Evaluation of activity of Graves' orbitopathy with multiparameter orbital magnetic resonance imaging (MRI).

Background: When quantitative magnetic resonance imaging (MRI) is used to assess the activity of Graves' orbitopathy (GO), the examination is generally focused on a specific orbital tissue, especially the extraocular muscles (EOMs). However, GO usually involves the entire intraorbital soft tissue. The aim of this study was to use multiparameter MRI on multiple orbital tissues to distinguish the active and inactive GO. Methods: From May 2021 to March 2022, consecutive patients with GO were prospectively enrolled at Peking University People's Hospital (Beijing, China) and divided into those with active disease and those with inactive disease based on a clinical activity score. Patients then underwent MRI, including sequences of conventional imaging, T1 mapping, T2 mapping, and mDIXON Quant. Width, T2 signal intensity ratio (SIR), T1 values, T2 values, and fat fraction of EOMs, as well as water fraction (WF) of orbital fat (OF), were measured. Parameters were compared between the 2 groups, and a combined diagnostic model was constructed using logistic regression analysis. Receiver operating characteristic analysis was used to test the diagnostic performance of the model. Results: Sixty-eight patients with GO (27 with active GO, 41 with inactive GO) were included in the study. The active GO group had higher values of EOM thickness, T2 SIR, and T2 values, as well as higher WF of OF. The diagnostic model, which included EOM T2 value and WF of OF, demonstrated a good ability to distinguish between active and inactive GO (area under the curve, 0.878; 95% CI: 0.776-0.945; sensitivity, 88.89%; specificity, 75.61%). Conclusions: A combined model incorporating the T2 value of EOMs and the WF of OF was able to identify cases of active GO, potentially offering an effective and noninvasive method to assess pathological changes in this disease.

Chemometric QSAR modeling of acute oral toxicity of Polycyclic Aromatic Hydrocarbons (PAHs) to rat using simple 2D descriptors and interspecies toxicity modeling with mouse.

The information of the acute oral toxicity for most polycyclic aromatic hydrocarbons (PAHs) in mammals are lacking due to limited experimental resources, leading to a need to develop reliable in silico methods to evaluate the toxicity endpoint. In this study, we developed the quantitative structure-activity relationship (QSAR) models by genetic algorithm (GA) and multiple linear regression (MLR) for the rat acute oral toxicity (LD50) of PAHs following the strict validation principles of QSAR modeling recommended by OECD. The best QSAR model comprised eight simple 2D descriptors with definite physicochemical meaning, which showed that maximum atom-type electrotopological state, van der Waals surface area, mean atomic van der Waals volume, and total number of bonds are main influencing factors for the toxicity endpoint. A true external set (554 compounds) without rat acute oral toxicity values, and 22 limit test compounds, were firstly predicted along with reliability assessment. We also compared our proposed model with the OPERA predictions and recently published literature to prove the prediction reliability. Furthermore, the interspecies toxicity (iST) models of PAHs between rat and mouse were also established, validated and employed for filling data gap. Overall, our developed models should be applicable to new or untested or not yet synthesized PAHs falling within the applicability domain (AD) of the models for rapid acute oral toxicity prediction, thus being important for environmental or personal exposure risk assessment under regulatory frameworks.