Influence of key histological characteristics on 18F-fluorodeoxyglucose /18F-choline positron emission tomography positivity in hepatocellular carcinoma: A machine learning study.

Purpose: To determine the characteristics influence of key histological on 18F-fluorodeoxyglucose (18F-FDG) and 18F-choline positron emission tomography (PET) positivity in hepatocellular carcinoma (HCC). Materials and methods: The 18F-FDG/18F-choline PET imaging findings of 103 histologically proven HCCs (from 62 patients, of which 47 underwent hepatectomy and 15 received liver transplantation) were retrospectively examined to assess the following key histological parameters: Grade, capsule, microvascular invasion (mVI), macrovascular invasion (MVI), and necrosis. Using a ratio of 70/30 for training and testing sets, respectively, a penalized classification model (Elastic Net) was trained using 100 repeated cross-validation procedures (10-fold cross-validation for hyperparameter optimization). The contribution of each histological parameter to the PET positivity was determined using the Shapley Additive Explanations method. Receiver operating characteristic curves with and without dimensionality reduction were finally estimated and compared. Results: Among the five key histological characteristics of HCC (Grade, capsule, mVI, MVI, and necrosis), mVI and tumor Grade (I-III) showed the highest relevance and robustness in explaining HCC uptake of 18F-FDG and 18F-choline. MVI and necrosis status both showed high instability in outcome predictions. Tumor capsule had a minimal influence on the model predictions. On retaining only mVI and Grades I-III for the final analysis, the area under the receiver operating characteristic (ROC) curve values were maintained (0.68 vs. 0.63, 0.65 vs. 0.64, and 0.65 vs. 0.64 for 18F-FDG, 18F-choline, and their combination, respectively). Conclusion: 18F-FDG/18F-choline PET positivity appears driven by both the Grade and mVI components in HCC. Consideration of the tumor microenvironment will likely be necessary to improve our understanding of multitracer PET positivity.

Is 18 F-FDG/ 18 F-Choline Dual-Tracer PET Behavior a Surrogate of Tumor Differentiation in Hepatocellular Carcinoma : A Tertiary Center Dedicated Study.

BACKGROUND: In hepatocellular carcinoma (HCC) setting, 18 F-FDG and 18 F-choline PET/CT radiotracers are classically considered surrogates of the degree of differentiation, a strong predictor of disease recurrence after curative treatment. Because the corresponding level of evidence has never been assessed as primary end point, the aim of this retrospective study was to specifically assess the relevance of 18 F-FDG combined to 18 F-choline PET imaging as a surrogate of tumor differentiation in HCC. PATIENTS AND METHODS: A total of 49 histologically proven HCCs (46 patients treated by surgery or liver transplantation) with available baseline 18 F-FDG and 18 F-choline PET/CT, dedicated liver contrast-enhanced CT scan, and histological key features were retrospectively reviewed. Hepatocellular carcinoma tumors with well, moderately, and poorly differentiation (grades I, II, and III of the World Health Organization classification) were compared on their PET findings (double-blinded visual analysis and 8 usual semiquantitative metrics) by using nonparametric Kruskal-Wallis analyses of variance. In the case of statistical significance, pairwise post hoc tests with family-wise error rate adjustment were performed. RESULTS: No statistical difference between the grades was observed for any of the patients' or lesions' characteristics ( P > 0.05), except for the macrovascular invasion between the grades I and II (adjusted P = 0.03). None of the PET findings showed statistical difference between the grades, except the tumor-to-background ratio of 18 F-FDG, higher for the grade III compared with grades I (adjusted P = 0.02) and II (adjusted P = 0.01). For less than one third of cases (14 lesions; 28.5%), the regional uptake was judged visually heterogeneous, but none of the related semiquantitative PET metrics were statistically discriminant ( P > 0.05). CONCLUSIONS: Contrary to a common belief, 18 F-FDG/ 18 F-choline dual-tracer PET behavior is not a relevant surrogate of tumor differentiation in HCC. Future multitracer PET studies are mandatory to refine our knowledges of their deep biological meaning in this field.

Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy.

OBJECTIVE: Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART). DESIGN: A French cross-sectional study from January 2013 to June 2016. METHODS: We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life. RESULTS: Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (<70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86; P  = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P  = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98; P  = 0.02). A nadir CD4+ T-cell count more than 200 cells / µl (aOR 0.22, 95% CI 0.07-0.65;P < 0.01) were protective. CONCLUSION: Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement.

Treatment of acromegaly has substantial effects on body composition: a long-term follow-up study.

BACKGROUND: Acromegaly is associated with changes in body composition. Long-term changes following acromegaly treatment and the impact of different treatments have been less investigated. METHODS: We performed a retrospective study in 201 patients with acromegaly. Body composition was assessed by dual-energy X-ray absorptiometry. To investigate the specific effects of treatment vs aging, changes in body composition were compared in one group of patients evaluated both at the time of active and controlled disease (active-to-controlled (A>C); n = 31) and in another group of patients evaluated two times while the disease was controlled (controlled-to-controlled (C>C); n = 32). RESULTS: In the whole cohort, insulin-like growth factor I (IGF-I) was correlated with fat (r = -0.369; P < 0.001) and lean mass (r = 0.383; P < 0.001). Patients from A>C and C>C groups were comparable for age, sex, BMI and follow-up duration (P = n.s.). Reduction in IGF-I levels was associated with an increase in fat mass and a decrease in lean mass in the A>C group, which was four and eight times more pronounced compared to the C>C group (fat mass: +39 ± 34% vs +10 ± 15%, P < 0.001; lean mass: -8 ± 8% vs -0.2 ± 6%, P < 0.001, respectively). Changes in fat mass were negatively associated with IGF-I (r = -0.450; P = 0.011) and independent of the individual therapy. The daily dose of pegvisomant correlated with fat mass (r = 0.421; P = 0.002) and insulin sensitivity index (r = -0.466; P < 0.001). CONCLUSIONS: Treatment of acromegaly strongly impacts body composition until biochemical disease remission, characterized by an increase in fat mass and a decrease in lean mass. These changes are closely associated with the normalization of IGF-I. Thereafter, body composition changes are similar to what is observed with aging.

[ 18 F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

Fully Integrated Quantitative Multiparametric Analysis of Non-Small Cell Lung Cancer at 3-T PET/MRI: Toward One-Stop-Shop Tumor Biological Characterization at the Supervoxel Level.

INTRODUCTION: The aim of this study was to study the feasibility of a fully integrated multiparametric imaging framework to characterize non-small cell lung cancer (NSCLC) at 3-T PET/MRI. PATIENTS AND METHODS: An 18F-FDG PET/MRI multiparametric imaging framework was developed and prospectively applied to 11 biopsy-proven NSCLC patients. For each tumor, 12 parametric maps were generated, including PET full kinetic modeling, apparent diffusion coefficient, T1/T2 relaxation times, and DCE full kinetic modeling. Gaussian mixture model-based clustering was applied at the whole data set level to define supervoxels of similar multidimensional PET/MRI behaviors. Taking the multidimensional voxel behaviors as input and the supervoxel class as output, machine learning procedure was finally trained and validated voxelwise to reveal the dominant PET/MRI characteristics of these supervoxels at the whole data set and individual tumor levels. RESULTS: The Gaussian mixture model-based clustering clustering applied at the whole data set level (17,316 voxels) found 3 main multidimensional behaviors underpinned by the 12 PET/MRI quantitative parameters. Four dominant PET/MRI parameters of clinical relevance (PET: k2, k3 and DCE: ve, vp) predicted the overall supervoxel behavior with 97% of accuracy (SD, 0.7; 10-fold cross-validation). At the individual tumor level, these dimensionality-reduced supervoxel maps showed mean discrepancy of 16.7% compared with the original ones. CONCLUSIONS: One-stop-shop PET/MRI multiparametric quantitative analysis of NSCLC is clinically feasible. Both PET and MRI parameters are useful to characterize the behavior of tumors at the supervoxel level. In the era of precision medicine, the full capabilities of PET/MRI would give further insight of the characterization of NSCLC behavior, opening new avenues toward image-based personalized medicine in this field.

AZTEK: Adaptive zero TE k-space trajectories.

PURPOSE: Because of short signal lifetimes and respiratory motion, 3D lung MRI is still challenging today. Zero-TE (ZTE) pulse sequences offer promising solutions as they overcome the issue of short T2∗ . Nevertheless, as they rely on continuous readout gradients, the trajectories they follow in k-space are not adapted to retrospective gating and inferred motion correction. THEORY AND METHODS: We propose AZTEK (adaptive ZTE k-space trajectories), a set of 3D radial trajectories featuring three tuning parameters, to adapt the acquisition to any moving organ while keeping seamless transitions between consecutive spokes. Standard ZTE and AZTEK trajectories were compared for static and moving phantom acquisitions as well as for human thoracic imaging performed on 3 volunteers (1 healthy and 2 patients with lung cancer). RESULTS: For the static phantom, we observe comparable image qualities with standard and AZTEK trajectories. For the moving phantom, spatially coherent undersampling artifacts observed on gated images with the standard trajectory are alleviated with AZTEK. The same improvement in image quality is obtained in human, so details are more delineated in the lung with the use of the adaptive trajectory. CONCLUSION: The AZTEK technique opens the possibility for 3D dynamic ZTE lung imaging with retrospective gating. It enables us to uniformly sample the k-space for any arbitrary respiratory motion gate, while preserving static image quality, improving dynamic image quality and guaranteeing continuous readout gradient transitions between spokes, which makes it appropriate to ZTE.

18F-FDG PET and DCE kinetic modeling and their correlations in primary NSCLC: first voxel-wise correlative analysis of human simultaneous [18F]FDG PET-MRI data.

OBJECTIVES: To decipher the correlations between PET and DCE kinetic parameters in non-small-cell lung cancer (NSCLC), by using voxel-wise analysis of dynamic simultaneous [18F]FDG PET-MRI. MATERIAL AND METHODS: Fourteen treatment-naïve patients with biopsy-proven NSCLC prospectively underwent a 1-h dynamic [18F]FDG thoracic PET-MRI scan including DCE. The PET and DCE data were normalized to their corresponding T1-weighted MR morphological space, and tumors were masked semi-automatically. Voxel-wise parametric maps of PET and DCE kinetic parameters were computed by fitting the dynamic PET and DCE tumor data to the Sokoloff and Extended Tofts models respectively, by using in-house developed procedures. Curve-fitting errors were assessed by computing the relative root mean square error (rRMSE) of the estimated PET and DCE signals at the voxel level. For each tumor, Spearman correlation coefficients (rs) between all the pairs of PET and DCE kinetic parameters were estimated on a voxel-wise basis, along with their respective bootstrapped 95% confidence intervals (n = 1000 iterations). RESULTS: Curve-fitting metrics provided fit errors under 20% for almost 90% of the PET voxels (median rRMSE = 10.3, interquartile ranges IQR = 8.1; 14.3), whereas 73.3% of the DCE voxels showed fit errors under 45% (median rRMSE = 31.8%, IQR = 22.4; 46.6). The PET-PET, DCE-DCE, and PET-DCE voxel-wise correlations varied according to individual tumor behaviors. Beyond this wide variability, the PET-PET and DCE-DCE correlations were mainly high (absolute rs values > 0.7), whereas the PET-DCE correlations were mainly low to moderate (absolute rs values < 0.7). Half the tumors showed a hypometabolism with low perfused/vascularized profile, a hallmark of hypoxia, and tumor aggressiveness. CONCLUSION: A dynamic "one-stop shop" procedure applied to NSCLC is technically feasible in clinical practice. PET and DCE kinetic parameters assessed simultaneously are not highly correlated in NSCLC, and these correlations showed a wide variability among tumors and patients. These results tend to suggest that PET and DCE kinetic parameters might provide complementary information. In the future, this might make PET-MRI a unique tool to characterize the individual tumor biological behavior in NSCLC.

Cherubism as a systemic skeletal disease: evidence from an aggressive case.

BACKGROUND: Cherubism is a rare autosomal dominant genetic condition caused by mutations in the SH3BP2 gene. This disease is characterized by osteolysis of the jaws, with the bone replaced by soft tissue rich in fibroblasts and multinuclear giant cells. SH3BP2 is a ubiquitous adaptor protein yet the consequences of SH3BP2 mutation have so far been described as impacting only face. Cherubism mouse models have been generated and unlike human patients, the knock-in mice exhibit systemic bone loss together with a systemic inflammation. CASE PRESENTATION: In light of these observations, we decided to search for a systemic cherubism phenotype in a 6-year-old girl with an aggressive cherubism. We report here the first case of cherubism with systemic manifestations. Bone densitometry showed low overall bone density (total body Z-score = - 4.6 SD). Several markers of bone remodelling (CTx, BALP, P1NP) as well as inflammation (TNFα and IL-1) were elevated. A causative second-site mutation in other genes known to influence bone density was ruled out by sequencing a panel of such genes. CONCLUSIONS: If this systemic skeletal cherubism phenotype should be confirmed, it would simplify the treatment of severe cherubism patients and allay reservations about applying a systemic treatment such as those recently published (tacrolimus or imatinib) to a disease heretofore believed to be localised to the jaws.

Diffusion-weighted Imaging Voxelwise-matched Analyses of Lung Cancer at 3.0-T PET/MRI: Reverse Phase Encoding Approach for Echo-planar Imaging Distortion Correction.

Background PET/MRI has drawn increasing interest in thoracic oncology due to the simultaneous acquisition of PET and MRI data. Geometric distortions related to diffusion-weighted imaging (DWI) limit the evaluation of voxelwise multimodal analyses. Purpose To assess the effectiveness of reverse phase encoding in correcting DWI geometric distortion for multimodal PET/MRI voxelwise lung tumor analyses. Materials and Methods In this prospective study, reverse phase encoding method was implemented with 3.0-T PET/MRI to correct geometric distortions related to DWI. The method was validated in dedicated phantom and then applied to 12 consecutive patients (mean age, 66 years ± 13 [standard deviation]; 10 men) suspected of having lung cancer who underwent fluorodeoxyglucose PET/MRI between October 2018 and April 2019. The effects on DWI-related image matching and apparent diffusion coefficient (ADC) regional map computation were assessed. Consequences on multimodal PET/MRI voxelwise lung tumor analyses were evaluated. Spearman correlation coefficients (rs) between the standardized uptake value (SUV) and ADC data corrected for distortion were computed from optimal realigned DWI PET data, along with bootstrap confidence intervals. Results Phantom results showed that in highly distorted areas, correcting the distortion significantly reduced the mean error against the ground truth (-25% ± 10.6 to -18.4% ± 12.6; P < .001) and the number of voxels with more than 20% error (from 85.3% to 31.4%). In the 12 patients, the coregistration of multimodal PET/MRI tumor data was improved by using the reverse phase encoding method (0.4%-44%). In all tumors, voxelwise correlations (rs) between ADC and SUV revealed null or weak monotonic relationships (mean rs of 0.016 ± 0.24 with none above 0.5). Conclusion Reverse phase encoding is a simple-to-implement method for improved diffusion-weighted multimodal PET/MRI voxelwise-matched analyses in lung cancer. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Colletti in this issue.

Hyperparathyroidism in Patients With X-Linked Hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Hyperparathyroidism may develop in XLH patients; however, its prevalence, pathogenesis, and clinical presentation are not documented. This observational study (CNIL 171036 v 0) recruited XLH adult patients in a single tertiary referral center. Each patient was explored in standardized conditions and compared with two healthy volunteers, matched for sex, age, and 25-OH vitamin D concentrations. The primary endpoint was the proportion of patients with hyperparathyroidism. The secondary endpoints were the factors influencing serum parathyroid hormone (PTH) concentrations and the prevalence of hypercalcemic hyperparathyroidism. Sixty-eight patients (51 women, 17 men) were enrolled and matched with 136 healthy volunteers. Patients had higher PTH concentrations compared with healthy controls (53.5 ng/L, interquartile range [IQR] 36.7-72.7 versus 36.0 ng/L, IQR 27.7-44.0, p < .0001). Hyperparathyroidism was observed in 17 patients of 68 (25%). In patients, a positive relationship between PTH and calcium concentrations and a negative relationship between PTH and phosphate concentrations were observed. Seven (10%) patients (3 premenopausal women, 1 postmenopausal woman, and 3 men) were diagnosed with hypercalcemic hyperparathyroidism. All underwent parathyroid surgery, with consecutive normalization of calcium and PTH concentrations. Hyperparathyroidism is a frequent complication in XLH adult patients. Disruption of the physiological regulation of PTH secretion contributes to parathyroid disease. Early-onset hypercalcemic hyperparathyroidism can be effectively and safely cured by surgical resection. © 2020 American Society for Bone and Mineral Research.

Efficacy and Safety of Intra-gastric Balloon Placement in Dialyzed Patients Awaiting Kidney Transplantation.

BACKGROUND: The number of obese patients who are candidates for renal transplantation has considerably increased, but obesity can be a barrier to kidney transplantation. Weight loss is often difficult through diet alone. We studied the efficacy and tolerance of the intra-gastric balloon (IGB) procedure in obese patients who were undergoing dialysis and were candidates for a renal transplantation. PATIENTS AND METHODS: Obese patients (BMI > 30 kg/m2) who were candidates for renal transplantation were prospectively included in the study between 2010 and 2012. The balloon was inserted and removed during a gastric endoscopy under general anesthesia. The treatment lasted 6 months. The end point was a decrease in BMI after 6 months. Body impedance spectrometry (BIS) and nutritional statute were evaluated initially and then after IGB removal. RESULTS: Seventeen patients (nine females and eight males) with a mean age of 53.4 years [19.4-69.4] were included. The decrease in body mass index (BMI) during the 6-month placement was 3 kg/m2 (from 37.7 to 34.4 kg/m2). The mean weight loss was 7 kg. The mean percentage of excess weight loss after 6 months was 20.2 (± 11.4). The tolerance was good without any complications. Eleven patients underwent kidney transplantation. CONCLUSION: IGB in obese dialyzed patients who are candidates for renal transplantation is safe and effective. However, the amount of weight loss can vary.

Comparative Study Between Functional MR Urography and Renal Scintigraphy to Evaluate Drainage Curves and Split Renal Function in Children With Congenital Anomalies of Kidney and Urinary Tract (CAKUT).

Background: Obstructive congenital anomalies of the kidney and urinary tract have a high risk of kidney failure if not surgically corrected. Dynamic renal scintigraphy is the gold standard technique to evaluate drainage curves and split renal function (SRF). Objectives: To compare functional magnetic resonance (MR) urography with dynamic renal scintigraphy in measuring volumetric SRF and in the classification of drainage curves in patients with congenital anomalies of the kidney and urinary tract. Materials and Methods: We retrospectively collected patients with hydroureteronephrosis or pelvicalyceal dilatation at renal ultrasound, who underwent both functional MR urography and dynamic renal scintigraphy (DRS) within 6 months. DRS studies were evaluated by a single nuclear medicine physician with a double reading. Functional MR urography renograms were blind evaluated twice by two radiologists. The functional MR urographyintra- and inter-reading agreements as well as the agreement between the two imaging techniques were calculated. SRF was evaluated by Area Under the Curve and Rutland-Patlak methods. Drainage curves were classified as normal, borderline or accumulation patterns by both the techniques. Results: Fifty-two children were studied, 14 with bilateral involvement. A total of 104 kidney-urinary tracts were considered: 38 normal and 66 dilated. Considering Area Under the Curve and Rutland-Patlak for SRF, the intra- and inter-reader agreements of functional MR urography had excellent and good results, respectively, and the two techniques demonstrated a good concordance (r2: 67% for Area Under the Curve and 72% for Rutland-Patlak). Considering drainage curves, the inter-readers agreement for functional MR urography and the concordance between the two techniques were moderate (Cohen's k, respectively, 55.7 and 56.3%). Conclusions: According to our results, there are no significant differences between functional MR urography and DRS in measuring volumetric SRF and in the classification of drainage curves in patients with congenital anomalies of the kidney and urinary tract.

Reduced bone mineral density among HIV-infected, virologically controlled young men: prevalence and associated factors.

OBJECTIVE: Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). We aimed to determine the prevalence of reduced BMD and its associated factors among young PLHIV men, virologically controlled by combination antiretroviral therapy (cART). DESIGN: A bicentric cross-sectional study. METHODS: We selected men, aged less than 50 years, treated by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis, respectively. Linear and polytomous logistic regression analyses were performed. RESULTS: Among 230 men with a median age of 43 [interquartile range (IQR), 36-47] years, BMI of 23.5 (21.3-25.3) kg/m(2) and median duration of cART of 4.2 (1.7-8.5) years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P < 0.01] and osteoporosis (OR = 1.24, P < 0.01). Oestradiol levels decrease were associated with osteoporosis (OR = 1.32, P < 0.05) and lower lean mass with osteopenia (OR = 2.98, P < 0.01). There was a protective effect of the duration of cART (OR = 0.87, P < 0.01), which was even greater when the duration was more than 3 years (OR = 0.44, P = 0.02). CONCLUSION: There is a high prevalence of reduced BMD among young men, despite persistent virological control of HIV-infection. This observation raises the question of extending current recommendations for BMD assessment to PLHIV aged < 50 years for whom BMD has stabilized after cART initiation, i.e. treated for more than three years.

Rapid Contour-based Segmentation for 18F-FDG PET Imaging of Lung Tumors by Using ITK-SNAP: Comparison to Expert-based Segmentation.

Purpose To assess the performance of the ITK-SNAP software for fluorodeoxyglucose (FDG) positron emission tomography (PET) segmentation of complex-shaped lung tumors compared with an optimized, expert-based manual reference standard. Materials and Methods Seventy-six FDG PET images of thoracic lesions were retrospectively segmented by using ITK-SNAP software. Each tumor was manually segmented by six raters to generate an optimized reference standard by using the simultaneous truth and performance level estimate algorithm. Four raters segmented 76 FDG PET images of lung tumors twice by using ITK-SNAP active contour algorithm. Accuracy of ITK-SNAP procedure was assessed by using Dice coefficient and Hausdorff metric. Interrater and intrarater reliability were estimated by using intraclass correlation coefficients of output volumes. Finally, the ITK-SNAP procedure was compared with currently recommended PET tumor delineation methods on the basis of thresholding at 41% volume of interest (VOI; VOI41) and 50% VOI (VOI50) of the tumor's maximal metabolism intensity. Results Accuracy estimates for the ITK-SNAP procedure indicated a Dice coefficient of 0.83 (95% confidence interval: 0.77, 0.89) and a Hausdorff distance of 12.6 mm (95% confidence interval: 9.82, 15.32). Interrater reliability was an intraclass correlation coefficient of 0.94 (95% confidence interval: 0.91, 0.96). The intrarater reliabilities were intraclass correlation coefficients above 0.97. Finally, VOI41 and VOI50 accuracy metrics were as follows: Dice coefficient, 0.48 (95% confidence interval: 0.44, 0.51) and 0.34 (95% confidence interval: 0.30, 0.38), respectively, and Hausdorff distance, 25.6 mm (95% confidence interval: 21.7, 31.4) and 31.3 mm (95% confidence interval: 26.8, 38.4), respectively. Conclusion ITK-SNAP is accurate and reliable for active-contour-based segmentation of heterogeneous thoracic PET tumors. ITK-SNAP surpassed the recommended PET methods compared with ground truth manual segmentation.

Flow MRI simulation in complex 3D geometries: Application to the cerebral venous network.

PURPOSE: Develop and evaluate a complete tool to include 3D fluid flows in MRI simulation, leveraging from existing software. Simulation of MR spin flow motion is of high interest in the study of flow artifacts and angiography. However, at present, only a few simulators include this option and most are restricted to static tissue imaging. THEORY AND METHODS: An extension of JEMRIS, one of the most advanced high performance open-source simulation platforms to date, was developed. The implementation of a Lagrangian description of the flow allows simulating any MR experiment, including both static tissues and complex flow data from computational fluid dynamics. Simulations of simple flow models are compared with real experiments on a physical flow phantom. A realistic simulation of 3D flow MRI on the cerebral venous network is also carried out. RESULTS: Simulations and real experiments are in good agreement. The generality of the framework is illustrated in 2D and 3D with some common flow artifacts (misregistration and inflow enhancement) and with the three main angiographic techniques: phase contrast velocimetry (PC), time-of-flight, and contrast-enhanced imaging MRA. CONCLUSION: The framework provides a versatile and reusable tool for the simulation of any MRI experiment including physiological fluids and arbitrarily complex flow motion.

Effect of CRP value on 18F-FDG PET vascular positivity in Takayasu arteritis: a systematic review and per-patient based meta-analysis.

PURPOSE: The aim of this study was to quantify the association between the CRP value and 18F-FDG PET vascular positivity in Takayasu arteritis (TAK) through a structured dedicated systematic review and meta-analysis. METHODS: From January 2000 to December 2016, the PubMed/MEDLINE database was searched for articles specifically dealing with the assessment of vascular inflammation using 18F-FDG PET and CRP biomarkers in TAK. Inclusion criteria for the qualitative analysis were (1) 18F-FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available. For the meta-analysis, PET-positive and PET-negative subgroups with the corresponding CRP concentrations were generated based on per patient data. The standard mean difference, which represents the effect of the CRP concentrations on the 18F-FDG PET vascular uptake, was computed for all studies, and then the results were pooled together. RESULTS: Among the 33 initial citations, nine complete articles including 210 patients fulfilled the inclusion criteria. Five studies found a significant correlation between the 18F-FDG PET and CRP concentration, one provided a trend towards association and three did not find any association between the two biomarkers. Six studies found a significant association between 18F-FDG PET and clinical disease activity, one found a trend towards association and the last two studies did not evaluate this correlation. The meta-analysis (121 patients) provided the following results: Standard Mean Deviation = 0.54 [0.15;0.92]; Chi2 = 3.35; I2 = 0%; Test for overall effect: Z = 2.70 (P = 0.007). CONCLUSION: The CRP concentration only moderately reflects the 18F-FDG PET vascular positivity in TAK, suggesting dissociated information. Standardized longitudinal prospective studies are necessary to assess the value of 18F-FDG PET as an independent biomarker for subtle vascular wall inflammation detection.