Comparison of Extracellular and Blood Pool Contrast Agents in MRA Essay

Introduction

Magnetic Resonance Angiography (MRA) has been employed as an imaging modality (1). Increased proportional use of MRA (2, 4) resulted in inverse proportional reliance on Digital Subtraction Angiography (DSA). The advancement of technology has played a leading role in the improvement of MRA spatial and temporal resolution (17). MRA contrast agents are divided into two broad categories based on the mode of action as a function of the presence of binding property of the contrast agent or absence of binding property of the contrast agent to different macromolecules like protein (6, 15, 17). The two categories of contrast agents are namely the extracellular contrast agents (ECCA) and the intravascular contrast agents (IVCA). The IVCA is also termed a blood pool contrast agent. This essay compares and contrasts ECCA and IVCA.

Contrast agents are named based on the mechanism through which they flow (2). For instance, contrast agents that could be intravenously injected and flow through extra-cellular spaces are termed ECCA (2, 12). The IVCA diffuses out of vascular spaces after injection into interstitial spaces. IVCA binds with molecules of protein. This makes it possible for the IVCA to demonstrate higher retention in the circulatory system compared to ECCA (13).

Main body

The use of gadolinium chelates in ECCA is responsible for shorter T1 relaxation (11). Reduction of T1 relaxation is an important element because it contributes to the improvement of visualization of arteries hence benefit to vascular pathology (9, 11, 13). As a result of shorter T1 relaxation, ECCA is easily eliminated.

By definition, a contrast agent (14, 16) satisfies conditions for classification as a blood pool contrast agent if the contrast agent demonstrates the capacity to slow elimination from a circulatory system. ECCA is eliminated fast from the circulatory system (4, 17). The retention of IVCA in the circulatory system is based on the capacity of IVCA to exhibit reversible binding that contributes to the establishment of dynamic equilibrium. Reversible binding as a characteristic property of IVCA is responsible for the failure of IVCA leakage into interstitial space (2, 3). IVCA increases in size. The increase in volume reduces opportunities for IVCA leakage via endothelial pores. A chemical change occurs after binding with protein molecules like albumin which contributes to a change of mechanism for IVCA elimination into interstitial space (10, 14, 16).

The sizes of ECCA and IVCA are different. ECCA is much bigger than IVCA. IVCA is much smaller. It is due to the small sizes that IVCA can diffuse from extra-cellular space into interstitial space (6). Upon binding with albumin, a large complex structure is formed. The increase in size contributes to the retention of IVCA in the interstitial space. This makes IVCA have a higher half-life compared to ECCA. This contributes to an increase in time that imaging could be carried out (12). Due to the increase in the size of IVCA after reversible binding, relaxation time for water molecules is enhanced. This influences shorter T1 relaxation times which improves efficiency compared to ECCA (14, 16, 17). This implies smaller doses of IVCA could be used. ECCA uses higher doses compared to IVCA.

The small sizes of IVCA for instance in cases of ultra superparamagnetic iron oxides, there is a demonstration of lower relaxivities (8, 9). This implies IVCA could share similar low relaxivities with ECCA. The IVCA lower relaxivities are preferred to ECCA lower relaxivities because of the sustainability of the IVCA T1/T2 ratio (15, 16). The T1/T2 ratio is important as a measure of outcomes in MRA and T1 weighted MRA techniques. The IVCA-albumin complex in interstitial spaces demonstrates slow rotation. These results in a rotational correlation time that is greater compared to smaller molecular weight gadolinium contrast agents (5, 7, 12). This property contributes to an increase of relaxivity which ECCA cannot achieve at clinical field strengths.

In the recent past, Contrast-Enhanced MRA (CE MRA) has been carried out via the use of ECCA. The ECCA doesn’t have binding properties to macromolecules like protein. Due to the flow of extracellular contrast agents through the extra-cellular spaces, the ECCA is readily excreted from the body (3). EVCA has binding properties. Different IVCA has different binding affinities for different molecules. ECCA utilizes gadolinium chelates that don’t demonstrate binding properties. As a result of the fast excretion of ECCA, their half-life is very short (7). The half-life of commonly available ECCA is documented to be 15 minutes (1, 13, 14).

This causes a disadvantage in terms of the speed required to carry out image processing and the quality of image processing in radiology. The process of image acquisition is very slow. This implies the use of ECCA contributes to processing constraints (16). The limitation of ECCA is based on a limited acquisition window that ranges between one and three minutes. Best outcomes from ECCA are achieved only when peak arterial enhancement is present.

This means, lack of peak arterial enhancement results in a lack of CE MRA acquisition (15). The quality of CE MRA depends on the quality of vessel to background contrast. Image acquisition that is initiated pre or post-peak arterial enhancement results in images that cannot be interpreted satisfactorily. This presents a disadvantage of ECCA since it requires critical timing of the peak arterial enhancement to achieve the required vessel to background contrast (9).

ECCA has a disadvantage compared to IVCA based on the relaxivity rate. ECCA has a very low relaxivity rate (15). The ECCA is disadvantaged in terms of MRA imaging hardware which results in a decrease in the vessel to background contrast. This makes ECCA incapable of imaging small-caliber diseased vessels (4, 6, 9). Imaging of small caliber vessels requires the use of high spatial resolution which cannot be achieved through the use of ECCA. IVCA is therefore preferred because it enhances arteries and veins in either first pass or steady-state MRA (13, 16).

Research into binding control agents resulted in the modification of gadolinium-based contrast agents through the incorporation of binding functional groups that could interact with protein functional groups into the formation of Modified Paramagnetic gadolinium chelates (7, 9). This formed foundation for superparamagnetic derivatives that demonstrate superior outcomes to modified paramagnetic gadolinium chelates. Imaging approaches in radiology would rely on emerging first-pass MRA control agents that would exhibit ECCA properties and steady rate MRA that would demonstrate IVCA properties (7, 12).

Compared to ECCA, IVCA have a higher relaxivity. This means IVC can result in higher vessel to background signals (12, 13). This makes it possible to conduct imaging of small caliber diseased vessels that require the use of higher spatial resolution. As a result of binding with protein molecules, IVCA gains a longer half-life. An increase of half-life results in an increase in imaging window (6, 7, 8). This means the use of IVCA eliminates the timing of peak arterial enhancement that is characteristic of the ECCA.

The longest documented half-life of IVCA is one hour. As a result of the higher half-life of IVCA, it is possible to carry out a variety of multiple arterial territories that could be imaged by using one IVCA injection (13, 15). Compared to ECCA, IVCA makes sit possible to evaluate a specific region. Region or section specificity imaging is achieved through a higher spatial resolution that IVCA can guarantee. ECCA cannot support multiple arterial territory imaging due to its characteristic short half-life.

ECCA could not be used to determine tissue blood volume (12, 16, 17). Tissue blood volume is accurately determined by IVCA. IVCA could also be employed to determine perfusion a role that ECCA cannot perform (17). This is due to the IVCA property of a higher half-life.

IVCA could be used to carry out studies on capillary membrane integrity (12, 14, 16, 17). The integrity of the capillary membrane is instrumental in detecting opportunities for slow bleeding. ECCA cannot be used to determine the integrity of the capillary membrane.

IVCA could be applied in enhanced-MRA or blood-pool enhanced MRA. This advantage is achieved either at an equilibrium state or in a steady-state (8, 12, 16). Another advantage of the use of IVCA over ECCA is based on the capability to use IVCA either in an equilibrium state or a steady state. The steady-state contributes to the clarity of separation between arteries and veins (6, 8, 10). This benefit is achieved due to the higher spatial resolution that is associated with IVCA.

This means IVCA could be used to conduct imaging during instances of the initial arterial passage of a contrast agent. ECCA cannot be applied to determine the initial arterial passage of contrast agent due to the dependence of ECCA on peak arterial enhancement. IVCA finds application in both arteries and veins. ECCA could only be applied in arteries (11, 14, 15).

IVCA imaging, subject to clarity in the separation of arteries and veins makes it possible for IVCA to find application in pre-operative planning (12). IVCA makes it possible for a vascular surgeon to identify autologous veins that could be used as bypass grafts. The ECCA could not be applied in bypass grafts because it is artery-based. IVCA demonstrates different pharmacokinetics from ECCA through T2 relaxation tomes and T1 shortening (14, 15).

Conclusion

In conclusion, the future of CE MRA lies in the use of IVCA due to limitations in the application of ECCA. IVCA could be used for first-pass imaging as well as capabilities for steady-state imaging, applications that are not possible with ECCA (10,11,13). The future of IVCA over ECCA would be based on a trade-off between spatial resolution and acquisition time and capability to quantify tissue perfusion. IVCA voxel sizes could also be reduced which makes IVCA achieve similar capabilities as X-ray angiography (14, 16). IVCA has wider application than ECCA. IVCA could be applied in the differentiation of healthy tissues. This could be used to form the foundation for determining diseased tissues or abnormal endothelial tissues.

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