Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats.

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.

A novel UHPLC‒MS/MS method for quantitative analysis of zanubrutinib in rat plasma: application to an in vivo interaction study between zanubrutinib and triazole antifungal.

BACKGROUND: This study establishes a UHPLC‒MS/MS method for the detection of zanubrutinib and explores its interaction with fluconazole and isavuconazole in rats. METHODS: A protein precipitation method using acetonitrile was used to prepare plasma samples using ibrutinib as an internal standard. Chromatographic separation and mass spectrometric detection of the analytes and internal standards were performed on a Shimadzu 8040 UHPLC‒MS/MS equipped with a Shim-pack velox C18 column (2.1 × 50 mm, 2.7 µm). Methanol and 0.1% formic acid-water were used as mobile phases. Intraday and interday precision and accuracy, extraction recoveries, and matrix effects of this method were determined. The linearity and sample stability of the method were assessed. Eighteen male Sprague‒Dawley (SD) rats were randomly divided into three groups with zanubrutinib (30 mg/kg) alone, zanubrutinib in combination with fluconazole (20 mg/kg) or zanubrutinib in combination with isavuconazole (20 mg/kg). Blood samples (200 µL) were collected at designated time points (ten evenly distributed time points within 12 h). The concentration of zanubrutinib was determined using the UHPLC‒MS/MS method developed in this study. RESULTS: The typical fragment ions were m/z 472.15 → 290.00 for zanubrutinib and m/z 441.20 → 138.10 for ibrutinib (IS). The range of the standard curve was 1-1000 ng/mL with a regressive coefficient (R2) of 0.999. The recoveries and matrix effects were 91.9-98.2% and 97.5-106.3%, respectively, at different concentration levels. The values for intra- and interday RSD% were lower than 9.8% and 5.8%, respectively. The RSD% value was less than 10.3%, and the RE% value was less than ± 4.0% under different storage conditions. Analysis of pharmacokinetic results suggested that coadministration with isavuconazole or fluconazole significantly increased the area under the curve (1081.67 ± 43.81 vs. 1267.55 ± 79.35 vs. 1721.61 ± 219.36), peak plasma concentration (332.00 ± 52.79 vs. 396.05 ± 37.19 vs. 494.51 ± 130.68), and time to peak (1.83 ± 0.41 vs. 2.00 ± 0.00 vs. 2.17 ± 0.41) compared to zanubrutinib alone. CONCLUSION: This study provides information to understand the metabolism of zanubrutinib with concurrent use with isavuconazole or fluconazole, and further clinical trials are needed to validate the results in animals.

Development and Validation of a UHPLC-MS/MS Method for Quantitation of Almonertinib in Rat Plasma: Application to an in vivo Interaction Study Between Paxlovid and Almonertinib.

Almonertinib was approved for the first-line treatment of advanced NSCLC patients with EGFR-TKI-sensitive genetic mutations by National Medical Products Administration (NMPA) in 2021.The purpose of this study was to establish and validate a fast, accurate, stable and facile ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of almonertinib in rat plasma, it was employed to explore the effect of Paxlovid on the pharmacokinetics of almonertinib in rats. Zanubrutinib was used as an internal standard (IS), and the plasma samples were prepared by the protein precipitation method using acetonitrile. Chromatographic separation was carried out on a Shimadzu LC-20AT ultra-performance liquid chromatography system using a Shim-pack velox C18 (2.1× 50 mm, 2.7 µM) column. The mobile phase consisted of methanol and 0.1% formic acid-water. Mass spectrum analysis was executed using Shimadzu 8040 Triple quadrupole mass spectrometry. The precursor and product ions of the analyte and internal standard were detected in multiple reaction monitoring (MRM) mode. The typical fragment ions were m/z 526.20 → 72.10 for almonertinib and m/z 472.15 → 290.00 for zanubrutinib (IS). The method was validated to have good linearity for quantifying almonertinib in rat plasma from 0.1-1000 ng/ml (R2 = 0.999), and the LLOQ was 0.1 ng/ml. The validity of this method was sufficiently verified for selectivity, specificity, extraction recovery, matrix effect, accuracy, precision and stability. The validated UHPLC-MS/MS method was successfully applied to the drug interaction study of almonertinib with Paxlovid in rats. Paxlovid significantly inhibits the metabolism of almonertinib and increased the exposure of almonertinib. This study can help us to understand the metabolic profile of almonertinib better, and further human trials should be conducted to validate the results.

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes.

BACKGROUND AND OBJECTIVES: Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer effects. Although there are in vitro studies showing that myricetin inhibits human cytochrome P450 (CYP) 2D6 and CYP3A, the inhibitory mechanisms of myricetin on CYP enzymes are still unclear. The aim of this study was to evaluate the inhibitory effects of myricetin on human and rat CYPs, including CYP3A2/3A4, CYP2B1/2B6, CYP2C9/2C11 and CYP2D1/2D6. METHODS: This study was performed to investigate the inhibitory effects of myricetin on human CYP3A4, CYP2B6, CYP2C9, CYP2D6 and rat CYP3A2, CYP2B1, CYP2C11, CYP2D1 through the cocktail approach using ultra-performance liquid chromatography tandem mass spectrometry. Typical probe substrates were used as follows-midazolam for CYP3A2/3A4, dextromethorphan for CYP2D1/2D6, tolbutamide for CYP2C9/2C11, and bupropion for CYP2B1/2B6. RESULTS: The results of this study showed that myricetin might not be a time-dependent inhibitor. Moreover, myricetin inhibited CYP3A4 in an uncompetitive way with an inhibition constant (Ki) value of 143.1 µM. It was also a noncompetitive inhibitor of CYP2C9 and CYP2D6 with Ki values of 31.12 and 53.44 µM and a competitive inhibitor of CYP2B1 with a Ki value of 69.70 µM, as well as a mixed inhibitor of CYP3A2, CYP2C11 and CYP2D1with Ki values of 37.57, 14.88 and 17.39 µM, respectively. CONCLUSIONS: In conclusion, this study indicates that myricetin inhibited CYP3A4/3A2, CYP2C9/2C11, CYP2D6/2D1 and CYP2B1 by various mechanisms with different Ki values. Given that our experiments are established in vitro, further in vivo work is needed to confirm the interaction between myricetin and CYP enzymes, thus providing better guidance for the safe clinical use of myricetin.

Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats.

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0-t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.

Inhibitory effect of resveratrol on the pharmacokinetic of ibrutinib by UPLC-MS/MS.

OBJECTIVE: To investigate the impact of resveratrol on the metabolism of ibrutinib in vitro and in vivo. METHODS: In vitro, rat liver microsomes (RLM) and human liver microsomes (HLM) were used to study. In vivo, 18 male SD rats were randomly divided into three groups (n = 6): ibrutinib and the multiple dose of 100 mg/kg resveratrol for consecutive 7 days (Group A), ibrutinib and the single dose of 100 mg/kg resveratrol (Group B), ibrutinib (Group C). Processed samples were analyzed by UPLC-MS/MS. RESULTS: Resveratrol showed inhibition on RLM and HLM in vitro. The IC50 of resveratrol was 8.745 µM in RLM and 7.789 µM in HLM. Furthermore, Groups A and B both increased the AUC and reduced the CLz/F. The Cmax of Group A and the MRT(0-t) of Group B were significantly improved. CONCLUSIONS: Resveratrol inhibits the pharmacokinetic of ibrutinib in vitro and in vivo. It is necessary to pay more attention to adjust the dose of the drug when resveratrol is used in combination with ibrutinib.

Evaluation of the inhibition effects of apatinib on human and rat cytochrome P450.

Apatinib, a small molecule anti-angiogenic drug, is proven to be safe and effective for treatment of advanced gastric cancer (AGC). It is also a single drug that significantly prolongs survival after failure of standard chemotherapy for AGC, which has attracted the research interest. The purpose of this study is to evaluate the inhibition effects of apatinib on human and rat cytochrome P450, including CYP3A2/4, CYP2B1/6, CYP2C9/11, CYP2D1/6, and CYP2E1. The IC50 and IC50-shift results indicated that apatinib might not be a time-dependent inhibitor. Apatinib was a weak inhibitor of human CYP2E1 (IC50>10 µM) but inhibited CYP2B6/2B1 and CYP2D6/2D1 in a competitive way (Ki = 3.84/0.59 and 5.41/0.87 µM), and inhibited CYP3A4/3A2 and rat CYP2E1 in a mixed way (Ki = 11.50/1.83 and 13.06 µM). On CYP2C9, apatinb exhibited the noncompetitive inhibition (Ki = 0.71 µM) while it inhibited CYP2C11 uncompetitively (Ki = 3.30 µM).

Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and O-desmethylvenlafaxine in SD Male Rats by UPLC-MS/MS.

The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty-one SD male rats were randomly divided into three groups (n = 7): group A (multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg apatinib) and group C (the control group). All samples were measured by UPLC-MS/MS. The results indicated that a single dose of apatinib increased the AUC(0-t) , AUC(0-∞) and Cmax of both venlafaxine and O-desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC(0-t) and CLz/F of venlafaxine were changed, while no parameters of O-desmethylvenlafaxine were altered. In addition, apatinib was determined to be a mixed inhibitor of venlafaxine.

Functional assessment of CYP3A4 allelic variants on lidocaine metabolism in vitro.

AIM: Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23 CYP3A4 alleles and evaluate their catalytic activities on the metabolism of lidocaine in vitro. METHODS AND RESULTS: The wild-type and 22 CYP3A4 variants were expressed in Spodoptera frugiperda 21 insect cells. Then the insect microsomes were incubated with the CYP3A4-specific substrate lidocaine. Reactions were performed with 50-3,000 µM for 60 min at 37°C. Lidocaine and its metabolite monoethylglycinexylidide were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system. Of the 23 CYP3A4 allelic variants tested, 2 variants (CYP3A4*17 and CYP3A4*30) had no detectable enzyme activity; and 5 variants (CYP3A4*2, CYP3A4*5, CYP3A4*9, CYP3A4*16 and CYP3A4*24) showed significantly decreased intrinsic clearance values compared with wild-type CYP3A4*1. CONCLUSION: As the first study of all these CYP3A4 alleles for lidocaine metabolism, our results in vitro assessment may provide novel insights into the allele-specific and substrate-specific activity of CYP3A4 and may also offer a reference to the personalized treatment of lidocaine in a clinical setting.

Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro.

BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 µM-1000 µM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS). RESULT: Catalytic activity of thirty-eight CYP2C9 alleles on ketamine metabolism to norketamine was surveyed. Compared with 2C9*1, three alleles (2C9*40, *49 and *51) was demonstrated dramatically increased intrinsic clearance (1.2-fold-3.75-fold); four subtypes (2C9*27, *31, *41 and *56) exhibited no significantly change on enzyme activity. The resting 31 alleles expressed different degrees of reduction compared with wild type. CONCLUSION: The result of research warns that attention should be more paid on individual who carry on the special 2C9 alleles under the situation of administrating ketamine.

Management complicated hepatolithiasis with operative rigid choledochoscope guided by computed tomography (CT)-based 3D reconstruction technique.

BACKGROUND: Treatment of complicated hepatolithiasis is complex and difficult. In this report, we present a novel approach to manage complicated hepatolithiasis using the rigid choledochoscope guided by CT-based 3D reconstruction technique with or without hepatectomy. METHODS: Between February 2012 to December 2013, 25 patients with complicated hepatolithiasis underwent rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy. 27 patients with complicated hepatolithiasis underwent a traditional operation (traditional method group) from June 2011 to January 2012. All operations were performed by the authors. RESULTS: The final stone clearance rate of the rigid choledochoscope group was 96%, whereas that of the traditional method group was 74.1% (P=0.032). There was no patient died of postoperative mortality in two groups. Moreover, the operative time in the traditional method group was significantly longer than that in the rigid choledochoscope group (P=0.010). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSIONS: Operative rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy may be an effective and safe treatment for complicated hepatolithiasis.

To assess the benefits of medical image three-dimensional visualization system assisted pancreaticoduodenctomy for patients with hepatic artery variance.

BACKGROUND: Our main aim was to evaluate the value of medical image three-dimensional visualization system (MI-3DVS) in pancreaticoduodenctomy patients with hepatic artery variance. METHODS: 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed. Clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional (3D) reconstruction. The findings were compared with those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery. RESULTS: The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. About (14/114 cases, 12.3%) had variant. The sensitivity, specificity and accuracy of MI-3DVS in variant hepatic artery diagnosis were 100%. It assisted in preoperative procedural planning that was consistent with intraoperative findings. CONCLUSIONS: MI-3DVS can be applied for accurate diagnosis of hepatic artery variance. It also provides detailed preoperative guidance for individualized procedural planning.

3D Reconstruction Aids Surgery For Complicated Hepatolithiasis.

BACKGROUND/AIMS: Three-dimensional (3D) imaging may improve surgical interventions for complicated hepatolithiasis. METHODOLOGY: Between July 2008 and December 2012 a total of 131 patients with complicated hepatolithiasis underwent surgical therapy in the Department of Hepatobiliary Surgery Zhujiang Hospital, Southern Medical University. 77 patients received preoperative planning using a computed tomography (CT)-based 3D reconstruction technique, and 54 received treatment based on preoperative planning with traditional imaging (CT, ultrasonography, magnetic resonance imaging/magnetic resonance cholangiography). Perioperative and long-term outcomes were analyzed. RESULTS: 3D reconstruction facilitated significantly more accurate diagnosis of pathological morphology than conventional imaging methods, as confirmed during surgery. Patients that received 3D reconstruction preoperative planning had significantly better clinical outcomes. The immediate stone clearance rates were 92.2% and 61.1%, respectively. Additional postoperative choledochoscopic lithotripsy raised the clearance rates to 94.8% and 81.5%, respectively. The hospital mortality rates were 0% and 1.9%, respectively, and the complication rates were 33.8% and 44.4%, respectively. With a median follow-up of 28 months (5-38 months), the long-term overall asymptomatic survival rates were 80.5% and 46.3%, respectively. 3D reconstruction preoperative planning was a significant prognostic protective factor of long-term asymptomatic survival for the patients with complicated hepatolithiasis (Cox regression analysis, RR = 0.348, 95% confidence interval 0.185-0.657, p = 0.001). CONCLUSION: Surgical therapy conducted following preoperative planning using 3D reconstruction achieved better clinical outcomes than conventional imaging techniques. Whilst conventional imaging techniques accurately identify intrahepatic stones, they are less capable of identifying bile duct stricture.

Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects.

BACKGROUND: The impact of hepatic venous anatomic variations on hepatic resection and transplantation is the least understood aspect of liver surgery. METHODS: A prospective three-dimensional computed tomography study was undertaken on 200 consecutive subjects with normal livers to determine the prevalence of surgically significant hepatic venous anatomic variations. RESULTS: The prevailing pattern of the three hepatic veins in these subjects was a right hepatic vein (RHV) and a common trunk for the middle (MHV) and left (LHV) hepatic veins (122/200, 61%). The remaining patients had the RHV, MHV, and LHV draining independently into the inferior vena cava (IVC). In 39% of patients, the RHV was small and was compensated by a large right inferior hepatic vein (21.0%), an accessory RHV (8.5%) or a well-developed MHV (6.5%). A segment 4 vein was seen in 51.5% of patients. This segment 4 vein joined the LHV (26%), the MHV (17.5%), or the IVC (8%). An umbilical vein and a segment 4 vein were seen in 3.5% of patients. These two veins joined either the LHV (2.0%) or the MHV (1.5%). CONCLUSIONS: Knowing the variations of hepatic veins before surgery is useful during both partial hepatectomy and donor operations for living related liver transplantation.

[Application of the medical image three-dimensional visualization system of abdomen in diagnosis and evaluating resectability of pancreatic tumors].

OBJECTIVE: To study the value and the clinical application of the Medical Image three-dimensional Visualization System of Abdomen (MI-3DVS) in diagnosis and evaluating resectability of pancreatic tumor. METHODS: Twelve patients with pancreatic tumor were tested with 64-slice helical CT (64-MSCT) angiography, and the CT data was reconstructed with MI-3DVS from November 2008 to August 2009. The 3D findings were adopted in diagnosis and evaluating resectability, and the results were compared with surgical operation and the pathological finding. There were 7 male and 5 female, aged from 14 to 83 years. Within the 12 cases, there were 4 cases with pancreatic carcinoma, 5 cases with pancreatic solid pseudopapillary tumor, 2 cases with pancreatic serous cystadenoma, 1 case with pancreatic cyst (ductal epithelial papillary hyperplasia). RESULTS: Nine tumors which had been regarded as removable pre-operatively with MI-3DVS were removed successfully. Three patients who were considered unresectable by other hospitals with CT were operated successfully with MI-3DVS. The other 3 patients' tumors were actually not able to be removed as pre-operative evaluation. CONCLUSION: MI-3DVS plays an important role in diagnosis and assessment of resectability of pancreatic tumor.

[Study on visualized virtual surgery of living-related donor liver transplantation].

OBJECTIVE: To investigate the significance of three dimensional visualization and virtual surgery system in living related donor liver transplantation surgery. METHODS: Two patients suffered biliary calculi were scanned by 64 slice helical computer tomography (CT) on livers and the data were imported into medical image proceeding system (MIPS) for sequence. Man-made segmentation and true-up on the image from the data were carried out. Three dimensional (3D) models of the liver and the intrahepatic vessels were reconstructed by VTK software respectively. The models were exported with format STL from it and then were imported into the FreeForm Modeling System for smoothing and modifying. At last, living related donor liver transplantation were simulated with the force-feedback equipment (PHANToM). RESULTS: It had great verisimilar image for the reconstructed 3D liver models with artery, hepatic vein, portal vein and bile duct. By seeing through liver, it had high fidelity and strong 3D effect for the intrahepatic artery, hepatic vein, portal vein and bile duct, and their spatial disposition and course and co-relationship were shown clearly. In the virtual surgery system, the virtual scalpel could be manipulated on 3D liver model with PHANToM. The simulating effect was the same as the clinic operation for living related donor liver transplantation. CONCLUSIONS: The visualized liver model reconstructed is 3D and verisimilar, and it is helpful to design reasonable scheme for liver transplantation. It can improve the surgical effect, decrease the surgical risk, reduce the complication, enhance the communication between doctor and patient through designing surgical plan and demonstrating visualized operation before surgery.

[Establishment of a three-dimensional pancreas model for simulating surgical resection of pancreatic tail carcinoma using virtual-reality technique].

OBJECTIVE: To assess the feasibility of visual-reality technique for simulating surgical resection of pancreatic tail carcinoma using a 3-dimensional pancreas model reconstructed on the basis of the CT data. METHODS: The original image data of 64-slice spiral CT was obtained from a patient with pancreatic tail carcinoma. Using adaptive region growing algorithm, the serial CT images were segmented and automatically extracted for 3-dimensional reconstruction of the pancreas and the anatomically related structures with a self-designed program. The model was then processed with Freeform Modeling System for image modification and smoothing. With the assistance of GHST SDK and PHANTOM software systems, preoperative simulation of surgical resection of the carcinoma was performed on the basis of the established pancreatic model. RESULTS: The reconstructed 3-dimensional pancreatic model with the related structures clearly visualized the 3-dimensional structures of the pancreas, the pancreatic tail compromised by the carcinoma, and the adjacent organs, displaying also the distribution, courses and the anatomical relations of the ductal systems including the main pancreatic duct, abdominal aorta, portal vein system, and the biliary tract. During simulated surgery for pancreatic tail carcinoma resection, the GHOST SDK system allowed effective application of the virtual surgical instruments, and the use of PHANTOM software produced a surgical experience with high resemblance of that from an actual operation. CONCLUSION: The serial CT data-based reconstruction of 3-dimensional pancreas model and simulated operation on this model using virtual-reality technique has great potentials for application in individualized surgical planning and surgical risk assessment in cases of pancreatic tail carcinoma, and also facilitates clinical training of the surgeons.

[Study on the three dimensional hepatic virtual operation based on the data of 64-slice helical CT scanning].

OBJECTIVE: To study the surgery plan and simulation effect of the three dimensional (3D) hepatic virtual operation based on the data of 64-slice helical CT scanning and to probe the feasibility of the virtual operation based on the FreeForm Modeling System. METHODS: The volunteer liver was scanned to collect two dimensional (2D) DICOM data of 64-slice helical CT scanning and the 3D hepatic and intrahepatic vessels model were reconstructed by MIMICS software. The reconstructed liver, the intrahepatic vessels model and the artificial tumor models were output into the FreeForm Modeling System in the STL format. The device PHANTOM with the characterization of dynamo-feedback was applied to make the operation on the 3D hepatic. RESULTS: The spatial relationship between the tumour and the intrahepatic vessels were clearly observed by rotation and enlargement of the target. According to the operation principle, the left lobe of liver resection was simulated by manipulating the device PHANToM. Through the liver transparence surface, the intrahepatic vessels were easily distinguished. The operation procedure was accord with the clinic hepatic surgery. Meanwhile, during the operation, by adjusting the incision objective intensity, the dynamo-feedback intensity was definitely touched. CONCLUSIONS: By using the FreeForm Modeling System,the hepatic operation procedure can be simulated ahead of time. The operation complication in the practical surgery can be anticipated and the individualization operation schema can be reasonable instituted.

[Image segmentation and three-dimensional reconstruction of the liver based on 64-slice spiral CT scanning data].

OBJECTIVE: To study the segmentation methods of the liver CT images and the value of 3-dimensional (3D) reconstruction of the liver in the planning of hepatic surgery. METHODS: The 2D Digital Imaging and Communications in Medicine (DICOM) format data of the liver obtained from healthy volunteers were transformed into bmp format image, and the liver image segmentation was performed using Photoshop software. The 3D model was reconstructed using MIMICS software. RESULTS: The DICOM format data of the liver obtained by 64 slice spiral CT included totally 658 slice images. The segmented liver image showed clear profiles and complete intrahepatic duct data were reserved. The segmented liver images were free of discontinuation during continuous observation. The liver surface and internal ductal system, including the hepatic arteries and veins, and the hepatic portal system and their branches, were represented clearly. The reconstructed liver allowed clear identification of the anatomic landmark and matched the actual liver volume. The reconstructed ductal structure were distinct and continuous with natural texture. The reconstructed liver and the hepatic internal duct system were simultaneously displayed by adjusting the transparency of the liver, and the blood vessels were also represented. CONCLUSION: Segmentation of the liver images in different phases using Photoshop can be feasible for liver reconstruction. The reconstructed liver and the intrahepatic ductal structure allow vivid 3D observation of the spatial relationship among the major tracts and accurate estimation of the liver volume.

[Virtual surgery of cholecystotomy for calculus removal and cholecystectomy in patients with cholecystolithiasis].

OBJECTIVE: To study the two-dimensional (2D) image segmentation, three-dimensional (3D) reconstruction and virtual surgery of cholecystectomy based on the 2D image data of the liver, biliary track and cholecystolithiasis obtained by 64-slice spiral CT. METHODS: The image data of the liver, biliary track and cholecystolithiasis were obtained by 64-slice spiral CT scanning. Segmentation and automatic extraction of the images were performed using auto-adapting region growing algorithm. 3D reconstruction of the segmented data was carried out using MIMICS10.0 and self-designed software, and the data of the 3D model of the liver with the billiary tract were imported into FreeForm Modeling System for registration and smoothing. Virtual surgery of cholecystotomy for calculus removal and cholecystectomy were performed with Phantom. RESULTS: The auto-adapting region growing algorithm allowed rapid image segmentation, and the 3D model of the liver based on the segmentation data clearly displayed vivid 3D structures of the liver. Virtual operations of cholecystectomy could be performed in the FreeForm Modeling System. CONCLUSION: The algorithm we proposed can correctly and rapidly complete image segmentation and 3D reconstruction of cholecystolithiasis from the data 64-slice spiral CT, and allows virtual operations on the gallbladder.