Magnetic resonance imaging (MRI) is a powerful imaging modality for diagnostic cardiology and research. This imaging method provides combined diagnostic information of different tissue characteristics, such as the visualisation of the vascular tree and cardiac anatomy and function, as well as measurements of blood flow in the vessels, ventricular wall motion, myocardial perfusion and viability. The inherent contrast between blood and myocardium with MRI depends largely on the proton concentration and longitudinal (T1) and transverse (T2) relaxation times. The use of MRI contrast agents or different pulse sequences can modulate this inherent contrast.¹ Most of the current applications for cardiovascular magnetic resonance (CMR) use contrast agents either to improve image quality (e.g. angiography) or generate contrast (e.g. late gadolinium enhancement or perfusion). Today, in most clinical applications contrast agents – which are based on gadolinium chelates – are used, causing significant shortening of T1 (leading to signal enhancement in T1 weighted images) and a minor shortening of T2. Until recently, all these agents had been extracellular respectively interstitial agents since they leak rapidly from the vascular into the interstitial space but not into the cell, typically with a plasma half-life in the order of 20 minutes.² Blood pool contrast agents (BPCAs) may have considerable advantages since they remain in the vascular space (thus causing no or minimal background enhancement) and have a longer half-life and a stronger T1 relaxivity. The plasma half-life for BPCAs differs between 10 and 30min for Gadomer-17,3 120 and 180min for gadofosveset4 and 224±30min for B-22956.5 In addition, gadolinium-based BPCAs have relaxivity values that are two to five times higher than those of extracellular contrast agents.6,7 The most promising indications for CMR with BPCAs are angiography, perfusion imaging and coronary artery imaging. Additional advantages of BPCAs are the ability to measure tissue blood volume and perfusion by using principles of indicator-dilution, and the ability to evaluate changes in capillary membrane integrity, which may be advantageous for pathology characterisation.

BPCAs are either paramagnetic or superparamagnetic agents. Most paramagnetic agents are gadolinium-based, whereas superparamagnetic agents are iron oxide particles.8 Several strategies can be applied to restrict the distribution of the contrast agent to the intravascular space, as follows.

• Creation of large molecules by conjugating the paramagnetic ligand to different back-bones, such as dextran, polylysine and dendrimers. However, care needs to be taken to allow for renal filtration.

• Addition of a site that reversibly binds to human serum albumin. The advantages of this concept are the increased T1 relaxivity (due to the slow tumbling rate) and the renal filtration of the fraction of the contrast agent that is unbound. However, the unbound fraction also diffuses into the interstitium, reducing the net gain of these agents.

Different BPCAs have been developed and tested for cardiovascular application in humans.9 A few clinical trials have been performed using gadofosveset;^10–12 Gadomer-^17;1,3,13,14 NC100150 superparamagnetic agent (Vistarem);^1,15 and gadocoletic acid (B-22956).^5,16
However, currently there is only one European Medicines Agency (EMEA)-approved BPCA (gadofosveset; tradename Vasovist®; Bayer- Schering Pharma AG Germany, development name MS-325, Epix Pharmaceuticals, US) for abdominal and peripheral angiographies in humans; at present, none of the agents is approved for cardiac imaging.¹⁷

Angiography

For MRI angiography the advantages of BPCA can be used in several ways.

• The higher relaxivity leads to a higher blood signal, which can improve diagnostic accuracy, spatial resolution or dose reduction.

• The longer plasma half-life without increase of background signal allows for longer scan times and repetitive imaging, independent of the first pass^.8,9

In dogs, NC100150 injection increases vessel conspicuity and allows visualisation of extensive anatomic regions including aorta, iliac, femoral, popliteal and peripheral arteries.⁸ In direct comparison with two extracellular contrast agents, Gadomer-17 led to a three- to four-fold increase in signal-to-noise ratio (SNR) during the arterial and equilibrium phases of thoracic and abdominal MRI angiography. Gadomer-17 improved the visualisation of the aorta, the inferior cava vein, the portal vein, the renal arteries and veins, the celiac trunk, the superior mesenteric artery and the pulmonary artery and veins.18