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Multiphasic Injection Method for Uniform Prolonged Vascular Enhancement at CT Angiography: Pharmacokinetic Analysis and Experimental Porcine Model¹

¹ From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. Received August 19, 1999; revision requested October 14; revision received November 16; accepted December 7. Supported by Mallinckrodt Medical, St Louis, Mo. Address correspondence to K.T.B. (e-mail: baet@mir.wustl.edu).

View larger version (17K): [in a new window]   Figure 1. Diagram depicts the compartmental model of early pharmacokinetics of contrast enhancement. Contrast medium is injected into an antecubital vein and is distributed to the right side of the heart, pulmonary compartment, left side of the heart, and aorta. It recirculates to the right heart via systemic circulation. Cc is the concentration of injected contrast medium. Cl, Cp, Cr, Cs, and Cv are, respectively, concentrations of contrast medium injected in the left heart, pulmonary compartment, right heart, systemic circulation, and peripheral vein (antecubital to right heart). Qc is the volumetric flow rate of injected contrast medium. Ql, Qp, Qr, and Qs are equal and are the cardiac outputs of the system. Qv is the volumetric flow rate of blood leaving the peripheral vein. Vl, Vp, Vr, Vs, and Vv are the volume of blood in the left heart, blood and interstitial space in the pulmonary compartment, blood in the right heart, blood and interstitial space in the systemic circulation, and blood in the peripheral vein (antecubital to right heart), respectively.

View larger version (22K): [in a new window]   Figure 2. Graph depicts three multiphasic injection profiles with an initial injection rate of 2 mL/sec and different exponential decay constants (0.007, dotted line; 0.017, solid line; 0.026, dashed line). Areas under the curves are the same; that is, a total of 50 mL of contrast medium was injected. Slower exponential decay results in a shorter injection duration with a higher final injection rate at the completion of injection.

View larger version (20K): [in a new window]   Figure 3. Graph depicts the simulated porcine aortic enhancement curve generated from the model shown in Figure 1 for a 25-kg pig with 50 mL of contrast medium (282 mg I/mL) injected at a uniphasic rate of 2 mL/sec. This curve was in good agreement with the empiric aortic enhancement curve in Figure 4a.

View larger version (20K): [in a new window]   Figure 4a. Graphs depict empiric aortic time-enhancement curves in pig A with (a) uniphasic injection (50 mL [282 mg I/mL] in each injection; rate, 2 mL/sec), which generated a continuously upsloping curve with the peak of enhancement occurring shortly after the completion of the injection, and (b) biphasic injection (25 mL at a rate of 2 mL/sec followed by 25 mL at rate of 1.4 mL/sec), which yielded enhancement that was more prolonged than that of uniphasic injection but which generated two enhancement peaks with a valley in between.

View larger version (19K): [in a new window]   Figure 4b. Graphs depict empiric aortic time-enhancement curves in pig A with (a) uniphasic injection (50 mL [282 mg I/mL] in each injection; rate, 2 mL/sec), which generated a continuously upsloping curve with the peak of enhancement occurring shortly after the completion of the injection, and (b) biphasic injection (25 mL at a rate of 2 mL/sec followed by 25 mL at rate of 1.4 mL/sec), which yielded enhancement that was more prolonged than that of uniphasic injection but which generated two enhancement peaks with a valley in between.

View larger version (25K): [in a new window]   Figure 5a. (a) Graph depicts exponential curves for three injection profiles for a 120-second injection with an initial injection rate of 2 mL/sec and decay coefficients of 0.01 (dotted line), 0.02 (solid line), and 0.03 (dashed line). Slower exponential decay results in a higher total amount of contrast medium injected (larger area under the curve) and a higher final injection rate. (b) Graph depicts aortic time-enhancement curves that were simulated with the mathematic model (with porcine physiologic parameters) by solving Equations (A1)-(A5) with input exponential injections. Uniform, plateau aortic enhancement was observed with an exponential decay coefficient of 0.02. With decay coefficients of 0.01 or 0.03, contrast enhancement either steadily increased above the plateau or decreased after a peak below the plateau, respectively.

View larger version (25K): [in a new window]   Figure 5b. (a) Graph depicts exponential curves for three injection profiles for a 120-second injection with an initial injection rate of 2 mL/sec and decay coefficients of 0.01 (dotted line), 0.02 (solid line), and 0.03 (dashed line). Slower exponential decay results in a higher total amount of contrast medium injected (larger area under the curve) and a higher final injection rate. (b) Graph depicts aortic time-enhancement curves that were simulated with the mathematic model (with porcine physiologic parameters) by solving Equations (A1)-(A5) with input exponential injections. Uniform, plateau aortic enhancement was observed with an exponential decay coefficient of 0.02. With decay coefficients of 0.01 or 0.03, contrast enhancement either steadily increased above the plateau or decreased after a peak below the plateau, respectively.

View larger version (20K): [in a new window]   Figure 6. Graph depicts simulated aortic contrast enhancement curves in a human model with uniphasic (dashed line; injection rate, 3 mL/sec; injection duration, 53 seconds) and multiphasic exponential (solid line; initial rate, 3 mL/sec; exponential decay coefficient, 0.01; injection duration 77 seconds) injections that were simulated with 160 mL of contrast medium (320 mg I/mL). Uniform, prolonged contrast enhancement was achieved with the multiphasic injection.

View larger version (22K): [in a new window]   Figure 7. Graph depicts simulated aortic contrast enhancement curves in a human model with normal and reduced cardiac outputs. Effect of reduced cardiac output on the enhancement was evaluated by reducing the cardiac output by 20% (1.3 L/min, dotted line) and 40% (2.6 L/min, dashed line) in the model. Exponential injection with a decay coefficient of 0.01, which generated uniform enhancement with normal cardiac output (solid line), was used as the input contrast medium injection. As cardiac output decreased, contrast enhancement curves became more dome-shaped and enhancement magnitude increased.

View larger version (25K): [in a new window]   Figure 8a. Graphs depict empiric porcine aortic enhancement curves in pigs (a) B (24.8 kg) and (b) D (40.6 kg) obtained by using multiphasic injections of 50 mL with an initial injection rate of 2 mL/sec and decay coefficients of 0.007 (*), 0.017 (), and 0.026 (). (Injection profiles depicted in Figure 2.) Injection with a decay coefficient of 0.017 produced the most uniform aortic enhancement curve. Injections with lower (0.007) or higher (0.026) decay coefficients resulted in aortic enhancement curves that steadily increased or decreased after reaching a peak, respectively. Magnitude of aortic enhancement in pig B was substantially higher than that of pig D, reflecting the difference in body weight. However, patterns of aortic enhancement produced with the three exponential decay coefficients were consistent.

View larger version (24K): [in a new window]   Figure 8b. Graphs depict empiric porcine aortic enhancement curves in pigs (a) B (24.8 kg) and (b) D (40.6 kg) obtained by using multiphasic injections of 50 mL with an initial injection rate of 2 mL/sec and decay coefficients of 0.007 (*), 0.017 (), and 0.026 (). (Injection profiles depicted in Figure 2.) Injection with a decay coefficient of 0.017 produced the most uniform aortic enhancement curve. Injections with lower (0.007) or higher (0.026) decay coefficients resulted in aortic enhancement curves that steadily increased or decreased after reaching a peak, respectively. Magnitude of aortic enhancement in pig B was substantially higher than that of pig D, reflecting the difference in body weight. However, patterns of aortic enhancement produced with the three exponential decay coefficients were consistent.

View larger version (25K): [in a new window]   Figure 9a. Graphs depict empiric porcine aortic enhancement with uniphasic () and multiphasic (*) contrast medium injections of (a) 50 mL (rate, 2 mL/sec) in pig B (24.8 kg) and (b) 70 mL (initial rate, 2 mL/sec; exponential decay coefficient, 0.017) in pig D (25.5 kg). Multiphasic injections yielded vascular enhancement that was more uniform and prolonged than that of uniphasic injections.

View larger version (23K): [in a new window]   Figure 9b. Graphs depict empiric porcine aortic enhancement with uniphasic () and multiphasic (*) contrast medium injections of (a) 50 mL (rate, 2 mL/sec) in pig B (24.8 kg) and (b) 70 mL (initial rate, 2 mL/sec; exponential decay coefficient, 0.017) in pig D (25.5 kg). Multiphasic injections yielded vascular enhancement that was more uniform and prolonged than that of uniphasic injections.

View larger version (70K): [in a new window]   Figure 10a. Sets of six sequential 5-mm transverse CT images of enhancing porcine aorta acquired 14, 20, 26, 38, 44, and 50 seconds after (a) uni- and (b) multiphasic injections of 70 mL contrast medium in pig D (25.5 kg) qualitatively demonstrate that the multiphasic injections yielded vascular enhancement that was more uniform and prolonged than that of uniphasic injections. Aortic enhancement measurements represent the six data points at these sampling times in Figure 9b.

View larger version (71K): [in a new window]   Figure 10b. Sets of six sequential 5-mm transverse CT images of enhancing porcine aorta acquired 14, 20, 26, 38, 44, and 50 seconds after (a) uni- and (b) multiphasic injections of 70 mL contrast medium in pig D (25.5 kg) qualitatively demonstrate that the multiphasic injections yielded vascular enhancement that was more uniform and prolonged than that of uniphasic injections. Aortic enhancement measurements represent the six data points at these sampling times in Figure 9b.

View larger version (24K): [in a new window]   Figure 11a. Graphs depict empiric porcine aortic enhancement curves in (a) pig D (weight, 40.6 kg; contrast medium volume, 90 mL; rate, 3 mL/sec), with uniphasic () and multiphasic (*) injection (multiphasic injection resulted in more uniform and prolonged but slightly decreased aortic enhancement) and (b) pig B (weight, 36.3 kg; contrast medium volume, 70 mL), with uniphasic (*), multiphasic (), and biphasic () injection.

View larger version (24K): [in a new window]   Figure 11b. Graphs depict empiric porcine aortic enhancement curves in (a) pig D (weight, 40.6 kg; contrast medium volume, 90 mL; rate, 3 mL/sec), with uniphasic () and multiphasic (*) injection (multiphasic injection resulted in more uniform and prolonged but slightly decreased aortic enhancement) and (b) pig B (weight, 36.3 kg; contrast medium volume, 70 mL), with uniphasic (*), multiphasic (), and biphasic () injection.