Presidential Greeting - American Society for Laser Medicine and ...

Background: The microvasculature is the primary route by
which nutrients are delivered to tissue. Direct visualization of the
microvasculature would enable detailed study of tissue during
disease progression. Typically, a histology-based approach is used
to characterize the microvasculature. This method is impractical
for characterization of the microvasculature in large tissue
organs, especially if the three-dimensional architecture of the
vascular network is desired. Therefore, there is a critical need for
a technique that will facilitate quick and efficient imaging of the
entire microvascular network of large tissue volumes. We have
developed an all-optical method that utilizes optical clearing of the
tissue and subsequent optical imaging to produce high-resolution,
depth-sectioned, three-dimensional images of the
microvasculature in thick tissues.
Study: Tissue microvasculature is first stained in vivo via cardiac
perfusion using DiI, a lipophilic dye that binds to the endothelial
cells of the microvasculature. Tissues are then excised and sliced
into 1 mm thick sections. These sections are incubated in
FocusClear (CelExplorer Labs, Hsinchu, Taiwan), a novel optical
clearing agent, for up to 120 minutes, and then visualized with
both a CCD based wide-field fluorescence imaging system and a
laser-scanning multiphoton microscope with the appropriate
excitation wavelengths and emission filters for DiI.
Results: We have successfully acquired both fluorescence and
three-dimensional images of brain and tumor sections 1mm in
thickness using both our wide-field fluorescence imaging system
and confocal laser scanning fluorescence microscope. Arterioles,
venules, and capillaries are readily visualized.
Conclusion: Tissue microvasculature structure can be visualized
in three dimensions and with high spatial resolution, in 1mm
thick tissue sections, using combined ex vivo optical clearing and
optical imaging techniques. Imaging of serial sections of tissue is
expected to enable visualization of entire microvascular networks
in entire organs.
#27
American Society for Laser Medicine and Surgery Abstracts 9
PHOTOACOUSTIC DETECTION OF MELANOMA
AND MICROSPHERES IN VITRO USING A MICE
MODEL
Sagar Gupta, Kirby Campbell, Adam Daily, Kiran
Bhattacharya, Luis Parada, John Viator
University of Missouri, Columbia, MO
Background: Metastasis is a complex physiological phenomenon
that involves the movement of cancer cells from one organ to
another by means of blood and lymph. An understanding about
metastasis is extremely important to device diagnostic systems to
detect and monitor its spread within the body. Photoacoustic
technology is a sunrise sector, which is gaining prominence as the
promising field in medical diagnostics. This article makes an effort
to understand metastasis in a mouse model and also plays a
crucial role in extending the boundary of photoacoustic circulating
tumor cell detection in animals.
Study: Human cultured melanoma cell line HS936 and
2 micrometer fluorescent microspheres were injected through
cardiac puncture to the female ICR mice and allowed to circulate
from 1.5 to 10 min. A study was also performed to identify the
accumulation of melanoma and microspheres in various organs of
the injected mice.
Results: We were able to successfully detect 5-cells/10 ml of the
injected melanoma and 5-microspheres/10 ml of the injected
microspheres obtained from the processed mice blood drawn at
various time intervals in a photoacoustic ultrasound detection
system. After 10 minutes of circulation time a decreasing
photoacoustic signal was observed due to increased accumulation
of cells in the organs.
Conclusion: Histological studies identified that lungs were the
most susceptible organs for the accumulation of the injected
cancer cells and microspheres. We further intend to study the
photoacoustic detection of induced cancer in mice.
#28
MULTIDOMAIN SIMULATION OF MECHANICAL
TISSUE OPTICAL CLEARING DEVICES: A
PLATFORM FOR DEVICE OPTIMIZATION
William Vogt, Alondra Izquierdo-Roman,
Christopher Rylander
Virginia Tech, Blacksburg, VA
Background: Biological tissues are naturally high-scattering
media as a result of mismatches in refractive index between
constituents, including water, fat, and proteins. As a result, the
efficacy of light-based diagnostic and therapeutic methods is
drastically reduced. Tissue optical clearing devices (TOCDs)
utilize localized mechanical loading to induce optical clearing in a
non-invasive reversible manner. Mechanical clearing is thought
to be the result of lateral water displacement from compression
regions in the tissue, but the nature of this water transport and
resulting clearing effect is not well understood. A coupled
mathematical model of mechanical deformation and the transport
of water and light will provide a framework for optimizing TOCDs
for specific theranostic applications.
Study: Afinite element model of ex vivo porcine skin compressed
under a hemispherically tipped indenter was developed using
Abaqus (Simulia, Providence, RI). A coupled porous medium
model based on Darcy’s law was used to simulate the coupling
between mechanical stress/strain and interstitial water transport.
Experimental stress/strain data were used to fit a hyperelastic
constitutive model to govern tissue mechanical response. After
determining spatial distribution of tissue water content, optical
Monte Carlo simulation was used to determine tissue fluence
distribution. Simulation was performed using TIM-OS, an open
source Monte Carlo simulator.
Results: Simulations indicate that water transport during
compression is highly sensitive to Poisson’s ratio as well as tissue
hydraulic conductivity. Fluence distributions are highly sensitive
to scattering coefficient, which is dependent on both local water
content and wavelength of light delivered to the tissue. Tissue
geometry changes may account for 65% of total light
transmission increase, with optical property changes contributing
35%.
Conclusion: This multidomain modeling framework can be used
to study the coupling of mechanical loading, water transport, and
light transport through biological tissues. Future work will focus
on experimentally determining key input parameters, including
mechanical, chemical, and optical properties.
#29
SIGNAL VARIATION OF FLUORESCEIN DYE IN
ANTERIOR AND POSTERIOR CHAMBERS OF EYE
Raiyan Zaman, Henry Rylander
The University of Texas, Austin, TX
Background: Identifying the location of a drug for treating
ocular disease is an important aspect for any drug delivery. Thus,