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Experimental evaluation of dynamic MRI for quantification of liver perfusion
Experimental Evaluation of Dynamic MRI for Quantification of Liver Perfusion C. Zapletal, A. Mehrabi, J. Scharf, T. Hess, D. Mihm, C. Jahnke, F. Scha¨ffer, M. Golling, T. Kraus, M.M. Gebhard, Ch. Herfarth, and E. Klar
L
IVER perfusion has proved to be a valid parameter for the quantification of ischemia-reperfusion injury.1 Furthermore quantification of liver blood flow and microcirculation are of great interest concerning diagnosis of early graft dysfunction after liver transplantation. Microcirculatory impairment can go along with ischemia-reperfusion injury, primary graft failure, and rejection as well as vascular thrombosis. There are methods available for quantification of liver perfusion in clinical routine. Intraoperatively Doppler flowmetry is used for quantification of liver blood flow. For intra- as well as postoperative measurement of liver microcirculation a thermodiffusion technique has been validated in a porcine animal model2 and is now applied in transplant patients.3 Unfortunately a noninvasive technique for perfusion measurement is not yet available for clinical purposes. Contrast-enhanced dynamic Magnetic Resonance Imaging (dMRI) is a new method for the assessment of organ perfusion and has additional advantages by combining perfusion analysis and imaging. Concerning postoperative care of liver transplant patients such a technique would be beneficial. It was the aim of this study to evaluate dMRI for the quantification of liver perfusion in a porcine model compared to total liver blood flow measured by Doppler flowmetry (DF) and liver perfusion assessed by thermodiffusion (TD). MATERIALS AND METHODS All experiments were approved by the Committee on Animal Care, Regierungspra¨sidium Karlsruhe, Germany. In 9 pigs (German landrace, 25 6 7 kg body weight) a median laparatomy and preparation of the liver hilus was performed under general anaesthesia (3.0 L/min N2O; infusion of ketamine 5 mg/kg, droperidol .25 mg/kg, fentanyl .005 mg/kg). Before and after performing dMRI, liver blood flow and microcirculation were quantified by means of Doppler flowprobes (Transonic System Inc, Ithaka, NY) positioned around the hepatic artery and portal vein and a thermodiffusion probe (Thermal Technologies Inc, Cambridge, MA) inserted into the liver parenchyma of the medial left liver lobe. Additional monitoring included: heart rate, mean arterial blood pressure, and blood gas analysis (BGA). After obtaining baseline values of all parameters partial occlusion of the portal vein was performed and all measurements were repeated. At the end of the © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
experiments all animals were sacrificed by intravenous application of potassium chloride.
dMRI The MRI was conducted on a 1.0-Tesla superconduction unit (Impact Expert, Siemens, Erlangen, Germany). The animals were fixed in a supine position and a phased array body coil was centered over the liver. The dynamic measurements were performed with a Saturation Recovery Turbo FLASH sequence. Gadolinium chloride (.2 mmol/kg) was used as contrast medium and applied by bolus injection.
Data Analysis Thermodiffusion data are given as mean value over a 5-minute sampling period (frequence of continuous measurements: 1 Hz; [mL/100g/min]). Calculation of portal blood flow was done by phase contrast angiography [L/min].4 For data analysis of liver microcirculation by dMRI measurements four standardized regions of interest (ROIs) have been defined: ventral, dorsal, medial, and global. Contrast enhancement in each ROI was analysed according to a signal–time curve by a modified mathematical two-compartment-model calculation.5 Results of liver perfusion measurement are described as kp-value [min21]. Statistical analysis was performed using Pearson Correlation, paired t test, and signed rank test.
RESULTS
Within the two phases of the experiments circulation, macrohemodynamic parameters, and BGA remained stable. Changes in hepatic perfusion were homogenous throughout the liver and comparable in the different ROIs. A close correlation between thermodiffusion measurements and dMRI in all four ROIs could be shown (TD vs dorsal ROI: r 5 .77; TD vs ventral ROI: r 5 .89; TD vs medial ROI: r 5 .9; TD vs global ROI: r 5 .7; P , .01). Correlation From the Department of General (C.Z., M.G., T.K., Ch.H., E.K.) and Experimental (C.J., F.B., M.M.G.) Surgery, Department of Radiology (J.S., T.H., D.M.), University of Heidelberg, Germany. This study was supported by grants from the Forschungsschwerpunkt Transplantation Heidelberg. Address reprint requests to Christina Zapletal, Department of Surgery, University of Heidelberg, INF 110, D-69120 Heidelberg, Germany. 0041-1345/99/$–see front matter PII S0041-1345(98)01688-1 421
Transplantation Proceedings, 31, 421–422 (1999)
422
ZAPLETAL, MEHRABI, SCHARF ET AL
Table 1. Significant Reduction of Microcirculation by Partial Portal Occlusion Was Equally Detected by Thermodiffusion and dMRI (Different ROI); P < .02, mean 6 SD
Baseline After occlusion
TD [ml/100g/min]
Ventral ROI (kp) [min21]
Medial ROI (kp) [min21]
Dorsal ROI (kp) [min21]
Global ROI (kp) [min21]
77.8 6 6.0 47.9 6 19.5*
13.8 6 7.9 2.9 6 1.6*
18.9 6 20.6 3.2 6 1.2*
19.7 6 24.4 4.0 6 0.96*
22.7 6 22.0 3.4 6 1.3*
between dMRI and Doppler flowmetry reached r 5 .95 (P , .01) concerning portal blood flow measurements. Partial occlusion of the portal vein (.82 6 .35 vs .28 6 0.17 L/min before vs after partial portal occlusion) was accurately detected by dMRI concerning microcirculation (Table 1) and liver blood flow (.8 6 .28 vs 41 6 0.21 L/min before vs after partial occlusion). DISCUSSION
The technical progress of rapid-sequence tomography techniques (CT as well as MRI) has opened new possibilities in assessing functional and hemodynamic parameters.4 –7 The indicator dilution technique has first been used by Axel for quantification of cerebral blood flow.8 Similar methods are used for characterisation of tumors, eg, of the female breast by perfusion analysis. The main finding of our study is that contrast-enhanced dMRI shows a close correlation with validated methods in the assessment of liver microcirculation and portal blood flow. Changes in liver perfusion can be detected accurately. With dMRI quantification of global as well as regional liver perfusion is possible. As this is done noninvasively, without exposure to radiation and with application of a contrast media of low toxicity9 assessment of liver perfusion can be performed at any time after transplantation. Simultaneous imaging can be directly correlated with the results of functional analysis. The combination of conventional imaging and assessment of hemodynamic data represents valuable information especially for diagnosis of posttransplant complications.
CONCLUSION
Gadolinium-DTPA enhanced dynamic MR imaging is a new method for the quantification of blood flow and tissue perfusion. In this study we evaluated dMRI comparing it with thermodiffusion and Doppler flowmetry in pig liver. A significant correlation concerning tissue as well as portal perfusion between dMRI and thermodiffusion, and respectively between dMRI and Doppler flowmetry, with respect to total the liver blood flow was detected. Dynamic MRI could become a valuable diagnostic method for the quantification of liver perfusion.
REFERENCES 1. Klar E, Bredt M, Kraus T, et al: Transplant Proc 29:362, 1997 2. Klar E, Kraus T, Bleyl J, et al: Transplant Proc 27:2610, 1995 3. Klar E, Kraus T, Bredt M, et al: Transplantation Int 9 (Suppl 1):140, 1996 4. Takashi T, Fuminori M, Shigeki O, et al: Radiology 173:639, 1989 5. Brix G, Semmler W, Port R, et al: J Comp Assist Tomogr 15:21, 1991 6. Gu ¨ckel F, Rempp K, Becker G, et al: Radiologe 34:619, 1994 7. Knopp MV, Hoffmann U, Brix G, et al: Radiologe 35:964, 1995 8. Axel L: Radiology 137:679, 1980 9. Werner J, Schmidt J, Warshaw AL, et al: Ann Surg (in press)
L
IVER perfusion has proved to be a valid parameter for the quantification of ischemia-reperfusion injury.1 Furthermore quantification of liver blood flow and microcirculation are of great interest concerning diagnosis of early graft dysfunction after liver transplantation. Microcirculatory impairment can go along with ischemia-reperfusion injury, primary graft failure, and rejection as well as vascular thrombosis. There are methods available for quantification of liver perfusion in clinical routine. Intraoperatively Doppler flowmetry is used for quantification of liver blood flow. For intra- as well as postoperative measurement of liver microcirculation a thermodiffusion technique has been validated in a porcine animal model2 and is now applied in transplant patients.3 Unfortunately a noninvasive technique for perfusion measurement is not yet available for clinical purposes. Contrast-enhanced dynamic Magnetic Resonance Imaging (dMRI) is a new method for the assessment of organ perfusion and has additional advantages by combining perfusion analysis and imaging. Concerning postoperative care of liver transplant patients such a technique would be beneficial. It was the aim of this study to evaluate dMRI for the quantification of liver perfusion in a porcine model compared to total liver blood flow measured by Doppler flowmetry (DF) and liver perfusion assessed by thermodiffusion (TD). MATERIALS AND METHODS All experiments were approved by the Committee on Animal Care, Regierungspra¨sidium Karlsruhe, Germany. In 9 pigs (German landrace, 25 6 7 kg body weight) a median laparatomy and preparation of the liver hilus was performed under general anaesthesia (3.0 L/min N2O; infusion of ketamine 5 mg/kg, droperidol .25 mg/kg, fentanyl .005 mg/kg). Before and after performing dMRI, liver blood flow and microcirculation were quantified by means of Doppler flowprobes (Transonic System Inc, Ithaka, NY) positioned around the hepatic artery and portal vein and a thermodiffusion probe (Thermal Technologies Inc, Cambridge, MA) inserted into the liver parenchyma of the medial left liver lobe. Additional monitoring included: heart rate, mean arterial blood pressure, and blood gas analysis (BGA). After obtaining baseline values of all parameters partial occlusion of the portal vein was performed and all measurements were repeated. At the end of the © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
experiments all animals were sacrificed by intravenous application of potassium chloride.
dMRI The MRI was conducted on a 1.0-Tesla superconduction unit (Impact Expert, Siemens, Erlangen, Germany). The animals were fixed in a supine position and a phased array body coil was centered over the liver. The dynamic measurements were performed with a Saturation Recovery Turbo FLASH sequence. Gadolinium chloride (.2 mmol/kg) was used as contrast medium and applied by bolus injection.
Data Analysis Thermodiffusion data are given as mean value over a 5-minute sampling period (frequence of continuous measurements: 1 Hz; [mL/100g/min]). Calculation of portal blood flow was done by phase contrast angiography [L/min].4 For data analysis of liver microcirculation by dMRI measurements four standardized regions of interest (ROIs) have been defined: ventral, dorsal, medial, and global. Contrast enhancement in each ROI was analysed according to a signal–time curve by a modified mathematical two-compartment-model calculation.5 Results of liver perfusion measurement are described as kp-value [min21]. Statistical analysis was performed using Pearson Correlation, paired t test, and signed rank test.
RESULTS
Within the two phases of the experiments circulation, macrohemodynamic parameters, and BGA remained stable. Changes in hepatic perfusion were homogenous throughout the liver and comparable in the different ROIs. A close correlation between thermodiffusion measurements and dMRI in all four ROIs could be shown (TD vs dorsal ROI: r 5 .77; TD vs ventral ROI: r 5 .89; TD vs medial ROI: r 5 .9; TD vs global ROI: r 5 .7; P , .01). Correlation From the Department of General (C.Z., M.G., T.K., Ch.H., E.K.) and Experimental (C.J., F.B., M.M.G.) Surgery, Department of Radiology (J.S., T.H., D.M.), University of Heidelberg, Germany. This study was supported by grants from the Forschungsschwerpunkt Transplantation Heidelberg. Address reprint requests to Christina Zapletal, Department of Surgery, University of Heidelberg, INF 110, D-69120 Heidelberg, Germany. 0041-1345/99/$–see front matter PII S0041-1345(98)01688-1 421
Transplantation Proceedings, 31, 421–422 (1999)
422
ZAPLETAL, MEHRABI, SCHARF ET AL
Table 1. Significant Reduction of Microcirculation by Partial Portal Occlusion Was Equally Detected by Thermodiffusion and dMRI (Different ROI); P < .02, mean 6 SD
Baseline After occlusion
TD [ml/100g/min]
Ventral ROI (kp) [min21]
Medial ROI (kp) [min21]
Dorsal ROI (kp) [min21]
Global ROI (kp) [min21]
77.8 6 6.0 47.9 6 19.5*
13.8 6 7.9 2.9 6 1.6*
18.9 6 20.6 3.2 6 1.2*
19.7 6 24.4 4.0 6 0.96*
22.7 6 22.0 3.4 6 1.3*
between dMRI and Doppler flowmetry reached r 5 .95 (P , .01) concerning portal blood flow measurements. Partial occlusion of the portal vein (.82 6 .35 vs .28 6 0.17 L/min before vs after partial portal occlusion) was accurately detected by dMRI concerning microcirculation (Table 1) and liver blood flow (.8 6 .28 vs 41 6 0.21 L/min before vs after partial occlusion). DISCUSSION
The technical progress of rapid-sequence tomography techniques (CT as well as MRI) has opened new possibilities in assessing functional and hemodynamic parameters.4 –7 The indicator dilution technique has first been used by Axel for quantification of cerebral blood flow.8 Similar methods are used for characterisation of tumors, eg, of the female breast by perfusion analysis. The main finding of our study is that contrast-enhanced dMRI shows a close correlation with validated methods in the assessment of liver microcirculation and portal blood flow. Changes in liver perfusion can be detected accurately. With dMRI quantification of global as well as regional liver perfusion is possible. As this is done noninvasively, without exposure to radiation and with application of a contrast media of low toxicity9 assessment of liver perfusion can be performed at any time after transplantation. Simultaneous imaging can be directly correlated with the results of functional analysis. The combination of conventional imaging and assessment of hemodynamic data represents valuable information especially for diagnosis of posttransplant complications.
CONCLUSION
Gadolinium-DTPA enhanced dynamic MR imaging is a new method for the quantification of blood flow and tissue perfusion. In this study we evaluated dMRI comparing it with thermodiffusion and Doppler flowmetry in pig liver. A significant correlation concerning tissue as well as portal perfusion between dMRI and thermodiffusion, and respectively between dMRI and Doppler flowmetry, with respect to total the liver blood flow was detected. Dynamic MRI could become a valuable diagnostic method for the quantification of liver perfusion.
REFERENCES 1. Klar E, Bredt M, Kraus T, et al: Transplant Proc 29:362, 1997 2. Klar E, Kraus T, Bleyl J, et al: Transplant Proc 27:2610, 1995 3. Klar E, Kraus T, Bredt M, et al: Transplantation Int 9 (Suppl 1):140, 1996 4. Takashi T, Fuminori M, Shigeki O, et al: Radiology 173:639, 1989 5. Brix G, Semmler W, Port R, et al: J Comp Assist Tomogr 15:21, 1991 6. Gu ¨ckel F, Rempp K, Becker G, et al: Radiologe 34:619, 1994 7. Knopp MV, Hoffmann U, Brix G, et al: Radiologe 35:964, 1995 8. Axel L: Radiology 137:679, 1980 9. Werner J, Schmidt J, Warshaw AL, et al: Ann Surg (in press)