We report a second derivative multispectral algorithm for quantitative assessment of cutaneous tissue oxygen saturation (StO2). The algorithm is based on a forward model of light transport in multilayered skin tissue and an inverse algorithm for StO2 reconstruction. Based on the forward simulation results, a parameter of a second derivative ratio (SDR) is derived as a function of cutaneous tissue StO2. The SDR function is optimized at a wavelength set of 544, 552, 568, 576, 592, and 600 nm so that cutaneous tissue StO2 can be derived with minimal artifacts by blood concentration, tissue scattering, and melanin concentration. The proposed multispectral StO2 imaging algorithm is verified in both benchtop and in vivo experiments. The experimental results show that the proposed multispectral imaging algorithm is able to map cutaneous tissue StO2 in high temporal resolution with reduced measurement artifacts induced by different skin conditions in comparison with other three commercial tissue oxygen measurement systems. These results indicate that the multispectral StO2 imaging technique has the potential for noninvasive and quantitative assessment of skin tissue oxygenation with a high temporal resolution.
Quantitative assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate detection, staging, and treatment of chronic wounds. However, few methods are available for simultaneous assessment of these tissue parameters in a noninvasive and quantitative fashion. We integrated hyperspectral, laser speckle, and thermographic imaging modalities in a single-experimental setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation characteristics. Algorithms were developed for appropriate coregistration between wound images acquired by different imaging modalities at different times. The multimodal wound imaging system was validated in an occlusion experiment, where oxygenation and perfusion maps of a healthy subject’s upper extremity were continuously monitored during a postocclusive reactive hyperemia procedure and compared with standard measurements. The system was also tested in a clinical trial where a wound of three millimeters in diameter was introduced on a healthy subject’s lower extremity and the healing process was continuously monitored. Our in vivo experiments demonstrated the clinical feasibility of multimodal cutaneous wound imaging.
The wound healing process involves the reparative phases of inflammation, proliferation, and remodeling. Interrupting
any of these phases may result in chronically unhealed wounds, amputation, or even patient death. Quantitative
assessment of wound tissue ischemia, perfusion, and inflammation provides critical information for appropriate
detection, staging, and treatment of chronic wounds. However, no method is available for noninvasive, simultaneous,
and quantitative imaging of these tissue parameters. We integrated hyperspectral, laser speckle, and thermographic
imaging modalities into a single setup for multimodal assessment of tissue oxygenation, perfusion, and inflammation
characteristics. Advanced algorithms were developed for accurate reconstruction of wound oxygenation and appropriate
co-registration between different imaging modalities. The multimodal wound imaging system was validated by an
ongoing clinical trials approved by OSU IRB. In the clinical trial, a wound of 3mm in diameter was introduced on a
healthy subject’s lower extremity and the healing process was serially monitored by the multimodal imaging setup. Our
experiments demonstrated the clinical usability of multimodal wound imaging.
Optical imaging has the potential to achieve high spatial resolution and high functional sensitivity in wound
assessment. However, clinical acceptance of many optical imaging devices is hampered by poor reproducibility, low
accuracy, and lack of biological interpretation. We developed an in vivo model of ischemic flap for non-contact
assessment of wound tissue functional parameters and spectral characteristics. The model was created by elevating
the bipedicle skin flaps of a domestic pig from the underlying vascular bed and inhibiting graft bed reperfusion by a
silastic sheet. Hyperspectral imaging was carried out on the ischemic flap model and compared with transcutaneous
oxygen tension and perfusion measurements at different positions of the wound. Hyperspectral images have also
been captured continuously during a post-occlusive reactive hyperemia (PORH) procedure. Tissue spectral
characteristics obtained by hyperspectral imaging correlated well with cutaneous tissue oxygen tension, blood
perfusion, and microscopic changes of tissue morphology. Our experiments not only demonstrated the technical
feasibility for quantitative assessment of chronic wound but also provided a potential digital phantom platform for
quantitative characterization and calibration of medical optical devices.
Temperature distribution is a crucial factor in determining the outcome of laser phototherapy in cancer treatment. Magnetic resonance imaging (MRI) is an ideal method for 3-D noninvasive temperature measurement. A 7.1-T MRI was used to determine laser-induced high thermal gradient temperature distribution of target tissue with high spatial resolution. Using a proton density phase shift method, thermal mapping is validated for in vivo thermal measurement with light-absorbing enhancement dye. Tissue-simulating phantom gels, biological tissues, and tumor-bearing animals were used in the experiments. An 805-nm laser was used to irradiate the samples, with laser power in the range of 1 to 3 W. A clear temperature distribution matrix within the target and surrounding tissue was obtained with a specially developed processing algorithm. The temperature mapping showed that the selective laser photothermal effect could result in temperature elevation in a range of 10 to 45°C. The temperature resolution of the measurement was about 0.37°C with 0.4-mm spatial resolution. The results of this study provide in vivo thermal information and future reference for optimizing laser dosage and dye concentration in cancer treatment.
The selective photothermal-tissue interaction using dye enhancement has been proven to be effective in
minimizing the peripheral normal tissue damage during cancer treatment. It is important that the tissue-thermal
damage be analyzed and the damage rate process be estimated before the photothermal-immunotherapy
for cancer treatment. In this study, we have used the EMT6 mouse tumor model for the
laser-tumor treatment with a simultaneous surface temperature measurement using infrared thermography.
The images acquired were processed to obtain the temperature profiles. The saturation temperature and
corresponding time of irradiation from the temporal profiles were used to calculate the damage parameter
using Arrhenius rate process equation. The damage parameters obtained from six mice were compared. Our
results of in vivo study show that the damage analyses agree with the previous in vitro study on skins.
An ideal cancer treatment method should not only cause primary tumor suppression but also induce an
antitumor immunity, which is essential for control of metastatic tumors. A combination therapy using a
laser, a laser-absorbing dye, and an immunoadjuvant guided by temperature measurement probes such as
magnetic resonance imaging thermometry (MRT) and infrared thermography (IRT) can be an ideal treatment
modality. Temperature distribution inside the target tissue is important in laser treatment. The surface
temperature often serves as an indicator of the treatment effect. However, real-time monitoring of surface
temperature during laser irradiation poses a great challenge. In this study, we investigated the surface
temperature distribution using direct measurement and theoretical simulation. The preliminary results of in
vitro and in vivo studies are presented. Gel phantom and chicken breast tissue were irradiated by an 805 nm
laser and the surface temperature distribution was obtained using an infrared thermal camera. EMT-6 breast
tumors in mice were treated using the 805 nm laser and with different dye and immunoadjuvant
combinations, including intratumor injections of indocyanine green (ICG) and glycated chitosan (GC).
Monte Carlo simulation for selective photothermal-tissue interaction was also performed for the surface
temperature distributions. Our results demonstrated that the tissue temperature can be accurately monitored
in real time and can be controlled by appropriate treatment parameters.
In cancer treatment and immune response enhancement research, Magnetic Resonance Imaging (MRI) is an
ideal method for non-invasive, three-dimensional temperature measurement. We used a 7.1-Tesla magnetic
resonance imager for ex vivo tissues and small animal to determine temperature distribution of target tissue
during laser irradiation. The feasibility of imaging is approved with high spatial resolution and high signal-noise-
ratio. Tissue-simulating gel phantom gel, biological tissues, and tumor-bearing animals were used in
the experiments for laser treatment and MR imaging. Thermal couple measurement of temperature in target
samples was used for system calibration. An 805-nm laser was used to irradiate the samples with a laser
power in the range of 1 to 2.5 watts. Using the MRI system and a specially developed processing algorithm,
a clear temperature distribution matrix in the target tissue and surrounding tissue was obtained. The
temperature profiles show that the selective laser photothermal effect could result in tissue temperature
elevation in a range of 10 to 45 °C. The temperature resolution of the measurement was about 0.37°C
including the total system error. The spatial resolution was 0.4 mm (128x128 pixels with field of view of
5.5x5.5 cm). The temperature distribution provided in vivo thermal information and future reference for
optimizing dye concentration and irradiation parameters to achieve optimal thermal effects in cancer
A highly accurate, fast three-dimensional in vivo temperature mapping method is developed using MRI water photon chemical shift. It is important to have the precise temperature distribution information during laser-tissue thermal treatment. Several methods can be used for temperature measurement including thermal couple, optical fiber sensor, and MRI (magnetic resonance imaging) methods. MRI is the only feasible method for 3D in vivo, non-invasive temperature distribution measurement for laser-tissue interaction. The water proton chemical shift method is used in 3D MRI mapping. Varies MRI parameters, such as flip angle, TE, TR, spatial resolution, and temporal repetition, were optimized for the temperature mapping. The laser radiation of 805nm wavelength and a light-absorbing dye, indocyanine green (ICG) was used for temperature elevation. The measurement was conducted using gel phantom, chicken tissue and rats. The phantom system was constructed with a dye-enhanced spherical gel embedded in uniform gel phantom, simulating a tumor within normal tissue. The normal temperature elevation within ex vivo tissue such as chicken breast can reach up to 45-50 degree C with a power density of 1.3W/cm2 (with laser power of 3W and 1.7cm beam size). The temperature resolution is 0.37 degree C with a 0.2-mm spatial resolution and repetition rate of around 40 seconds. The external magnetic field drift effect is also evaluated.
Selective photothermal interaction using dye enhancement has proven to be effective in minimizing surrounding tissue damage and delivering energy to target tissue. During laser irradiation, the process of photon absorption and thermal energy diffusion in the target tissue and its surrounding tissue are crucial. Such information allows the selection of proper operating parameters such as dye concentrations, laser power, and exposure time for optimal therapeutic effect. Combining the Monte Carlo method for energy absorption and the finite difference method for heat diffusion, the temperature distributions in target tissue and surrounding tissue in dye enhanced laser photothermal interaction are obtained. Different tissue configurations and dye enhancement are used in the simulation, and different incident beam sizes are also used to determine optimum beam sizes for various tissue configurations. Our results show that the algorithm developed in this study could predict the thermal outcome of laser irradiation. Our simulation indicates that with appropriate absorption enhancement of the target tissue, the temperature in the target tissue and in the surrounding tissue can be effectively controlled. This method can be used for optimization of lesion treatment using laser photothermal interactions. It may also provide guidance for laser immunotherapy in cancer treatment, since the immunological responses are believed to be related to tissue temperature changes.
Temperature distribution in tissue can be a crucial factor in laser treatment for inducing immunization responses. In this study, Magnetic Resonance Imaging (MRI) was used to measure thermal temperature distribution in target tissue in laser treatment of metastatic tumors. It is the only feasible method for in vivo, non-invasive temperature distribution measurement. The measurement was conducted using phantom gel and tumor-bearing rats. The thermal couple measurement of target temperature was also was used to
calibrate the relative temperature increase. The phantom system was constructed with a dye-enhanced spherical gel embedded in uniform gel phantom, simulating a tumor within normal tissue. Irradiation by an
805-nm laser increased the system temperature. Using an MRI system and proper algorithm processing for small animal studies, a clear temperature distribution matrix was obtained. The temperature profiles of rat tumors, irradiated by the laser with a power in the range of 2-3.5W and injected with a light-absorbing dye, ICG, and an immunoadjuvant, GC, were obtained. The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to reach the
optimum tumor destruction and immunization effects.