John Ching Kwong Kwok

Human placenta as an ex vivo vascular model for neurointerventional research.

Background Human placenta is a convenient resource for biomedical research, and has not yet been used for neurointerventional surgery research. Objective Our objective was to explore the feasibility of using human placenta to test various endovascular interventions and for training. Design 18 placentas soon after delivery were prepared for six pilot studies. (1) Study on anatomical similarity to human cerebral vessel. (2) Simulation of stent assisted coiling and flow diversion on an aneurysm model. (3) Simulation of intra-arterial thrombolysis. (4) Simulation of embolization of arteriovenous malformation with glues. (5) Simulation of mechanical thrombolysis and comparison of different devices. (6) Vascular model for training of neurointerventionalists. Results When the chorionic plate vessels were compared with the cerebral cortical vessels, similarities were found in vascular branch patterns, histological cross sections, and angiographic appearances. Due to the semitransparency of its vessel wall, performance of flow diverter and stent assisted coiling of an aneurysm could be visualized under direct microscopic observation. Similarly, timing of clot lysis and glue polymerization could be estimated. Endothelial change after thrombectomy could be assessed by histological methods. From these pilot studies, the placenta model could be adopted to simulate various clinical situations. It is also ideal for interventional radiology training. Conclusions It is feasible to adopt the human placenta as an ex vivo vascular model in neurointerventional surgery research due to the fact that its vessels resemble the brain vasculature.

Characterization of pressure reduction in coil-filled aneurysm under flow of human blood with and without anti-coagulant

Filling aneurysms with embolization coils is a widely used part of the treatment to stop intracranial aneurysm from rupturing. However, the effect of coiling on aneurysmal pressure has not been established. In this study, the effect of intra-aneurysmal coiling on pressure reduction was characterized. Coil deployment in the aneurysm will disturb flow and may induce aneurysmal coagulation. These effects were experimentally examined in this study using silicone rubber saccular aneurysm models. Changes in aneurysmal blood pressure under pulsatile flow were characterized. With coils in the aneurysm, results showed that flow reduction of anti-coagulated blood in the aneurysm did not reduce aneurysmal pressure. Significant pressure reduction was observed only when the bloods coagulation ability is restored to normal. These results suggest that blood coagulation is pivotal to pressure reduction and concomitant with rupture risk reduction in treatments of aneurysm with coils.

Feasibility examination of isolated zonal thrombolysis using Raman spectroscopy

Intravenous thrombolysis for the treatment of ischemic stroke requires long treatment time and high drug dosage which increases the risk of hemorrhage. Localized zonal dosage of urokinase between 100 - 500 International Units (IU), i.e., less than 5% of typical systemic dosage (60,000 - 120,000 IU) at the thrombus can shorten the treatment time to less than 30 minutes while reducing the risk of hemorrhage. The effect of zonal-delivered urokinase on the molecular changes in a 100 μm thick by 20 mm diameter blood clot was quantified using Raman spectroscopy. In situ Raman spectra showed that the fibrin concentration in the clot decreased with time. The results verified that a zonal-delivered urokinase can dissolve the clot and reduce the treatment time. Further trials on animals will be conducted to examine the potential of zonal-delivery to accelerate clot dissolution for ischemic stroke while minimizing the risk of hemorrhage.

Characterization of thrombus stiffening in radio frequency (rf Mechanical thrombectomy

Intra-arterial mechanical thrombectomy (IAMT) for ischemic stroke has high recanalization rate, long treatment time window and low risk of symptomatic intracerebral haemorrhage (sICH), but thrombus fragments produced during treatment can lead to distal embolization. Fragmentation can be reduced if the thrombus is strengthened by increasing the thrombuss crosslink density. Radio frequency (rf) electric current commonly used in surgery to cut and coagulate tissue can induce crosslinking in thrombus. The increase in thrombus stiffness as a result of the increase in crosslinking from rf treatment is characterized in this study. Test results showed that the stiffness of thrombus is increased by more than 8 times after rf treatment. The dramatic increase in stiffness suggests that thrombus fragmentation and distal embolization can be reduced by applying rf during thrombectomy treatment.Intra-arterial mechanical thrombectomy (IAMT) for ischemic stroke has high recanalization rate, long treatment time window and low risk of symptomatic intracerebral haemorrhage (sICH), but thrombus fragments produced during treatment can lead to distal embolization. Fragmentation can be reduced if the thrombus is strengthened by increasing the thrombuss crosslink density. Radio frequency (rf) electric current commonly used in surgery to cut and coagulate tissue can induce crosslinking in thrombus. The increase in thrombus stiffness as a result of the increase in crosslinking from rf treatment is characterized in this study. Test results showed that the stiffness of thrombus is increased by more than 8 times after rf treatment. The dramatic increase in stiffness suggests that thrombus fragmentation and distal embolization can be reduced by applying rf during thrombectomy treatment.

In-vitro testing of RF-enabled low force mechanical thrombectomy for ischemic stroke

Mechanical thrombectomy for ischemic stroke has high recanalization rate, long treatment time window and low hemorrhage risk. However, the clot engagement approach of caging the clot against the vessel wall can cause vessel stenosis and stroke recurrence. A device with reduced radial stenting force that reduces vessel wall friction would minimize stenosis and damage. The use of localized Radio Frequency (RF) to enable clot engagement and retrieval with minimal stenting force is explored in this study. New mechanical thrombectomy devices enabled with RF (Patent No.: US 62/172,043) were built and tested on human blood clots in vessels ex vivo. Test results showed that the RF-mechanical thrombectomy successfully and reproducibly captured and retrieved the clots without relying on stent caging of the clot against the vessel wall. Further work will be conducted on animals to compare vessel wall damage between conventional and RF-mechanical thrombectomy.

Bedside external ventricular drain placement for haemorrhagic stroke patients with brain herniation and acute hydrocephalus: A case series: Bedside EVD for hemorrhagic stroke

External ventricular drainage (EVD) for patients with acute hydrocephalus is a potentially life‐saving neurosurgical procedure that can be quickly performed at the bedside, but is rarely carried out in Hong Kong.

Mechanical behavior of rf-treated thrombus in mechanical thrombectomy

Intra-arterial mechanical thrombectomy (IAMT) treatments for ischemic stroke have higher recanalization rate, longer treatment time window and lower risk of symptomatic intracerebral hemorrhage (sICH). However, distal embolization may occur because of loose fragments produced during maceration and engagement. The naturally coagulated thrombus is fragile and has poor binding with thrombectomy device. Improvement of thrombus-device binding can reduce fragments breaking loose during wire pull and enhance protein crosslinking in the thrombus that can increase fragmentation resistance. The effects of in-situ applied radio frequency (rf) treatment on thrombus-wire binding and interfacial fracture have been examined in this study using wire pull tests that are mechanically analogous to the embolus retrieval method in thrombectomy. Wire inserted into a thrombus was pull tested after rf-treatment. Pull test results showed that rf-treatment improves binding and reduces thrombus slippage from over 90% to less than 10%. Fracture pull test results also showed that fracture energy density of thrombus-device interface increased 40X after rf-treatment. The dramatic increase in resistance against fracture suggests that the use of in-situ rf-treatment is a promising treatment addition to reduce distal embolization and improve clinical outcomes in mechanical thrombectomy.

In vitro examination of the pressure effect on clot dissolution with thrombolytic patch

Bio-kinetic thrombus dissolution model has been developed to describe the thrombus dissolution behavior during endoluminal thrombolytic patch treatment to recanalize blocked vessel in ischemic strokes. The initial model ignored the effect of pulsatile pressure in the lumen. However, pulsatile pressure in the lumen may affect molecule diffusion and bio-chemical reaction rate and accelerate clot dissolution. The effect of pressure on the dissolution rate was examined in this study. The dissolution behaviors of 100-400 μm thick blood clot specimens subject to diastolic, systolic, and pulsatile pressure were characterized using Raman spectroscopy. The results showed that dissolution time was reduced by less than 2 mins and is negligible in comparison with total treatment time. The effect of pressure may be ignored and the developed bio-kinetic model may be used in surgical applications of endoluminal thrombolytic patch to estimate treatment time in ischemic stroke.

Lipomatous meningioma: Diagnostic pitfalls and pathological updates

We present a case of histologically confirmed lipomatous meningioma, the first to our knowledge reported in Hong Kong. A 75‐year‐old woman presented to us with on and off dizziness for 1 month. Computed tomography (CT) of the brain showed an extra‐axial mass lesion containing fat and solid enhancing foci at her right frontal region. The definitive diagnosis could be made preoperatively. Postoperative histological examination of the tumour revealed the diagnosis of lipomatous meningioma. We have reviewed the literature and discussed the diagnostic clues, clinical presentation and pathology of this rare tumour.