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
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.
2016
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.
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.
2015
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
OBJECTIVE:
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.
CONCLUSION:
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.
