Reducing iodine levels in coronary angiography

Contrast material administration has become a very important parameter with the introduction of computed tomography coronary angiography (CTCA). In fact, in the early days of CTCA, several publications pinpointed the importance of achieving an adequate contrast enhancement inside the coronary lumen in order to grant better images and, ultimately, better diagnostic accuracy.1–5 At the same time, other sides showed that intravascular attenuation was affecting significantly the actual attenuation measurements for the non-calcified coronary plaques.6–9 This is not a trivial effect and we can define it properly as a true artifact of the imaging modality. Its relevance is related to the fact that ‘high-risk’ coronary plaques, the ones more likely to rupture and determine an acute thrombotic obstruction (that is, acute myocardial infarction), have a relatively low density, which is increased when lumen enhancement is very high.

These two borders are the ones within which we have to move to find the proper balance between having high quality diagnostic images and being able to better stratify risk in each individual patient.

The usual approach to intravenous contrast material administration is based on some rules:

The rapid intravenous administration of iodinated contrast material is required to create a peak of attenuation, which is mandatory to obtain good angiographic images. Flow rates used are no less than 4ml/s and can reach up to 6–8ml/s. It is not easy to obtain very high flow rates in all types of patients; the venous system of the arm is not always adequate, therefore it is better to reach no more than 6ml/s.

Arterial synchronisation can be achieved by two main techniques: bolus tracking and test bolus. They are equivalent with their own procedure. They do not significantly affect the final result, except for the fact that with test bolus there is an additional burden of contrast material (15–20ml) that has to be administered.

In the bolus tracking technique, a region of interest (ROI) is plotted inside the lumen of an artery close to the region that has to be studied and a trigger attenuation value (threshold) is arbitrarily chosen before starting the CTCA data acquisition. A single level low dose dynamic scan is performed at determined intervals of time during the injection of contrast material. When the contrast material arrives at the level of the ROI, the change in attenuation is detected and a CT scan is started after reaching the triggering threshold.

The CT scanner needs 4–5 seconds to give the patient breathing instructions. The threshold should be 80–100HU above the baseline level of the ROI.

In the test bolus technique, an ROI is plotted inside the lumen of an artery close to the region that has to be studied. A small amount of contrast material (10–15ml) at the same rate of the main bolus is injected while a single level low dose dynamic scan is performed at determined intervals of time. When the contrast material arrives inside the lumen of the artery at the level of the ROI the test bolus geometry is assessed and the time between the start of the test bolus injection and a determined point of the time/attenuation curve of the test bolus is used as delay time for the injection of the main bolus.

Test bolus has a different geometry than the main bolus, which is related to the lack of injection power after the injection of the test bolus, which determines a pooling of the test bolus in the venous system. Usually it needs 4–6 seconds to be added to the delay calculated from test bolus.

The minimum amount of contrast depends heavily of the CT technology available. The latest CT technologies are very fast and they can allow performing the CTCA within one heartbeat. This means that we need to have adequate enhancement in the heart and coronary lumen, in principle, just for one heartbeat. This result has a number of advantages for the patients: less contrast (that is, less risk of renal damage in patients with altered kidney function) and lower costs.

As anticipated, the debate around the need for higher intracoronary attenuation has been ongoing for some time. Very few randomised studies have been performed and they mainly demonstrated that a concentration of 320mg iodine/ml delivers significantly worse intracoronary attenuation as compared with 400mg iodine/ml.

In some cases, the recommended intravascular attenuation that was deemed adequate for coronary stenosis detection was >250HU, in other cases was >320HU. In no cases at that stage (between 2002 and 2004), was diagnostic accuracy verified in relation to intravascular attenuation; most of the concepts were based on individual experience and clinical practice. At that time clinical practice was also limited by the fact that CTCA was a new technology mostly performed in large academic centres for research purposes.

Studies on diagnostic accuracy for the detection of significant stenosis by means of CTCA have been performed extensively between 2000 and 2006, but after then, the negative predictive value of CTCA was so high (usually above 95%) that it became very difficult to have conventional coronary angiography validation in all patients. Therefore, most of the studies performed after 2006 have to rely on subjective image quality judged by experienced operator and quantitative measurements absolute intravascular attenuation and on signal to noise ratio. These measurements are surrogate of diagnostic time accuracy.

At the same plaque imaging with CTCA has become an important topic in the context of risk stratification. Being able to see plaques, define their features accurately and quantify those features may play a very important role in the future of cardiovascular medicine. In fact treatment strategies, especially pharmacological ones might be influenced in the future by coronary plaque features.

A major role in the debate has been played by the tumultuous development of CT technology. Given the fact that every two to three years a new CT scanner generation is available on the market, it becomes somehow difficult to provide uniform rules and protocols that fit any technology and any setting. In the early days of CTCA, with four-slice CT technology, it was necessary to obtain a breath-hold of about 40s from patients undergoing the investigation. This long apnea needed a long plateau of intravascular enhancement in order to have adequate and homogeneous visualization of coronary arteries throughout the dataset. Of course the amount of contrast material required for such a scan was very impressive (140ml). During the years we have seen 16-slice, 64-slice, and today 640-slice and Dual Source technologies. The speed of the examination has dramatically changed, in a positive way. Very short breath-hold is necessary with the latest technologies; very few seconds. With these latest CT technologies we can use between 40 and 60ml of contrast, which is much less than before.

Recently, the results of X-ACT trial have been presented at the RSNA in Chicago, the most important radiology congress. This trial has focused specifically on one aspect of contrast administration in CTCA: the amount of iodine, and therefore the amount of contrast material. By comparing the three contrast material compounds with different iodine concentrations (iobitridol 350mg iodine/ml (Xenetix®, Guerbet); iopromide 370mg/ml (Ultravist®, Bayer Healthcare); iomeprol 400mg/ml (Iomeron®, Bracco), the study demonstrated the non-inferiority of iobitridol 350mg iodine/ml compared with the other compounds, supporting the thesis that using lower iodine concentration allows adequate results to be achieved.

Contrast material will remain a very important parameter for CTCA and the ongoing development of CT technology will determine a continuous modification of our approach to this topic. In particular, the introduction of iterative image reconstructions associated with the possibility to use lower kilovolt setting (<100kV) and higher mAmp/second may further change the approach to contrast material administration. In fact, higher intravascular attenuation is more easily obtained at lower kV setting.