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Peak Contrast Enhancement in CT and MR Angiography: When Does It Occur and Why? Pharmacokinetic Study in a Porcine Model¹

¹ From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. Received February 13, 2002; revision requested April 17; final revision received August 9; accepted September 27. Address correspondence to the author (e-mail: baet@mir.wustl.edu).

View larger version (22K): [in a new window]   Figure 1. Diagram depicts a compartmental model for early contrast enhancement pharmacokinetics. Contrast medium is injected into the antecubital vein and distributed to the right side of the heart, the pulmonary compartment, the left side of the heart, and the aorta. It then recirculates back to the right side of the heart via the systemic circulation. The concentration of contrast medium is represented by C: CL = left side of the heart, CP = pulmonary compartment, CR = right side of the heart, CS = systemic circulation, and CV = peripheral vein from the antecubital vein to the right side of the heart. The corresponding compartmental (blood and interstitial) volume is represented by V: VL = left side of the heart, VP = pulmonary compartment, VR = right side of the heart, VS = systemic circulation, and VV = peripheral vein from the antecubital vein to the right side of the heart. The volumetric flow rate is represented by Q: QC = injected contrast medium; QL = QP = QR = QS (cardiac output of the system), and QV = blood leaving the peripheral vein.

View larger version (45K): [in a new window]   Figure 2. Porcine aortic enhancement curves generated from the compartmental model at various injection durations. Porcine aortic enhancement curves are generated from the model in Figure 1 for a range of injection durations (1, 3, 5, 8, 12, 20, and 30 seconds) at a fixed injection rate of 2 mL/sec. As injection duration increases, the enhancement curves broaden and become more asymmetric, peaking near completion of injection. The time to peak aortic enhancement from the start of injection increases with increasing injection duration.

View larger version (52K): [in a new window]   Figure 3. Empiric aortic enhancement curves obtained from pig 3 at various injection durations. The empiric and compartmental model enhancement curves show marked similarity, especially in changes in enhancement curve shape and time to peak enhancement with increasing injection duration. The empiric and compartmental model enhancement curves differ notably in the portion after the peak. This discrepancy is not surprising, since the simplified compartment model focuses mainly on the early or first pass of contrast bolus pharmacokinetics.

View larger version (37K): [in a new window]   Figure 4. Graph shows time to peak porcine aortic enhancement at various injection durations (data from compartmental model and four pigs). The empiric and compartmental model times to peak aortic enhancement at various injection durations are plotted along the line of equality (dotted line). High correlation was observed between the empiric data and compartmental model data (R2 = 0.97). A nonlinear relationship between time to peak aortic enhancement and injection duration is apparent. With short injections (1, 3, and 5 seconds), time to peak aortic enhancement increases gradually with injection duration. With longer injections (20, 30, and 40 seconds), time to peak aortic enhancement is linearly proportional to the injection duration and occurs shortly after completion of injection.

View larger version (41K): [in a new window]   Figure 5. Simulated porcine aortic enhancement curves after ignoring injection volume flow and recirculation in the model of Figure 1. Contrast enhancement curves were generated by using the same parameters as those in Figure 2 except for ignoring the effects of injection volume flow and recirculation (ie, volumetric flow rate of contrast medium = systemic recirculation blood flow = zero, or mathematic linearity of the circulatory transport). In this situation, the enhancement curves for long injection duration correspond to a time-displaced sum of the enhancement curves for shorter injection duration. For example, the enhancement curve for the 3-second injection corresponds to the summation curve of three separate 1-second enhancement curves that are delayed by 1-second interval. The 1-second injection curve begins its enhancement at 5.8 seconds, the time to initial contrast medium arrival from the start of injection (TARR); peaks at 10.8 seconds, shortly prior to its mean transit time (12 seconds, TMT1); and then returns to baseline at 19.1 seconds, the time to the beginning of the contrast enhancement plateau (TPLAT). The 30-second curve also begins its enhancement at TARR and shows a plateau without a discernible peak. Its mean transit time is located within the plateau (26.5 seconds, TMT30). The plateau begins approximately at TPLAT and terminates at the end of the plateau (TEND; 35.8 seconds = 30 second injection duration + TARR).

View larger version (33K): [in a new window]   Figure 6. Graph shows mean transit time generated from a compartmental model at various injection durations, including and excluding the contrast medium volumetric flow component. When the contrast medium volumetric flow is ignored (ie, Fig 5), the observed mean transit time follows Equation (A7) (ie, observed mean transit time = circulatory mean transit time + one-half the injection duration) with a constant circulatory mean transit time and mathematic linearity. For example, the mean transit time for a 1-second injection is 12.0 seconds (11.5 seconds + 0.5), while that for a 30-second injection is 26.5 seconds (11.5 seconds + 15). This mathematic linearity is no longer valid, however, when the contrast medium injection flow is considered. The circulatory flow rate is increased because of the injected contrast medium volumetric flow. As a result, the circulatory mean transit time, the contrast medium arrival time, and the length of the plateau are shortened. In addition to this temporal shortening, the shape of the contrast enhancement curves for long injections changes from a completely flat plateau to a gradually inclining slope with a peak enhancement occurring shortly after completion of injection.