Based Radiomics for Molecular Subtyping of Gliomas

Chia-Feng Lu*Fei-Ting Hsu,Kevin Li-Chun Hsieh,Yu-Chieh Jill Kao,Sho-Jen Cheng, Justin Bo-Kai Hsu,Ping-Huei Tsai,Ray-Jade Chen,Chao-Ching Huang,Yun Yen,and Cheng-Yu Chen

Clin Cancer Res; 24(18) September 15, 2018PDF

Purpose: The new classification announced by the World Health Organization in 2016 recognized five molecular subtypes of diffuse gliomas based on isocitrate dehydrogenase (IDH) and 1p/19q genotypes in addition to histologic phenotypes. Weaim to determine whether clinical MRI can stratify these molecular subtypes to benefit the diagnosis and monitoring of gliomas. Experimental Design: The data from 456 subjects with gliomas were obtained from The Cancer Imaging Archive. Overall, 214 subjects, including 106 cases of glioblastomas and 108 cases of lower grade gliomas with preoperative MRI, survival data, histology, IDH, and 1p/19q status were included. We proposed a three-level machine-learning model based on multimodal MR radiomics to classify glioma subtypes. An independent dataset with 70 glioma subjects was further collected to verify the model performance. Results: The IDH and 1p/19q status of gliomas can be classified by radiomics and machine-learning approaches, with areas under ROC curves between 0.922 and 0.975 and accuracies between 87.7% and 96.1% estimated on the training dataset. The test on the validation dataset showed a comparable model performance with that on the training dataset, suggesting the efficacy of the trained classifiers. The classification of 5 molecular subtypes solely based on the MR phenotypes achieved an 81.8% accuracy, and a higher accuracy of 89.2% could be achieved if the histology diagnosis is available. Conclusions: The MR radiomics-based method provides a reliable alternative to determine the histology and molecular subtypes of gliomas.

Changes in sensorimotor-related thalamic diffusion properties and cerebrospinal fluid hydrodynamics predict gait responses to tap test in idiopathic normal-pressure hydrocephalus

Ping-Huei Tsai*,Yung-Chieh Chen,Shih-Wei Chiang,Teng-Yi Huang,Ming-Chung Chou,Hua-Shan Liu,Hsiao-Wen Chung,Giia-Sheun Peng,Hsin-I Ma,Hung-Wen Kao,Cheng-Yu Chen

European Radiology (2018) 28:4504–4513PDF

Objectives To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients. Methods In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DTrelated indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients. Results Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FAvalue were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses. Conclusions Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH.

Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI

Ahmed Atef Ahmed Ali, Fei-Ting Hsu* , Chia-Ling Hsieh, Chia-Yang Shiau, Chiao-Hsi Chiang, Zung-Hang Wei, Cheng-Yu Chen* and Hsu-Shan Huang.

Scientific Reports 2016 Nov 11;6:36650. PDF

We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR-ERK-NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.

Curcumin Sensitizes Hepatocellular Carcinoma Cells to Radiation via Suppression of Radiation-Induced NF-kB Activity

Hsu FT*, Liu YC, Hwang JJ.

Journal of Biomedicine and Biotechnology (2015.07 Accept). PDF

The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC) cells in vitro were evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-κB activation, and expressions of NF-κB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene, mitochondrial membrane potential (MMP), electrophoretic mobility shift (EMSA), and Western blot assays in Huh7-NF-κB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IκBαM) vector, a specific inhibitor of NF-κB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-κB activity and expressions of NF-κB downstream proteins in HCC cells. IκBαM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-κB activation.

Revisiting Neuroimaging of Abusive Head Trauma in Infants and Young Children

Kevin Li-Chun Hsieh*, Robert A. Zimmerman, Hung Wen Kao and Cheng-Yu Chen*.

American Journal of Roentgenology. 2015 May 204(5):944-52. PDF


The purpose of this article is to use a mechanism-based approach to review the neuroimaging findings of abusive head trauma to infants. Advanced neuroimaging provides insights into not only the underlying mechanisms of craniocerebral injuries but also the long-term prognosis of brain injury for children on whom these injuries have been inflicted.


Knowledge of the traumatic mechanisms, the key neuroimaging findings, and the implications of functional imaging findings should help radiologists characterize the underlying causes of the injuries inflicted, thereby facilitating effective treatment.