Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 471

16.4.5 imaging of the nervous system

As the science community entered the twenty-first century, neurological studies have
become a prominent mainstay within all disciplines and modalities. CNS disorders
and injuries have been under intensive study since the beginning of the so-called
(brain age) of medical studies. Studying the CNS has proven difficult however due to
its complexity and depth. Also, due to the relatively nonregenerative properties of
cells within the CNS, finding means to repair the CNS has become the main goal
of those within the field of research.
Alzheimer's disease is a growing health concern for older generations of humans.
It is a degenerative disease that slowly erodes the neuronal structure and pathways
within the brain. How and why the disease develops is still relatively unknown;
however, advances in imaging techniques are providing an in-depth look into the
formation and progression of the disease.
The challenge in neurological disease has always been developing methods to
image across the BBB. The BBB is a semipermeable membrane that is glucose sol-
uble. This creates difficulties in crossing the barrier with bioluminescence and other
fluorescent materials that are required for imaging the brain. As nanomaterials are
generally excluded from crossing the BBB, nanomaterial contrast agents are limited
to imaging of intravascular disease such as stroke or cancer in which the BBB is
broken. In the case of a compromised BBB, tissue uptake is primarily nonspecific.
Nanomaterials have shown great promise in the delivery of small-molecule therapeutic
agents to the brain and facilitate crossing of the BBB. This strategy is beginning to
show promising results for imaging purposes.
A biodegradable nanocarrier system made up of poly-n-butyl cyanoacrylate
(PBCA) dextran polymers coated with polysorbate 80 (PBCA NPs) has shown great
promise in having the ability to cross the BBB [31]. PBCA has great potential
because it is able to carry BBB-impermeable materials across the barrier and allows
for advancement of diagnostic neuroimaging. The process begins with a Nissl stain
for cellular imaging; then moves to visualization of amyloid plaques, in vivo , using
non-BBB-permeable reagents that detect plaques; and finally finishes with the
delivery of a gadolinium-based contrast agent into the brain of the mouse for a whole-
brain MRI in vivo [31]. Diagnostic neuroimaging of the mouse will provide key
information to the mechanisms of Alzheimer's disease, as well as insight into how to
repair the damaged tissue and how to prevent the disease from progressing.
one recent report indicates that nanomaterials have demonstrated drug delivery to
the brain by incorporating mechanisms for translocation of agents across/through the
BBB. It was shown that the PBCA NPs encapsulated with different fluorophores were
successful at crossing the BBB. The NPs were administered IV into mice, and then
the first several hundred micrometers of cortex were imaged in vivo using intravital
multiphoton microscopy through a craniotomy sealed with a glass coverslip [31]
(Fig. 16.5).
Stem cell transplantation has shown promise in therapeutic treatment strategies
for CNS disorders and injuries; however, there is no definitive model for evaluating
stem cell graft survival and interaction with the CNS environment postimplantation