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Capítulo Trece:
Agentes de Contraste

13-01 Agentes de Contraste: Introducción

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).

Figura 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.

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

Tabla 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.

Tabla 13-03:
Clasificación de algunos agentes de contraste en RM aprobados, pendientes de aprobación, en el mercado, o retirados del mercado. Hay numerosos otros en fase de des­ar­ro­llo.

  = agente disponible para uso clínico y/o aplicación de investigación;
  = agente para aplicaciones clínicas con indicaciones limitadas y/o de in­vesti­ga­ción;
  = agente en fase de des­ar­ro­llo o cuyo desarrollo se ha detenido;
  = agente retirado del mercado.
  = agente suspendido por la Agencia Europea de Medicamentos (10 de julio de 2017).

  = agente de realce positivo;   = agente de realce negativo;
  = globalmente cargado;   = globalmente neutro.

 M = macrociclico; L = lineal.

 ¹ No confundir con el agente genérico Gd-DOTA del mismo nombre.

 * = marca comercial o registrada;
 ** = a altas concentraciones, se puede obtener contraste ne­ga­ti­vo (ej: first-track bolus);
 *** = todos los agentes EFC (del espacio extracelular) son también es­pe­cí­fi­cos renales;
 (et al.) = el compuesto se vende bajo distintos nombres comerciales.