Rendon Nelson, MD
Professor and Vice-Chairman of Radiology, Duke University Medical Center, Durham, NC

Faster multislice CT scanners create the opportunity to image with increased speed, more reasonable breathhold times, better image quality, and im-proved three-dimensional and multiplanar reconstructions. ¹ Advances in CT technology also open the door to new approaches to the administration of iodinated contrast. One possibility is the use of higher-concentration, lower-volume contrast agents. Whether such an approach could provide equivalent enhancement to that achieved with standard-concentration contrast media is a question we recently investigated at Duke University Medical Center.

We focused primarily on hepatic imaging. Therefore, a brief review of both liver enhancement and key considerations in using the new multislice CT technology may be helpful.

Balancing Speed and Image Quality

When upgrading from a scanner that acquires 4 slices per rotation to one that acquires 8 slices per rotation, the first option is to image much faster, for example, to reduce breathhold times. With this approach, image quality remains about the same. Another option is to image a little bit faster and enhance image quality by decreasing noise and artifacts. The third option, when acquisition and breathhold times are already acceptable with the 4-slice scanner, is to leave imaging speed unchanged and, instead, attempt to achieve a data set with much higher image quality.

Radiation dose is also a consideration in selecting scanning parameters. A 4 * 1.25-mm detector configuration uses a beam collimation of 5 mm. On an 8-slice scanner, a slice width of 1.25 mm doubles the beam collimation to 10 mm, which raises concerns about the radiation dose. When advancing from a 4-slice to an 8-slice scanner, it may be preferable to keep the beam collimation approximately the same or use faster table speeds to prevent an increase in radiation dose.

Hepatic Imaging

In liver imaging, lesion detection is determined by conspicuity, ² which in turn is determined by liver-to-lesion contrast. ³ In tracking the phases of liver enhancement, the artery starts enhancing approximately 15 seconds after contrast injection, and then enhancement drops off a little bit. The portal vein starts enhancing at about 30 seconds and peaks a few seconds after that. The liver follows suit, and at about 60 seconds the liver enhancement curve is characterized by an upslope and then a plateau of enhancement.

It is important to avoid imaging during the equilibrium phase, which takes place at approximately the 3-minute mark. During this time, lesions that can be clearly seen on the portal venous phase tend to disappear (Figure 1).

Foley et al ⁴ characterized the phases of liver enhancement by scanning twice in the arterial phase and once in the venous phase. They showed that, for a hypervascular tumor, the enhancement curve tends to peak during the later part of the arterial phase. At baseline, the lesions may or may not appear as hypoattenuating masses. Many are invisible, particularly if small. By about 20 seconds, contrast fills the artery only, not having reached the hepatic parenchyma. This early hepatic arterial phase is valuable for CT angiography, but it is not very helpful for detection of hypervascular lesions.

At about 30 seconds, contrast is in the parenchymal arteries and, to some degree, in the portal vein. This is what Foley calls the portal venous inflow phase and others have referred to as the late hepatic arterial phase. During this phase, a hypervascular lesion will light up. At about 70 seconds, however, hypervascular lesions can disappear. Foley called this the hepatic venous outflow phase. It is also known as the portal venous phase (Figure 2).

In summary, in hepatic imaging, enhancement during the arterial phase is predicated primarily upon the rate of injection, as well as the timing. Timing can be determined by using a fixed delay, a timing bolus, or automated triggering, which I prefer for arterial-phase imaging of the liver and for CT angiography.

During the venous phase, however, enhancement is predicated not so much on the timing or the rate of contrast delivery, but on the total dose of iodine. ⁵ My colleagues and I at Duke University Medical Center decided to further investigate this possibility with a randomized study.

The Duke Study: Methods

The hypothesis of the study was that a smaller dose of a more highly concentrated iodinated contrast agent could be used to obtain similar quality multislice helical CT images of the liver. To test this hypothesis, we compared two contrast media injection protocols, determining their liver and vascular enhancement characteristics both quantitatively and qualitatively.

The prospective, randomized, double- blind study enrolled 20 patients with suspected or known liver lesions who were scheduled to undergo abdominal CT. Our imaging parameters were as follows (Table 1): For the non-contrast images, hepatic arterial phase, and portal venous phase, we used a 5-mm collimation. We used a fixed scan delay for both the arterial and venous phases, an approach we debated, as this somewhat dated method does not reflect our standard practice. Ultimately, we decided that we did not want timing to be a confounding issue, since we were constructing time attenuation curves. For the arterial phase, we selected a fixed delay of 30 seconds, aiming for the later arterial phase. For the venous phase, we selected a fixed delay of 65 seconds.

The table speed for the arterial phase was a little faster than for the venous phase--22.5 mm/rotation, as compared with 15 mm/rotation--because the arterial phase is the shorter of the two. Pitch also differed: It was 6-to-1 in the arterial phase and 3-to-1 in the venous phase. (It should be noted that to reduce the radiation, we have recently changed our protocol for venous-phase studies to specify a 4 * 2.5-mm detector collimation and a 6-to-1 pitch.) In the study, we also used a 0.8-second rotation time, since not all of our scanners are capable of a 0.5-second gantry rotation.

The contrast injection protocol in one arm of the study consisted of 150 mL of Isovue 300 (iopamidol, Bracco Diagnostics, Princeton, NJ) delivered at 5 mL/sec, for a total iodine dose of 45 grams. That was compared with 100 mL of Isovue 370 delivered at 4 mL/sec for a total iodine dose of 37 grams. Therefore, the total volume of contrast is reduced by one-third, while the iodine dose is reduced by 18%.

When the iodine dose is analyzed by the number of grams delivered per second, however, the difference is not substantial. Administering 150 mL of Isovue 300 at 5 mL/sec delivers an iodine dose of 1.5 gm/sec for 30 seconds. Administering 100 mL of Isovue 370 at 4 mL/sec delivers an iodine dose of 1.48 gm/sec for 25 seconds.

We analyzed the images quantitatively, performing regions-of-interest analyses on the liver in three places, and on the aorta. We did this on every slice, and from that data we constructed time attenuation curves. The images were analyzed qualitatively as well by three abdominal radiologists who scored them from 1 to 5--5 being the best--for liver enhancement, vascular enhancement, and overall image quality.

Study Findings

In the liver, quantitative analysis of arterial-phase images demonstrated enhancement ranging from approximately 13 to 15 HU (Figure 3). En-hancement was a little greater with Isovue 370 than with Isovue 300, but the difference was not statistically significant ( P = 0.89).

In the portal venous phase, en-hancement was approximately 50 HU after 150 mL of Isovue 300 and slightly less after 100 mL of Isovue 370, a not unexpected finding since, as noted above, total iodine dose was 18% less with Isovue 370. However, the difference, again, was not statistically significant (Figure 4). A P value of 0.12 raises the possibility of a statistical trend, but it was not demonstrated in the 20 patients we studied.

In the aorta, there was more enhancement during the arterial phase with Isovue 370, in the range of 250 to 270 HU (Figure 5), but the differences between Isovue 300 and Isovue 370 were insignificant.

This, however, was not the case during the portal venous phase. For Isovue 300, enhancement in the aorta was approximately 100 HU, while for Isovue 370, enhancement in the aorta was closer to 90 HU (Figure 6), a statistically significant difference ( P = 0.01). Again, the study design, which called for a shorter injection, less volume, and less total iodine with Isovue 370, makes this an expected result. Qualitative data, however, again showed no difference between the two agents.

We concluded, therefore, that giving 100 mL of Isovue 370 at a similar rate of iodine delivery and injection duration provided comparable liver parenchyma enhancement in both the arterial and the venous phases, when compared with 150 mL of Isovue 300.

There was a modest cost difference, however. Using the Isovue 370 protocol resulted in a 14% reduction in contrast use. That could translate into an annual savings of nearly $54,000 at our institution.

Conclusion

In adjusting CT scanning protocols for lower-volume, higher-concentration contrast media, it is advisable to consider the number of grams of iodine per milliliter, the rate of contrast injection, and the duration of the injection and exam. In this way, it is possible to tailor the protocol to achieve a similar rate of iodine delivery per second as would be possible using standard contrast media and, therefore, achieve a similar level of enhancement in the target organ. *