JBiSE  Vol.8 No.2 , February 2015
Dynamic Contrast-Enhanced MRI of Mouse Liver: A Feasibility Study Using a Dual-Input Two-Compartment Tracer Kinetic Model
Abstract: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been widely applied to evaluate microcirculatory parameters in clinical settings. However, pre-clinical studies involving DCE-MRI of small animals remain challenging with the requirement for high spatial and temporal resolution for quantitative tracer kinetic analysis. This study illustrates the feasibility of applying a high temporal resolution (2 s) protocol for liver imaging in mice by analyzing the DCE-MRI datasets of mice liver with a dual-input two-compartment tracer kinetic model. Phantom studies were performed to validate the T1 estimates derived by the proposed protocol before applying it in mice studies. The DCE-MRI datasets of mice liver were amendable to tracer kinetic analysis using a dual-input two-compartment model. Estimated micro-circulatory parameters were consistent with liver physiology, indicating viability of applying the technique for pre-clinical drug developments.
Cite this paper: Hartono, S. , Thng, C. , Chuang, K. , Hung, H. and Koh, T. (2015) Dynamic Contrast-Enhanced MRI of Mouse Liver: A Feasibility Study Using a Dual-Input Two-Compartment Tracer Kinetic Model. Journal of Biomedical Science and Engineering, 8, 90-97. doi: 10.4236/jbise.2015.82009.

[1]   Huwart, L., Peeters, F., Sinkus, R., Annet, L., Salameh, N., terBeek, L.C., Horsmans, Y. and Van Beers, B.E. (2006) Liver Fibrosis: Non-Invasive Assessment with MR Elastography. NMR in Biomedicine, 19, 173-179.

[2]   Huwart, L., Sempoux, C., Salameh, N., Jamart, J., Annet, L., Sinkus, R., Peeters, F., terBeek, L.C., Horsmans, Y. and Van Beers, B.E. (2007) Liver Fibrosis: Noninvasive Assessment with MR Elastography Versus Aspartate Aminotransferase-to-Platelet Ratio Index. Radiology, 245, 458-466.

[3]   Koh, T.S., Thng, C.H., Lee, P.S., Hartono, S., Rumpel, H., Goh, B.C. and Bisdas, S. (2008) Hepatic Metastases: In Vivo Assessment of Perfusion Parameters at Dynamic Contrast-Enhanced MR Imaging with Dual-Input Two-Compartment Tracer Kinetic Model. Radiology, 249, 307-320.

[4]   Thng, C.H., Koh, T.S., Collins, D.J. and Koh, D.M. (2010) Perfusion Magnetic Resonance Imaging of the Liver. World Journal of Gastroenterology, 16, 1598-1609.

[5]   Koh, T.S., Thng, C.H., Hartono, S., Lee, P.S., Choo, S.P., Poon, D.Y.H., Toh, H.C. and Bisdas, S. (2009) Dynamic Contrast-Enhanced CT Imaging of Hepatocellular Carcinoma in Cirrhosis: Feasibility of a Prolonged Dual-Phase Imaging Protocol with Tracer Kinetics Modeling. European Radiology, 19, 1184-1196.

[6]   Wang, H.Z., Riederer, S.J. and Lee, J.N. (1987) Optimizing the Precision in T1 Relaxation Estimation Using Limited Flip Angles. Magnetic Resonance in Medicine, 5, 399-416.

[7]   Brookes, J.A., Redpath, T.W., Gilbert, F.J., Needham, G. and Murray, A.D. (1996) Measurement of Spin-Lattice Relaxation Times with FLASH for Dynamic MRI of the Breast. The British Journal of Radiology, 69, 206-214.

[8]   Hayton, P., Brady, M., Tarassenko, L. and Moore, N. (1997) Analysis of Dynamic MR Breast Images Using a Model of Contrast Enhancement. Medical Image Analysis, 1, 207-224.

[9]   Brix, G., Bahner, M.L., Hoffmann, U., Horvath, A. and Schreiber, W. (1999) Regional Blood Flow, Capillary Permeability, and Compartmental Volumes: Measurement with Dynamic CT—Initial Experience. Radiology, 210, 269-276.

[10]   Port, R.E., Knopp, M.V., Hoffmann, U., Milker-Zabel, S. and Brix, G. (1999) Multicompartment Analysis of Gadolinium Chelate Kinetics: Blood-Tissue Exchange in Mammary Tumors as Monitored by Dynamic MR Imaging. Journal of Magnetic Resonance Imaging, 10, 233-241.<233::AID-JMRI3>3.0.CO;2-M

[11]   McDonald, T., Clift, R. and Cottrell, M. (1992) Large, Chronic Doses of Erythropoietin Cause Thrombocytopenia in Mice. Blood, 80, 352-358.

[12]   Trune, D.R., Kempton, J.B. and Gross, N.D. (2006) Mineralocorticoid Receptor Mediates Glucocorticoid Treatment Effects in the Autoimmune Mouse Ear. Hearing Research, 212, 22-32.

[13]   Wisse, E. (1970) An Electron Microscopic Study of the Fenestrated Endothelial Lining of Rat Liver Sinusoids. Journal of Ultrastructure Research, 31, 125-150.

[14]   Wisse, E. (1972) An Ultrastructural Characterization of the Endothelial Cell in the Rat Liver Sinusoid under Normal and Various Experimental Conditions, as a Contribution to the Distinction between Endothelial and Kupffer Cells. Journal of Ultrastructure Research, 38, 528-562.

[15]   Smedsrod, B., De Bleser, P.J., Braet, F., Lovisetti, P., Vander-kerken, K., Wisse, E. and Geerts, A. (1994) Cell Biology of Liver Endothelial and Kupffer Cells. Gut, 35, 1509-1516.

[16]   Baratta, J., Ngo, A., Lopez, B., Kasabwalla, N., Longmuir, K. and Robertson, R. (2009) Cellular Organization of Normal Mouse Liver: A Histological, Quantitative Immunocytochemical, and Fine Structural Analysis. Histochemistry and Cell Biology, 131, 713-726.

[17]   Chiandussi, L., Greco, F., Sardi, G., Vaccarino, A., Ferraris, C. and Curti, B. (1968) Estimation of Hepatic Arterial and Portal Venous Blood Flow by Direct Catheterization of the Vena Porta through the Umbilical Cord in Man: Preliminary Results. Acta Hepatosplenologica, 15, 166-171.

[18]   Davies, B. and Morris, T. (1993) Physiological Parameters in Laboratory Animals and Humans. Pharmaceutical Research, 10, 1093-1095.

[19]   Pandharipande, P.V., Krinsky, G.A., Rusinek, H. and Lee, V.S. (2005) Perfusion Imaging of the Liver: Current Challenges and Future Goals. Radiology, 234, 661-673.

[20]   Larson, K.B., Markham, J. and Raichle, M.E. (1987) Trace-Kinetic Models for Measuring Cerebral Blood Flow Using Externally Detected Radiotracers. Journal of Cerebral Blood Flow & Metabolism, 7, 443-463.

[21]   Brown, R.P., Delp, M.D., Lindstedt, S.L., Rhomberg, L.R. and Beliles, R.P. (1997) Physiological Parameter Values for Physiologically Based Pharmacokinetic Models. Toxicology and Industrial Health, 13, 407-484.

[22]   Koh, T.S., Thng, C.H., Hartono, S., Kwek, J.W., Khoo, J.B.K., Miyazaki, K., Collins, D.J., Orton, M.R., Leach, M.O., Lewington, V. and Koh, D.M. (2011) Dynamic Contrast-Enhanced MRI of Neuroendocrine Hepatic Metastases: A Feasibility Study Using a Dual-Input Two-Compartment Model. Magnetic Resonance in Medicine, 65, 250-260.