• Journal of computational fluids engineering
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• v.6 no.1
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• pp.40-46
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• 2001

Pressure-flow control characteristics of a commercially available cerebrospinal flow(CSF) control shunt valve was studied using flow/structure interaction analyses. Pre-stress of the valve diaphragm(membrane) was accounted for the simulation of an actual valve. The present results were in good agreement with the valve specification listed in the commercially available CSF control valve. The flow/structure interaction analysis of the present study can be effectively used to design a variety of CSF control shunt valves.

• 한국전산유체공학회:학술대회논문집
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• 2000.05a
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• pp.21-26
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• 2000

Pressure-flow control characteristics of a commercially available cerebrospinal flow(CSF) control shunt valve was tested using fluid-solid interaction analysis. Pre-stress of the valve diaphragm(membrane) was computed for proper valve opening. The results were ir good agreements with the valve specification listed in the commercially available CSF control valve. The results of the study can be effectively used to design variety of CSF control shunt valves.

• Journal of Korean Neurosurgical Society
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• v.29 no.12
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• pp.1634-1641
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• 2000

Objective : The cerebrospinal fluid(CSF) pulsates within the craniospinal axis in response to rhythmic cerebral blood volume variation during the cardiac cycle. The aim of this study is to characterize the normal and abnormal CSF flow and its waveforms in the cervical spinal subarachnoid space. Methods : The magnetic resonance(MR) images were obtained with 1.5 T(GE Signa, GE Medical Systems, Milwaukee, USA) unit using the 2 dimensional cine PC(phase contrast) sequence with cardiac gating and gradient recalled echo imaging. This pulse sequence yielded 16 quantitative flow-encoded images per cardiac cycle. Sagittal and axial images of the cervical spinal CSF space were obtained, and target sites were analyzed for characteristic CSF flow (TR=50ms, TE=12.5-15ms). The region of interest(ROI) was 1mm 3 in volume. Twenty six persons were included in this study : 10 healthy volunteers and 16 patients with cervical myelopathy. The post-operative cine MR study were also done in five patients. Results : The normal CSF pulsation dynamics in the cervical spine showed discrete systolic and diastolic components. The CSF flow revealed a sine wave pattern, in which the systolic phase was shorter than the diastolic phase(ratio=2 : 3). The patient group revealed decreased amplitudes of the CSF flow and irregularly distored flow waves. The systolic phase was elongated in the ROI above the stenotic level, whereas the diastolic phase was lengthened below the level. In the postoperative images, the abnormal pattern and amplitude were found to be corrected. Conclusion : From these results, the authors believe that the CSF flow study provides valuable informations regarding the extent of cervical stenosis and may be useful for the surgical planning and post-operative evaluation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.99-113
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• 1996

Taurine, a ${\beta}$-amino acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine does not cross the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier is likely to play a role in taurine transport between the central nervous system and the systemic circulation. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to characterize in vivo kinetics of elimination for taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for up to 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005), indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e.g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of the labeled taurine was reduced (p<0.01), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment Collectively, our results demonstrate that taurine is transported in the choroid plexus via a taurine is cleared from the CSF via a saturable process. This process may be functionally relevant to taurine homeostasis in the brain.

• Journal of Korean Neurosurgical Society
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• v.39 no.1
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• pp.20-25
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• 2006

Objective : The authors analyze prospectively the result of transcranial doppler[TCD] in normal pressure hydrocephalus and compared its cerebral blood flow parameters to radionuclide cerebrospinal fluid[CSF] flow study, postoperative brain computed tomography[CT] findings and clinical outcome, and studied the relationship between cerebral hemodynamics and clinical performance. Methods : Twenty five patients with hydrocephalus undertook pre- and post-operative TCD but only preoperative CSF flow study was performed. Mean flow velocity[Vm], pulsatility index[PI] and resistance index[RI] were assessed through TCD and changes in ventricle size and cortical gyral atrophy were checked through brain CT. Results : Postoperative hydrocephalus showed an increase in Vm[ACA P=0.037, MCA P=0.034], decrease in PI[ACA P=0.019, MCA P=0.017] and decrease in RI [ACA P=0.017, MCA P=0.021] compared to preoperative TCD parameters in the postoperative improvement group. In the postoperative improvement group, postoperative TCD parameters correlated with CSF flow study grade [Vm : $R^2=-0.75$, PI : $R^2=0.86$, RI : $R^2=0.78$] and ventriculocranial ratio change correlated with PI change [$R^2=0.73$]. The convexity gyral atrophy and initial TCD parameters showed close relationship to outcome. Conclusion : PI and RI can be used as an indicator of post operative prognosis, and with the addition of CSF flow study values, can also be used as a tool to predict pre-op and post-op patient status and successful shunt surgery.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• 한국전산유체공학회:학술대회논문집
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• 2004.10a
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• pp.15-18
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• 2004

A numerical method for simulating two-phase flows including surface force is presented. The method is based on fractional step method of finite volume formulation and the interface is tracked with PLIC VOF method. In the CSF model, as color function, f, representing the location of interface varies steeply in the interface region, we need to use smoothed function f to get accurate unit normal and the curvature. Peskin kernel is used to get smoothed function f. A spherical drop in static equilibrium and three-dimensional merging of gas bubble are tested, resulting in the validation of this method

• Proceedings of the Korean Society of Precision Engineering Conference
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• 2000.05a
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• pp.1051-1054
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• 2000

We developed the micro CSF (celebrospinal fluid) shunt valve with surface and bulk micromachining technology in polymer MEMS. This micro CSF shunt valve was formed with four micro check valves to have a membrane connected to the anchor with the four bridges. The up-down movement of the membrane made the CSF on & off and the valve characteristic such as open pressure was controlled by the thickness and shape of the bridge and the membrane. The membrane, anchor and bridge layer were made of the $O_2$ RIE (reactive ion etching) patterned Parylene thin film to be about 5~10 microns in thickness on the silicon wafer. The dimension of the rectangular nozzle is 0.2＊0.2 $\textrm{mm}^2$ and the membrane 0.45 mm in diameter. The bridge width is designed variously from 0.04 mm to 0.12 mm to control the valve characteristics. To protect the membrane and bridge in the CSF flow, we developed the packaging system for the CSF micro shunt valve with the deep RIE of the silicon wafer. Using this package, we can control the gap size between the membrane and the nozzle, and protect the bridge not to be broken in the flow. The total dimension of the assembled system is 2.5＊2.5 $\textrm{mm}^2$ in square, 0.8 mm in height. We could precisely control the burst pressure and low rate of the valve varing the design parameters, and develop the whole CSF shunt system using this polymer MEMS fabricated CSF shunt valve.

• Korean Journal of Radiology
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• v.1 no.1
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• pp.11-18
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• 2000

Objective: To evaluate the hydrodynamic changes occurring in cerebrospinal fluid (CSF) flow in cervical spinal stenosis using the spatial modulation of magnetization (SPAMM) technique. Materials and Methods: Using the SPAMM technique, 44 patients with cervical spinal stenosis and ten healthy volunteers were investigated. The degree of cervical spinal stenosis was rated as low-, intermediate-, or high-grade. Low-grade stenosis was defined as involving no effacement of the subarachnoid space, intermediate-grade as involving effacement of this space, and high-grade as involving effacement of this space, together with compressive myelopathy. The patterns of SPAMM stripes and CSF velocity were evaluated and compared between each type of spinal stenosis and normal spine. Results: Low-grade stenosis (n = 23) revealed displacement or discontinuity of stripes, while intermediate- (n = 10) and high-grade (n = 11) showed a continuous straight band at the stenotic segment. Among low-grade cases, 12 showed wave separation during the systolic phase. Peak systolic CSF velocity at C4-5 level in these cases was lower than in volunteers (p < .05), but jet-like CSF propulsion was maintained. Among intermediate-grade cases, peak systolic velocity at C1-2 level was lower than in the volunteer group, but the difference was not significant (p > .05). In high-grade stenosis, both diastolic and systolic velocities were significantly lower (p < .05). Conclusion: Various hydrodynamic changes occurring in CSF flow in cervical spinal stenosis were demonstrated by the SPAMM technique, and this may be a useful method for evaluating CSF hydrodynamic change in cervical spinal stenosis.

• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.