Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 467

investigation of cancer-inducing genes and targeted therapy. It has been known for
years that viral infections can result in tumor development. Recently, immunization
against HPV has been recommended for women to prevent HPV-induced cervical
cancer. Some preclinical cancer models have since been developed, which involve
viral infections that result in cancer formation. These models do not include the
potential for genetic engineering through viral vectors to introduce oncogenes. In
general, viral-induced cancer development is used to investigate early stages of
cancer development as the progression from dysplasia to neoplasia and metastasis
can be monitored in the presence of a fully functioning immune system. These
models are fully nonhuman at this time, though humanized variants could be devel-
oped. Introduction of imaging reporter genes could enable detection of molecular
events during carcinogenesis.

16.4.3 Animal models for cardiovascular disease imaging

16.4.3.1 GEM/Diet and Surgical Modification/Injury Imaging of cardiovas-
cular disease primarily involves ischemic injury, atherosclerosis, cholesterol plaques,
and stroke. Stroke will be discussed in the neuroimaging Section “Imaging of the
nervous system” as it is more concerned with neurologic dysfunction.
In humans, atherosclerosis is commonly associated with poor diet and lack of
exercise, but often includes a genetic predisposition. Plaques develop presumably as
a result of inflammation of the arterial walls followed by cholesterol deposition and
further infiltration by white blood cells. Cholesterol deposition can constrict the
lumen of blood vessels and effectively block blood flow resulting in a “heart attack”
when coronary blood vessels are affected. Prolonged obstruction causes tissue
ischemia and loss of heart function.
Another sequela to cholesterol deposition is development of “unstable plaque” that
can release small fragments into the bloodstream or completely rupture with large
pieces breaking free. These fragments may lodge in smaller blood vessels with disas-
trous results, particularly if they block vessels in the brain (stroke). Thus, detection of
cholesterol plaques within vessels is an important goal in diagnosis of atherosclerosis.
Detection of unstable plaque is even more crucial in the diagnosis, therapy, and periodic
monitoring to prevent stroke. Unstable plaque can be modeled in animals by a two-step
injury process, which causes damage to the smooth muscle as well as endothelial lining
of a large blood vessel. Rabbits are most commonly used for this model, and the injury
is induced intravascularly, which can be difficult to perform in smaller animals.
This small size of blood vessels in animals makes imaging of plaques difficult as
well. MRI is used to diagnose atherosclerosis and to visualize cholesterol deposition
in humans and is therefore used predominantly in preclinical research. The resolution
of PET/CT is sufficiently low as to reduce the utility of this modality. Intravascular
ultrasound and optical imaging techniques are being developed to aid in diagnosis
and intervention as well and also requires large vessels. Due to the depth of lesions
and the relatively poor spatial resolution of optical imaging, most atherosclerotic
plaque imaging studies have utilized invasive, postmortem optical imaging or have
focused on peripheral models. Recently, atherosclerosis of the aortic arch has been
imaged using noninvasive diffuse optical tomography.