An infrared (IR) camera system has been developed for use in pleural photodynamic therapy (PDT). This system was
introduced to pleural PDT to provide uniform light dose distribution to ensure predictable PDT outcome. Light is
delivered through a fiber that is in an endotracheal (ET) tube filled with Intralipid as scattering media. A tracking tool is
attached to the ET tube to monitor the position of the optical fiber based point source. An anisotropic light distribution
model is introduced to correct the angle dependent light distribution due to a capped end by design of the ET tube, which
scatters light differently than the sides. In this study, the anisotropic nature of the balloon was characterized and
incorporated into the calculation for light fluence during treatment. This model is verified by the light dose calculation
from a phantom study. Furthermore, a new tracking tool was designed with multiple faces to increase the angular field of
view and thus collect more viable data during treatment. The new tracking tool is directly entered into the ET tube with
the light delivering fiber, thus eliminating the need to calibrate the laser source position prior to treatment via an
optimization method. With this improved system, the calculated light fluence and the measured isotropic detector
readings are more accurately matched.
Photosensitizer fluorescence emitted during photodynamic therapy (PDT) is of interest for monitoring the local concentration of the photosensitizer and its photobleaching. In this study, we use Monte Carlo (MC) simulations to evaluate the relationship between treatment light and fluorescence, both collected by an isotropic detector placed on the surface of the tissue. In treatment of the thoracic and peritoneal cavities, the light source position changes continually. The MC program is designed to simulate an infinitely broad photon beam incident on the tissue at various angles to determine the effect of angle. For each of the absorbed photons, a fixed number of fluorescence photons are generated and traced. The theoretical results from the MC simulation show that the angle theta has little effect on both the measured fluorescence and the ratio of fluorescence to diffuse reflectance. However, changes in the absorption and scattering coefficients, μa and μ's do cause the fluorescence and ratio to change, indicating that a correction for optical properties will be needed for absolute fluorescence quantification. Experiments in tissue-simulating phantoms confirm that an empirical correction can accurately recover the sensitizer concentration over a physiologically relevant range of optical properties.
Photodynamic therapy (PDT) offers a cancer treatment modality capable of providing minimally invasive localized
tumor necrosis. To accurately predict PDT treatment outcome based on pre-treatment patient specific parameters, an
explicit dosimetry model is used to calculate apparent reacted 1O2 concentration ([1O2]rx) at varied radial distances
from the activating light source inserted into tumor tissue and apparent singlet oxygen threshold concentration for
necrosis ([1O2]rx, sd) for type-II PDT photosensitizers. Inputs into the model include a number of photosensitizer
independent parameters as well as photosensitizer specific photochemical parameters ξ σ, and β. To determine the
specific photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were treated with BPDPDT
with varied light source strengths and treatment times. All photosensitizer independent inputs were assessed
pre-treatment and average necrotic radius in treated tissue was determined post-treatment. Using the explicit
dosimetry model, BPD specific ξ σ, and β photochemical parameters were determined which estimated necrotic
radii similar to those observed in initial BPD-PDT treated mice using an optimization algorithm that minimizes the
difference between the model and that of the measurements. Photochemical parameters for BPD are compared with
those of other known photosensitizers, such as Photofrin. The determination of these BPD specific photochemical
parameters provides necessary data for predictive treatment outcome in clinical BPD-PDT using the explicit
The ability to deliver uniform light dose in Photodynamic therapy (PDT) is critical to treatment efficacy. Current
protocol in pleural photodynamic therapy uses 7 isotropic detectors placed at discrete locations within the pleural cavity
to monitor light dose throughout treatment. While effort is made to place the detectors uniformly through the cavity,
measurements do not provide an overall uniform measurement of delivered dose. A real-time infrared (IR) tracking
camera is development to better deliver and monitor a more uniform light distribution during treatment. It has been
shown previously that there is good agreement between fluence calculated using IR tracking data and isotropic detector
measurements for direct light phantom experiments. This study presents the results of an extensive phantom study which
uses variable, patient-like geometries and optical properties (both absorption and scattering). Position data of the
treatment is collected from the IR navigation system while concurrently light distribution measurements are made using
the aforementioned isotropic detectors. These measurements are compared to fluence calculations made using data from
the IR navigation system to verify our light distribution theory is correct and applicable in patient-like settings. The
verification of this treatment planning technique is an important step in bringing real-time fluence monitoring into the
clinic for more effective treatment.
Photodynamic therapy (PDT) is an important treatment modality for cancer and other localized diseases. In addition to
PDT dose, singlet oxygen (1O2) concentration is used as an explicit PDT dosimetry quantity, because 1O2 is the major
cytotoxic agent in photodynamic therapy, and the reaction between 1O2 and tumor tissues/cells determines the treatment
efficacy. 1O2 concentration can be obtained by the PDT model, which includes diffusion equation for the light transport
in tissue and macroscopic kinetic equations for the generation of the singlet oxygen. This model was implemented using
finite-element method (FEM) by COMSOL. In the kinetic equations, 5 photo-physiological parameters were determined
explicitly to predict the generation of 1O2. The singlet oxygen concentration profile was calculated iteratively by
comparing the model with the measurements based on mice experiments, to obtain the apparent reacted 1O2concentration as an explicit PDT dosimetry quantity. Two photosensitizers including Photofrin and BPD Verteporfin,
were tested using this model to determine their photo-physiological parameters and the reacted 1O2 concentrations.
A light blanket is designed with a system of cylindrically diffusing optical fibers, which are spirally oriented. This 25x30
cm rectangular light blanket is capable of providing uniform illumination during intraoperative photodynamic therapy.
The flexibility of the blanket proves to be extremely beneficial when conforming to the anatomical structures of the
patient being treated. Previous tests of light distribution from the blanket have shown significant loss of intensity with
the length of the fiber. This can be improved through the use of an optical adaptor which will be able to match the
numerical aperture of the laser source to the numerical aperture of the blanket fiber; thus transmitting a higher
percentage of light.
Photodynamic therapy (PDT) is an important treatment modality for localized diseases such as prostate cancer. In
prostate PDT, light distribution is an important factor because it is directly related to treatment efficacy. During PDT,
light distribution is determined by tissue optical property distributions (or heterogeneity). In this study, an interstitial
diffuse optical tomography (iDOT) method was used to characterize optical properties in tissues. Optical properties
(absorption and reduced scattering coefficients) of the prostate gland were reconstructed by solving the inverse problem
using an adjoint model based on diffusion equation using a modified matlab public user code NIRFAST. In the modified
NIRFAST method, linear sources were modeled for the reconstruction. Cross talking between absorption coefficients
and reduced scattering coefficients were studied to have minimal effect, and a constrained optical property method (set
either absorption coefficient or reduced scattering coefficient to be homogeneous) is also studied. A prostate phantom
with optical anomalies was used to verify the iDOT method. The reconstructed results were compared with the known
optical properties, and the spatial distribution of optical properties for this phantom was successfully reconstructed.
Intrapleural photodynamic therapy (PDT) has been used as an adjuvant treatment with lung-sparing surgical treatment
for mesothelioma. In the current intrapleural PDT protocol, a moving fiber-based point source is used to deliver the light
and the light dose are monitored by 7 detectors placed in the pleural cavity. To improve the delivery of light dose
uniformity, an infrared (IR) camera system is used to track the motion of the light sources. A treatment planning system
uses feedback from the detectors as well as the IR camera to update light fluence distribution in real-time, which is used
to guide the light source motion for uniform light dose distribution. We have reported previously the success of using IR
camera to passively monitor the light fluence rate distribution. In this study, the real-time feedback has been
implemented in the current system prototype, by transferring data from the IR camera to a computer at a rate of 20 Hz,
and by calculation/displaying using Matlab. A dual-correction method is used in the feedback system, so that fluence
calculation can match detector readings. Preliminary data from a phantom showed superior light uniformity using this
method. Light fluence uniformity from patient treatments is also shown using the correction method dose model.
Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable
PDT outcome. However, common practice uses a point source to deliver light to the pleural cavity with the light
uniformity monitored by 7 detectors placed within the pleural cavity. To improve the uniformity of light fluence rate
distribution, we have used a real-time infrared (IR) tracking camera to track the movement of the light point source. The
same tracking device is used to determine the surface contour of the treatment area. This study examines the light
fluence (rate) delivered between the measurement and calculation in phantom studies. Isotropic detectors were used for
in-vivo light dosimetry. Light fluence rate in the pleural cavity is calculated and compared with the in-vivo calculation.
Phantom studies show that the surface contour can be determined with an accuracy of 2 mm, with maximum deviation of
5 mm. We can successfully match the calculated light fluence rates with the in-vivo measurements. Preliminary results
indicate that the light fluence rate can have up to 50% deviation compared to the prescription in phantom experiments.
The IR camera has been used successfully in pleural PDT patient treatment to track the motion of light source in realtime.
We concluded that it is feasible to develop an IR camera based system to guide the motion of the light source to
improve the uniformity of light distribution.
Magnetomotive microscopy techniques are introduced to investigate cell dynamics and biomechanics. These techniques
are based on magnetomotive transducers present in cells and optical coherence imaging techniques. In this study,
magnetomotive transducers include magnetic nanoparticles (MNPs) and fluorescently labeled magnetic microspheres,
while the optical coherence imaging techniques include integrated optical coherence (OCM)and multiphoton (MPM)
microscopy,and diffraction phase microscopy (DPM). Samples used in this study are murine macrophage cells in culture
that were incubated with magnetomotive transducers. MPMis used to visualize multifunctional microspheres based on
their fluorescence, while magnetomotive OCM detects sinusoidal displacements of the sample induced by a magnetic
field. DPM is used to image single cells at a lower frequency magnetic excitation, and with its Fourier transform light
scattering (FTLS) analysis, oscillation amplitude is obtained, indicating the relative biomechanical properties of
macrophage cells. These magnetomotive microscopy method shave potential to be used to image and measure cell
dynamics and biomechanical properties. The ability to measure and understand biomechanical properties of cells and
their microenvironments, especially for tumor cells, is of great importance and may provide insight for diagnostic and
subsequently therapeutic interventions.
Dynamic optical coherence elastography, an emerging optical technique to measure material mechanical properties using
the non-invasive imaging modality of optical coherence tomography is introduced. Dynamic mechanical excitations were
applied to the samples while a spectral domain optical coherence tomography system was used for detection. Based on a
simple mechanical model, material mechanical properties such as Young's moduli can be extracted from detected phaseresolved
signals. Biological tissues and their biomechanical properties are currently the main objects for this technique
due to its micron-scale resolution and relatively deep penetration. Quantitative results were achieved by this technique on
tissue phantoms and rat tumor tissues. Different excitation approaches and applications for dynamic optical coherence
elastography are also discussed.
Mechanical forces play crucial roles in tissue growth, patterning and development. To understand the role of mechanical
stimuli, biomechanical properties are of great importance, as well as our ability to measure biomechanical properties of
developing and engineered tissues. To enable these measurements, a novel non-invasive, micron-scale and high-speed
Optical Coherence Elastography (OCE) system has been developed utilizing a titanium:sapphire based spectral-domain
Optical Coherence Tomography (OCT) system and a mechanical wave driver. This system provides axial resolution of
3 microns, transverse resolution of 13 microns, and an acquisition rate as high as 25,000 lines per second. External lowfrequency
vibrations are applied to the samples in the system. Step and sinusoidal steady-state responses are obtained to
first characterize the OCE system and then characterize samples. Experimental results of M-mode OCE on silicone
phantoms and human breast tissues are obtained, which correspond to biomechanical models developed for this analysis.
Quantified results from the OCE system correspond directly with results from an indentation method from a commercial.
With micron-scale resolution and a high-speed acquisition rate, our OCE system also has the potential to rapidly
measure dynamic 3-D tissue biomechanical properties.