The usefulness of 18F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD)

Background: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for MTX-LPD. Methods: We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by 18F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of 18F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX. Results: MTX-LPD lesions were observed in 92/324 (28.4 %) regions. 18F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8-47.1), 44.3 (range 0-362.6) ml, 181.8 (range 0-2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0-24.9), 15.7 (range 0-250.1) ml, and 97.4 (range 0-1052.1) ml. Conclusions: Although 18F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the 18F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with O-15-H2O PET

This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against O-15-H2O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 +/- 0.8) was significantly lower than that in the validation group (5.2 +/- 1.8) (P = 0.0011). We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. aEuro cent MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. aEuro cent MBF and CFR showed good correlation between dynamic CTP and PET. aEuro cent Lower CFR was well demonstrated in CAD patients by dynamic CTP

Assessment of Coronary Flow Velocity Reserve in the Left Main Trunk Using Phase-contrast MR Imaging at 3T : Comparison with O-15-labeled Water Positron Emission Tomography

Purpose: The aim of this study was to verify coronary flow velocity reserve (CFVR) on the left main trunk (LMT) in comparison with myocardial flow reserve (MFR) by O-15-labeled water positron emission tomography (PET) (MFR-PET) in both the healthy adults and the patients with coronary artery disease (CAD), and to evaluate the feasibility of CFVR to detect CAD. Methods: Eighteen healthy adults and 13 patients with CAD were evaluated. CFVR in LMT was estimated by 3T magnetic resonance imaging (MRI) with phase contrast technique. MFR-PET in the LMT territory including anterior descending artery and circumflex artery was calculated as the ratio of myocardial blood flow (MBF)-PET at stress to MBF-PET at rest. Results: There was a significant positive relationship between CFVR and MFR-PET (R = 0.45, P < 0.0001). Inter-observer calculations of CFVR showed good correlation (R-2 = 0.93, P < 0.0001). The CFVR in patients with CAD was significantly lower than that in healthy adults (1.90 +/- 0.61 vs. 2.77 +/- 1.03, respectively, P = 0.01), which were similar to the results of MFR-PET (2.23 +/- 0.84 vs. 3.96 +/- 1.04, respectively, P < 0.0001). For the detection of patients with CAD, the area under the curve was 0.78 (P = 0.01). The sensitivity was 0.77 and specificity was 0.72 when a cut-off of 2.15 was used. Conclusion: CFVR by 3T was validated with MFR-PET. CFVR could detect the patients with CAD. This method is a simple and reliable index without radiation or contrast material

A Deep Learning-Based Model for Classifying Osteoporotic Lumbar Vertebral Fractures on Radiographs: A Retrospective Model Development and Validation Study

Early diagnosis and initiation of treatment for fresh osteoporotic lumbar vertebral fractures (OLVF) are crucial. Magnetic resonance imaging (MRI) is generally performed to differentiate between fresh and old OLVF. However, MRIs can be intolerable for patients with severe back pain. Furthermore, it is difficult to perform in an emergency. MRI should therefore only be performed in appropriately selected patients with a high suspicion of fresh fractures. As radiography is the first-choice imaging examination for the diagnosis of OLVF, improving screening accuracy with radiographs will optimize the decision of whether an MRI is necessary. This study aimed to develop a method to automatically classify lumbar vertebrae (LV) conditions such as normal, old, or fresh OLVF using deep learning methods with radiography. A total of 3481 LV images for training, validation, and testing and 662 LV images for external validation were collected. Visual evaluation by two radiologists determined the ground truth of LV diagnoses. Three convolutional neural networks were ensembled. The accuracy, sensitivity, and specificity were 0.89, 0.83, and 0.92 in the test and 0.84, 0.76, and 0.89 in the external validation, respectively. The results suggest that the proposed method can contribute to the accurate automatic classification of LV conditions on radiography

Systemic Oxidative Stress Is Associated With Lower Aerobic Capacity and Impaired Skeletal Muscle Energy Metabolism in Patients With Metabolic Syndrome

OBJECTIVE-Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS-The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using P-31- and (1)proton-magnetic resonance spectroscopy, respectively. RESULTS-Serum TBARS were elevated (12.4 +/- 7.1 vs. 3.7 +/- 1.1 mu mol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 +/- 51.2 vs. 398.7 +/- 105.2 mu mol/L, P < 0.01; and 22.2 +/- 8.4 vs. 31.5 +/- 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = -0.49 and r = -0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively). CONCLUSIONS-Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS

Reduced SHARPIN and LUBAC Formation May Contribute to CCl4- or Acetaminophen-Induced Liver Cirrhosis in Mice

Linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on nuclear factor-κB (NF-κB) essential modulator (NEMO) and induces NF-κB pathway activation. SHARPIN expression and LUBAC formation were significantly reduced in the livers of mice 24 h after the injection of either carbon tetrachloride (CCl4) or acetaminophen (APAP), both of which produced the fulminant hepatitis phenotype. To elucidate its pathological significance, hepatic SHARPIN expression was suppressed in mice by injecting shRNA adenovirus via the tail vein. Seven days after this transduction, without additional inflammatory stimuli, substantial inflammation and fibrosis with enhanced hepatocyte apoptosis occurred in the livers. A similar but more severe phenotype was observed with suppression of HOIP, which is responsible for the E3 ligase activity of LUBAC. Furthermore, in good agreement with these in vivo results, transduction of Hepa1-6 hepatoma cells with SHARPIN, HOIL-1L, or HOIP shRNA adenovirus induced apoptosis of these cells in response to tumor necrosis factor-α (TNFα) stimulation. Thus, LUBAC is essential for the survival of hepatocytes, and it is likely that reduction of LUBAC is a factor promoting hepatocyte death in addition to the direct effect of drug toxicity