Evaluation the injectability of injectable microparticle delivery systems on the basis of injection force and discharged rate.

BACKGROUND: Subcutaneous injection of biopharmaceutical agents or microparticles is challenging due to issues with low injection efficiency and high residual amounts. OBJECTIVE: This study aimed to determine the important factors affecting the injectability of microparticle delivery systems, establish a suitable injection system with lower injection force and higher discharge rate, and eventually develop a reliable injectability evaluation system for injectable microparticle delivery systems in vitro and in vivo. METHODS: The effects of various parameters, including particle size, injection speed, concentration of microspheres suspension, vehicle viscosity, needle length and gauge were evaluated by measuring the injection force and discharge rate. The characteristics of microparticles and rheological measurement of the suspension systems were studied. A design of experiment approach was utilized to evaluate the interaction between the microsphere suspension, vehicle viscosity and needle gauges. Both in vitro sieve tests and in vivo tests in rats were conducted to evaluate injectability. RESULTS: The in vitro test results showed that the vehicle viscosity and injection speed have varying effects on discharge rate and injection force, respectively. Particle size and needle gauge have substantial influence on injectability, larger particle size and smaller needle gauges resulting in poor injectability, while the needle gauge was found to have the greatest influence on injectability. Levonorgestrel (LNG) microsphere and glass bead were relatively uniform spherical, the glass bead had extremely smooth surface; while mesoporous silica had irregular shape. The settling rate of glass bead was the fastest, which was about 18 times faster than the LNG microsphere. The CMC-Na had a poor interaction with the LNG microspheres, glass bead and mesoporous silica and showed basically Newtonian behavior in the shear rate range of 0.1 s-1-100 s-1. When shear rate increased to more than 100 s-1, no obvious shear thinning behavior was observed. CMC-Na formed a nodule structure with whether LNG microspheres or the glass beads, which were much lower than that with the mesoporous silica in static state, among which the glass beads were the weakest. The viscosity of the suspension increased with the rising of the volume fraction of particles. Fundamentals of hydrodynamics in capillaries were referenced, such as Navier-Stokes Law equation, Krieger-Dougherty (K-D) equation, Hagen-Poiseuille equation. The best results achieved was using a suspension concentration of 120-240 mg /mL and a viscosity of 60 cP at 20 °C with 23-gauge needles. The optimized conditions were verified in vivo tests. It was proven that the LNG microsphere suspension had a good injectability when injected into subcutaneous tissue of rats. CONCLUSION: The injection system of injectable microparticle delivery system with lower injection force and higher discharge rate was established and the evaluation method was suitable for the injectability evaluation both in vivo and in vitro. Improved injectability would promote the clinical translation of microparticle delivery systems.

[Research on injection flow velocity planning method for embolic agent injection system].

Interventional embolization therapy is widely used for procedures such as targeted tumour therapy, anti-organ hyperactivity and haemostasis. During embolic agent injection, doctors need to work under X-ray irradiation environment. Moreover, embolic agent injection is largely dependent on doctors' experience and feelings, and over-injection of embolic agent can lead to reflux, causing ectopic embolism and serious complications. As an effective way to reduce radiation exposure and improve the success rate of interventional embolization therapy, embolic agent injection robot is highly anticipated, but how to decide the injection flow velocity of embolic agent is a problem that remains to be solved. On the basis of fluid dynamics simulation and experiment, we established an arterial pressure-injection flow velocity boundary curve model that can avoid reflux, which provides a design basis for the control of embolic agent injection system. An in vitro experimental platform for injection system was built and validation experiments were conducted. The results showed that the embolic agent injection flow speed curve designed under the guidance of the critical flow speed curve model of reflux could effectively avoid the embolic agent reflux and shorten the embolic agent injection time. Exceeding the flow speed limit of the model would lead to the risk of embolization of normal blood vessels. This paper confirms the validity of designing the embolic agent injection flow speed based on the critical flow speed curve model of reflux, which can achieve rapid injection of embolic agent while avoiding reflux, and provide a basis for the design of the embolic agent injection robot.

Using Gas Counter Pressure and Combined Technologies for Microcellular Injection Molding of Thermoplastic Polyurethane to Achieve High Foaming Qualities and Weight Reduction.

Microcellular injection molding technology (MuCell®) using supercritical fluid (SCF) as a foaming agent offers many advantages, such as material and energy savings, low cycle time, cost-effectiveness, and the dimensional stability of products. MuCell® has attracted great attention for applications in the automotive, packaging, sporting goods, and electrical parts industries. In view of the environmental issues, the shoe industry, particularly for midsole parts, is also seriously considering using physical foaming to replace the chemical foaming process. MuCell® is thus becoming one potential processing candidate. Thermoplastic polyurethane (TPU) is a common material for molding the outsole of shoes because of its outstanding properties such as hardness, abrasion resistance, and elasticity. Although many shoe manufacturers have tried applying Mucell® processes to TPU midsoles, the main problem remaining to be overcome is the non-uniformity of the foaming cell size in the molded midsole. In this study, the MuCell® process combined with gas counter pressure (GCP) technology and dynamic mold temperature control (DMTC) were carried out for TPU molding. The influence of various molding parameters including SCF dosage, injection speed, mold temperature, gas counter pressure, and gas holding time on the foaming cell size and the associated size distribution under a target weight reduction of 60% were investigated in detail. Compared with the conventional MuCell® process, the implementation of GCP technology or DMTC led to significant improvement in foaming cell size reduction and size uniformity. Further improvement could be achieved by the simultaneous combination of GCP with DMT, and the resulting cell density was about fifty times higher. The successful possibility for the microcellular injection molding of TPU shoe midsoles is greatly enhanced.

Development of an Online Quality Control System for Injection Molding Process.

This research developed an adaptive control system for injection molding process. The purpose of this control system is to adaptively maintain the consistency of product quality by minimize the mass variation of injection molded parts. The adaptive control system works with the information collected through two sensors installed in the machine only-the injection nozzle pressure sensor and the temperature sensor. In this research, preliminary experiments are purposed to find master pressure curve that relates to product quality. Viscosity index, peak pressure, and timing of the peak pressure are used to characterize the pressure curve. The correlation between product quality and parameters such as switchover position and injection speed were used to produce a training data for back propagation neural network (BPNN) to compute weight and bias which are applied on the adaptive control system. By using this system, the variation of part weight is maintained to be as low as 0.14%.

Research on injection flow velocity planning method for embolic agent injection system / 生物医学工程学杂志

Interventional embolization therapy is widely used for procedures such as targeted tumour therapy, anti-organ hyperactivity and haemostasis. During embolic agent injection, doctors need to work under X-ray irradiation environment. Moreover, embolic agent injection is largely dependent on doctors' experience and feelings, and over-injection of embolic agent can lead to reflux, causing ectopic embolism and serious complications. As an effective way to reduce radiation exposure and improve the success rate of interventional embolization therapy, embolic agent injection robot is highly anticipated, but how to decide the injection flow velocity of embolic agent is a problem that remains to be solved. On the basis of fluid dynamics simulation and experiment, we established an arterial pressure-injection flow velocity boundary curve model that can avoid reflux, which provides a design basis for the control of embolic agent injection system. An in vitro experimental platform for injection system was built and validation experiments were conducted. The results showed that the embolic agent injection flow speed curve designed under the guidance of the critical flow speed curve model of reflux could effectively avoid the embolic agent reflux and shorten the embolic agent injection time. Exceeding the flow speed limit of the model would lead to the risk of embolization of normal blood vessels. This paper confirms the validity of designing the embolic agent injection flow speed based on the critical flow speed curve model of reflux, which can achieve rapid injection of embolic agent while avoiding reflux, and provide a basis for the design of the embolic agent injection robot.

Effect of Injection Speed on Oocyte Deformation in ICSI.

Oocyte deformation during injection is a major cause of potential cell damage which can lead to failure in the Intracytoplasmic Sperm Injection (ICSI) operation used as an infertility treatment. Injection speed plays an important role in the deformation creation. In this paper the effect of different speeds on deformation of zebrafish embryos is studied using a specially designed experimental set-up. An analytical model is developed in order to link injection force, deformation, and injection speed. A finite element (FE) model is also developed to analyse the effect of injection speed, allowing the production of additional information that is difficult to obtain experimentally, e.g., deformation and stress fields on the oocyte. The numerical model is validated against experimental results. Experimental results indicate that by increasing the injection speed, the deformation decreases. However, higher speeds cause higher levels of injection force and force fluctuation, leading to a higher vibration during injection. For this reason, an optimum injection speed range is determined. Finally, the FE model was validated against experimental results. The FE model is able to predict the force-deformation variation during injection for different speeds. This proves to be useful for future studies investigating different injection conditions.

Inter-individual Comparison of Gadobutrol and Gadoteridol Tissue Time-intensity Profiles for Dynamic Susceptibility Contrast Perfusion MR Imaging.

PURPOSE: Gadobutrol is a gadolinium-based contrast material (GBCM) with a high concentration of gadolinium and high relaxivity. Our purpose was to evaluate the signal intensity profiles in brain tissue for the bolus width and degree of signal change after bolus injection using an echo planar dynamic susceptibility contrast (DSC) sequence. We compared gadobutrol to gadoteridol using various injection speeds and saline flush volumes. METHODS: We studied 97 patients who underwent brain MRI. Datasets for perfusion studies were acquired using a 3T scanner with an echo planar imaging (EPI) sequence. The injection protocols were set up with combinations of injection speed and saline flush volume for both gadobutrol and gadoteridol. The full width at half maximum (FWHM) and the maximum signal change ratio (SCRmax) of the time intensity curves were measured. RESULTS: The FWHM did not show a statistically significant difference according to injection speed, flush volume, or type of GBCM. The SCRmax showed a greater change with a faster injection speed, larger saline flush, and gadobutrol administration. The difference between gadobutrol and gadoteridol became smaller with a faster injection speed and a larger saline flush. CONCLUSION: The maximum signal drop was larger with gadobutrol when the injection speed was slow and the saline flush was small. Thus, gadobutrol may be useful to obtain a better profile for DSC perfusion MRI in conditions requiring a slower injection speed and/or a smaller volume of saline flush.

The effect of rate of injection on injection pressure profiles measured using in-line and needle-tip sensors: an in-vitro study.

Alongside ultrasonic visualisation, measurement of injection pressure is an effective tool for reducing the risk of intraneural injection during peripheral nerve block. The aim of this study was to compare injection pressure profiles when measured along the injection line with the pressure measured directly at the needle tip using different rates of injection. A syringe pump delivered a 5-ml injection of saline into silicone gel at three different speeds (5 ml.min-1 , 10 ml.min-1 and 15 ml.min-1 ). Fibreoptic pressure sensors recorded real-time pressure profiles of the injection pressure directly at the needle tip and along the injection line. A total of 15 injections were successfully performed, five for each injection rate, totalling 30 recorded pressure profiles. More rapid rates of injection caused peak pressure measured in-line to increase, whereas pressure measured at the needle tip remained constant (mean (SD) pressure in-line 30.76 (3.45) kPa vs. 72.25 (1.55) kPa and mean (SD) pressure at needle tip 19.92 (1.22) kPa vs. 20.93 (2.66) kPa at 5 ml.min-1 and 15 ml.min-1 , respectively). Injection pressure profiles showed that in-line pressure measurement failed to record precise real-time pressure changes occurring at the needle tip (mean (95%CI) pressure difference 10.8 (6.98-14.70) kPa vs. 51.2 (47.52-54.89) kPa for in-line and needle-tip measures, respectively). We conclude that, in order to accurately monitor the true injection pressure generated, independent from operator and injection parameters, measurement at the needle tip is necessary, as injection pressure measured along the injection line is an unreliable surrogate.

[Unilateral spinal anesthesia : Literature review and recommendations]. / Einseitige Spinalanästhesie : Literaturübersicht und Handlungsempfehlung.

Unilateral spinal anesthesia is a cost-effective and rapidly performed anesthetic technique. An exclusively unilateral block only affects the sensory, motor and sympathetic functions on one side of the body and offers the advantages of a spinal block without the typical adverse side effects seen with a bilateral block. The lack of hypotension, in particular, makes unilateral spinal anesthesia suitable for patients with cardiovascular risk factors e. g. aortic valve stenosis or coronary artery disease. Increasing numbers of surgical procedures are now being performed on an outpatient basis. Until now, spinal anesthesia has been considered unsuitable for this, not only because of the high incidence of intraoperative hypotension and postoperative urinary retention but also because of the prolonged postoperative stay before home discharge. This is not the case with unilateral spinal anesthesia: motor function returns rapidly, the incidence of urinary retention is extremely low, and patients are usually eligible for home discharge sooner than after bilateral spinal anesthesia or general anesthesia. The success of the technique depends on a number of factors. In addition to the local anesthetic, its concentration and dose, and the baricity of the injected solution, the shape of the spinal needle, the injection speed, the patient's position during injection, and the time the patient remains in this position after injection are equally important parameters. A number of intrathecally applied adjuvant drugs are used to give a more intense and/or longer-lasting block. For this review, we collated the published data on unilateral spinal anesthesia from journals with an impact factor greater than 1.0 and defined an optimized method for performing the technique. In order to achieve an exclusively unilateral block one should use 0.5 % hyperbaric bupivacaine injected at a rate of 0.33 ml/min or slower. During the injection and the following 20 min the patient should lie in the lateral decubitus position on the side intended for surgery with knees drawn to the chest. An injection of 5 mg (1 ml) hyperbaric bupivacaine 0.5 % provides an hour-long block to T 12, and a dose of 7.5 to 10 mg (1.5-2.0 ml) extends the block to T 6. Adding clonidine (0.5 to 1.0 µg/kg BW) to the injection prolongs the duration of the block to approximately two to three hours. During the 20-minute fixation period, the cephalad spread of the block can be influenced to a certain extent by raising or lowering the head of the table.

Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance.

AIM: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance. METHODS: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8-10, and 15-20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images. RESULTS: Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. CONCLUSION: The results of this study suggest that solutions of up to 3 mL and up to 15-20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain.

The Effect of 2 Injection Speeds on Local Anesthetic Discomfort During Inferior Alveolar Nerve Blocks.

This randomized double-blind crossover trial investigated the discomfort associated with 2 injection speeds, low (60 seconds) and slow (100 seconds), during inferior alveolar nerve block by using 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine. Three phases were considered: (a) mucosa perforation, (b) needle insertion, and (c) solution injection. Thirty-two healthy adult volunteers needing bilateral inferior alveolar nerve blocks at least 1 week apart were enrolled in the present study. The anesthetic procedure discomfort was recorded by volunteers on a 10-cm visual analog scale in each phase for both injection speeds. Comparison between the 2 anesthesia speeds in each phase was performed by paired t test. Results showed no statistically significant difference between injection speeds regarding perforation (P = .1016), needle placement (P = .0584), or speed injection (P = .1806). The discomfort in all phases was considered low. We concluded that the 2 injection speeds tested did not affect the volunteers' pain perception during inferior alveolar nerve blocks.

The effect of injection speed on remifentanil-induced cough in children.

BACKGROUND: Remifentanil sometimes elicits cough during induction of anesthesia, as with the use of other fentanyl congeners. We designed this study to investigate the incidence of remifentanil-induced cough (RIC) in children and to evaluate the effect of injection speed on RIC. METHODS: One hundred twenty ASA physical status I-II patients, aged 3-12 yr, undergoing general anesthesia were enrolled in the study. Patients were randomly assigned to one of the three groups. Patients in Group R30 received remifentanil 1.5 µg/kg at a constant rate over 30 s. Patients in Group R45 received remifentanil 1.5 µg/kg over 45 s, and patients in Group R60 received remifentanil 1.5 µg/kg over 60 s, respectively. Episodes of cough were recorded and graded as mild (1-2), moderate (3-4), or severe (5 or more). Mean arterial pressure (MAP), heart rate (HR), and SpO2 were recorded on arrival in the operating room (baseline) and 1 min after remifentanil infusion. RESULTS: The incidence of RIC was 33.3% in Group R30 (13 of 39 patients), 17.9% in Group R45 (7 of 39 patients), and 5.0% in Group R60 (2 of 40 patients). Patients in Group R60 had a significantly lower incidence of RIC than those in Group R30 (P = 0.001). The MAP, HR, and SpO2 values were not significantly different between groups. CONCLUSIONS: When intravenous remifentanil 1.5 µg/kg was administered in pediatric patients, the incidence of RIC decreased from 33 to 5% by increasing the injection time from 30 to 60 s. Remifentanil should be administered slowly over 60 s in children to suppress cough during anesthesia induction.

Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single-centre, randomized controlled trial.

AIM: The aim of this study was to assess pain associated with subcutaneous injection into the abdomen and thigh of different combinations of injection speeds and volumes. METHODS: The study was a single-centre, one-visit, double-blinded, randomized controlled trial in 82 adults with type 1 or type 2 diabetes receiving daily injections of insulin or glucagon-like peptide-1 (GLP-1) agonists. Participants received 17 subcutaneous injections (12 in abdomen, 5 in thigh) of saline at different injection speeds (150, 300 and 450 µl/s), with different volumes (400, 800, 1200 and 1600 µl), and two needle insertions without any injection. Pain was evaluated on a 100-mm visual analogue scale (VAS) (0 mm no pain, 100 mm worst pain) and on a yes/no scale for pain acceptability. RESULTS: Injection speed had no impact on injection pain (p = 0.833). Injection of larger volumes caused significantly more pain [VAS least square mean differences 1600 vs. 400 µl, 7 · 2 mm (95% confidence interval - CI; 4.6-9.7; p < 0.0001); 1600 vs. 800 µl, 7.2 mm (4.4-10.0; p < 0.0001); 1200 vs. 400 µl, 3.5 mm (0.4-6.6; p = 0.025) and 1200 vs. 800 µl, 3.6 mm (0.4-6.7; p = 0.027)]. Significantly more pain occurred in the thigh versus the abdomen [9.0 mm (6.7-11.3; p < 0.0001)]. CONCLUSIONS: Injection speed had no effect on injection pain, whereas higher injection volumes caused more pain. The results of this study may be of value for guiding patients to use the appropriate injection site and technique to reduce their injection pain. Furthermore, these findings may have important implications for the development of new injection devices and drug formulations for clinical practice.

The effect of injection speed on remifentanil-induced cough in children / 대한마취과학회지

BACKGROUND: Remifentanil sometimes elicits cough during induction of anesthesia, as with the use of other fentanyl congeners. We designed this study to investigate the incidence of remifentanil-induced cough (RIC) in children and to evaluate the effect of injection speed on RIC. METHODS: One hundred twenty ASA physical status I-II patients, aged 3-12 yr, undergoing general anesthesia were enrolled in the study. Patients were randomly assigned to one of the three groups. Patients in Group R30 received remifentanil 1.5 microg/kg at a constant rate over 30 s. Patients in Group R45 received remifentanil 1.5 microg/kg over 45 s, and patients in Group R60 received remifentanil 1.5 microg/kg over 60 s, respectively. Episodes of cough were recorded and graded as mild (1-2), moderate (3-4), or severe (5 or more). Mean arterial pressure (MAP), heart rate (HR), and SpO2 were recorded on arrival in the operating room (baseline) and 1 min after remifentanil infusion. RESULTS: The incidence of RIC was 33.3% in Group R30 (13 of 39 patients), 17.9% in Group R45 (7 of 39 patients), and 5.0% in Group R60 (2 of 40 patients). Patients in Group R60 had a significantly lower incidence of RIC than those in Group R30 (P = 0.001). The MAP, HR, and SpO2 values were not significantly different between groups. CONCLUSIONS: When intravenous remifentanil 1.5 microg/kg was administered in pediatric patients, the incidence of RIC decreased from 33 to 5% by increasing the injection time from 30 to 60 s. Remifentanil should be administered slowly over 60 s in children to suppress cough during anesthesia induction.

The Effect of Injection Speed of Local Anesthetic on Success Rate of Unilateral Spinal Anesthesia / 대한마취과학회지

BACKGROUND: The relationship between the injection speed of a local anesthetic and the success rate of unilateral spinal anesthesia has been a controversial issue. The aim of this thesis was to identify any significant effects of the drug injection speed on the success rate of unilateral spinal anesthesia. METHODS: Forty patients were randomly allocated into 2 groups, group R and S. The injection speed was 4 ml/min in group R (n = 20) and 1 ml/min in group S (n = 20). Hyperbaric 0.5% bupivacaine 10 mg was injected via a syringe pump. The drug was administered at the L3-4 intervertebral space with the patient in the lateral decubitus position, which was maintained for 20 minutes after the injection. A spinal sensory block was assessed by examining the temperature sensation using an alcohol-sponge. The motor block was evaluated using the modified Bromage scale and the dependent and non-dependent sides were compared. RESULTS: Significant differences (P<0.05) were observed in the success rate of unilateral motor paralysis (45% in group R vs 90% in group S). There were no significant blood pressure differences between the two groups 5, 10, 15, 30 and 60 minutes after injecting the hyperbaric 0.5% bupivacaine. CONCLUSIONS: The injection speed of local anesthetics is one of the crucial factors for achieving a unilateral spinal anesthesia. Therefore, it is important to maintain a slow injection speed of a local anesthetic in unilateral spinal anesthesia.

Effect of Injection Speed on the Anesthetic Level and Duration of Hypobaric Spinal Anesthesia with 0.1% Tetracaine in Jack-Knife Position at 15o Head-down Tilting / 대한마취과학회지

BACKGROUND: The speed of injection of local anesthetic solutions into the subarachnoid space may influence the spread of these agents in the cerebrospinal fluid by the amount of turbulence generated, especially with large volume. To determine the proper injection speed of anesthetics in hypobaric spinal anesthesia on jack-knife position, the anesthetic level and duration were measured with the fast or slow injection speed. METHODS: Twenty patients for perianal surgery in jack-knife position under hypobaric spinal anesthesia were randomly assigned to one of two groups. Tetracaine (0.1%) in distilled water 5 ml was administered to all the patients. Group I patients received the drug with the speed of injection as 5 ml/20 sec (15 ml/min) and the others (Group II) as 5 ml/4 min (1.25 ml/min). The mean arterial pressures and heart rates at the preanesthetic period, and 5, 10, 15 and 20 min after the end of injection were measured. The anesthetic levels at 5, 10, 15 and 20 min after the injection and anesthesia duration were measured. RESULTS: There was no significant difference in mean arterial pressures, heart rates and anesthetic duration between two groups. The anesthetic level 20 min after the injection was higher in Group I than Group II, and not different at the other time sequences. CONCLUSION: At the injection speed within 1.25-15 ml/min in hypobaric spinal anesthesia on jack-knife position at 15o head-down, we acquired appropriate anesthetic level and duration for perianal surgery without any undesirable effects.

An Experimental Study on the Effect of Measurement Parameters and Hydrocephalus on the Pressure Volume Index

To study the effect of measurement parameters and hydrocephalus on the pressure volume index(PVI), PVI study was performed in 5 normal and 5 kaolin-induced hydrocephalic cats. The effects of injection volume, speed, laterality and influence of increased intracranial pressure(ICP) in normal and hydrocephalic cats on the PVI value were evaluated. The results were as follows; 1) Larger injection volume, increased ICP by continuous infusion, and presence of ventriculomegaly made the PVI value significantly higher(p<0.01, p<0.001, p<0.05, respectively). 2) Rapid injection made the PVI value significantly lower(p<0.01). 3) Increase of ICP accentuated the effects of injection volume and speed significantly(p<0.01). 4) There was no difference between the PVI values measured with injection into the ipsilateral lateral ventricle and those measured with injection into the cantralateral lateral ventricle. 5) With the above results, it is considered advisable to perform the PVI study with constant injection volume, speed and ICP.