Project description:BackgroundDiagnosis of vasculitis is challenging. To avoid invasive approaches, clinical guidelines recommend the use of diagnostic imaging. This study aimed at evaluating the diagnostic accuracy of [18F]-fluorodeoxyglucose ([18F]FDG) position emission tomography/computed tomography (PET/CT) in large vessel vasculitis (LVV) and how this is affected by inter-operator variability.MethodsA total of 279 patients who performed [18F]-FDG PET/CT for suspicion of LVV were retrospectively analyzed. We tested the qualitative and semi-quantitative analysis and parameters influencing image quality and interpretation. Exams were evaluated by two readers with different experience and their performance was compared.ResultsLVV diagnosis was confirmed in 81 patients. [18F]-FDG PET/CT accuracy was 73% and 67% for the expert reader and less experienced reader, respectively. The expert reader overall performed better than the less experienced one, with higher accuracy in patients with normal BMI (77.3 vs. 63.8%), normal level of glycemia (73.3 vs. 65%), younger age (76.6 vs. 68.2%), and when no therapy was in course at time of imaging (76.7 vs. 66.7%). The diagnostic performance of both readers did not improve using semi-quantitative parameters.ConclusionsWe confirmed the appropriateness of the recommended criteria for image acquisition and interpretation, underlining the importance of experience in image interpretation for the optimal diagnostic performance of [18F]FDG PET/CT in vasculitis.
Project description:BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging.MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD).ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication.ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.
Project description:BackgroundAssessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.ObjectivesWe aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV.MethodsIn a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.ResultsSixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.ConclusionsSST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810).
Project description:BackgroundThe lack of visualization of the spinal cord hinders the evaluation of [18F]Fluoro-deoxy-glucose (FDG) uptake of the spinal cord in PET/CT. By exploiting the capability of MRI to precisely outline the spinal cord, we performed a retrospective study aimed to define normal pattern of spinal cord [18F]FDG uptake in PET/MRI.MethodsForty-one patients with lymphoma without clinical or MRI signs of spinal cord or bone marrow involvement underwent simultaneous PET and MRI acquisition using Siemens Biograph mMR after injection of 3.5 MBq/kg body weight of [18F]FDG for staging purposes. Using a custom-made software, we placed ROIs of 3 and 9 mm in diameter in the spinal cord, lumbar CSF, and vertebral marrow that were identified on MRI at 5 levels (C2, C5, T6, T12, and L3). The SUVmax, SUVmean, and the SUVmax and SUVmean normalized (NSUVmax and NSUVmean) to the liver were measured. For comparison, the same ROIs were placed in PET-CT images obtained immediately before the PET-MRI acquisition following the same tracer injection.ResultsOn PET/MRI using the 3 mm ROI, the following average (all level excluding L3) spinal cord median (1st and 3rd quartile) values were measured: SUVmean, 1.68 (1.39 and 1.83); SUVmax, 1.92 (1.60 and 2.14); NSUVmean, 1.18 (0.93 and 1.36); and NSUVmax, 1.27 (1.01 and 1.33). Using the 9 mm ROI, the corresponding values were SUVmean, 1.41 (1.25-1.55); SUVmax, 2.41 (2.08 and 2.61); NSUVmean, 0.93 (0.79 and 1.04); and NSUVmax, 1.28 (1.02 and 1.39). Using the 3 mm ROI, the highest values of PET-MRI SUVmax, SUVmean, NSUVmax, and NSUVmean were consistently observed at C5 and the lowest at T6. Using a 9 mm ROI, the highest values were consistently observed at C5 and the lowest at T12 or T6. The spinal cord [18F]FDG-uptake values correlated with the bone marrow uptake at the same level, especially in case of NSUVmax. Comparison with PET-CT data revealed that the average SUVmax and SUVmean of the spinal cord were similar in PET-MRI and PET-CT. However, the average NSUVmax and NSUVmean of the spinal cord were higher (range 21-47%) in PET-MRI than in PET-CT.ConclusionsUsing a whole-body protocol, we defined the maximum and mean [18F]FDG uptake of the normal spinal cord in PET/MRI. While the observed values show the expected longitudinal distribution, they appear to be higher than those measured in PET/CT. Normalization of the SUVmax and SUVmean of the spinal cord to the liver radiotracer uptake could help in multi-institutional comparisons and studies.
Project description:Aim[18F]FDG PET/CT proved accurate in the diagnostic work-up of large vessel vasculitis (LVV). While a visual interpretation is currently considered adequate, several attempts have been made to integrate it with a semiquantitative evaluation. In this regard, there is the need to validate current or new thresholds for the semiquantitative parameters on long-axial field of view (LAFOV) scanners.MethodsWe retrospectively evaluated 100 patients (50 with LVV and 50 controls) who underwent [18F]FDG LAFOV PET/CT. Semiquantitative parameters (SUVmax and SUVmean) were calculated for large vessels in 3 districts (supra-aortic [SA], thoracic aorta [TA], and infra-aortic [IA]). Values were also normalized to liver activity (SUVmax/L-SUVmax, and SUVmax/L-SUVmean).ResultsOf the 50 patients diagnosed with LVV, SA vessels were affected in 38 (76%), TA in 42 (84%) and IA vessels in 26 (52%). To-liver normalized values had higher diagnostic accuracy than non-normalized values (AUC always ≥ 0.90 vs. 0.74-0.89). For the SA vessels, best thresholds were 0.66 for SUVmax/L-SUVmax and 0.88 for SUVmax/L-SUVmean; for the TA, 1.0 for SUVmax/L-SUVmax and 1.30 for SUVmax/L-SUVmean; finally, for IA vessels, the best threshold was 0.83 for SUVmax/L-SUVmax and 1.11 for SUVmax/L-SUVmean.ConclusionLAFOV [18F]FDG-PET/CT is accurate in the diagnostic workup of LVV, but different threshold in semi-quantitative parameters than reported in literature for standard scanners should be considered.
Project description:BackgroundThe clinical diagnosis of deep sternal wound infection (DSWI) is supported by imaging findings including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). To avoid misinterpretation due to normal post-surgery inflammation we assessed normal imaging findings in non-infected patients after sternotomy.MethodsThis is a prospective cohort study including non-infectious patients with sternotomy. All patients underwent 18F-FDG-PET/CT at either 5 weeks (group 1), 12 weeks (group 2) or 52 weeks (group 3) post-surgery. 18F-FDG uptake was scored visually in five categories and assessed quantitatively.ResultsA total of 44 patients were included. Sternal mean SUVmax was 7.34 (± 1.86), 5.22 (± 2.55) and 3.20 (± 1.80) in group 1, 2 and 3, respectively (p < 0.01). Sternal mean SUVmean was 3.84 (± 1.00), 2.69 (± 1.32) and 1.71 (± 0.98) in group 1, 2 and 3 (p < 0.01). All patients in group 1 had elevated uptake whereas group 2 and 3 showed 2/15 (13%) and 11/20 (55%) patients respectively with no elevated uptake. Group 3 still showed an elevated uptake pattern in in 9/20 (45%) and in 3/9 (33%) with a high-grade diffuse uptake pattern.ConclusionThis study shows significant lower sternal 18F-FDG at 55 weeks compared to 5 weeks post-sternotomy however elevated uptake patterns may persist.
Project description:BackgroundSimultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) is a novel hybrid imaging method integrating the advances of morphological tissue characterization of MRI with the pathophysiological insights of PET applications.AimThis study evaluated the use of simultaneous 18-FDG PET/MR imaging for characterizing atherosclerotic lesions in lower extremity arterial disease (LEAD).MethodsEight patients with symptomatic stenoses of the superficial femoral artery (SFA) under simultaneous acquisition of 18-FDG PET and contrast-enhanced MRI using an integrated whole-body PET/MRI scanner. Invasive plaque characterization of the SFA was performed by intravascular imaging using optical coherence tomography. Histological analysis of plaque specimens was performed after directional atherectomy.ResultsMRI showed contrast enhancement at the site of arterial stenosis, as assessed on T2-w and T1-w images, compared to a control area of the contralateral SFA (0.38 ± 0.15 cm vs. 0.23 ± 0.11 cm; 1.77 ± 0.19 vs. 1.57 ± 0.15; p-value <0.05). On PET imaging, uptake of 18F-FDG (target-to-background ratio TBR > 1) at the level of symptomatic stenosis was observed in all but one patient. Contrast medium-induced MR signal enhancement was detected in all plaques, whereas FDG uptake in PET imaging was increased in lesions with active fibroatheroma and reduced in fibrocalcified lesions.ConclusionIn this multimodal imaging study, we report the feasibility and challenges of simultaneous PET/MR imaging of LEAD, which might offer new perspectives for risk estimation.
Project description:Motion of the myocardium deteriorates the quality and quantitative accuracy of cardiac PET images. We present a method for MR-based cardiac and respiratory motion correction of cardiac PET data and evaluate its impact on estimation of activity and kinetic parameters in human subjects. Three healthy subjects underwent simultaneous dynamic 18F-FDG PET and MRI on a hybrid PET/MR scanner. A cardiorespiratory motion field was determined for each subject using navigator, tagging and golden-angle radial MR acquisitions. Acquired coincidence events were binned into cardiac and respiratory phases using electrocardiogram and list mode-driven signals, respectively. Dynamic PET images were reconstructed with MR-based motion correction (MC) and without motion correction (NMC). Parametric images of 18F-FDG consumption rates (Ki) were estimated using Patlak's method for both MC and NMC images. MC alleviated motion artifacts in PET images, resulting in improved spatial resolution, improved recovery of activity in the myocardium wall and reduced spillover from the myocardium to the left ventricle cavity. Significantly higher myocardium contrast-to-noise ratio and lower apparent wall thickness were obtained in MC versus NMC images. Likewise, parametric images of Ki calculated with MC data had improved spatial resolution as compared to those obtained with NMC. Consistent with an increase in reconstructed activity concentration in the frames used during kinetic analyses, MC led to the estimation of higher Ki values almost everywhere in the myocardium, with up to 18% increase (mean across subjects) in the septum as compared to NMC. This study shows that MR-based motion correction of cardiac PET results in improved image quality that can benefit both static and dynamic studies.
Project description:Radiomic studies link quantitative imaging features to patient outcomes in an effort to personalise treatment in oncology. To be clinically useful, a radiomic feature must be robust to image processing steps, which has made robustness testing a necessity for many technical aspects of feature extraction. We assessed the stability of radiomic features to interpolation processing and categorised features based on stable, systematic, or unstable responses. Here, 18F-fluorodeoxyglucose (18F-FDG) PET images for 441 oesophageal cancer patients (split: testing = 353, validation = 88) were resampled to 6 isotropic voxel sizes (1.5 mm, 1.8 mm, 2.0 mm, 2.2 mm, 2.5 mm, 2.7 mm) and 141 features were extracted from each volume of interest (VOI). Features were categorised into four groups with two statistical tests. Feature reliability was analysed using an intraclass correlation coefficient (ICC) and patient ranking consistency was assessed using a Spearman's rank correlation coefficient (ρ). We categorised 93 features robust and 6 limited robustness (stable responses), 34 potentially correctable (systematic responses), and 8 not robust (unstable responses). We developed a correction technique for features with potential systematic variation that used surface fits to link voxel size and percentage change in feature value. Twenty-nine potentially correctable features were re-categorised to robust for the validation dataset, after applying corrections defined by surface fits generated on the testing dataset. Furthermore, we found the choice of interpolation algorithm alone (spline vs trilinear) resulted in large variation in values for a number of features but the response categorisations remained constant. This study attempted to quantify the diverse response of radiomics features commonly found in 18F-FDG PET clinical modelling to isotropic voxel size interpolation.
Project description:BackgroundInflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover.ObjectivesThis study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation.MethodsWe confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis.ResultsTarget SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients.ConclusionsWe validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).