Three-Dimensional Optical-Resolution Photoacoustic Microscopy - Biomedical Optical Imaging Technologies: Design and Applications - page 73

physiological, pathophysiological, and clinical studies. Here, we only highlight
the longitudinal monitoring capability of OR-PAM, which enables real-time study
of disease progression and drug functioning. More biomedical applications of
OR-PAM can be found in the literature [ 8 , 10 , 11 , 13 , 16 , 31 ].
For technical demonstration, OR-PAM monitored the healing process of
a laser-induced microvascular lesion in a mouse ear model [ 9 ]. Commercial
transmission-mode optical microscopy was also used to monitor the same process,
as a reference to OR-PAM. At the beginning of the chronic imaging, a 1 1 mm 2
ROI in the mouse ear (Hsd:Athymic Nude-Foxn 1 NU , Harlan; body weight: 25 g)
was selected and photographed by the transmission-mode optical microscope,
after which the ROI was imaged by dual wavelengths (570 and 578 nm) OR-
PA M [ F i g . 2.11 A]. Then, we switched to a continuous-wave laser (MGL-III-532,
Changchun New Industries; output power: 150 mW, wavelength: 532 nm), removed
the pinhole, and scanned the central part of the ROI (0:25 0:25 mm 2 ) with the
focused laser beam (diameter: 30 m) for 10 min to create a microvascular
lesion. The ROI was imaged immediately after the laser destruction [Fig. 2.11 B]
and in the subsequent 12 days [Fig. 2.11 C-1 to C-12]. Our results clearly show
a four-step wound healing process that has been documented in physiology
topics [ 32 ]:
1. Vessel regression and hemostasis occurred right after the laser destruction
[Fig. 2.11 B].
2. Vasodilation was induced by inflammation 1 day after the injury and lasted for
about 5 days [Figs. 2.11 C-1 to C-5]. Tissue hypoxia occurred right after the laser
destruction to trigger angiogenesis [Figs. 2.11 BandC-1toC-5].
3. The ingrowth of neocapillaries started to restore the microcirculation 3 days after
the wound occurred [Fig. 2.11 C-3].
4. The damaged arteriole-venule pair recovered morphologically and functionally
after 12 days [Fig. 2.11 C-12].
Note that, as an enabling technology for noninvasive label-free longitudinal
monitoring of microhemodynamics, OR-PAM has potentially broader applications.
In vascular physiological study, OR-PAM can help understand the signaling path-
way of vascular regulation by perturbing the pathway and monitor the consequential
anatomical and functional changes [ 31 ]. In cancer research, OR-PAM can monitor
tumor neovascularization and evaluate cancer therapy. In vascular-related drug
development, OR-PAM can trace drug functioning and evaluate drug efficacy.
In laser microsurgery, surgical lasers can be readily integrated with OR-PAM
to perform on-site high-precision microsurgery with presurgery diagnosis and
postsurgery evaluation. In neuroscience, the minimally invasive feature of OR-PAM
is ideal for chronic studies of cortical plasticity and neurovascular coupling at the
capillary level.