Anderson Chun On Tsang

Long non-coding RNA expression profiles predict clinical phenotypes in glioma.

Glioma is the commonest form of primary brain tumor in adults with varying malignancy grades and histological subtypes. Long non-coding RNAs (lncRNAs) are a novel class of non-protein-coding transcripts that have been shown to play important roles in cancer development. To discover novel tumor-related lncRNAs and determine their associations with glioma subtypes, we first applied a lncRNA classification pipeline to identify 1970 lncRNAs that were represented on Affymetrix HG-U133 Plus 2.0 array. We then analyzed the lncRNA expression patterns in a set of previously published glioma gene expression profiles of 268 clinical specimens, and identified sets of lncRNAs that were unique to different histological subtypes (astrocytic versus oligodendroglial tumors) and malignancy grades. These lncRNAs signatures were then subject to validation in another non-overlapping, independent data set that contained 157 glioma samples. This is the first reported study that correlates lncRNA expression profiles with malignancy grade and histological differentiation in human gliomas. Our findings indicate the potential roles of lncRNAs in the biogenesis, development and differentiation of gliomas, and provide an important platform for future studies.

High Sensitivity, Wearable, Piezoresistive Pressure Sensors Based on Irregular Microhump Structures and Its Applications in Body Motion Sensing.

UNLABELLED A pressure sensor based on irregular microhump patterns has been proposed and developed. The devices show high sensitivity and broad operating pressure regime while comparing with regular micropattern devices. Finite element analysis (FEA) is utilized to confirm the sensing mechanism and predict the performance of the pressure sensor based on the microhump structures. Silicon carbide sandpaper is employed as the mold to develop polydimethylsiloxane (PDMS) microhump patterns with various sizes. The active layer of the piezoresistive pressure sensor is developed by spin coating PEDOT PSS on top of the patterned PDMS. The devices show an averaged sensitivity as high as 851 kPa(-1) , broad operating pressure range (20 kPa), low operating power (100 nW), and fast response speed (6.7 kHz). Owing to their flexible properties, the devices are applied to human body motion sensing and radial artery pulse. These flexible high sensitivity devices show great potential in the next generation of smart sensors for robotics, real-time health monitoring, and biomedical applications.

Complications of post-craniectomy cranioplasty: risk factor analysis and implications for treatment planning.

The aim of this study was to review all post-craniectomy cranioplasties performed in a single institution, with an emphasis on procedure-related complications and risk factor analysis. Post-craniectomy cranioplasty is known to be associated with significant complications. Previous studies on predictors of complications have yielded conflicting results. We conducted a retrospective study on prospectively collected data on all cranioplasties done between 1 January 2003 and 31 December 2012. Multivariate analysis was performed to interrogate potential risk factors predisposing to procedure-related complications. Of the 162 procedures, the overall complication rate was 16.7%. Infection and flap depression occurred in 13 (8%) and five patients (3.1%), respectively. These led to reoperations in 12 patients. The presence of a ventriculoperitoneal shunt during cranioplasty was the only significant factor associated with a higher rate of infection (28.6% versus 9.7%, p=0.001) and flap depression (14.3% versus 3.3%, p=0.03). Indications for the initial craniectomy, choice of graft materials and the time interval between craniectomy and cranioplasty had no significant association with complications. The presence of ventriculoperitoneal shunt at the time of cranioplasty is a significant risk factor for cranioplasty complications. Early cranioplasty is safe. Whether temporizing lumbar or external ventricular drainage is a better alternative to shunting in patients who are drainage-dependent at the time of cranioplasty remain to be determined.

Failure of Flow Diverter Treatment of Intracranial Aneurysms Related to the Fetal-type Posterior Communicating Artery.

Purpose The pipeline embolization device (PED) is a flow diverter that has shown promise in the treatment of intracranial aneurysms. Close to one-fifth of aneurysms, however, fail to occlude after PED placement. This study aims to identify anatomical features and clinicopathologic factors that may predispose failed aneurysm occlusion with the PED. Materials and Methods We retrospectively reviewed all anterior circulation unruptured saccular aneurysms treated with the PED in a single-center. The primary outcome measure was angiographic occlusion. Anatomical features and potential predictors, including gender, aneurysm location, size, height, aspect ratio, neck width, prior treatment and the number of PED, were studied using binary logistic regression. Results 29 anterior circulation unruptured saccular aneurysms with a mean size of 6.99 mm treated with the PED in a single center were retrospectively studied. The overall occlusion rate was 79.3% after a mean follow-up of 9.2 months. Four aneurysms were related to the fetal-type posterior communicating artery (PComA), and all were refractory to flow diverter treatment. Female gender was significantly associated with a higher occlusion rate. We present the anatomical features and propose possible pathophysiological mechanisms of these PComA aneurysms that failed flow diverter treatment. Conclusion A PComA aneurysm with persistent fetal-type circulation appears to be particularly refractory to flow diverter treatment, especially when the aneurysm incorporates a significant portion of the PComA. Our experience suggested that flow diverting stents alone may not be the ideal treatment for this subgroup of aneurysms, and alternative modalities should be considered. Female patients were found to have a significantly higher rate of treatment success.

Primary endovascular treatment of post-irradiated carotid pseudoaneurysm at the skull base with the Pipeline embolization device

Background A post-irradiated carotid pseudoaneurysm at the skull base can cause life-threatening blowout syndrome. Conventional treatments include parent vessel occlusion, endovascular coiling or covered stenting. Use of the Pipeline embolization device (PED) for pseudoaneurysm exclusion at the skull base is not well described. Objective To report the clinical and angiographic outcome after using multiple PEDs to treat recently ruptured radiation-induced carotid pseudoaneurysms at the skull base. Methods Retrospective review of the clinical and angiographic records of patients who received PEDs as primary treatment for skull base carotid pseudoaneurysm between April 1, 2011 to March 31, 2013. Results Seven patients (five men, two women) with a mean age of 58 years (range 47–65) were treated in the study period. Primary treatment with the PED alone, with adjunct coil embolization in two patients, achieved immediate hemostasis in all patients, with no pseudoaneurysm rebleeding after a mean follow-up of 15.3 months (range 4–24 months). One patient had periprocedural cerebral infarction. Delayed internal carotid artery occlusion secondary to in-stent thrombosis occurred in three patients, one of whom had lacunar infarct and two remained asymptomatic. Conclusions Endovascular treatment with the PED was effective in excluding skull base post-irradiated carotid pseudoaneurysms and preventing recurrent blowout. However, the risk of ischemic complications in this group of patients was high and our experience did not support the use of flow diverters as a first-line treatment for this condition.

Computational Fluid Dynamics Study of Bifurcation Aneurysms Treated with Pipeline Embolization Device: Side Branch Diameter Study.

Abstract An intracranial aneurysm, abnormal swelling of the cerebral artery, may lead to undesirable rates of mortality and morbidity upon rupture. Endovascular treatment involves the deployment of a flow-diverting stent that covers the aneurysm orifice, thereby reducing the blood flow into the aneurysm and mitigating the risk of rupture. In this study, computational fluid dynamics analysis is performed on a bifurcation model to investigate the change in hemodynamics with various side branch diameters. The condition after the deployment of a pipeline embolization device is also simulated. Hemodynamic factors such as flow velocity, pressure, and wall shear stress are studied. Aneurysms with a larger side branch vessel might have greater risk after treatment in terms of hemodynamics. Although a stent could lead to flow reduction entering the aneurysm, it would drastically alter the flow rate inside the side branch vessel. This may result in side-branch hypoperfusion subsequent to stenting. In addition, two patient-specific bifurcation aneurysms are tested, and the results show good agreement with the idealized models. Furthermore, the peripheral resistance of downstream vessels is investigated by varying the outlet pressure conditions. This quantitative analysis can assist in treatment planning and therapeutic decision-making.

Blood flow in intracranial aneurysms treated with Pipeline embolization devices: computational simulation and verification with Doppler ultrasonography on phantom models

Purpose: The aim of this study was to validate a computational fluid dynamics (CFD) simulation of flow-diverter treatment through Doppler ultrasonography measurements in patient-specific models of intracranial bifurcation and side-wall aneurysms. Methods: Computational and physical models of patient-specific bifurcation and sidewall aneurysms were constructed from computed tomography angiography with use of stereolithography, a three-dimensional printing technology. Flow dynamics parameters before and after flow-diverter treatment were measured with pulse-wave and color Doppler ultrasonography, and then compared with CFD simulations. Results: CFD simulations showed drastic flow reduction after flow-diverter treatment in both aneurysms. The mean volume flow rate decreased by 90% and 85% for the bifurcation aneurysm and the side-wall aneurysm, respectively. Velocity contour plots from computer simulations before and after flow diversion closely resembled the patterns obtained by color Doppler ultrasonography. Conclusion: The CFD estimation of flow reduction in aneurysms treated with a flow-diverting stent was verified by Doppler ultrasonography in patient-specific phantom models of bifurcation and side-wall aneurysms. The combination of CFD and ultrasonography may constitute a feasible and reliable technique in studying the treatment of intracranial aneurysms with flow-diverting stents.

Wall-Less Flow Phantoms With Tortuous Vascular Geometries: Design Principles and a Patient-Specific Model Fabrication Example

Flow phantoms with anatomically realistic geometry and high acoustic compatibility are valuable investigative tools in vascular ultrasound studies. Here, we present a new framework to fabricate ultrasound-compatible flow phantoms to replicate human vasculature that is tortuous, nonplanar, and branching in nature. This framework is based upon the integration of rapid prototyping and investment casting principles. A pedagogical walkthrough of our engineering protocol is presented in this paper using a patient-specific cerebral aneurysm model as an exemplar demonstration. The procedure for constructing the flow circuit component of the phantoms is also presented, including the design of a programmable flow pump system, the fabrication of blood mimicking fluid, and flow rate calibration. Using polyvinyl alcohol cryogel as the tissue mimicking material, phantoms developed with the presented protocol exhibited physiologically relevant acoustic properties [attenuation coefficient: 0.229±0.032 dB/(cm·MHz) and acoustic speed: 1535±2.4 m/s], and their pulsatile flow dynamics closely resembled the flow profile input. As a first application of our developed phantoms, the flow pattern of the patient-specific aneurysm model was visualized by performing high-frame-rate color-encoded speckle imaging over multiple time-synchronized scan planes. Persistent recirculation was observed, and the vortex center was found to shift in position over a cardiac cycle, indicating the 3-D nature of flow recirculation inside an aneurysm. These findings suggest that phantoms produced from our reported protocol can serve well as acoustically compatible test beds for vascular ultrasound studies, including 3-D flow imaging.

A joint computational-experimental study of intracranial aneurysms: importance of the aspect ratio

Rupture of a cerebral aneurysm (abnormal swelling of blood vessel in the brain) will cause subarachnoid hemorrhage, and will result in an alarming rate of mortality and morbidity. A joint computational-experimental study is conducted to assess the importance of the aspect ratio in the dynamics of blood flow. The aspect ratio is defined here to be the ratio of the height of the aneurysm to the linear dimension of the neck. Idealized models of such aneurysms located near a bifurcation point were investigated. Numerical simulations for hemodynamic properties like shear stress and flow rate were performed. The computational results were verified experimentally with specially fabricated phantoms, blood mimicking fluid and Doppler ultrasound imaging. Excellent agreements were obtained. Two features are highlighted, providing information in the intensely debated link between rupture risk and geometric factors. On increasing the aspect ratios, firstly, a jet impinging on the distal part of the neck can be observed, and secondly, a region of positive shear stress gradient can be found there. Furthermore, computational analyses for four patient-specific models were conducted to correlate with the results of idealized models and to provide further clinical insight.

Correlating Hemodynamic Changes and Occlusion Time after Flow Diverter Treatment of Bilateral Large Internal Carotid Artery Aneurysms.

A middle-aged lady in good health presented right abducens nerve palsy. Magnetic resonance imaging (MRI) of the brain showed bilateral cavernous ICA aneurysms. The left aneurysm measured 9 × 7 mm whereas the right aneurysm measured 22 × 15 mm, with mass effect on the cavernous sinus, explaining her symptoms (Fig. 1). Both were wide-neck aneurysms and were treated with PED alone sequentially, 3 months apart. She was loaded with Aspirin 300 mg and Clopidogrel 300 mg before treatment, with Aspirin continuing for 6 months and Clopidogrel for 3 months afterwards. There were no procedural complications. Digital subtraction angiogram at 1 year showed that the left aneurysm was completely occluded, whereas the right aneurysm had partially thrombosed but with a persistent filling. The right aneurysm persisted on CT angiogram at 2 years but with significant shrinkage and finally occluded at a 3-year follow-up (Fig. 2). The patient’s diplopia gradually improved after 3 years.