Advertisement
Research Article| Volume 48, ISSUE 6, P974-982, June 2008

Quantification of liver perfusion with [15O]H2O-PET and its relationship with glucose metabolism and substrate levels

Published:March 04, 2008DOI:https://doi.org/10.1016/j.jhep.2008.01.029

      Background/Aims

      Hepatic perfusion plays an important role in liver physiology and disease. This study was undertaken to (a) validate the use of Positron Emission Tomography (PET) and oxygen-15-labeled water ([15O]H2O) to quantify hepatic and portal perfusion, and (b) examine relationships between portal perfusion and liver glucose and lipid metabolism.

      Methods

      Liver [15O]H2O-PET images were obtained in 14 pigs during fasting or hyperinsulinemia. Carotid arterial and portal venous blood were sampled for [15O]H2O activity; Doppler ultrasonography was used invasively as the reference method. A single arterial input compartment model was developed to estimate portal tracer kinetics and liver perfusion. Endogenous glucose production (EGP) and insulin-mediated whole body glucose uptake (wbGU) were determined by standard methods.

      Results

      Hepatic arterial and portal venous perfusions were 0.15 ± 0.07 and 1.11 ± 0.34 ml/min/ml of tissue, respectively. The agreement between ultrasonography and [15O]H2O-PET was good for total and portal liver perfusion, and poor for arterial perfusion. Portal perfusion was correlated with EGP (r = +0.62, p = 0.03), triglyceride (r = +0.66, p = 0.01), free fatty acid levels (r = +0.76, p = 0.003), and plasma lactate levels (r = −0.81, p = 0.0009).

      Conclusions

      Estimates of liver perfusion by [15O]H2O-PET compared well with those by ultrasonography. The method allowed to predict portal tracer concentrations which is essential in human studies. Portal perfusion may affect liver nutrient handling.

      Abbreviations:

      PET (Positron Emission Tomography), EGP (endogenous glucose production), wbGU (whole body glucose uptake), [15O]H2O (15-oxygen-labeled water)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Duvoux C.
        • Radier C.
        • Roudot-Thoraval F.
        • Maille F.
        • Anglade M.C.
        • Van Nhieu J.T.
        • et al.
        Low-grade steatosis and major changes in portal flow as new prognostic factors in steroid-treated alcoholic hepatitis.
        Hepatology. 2004; 40: 1370-1378
        • Magalotti D.
        • Marchesini G.
        • Ramilli S.
        • Berzigotti A.
        • Bianchi G.
        • Zoli M.
        Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological treatment. A pilot study.
        Dig Liver Dis. 2004; 36: 406-411
        • Bearn A.G.
        • Billing B.
        • Edholm O.G.
        • Sherlock S.
        Hepatic blood flow and carbohydrate changes in man during fainting.
        J Physiol. 1951; 115: 442-455
        • Topping D.L.
        • Storer G.B.
        • Trimble R.P.
        Effects of flow rate and insulin on triacylglycerol secretion by perfused rat liver.
        Am J Physiol. 1988; 255: E306-E313
        • Arai K.
        • Matsui O.
        • Takashima T.
        • Ida M.
        • Nishida Y.
        Focal spared areas in fatty liver caused by regional decreased portal flow.
        AJR Am J Roentgenol. 1988; 151: 300-302
        • Gabata T.
        • Kadoya M.
        • Matsui O.
        • Ueda K.
        • Kawamori Y.
        • Terayama N.
        • et al.
        Peritumoral spared area in fatty liver: correlation between opposed-phase gradient-echo MR imaging and CT arteriography.
        Abdom Imaging. 2001; 26: 384-389
        • Katz M.L.
        • Bergmann E.N.
        Simultaneous measurement of hepatic and portal venous blood flow in the sheep and dog.
        Am J Physiol. 1969; 216: 946-952
        • Johnson D.J.
        • Muhlbacher F.
        • Wilmore D.W.
        Measurement of hepatic blood flow.
        J Surg Res. 1985; 39: 470-481
        • Ziegler S.I.
        • Haberkorn U.
        • Byrne H.
        • Tong C.
        • Kaja S.
        • Richolt J.A.
        • et al.
        Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: limitations of model description.
        Eur J Nucl Med. 1996; 23: 169-177
        • Greenway C.V.
        Hepatic plethysmography.
        in: Lautt W.W. Hepatic circulation in health and disease. Raven Press, New York1981: 41-54
        • Anderson M.F.
        Pulsed Doppler ultrasonic flowmeter: application to the study of hepatic blood flow.
        in: Granger D.N. Bulkley G.B. Measurement of blood flow applications to the splanchnic circulation. Williams & Wilkins, Baltimore1981: 395-398
        • Huet P.M.
        • Goresky C.A.
        • Villeneuve J.P.
        • Marleau D.
        Assessment of liver microcirculation in human cirrhosis.
        J Clin Invest. 1982; 70: 1234-1244
        • Seifalian A.M.
        • Piasecki C.
        • Agarwal A.
        • Davidson B.R.
        The effect of graded steatosis on flow in the hepatic parenchymal microcirculation.
        Transplantation. 1999; 68: 780-784
        • Ruotsalainen U.
        • Raitakari M.
        • Nuutila P.
        • Oikonen V.
        • Sipila H.
        • Teras M.
        • et al.
        Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and PET.
        J Nucl Med. 1997; 38: 314-319
        • Viljanen K.A.
        • Lonnroth P.
        • Parkkola R.
        • Peltoniemi P.
        • Asola M.
        • Viljanen T.
        • et al.
        Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans.
        J Clin Endocrinol Metab. 2002; 87: 3902-3910
        • Bergmann S.R.
        • Fox K.A.
        • Rand A.L.
        • McElvany K.D.
        • Welch M.J.
        • Markham J.
        • et al.
        Quantification of regional myocardial blood flow in vivo with H215O.
        Circulation. 1984; 70: 724-733
        • Herscovitch P.
        • Markham J.
        • Raichle M.E.
        Brain blood flow measured with intravenous H215O. I. Theory and error analysis.
        J Nucl Med. 1983; 24: 782-789
        • Raichle M.E.
        • Martin W.R.W.
        • Herscovitch P.
        • Mintun M.A.
        • Markham J.
        Brain blood flow measured with intravenous H215O. II. Implementation and validation.
        J Nucl Med. 1983; 24: 790-798
        • Taniguchi H.
        • Kunishima S.
        • Koh T.
        The reproducibility of independently measuring human regional hepatic arterial, portal and total hepatic blood flow using [15O]water and positron emission tomography.
        Nucl Med Commun. 2003; 24: 497-501
        • Taniguchi H.
        • Yamaguchi A.
        • Kunishima S.
        • Koh T.
        • Masuyama M.
        • Koyama H.
        • et al.
        Using the spleen for time-delay correction of the input function in measuring hepatic blood flow with oxygen-15 water by dynamic PET.
        Ann Nucl Med. 1999; 13: 215-221
        • Taniguchi H.
        • Oguro A.
        • Koyama H.
        • Masuyama M.
        • Takahashi T.
        Analysis of models for quantification of arterial and portal blood flow in the human liver using PET.
        J Comput Assist. 1996; 20: 135-144
        • Munk O.L.
        • Bass L.
        • Feng H.
        • Keiding S.
        Determination of regional flow by use of intravascular PET tracers: microvascular theory and experimental validation for pig livers.
        J Nucl Med. 2003; 44: 1862-1870
        • Iozzo P.
        • Jarvisalo M.J.
        • Kiss J.
        • Borra R.
        • Naum G.A.
        • Viljanen A.
        • et al.
        Quantification of liver glucose metabolism by positron emission tomography: validation study in pigs.
        Gastroenterology. 2007; 132: 531-542
        • Iozzo P.
        • Gastaldelli A.
        • Jarvisalo M.J.
        • Kiss J.
        • Borra R.
        • Buzzigoli E.
        • et al.
        18F-FDG assessment of glucose disposal and production rates during fasting and insulin stimulation: a validation study.
        J Nucl Med. 2006; 47: 1016-1022
        • Iozzo P.
        • Hallsten K.
        • Oikonen V.
        • Virtanen K.A.
        • Kemppainen J.
        • Solin O.
        • et al.
        Insulin-mediated hepatic glucose uptake is impaired in type 2 diabetes: evidence for a relationship with glycemic control.
        J Clin Endocrinol Metab. 2003; 88: 2055-2060
        • Muscelli E.
        • Mari A.
        • Natali A.
        • Astiarraga B.D.
        • Camastra S.
        • Frascerra S.
        • et al.
        Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance.
        Am J Physiol Endocrinol Metab. 2006; 291: E1144-E1150
        • Kety S.S.
        • Schmidt C.F.
        The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values.
        J Clin Invest. 1948; 27: 476-483
      1. SAAM Institute 1998 SAAM II User’s guide version 1.1.1. WA: SAAM Institute, Seattle.

        • Cobelli C.
        • Foster D.
        • Toffolo G.
        Tracer kinetics in biomedical research: from data to model.
        Kluwer Academic/Plenum, New York2001
        • Bland J.M.
        • Altman D.G.
        Statistical methods for assessing agreement between two methods of clinical measurement.
        Lancet. 1986; 1: 307-310
        • Keiding S.
        • Munk O.L.
        • Vilstrup H.
        • Nielsen D.T.
        • Roelsgaard K.
        • Bass L.
        Hepatic microcirculation assessed by positron emission tomography of first pass ammonia metabolism in porcine liver.
        Liver Int. 2005; 25: 171-176
        • Sherman I.A.
        • Dlugosz J.A.
        • Barker F.
        • Sadeghi F.M.
        • Pang K.S.
        Dynamics of arterial and portal venous flow interactions in perfused rat liver: an intravital microscopic study.
        Am J Physiol. 1996; 271: G201-G210
        • Doi R.
        • Inoue K.
        • Kogire M.
        • Sumi S.
        • Takaori K.
        • Suzuki T.
        • et al.
        Simultaneous measurement of hepatic arterial and portal venous flows by transit time ultrasonic volume flowmetry.
        Surg Gynecol Obstet. 1988; 167: 65-69
        • Kleber G.
        • Steudel N.
        • Behrmann C.
        • Zipprich A.
        • Hübner G.
        • Lotterer E.
        • et al.
        Hepatic arteriel flow volume and reserve in patients with cirrhosis: use of intra-arteriel Doppler and adenosine infusion.
        Gastroenterology. 1999; 116: 906-914
        • Hubner G.H.
        • Steudel N.
        • Kleber G.
        • Behrmann C.
        • Lotterer E.
        • Fleig W.E.
        Hepatic arteriel blood flow velocities: assessment by transcutaneous and intravascular Doppler sonography.
        J Hepatol. 2000; 32: 893-899
        • Materne R.
        • Van Beers B.E.
        • Smith A.M.
        • Leconte I.
        • Jamart J.
        • Dehoux J.P.
        • et al.
        Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model.
        Clin Sci (Lond). 2000; 99: 517-525
        • Satake S.
        • Moore M.C.
        • Igawa K.
        • Converse M.
        • Farmer B.
        • Neal D.W.
        • et al.
        Direct and indirect effects of insulin on glucose uptake and storage by the liver.
        Diabetes. 2002; 51: 1663-1671
        • Simonsen L.
        • Coker R.
        • Mulla N.A.L.
        • Kjaer M.
        • Bulow J.
        The effect of insulin and glucagon on splanchnic oxygen consumption.
        Liver. 2002; 22: 459-466
        • Capaldo B.
        • Gastaldelli A.
        • Antoniello S.
        • Auletta M.
        • Pardo F.
        • Ciociaro D.
        • et al.
        Splanchnic and leg substrate exchange after ingestion of a natural mixed meal in humans.
        Diabetes. 1999; 48: 958-966
        • Jakob S.M.
        • Tenhunen J.J.
        • Laitinen S.
        • Heino A.
        • Alhava E.
        • Takala J.
        Effects of systemic arterial hypoperfusion on splanchnic hemodynamics and hepatic arterial buffer response in pigs.
        Am J Physiol Gastrointest Liver Physiol. 2001; 280: G819-G827
        • Seifalian A.M.
        • El-Desoky A.
        • Davidson B.R.
        Hepatic indocyanine green uptake and excretion in a rabbit model of steatosis.
        Eur Surg Res. 2001; 33: 193-201
        • Lautt W.W.
        Relationship between hepatic blood flow and overall metabolism: the hepatic arterial buffer response.
        Fed Proc. 1983; 42: 1662-1666
        • Kakkos S.K.
        • Yarmenitis S.D.
        • Tsamandas A.C.
        • Gogos C.A.
        • Kalfarentzos F.
        Fatty liver in obesity: relation to Doppler perfusion index measurement of the liver.
        Scand J Gastroenterol. 2000; 35: 976-980