Atsushi Oguro

Difference in regional hepatic blood flow in liver segments--non-invasive measurement of regional hepatic arterial and portal blood flow in human by positron emission tomography with H2(15)O.

Organ blood flow can be quantitatively measured by positron emission tomography (PET). As the liver has dual blood supplies, arterial and portal, regional hepatic blood flow had not been measured quantitatively. However, we succeeded in simultaneously measuring both regional hepatic arterial and portal blood flow by PET in non-stressed patients. Mean regional portal hepatic blood flow in patients with normal liver and cirrhotic liver was 57.5 and 36.7 ml/minutes/100 g, respectively. Mean regional arterial blood flow was 42.5 and 30.7 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in normal and cirrhotic patients was noted. Mean regional portal hepatic blood flow in the lateral, medial, anterior, and posterior segments of the liver was 29.8, 43.4, 50.0, and 40.9 ml/minutes/100 g, respectively. Mean regional arterial blood flow in each liver segment was 37.6, 30.0, 28.2, and 31.6 mi/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in lateral and anterior segment was noted. The p value was less than 0.025 and the 95 % confidence interval of the difference between means was from −20.2 to −2.7 ml/minutes/100 g by ANOVA. These results showed that regional hepatic blood flow is not the same in all the liver segments.

Factors Relating to Coagulation, Fibrinolysis and Hepatic Damage After Liver Resection

A survey of the blood of twenty-two patients who had undergone hepatic resection was performed. Serum levels of α-2 plasmin inhibitor-plasmin complex initially decreased from 1.58 ± 0.31 μg/ml on the preoperative day (PREOP), to 0.92 ± 0.14 μ/ml on the first postoperative day (POD 1), and then increased to 3.13 ± 0.92 μg/ml on the seventh postoperative day (POD 7) (mean ± SE)). Thrombin-anti-thrombin III complex (14.2 ± 4.3 ng/ml on PREOP and 26.0 ± 4.1 ng/ml on POD 7 (mean ± SE)) and D-dimer (335 ± 96 ng/ml on PREOP and 1859 ± 258 ng/ml on POD 7 (mean ± SE)) increased in the early postoperative stage. The level of 6-keto-prostaglandin F1α increased after the operations (from 13.2 ± 1.8 pg/ml on PREOP to 37.8 ± 12.8 pg/ml on POD 7 (mean ± SE)). The level of thromboxane B-2 decreased at first, and then gradually increased and returned to its preoperative level on POD 7 (144.7 ± 43.8 pg/ml on PREOP, 57.6 ± 27.5 pg/ml on POD1 and 152.5 ± 58.4 pg/ml on POD 7 (mean ± SE)). Superoxide dismutase activity increased at first, and then gradually decreased, postoperatively (2.8 ± 0.5 NU/ml on PREOP, 4.8 ± 0.8 NU/ml on POD1 and 2.6 ± 0.3 NU/ml on POD 7 (mean ± SE)). That is, biodefensive reactions which protect patients against the shift to disseminated intravascular coagulation (DIC) were inferred with by the increase in antiplatelet aggregation, despite the activation of coagulation and fibrinolytic mechanisms after hepatic resection.

Using the spleen for time-delay correction of the input function in measuring hepatic blood flow with oxygen-15 water by dynamic PET.

By the spleen, we calculated a time-delay correction of the input function for quantitation of hepatic blood flow with oxygen-15 water and dynamic positron emission tomography. The time delay (Δt) between the sample site and the spleen was calculated based on nonlinear multiple regression analysis when splenic blood flow was determined. Then hepatic blood flow was quantified by a method using the input function and incorporating Δt, which was assumed to be equal to the time delay between the sample site and the liver. Then hepatic arterial and portal blood flows were estimated separately as well as the delay time for passage within the organs of the portal circulation. The mean coefficient of variation and the mean sum of squares of errors decreased to about 70% when total hepatic blood flow was calculated from the results for regions of interest in three slices of the same liver segment. We concluded that using the spleen for time-delay correction of the input function for measuring hepatic blood flow by this method gave satisfactory results.

Quantification of human splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 1).

Positron emission tomography (PET) by means of a dynamic state method and H215O was performed to quantify splenic blood flow in 20 patients who had no hepatic functional disorders. Non-linear regression analysis was applied to determine splenic blood flow. In calculating arterial input function for the spleen, our originalexponential method was used to facilitate computerization. Mean splenic blood flow per 100 g of spleen (SBF) was 168.0 ml/min/100 g with a standard error (SE) of 12.4 ml/min. The mean spleen-blood partition coefficient for water(ρ) was 0.767 with a SE of 0.020. Significant correlations were noted between the values for SBF obtained by theexponential method andlinear method in which individual increasing values for arterial15O concentration were used rectilinearly (r=0.96, p< 0.005) and also between the values for ρ obtained by the two methods (r=0.95, p< 0.005). In order to validate the application of a one compartment model to an organ with a large blood volume such as the spleen, a further experiment was performed with a water flow model simulating splenic circulation.We succeeded in quantifying regional splenic blood flow by PET. It was thought that the quantification of splenic blood flow by our method would be beneficial in the study of splenic circulation, which is expected to be altered under conditions of portal hypertension, liver dysfunction and shock, etc.

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2).

We measured splenic blood flow in 55 patients by means of quantitative splenic positron emission tomography (PET), a novel, dynamic state method with H215O as a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25 showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF) was significantly correlated with splenic volume (r = −0.39, p< 0.005). The indocyanine green retention test at 15 min (r = −0.39, p< 0.005) and the hepaplastin test (r=0.37, p< 0.025) also correlated significantly with SBF. The means and 95% confidence intervals for the LC, CH, and NR groups were 117.5 ml/min/100 g (96.6–138.4), 102.5 ml/min/100 g (60.6–144.4), and 160.3 ml/min/100 g (139.8–180.8), respectively. The differences in SBF between these 3 groups were significant (p< 0.01). We conclude that regional splenic blood flow is not proportionate to splenic volume, although the splenic volume does increase with the progressive chronic changes observed in hepatic diseases.

Non-Invasive Quantification of Human Liver Neoplasms by Positron Emission Tomography(PET) Using C15O2 Steady State Method

Quantification of blood flow in hepatic tumors was successfully carried out by positron emission tomography using C1502 steady state method, although this method has never been performed elsewhere. There was a significant difference between HCC blood flow and metastatic liver rumor blood flow (p<0.01). In addition, it was found that HCC blood flow was higher than liver blood flow while metastatic liver tumor blood flow was lower than liver blood flow. Because it is important to know tumor blood flow for diagnosis and treatment, PET measurement of the liver tumor is expected to become indispensable in the near future.

Effects of Continuous Venous or Portal Administration of Carboplatin Against VX2 Tumor Metastasizing to the Liver

To prevent the liver metastases induced by inoculating lxlO6 VX2 cells into the mesenteric vein of rabbits, carboplatin (7 mg/kg) was administered continuously for 7 days via either the portal or jugular vein with mini osmotic pump. On 14 days after inoculation, untreated rabbits had 126.2±19.2 (mean±s.e.) metastatic colonies on the surface of their’livers, whereas those receiving the carboplatin via the mesenteric or jugular vein had substantially fewer with only 22.8±9.5 and 50.4±6.3 colonies, respectively. These results suggest that the continuous venous administration of carboplatin (especially via the portal vein) may be an effective means for treating liver metastases arising from colorectal cancers.