Photoacoustic and Ultrasound Imaging with Nanosized Contrast Agents - Nanotechnology for Biomedical Imaging and Diagnostics - page 292

intact internal organs (e.g., spleen, liver, kidney, and major blood vessels) in a nude
mouse in vivo [71].
Various functional parameters, such as the total hemoglobin concentration (HbT),
oxygen saturation of hemoglobin (So 2 ), blood flow, and metabolic rate of oxygen
consumption (Mro 2 ), can be directly measured by PAT using only intrinsic contrast
[60]. Label-free PAT is the only available imaging modality that can solely provide
all these information in vivo . These variables can be used to study brain hemody-
namic and activation, tumor hypermetabolism, wound healing process, and gene
expression.
Both vessel-by-vessel mapping of HbT and So 2 can be photoacoustically acquired
by considering that the two types of hemoglobin are dominant absorbers in tissues
and have different molar extinction spectra. Because the initial PA amplitudes are
proportional to the local energy deposition, the absorption coefficient can be replaced
with the measured PA amplitude. At the isosbestic light wavelengths, where oxyhe-
moglobin and deoxyhemoglobin have the same molar extinction coefficients, the PA
contrast is only sensitive to HbT. Further, to measure So 2 , the concentration of each
type of hemoglobin needs to be estimated by using at least two optical wavelengths.
As another parameter, the transverse blood flow velocity can be photoacoustically
measured by using PA doppler bandwidth broadening. If one uses all aforementioned
photoacoustically measured parameters, Mro 2 can be calculated, a measurement of
the rate of direct oxygen consumption within a region of interest (roI). With the
well-defined input and output blood vessels within the roI, Mro 2 can be estimated
as follows:

( )

MRO bT SO =× × ε × ×− ×× AV AVW SO / (10.2)

2 2 - in in in 2 - out out out

where ε is the constant oxygen binding capacity of hemoglobin (1.36 ml o 2 /g hemo-
globin), HbT is the total hemoglobin concentration (in grams of hemoglobin/ml
blood), So 2 is the oxygen saturation of hemoglobin (in %), A is the cross-sectional
area (in mm 2 ) of the blood vessels, V is the blood flow speed (in mm/s), and W is the
weight of the roI (in grams). Further, oxygen extraction fraction (oEF), defined as

( )

SO − SO

2 - in 2 - out

SO

2 - in

can be calculated by PAT. oEF represents the fraction of oxygen molecules across
the capillary wall. Figure 10.5 shows metabolic PA measurements of U87 glio-
blastoma xenograft in a nude mouse in vivo . Early-stage tumor hyperoxia and
angiogenesis were observed (Fig. 10.5b and c). PA quantification of blood flow,
oEF, and Mro 2 was compared between 0 and 7 days after tumor inoculation
(Fig. 10.5d). Furthermore, the PA So 2 values were quantified within the intra- and
extratumoral vasculatures (Fig. 10.5e). These results prove that PAT is the perfect
imaging modality to quantify the functional parameters of biological tissues in
various diseases.