18F-sodium Fluoride Research Articles

Atherogenic Indices as a Predictor of Aortic Calcification in Prostate Cancer Patients Assessed Using 18F-Sodium Fluoride PET/CT.

A major pathophysiological cause of cardiovascular disease is vascular plaque calcification. Fluorine 18−Sodium Fluoride (18F-NaF) PET/CT can be used as a sensitive imaging modality for detection of vascular calcification. The aim of this study was to find a non-invasive, cost-efficient, and readily available metric for predicting vascular calcification severity. This retrospective study was performed on 36 participants who underwent 18F-NaF fused PET/CT scans. The mean standard uptake values (SUVs) were calculated from manually sectioned axial sections over the aortic arch and thoracic aorta. Correlation analyses were performed between SUVs and calculated atherogenic indices (AIs). Castelli’s Risk Index I (r = 0.63, p < 0.0001), Castelli’s Risk Index II (r = 0.64, p < 0.0001), Atherogenic Coefficient (r = 0.63, p < 0.0001), Atherogenic Index of Plasma (r = 0.51, p = 0.00152), and standalone high-density lipoprotein (HDL) cholesterol (r = −0.53, p = 0.000786) were associated with aortic calcification. AIs show strong association with aortic arch and thoracic aorta calcifications. AIs are better predictors of vascular calcification compared to standalone lipid metrics, with the exception of HDL cholesterol. Clinical application of AIs provides a holistic metric beneficial for enhancing screening and treatment protocols.

18F-sodium fluoride positron emission tomography and coronary plaque radiomics derived from computed tomography angiography for prediction of myocardial infarction

Abstract Background Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography (18F-NaF PET) and radiomics-based precision coronary plaque phenotyping derived from contrast-enhanced computed tomography (CT) have both been shown to enhance risk stratification in patients with coronary artery disease (CAD). To date, no study has investigated whether these two promising methods (which can be obtained during a single imaging session on a hybrid PET/CT scanner) are interchangeable or can provide superior predictive performance when used in combination. Purpose We sought to investigate whether the prognostic information provided by latent morphological radiomic coronary plaque features and assessments of disease activity by 18F-NaF PET are complementary in prediction of myocardial infarction. Methods Patients with known CAD underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA). We performed quantitative plaque analysis of coronary CT angiography datasets. Additionally, coronary plaque segmentations on CT angiography were used to extract 1103 radiomic features. Using weighted correlation network analysis we derived latent morphological features of coronary plaques which were aggregated to patient-level radiomic normograms to predict myocardial infarction using univariate and multivariate Cox proportional hazard models. Results The study cohort comprised of 260 patients with established CAD (age: 65±9 years; 84% men); 179 (69%) participants showed increased coronary 18F-NaF activity (CMA &amp;gt;0). Over 53 [40–59] months of follow-up 18 patients had a myocardial infarction. Using weighted correlation network analysis, from the 1103 radiomic features we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns. On univariate cox modelling 7 of these emerged as predictors of myocardial infarction (Figure). Following adjustments for calcified, noncalcified and low-density noncalcified plaque volumes and 18F-NaF CMA 4 radiomic features (related to texture and geometry) remained independent predictors of myocardial infarction (Figure). Conclusion(s) In patients with established CAD latent morphological features of coronary plaques are predictors of myocardial infarction above and beyond plaque volumes and 18F-NaF uptake. Comprehensive plaque analysis with radiomics may enhance risk stratification of CAD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIH, Wellcome Trust

“Global” cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison

BackgroundArtificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden. MethodsA trained convolutional neural network (CNN) was used for cardiac segmentation in 18F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans. ResultsMean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were − 89.42 to 74.2, − 0.02 to 0.02, − 1.52 to 1.32, and − 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators. ConclusionThe CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart.

After Total Ankle Arthroplasty, When Does Bone Perfusion and Metabolic Activity at the Bone-Implant Interface Normalize? A PET/CT Study

Category: Ankle Arthritis Introduction/Purpose: Radionuclide bone scintigraphy in combination with computed tomography (CT) has been used to evaluate painful total hip and knee arthroplasties, and has also been used in the evaluation of the painful total ankle arthroplasty (TAA). Increased tracer uptake around implants may indicate loosening, but uptake characteristics of bone-seeking radiopharmaceuticals in asymptomatic total ankle patients have not been clarified. While findings of increased metabolic activity may prompt surgical intervention, there has been no work performed to define when postoperatively periprosthetic activity normalizes, if at all. In this study, we plan to establish normative data on 18F sodium fluoride (18F-NaF) positron emission tomography/CT (PET/CT) uptake ratios around TAA implants at various time intervals after surgery in asymptomatic TAA patients. Methods: The majority of the arthroplasty literature has investigated use of SPECT/CT performed with 99mTc-labeled bisphosphonates. However, data suggest that 18F-NaF PET/CT may be superior for this indication, with more favorable pharmacokinetics and similar sensitivity to detect aseptic loosening. In the present study, asymptomatic patients who underwent TAA with a modern fixed-bearing TAA prosthesis (either the Wright Infinity Adaptis or Exactech Vantage prosthesis) for posttraumatic arthritis were eligible for inclusion. Patients with ipsilateral hindfoot fusion and with any periprosthetic lucencies or cysts were excluded. Patients were enrolled at one of four time intervals following TAA: 6, 12, 18, or 24 months. Standard uptake values were measured at the bone-implant interface for the tibial and talar components on static PET, in regions of interest defined on axial CT scan slices. Periprosthetic bone blood flow (K1) and bone turnover (flux) were assessed at each time interval in each periprosthetic region using dynamic PET. Results: Sixteen asymptomatic patients underwent PET/CT: 4 patients at 6 months postoperatively, 6 at 12 months, and 6 at 24 months. We are currently still in data collection and at this time only 2 patients at 18 months have completed the scan, therefore their data were excluded. The average age was 65 years (range, 55 to 80) and 6 patients were female (38%), with individual patient data shown in the Table. Talar K1 and flux both appeared to increase from 6 to 12 months, and decrease between 12 and 24 months, although there was no statistically significant difference between timepoints. Overall tibial K1 and flux appeared to decrease slightly from 6 to 12 months, and stayed relatively stable between 12 and 24 months, again with no significant difference between timepoints (Figure). Conclusion: There is currently no normative data to help guide interpretation of radionuclide bone scintigraphy for the painful TAA. The present study utilizing 18F-NaF PET/CT scans demonstrates that even in asymptomatic patients, periprosthetic bone blood flow and bone turnover remain elevated up to 24 months following modern fixed-bearing TAA. Not only do these values remain elevated at 24 months, but we found that there does not appear to be any significant decrease in either measurement over time from 6 to 24 months postoperatively. Our findings suggest that radionuclide bone scintigraphy should be cautiously interpreted when performed within 2 years of TAA.

Longitudinal monitoring of fetlock lesions in Thoroughbred racehorses using standing 18F-sodium fluoride positron emission tomography.

To assess the repeatability of equine 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) findings, and to evaluate the ability of PET to monitor the progression of areas of increased radiopharmaceutical uptake (IRU) in the fetlocks of Thoroughbred racehorses. 25 racehorses with clinical signs related to fetlock injuries. This study is a prospective, longitudinal clinical study. Twenty-five racehorses (54 fetlocks) underwent three 18F-NaF PET scans 6 weeks apart. The first 18F-NaF PET scan was performed at the start of a 12-week period of rest from racing (lay-up). Areas of IRU in the fetlock joints were quantified using maximal standardized uptake values (SUVmax) and were graded by 2 experienced observers. Statistical comparisons were made between scans to detect changes in IRU grade and SUVmax over time. Standing PET findings were repeatable, with 131/149 (88%) areas of IRU identified on the initial scans seen again at the 6-week follow-up scan. The palmar/plantar condyles were the sites most commonly presenting with IRU, followed by the proximal sesamoid bones. Overall, 65% of fetlocks demonstrated improvement in IRU grade during the 12-week period of rest from racing. Areas of higher IRU grade took longer to resolve than the lower graded areas. Standing PET findings in the racehorse fetlock were repeatable. The SUV-based grading system may be helpful when determining appropriate lay-up duration for Thoroughbred racehorses. PET may be used to monitor areas of the fetlock involved in catastrophic breakdown injuries in Thoroughbred racehorses.

The Efficacy of Trabecular Titanium Cages to Induce Reparative Bone Activity after Lumbar Arthrodesis Studied through the 18f-Naf PET/CT Scan: Observational Clinical In-Vivo Study.

Background: Titanium trabecular cages (TTCs) are emerging implants designed to achieve immediate and long-term spinal fixation with early osseointegration. However, a clear radiological and clinical demonstration of their efficacy has not yet been obtained. The purpose of this study was to evaluate the reactive bone activity of adjacent plates after insertion of custom-made titanium trabecular cages for the lumbar interbody with positron emission tomography (PET)/computed tomography (CT) 18F sodium fluoride (18F-NaF). Methods: This was an observational clinical study that included patients who underwent surgery for degenerative disease with lumbar interbody fusion performed with custom-made TTCs. Data related to the metabolic-reparative reaction following the surgery and its relationship with clinical follow-up from PET/CT performed at different weeks were evaluated. PET/CTs provided reliable data, such as areas showing abnormally high increases in uptake using a volumetric region of interest (VOI) comprising the upper (UP) and lower (DOWN) limits of the cage. Results: A total of 15 patients was selected for PET examination. Timing of PET/CTs ranged from one week to a maximum of 100 weeks after surgery. The analysis showed a negative correlation between the variables SUVmaxDOWN/time (r = −0.48, p = 0.04), ratio-DOWN/time (r = −0.53, p = 0.02), and ratio-MEAN/time (r = −0.5, p = 0.03). Shapiro−Wilk normality tests showed significant results for the variables ratio-DOWN (p = 0.002), ratio-UP (0.013), and ratio-MEAN (0.002). Conclusions: 18F-NaF PET/CT has proven to be a reliable tool for investigating the metabolic-reparative reaction following implantation of TTCs, demonstrating radiologically how this type of cage can induce reparative osteoblastic activity at the level of the vertebral endplate surface. This study further confirms how electron-beam melting (EBM)-molded titanium trabecular cages represent a promising material for reducing hardware complication rates and promoting fusion.

Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

Aortic wall segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based versus manual segmentation

BackgroundWe aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans. MethodsFor segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on 18F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland–Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans. ResultsCNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%. ConclusionsThe automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation.

The effect of Vitamin-K1 and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial

BackgroundThere is currently no treatment for attenuating progression of arterial calcification. 18F-sodium fluoride positron emission tomography (18F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K1 or colchicine affected arterial calcification activity. Methods154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K1 [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K1 [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on 18F-NaF PET. Results149 subjects completed follow-up (vitamin-K1: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K1 nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K1. ConclusionsIn patients with type 2 diabetes, neither vitamin-K1 nor colchicine significantly decreases coronary calcification activity, as estimated by 18F-NaF PET, over a period of 3 months. Clinical trial registration: ACTRN12616000024448.

Alzheimer's Disease at a Crossroad: Time to Part from Amyloid to More Promising Aspects-Atherosclerosis for a Start.

Three decades with the amyloid hypothesis, nearly two with amyloid-PET imaging, and one with testing of anti-amyloid therapy have not yielded benefits to patients with Alzheimer's disease (AD). It is time to focus on more promising options, e.g., infection, low dose radiation, and atherosclerosis. The relevance of the latter in managing AD has fluctuated from being significant to insignificant. Current methodologies for detecting cerebral atherosclerosis reflect advanced changes in only major arteries. In contrast, 18F-sodium fluoride PET imaging assessing early-stage cerebral atherosclerosis regionally or in the entire vascular bed may provide new insight in this age-related process in dementia.

Anatomical validation of automatic respiratory motion correction for coronary 18F-sodium fluoride positron emission tomography by expert measurements from four-dimensional computed tomography.

Respiratory motion correction is of importance in studies of coronary plaques employing 18 F-NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test-retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four-dimensional cine-computed tomography (CT) by an expert observer. To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of 18 F-NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine-CT images. This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using 18 F-sodium fluoride (18 F-NaF). All patients underwent a 5-s cine-CT (4D-CT), a coronary CT angiography (CTA), and 18 F-NaF PET. The 4D-CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non-contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D-CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t-tests. Signal-to-noise ratios (SNR) are reported for the single-phase images (end-expiratory phase) and for the motion-corrected image-series (employing the motion vector fields extracted during the diffeomorphic registrations). In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT=2.5±1.5mm, PET=2.4±3.2mm; Y direction: 4D CT=2.3±1.9mm, PET=0.7±2.9mm, 3D motion: 4D CT=6.6±3.1mm, PET=5.7±2.6mm, all p≥0.05). Significant differences in respiratory motion were observed in the systems' Z direction: 4D CT=4.9±3.4mm, PET=2.3±3.2mm, p=0.04. Significantly improved SNR is reported for the motion corrected images compared to the end-expiratory phase images (end-expiratory phase=6.8±4.8, motion corrected=12.2±4.5, p=0.001). Similar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images.

Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity.

Background:Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established.Methods:One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography.Results:Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71–10.39]; P≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87–11.80]; P<0.042) compared with control samples (n=18; 0.79 [0.36–1.90]). Alkaline phosphatase (n=26; P=0.0019) and OPN (osteopontin; n=26; P=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, −0.51; P<0.0001)—a process closely linked with elastin loss (n=82; Spearman ρ, −0.43; P<0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P=0.026).18F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76; P<0.001) and identified areas of focal weakness in vivo.Conclusions:Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.18F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.

Molecular Imaging of Aortic Valve Stenosis with Positron Emission Tomography

Aortic valve stenosis (AVS) is an increasingly prevalent disease in our aging population. Although multiple risk factors for AVS have been elucidated, medical therapies capable of slowing down disease progression remain unavailable. Molecular imaging technologies are opening up avenues for the non-invasive assessment of disease progression, allowing the assessment of (early) medical interventions. This review will focus on the role of positron emission tomography of the aortic valve with 18F-fluorodeoxyglucose and 18F-sodium fluoride but will also shed light on novel tracers which have potential in AVS, ranging from the healthy aortic valve to end-stage valvular disease.

Bone Turnover, Mineralization, and Volume Estimated by 18F-Sodium Fluoride PET/CT and Biomarkers in Chronic Kidney Disease: Mineral and Bone Disorder Compared with Bone Biopsy

Introduction: Invasive bone biopsy to assess bone metabolism in patients with chronic kidney disease-mineral and bone disorder may be replaced by the noninvasive ¹⁸F-NaF PET/CT and biomarkers of bone metabolism. We aimed to compare parameters of bone turnover, mineralization, and volume assessed by bone biopsies with results derived from ¹⁸F-NaF PET/CT and biomarkers (bone-specific alkaline phosphatase, osteocalcin, fibroblast growth factor 23, and osteoprotegerin). Methods: A cross-sectional study included 17 dialysis patients, and results from ¹⁸F-NaF PET/CT scans and the biomarkers were directly compared with the results of histomorphometric analyses of tetracycline double-labeled trans-iliac bone biopsies. Results: Bone biopsies showed 40% high, 20% normal, and 40% low bone turnover. No biopsies had generalized abnormal mineralization, and the bone volume/total tissue volume was low in 80% and high in 7%. The pelvic skeletal plasma clearance (K_i) from ¹⁸F-NaF PET/CT correlated with bone turnover parameters obtained by bone biopsy (activation frequency: r = 0.82, p < 0.01; bone formation rate/bone surface: r = 0.81, p < 0.01), and K_i defined low turnover with high sensitivity (83%) and specificity (100%). CT-derived radiodensity correlated with bone volume, r = 0.82, p < 0.01. Of the biomarkers, only osteocalcin showed a correlation with turnover assessed by histomorphometry. Conclusion: In conclusion, ¹⁸F-NaF PET/CT may be applicable for noninvasive assessment of bone turnover and volume in CKD-MBD.

Comparison of 18F-sodium fluoride positron emission tomography imaging and 99mTc-pyrophosphate in cardiac amyloidosis

BackgroundPyrophosphate (PYP) scintigraphy provides high diagnostic accuracy for the detection of transthyretin (ATTR) cardiac amyloidosis (CA). There has recently been emerging interest in using 18F-sodium fluoride (NaF) for this application, yet its sensitivity has never been directly compared to that of PYP, the current molecular gold standard MethodsTwelve subjects with ATTR-CA and 5 controls referred for PYP-SPECT were prospectively enrolled. 18F-NaF PET/CT scans were performed at 1 and 3 hours. Qualitative and quantitative analyses of the images were performed, and the sensitivity of 18F-NaF PET/CT and PYP-SPECT were compared ResultsVisual interpretation of NaF PET/CT yielded a sensitivity of 0.25 (95% CI 0.089 to 0.53) for the detection of ATTR-CA, which is significantly inferior to that of PYP-SPECT/CT (100%, P = .016). Visual interpretation at 3 hours yielded a similar sensitivity of 0.30 (95% CI 0.11 to 0.60, P = 1.00). There were no false-positive NaF PET studies. Mean target-to-background ratio (TBRmean) at 1h did not differ significantly (P = .21) in ATTR-CA subjects (0.83 ± 0.15) compared to controls (0.72 ± 0.15). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.69 ± 0.16 (95% CI 0.37 to 1.00, P = .23). ConclusionWith qualitative and quantitative analyses, sensitivity of NaF PET/CT is significantly inferior to that of PYP-SPECT for the diagnosis of ATTR-CA

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

BackgroundPrevious studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. Methods and resultsWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. Conclusions18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

Quantifying microcalcification activity in the thoracic aorta

BackgroundStandard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. MethodsTwenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. ResultsAortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. ConclusionsAMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

PET-CT in Clinical Adult Oncology: II. Primary Thoracic and Breast Malignancies.

Simple SummaryPositron emission tomography (PET), typically combined with computed tomography (CT), has become a critical advanced imaging technique in oncology. With PET-CT, a radioactive molecule (radiotracer) is injected in the bloodstream and localizes to sites of tumor because of specific cellular features of the tumor that accumulate the targeting radiotracer. The CT scan, performed at the same time, provides information to facilitate assessment of the amount of radioactivity from deep or dense structures, and to provide detailed anatomic information. PET-CT has a variety of applications in oncology, including staging, therapeutic response assessment, restaging, and surveillance. This series of six review articles provides an overview of the value, applications, and imaging and interpretive strategies of PET-CT in the more common adult malignancies. The second article in this series addresses the use of PET-CT in breast cancer and other primary thoracic malignancies.Positron emission tomography combined with x-ray computed tomography (PET-CT) is an advanced imaging modality with oncologic applications that include staging, therapy assessment, restaging, and surveillance. This six-part series of review articles provides practical information to providers and imaging professionals regarding the best use of PET-CT for the more common adult malignancies. The second article of this series addresses primary thoracic malignancy and breast cancer. For primary thoracic malignancy, the focus will be on lung cancer, malignant pleural mesothelioma, thymoma, and thymic carcinoma, with an emphasis on the use of FDG PET-CT. For breast cancer, the various histologic subtypes will be addressed, and will include 18F fluorodeoxyglucose (FDG), recently Food and Drug Administration (FDA)-approved 18F-fluoroestradiol (FES), and 18F sodium fluoride (NaF). The pitfalls and nuances of PET-CT in breast and primary thoracic malignancies and the imaging features that distinguish between subcategories of these tumors are addressed. This review will serve as a resource for the appropriate roles and limitations of PET-CT in the clinical management of patients with breast and primary thoracic malignancies for healthcare professionals caring for adult patients with these cancers. It also serves as a practical guide for imaging providers, including radiologists, nuclear medicine physicians, and their trainees.

Associations between coronary/aortic 18F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease

Background18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). MethodsPatients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. Results100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. ConclusionsCoronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

Can Target-to-Background Ratio Measurement Lead to Detection and Accurate Quantification of Atherosclerosis With FDG PET? Likely Not.

The introduction of FDG in 1976 started a new discipline and enhanced the role of molecular imaging in medicine. While the initial intent with this tracer was to determine brain function in a variety of neuropsychiatric disorders, over time, this powerful approach has made a major impact on managing many other diseases and disorders. During the past 2 decades, FDG PET has been used to detect inflammatory lesions in the atherosclerotic plaques and in other settings. However, the suboptimal spatial resolution of PET limits its ability to visualize plaques that are very small in size. Furthermore, this tracer remains in the blood for an extended period and therefore provides suboptimal results. Target-to-background ratio (TBR) has been suggested to correct for this source of error. Unfortunately, TBR values vary substantially, depending on the timing of image acquisition. Delayed imaging at later time points (3–4 hours) may obviate the need for TBR measurement, but it is impractical with conventional PET instruments. Recently, 18F-sodium fluoride (NaF) has been used for detection and quantification of molecular calcification in the plaques. This tracer is highly specific for calcification and is rapidly cleared from the circulation. In addition, global atherosclerotic burden as measured by NaF PET can be determined accurately either in the heart or major arteries throughout the body. Therefore, the role of FDG PET–based TBR measurement for detection and quantification of atherosclerotic plaques is questionable at this time.