• Chapters 12+13 • Contents
  More Magnetism  MR Contrast Agent Terms Contrast Agents: Introduction  Classification (Table) Positive and Negative Contrast Agents Gadolinium-Based Extracellular Fluid Space Agents  Chelates  Dose  Imaging Parameters  Tissue Uptake  Adverse Events Targeted and Organ-Specific Contrast Agents  Liver Agents  Targeted Manganese Agents Further Applications  Dysprosium  Ventilation Imaging  Enteral Agents Molecular Imaging

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Chapter Thirteen
MR Contrast Agents

13-01 MR Contrast Agents: Introduction

espite the fact that inherent contrast in MR imaging can be manipulated to a much greater extent than in other imaging techniques, cer­tain dia­gnos­tic questions cannot be answered easily and require the application of contrast agents (Figure 13-01).

Figure 13-01:
Nature likes mimicry; radiologists like to highlight lesions. With plain photography (or MR imaging), the ob­ject of the examination might be visible but nor clearly delineated. Changing contrast with an ex­trin­sic agent may help … for instance, painting the wall in the background or injecting a con­trast agent.

In general, contrast manipulation in MR imaging by application of contrast agents (sometimes also called molecular imaging) is most useful when inherent contrast cannot be attained successfully.

Since it is nearly impossible to al­ter the water content of tissues, con­trast agents on the market or in cli­ni­cal or pre-clinical trials focus on relaxation time and sus­cep­ti­bi­li­ty changes.

As early as 1946, in one of the first papers describing NMR, pa­ra­mag­ne­tic ca­ta­lysts were mentioned to accelerate the T1 relaxation process [⇒ Bloch]. This concept was recognized by Paul C. Lauterbur shortly after his invention of MR imaging and tested and proved in imaging studies in animals: the first pathologies enhanced by a contrast agent [⇒ Lauterbur].

The most efficient elements are listed in Table 13-01. Particulate agents form a different class. Important goals and re­qui­re­ments for the de­ve­lop­ment and use of MR con­trast agents are listed in Table 13-02.

Table 13-01:
Some paramagnetic elements and their properties: gadolinium, manganese, dysprosium, and iron.

Table 13-02:
Primary and secondary goals and re­qui­re­ments for the development of contrast agents for magnetic re­so­nance imaging.

In many instances, the pattern of enhancement of paramagnetic contrast agents in MR imaging is very similar to that of contrast-enhanced x-ray CT. How­ever, it should be taken into account that in reality MR contrast agents be­have differently from CT agents and do not in any case follow the CT en­han­ce­ment patterns: In x-ray CT one sees the agent, in MR imaging one sees the effect of the agent on tissues.

Many efforts in contrast agent development were channeled in certain directions more by the relative ease of chemical synthesis than by the goal of specific medical applications or product safety. Thus, when applied properly, contrast agents available for clinical routine examinations today are safe and good enhancers — however, they are unspecific. This means that they do not highlight specific pathologies but rather unspecific pathological tissue changes.

A detailed and exhaustive description of the state of R&D in the field can be found in a review from 2019 [⇒ Wahsner 2019].

13-01-01 Classification of Contrast Agents

At present, paramagnetic contrast agents are the most frequently used. Yet, despite the fact that approximately one thousand compounds were developed during the last forty years, only very few agents are on the market. How­ever, the num­ber of trade names is far higher and an over­view of dif­fe­rent brands of the same product can be dif­fi­cult.

Table 13-03 gives an overview of some of the MR contrast agents currently in use, already withdrawn from the market, or being developed.

Table 13-03:
Classification of some magnetic resonance contrast agents being developed, to be approved, ap­pro­ved, marketed, or withdrawn from development or the mar­ket. There are numerous other agents in de­ve­lop­ment.

  = agent available for clinical and/or research application;
  = agent available for clinical and/or research application with limited indications;
  = de­ve­lop­ment interrupted or dis­con­ti­nued;
  = agent withdrawn from one or all major markets;
  = agent suspended by the European Medicines Agency (10 July 2017).

= positively enhancing agent;   = negatively enhancing agent.
= globally charged agent;   = globally neutral agent.

 M = macrocyclic; L = linear.

 ¹ Do not mistake for the generic Gd-DOTA agent of the same name.

* = trademark or registered trademark;
** = with high concentrations, negative contrast can be achie­ved (e.g., first-track bolus);
*** = all ECF agents are also kidney-specific agents;
(et al.) = the compund is sold under different trade names.