Nanoparticles as Contrast Agents for Optoacoustic Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 112

the formation of new blood vessels, and noninvasive OAT of tumor angiogenesis
could play a fundamental role in many aspects of preclinical research and for
cancer patient management [44-46]. OA imaging capability for imaging blood
vessels in highly scattering samples was demonstrated in 1998 [47]. The authors
have shown that the sensitivity of this technique could reach single red blood cell
detection on a glass plate. Later OA images of tumor neovascularization were
obtained in dynamic state after subcutaneous inoculation of pancreatic tumor
cells in rats [35]. 3D datasets were acquired to visualize the development of the
blood vessels as well as to quantify the extent of individual blood vessels around
the growing tumor and measure the blood concentration changes inside the
tumor [35].

5.2.2 melanin

The melanin layer serves as an optical gradient filter for sunlight, strongly absorbing
ultraviolet and allowing sufficient transmission of visible light while modestly
absorbing NIR due to its small thickness. In addition to hemoglobin, melanin is
another primary absorber in tissue featuring a broad absorption spectrum [48, 49]
that provides a strong absorption contrast for OA imaging [11]. OA imaging with
melanin is mainly used for the diagnosis, prognosis, and treatment planning of mel-
anotic melanoma (>90% of all melanomas) [50]. The combination of hemoglobin
and melanin can be used for more accurate detection of melanomas, because more
parameters can be measured. Dual-wavelength reflection-mode OA imaging has
been developed to noninvasively obtain 3D images of subcutaneous melanomas and
their surrounding vasculature in living nude mice [50]. At the two wavelengths used
for hemoglobin and melanin, 584 and 764 nm, respectively, the absorption coeffi-
cients of blood and melanin-pigmented melanomas vary greatly relative to each
other. In vivo OA imaging with a 764 nm light source was able to image the 3D mel-
anin distribution inside the skin to a maximum thickness of 0.5 mm of melanoma. In
another study, OAT was reported to be capable of detecting melanoma cells within
the human circulation system [51, 52].
several OA imaging applications are focused on tyrosinase, an enzyme respon-
sible for melanin production in melanogenic cells, such as melanocytes. In addition
to melanogenic cells, tyrosinase can be introduced into nonmelanogenic cells result-
ing in their pigmentation [53]. This effect was successfully used in the development
of OA imaging focused on melanin-induced contrast [54]. Tyrosinase was used as a
reporter gene, yielding melanin contrast for OAT in vivo [55]. In this study, the
expression of melanin in cells was variable and depended on the efficiency of trans-
fection, with some cells producing little melanin. Despite the fact that the extinction
coefficient of melanin was lower than that of hemoglobin for the wavelengths
studied, and despite the variable expression, there was enough melanin production in
the transfected cells to increase concentration to detectable levels [55]. figure 5.3
shows the estimated melanin concentration in a mouse model (ear) demonstrating
that tyrosinase-derived melanin sufficiently increases the contrast for visualization
of normally nonmelanogenic in vivo [55].