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Iobitridol in abdominal MDCT angiography

Christian Loewe
1 July, 2013  
The results of a major clinical study will influence clinical practice and choice of contrast agent for imaging of the abdominal arteries 
Christian Loewe MD
Section of Cardiovascular and Interventional Radiology,
Department of Radiology, 
Medical University Vienna, Austria
Because of exciting technical progress and the combination of high spatial resolution and fast acquisition times, multi-detector row computed tomography (MDCT) has been established as the method of choice for the diagnosis, treatment planning and follow-up of most diseases of the abdominal arteries. As a consequence of these advantages and its non-invasiveness, MDCT has already replaced the invasive intra-arterial digital subtraction angiography for diagnosis of vascular diseases within the abdomen.(1)
Optimising contrast administration
Because the image quality in computed tomography (CT) angiographies mainly depends on the contrast between the enhanced vessel lumen and the non-enhanced surrounding tissue, contrast enhancement, and consequently contrast administration, was deemed of great importance for image quality in this technique. Many articles evaluating the possible influence of different parameters for contrast administration (iodine concentration, injection rate and contrast volume) on image quality and diagnostic confidence have been published over the past decade.(2–5)
However, there was no clear consensus on recommendations for optimal contrast administration for CT angiographies of the abdomen because the results were sometimes contradictory. This information is not only of importance for optimal diagnostic image quality, but also from the point of view of patient safety: the direct relationship between the total amount of iodine given and the risk of contrast induced nephropathy (CIN) is well documented.(6–8) Thus, optimised contrast administration protocols combining maximal diagnostic accuracy with minimal total amount of iodine are required.
Clinical evidence
To answer some of the pending questions regarding the optimised contrast administration in abdominal CT angiographies, a large randomised, multicentre trial was carried out in nine centres from five European countries. The results of this trial were published in 2010.(9) Patients were prospectively enrolled and randomised into two groups: one group underwent MDCT angiography of the abdominal arteries during administration of iobitridol, whereas the second group received iomeprol.
The main difference between the two products – beside some differences in the galenic preparation – is their iodine content. Iomeprol was used at an iodine concentration of 400mg/ml and iobitridol was used at a concentration of 350mg/ml. A key factor in this study was that the examinations were performed in a blinded fashion, without any information about the contrast material used available. No adaptation to the iodine content of the agent was possible, leading to the fact that patients in the iobitridol group received 12.5% less iodine compared with the patients in the iomeprol group.
Another key issue was the fact that the different centres used different imaging protocols; each centre was allowed to use its own institution-specific examination protocol. For comparison, diagnostic efficacy, image quality and arterial enhancement were assessed alongside a number of additional secondary parameters, including visualisation of vessel wall and safety of the contrast materials used.
A total of 310 patients were randomised to one of the two groups and for CT angiography of the abdominal arteries either during administration of iomeprol or iobitridol. Both examination protocols were stable, reliable and safe. Most of all, examinations reached high diagnostic image quality; examinations (305 out of 307 eligible) were rated as satisfactory or totally satisfactory in terms of diagnostic efficacy in both groups without any difference between the two protocols.
Additionally, 4655 of the 4912 vascular segments assessed were of good or excellent image quality, again without any difference between the two groups. Furthermore, the intra-arterial contrast enhancement compared with baseline (relative enhancement) was not significantly different between the two groups, although the relative enhancement was slightly higher in the iomeprol group owing to the higher amount of iodine administered. Finally, both contrast materials were safe: only five mild adverse events in three patients have been reported, including nausea and pain, without any differences in the frequency of events between the two groups.
Two major conclusions can be reached on the basis of the trial results: first, CT angiography is a safe, stable and reliable method for visualisation of the abdominal arteries, and second, the use of highly concentrated contrast agents (400mg iodine/ml) did not confer advantages compared with a lower iodine content of 350mg iodine/ml.
Because all centres involved in this trial were allowed to use their own imaging protocols, different contrast administration schemes were applied. The total amount of iodine administered varied broadly throughout the study, ranging from 25g to 56g iodine per CT angiograph. Regarding the fact that more or less all examinations and arterial segments evaluated were of good or excellent quality, it can be concluded that there is a general trend of overusing contrast: confronted with the results that a total iodine load to the patients of 25g led to the same diagnostic and satisfactory result as 56g, recommendations for protocols requiring a high total amount of iodine cannot be explained and supported anymore. 
Additionally, in times of ultrafast CT acquisitions, the influence of contrast administration protocol on diagnostic image quality seems to decrease compared with what was previously thought. Independent of the protocol used, all examinations could be assessed and were of good or excellent diagnostic efficacy, underlying that CT angiography of the abdominal arteries is robust and reliable.
Another interesting finding was the lack of difference in diagnostic efficacy and image quality regardless of the iodine concentration of the contrast agents used. Thus, a beneficial effect of using very high iodine concentrations (400mg iodine/ml) for the diagnostic image quality of CT angiographies of the abdominal arteries – as proposed by some previous papers – was not demonstrated in this study.(10) No differences between the two contrast agents were detected with regard to safety, diagnostic confidence and image quality.
Conclusions
What could be learned from this large multinational, multicentre, randomised trial? How might the results of this study influence clinical practice with regard to CT angiography of the abdominal arteries?
First, people involved should be encouraged – where needed – to use CT angiography as the first-line method in suspected vascular diseases of the abdominal arteries. Good safety and high diagnostic confidence underline the power and usefulness of this method. The finding that results have been good or excellent, independent of site and injection protocol, underlines the fact that CT angiography is a robust and reliable test for the abdominal arteries. Thus it can be hypothesised that no special training for CT angiographies is necessary to perform a diagnostic CT angiogram if a scan/ injection protocol is predefined. 
Second, this study shows that, in general, the total amount of iodine during CT angiographies of the abdominal arteries can be further reduced, given the fact that diagnostic CT angiograms of diagnostic image quality were also produced at a dose of only 25g iodine per patient. This will help to further reduce the incidence of CIN.(7)
 
Finally, besides the general trend of using highly concentrated contrast agents, especially for CT angiographies, the scientific basis for that trend is not confirmed by the present study. This study shows no differences in image quality, diagnostic efficacy or safety between the two agents (iomeprol and iobitridol), regardless of the differences in their iodine content. Thus, given that less iodine is better for patient safety, iobitridol, with an iodine content of 350mg/ml, is a preferable contrast agent compared with iomeprol 400 for imaging the abdominal arteries by means of CT angiography.
 
References
  1. Johnson PT, Fishman EK. IV contrast selection for MDCT: current thoughts and practice. Am J Roentgenol 2006;186:406–15.
  2. Behrendt FF et al. Contrast enhancement in multidetector-row computed tomography (MDCT) of the abdomen: intraindividual comparison of contrast media containing 300 mg versus 370 mg iodine per ml. Eur Radiol 2008:18;1199–205.
  3. Furuta A et al. Hepatic enhancement in multiphasic contrast-enhanced MDCT: comparison of high- and low-iodine-concentration contrast medium in same patients with chronic liver disease. Am J Roentgenol 2004;183:157–62.
  4. Awai K et al. Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the effect of different concentrations of contrast material at multi-detector row helical CT. Radiology 2002;224:757–63.
  5. Suzuki H et al. Comparison of two contrast materials with different iodine concentrations in enhancing the density of the aorta, portal vein and liver at multi-detector row CT: a randomized study. Eur Radiol 2004;14:2099–104.
  6. Katzberg RW, Barrett BJ. Risk of iodinated contrast material-induced nephropathy with intravenous administration. Radiology 2007;243:622–8.
  7. Thomsen HS, Morcos SK, Barrett BJ. Contrast-induced nephropathy: the wheel has turned 360 degrees. Acta Radiol 2008;49:646–57.
  8. Nyman U et al. Contrast-medium-induced nephropathy correlated to the ratio between dose in gram iodine and estimated GFR in ml/min. Acta Radiol 2005;46:830–42.
  9. Loewe C et al. 64-Slice CT angiography of the abdominal aorta and abdominal arteries: comparison of the diagnostic efficacy of iobitridol 350 mgI/ml versus iomeprol 400 mgI/ml in a prospective, randomised, double-blind multi-centre trial. Eur Radiol 2010;20(3):572–83.
  10. Awai K et al. Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the effect of different concentrations of contrast material at multi-detector row helical CT. Radiology 2002;224:757–63.