We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.
Predicting tumor metastatic potential remains a challenge in cancer research and clinical practice. Our goal was to identify novel biomarkers for differentiating human breast tumors with different metastatic potentials by imaging the in vivo mitochondrial redox states of tumor tissues. The more metastatic (aggressive) MDA-MB-231 and less metastatic (indolent) MCF-7 human breast cancer mouse xenografts were imaged with the low-temperature redox scanner to obtain multi-slice fluorescence images of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp). The nominal concentrations of NADH and Fp in tissue were measured using reference standards and used to calculate the Fp redox ratio, Fp/(NADH+Fp). We observed significant core-rim differences, with the core being more oxidized than the rim in all aggressive tumors but not in the indolent tumors. These results are consistent with our previous observations on human melanoma mouse xenografts, indicating that mitochondrial redox imaging potentially provides sensitive markers for distinguishing aggressive from indolent breast tumor xenografts. Mitochondrial redox imaging can be clinically implemented utilizing cryogenic biopsy specimens and is useful for drug development and for clinical diagnosis of breast cancer.
Our purpose is to compare the changes in muscle oxygenation in the vastus lateralis (VL) and biceps brachii (BB) muscles simultaneously using near-infrared spectroscopy (NIRS) during incremental rowing exercise in eight rowers. Based on the BB and VL muscle oxygenation patterns, two points are used to characterize the muscle oxygenation kinetics in both the arm and the leg muscles. The first point is the breaking point (Bp), which refers to an accelerated fall in muscle oxygenation that correlates with the gas exchange threshold (GET). The second point is the leveling-off point (Lo), which suggests the upper limit of O2 extraction. The GET occurred at 63.3±2.4% of maximal oxygen uptake (O2 max). The Bp appeared at 45.0±3.8% and 55.6±2.4% O2 max in the BB and VL, respectively. The Lo appeared at 63.6±4.1% and 86.6±1.0% O2 max in these two muscles, respectively. Both the Bp and the Lo occurred earlier in BB compared with VL. These results suggest that arm muscles have lower oxidative capacity than leg muscles during rowing exercise. The rowers with higher exercise performances showed heavier workloads, as evaluated by Bp and Lo. The monitoring of muscle oxygenation by NIRS in arm and leg muscles during rowing could be a useful guide for evaluation and training.
Clinically-translatable redox imaging methods developed in the Chance laboratory have been used for imaging
mitochondrial metabolic states in tissues. The fluorescence of reduced pyridine nucleotide (PN or NADH) and oxidized
flavoproteins (Fp) in the respiratory chain is sensitive to intracellular redox states. The redox ratios, i.e., Fp/(Fp+NADH)
and NADH/(Fp+NADH) provide important metabolic information in living tissues. Usually the higher the metabolic
flux, the less NADH, the more oxidized Fp, and the higher Fp redox ratio. Snap-freezing tissue samples under the liquid
nitrogen condition preserves the tissue metabolic state in vivo. Here we report our work on the calibration of a homebuilt
Charged Coupled Device (CCD) cryogenic redox imager using a series of snap-frozen solution standards of NADH
and Fp. The NADH concentration ranged from 0-1318 μM and Fp from 0-719 μM. The sensitivity ratio of NADH and
Fp channels was determined from the slope ratio of the two calibration curves and was used to correct the redox ratio of
a human melanoma mouse xenograft. The NADH and Fp reference standards were placed adjacent to the tissue samples
and their emission intensities were used to quantitatively determine the concentrations of NADH and Fp in a mouse
xenograft of a human breast cancer line. Our method of imaging tissue samples along with reference NADH and Fp
standards should facilitate the comparison of redox images obtained at different times or with different instrument
parameters.
The fluorescence properties of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) such
as flavin adenine dinucleotide (FAD) in the respiratory chain are sensitive indicators of intracellular redox states and
have been applied to the studies of mitochondrial function with energy-linked processes. The redox scanner, a threedimensional
(3D) redox cryo-imager previously developed by Chance et al., can quantitatively determine the metabolic
properties of tissue samples by acquiring the fluorescence images of NADH and Fp. The redox ratios, i.e.,
Fp/(Fp+NADH) and NADH/(Fp+NADH), obtained on the basis of relative signal intensity ratios, provide a sensitive
index of steady-state of the mitochondrial metabolism that has been determined for a variety of biological tissues. This
paper presents the further development of the instrument by establishing a calibration method to quantify the
concentration of the fluorophores and facilitate the comparison of redox images obtained at different time or with
different instrument functions. Calibration curves of both NADH and Fp have been obtained using snap-frozen standard
references with NADH concentration ranging from 150-1400 μM and Fp from 80-720 μM. Snap-freeze tissue samples
such as human breast tumors xenografted in mice, normal mouse pancreases and spleens were imaged. The NADH and
Fp concentrations as well as the redox ratios in the tissue samples were quantified based on the adjacent solution
standards of NADH and Fp. The obtained multi-slice redox images revealed high heterogeneity of the tissue samples
which can be quantitatively interpreted.
This study examines differences in concentration changes of hemoglobin in the brain while finding algebraic solutions
versus geometrical solutions. We use Near Infrared Spectroscopy imaging system to measure the hemoglobin changes
while subjects are solving algebraic task and geometrical task. NIRS imaging system can measure changes in the
concentration of hemoglobin. This brain activity data shows a difference between the two different experimental tasks
which helps us to identify the characteristics of thinking processes.
Over the past decade, the application of results from brain science research to education research has been a
controversial topic. A NIRS imaging system shows images of Hb parameters in the brain. Measurements using NIRS are
safe, easy and the equipment is portable, allowing subjects to tolerate longer research periods. The purpose of this
research is to examine the characteristics of Hb using NIRS at the moment of understanding. We measured Hb in the
prefrontal cortex of children while they were solving mathematical problems (tangram puzzles). As a result of the
experiment, we were able to classify the children into three groups based on their solution methods. Hb continually
increased in a group which could not develop a problem solving strategy for the tangram puzzles. Hb declined steadily
for a group which was able to develop a strategy for the tangram puzzles. Hb was steady for a certain group that had
already developed a strategy before solving the problems. Our experiments showed that the brain data from NIRS
enables the visualization of children's mathematical solution processes.
This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO2), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO2, and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO2, and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7±9.7)% in the first week and decreases (42.4±7.0)% in the second week. Averaged StO2 increases from (62.9±3.4)% baseline value to (70.4±3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7±7.0) [µM] to (73.3±8.3) [µM] at the end of the second week and to (63.0±8.1) [µM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.
This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO2), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO2, and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO2, and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7±9.7)% in the first week and decreases (42.4±7.0)% in the second week. Averaged StO2 increases from (62.9±3.4)% baseline value to (70.4±3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7±7.0) [µM] to (73.3±8.3) [µM] at the end of the second week and to (63.0±8.1) [µM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.
In this work, we present spatially resolved pharmacokinetic rate images of indocyanine green (ICG) obtained from three breast cancer patients using near infrared imaging methods. We used a two-compartment model, namely, plasma and extracellular extravascular (EES), to model ICG kinetics around the tumor region. We introduced extended Kalman filtering (EKF) framework to estimate the ICG pharmacokinetic rate images. The EKF framework allows simultaneous estimation of pharmacokinetic rates and the ICG concentrations in each
compartment. Based on the pharmacokinetic rate images, we observed that the rates from inside and outside the tumor region are statistically different with a p-value of 0.0001 for each patient. Additionally, we observed that the ICG concentrations in plasma and the EES compartments are higher around the tumors agreeing with the hypothesis that ICG may act as a diffusible extravascular flow in leaky capillary of cancer vessels. Our study shows that spatially resolved pharmacokinetic rate images can be potentially useful for breast cancer screening and diagnosis.
Gadolinium (Gd) pharmacokinetics are useful in diagnosis of breast cancer with MRI; previous work has suggested that the pharmacokinetics of indocyanine green (ICG) may prove to be similarly useful in optical mammography. Here, we describe a fast optical imaging device to acquire images of ICG kinetics simultaneously with Gd kinetics and coregister the images. This direct comparison between the widely accepted Gd diagnostic techniques and optical methods is essential for clinical acceptance of optical techniques by the radiological community.
A continuous-wave (cw) near-infrared spectroscopy (NIRS) instrument has been developed to noninvasively quantify fetal cerebral blood oxygen saturation (StO2). A linear Green's function formulism was used to analytically solve the photon diffusion equation and extract the time-varying fetal tissue oxy- and deoxy-hemoglobin concentrations from the NIR measurements. Here we explored the accuracy with which this instrument can be expected to perform over a range of fetal hypoxic states. We investigated the dependence of this accuracy on the accuracy of the reference optical properties chosen based on the literature. The fetal oxygenation of a pregnant ewe model was altered via maternal aortic occlusion. The NIR cw instrument was placed on the maternal abdomen directly above the fetal head, continuously acquiring diffuse optical measurements. Blood was sampled periodically from the fetus to obtain fetal arterial saturation (SaO2) measurements from blood gas analysis. The NIR StO2 values were compared with the fetal SaO2 measurements. Variations in the NIR results due to uncertainty in the reference optical properties were relatively small within the fetal SaO2 range of 30 to 80%. Under hypoxic conditions, however, the variability of the NIR StO2 calculations with changes in the assumed reference properties became more significant.
The aim is to evaluate the usefulness of optical blood flow measurements for predicting early tumor response to radiation therapy in patients with head and neck tumors. The results suggest a correlation between tumor blood flow changes with clinical outcome.
NIR handheld LED breast cancer imaging is a novel design that we are using widely in clinical study. During the test, we found the pressure change may affect the signal from the breast, especially to the blood flow inside of tissue. In this paper, we will show a new design of the probe combined with pressure sensors. And, we also did 15 cases of normal person’s breast test by using this design. We try to dig out how the pressure works and the relationships between the pressure effect to blood flow, also oxygen saturation in vivo. Some patients’ data may be presented here too.
The goal of our study is to develop a time-dependent three-compartment model of beacon delivery to simulate the distribution of Indocynanine Green (ICG) in cancer tissue by using JSIM development environment of model simulation and data analysis. We studied the major factors that contribute to distribution of ICG in our model. The simulation results show that our time-dependent three-compartment model can describe the delivery of ICG injected intravenously into the human subject and assist in breast cancer detection.
Near Infrared Spectroscopy (NIRS) has been widely used in cancer imaging spectroscopy because cancer tissue has more blood volume and less oxygen than normal tissue. The neck squamous cell carcinoma is ideal for our study because it’s a surface mass can be easily feel through the skin. We use a simple homodyne phase modulation system, In-phase and Quadrature Phase (I&Q) Detection system, to study the curative effect of therapy in neck cancer patients. Clinical treatment includes mainly chemical and radiation therapy, both of which alter the blood volume and the oxygenation saturation in cancer tissue. The I&Q detection system is capable of the quantification measurement of those biological changes. In this paper, we will simply introduce the I&Q detection system’s principle and constitution, and mainly explain the analysis of patients’ data.
This paper focuses on breast cancer diagnosis using the newly developed low-noise threewavelength (?=730nm, 805nm and 850nm) NIR light emitting diode (LED) continuous-wave (CW) imager. The NIR CW imager has its advantage of simplicity, and potential for a portable instrument. The imaging rate is 5 frame/second. The signal to noise ratio is larger than 2000 when measuring at a breast model ( ?a=0.04/cm, ?'= 8/cm), which corresponds to 4x 10-4 optical density (OD) error. Phantom test was carried out, and indicated good localization of heterogeneity. It was known that cancer has more blood concentration and de-oxygenation than normal tissue, which is the principle of breast cancer detection using NIR spectroscopy. Clinical results of breast cancer studies will be presented. Keywords: LED, Breast Cancer Imaging, CW
In-phase and Quadrature Phase Detection System (I&Q System) can be used to detect the clinic-related parameters such as hemoglobin concentration and saturation. We set up an effective multi-wavelength fitting model and method to calibrate the tissue optical properties such as the reduced scattering factor ((mu) s) and the absorption factor ((mu) a), which can be calculated from the measured amplitude and phase shift of I&Q system. Then using the calibrated tissue optical parameters, we can get better results for hemoglobin concentration and saturation by our proposed algorithm of fitting multi-wavelength absorption coefficient ((mu) a) of the medium than those from the previous I&Q system based on the two-wavelength absorption coefficient calculation. Our algorithm is used in the clinical experiments with five wavelengths (680 nm, 750 nm, 780 nm, 810 nm, 830 nm) for the necks' and arms' saturation test between normal persons and tumor-bearing patients.
Diffuse Optical Tomography (DOT) in the Near Infrared Spectral window (NIR) offers new possibilities for medical imaging. And using DOT, Indocyanine green (ICG) is found to be a useful blood pooling contrast agent for optical tumor detection. Here we introduce our efforts on study of breast cancer image reconstruction using ICG as a contrast agent. To improve the signal-to-noise ratio, we developed an effective method to analyze and process the raw data acquired from a CWS (Continuous Wave Spectroscopy) system. Differential absorption images of breast cancers are reconstructed by using ART (Algebraic Reconstruction Technique) which uses the diffusion equation within the Rytov approximation. The experiment device is a combination of sixteen light sources (tungsten bulb) and sixteen light detectors (silicon photodiodes). These sources and detectors are located on a circular holder where the human breasts are placed, each other at equal distance (11 angle apart). It takes a few seconds to acquire data since one source is on, while all the detectors simultaneously detect the photons. So an image includes 16*16 data points. Results from clinical trial in Japan and China show that there is a high concentration of ICG in the location of a cancer, suggesting high blood volume pooling and the usefulness of ICG detecting optically breast cancers.
This paper summarizes the design steps that are followed during the development of the portable optical imager for breast cancer screening. The design steps considered the parameters such as total power consumption versus battery weight and size, speed of data acquisition versus cost and complexity of the design (functionality), graphical display versus operating system choice. We have used a single board computer system that uses Windows CE as the real time operating system. This choice was preferred since our graphical display requirements can only be carried out with the CE environment's GUI kernels.
It was demonstrated that the dynamics of muscle oxygen utilization can readily be measured using dual wavelength hemoglobin oximetry. This method can be used for muscle training exercise and also for evaluation of exercise performance where the anaerobic threshold must be avoided. It was shown that CW imaging technology gives images along the surface of the muscle while the time resolved spectroscopy gives images transverse to the muscle.
We present tissue phantom experimental results and theoretical simulations to study photon migration through the fetal head in-utero. A continuous-wave (CW), dual wavelength (760 & 850 nm) spectrometer was developed and employed for the experiments at a source-detector separation of 10 cm. Theoretical simulations were performed using time-independent, finite-difference, discrete-ordinate, radiative-transport and diffusion equations. Two phantom geometries viz. circular and rectangular were considered. The tissue phantom incorporates a fetal head (absorption coefficient, .?a: 0.15 cm-1 & reduced scattering coefficient, ?s': 5.0 cm-1), an amniotic fluid sac (?a=0.02 cm-1, ?s= 0. 1 cm-1) and a maternal tissue layer (?a= 0.08 cm-1, ?s'= 5.0 cm-1). Photon fluence from the tissue phantom was quantified as a function of fetal head depth and its position relative to probe placement. Experimental results obtained with spectrometer were found to be congruent with theoretical results and clinical investigations. The results indicate that photon fluence decreases with increase in fetal head depth for circular geometry, while it increases with increase in fetal head depth for rectangular geometry. This paradoxical result observed may be attributed to the effect of amniotic fluid in the light path. Photon fluence is sensitive for fetal head depths within 40 mm. This is well within the fetal head depths expected in near-term patients (~20 mm)
We present a preliminary assessment of the feasibility of using a frequency domain spectrometer for measuring fetal cerebral blood oxygenation in-utero at 750 and 780 nm of modulation at 70 MHz. The amplitude and phase of the diffuse photon density wave which propagates through the tissue is detected by a photomultiplier tube. The absorption coefficient ?a and the reduced scattering coefficient ?'s are calculated based on the analytic solution of the photon diffusion equation for a semi-infinite geometry. The accuracy of the instrument and the algorithm in measuring ?a is tested by an experiment performed on a homogeneous ink/intralipid tissue phantom. Also the sensitivity of the system to the change of blood volume and oxgenation is evaluated through a homogeneous blood/intralipid tissue phantom experiment. Clinical data was recorded during the elective Cesarean section of human subjects. The measurements were made on maternal abdomen in the post-epidural stage and on the fontanel region of neonate before (pre-cord) and after (post-cord) the umbilical cord was detached. The source detector separation used were 7 and 3(or 4) cm respectively. The deoxygenated and oxygenated hemoglobin concentration, blood volume and saturation were calculated based on ?a of 2 wavelength. The averaged optical properties and blood parameters for each stage are presented. The post-epidural blood saturation value correlates well with the pre-cord saturation value. A larger number of human subjects are being evaluated to provide statistically significant results.
The possibility that a highly portable, fast, safe and affordable imaging system could obtain interpretable images of brain function in full- and pre-term neonates in a few seconds, has been explored in this paper. We have used a uniquely sensitive optical tomography system, termed phased array, which has revealed significant functional responses, particularly to parietal stimulation in normal and pathological states of neonate brain. This two-wavelength, frequency encoded phased array system can indicate the blood concentration and oxygenation change during the parietal brain activation in neonates. The preliminary clinical results are presented in this paper.
For X-ray mammography, we are unable to apply to younger subjects of woman under 40 years old. The under 40 years old BRCA-1 population has a serious diagnostic problem. So we have chosen to develop an optical technique for breast cancer detection. In order to provide a safe, fast and portable dual wavelength breast imager, We have used high sensitive cancellation techniques (amplitude cancellation image system) as an imaging system that can better to localize the metabolic and blood volume responses. This device consists of 8 sources (750 nm, 830 nm) and 21 silicon photodiodes. The sources are modulated by 50 us pulse and pulse encode the dual wavelength sources (750nm, 830 nm). Using programmed amplifies, the image system is first calibrated on a breast model by adjusting all outputs to be equal, hence their differential amplifier outputs are zero. The high sensitive null (zero) plane is applied to detect small objects. By averaging of the imaged data over 8 sec. The system indicated a very high signal to noise ratio (100) in detecting inhomogeneity of the breast with respect to the surrounding tissue or to the contralateral breast in voxeis containing blood volume and oxygenation changes corresponding to the presence of tumors or related tissue pathologies.
Optical imaging technologies have been proven to be useful in brain function studies. Here we show the feasibility of this technology for studying muscle function. We have tested the functions of two important lower extremity muscle groups: gastrocnemius in the calf muscle and two muscles in the quadriceps muscle group during several common muscle exercises. Images obtained during the exercises demonstrated clearly the degree of muscle functions with respect to deoxygenation and blood volume changes. The optical imaging technologies can be applied to exercise physiology and training. It can be also useful for diagnoses, prognoses of certain muscle conditions in clinical and pathological cases.
A highly portable, fast, safe and affordable imaging system that provides interpretable images of brain function in full- and pre-term neonates within a few seconds has been applied to neonates with normal and pathological states. We have used a uniquely sensitive optical tomography system, termed phased array, which has revealed significant functional responses, particularly to parietal stimulation in neonate brain. This system can indicate the blood concentration and oxygenation change during the parietal brain activation in full- and pre-term neonates. The preliminary clinical results, especially a longitudinal study of a cardiac arrest neonate, suggest a variety of future applications.
A real time functional Near-InfraRed Imager (fNIRI) was presented in this paper. We developed a continuous wave (cw) light imaging probe which includes 9 light sources and 4 pairs detectors (each pair has one 850 nm filtered detector and one 760 nm filtered detector). There are 16 measurement sections and total detection area is 9 cm X 4 cm. The detector- source uses 2.5 cm spacing. The light sources are controlled by a computer and the signals from the detectors are converted and processed in real time by the computer. The user-friendly software was programmed with Visual C++ language. Relative changes of oxy-Hb, Hb, and total blood concentration in 16 channels and the corresponding images combined by 16 channels could be displayed in real time on computer. With this cw imaging probe, we have measured motor function in motor cortex area, visual function in occipital area, and cognitive activity in frontal forehead area of the human brain when the subjects are stimulated by moving fingers, viewing a flashing light and doing an analogy test, respectively. The experimental results show that the cw imaging probe can be used for functional images of brain activity, based upon changes of oxygenation and blood volume due to the stimulus.
Noninvasive measurement of changes in oxygenation of human skeletal muscle can be done with a dual-wavelength near infrared (NIR) spectrophotometer. This allows a noninvasive investigation of muscle mitochondria. An exercise protocol was developed to study the load dependent changes in oxygenation of m. vastus lateralis of myopathic patients. On a bicycle ergometer exercise was done periodically. One period consisted of 1.5 min exercise followed by 3 min rest. Work load in the first period was 20 W, and was increased by 10 W for each subsequent period until maximal work load was reached. In 12 healthy volunteers we observed oxygenation of muscle during periods of low work load (warm-up effect). During periods of high work load the muscle deoxygenated. The work load at transition from oxygenation to deoxygenation (deoxygenation threshold) in controls was 75 W. In 3 patients with myopathies, in addition to NIR- spectroscopy, function of mitochondria of specimen of m. vastus lateralis was investigated biochemically. Muscle fibers were skinned with saponin and investigated with high resolution respirometry and multiple substrate-inhibitor- titration. Mitochondrial function was impaired in patients who had abnormal findings in NIR spectroscopy.
Localization of absorbers/fluorochromes deep within a highly scattering large body of tissue such as the human breast can be affected most precisely by photon diffusive waves (yodh, physical Review) that are in and out of phase amplitude modulated sources in the MHz region. The detector of in-phase and anti-phase signal establishes a null plane. Such a null is highly sensitive to perturbations by extremely small objects, of the order of the size of 70 microliters volume and containing as little as 20 picamole of an absorber (ICG). In order to enlarge the search field for phased array, the relative amplitude of the rf (200 Mhz or 50 MHz) is modulated by a second lower frequency signal (60 Hz), the phase transition plane moves back and forth at the lower frequency. The phased array system is applied to the detection the blood concentration and its oxygenation/deoxygenation in human breast pendant within a 'breast box' 40 cm X 15 cm X 15 cm, containing a breast matching intralipid and 1 cm3 tumor phantom used as a blood volume, blood oxygenation calibrator. The breast is located by a pair of soft compression plates during the phased array scan. The sensitivity of the system is estimated by the detectable blood concentration and the corresponding oxygenation/deoxygenation of the blood in the 1 cm3 tumor phantom. We have done over 40 experiments for human breast test.
Near-infrared spectroscopy (NIRS) can detect changes in cerebral hemoglobin oxygenation in response to motor, visual or cognitive stimulation. This study explored potential improvements for functional human brain mapping with NIRS: (1) So far, only primary cortical areas, like motor cortex or primary visual areas were studied. We tested the feasibility of identifying an extrastriate visual motion area (MT) with single site NIRS. (2) The temporal resolution of commercial systems is on the order of seconds and their spectral resolution is poor. We tested the feasibility of the detection of cerebral hemoglobin oxygenation changes during visual stimulation at high temporal (100 ms) and spectral resolution (5 nm) using a whole spectrum approach (CCD-NIRS). (3) The spatial resolution of commercial systems is poor. In this study we used a 16 channel functional NIRS-imaging device to test the feasibility of mapping changes in cortical blood volume during visual stimulation (over primary and secondary areas). We show that (1) even conventional single site NIRS allows to identify secondary visual areas, (2) a CCD-NIRS system affords a high temporal (100 ms) and spectral (5 nm) resolution for the detection of changes in cerebral hemoglobin oxygenation during visual stimulation, (3) functional NIRS- imaging can localize focal blood volume changes over both primary and secondary cortical areas.
In the present study we evaluated a new 50 MHz single wavelength multi-source detector imaging system for noninvasive optical imaging of human brain function. The system is based on phase resolved technology and allows measurements in remission mode of changes in phase shift and light intensity in the phased array approach and the conventional phase modulation approach. To evaluate the potentials and limitations of the system with respect to functional brain imaging we assessed the sensitivity of imaging based on photon migration pattern and absorption changes in the two different approaches as a function of object depth in a homogeneous brian model under controlled conditions. Furthermore first results using this technique for noninvasive optical imaging of functional brain activation in human subjects are presented and discussed with respect to potentials and limitations of the respective parameter.
We developed a continuous wave (cw) light imaging probe which includes 9 light sources and four pairs detectors (each pair has one 850 nm filtered detector and one 760 nm filtered detector). The light sources are controlled by a computer and the signals from the detectors are converted and processed in the computer. There are 16 measurement sections and total detection area is 9 cm multiplied by 4 cm which can be scanned every 8 seconds. The detector-source uses 2.5 cm spacing. In this study, we present the noise, drift, detectivity and spatial resolution test results of the imager. Changes of oxygenation and blood volume in about 2 cm depth from the surface of brain model can be detected. The temporal resolution is 8 seconds and spatial resolution is about 2 cm. The detectivity of OD changes can reach 0.008. With this cw imaging probe, we measured motor function in motor cortex area, visual function in occipital area, and cognitive activity in frontal forehead area of the human brian when the subjects are stimulated by moving fingers, viewing a flashing light and doing an analogy test, respectively. The experimental results show that the cw imaging probe can be used for functional images of brain activity, base upon changes of oxygenation and blood volume due to the stimulus.
The detection of small amounts of indocyanine green (ICG) in small volumes would suggest its potential use in the detection of early breast tumors. While phased array has already shown its ability to sharply localize small amounts of ICG in the picomole region, the question has arisen, what would be the comparable sensitivity of continous light systems for the same purpose? If this were a comparable sensitivity, the advantages of the simplest of opto- electronic systems and the use of light intensity not limited to those available under FDA regulations for laser diodes could be realized. In this research work, we investigate two methods of enhancing the contrast agent between diseased and healthy tissue using low frequency amplitude modulated light sources. The first method exploits the symmetry between the left and right breast and the second exploits the cylindrical symmetry of the breast. Both effect are enhanced by the use of an injected contrast agent (ICG). Based on the theory and model study, several human subjects cases were studied in the Hospital of the University of Pennsylvania. The results show that the peak signal can get about 60 seconds after ICG injection through the vein and then will take few minutes to get back to the baseline. The half decay time and maximum (Delta) OD are dependent of the characteristics of the breast tissue.
The permeability of tumor blood vessels to contrast agents (Gd chelates) has formed the basis for MRI breast tumor identification. It is also believed that angiogenesis starts before further tumor growth. Here we report tumor detection and localization using the fluorescence of Indocyanine Green (ICG). ICG fluorescence is excited by CW NIR laser light with a central wavelength of 830 nm is recored as a function of time. Differential fluorescence signals were observed after a low-dose intraveneous injection of ICG aqueous solution in rat model experiments. The difference between the fluorescence signal from the tumor side and the fluorescence signal from the control side is detectable even when the tumor is very small. During the tumor exponential growth phase, the ratio of these two signals is approximately 2.5; the ratio of the initial ICG clearance velocity in the tumor leg to that in the control leg is about 3. New investigations on human subjects with breast tumors, or reoccurrence after breast tumors were removed, are underway, and preliminary differential fluorescence signals have been observed.
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