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New contrast agents give far clearer MRI images at lower and safer doses

A new generation of high signal-intensity contrast agents is improving patient safety and giving radiologists greater confidence in their diagnoses

Dr Henrik Michaely
Associate professor of radiology and section chief of vascular and abdominal imaging
Institute of Clinical Radiology and Nuclear Medicine
University Medical Centre

Email: [email protected]

Until relatively recently, patient safety was not considered a critical factor in use of contrast agents for magnetic resonance imaging (MRI). Most contrast agents were in high use in hospitals across the world and were considered safe, particularly when weighed against the diagnostic benefits of MRI in identifying serious conditions in patients.
But with the unexpected advent of nephrogenic systemic fibrosis (NSF), the focus has understandably and correctly shifted towards the safety of contrast agents, the dosage used and the herewith achieved signal intensity.
High signal-intensity contrast agents for MRI – which achieve a higher enhancement of the target structures such as vessels, tumours or areas of inflammation – are an area that is being explored as offering a solution to this risk. These contrast agents allow the radiologist to see much more than with standard gadolinium-chelate contrast agents and hence offer a higher degree of confidence in the diagnosis at a same or even lower dose.
Recent research findings indicate that less stable non-ionic linear agents – which are more likely to release free gadolinium – have been associated with NSF in patients with renal failure. The risk of NSF with the more stable macrocyclic agents is lower, which has recently also been acknowledged by the European Medicines Agency (EMEA).
Based on preclinical studies and the number of so far reported cases of NSF, gado butrol as a high signal-intensity contrast agent can be considered safer and more effective than other contrast agents on the market.
Generally speaking, the higher the signal intensity, the higher the image quality, and this increase of signal intensity is being sought through newer contrast agents and via scanners that operate at 3 Tesla rather than 1.5T, to help offer radiologists the opportunity of reducing the dose of contrast agent and minimise the risk to the patient while maintaining or even enhancing the quality of the image.

The Holy Grail of imaging
With regard to dynamic MRI – magnetic resonance angiography (MRA) and perfusion – the Holy Grail is increasing the signal-to-noise ratio – a quantitative measure of the image quality – leading to better imagery. The background noise is always the same and cannot be altered, but what can change is the contrast enhancement, i.e. the signal intensity of the images. With higher signal intensity, the resulting higher signal-to-noise ratio can be sacrificed to gain speed and resolution.
This enhanced imaging through higher intensity signal can present a new aspect to diagnosis especially in MRA; that smaller vessels, collateral vessels and high-grade stenosis and occlusions that may not have been identified can now be better diagnosed with MRA. This improved diagnosis can make a significant difference to clinical outcome and the quality of life for a patient.


For those with the most severe disease, such as high degree PAOD (peripheral artery occlusive disease), it can mean highlighting collateral vessels for a surgeon and make the difference between a patient losing a foot or part of a leg by identifying where a bypass graft can be sited to allow enough blood flow to supply a patient’s foot, for example. Three years ago, few people were concerned about MRI contrast agent safety because they were generally considered safe, even in higher doses. Nowadays, with advent of NSF, what everybody is concerned about is the dose of a contrast agent. With regard to this, high signal-intensity agents have been a breakthrough because they provide images of equal quality but at a lower dose than with standard chelates. It is possible to administer 60-70% of a standard dose and still achieve images of a quality comparable to those obtained with single dose or standard dose of standard contrast agent.
Using gadobutrol, we have been able to see more vessels and collateral branches and improve the signal-to-noise ratio.
Gadobutrol is beneficial because it combines the properties that we are looking for: high R1 relaxivity with a good signal-to-noise ratio when compared to standard chelates; and improved patient safety because we have been able to reduce the dose.
It is the combination of high safety profile, a macrocyclic structure and high relaxivity that makes this a very good and a very preferable contrast agent.

Testing effectiveness
There have been studies to help quantify the effectiveness of high signal-intensity contrast agents. In brain imaging, this implies that lesions can be depicted at a better quality than with standard chelates and even additional lesions, such as satellite lesions, and different metastases missed with standard chelates can be seen. That translates into better patient care in terms of a more comprehensive and safer diagnosis.
What we have conducted recently is perform MR angiography of the entire legs with a very low dose of gadobutrol. The findings revealed that with the dose reduced to 70% of the standard of dose – and to 35% of what has been given before because double dose was always considered standard – the fine detail is still visible, enabling a safe diagnosis.
We are now comparing MR angiography results to the results of the invasive angiography. Interim analysis looks good, even though very little contrast agent was used and a severely ill patient collective was included in this study.

Alternative methods
A next step is to compare alternative methods such as non-enhanced angiography of the lower leg, but that has, so far, not shown such good results. To date, the non-enhanced technique is not very robust and up to 40% of patients dropped out because of leg movements leading to non-diagnostic images.
Not all parts of the body have been researched with comparative studies for high signal-intensity contrast agents, but they are very effective when examining the central nervous system – the brain and the spine – in looking for small metastases enhancement.
A key area is MR angiography where the ability to see smaller vessels is crucial and can only be achieved when you have enough signal intensity to support the high resolution to see those vessels.
There are clear benefits in vascular imaging because that is an area that is extremely demanding in terms of technical requirements and spatial resolution and is a discipline where the difference between standard chelates and high-signal chelates is best demonstrated.
Overall, high signal-intensity contrast agents offer a safe and highly accurate diagnostic alternative to other contrast agents:

  • The radiologist can have more confidence in the diagnosis with stronger enhancement facilitating greater belief in the images.
  • The risk of incorrect diagnosis for the patient is reduced, meaning treatment can be better and more directly targeted
  • Those two advantages can dovetail to translate into clear efficiency and cost-effective benefits for a hospital or health system.