Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 469

Postarthroplasty infection models using bioluminescent Staphylococcus aureus
have shown success in determining bacterial load within the joint. S. aureus is an
advantageous bacterium, which given the opportunity will spread and cause a poten-
tially serious infection. During orthopedic surgery, complications can arise with post-
arthroplasty infections caused by S. aureus during both acute and chronic recovery
periods. Acute postarthroplasty infections are less severe and are more amenable to
treatment. Treatment of chronic infections is much more difficult and often requires
reoperation, which can lead to prolonged disability and require extended antibiotics
[22]. In cases where biomaterials or devices are implanted, the infection can adhere to
the implant, creating a biofilm that prevents immune cells or antibiotics to penetrate.
Using bioluminescent bacterial agents, the pathogenesis of the infection can be tracked
and the bacterial burden can be determined over time.
In research, the advantage of in vivo bioluminescence is the ability to have the
animal survive and allow for longitudinal quantification of bacterial burden as
opposed to performing multiple histologic analyses. This allows for reduction of
overall animal numbers as well as for valuable animals to be evaluated over time.
optical imaging of bacterial infection in animal models also has been demonstrated
using fluorescent contrast agents that specifically target the bacteria. Yersinia pestis
(black plague) infection has been reoccurring for centuries and has never been fully
eradicated. Recently, bioluminescence has been used to monitor microbial dissemina-
tion in infected animals, in vivo , without the need to sacrifice animals to determine
infection [23]. The ability to monitor bacterial dissemination with bioluminescents
creates a successful noninvasive procedure that is comparable to viable plate counts.
Combining both bioluminescent and fluorescent optical imaging using microCT
and X-ray has shown the ability to provide noninvasive and longitudinal measurements
of the dynamic changes in bacterial burden, neutrophil recruitment, and bone damage
in a mouse orthopedic implant infection model [24]. Combining information from
both optical and structural imaging allows for the observation of biological process in
a 3D model. With these dual modalities, the accuracy of the images increases, as well
as the precision of the measurements for pathological changes.
16.4.4.2 Fungal Infections Diagnoses of fungal infections associated with immu-
nocompromised patients has increased over the last several decades, but the number
of effective antifungal drugs remains relatively unchanged and limited. Resistance to
these drugs is becoming an increasing concern, and there is an increasing demand for
new antifungal treatments. In addition, little progress has been made toward finding
new modalities to detect fungal infections and identify regression of the disease.
Candida albicans is the most common fungal infection in people and can progress
to disseminated candidiasis. Fifty percent of these cases progress to the CNS leading
to a 90% mortality rate. Disseminated candidiasis is a fungal infection that can be
modeled in mice and typically targets the kidneys and brain, but can also affect other
viscera such as the liver, spleen, and heart [25]. The infection has shown the ability to
deteriorate the blood-brain barrier (BBB), which can lead to fungal meningoenceph-
alitis. An MRI following the injection of gadolinium-diethylenetriaminepentaacetic
acid (Gd-DTPA) demonstrated that the integrity of the BBB was lost during the fungal