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Chapter 13

13-01
Introduction

Classification (Table)
13-02
Positive and Negative Contrast Agents

13-03
Gadolinium-Based Extracellular Fluid Space Agents

Chelates
Dose
Imaging Parameters
Tissue Uptake
Indications
Adverse Events
13-04
Targeted and Organ-Specific Contrast Agents

Liver Agents
13-05
Further Applications

Ventilation Imaging
Enteral Agents
Manganese (MEMRI)
Dysprosium
13-06
Molecular Imaging


Chapter Thirteen
Contrast Agents

13-01 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. Important goals and re­qui­re­ments for the de­ve­lop­ment and use of MR con­trast agents are listed in Table 13- 01. 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.

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 [⇒ Lauterbur].


Table 13-01:
Primary and secondary goals and re­qui­re­ments for the development of contrast agents for magnetic resonance imaging.

Many efforts in contrast agent development were channelled in certain di­rec­tions more by the relative ease of chemical synthesis than by the goal of specific medical applications. Thus, the first-generation contrast agents available for cli­ni­cal rou­tine examinations today are relatively safe, good enhancers, but un­spe­ci­fic. This means that they do not highlight specific pathologies but rather un­spe­ci­fic pa­tho­lo­gi­cal tissue changes. At present, paramagnetic contrast agents are the most fre­quent­ly used. The most efficient elements are listed in Table 13-02. Particulate agents form a different class.



Table 13-02: Some paramagnetic elements (transition metals) and their properties: gadolinium, manganese, dysprosium, and iron.


13-01-01 Classification of Contrast Agents

Table 13-03 gives an overview of a number of MR contrast agents currently in use, already withdrawn from the market, or being developed. Only perhaps a dozen agents are on the mar­ket; how­ever, the num­ber of trade names is far higher and an over­view of dif­fe­rent brands of the same product dif­fi­cult.



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 severely limited indications ("high risk");   = agent being developed;   = de­ve­lop­ment interrupted or dis­con­ti­nued;   = agent withdrawn from one or all major markets.

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

* = 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.

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