Spin-lock based fast whole-brain 3D macromolecular proton fraction mapping of relapsing-remitting multiple sclerosis.

A sensitive and efficient imaging technique is required to assess the subtle abnormalities occurring in the normal-appearing white matter (NAWM) and normal-appearing grey matter (NAGM) in patients with relapsing-remitting multiple sclerosis (RRMS). In this study, a fast 3D macromolecular proton fraction (MPF) quantification based on spin-lock (fast MPF-SL) sequence was proposed for brain MPF mapping. Thirty-four participants, including 17 healthy controls and 17 RRMS patients were prospectively recruited. We conducted group comparison and correlation between conventional MPF-SL, fast MPF-SL, and DWI, and compared differences in quantified parameters within MS lesions and the regional NAWM, NAGM, and normal-appearing deep grey matter (NADGN). MPF of MS lesions was significantly reduced (7.17% ± 1.15%, P < 0.01) compared to all corresponding normal-appearing regions. MS patients also showed significantly reduced mean MPF values compared with controls in NAGM (4.87% ± 0.38% vs 5.21% ± 0.32%, P = 0.01), NAWM (9.49% ± 0.69% vs 10.32% ± 0.59%, P < 0.01) and NADGM (thalamus 5.59% ± 0.67% vs 6.00% ± 0.41%, P = 0.04; caudate 5.10% ± 0.55% vs 5.53% ± 0.58%, P = 0.03). MPF and ADC showed abnormalities in otherwise normal appearing close to lesion areas (P < 0.01). In conclusion, time-efficient MPF mapping of the whole brain can be acquired efficiently (< 3 min) using fast MPF-SL. It offers a promising alternative way to detect white matter abnormalities in MS.

Deep learning for the automatic detection and segmentation of parotid gland tumors on MRI.

OBJECTIVES: Parotid gland tumors (PGTs) often occur as incidental findings on magnetic resonance images (MRI) that may be overlooked. This study aimed to construct and validate a deep learning model to automatically identify parotid glands (PGs) with a PGT from normal PGs, and in those with a PGT to segment the tumor. MATERIALS AND METHODS: The nnUNet combined with a PG-specific post-processing procedure was used to develop the deep learning model trained on T1-weighed images (T1WI) in 311 patients (180 PGs with tumors and 442 normal PGs) and fat-suppressed (FS)-T2WI in 257 patients (125 PGs with tumors and 389 normal PGs), for detecting and segmenting PGTs with five-fold cross-validation. Additional validation set separated by time, comprising T1WI in 34 and FS-T2WI in 41 patients, was used to validate the model performance. RESULTS AND CONCLUSION: To identify PGs with tumors from normal PGs, using combined T1WI and FS-T2WI, the deep learning model achieved an accuracy, sensitivity and specificity of 98.2% (497/506), 100% (119/119) and 97.7% (378/387), respectively, in the cross-validation set and 98.5% (67/68), 100% (20/20) and 97.9% (47/48), respectively, in the validation set. For patients with PGTs, automatic segmentation of PGTs on T1WI and FS-T2WI achieved mean dice coefficients of 86.1% and 84.2%, respectively, in the cross-validation set, and of 85.9% and 81.0%, respectively, in the validation set. The proposed deep learning model may assist the detection and segmentation of PGTs and, by acting as a second pair of eyes, ensure that incidentally detected PGTs on MRI are not missed.

Dual-Level Augmentation Radiomics Analysis for Multisequence MRI Meningioma Grading.

BACKGROUND: Preoperative, noninvasive prediction of meningioma grade is important for therapeutic planning and decision making. In this study, we propose a dual-level augmentation strategy incorporating image-level augmentation (IA) and feature-level augmentation (FA) to tackle class imbalance and improve the predictive performance of radiomics for meningioma grading on Magnetic Resonance Imaging (MRI). METHODS: This study recruited 160 consecutive patients with pathologically proven meningioma (129 low-grade (WHO grade I) tumors; 31 high-grade (WHO grade II and III) tumors) with preoperative multisequence MRI imaging. A dual-level augmentation strategy combining IA and FA was applied and evaluated in 100 repetitions in 3-, 5-, and 10-fold cross-validation. RESULTS: The best area under the receiver operating characteristics curve of our method in 100 repetitions was ≥0.78 in all cross-validations. The corresponding cross-validation sensitivities (cross-validation specificity) were 0.72 (0.69), 0.76 (0.71), and 0.63 (0.82) in 3-, 5-, and 10-fold cross-validation, respectively. The proposed method achieved significantly better performance and distribution of results, outperforming single-level augmentation (IA or FA) or no augmentation in each cross-validation. CONCLUSIONS: The dual-level augmentation strategy using IA and FA significantly improves the performance of the radiomics model for meningioma grading on MRI, allowing better radiomics-based preoperative stratification and individualized treatment.

3D Lightweight Network for Simultaneous Registration and Segmentation of Organs-at-Risk in CT Images of Head and Neck Cancer.

Image-guided radiation therapy (IGRT) is the most effective treatment for head and neck cancer. The successful implementation of IGRT requires accurate delineation of organ-at-risk (OAR) in the computed tomography (CT) images. In routine clinical practice, OARs are manually segmented by oncologists, which is time-consuming, laborious, and subjective. To assist oncologists in OAR contouring, we proposed a three-dimensional (3D) lightweight framework for simultaneous OAR registration and segmentation. The registration network was designed to align a selected OAR template to a new image volume for OAR localization. A region of interest (ROI) selection layer then generated ROIs of OARs from the registration results, which were fed into a multiview segmentation network for accurate OAR segmentation. To improve the performance of registration and segmentation networks, a centre distance loss was designed for the registration network, an ROI classification branch was employed for the segmentation network, and further, context information was incorporated to iteratively promote both networks' performance. The segmentation results were further refined with shape information for final delineation. We evaluated registration and segmentation performances of the proposed framework using three datasets. On the internal dataset, the Dice similarity coefficient (DSC) of registration and segmentation was 69.7% and 79.6%, respectively. In addition, our framework was evaluated on two external datasets and gained satisfactory performance. These results showed that the 3D lightweight framework achieved fast, accurate and robust registration and segmentation of OARs in head and neck cancer. The proposed framework has the potential of assisting oncologists in OAR delineation.

To explore the mechanism of tobacco addiction using structural and functional MRI: a preliminary study of the role of the cerebellum-striatum circuit.

Previous studies have found that the striatum and the cerebellum played important roles in nicotine dependence, respectively. In heavy smokers, however, the effect of resting-state functional connectivity of cerebellum-striatum circuits in nicotine dependence remained unknown. This study aimed to explore the role of the circuit between the striatum and the cerebellum in addiction in heavy smokers using structural and functional magnetic resonance imaging. The grey matter volume differences and the resting-state functional connectivity differences in cerebellum-striatum circuits were investigated between 23 heavy smokers and 23 healthy controls. The cigarette dependence in heavy smokers and healthy controls were evaluated by using Fagerström Test. Then, we applied mediation analysis to test whether the resting-state functional connectivity between the striatum and the cerebellum mediates the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Compared with healthy controls, the heavy smokers' grey matter volumes decreased significantly in the cerebrum (bilateral), and increased significantly in the caudate (bilateral). Seed-based resting-state functional connectivity analysis showed significantly higher resting-state functional connectivity among the bilateral caudate, the left cerebellum, and the right middle temporal gyrus in heavy smokers. The cerebellum-striatum resting-state functional connectivity fully mediated the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Heavy smokers showed abnormal interactions and functional connectivity between the striatum and the cerebellum, which were associated with the striatum morphometry and nicotine dependence. Such findings could provide new insights into the neural correlates of nicotine dependence in heavy smokers.

MALT1 Is a Targetable Driver of Epithelial-to-Mesenchymal Transition in Claudin-Low, Triple-Negative Breast Cancer.

MALT1 is the effector protein of the CARMA/Bcl10/MALT1 (CBM) signalosome, a multiprotein complex that drives pro-inflammatory signaling pathways downstream of a diverse set of receptors. Although CBM activity is best known for its role in immune cells, emerging evidence suggests that it plays a key role in the pathogenesis of solid tumors, where it can be activated by selected G protein-coupled receptors (GPCR). Here, we demonstrated that overexpression of GPCRs implicated in breast cancer pathogenesis, specifically the receptors for Angiotensin II and thrombin (AT1R and PAR1), drove a strong epithelial-to-mesenchymal transition (EMT) program in breast cancer cells that is characteristic of claudin-low, triple-negative breast cancer (TNBC). In concert, MALT1 was activated in these cells and contributed to the dramatic EMT phenotypic changes through regulation of master EMT transcription factors including Snail and ZEB1. Importantly, blocking MALT1 signaling, through either siRNA-mediated depletion of MALT1 protein or pharmacologic inhibition of its activity, was effective at partially reversing the molecular and phenotypic indicators of EMT. Treatment of mice with mepazine, a pharmacologic MALT1 inhibitor, reduced growth of PAR1+, MDA-MB-231 xenografts and had an even more dramatic effect in reducing the burden of metastatic disease. These findings highlight MALT1 as an attractive therapeutic target for claudin-low TNBCs harboring overexpression of one or more selected GPCRs. IMPLICATIONS: This study nominates a GPCR/MALT1 signaling axis as a pathway that can be pharmaceutically targeted to abrogate EMT and metastatic progression in TNBC, an aggressive form of breast cancer that currently lacks targeted therapies.

Fully-Automated Segmentation of Nasopharyngeal Carcinoma on Dual-Sequence MRI Using Convolutional Neural Networks.

In this study, we proposed an automated method based on convolutional neural network (CNN) for nasopharyngeal carcinoma (NPC) segmentation on dual-sequence magnetic resonance imaging (MRI). T1-weighted (T1W) and T2-weighted (T2W) MRI images were collected from 44 NPC patients. We developed a dense connectivity embedding U-net (DEU) and trained the network based on the two-dimensional dual-sequence MRI images in the training dataset and applied post-processing to remove the false positive results. In order to justify the effectiveness of dual-sequence MRI images, we performed an experiment with different inputs in eight randomly selected patients. We evaluated DEU's performance by using a 10-fold cross-validation strategy and compared the results with the previous studies. The Dice similarity coefficient (DSC) of the method using only T1W, only T2W and dual-sequence of 10-fold cross-validation as different inputs were 0.620 ± 0.0642, 0.642 ± 0.118 and 0.721 ± 0.036, respectively. The median DSC in 10-fold cross-validation experiment with DEU was 0.735. The average DSC of seven external subjects was 0.87. To summarize, we successfully proposed and verified a fully automatic NPC segmentation method based on DEU and dual-sequence MRI images with accurate and stable performance. If further verified, our proposed method would be of use in clinical practice of NPC.