Cerebral blood flow (CBF) dysregulation has been implicated in a wide variety of conditions. Cerebrovascular reactivity (CVR) to CO2 may be a biomarker of CBF dysregulation. NIRS-measured regional cerebral tissue oxygen saturation (rSO2) is a non-invasive measurement made with portable and relatively inexpensive devices. We previously reported that monitoring rSO2 can identify changes in cerebrovascular dynamics in response to hypercapnic breathing challenges. The present study builds on this work, employing rSO2 to characterize changes in CBF correlates during hypercapnic breathing challenges, with a new focus on correlations with NIRS-measured vital signs. A custom breathing circuit was used to deliver a series of hypercapnic breathing challenges and recovery periods to healthy young adult subjects grouped into three exercise factors. Change in rSO2 from intra- to pre-challenge (ΔrSO2) correlated positively with change in heart rate (ΔHRhyp). Athletes showed higher ∆HRhyp than casual and non-exercisers. We previously established that athletes showed higher ΔrSO2 responses to hypercapnic breathing challenges. While the relationships between ΔrSO2 and ΔHRhyp and change in end tidal CO2 (ΔPETCO2) in response to hypercapnic breathing challenges appears to be in tact in the healthy young adults studied, and more pronounced in athletes, these relationships may not be preserved in cases of compromised CVR. Change in respiration rate correlated negatively with ΔPETCO2. Establishing baseline values of rSO2, PETCO2, HR, and RR may be useful in identifying changes in an individual’s CVR. Combined monitoring of rSO2, PETCO2, HR, and RR presents a portable, inexpensive, noninvasive NIRS-based modality for detecting changes in cerebrovascular health.
Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions. Near-infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of interrogated cerebral volume useful in identifying variations in oxygen supply to cerebral tissue and in monitoring cerebrovascular function. CO2-inhalation-based hypercapnic breathing challenges were used to simulate CBF dysregulation, utilizing NIRS to monitor the CBF autoregulatory response. A breathing circuit was designed to administer CO2-compressed air mixtures and assess CBF regulatory responses to hypercapnia in 26 healthy young adults. One to three hypercapnic challenges of 5 or 10 min duration were delivered to each subject while continuously monitoring rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs. Change in rSO2 (ΔrSO2) during CO2 inhalation positively correlated to ΔPETCO2 (R2=0.40). Grouping subjects into three exercise factor levels (h/week), (1) 0, (2) >0 and <10, and (3) >10 showed significantly greater ΔrSO2 responses to CO2 challenges for level 3 subjects but similar PETCO2 responses for the three groups. Exercising greater than 10 h/week may produce a higher resting cerebrovascular reactivity (CVR) to CO2 inhalation. Establishing baseline values of rSO2 and CVR to CO2 may aid in early detection of CBF changes.
Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild
traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and
Alzheimer’s disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2)
provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes
in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation.
In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation,
and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of
CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy
young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3
hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end
tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge
(ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels
(hr/wk), 1: 0, 2:>0 and <10, and 3:>10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to
CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels.
Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.
Medical laser applications are promoted as safe, effective treatments for a multiplicity of concerns, ranging from hyperthermal skin rejuvenation to subcutaneous tumor ablation. Chromophore and structural protein concentration and distribution within a patient’s tissue vary from patient to patient and dictate the interaction of incident radiative energy of a specific wavelength with the target tissue. Laser parameters must be matched to tissue optical and thermal properties in order to achieve the desired therapeutic results without inducing unnecessary tissue damage, although accurate tissue optical properties are not always measured prior to and during laser therapies. A weighted variable step size Monte Carlo simulation of laser irradiation of skin tissue was used to determine the effects of variations in absorption (μa) and scattering coefficients (μs) and the degree of anisotropy (g) on the radiant energy transport per mm2 in response to steady-state photon propagation. The three parameters were varied in a factorial experimental design for the ranges of 0.25/mm ≤ μa ≤ 2.0/mm, 30.0/mm ≤ μs ≤ 140.0/mm, and 0.65 ≤ g ≤ 0.99 in order to isolate their impacts on the overall fluence distribution. Box plots of the resulting fluence profiles were created and compared to identify ranges in which optical property variance could be considered to significantly impact the spatial variance of fluence within the simulation volume. Results indicated that accurate prediction of the fluence profiles that will be achieved by any given medical laser treatment is unlikely without pre-treatment assessment of the tissue optical properties of individual patients.
Short pulse lasers are used for a variety of therapeutic applications in medicine. Recently ultra-short pulse lasers have gained prominence due to the reduction in collateral thermal damage to surrounding healthy tissue during tissue ablation. In this paper, ultra-short pulsed laser ablation of mouse skin tissue is analyzed by assessing the extent of damage produced due to focused laser beam irradiation. The laser used for this study is a fiber-based desktop laser (Raydiance, Inc.) having a wavelength of 1552 nm and a pulse width of 1.3 ps. The laser beam is focused on the sample surface to a spot size on the order of 10 microns, thus producing high peak intensity necessary for precise clean ablation. A parametric study is performed on in vitro mouse tissue specimens and live anaesthetized mice with mammary tumors through variation of laser parameters such as time-averaged laser power, repetition rate, laser scanning rate and irradiation time. Radial temperature distribution is measured using thermal camera to analyze the heat affected zone. Temperature measurements are performed to assess the peak temperature rise attained during ablation. A detailed histological study is performed using frozen section technique to observe the nature and extent of laser-induced damages.
Over the past few decades, many efforts were devoted to study low power laser and cellular interaction. Some of the
investigations were performed on cell populations. In this work fiber-optic based nano-probe is used for the precise
delivery of laser light on to a single cell and the mechanism of light interaction with the cell during irradiation was
studied. A human skin fibroblast cell line was utilized in this investigation. The human fibroblasts were irradiated under
two different schemes of exposure: (1) entire cell population was irradiated within a Petri dish using a fan beam, (2)
laser energy was precisely delivered on to a single cell using fiber-optic nano-probe. Studies were conducted by
variation of laser intensity, exposure time, and the energy dose of exposure. Proliferative effect of laser irradiation was
determined through cell counting for both exposure schemes. Enhancement of the rate of proliferation was observed to
be dependent on laser parameters and method of laser delivery. Variation of total energy dose had greater effect on the
enhancement of the rate of cellular proliferation compared to that of laser intensity. The photobiostimulative effect was
also observed to have a finite life-time. Fluorescent life-time imaging of reactive oxygen species (ROS) was performed
during the single cell exposure method. ROS generation was found to depend strongly on both laser energy doses and
irradiation time. It is demonstrated in this communication that by using specially engineered nano-probes, laser light can
be precisely delivered on to a targeted single cell.
The role of low light intensity in suppressing metabolic activity of transformed
cell lines was investigated through the applications of a 1,552nm wavelength pulsed
picosecond laser. Human malignant glioblastoma, human leukemia HL-60, and the NIH
3T3 cell lines were used. The cells were grown in 96 well plates and exposed in their
respective growth culture media with 10% (v/v) fetal bovine serum under various fluence
exposure conditions ranging from 0.115 - 100 J/cm2. All cell lines were exposed at a
constant average intensity value of 0.115 W/cm2; 25 kHz repetition rate with 1.6 micro-joule
per pulse; pulse duration = 2.93 picosecond. The human malignant glioblastoma
and the HL-60 cell lines exhibited a monotonic decline in metabolic activity (down 50 - 60%) relative to their respective sham exposed control counterparts between the fluence
values of 0.115 J/cm2 to 10 J/cm2. The NIH 3T3 cells exhibited a maximum suppression
of metabolic activity at the fluence value of 50 J/cm2. Metabolic activity was measured
through the colorimetric MTS metabolic assay. Interestingly, for all cell lines the
metabolic activity was found to return back to the sham exposed control levels as the
fluence of exposure was increased up to 100J/cm2.
The objective of this paper is to perform a comprehensive experimental and numerical analysis of the short pulse laser interaction with tissue medium with the goal of tumor / cancer diagnostics. For short pulse laser source, the shape of output signal is a function of the optical properties of the medium and hence the scattered temporal optical signal helps in understanding of the medium characteristics. Initially experiments are performed on tissue phantoms imbedded with inhomogeneities in order to optimize the time-resolved optical detection scheme. Both the temporal and the spatial profiles of the scattered reflected and transmitted optical signals are compared with the numerical modeling results obtained by solving the transient radiative transport equation using the discrete ordinates technique. Next experiments are performed on in vitro rat tissue samples to characterize the interaction of light with skin layers and to validate the time varying optical signatures with the numerical model. The numerical modeling results and the experimental measurements are in excellent agreement for the different parameters studied in this paper. The final step is to perform in vivo imaging of anaesthetized rats with tumor-promoting agents injected inside skin tissues in order to demonstrate the feasibility of the technique in detecting tumors in animal model.
With the development of femtosecond and shorter pulsewidth lasers and the ability to amplify these pulses to incredibly high pulsed power has come the ability to produce ultrashort pulses of x-rays. In previous years sessions of this conference we have proposed use of these ultrashort pulses of x-rays to produce high resolution, high image quality three dimensional x-ray images of breast and other areas of the body. Theoretical studies of the impact of increasing higher power of UV and X-Ray sources for sterilization lead us to question whether very short pulses of extremely high power (but low dose, i.e. J/cm2) may have less carcinogenic effect. If this is true, it could potentially allow greater use of such x-ray systems for breast cancer surveillance as well as other areas such as deep body inspection. In addition, it could allow for creation of better images by use of higher resolution, noise reduction and higher repetition rates. Better images should improve detection.
A pushbroom sensor motion control system was developed for use in conjunction with a pulsed laser fan beam, streak tube camera, and a high speed low light level camera . The LIDAR and camera control system was tested to study the influence of water waves upon active-passive remote sensing systems and associated models that require pushbroom sensor motion. A pulsed laser fan beam signal at 532 nm was recorded using a streak tube camera and a (high speed, low light level, high quantum efficiency) digital CCD camera. Tests were conducted in 3 different water tanks, including 2 tanks with water waves (the longest wave tank or channel is 60 m long). Capillary waves, ~1 cm wavelength) were generated using an acoustic wave source generator. Streak tube camera and CCD images were collected in conjunction with a 532 nm pico-second short pulse laser. Images collected demonstrate the pulse stretching around submerged water
targets as well as the ability to discriminate water depth of submerged targets in shallow water types. In turbid water, the
pulsed layer backscatter structure showed a nearly random return as a function of depth if the signal was attenuated before reaching the bottom of the water column. The data collected indicated the motion control testing system can accommodate a variety of cameras and instruments in the lab and in the outdoor water wave channel. Data from these camera systems are being used to help validate analytical and Monte Carlo models of the water surface structure, and the
underwater light field structure (pulse stretching) as well as to validate other LIDAR applications used in bathymetric and hydrographic surveys of coastal waters and marine inlets for physical and biological (submerged vegetation) surveys.
Early detection and treatment of breast cancer is least costly in terms of dollars, morbidity and mortality. With new early detection x-ray technology, tumors can be found, diagnosed and treated at a much smaller size than is currently possible. This paper proposes the development of a high resolution, high quality imaging system. It is a laser-driven x-ray system with time-gated detection that removes scattering noise in the image and produces resolution on the order of 10 μm. This higher resolution and higher image quality will enable the detection of one or two millimeter tumors hopefully detecting them before metastasis. We also propose that tumor detection should be followed by an immediate needle-directed, optical fiber biopsy to instantly determine if cancer is present and, if present, the tumor should immediately be given a lethal treatment of laser or x-radiation through the same needle using fiber optics or hollow waveguides. This technology will help prevent multiple interventions resulting in both the lowest overall cost and a more efficacious therapy. The approach can be stopped at the first negative (benign) indication and will help forestall repeated examination as well as reduce patient anxiety.
An experimental and numerical study is performed to analyze short pulse laser propagation through tissue phantoms without and with inhomogeneities / tumors imbedded in it. Short pulse laser probing techniques has distinct advantages over conventional very large pulse width or cw lasers primarily due to the additional information conveyed about the tissue interior by the temporal variation of the observed signal. Both the scattered temporal transmitted and reflected
optical signals are measured experimentally using a streak camera for samples irradiated with a short pulse laser source. Parametric study involving different scattering and absorption coefficients of tissue phantoms and inhomogeneities as well as the detector position and orientation is performed. The temporal and spatial profiles of the scattered optical signals are compared with the numerical modeling results obtained by solving the transient radiative transport equation
using discrete ordinates technique.
In this paper, a two-dimensional transient radiation transport algorithm is developed to analyze short pulse laser transport through a tissue medium having tumors and inhomogeneities imbedded in it. Short pulse probing techniques have distinct advantages over conventional very large pulse width or cw lasers primarily due to the additional information conveyed about the tissue interior by the temporal variation of the observed signal. The distinct feature is the multiple scattering induced temporal signatures that persists for time periods greater than the duration of the source pulse and is a function of the source pulse width, the scattering/absorbing properties and nature of the medium, the location in the medium where the properties undergo changes. A wide range of parameters such as tissue and tumor size, scattering/absorbing properties and phase function of tissues and tumors, tumor location, laser beam diameter will affect the temporal and spatial distribution of the reflected and transmitted optical signals. The goal is to perform a parametric study in order to gain insight about laser-tissue interaction characteristics with the goal to detect tumors.
We have investigated the transmission characteristics of an alternative all-optical-waveguide system for x-ray delivery to a precise tissue area. The delivery system includes two basic optical elements: a funnel-shaped uncoated hollow glass taper and a flexible hollow delivery waveguide. The hollow taper provides direct launching of the input x-ray radiation into a delivery waveguide. It is an uncoated glass taper whose operating principle is based on the grazing-incidence effect. We investigated both experimentally and theoretically how the transmission properties of the hollow taper depend on its geometrical parameters such as cone shape, length, input and output core diameters. The x-ray-source-to-taper coupling efficiency obtained was about 20-25%. That is relatively low in comparison with typical laser-to-taper coupling efficiencies due to the poorly collimated x-ray beam. Furthermore, we have studied the x-ray beam profile conversion by the grazing-incidence-based hollow taper. The x-ray radiation was launched into the delivery waveguide by a direct taper-to-waveguide coupling. In our experiment, we used both uncoated and metal-coated hollow waveguides with various geometrical parameters. The waveguide transmission characteristics, including the coupling efficiencies and beam profile conversion, were investigated for both straight and bent delivery waveguides. The results obtained as presented in this report give considerable confidence for successful application of the all-waveguide system as an alternative x-ray delivery technique for biomedical use.
This paper analyzes the short pulse laser propagation through tissues for development of a time-resolved optical tomography system for detection of tumors and inhomogeneities in tissues. Traditional method for analyzing optical transport in tissues is the parabolic or diffusion approximation in which the energy flux is assumed proportional to the fluence (intensity averaged over all solid angles) gradients. The inherent drawback in this model is that it predicts infinite speed of propagation of the optical signal. In this paper accurate hyperbolic or wave nature of transient radiative transfer formulation is used to overcome such drawbacks. The transmitted and reflected intensity distributions are obtained using hyperbolic P1 and discrete ordinates method and the results are compared with the parabolic diffusion P1 approximation. Parametric study of tissue thickness, pulse width, scattering and absorption coefficients of tissues, tumor location, size and properties, and scattering phase function distribution is also performed to analyze their effect on the transmitted and reflected optical signals.
We are studying the potential use of x-rays, which are collected by non-imaging optics and delivered through stereotactically guided needles by hollow waveguides, for irradiation of tumors. X-rays have greater transparency in tissue than most longer optical wavelengths and may provide a more uniform dose to a tumor without harming normal tissue. Dosimetry is the key to minimal damage. We are investigating the use of fiber optics, tipped with calibrated scintillators and strategically located near the tumor, to measure the delivered dose. We are testing this procedure by using a 3 ns, variable accelerator voltage Fexitron 706 to produce approximately 50 mrads of x-ray energy. We concentrate, homogenize and inject this radiation into meter length, submillimeter hollow waveguides. We place the waveguides in a simulated tumor (a phantom breast). Streak and thermal cameras monitor the energy distribution during the irradiation by observing the distribution of energy as evidenced by fluorescence and heat. Once optimum exposure conditions of placement and dose are determined, tissue studies will begin.
This paper calculates signal levels that would be obtained from oceanographic lidar by solving the one-dimensional transient radiative transfer equation for remote sensing. As an example, detection of fish schools is considered. In this technique a pulsed laser is directed into the ocean, and the time-dependent back-scattered flux is measured at different locations. A large number of parameters such as the spatial and temporal variability of optical properties within the ocean, ocean depth, type of ocean water, and presence of biological matters can significantly affect the radiative transport through oceans. But since the emphasis of the work is on the scattering phenomenon, important parameters associated with it, namely the scattering albedo and scattering phase function distribution, are considered in detail.
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