MRI with Gadolinium-Based Nanoparticles - Nanotechnology for Biomedical Imaging and Diagnostics - page 217

In this chapter, we first describe the mechanisms involved in the production of
contrasted images with Gd 3+ -based CAs and detail the parameters to consider when
designing Gd 3+ complexes. The advantages and limitations of the currently approved
CAs are discussed. These considerations should provide the reader the important
points that have guided the design of the nanoparticles reviewed in this chapter.

8.2 GadolInIuM as a contRast aGent In MRI

CAs are species that alter the de-excitation signal of the surrounding water molecule
that has been submitted to a magnetic field. The de-excitation, or relaxation of
protons (present in the body mostly in water and fat), after absorption of a specific
pulsed radio frequency (RF), can be divided into two time components: the
longitudinal relaxation time ( T 1 ) and the transverse relaxation time ( T 2 ). T 1 and T 2
values of water differ within the kind of tissues (for instance, blood, fat, or gray
matter produce signals that can be differentiated). Also, depending on the nature of
the CA, T 1 and/or T 2 can be altered. The measurement of the differences in relaxation
times allows reconstitution of images with contrasted area depending on the nature
of tissues or the presence or absence of the CA in the area of interest. It is beyond the
scope of this chapter to detail the mechanisms involved in the production of images
in an MRI experiment. The theory of MRI can be found in recent topics [1, 2]. The
progresses in MRI diagnosis are also strongly dependent on the advances in instru-
mentation. The primary parameter that impacts the sensitivity of MRI is the magnetic
field strength of the scanner, which is expressed in tesla (T). While most of the scanners
currently used in clinics are of 1.5-3 T, higher magnetic fields can now be reached.
15-20 T scanners have become available, mostly for animal studies but also for
human, especially in neurological [3], musculoskeletal [4], or cardiac [5] imaging
where high sensitivity and resolution are required. These hardware improvements
come along with software evolutions and with the design of new RF pulse sequences,
allowing visualization of tissues of interest with increasing accuracy and sensitivity
by, for example, suppression of unwanted tissue signal during image acquisition or
by making possible the production of three-dimensional images. Recent advances
and perspectives in the technology of MRI have been reviewed by Blamire [6].

8.2.1 Gadolinium and Relaxivity

The relaxation of a nucleus is mostly caused by the inhomogeneities in the local
magnetic field and the dipole-dipole interactions with the surrounding nuclei.
Introduction of a paramagnetic species such as Gd 3+ in the environment of a proton
nucleus can accelerate the relaxation process. The efficiency of a paramagnetic
substance to increase the proton relaxation rate is termed relaxivity. The relaxation
rate is proportional to the relaxivity of the paramagnetic species r i and to the
concentration of the paramagnetic species [ M ]:

1 1 11

=+=+ []

T TT rM

i

T

i , obs i , d i , p i , d