Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir and BMS-788329 combination therapy in human hepatocyte chimeric mice.

We previously reported that interferon (IFN)-free direct-acting antiviral combination treatment succeeded in eradicating genotype 1b hepatitis C virus (HCV) in human hepatocyte chimeric mice. In this study, we examined the effect of vaniprevir (MK7009, NS3/4A protease inhibitor) and BMS-788329 (NS5A inhibitor) combination treatment on HCV genotype 1b and the expression of IFN-stimulated genes (ISGs) using a subgenomic replicon system and the same animal model. Combination treatment with vaniprevir and BMS-788329 significantly reduced HCV replication compared to vaniprevir monotherapy in HCV replicon cells (Huh7/Rep-Feo cells). HCV genotype 1b-infected human hepatocyte chimeric mice were treated with vaniprevir alone or in combination with BMS-788329 for four weeks. Vaniprevir monotherapy reduced serum HCV RNA titers in mice, but viral breakthrough was observed in mice with high HCV titers. Ultra-deep sequence analysis revealed a predominant replacement by drug-resistant substitutions at 168 in HCV NS3 region in these mice. Conversely, in mice with low HCV titers, HCV was eradicated by vaniprevir monotherapy without viral breakthrough. In contrast to monotherapy, combination treatment with vaniprevir and BMS-788329 succeeded in completely eradicating HCV regardless of serum viral titer. IFN-alpha treatment significantly increased ISG expression; however, vaniprevir and BMS-788329 combination treatment caused no increase in ISG expression both in cultured cells and in mouse livers. Therefore, combination treatment with vaniprevir and BMS-788329 eliminated HCV via a non-ISG-mediated mechanism. This oral treatment might offer an alternative DAA combination therapy for patients with chronic hepatitis C.

Rapid, Sensitive, and Accurate Evaluation of Drug Resistant Mutant (NS5A-Y93H) Strain Frequency in Genotype 1b HCV by Invader Assay.

Daclatasvir and asunaprevir dual oral therapy is expected to achieve high sustained virological response (SVR) rates in patients with HCV genotype 1b infection. However, presence of the NS5A-Y93H substitution at baseline has been shown to be an independent predictor of treatment failure for this regimen. By using the Invader assay, we developed a system to rapidly and accurately detect the presence of mutant strains and evaluate the proportion of patients harboring a pre-treatment Y93H mutation. This assay system, consisting of nested PCR followed by Invader reaction with well-designed primers and probes, attained a high overall assay success rate of 98.9% among a total of 702 Japanese HCV genotype 1b patients. Even in serum samples with low HCV titers, more than half of the samples could be successfully assayed. Our assay system showed a better lower detection limit of Y93H proportion than using direct sequencing, and Y93H frequencies obtained by this method correlated well with those of deep-sequencing analysis (r = 0.85, P <0.001). The proportion of the patients with the mutant strain estimated by this assay was 23.6% (164/694). Interestingly, patients with the Y93H mutant strain showed significantly lower ALT levels (p=8.8 x 10-4), higher serum HCV RNA levels (p=4.3 x 10-7), and lower HCC risk (p=6.9 x 10-3) than those with the wild type strain. Because the method is both sensitive and rapid, the NS5A-Y93H mutant strain detection system established in this study may provide important pre-treatment information valuable not only for treatment decisions but also for prediction of disease progression in HCV genotype 1b patients.

Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy.

Although interferon-free antiviral treatment is expected to improve treatment of hepatitis C, it is unclear to what extent pre-existing drug-resistant amino acid substitutions influence response to therapy. The impact of pre-existing drug-resistant substitutions on virological response to daclatasvir and asunaprevir combination therapy was studied in genotype 1b hepatitis C virus (HCV)-infected patients. Thirty-one patients were treated with daclatasvir and asunaprevir for 24 weeks. Twenty-six patients achieved sustained virological response (SVR), three patients experienced viral breakthrough, and two patients relapsed. Direct sequencing analysis of HCV showed the existence of daclatasvir-resistant NS5A-L31M or -Y93H/F variants in nine out of 30 patients (30%) prior to treatment, while asunaprevir-resistant NS3-D168 mutations were not detected in any patient. All 21 patients with wild-type NS5A-L31 and -Y93 achieved SVR, whereas only four out of nine patients (44%) with L31M or Y93F/H substitutions achieved SVR (P = 0.001). Ultra-deep sequencing analysis showed that treatment failure was associated with the emergence of both NS5A-L31/Y93 and NS3-D168 variants. NS5A-L31/Y93 variants remained at high frequency through post-treatment weeks 103 through 170, while NS3-D168 variants were replaced by wild-type in all patients. In conclusion, pre-existence of NS5A inhibitor-resistant substitutions compromised the response to daclatasvir and asunaprevir combination therapy, and treatment failure was associated with the emergence of both NS5A-L31/Y93 and NS3-D168 variants. While asunaprevir-resistant variants that emerged during therapy returned to wild-type, daclatasvir-resistant variants tended to persist in the absence of the drug.

Evaluation of antibiotic use to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the relationship between prophylactic antibiotic use and complications following endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: We retrospectively evaluated 605 consecutive patients who underwent ERCP in our hospital between September 2009 and November 2011. The antibiotic group included patients who underwent their procedure before October 2010, while the control group included patients after October 1, 2010, who did not receive antibiotics. We compared the incidence of postoperative pancreatitis and cholangitis between the groups. RESULTS: There were no significant differences in the backgrounds of the 304 control and the 301 antibiotic-treated patients. The incidence of post-ERCP pancreatitis was 4.9% in the control group and 4.3% in the antibiotic group (p = 0.72). The incidence of postoperative cholangitis was 2.0% in the control group and 1.7% in the antibiotic group (p = 0.99). Choledocholithiasis, pancreatic duct injection, and female gender were detected as significant risk factors for postoperative pancreatitis by multivariate analysis; sclerosing cholangitis and incomplete biliary drainage were significant risk factors for postoperative cholangitis. Even in cases with these risk factors, prophylactic antibiotic use did not influence the incidence of pancreatitis or cholangitis. CONCLUSION: Prophylactic antibiotics do not reduce the incidence of either pancreatitis or cholangitis following ERCP.

Occupational Radiation Exposure during Endoscopic Retrograde Cholangiopancreatography and Usefulness of Radiation Protective Curtains.

Objective. To evaluate the effectiveness of radiation protective curtains in reducing the occupational radiation exposure of medical personnel. Methods. We studied medical staff members who had assisted in 80 consecutive therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures. Use of radiation protective curtains mounted to the X-ray tube was determined randomly for each procedure, and radiation doses were measured with electronic pocket dosimeters placed outside the protective apron. Results. When protective curtains were not used, the mean radiation doses to endoscopists, first assistants, second assistants, and nurses were 340.9, 27.5, 45.3, and 33.1 µSv, respectively; doses decreased to 42.6, 4.2, 13.1, and 10.6 µSv, respectively, when protective curtains were used (P < 0.01). When the patient had to be restrained during ERCP (n = 8), the radiation dose to second assistants without protective curtains increased by a factor of 9.95 (P < 0.01) relative to cases in which restraint was not required. Conclusions. During ERCP, not only endoscopists, but also assistants and nurses were exposed to high doses of radiation. Radiation exposure to staff members during ERCP was reduced with the use of protective curtains.

[Hepatic artery pseudoaneurysm after endoscopic biliary stenting for pancreatic cancer].

A man in his sixties presented to our hospital with obstructive jaundice and was diagnosed with inoperable pancreatic cancer. Chemoradiotherapy was initiated, and an expandable metallic stent was inserted endoscopically to drain the biliary system. Six months later, he was referred to our hospital with 1-week history of epigastric pain and obstructive jaundice. On admission for further evaluation, he experienced hematemesis and went into severe shock. Upper gastrointestinal endoscopy and endoscopic retrograde cholangiopancreatography showed active bleeding from the duodenal papilla. Therefore, we performed endoscopic nasobiliary drainage (ENBD). On day 4, blood was detected in the ENBD tube, and the patient again experienced hematemesis. Emergent enhanced computed tomography revealed a right hepatic arterial aneurysm that had likely ruptured and caused the hemobilia. The aneurysm was successfully embolized, and the patient was discharged on hospital day 21.

Timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: We retrospectively studied the timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis (AIP). MATERIAL AND METHODS: Patients with AIP (n = 31) received steroids followed by diagnostic imaging within 1 month. Pancreatic swelling, pancreatic and bile duct features, and apparent diffusion coefficient (ADC) were compared before and after treatment. The period from treatment initiation to evaluation was divided into five phases: early phase (days 3-5), week 1 (days 6 and 7), week 2 (days 8-14), week 3 (days 15-21), and week 4 (days 22-28). Five gastroenterologists evaluated pancreatic swelling and duct features (good/intermediate/no response), and the "good response" rate (response rate) was calculated for each phase. In addition, pancreatic volumes were measured with a 3D workstation before and after treatment, and the percentage change in volume was calculated. ADC values were calculated in 14 patients. RESULTS: The median ratio of pancreatic volume after relative to before treatment was 0.89, 0.79, 0.67, 0.59, and 0.47 for early phase, week 1, week 2, week 3, and week 4, respectively. The response rate of the pancreatic swelling was 37.5%, 57.1%, 83.3%, 100%, and 100%; response rate of the pancreatic duct was 0%, 20%, 75%, 75% and 100%; and response rate of the bile duct was 0%, 66.7%, 83.3%, 100%, and 80%. The ADC increased after treatment in all 14 patients, including the 7 patients evaluated in the early phase. CONCLUSIONS: Evaluation of pancreatic swelling and duct features is recommended in week 2 and thereafter. The ADC increased soon after treatment initiation, suggesting its usefulness for evaluating early treatment responses.

Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial.

BACKGROUND AND AIM: Despite the benefits of endoscopic nasobiliary drainage (NBD) in endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) and nose/throat discomfort can result. We aimed to determine whether the use of a smaller catheter alleviates these complications. METHOD: A randomized, controlled trial at a tertiary care center compared 4 Fr and 6 Fr NBD catheters; 165 ERCP patients with naïve papillae were randomly assigned to a catheter-size group. RESULTS: The prevalence of PEP was significantly lower in the 4 Fr group (3.7%; 3/82) than in the 6 Fr group (15.7%; 13/83; P = 0.019). No spontaneous catheter displacement occurred within 24 h. Discomfort visual analog scores were 2.6 and 4.3 in the 4 Fr and 6 Fr groups, respectively (P = 0.0048) on procedure day; on the following day, the scores were 2.3 and 3.6 (P = 0.028). Bile output was 16.3 mL/h and 21.4 mL/h in the 4 Fr and 6 Fr groups (P = 0.051). On obstructive jaundice subgroup analysis, bile drainage was 19.2 mL/h and 22.1 mL/h in the 4 Fr and 6 Fr groups (P = 0.40). The 4 Fr group required 5.6 days to reduce bilirubin levels versus 6.1 days in the 6 Fr group (P = 0.51). CONCLUSIONS: In patients with naïve papillae, lower rates of PEP and less nose/throat discomfort are associated with the use of 4 Fr NBD catheters. In patients with obstructive jaundice, 4 Fr and 6 Fr catheters are comparable with regard to bile output and bilirubin level reduction.

Characteristic Features of Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is often complicated by cholangiocarcinoma (CCA); thus, early detection of CCA is an important way to improve PSC prognosis. METHODOLOGY: In a retrospective study, 23 cases of PSC were included. Seven cases were complicated by CCA (CCA group) and 16 cases were not (control group). Blood examinations, bile duct imagings from direct cholangiography, intraductal ultrasonography (IDUS) findings and pathological diagnosis results (bile juice cytology, brush cytology, and forceps biopsy) were referenced. RESULTS: Blood examinations showed that serum carbohydrate antigen 19-9 (CA19-9), total bilirubin, and aspartate aminotransferase were significantly higher in the CCA group, whereas cholangiography showed that the dominant stricture was significantly longer in the CCA group. No significant difference in the IDUS findings was observed between the 2 groups. Cholangioscopy enabled CCA diagnosis via identification of the papillary mucosa in sites other than the stricture. Forceps biopsy was the most useful pathological diagnostic technique, with a sensitivity of 86% and a specificity of 100%. CONCLUSIONS: The CA19-9 level and bile duct stricture morphology were useful for diagnosing CCA complicating PSC. Aggressive performance of cholangioscopy and pathological diagnostic techniques, such as brush cytology and forceps biopsy, are essential for identification.

A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections.

The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs.

Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: ιmplications for cholangiocarcinogenesis.

Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.

[Malignant phyllodes tumor metastatic to the pancreas: a case report].

A woman in her 50s was admitted with obstructive jaundice due to a pancreatic mass. She had a history of a right breast phyllodes tumor treated with mastectomy 3 years previously. Diagnostic imaging (endoscopic ultrasonography (EUS), CT, and MRI) demonstrated a well-demarcated mass in the pancreatic head. EUS-FNA showed spindle shaped tumor cells. The pancreaticoduodenectomy specimen showed a malignant spindle cell tumor consistent with a metastatic malignant phyllodes tumor. In addition, immunohistochemical staining demonstrated that the staining pattern of pancreatic tumor was similar to that of the breast phyllodes tumor. Pancreatic metastases from breast phyllodes tumors have rarely been reported in the literature.

[A new method for measuring temporal resolution in electrocardiogram-gated reconstruction image with area-detector computed tomography].

The purpose of this study was to design and construct a phantom for using motion artifact in the electrocardiogram (ECG)-gated reconstruction image. In addition, the temporal resolution under various conditions was estimated. A stepping motor was used to move the phantom over an arc in a reciprocating manner. The program for controlling the stepping motor permitted the stationary period and the heart rate to be adjusted as desired. Images of the phantom were obtained using a 320-row area-detector computed tomography (ADCT) system under various conditions using the ECG-gated reconstruction method. For estimation, the reconstruction phase was continuously changed and the motion artifacts were quantitatively assessed. The temporal resolution was calculated from the number of motion-free images. Changes in the temporal resolution according to heart rate, rotation time, the number of reconstruction segments and acquisition position in z-axis were also investigated. The measured temporal resolution of ECG-gated half reconstruction is 180 ms, which is in good agreement with the nominal temporal resolution of 175 ms. The measured temporal resolution of ECG-gated segmental reconstruction is in good agreement with the nominal temporal resolution in most cases. The estimated temporal resolution improved to approach the nominal temporal resolution as the number of reconstruction segments was increased. Temporal resolution in changing acquisition position is equal. This study shows that we could design a new phantom for estimating temporal resolution.

[Evaluation of 320-row area detector computed tomography (ADCT) coronary angiography for patients with atrial fibrillation].

The aim of this study was to evaluate 320-row area detector CT (ADCT) for patients with atrial fibrillation (Af) based on simulated exposure using electrocardiogram RR intervals and comparison with the findings of coronary CT angiography (CCTA) using 64-row multi slice CT (MSCT). The probability of including RR intervals of 900 ms or more was calculated when the acquisition time was varied from 1 to 4 beats. Overall, 51 patients with Af who underwent CCTA were examined. The exposure time for CCTA, the total dose length product (DLP) for the examination, and the image quality (scored 0 to 3: poor to excellent) were compared between ADCT and MSCT. The probability of including RR intervals of 900 ms or more was highly significantly increased at 3 beats of acquisition time. The exposure time using ADCT was reduced by 75% compared with MSCT (ADCT/MSCT: 2.8/11.3 s), and the total DLP was reduced by 40% (ADCT/MSCT: 1398/2277 mGy·cm). Moreover, ADCT provided diagnosable images in all cases, and the mean image quality score for ADCT was significantly higher than that for MSCT (ADCT/MSCT: 2.8/2.4). Thus, 320-row ADCT at 3 beats of acquisition time can provide CCTA images of acceptable quality for patients with Af.

[A case of drug-induced interstitial pneumonia caused by S-1 and CPT-11 combination therapy for advanced colon cancer].

The patient was a 77-year-old woman admitted for nausea and abdominal pain. Computed tomography (CT) revealed advanced ascending colon cancer with liver metastasis. After operation, we started combination chemotherapy of S-1 and irinotecan (CPT-11); S-1(80 mg/m²) administered orally for consecutive days followed by 14 days rest.CPT -11 (100 mg/m²) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent dyspnea with severe hypoxemia after the first course of combination chemotherapy of S-1 and CPT-11.CT scan showed diffuse interstitial lesions with ground glass opacity on both lungs. Steroid pulse therapy with oxygen therapy remarkably improved her symptoms, and abnormal findings on CT scan also resolved. Drug lymphocyte stimulation test was positive against S-1 and negative against CPT-11. These findings were consistent with S-1-induced lung injury. Drug -induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1 and CPT-11 combination therapy present high fever and dyspnea.

[A case of effective chemotherapy using S-1 and CPT-11 following chemoradiotherapy with UFT and Leucovorin for unresectable advanced sigmoid colon cancer].

The patient was a 75-year-old man who was admitted because of diarrhea and anemia. Endoscopic examination revealed advanced sigmoid colon cancer. Serum CEA levels were markedly elevated. In July 2007, surgery was performed, but the sigmoid colon cancer was unresectable. After surgery, the patient was treated with chemotherapy and concurrent radiotherapy. The chemotherapy consisted of oral UFT (420 mg/body/day)and Leucovorin (75 mg/body/day) administered for 6 weeks. Radiotherapy at 2 Gy/day was administered 30 times (total dose 60 Gy). The tumor decreased slightly in size and serum CEA levels also decreased. The patient refused surgery as an additional therapy. In August 2007, we started combination chemotherapy using oral S-1 (100 mg/body/day, day 1-14) and intravenous CPT-11 (140 mg/body/day, day 1 and 15) as one course for 4 weeks. After 4 courses, serum CEA levels were normal, the sigmoid colon cancer was not found by endoscopy and a biopsy specimen revealed no malignant cells. Moreover, after 8 courses, the tumor disappeared, as confirmed by computed tomography (CT) and positron emission tomography-CT, representing a complete response. Chemoradiotherapy using UFT and Leucovorin, and chemotherapy consisting of S-1 and CPT-11 as an additional therapy may be effective for treating unresectable advanced sigmoid colon cancer.

[A case of effective chemoradiotherapy using S-1 and CDDP for left inguinal lymph node metastasis of anal canal carcinoma].

We report a case of left inguinal lymph node metastasis of anal canal carcinoma, treated effectively with chemotherapy consisting of S-1 and CDDP combined with radiotherapy. In February 2006, a 76-year-old woman underwent resection of a tumor diagnosed as squamous cell carcinoma of the anal canal. The patient refused additional surgical therapy. In August 2007, a painful lymphnode swelling was noticed in the left inguinal region. Biopsy was performed, and specimens were shown to include squamous cell carcinoma cells. The patient was treated using chemotherapy concurrent with radiotherapy. The chemotherapy consisted of oral S-1 (80 mg/body/day; 5 days/week) and intravenous CDDP (5 mg/body/day; 5 days/week), both administered for 4 weeks. Radiotherapy at 2 Gy/day was administered 25 times (total dose 50 Gy). The metastatic tumor in the lymph node responded well to the treatment and decreased remarkably in size by December 2007. After chemoradiotherapy, the oral administration of S-1 alone (80 mg/body) for 2 weeks followed by a 2-week rest period as one course was continued for 1 year. The lymph node metastasis had disappeared 1 year after chemoradiotherapy, as determined by computed tomography (CT) and positron emission tomography-CT, representing a complete response. Chemotherapy consisting of S-1 and CDDP concurrent with radiotherapy maybe effective for treating metastatic lymph node metastasis of anal canal carcinoma.

[Yakon tea induced hepatitis in a patient with alcoholic liver cirrhosis].

A 66-year-old woman, given a diagnosis of alcoholic liver cirrhosis in 2004, had improved her liver function by abstinence from drinking. Since then, she has drunk 1 to 2 liters of Yakon tea per day. Her liver function deteriorated and T. Bil was 13.2mg/dl and AST was 291U/l in February 2005. Given the positive DLST for Yakon tea, Yakon tea-induced hepatitis was diagnosed. After cessation of the intake of the tea, her liver function gradually improved. Since there has been no report on Yakon induced hepatitis and it has been thought to be a safe supplement, we here report this intriguing case.

[The improvement in the cerebral blood flow analysis software in case of CT-perfusion inspection and the examination of the scan protocol].

In our hospital, CT-perfusion was introduced in April, 2002. It is used to diagnose, to determine what treatment to use and to prognosticate cerebral blood flow after operation in super acute period brain infarct. At the beginning of the introduction, processing time and dosage for partial areas needed improvement. Therefore, we investigated the possibility of shorter processing time and lower dosage of radiation with the help of improvement in the analysis software as well as a different scan method. Two methods of reducing radiation dosage were examined. (1) The speed of X-ray rotation was slowed down; while photon per image was maintained, total mAs was lowered. (2) Continuation scan was replaced by intermission one. Analyzing time with older and newer version of analysis software was compared. The dosage was able to decrease by 25% as a result of the rotation speed slowed down; it became further less by 50% with the intermission scan. Processing such as the vein extraction was automated by using new analysis software and successfully shorten the analysing time without damaging the reliability of analyses. We forecast that more clinical research on further lowering dosage and stabilization of analyzing will enable us to provide better information.