system for psoriasis. Thirty-three subjects and a total of 84 FDG-PET/CT scans from a prospective clinical trial [NCT01553058] with >2 months moderate-to-severe psoriasis were included. Subjects underwent whole-body FDG-PET/CT imaging 60 min after intravenous FDG administration, prior to the start of treatment. Scans were repeated 12 weeks and 52 weeks after baseline scans were conducted and after treatment or placebo administration was initiated. Each subject and scan was graded by our "PET-PASI" scoring system, a qualitative review of multi-plane reconstructions for both attenuation-corrected (AC) and non-attenuation-corrected (NAC) PET images. PASI and PET-PASI scores were correlated using Spearman's rho analysis. Our study demonstrated a significant positive correlation between each subject's corresponding PET-PASI and PASI scores before and during treatment or placebo administration (r=0.53, P<0.001). We also found positive correlations between PET-PASI and PASI scores across different regions of the body (head and neck: r=0.22, upper extremities: r=0.26, trunk: r=0.48, and lower extremities: r=0.58). In conclusion, AC and NAC FDG-PET/CT images may be utilized to evaluate lesions in subjects with moderate-to-severe psoriasis. Our methodology could have future implications in the diagnosis and therapeutic management of psoriasis.

Role of 18F-NaF-PET in assessing aortic valve calcification with age.

Aortic valve calcification is a slow and progressive pathological process that can manifest in various degrees from mild thickening of the valve known as aortic sclerosis to severe calcification that hinders the leaflet motion, known as aortic stenosis. The evolving concept of aortic calcification is thought to result from infiltration of macrophages and T-lymphocytes. Moreover, the incidence of aortic valve calcification increases with age, in particular over the age of 50. In this study, we aimed to assess 18F-sodium fluoride (18F-NaF) uptake by the aortic valve on PET/CT scans performed in two age groups; 25-35 and 50-75 years of age. We hypothesized that patients aged 50-75, comprising of both healthy and high risk for cardiovascular disease (CVD), would have higher uptake of 18F-NaF than patients aged 25-35 and further that in the former group those who were at high risk for CVD had also higher 18F-NaF uptake. The 25-35-year group comprised of 6 males and 6 females, mean age 30 ± 3.5 years, while the 50-75-year group included 18 males and 20 females, mean age 61 ± 6.2 years. All underwent PET/CT imaging 90 minutes following the injection of 2.2 MBq of 18F-NaF per kg body weight. Aortic valve analysis was performed on axial sections using standard guided computer software (OsiriX MD software, version 9.0.02). The average aortic valve SUVmean was calculated for each patient. Univariate regression models stratified by age group were employed to determine the association of SUVmean with age. In the 50-75-year group, explanatory multivariable regression modeling was applied using available demographic and baseline information. SUVmean was found to be higher in the 50-75 age group than in the 25-35 age group: 0.91 ± 0.25 and 0.86 ± 0.26, respectively. The association of SUVmean with age was much stronger in individuals aged 50-75 years (r = 0.64, P<0.001) than individuals aged 25-35 years (r = 0.20, P = 0.53). In addition, in the 50-75 age group the association was much stronger in subjects with a high risk of CVD than in individuals without: r = 0.68, P = 0.001 versus r = 0.48, P = 0.042. Furthermore, the SUVmean was found to be higher in the high-risk group aged 50-75 than in the low-risk healthy group aged 50-75: 0.98 ± 0.32 and 0.83 ± 0.13. Aortic valve 18F-NaF uptake was higher in patients belonging to the age group of 50-75 years and correlated positively with age and high risk of CVD. These data provide evidence for a potential role of 18F-NaF PET/CT in identifying calcific changes in the aortic valve and may help direct therapeutic intervention prior to the development of symptomatic valvular disease.

Role of FDG-PET/CT in Assessing the Correlation Between Blood Pressure and Myocardial Metabolic Uptake.

OBJECTIVES: We aimed to assess the association between blood pressure and LV myocardial uptake of FDG, hypothesizing that subjects with raised blood pressure would have higher FDG uptake. METHODS: We analyzed 86 healthy controls who underwent PET/CT imaging 180 minutes following FDG (4 MBq/Kg) administration. LV myocardial analysis was performed on axial sections using standard operator guided computer software (OsiriX MD). The average LV myocardial SUVmean (MSUVmean) was calculated for each subject. Subjects were assessed according to the 2017 ACC/AHA guidelines for high blood pressure in adults. Mean arterial blood pressure (MABP) was calculated for each patient. Regression models were employed for statistical analysis. RESULTS: The association of MSUVmean was more pronounced with DP (r=0.32, p=0.003) than SP (r=0.28, p=0.010); MABP was comparable (r=0.33, p=0.002). Correlations of MSUVmean with categorized BPs were: normal SP (r=0.27, p=0.010), elevated SP (r=0.28, p=0.009), stage 1 SP (r=0.27, p=0.010), stage 2 SP (r=0.28, p=0.008); normal DP (r=0.33, p=0.001), stage 1 DP (r=0.34, p=0.001), stage 2 DP (r=0.35, p=0.001). Multivariate analysis demonstrated DP (p=0.006), MABP (p=0.007), and SP (0.026). CONCLUSION: LV myocardial FDG uptake was higher in subjects with elevated blood pressure and correlated positively with SBP and in particular DBP and MABP.

18F-NaF Uptake in Ocular Prosthesis (Implant).

Ocular prosthesis is used as a replacement in the orbit following enucleation or evisceration of the eye. Polymethyl methacrylate (PMMA), hydroxyapatite (HA) and porous polyethylene (PP) are some examples of the materials used in ocular prosthesis. We present a case of an 82-year-old man with prostate cancer who underwent F-NaF PET/CT imaging for evaluation of bone metastases and was incidentally found to have increased NaF uptake in the ocular prosthesis.

18F-FDG-PET/CT in measuring volume and global metabolic activity of thigh muscles: a novel CT-based tissue segmentation methodology.

PURPOSE: We present a novel computed tomography-based tissue segmentation methodology for determining volume and global uptake of FDG of the thigh muscles and correlate these parameters with age. MATERIALS AND METHODS: A total of 71 subjects from a prospective clinical trial (NCT01724749) were included. PET/CT scans were acquired 180 minutes after intravenous injection of FDG. A 3D growing region algorithm with neighborhood Hounsfield unit threshold between one and 150 was used to highlight the muscle. FDG uptake was expressed as the average mean standardized uptake value normalized for lean body mass (average SULmean). Femur volume was used to normalize thigh muscle volume to calculate normalized volume and correlate with age. RESULTS: We found a significant negative correlation between normalized volume and age (left side r = -0.262, P = 0.02; right side r = -0.286, P = 0.01). No statistically significant difference was found between SUL and age or between SUL and BMI. There was no statistically significant difference in muscle volume on the two sides. Statistically significant difference was noted in the global metabolic activity (SUL) between the two sides (left 0.39 ± 0.06, right 0.42 ± 0.08, P < 0.001), with 56/71 (78.8%) subjects having higher uptake on the right side. CONCLUSION: FDG-PET/CT using CT-based segmentation is a novel imaging modality assessing the volume and global metabolic activity of the thigh muscles. It could be possible to utilize this methodology for the research and understanding of lower limb muscle pathophysiology.

Sacroiliac Joint Asymmetry Regarding Inflammation and Bone Turnover: Assessment by FDG and NaF PET/CT.

OBJECTIVES: This study was undertaken to determine the role of computed tomography (CT)-based methodology to segment the SI joint and quantify the metabolic activity using positron emission tomography (PET). We measured tracer uptake in the right and left SI joints independently to look for differences between the two sides. Further, we correlated tracer uptake with BMI and studied the inter-observer variation with regard to estimated tracer uptake in the SI joints. METHODS: In this retrospective study, a total of 103 subjects (48 females, 55 males) from the CAMONA study database collected 2012-2016 at Odense University Hospital in Denmark were included. Mean age was 48±14.59 years, mean BMI was 26.68±4.31 kg/m2. The SI joints were segmented on fused PET/CT images using a 3D growing algorithm with adjustable upper and lower Hounsfield Units (HU) thresholds. The metabolic activities on the two sides were correlated with BMI. RESULTS: For FDG, we found a higher average SUVmean on the right side (right: 1.3±0.33, left: 1.13±0.30; <0.0001). Similarly, for NaF, the uptake was higher on the right side (right: 5.9±1.29, left: 4.27±1.23; <0.0001). Positive correlations were present between BMI and FDG uptake (P<0.01) as well as NaF uptake (P<0.01). CONCLUSION: The PET-based molecular imaging probes along with the CT-based segmentation techniques revealed a significant difference in the metabolic activity between the two SI joints with higher inflammation and reactive bone formation on the right side. FDG and NaF uptakes correlated significantly and positively with BMI.

18F-NaF Uptake in Calcified Uterine Leiomyoma.

Uterine leiomyomas (fibroids) represent the most common benign pelvic tumors in women as well as the leading indication for hysterectomies in the United States. Risk factors for the development of fibroids include increasing age, hormonal changes, genetics, and race, among others. The lifetime risk of developing fibroids is greater than 80% among African American women, who also have the more severe form of this condition. We are presenting a case of incidental F-NaF uptake in the calcified uterine leiomyoma of a 52-year-old African American woman.

Evolving Role of PET-Based Novel Quantitative Techniques in the Management of Hematological Malignancies.

"The role of 18F-fluorodeoxyglucose PET/computed tomography in hematological malignancies continues to expand in disease diagnosis, staging, and management. A key advantage of PET over other imaging modalities is its ability to quantify tracer uptake, which can be used to determine degree of disease activity. Although tracer uptake with PET is conventionally measured in focal lesions, novel quantitative techniques are being investigated that set objective protocols and produce robust parameters that represent total disease activity portrayed by PET. This article discusses recent advances in PET quantification that can improve reliability and accuracy of characterizing hematological malignancies."

Evolving Roles of Fluorodeoxyglucose and Sodium Fluoride in Assessment of Multiple Myeloma Patients: Introducing a Novel Method of PET Quantification to Overcome Shortcomings of the Existing Approaches.

PET with fluorodeoxyglucose and sodium fluoride (NaF) radiotracers has shown a great promise in assessing patients with multiple myeloma (MM). However, the standardization of PET/computed tomography scans interpretation in patients with myeloma in clinical practice is still debatable. This article reviews available data regarding the use of fluorodeoxyglucose and NaF PET in patients with MM. Introduced is a novel method of PET quantification as applied to patients with MM. A new concept for PET-based evaluation of patients with MM is also discussed: dual time point imaging. Finally, the role of NaF in assessment of cardiovascular complications of MM is described.

An update on the role of 18F-FDG-PET/CT in major infectious and inflammatory diseases.

For decades, conventional nuclear medicine techniques have been utilized for the assessment of many infectious and inflammatory diseases. Most of these techniques have limitations such as the relatively low spatial resolution, being time consuming and low sensitivity or specificity. In recent years, FDG-PET/CT has shown promising role in the management of such diseases. An expanding set of studies illustrate the multifarious roles of FDG-PET/CT in the assessment of these conditions, both systemic diseases and more regional. Specifically, PET can provide vital information at a molecular level and consequently detect the disease activity at their earliest manifestation. With the continuing research on the diagnosis and treatment monitoring of patients with infectious and inflammatory diseases, the role of PET/CT can be further extended.

Assessing respitatory muscle activity with 18F-FDG-PET/CT in patients with COPD.

The purpose of this study was to investigate the metabolic activity of the respiratory muscles in patients with chronic obstructive pulmonary diseases (COPD) and correlate with pulmonary function test results. Thirty-three male patients with a past medical history of smoking and COPD referred to 2-deoxy-2-[18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) because of clinical suspicion of pulmonary cancer were included. The degree of 18F-FDG uptake was visually quantified (grade 0-3) in the respiratory muscles of the neck, intercostal muscles, and abdominal muscles using mediastinal blood pool uptake and liver uptake as references. Visual grade of 18F-FDG uptake was compared to forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and FEV1 percent predicted (FEV1 % pred) by the Wilcoxon-type test for trend. We found significant correlation between the visual grading score and both FEV1/FVC (P=0.017) and FEV1 % predicted (P=0.045) for the intercostal muscles. Grade was not significantly associated with pulmonary function tests in either the neck or abdominal muscle groups. 18F-FDG-PET/CT of the respiratory muscles may have potential in characterization of COPD. Future prospective studies with a larger number of subjects should be undertaken to better understand respiratory muscle physiology in patients with COPD.

Clinical Applications of Positron Emission Tomography in the Evaluation of Spine and Joint Disorders.

Over the last decade, major advances have been made in PET imaging, including the introduction of hybrid PET/computed tomography and PET/MR imaging systems, facilitating a better understanding of the pathophysiology underlying a vast array of human diseases. PET has not only remained the clinical standard for most oncological disorders but also emerged as a potentially viable modality in nononcological disorders, including many musculoskeletal pathologies.

Evolving Role of PET/CT-MRI in Assessing Muscle Disorders.

2-Deoxy-2-[18F]fluoroglucose (FDG) uptake in muscle is influenced by many normal physiologic processes and can also indicate pathology. Variability in physiologic uptake can be reduced with proper patient preparation, allowing for a better determination of abnormal activity. Although malignant diseases, such as rhabdomyosarcoma and skeletal muscle metastasis, are clear applications of FDG-PET/CT, there may be additional applications in infection and benign inflammatory disorders that warrant further research.

Incidental 18F-NaF Uptake in Drug-Induced Gynecomastia.

Gynecomastia is not uncommon in men older than 50 years of age and is characterized by glandular proliferation of breast tissue. Non-physiologic gynecomastia is mostly caused by a variety of external medical interventions. Medications that belong to classes of antiandrogens, antipsychotics, or antibiotics alter the levels of estrogen and testosterone and are commonly implicated in patients with gynecomastia. We are presenting a case of bilateral F-NaF uptake in the breast tissue of a 56-year-old man with known history of prostate cancer.

Efficacy of 18F-FDG and 18F-NaF PET/CT imaging: A novel semi-quantitative assessment of the effects of age and obesity on hip joint inflammation and bone degeneration.

OBJECTIVE: Osteoarthritis (OA) is characterized by synovial tissue inflammation and underlying bone degeneration in the joints. Aging and obesity are among the major risk factors. This study evaluated the effects of aging and body mass index (BMI) on hip joint inflammation and bone degeneration using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and fluorine-18 sodium fluoride (18F-NaF) PET/CT imaging, respectively. SUBJECTS AND METHODS: In this retrospective study, a total of 116 subjects (58 males and 58 females) who had undergone both 18F-FDG and 18F-NaF PET/CT imaging were analyzed. The mean age of these subjects was 48.6±14.5 with an age range of 21-75 years. Fluorine-18-FDG and 18F-NaF PET/CT imaging was conducted 180min and 90min (respectively) after intravenous administration of the appropriate tracer. The hip joint was segmented on fused PET/CT images using OsiriX MD v.9.5 (DICOM viewer and image-analysis program, Pixmeo SARL; Bernex, Switzerland). The region of interest (ROI) for the hip joint was indicated by using a 3D-growing region algorithm with upper/lower Hounsfield Units (HU) followed by a morphological closing algorithm. The metabolic activity for the left and right side of the joint was measured and correlated with age and BMI. RESULTS: Fluorine-18-FDG uptake in the hip was 0.83±0.22 (right side: 0.83±0.23, left side: 0.83±0.22, P=0.82). Fluorine-18-NaF uptake in the hip was 3.20±1.07 (right side: 3.25±1.14, left side: 3.15±1.04, P=0.02). Body mass index positively correlated with both 18F-FDG (r=0.29, P=0.001) and NaF (r=0.26, P=0.005) uptake. No significant correlation was seen between age and either 18F-FDG (r=0.12, P=0.19) or 18F-NaF (r=0.03, P=0.78) uptake. CONCLUSION: Body mass index had a significant impact on 18F-FDG and 18F-NaF uptake, whereas age had no correlation with either tracer uptake. Obesity increases the mechanical forces applied on weight-bearing joints such as the hip. Body mass index was related to increased joint inflammation and bone degeneration. These findings further support the studies explaining the role of adipose tissue in promoting OA.