Regular monitoring of brain perfusion at the bedside in neurointensive care is desirable. Currently used imaging
modalities are not suited for constant monitoring and often require a transport of the patient. Noninvasive near infrared
spectroscopy (NIRS) in combination with an injection of a safe dye (indocyanine green, ICG) could serve as a quasi-continuous
brain perfusion monitor. In this work, we evaluate prerequisites for the development of a brain perfusion
monitor using continuous wave (cw) NIRS technique. We present results from a high-resolution diffuse optical
tomography (HR-DOT) experiment in humans demonstrating the separation of signals from skin from the brain. This
technique can help to monitor neurointensive care patients on a regular basis, detecting changes in cortical perfusion in
time.
Near infrared spectroscopy (NIRS) and diffuse optical tomography (DOT) of the brain reveal no information about the
measurement's underlying anatomical structures. An independent anatomical mapping of DOT results onto the subject's
brain or a generic brain model is desirable, especially when regions prone to large inter-subject variability are studied.
We show two methods to match DOT data from high density fiber grids to anatomical structures. The forward model that
is used to predict the light propagation is based on one generic anatomical MR scan. In both approaches we use this
model MR-scan to translocate the position of the optical fiber grid from our experimental setup to the FEM model space.
The first method, using fiduciary marks, achieves the spatial normalization of the subject's MR-scan (with marked
corners of the fiber grid) and the model's MR scan, leading to a translocation of the fiber pad position to the FEM-Model
space. The second, anatomic landmark based, approach does not require the individual's MR scan. For this, 19 reference
points and the position of the fiber pad corners are determined using photogrammetry software. These coordinates are
translocated to the FEM model space by solving the least square problem of the subject's and the model's reference
points. We illustrate and compare both methods and show results from a vibrotactile stimulation experiment in humans.
For much of the past decade, we have developed most of the essential hardware and software components needed for
practical implementation of dynamic NIRS imaging. Until recently, however, these efforts have been hampered by the
lack of calibrating phantoms whose dynamics substantially mimic those seen in tissue. Here we present findings that
document the performance of a dynamic phantom based on use of twisted nematic liquid crystal (LC) technology.
Programmable time courses of applied voltage cause the opacity of the LC devices, which are embedded in a background
matrix consisting of polysiloxane (silicone) admixed with scattering and absorbing materials, to vary in a manner that
mimics the spatiotemporal hemodynamic pattern of interest. Methods for producing phantoms with selected absorption
and scattering, internal heterogeneity, external geometry, hardness, and number and locations of embedded LCs are
described. Also described is a method for overcoming the apparent limitation that arises from LCs being mainly
independent of the illumination wavelength. The results presented demonstrate that: the opacity vs. voltage response of
LCs are highly stable and repeatable; the dynamic phantom can be driven at physiologically relevant speeds, and will
produce time-varying absorption that follows the programmed behavior with high fidelity; image time series recovered
from measurements on the phantom have high temporal and spatial location accuracy. Thus the dynamic phantom can
fill the need for test media that practitioners may use to confirm the accuracy of computed imaging results, assure the
correct operation of imaging hardware, and compare performance of different data analysis algorithms.
KEYWORDS: Digital signal processing, Signal processing, Sensors, Analog electronics, Signal detection, Data acquisition, Tomography, Imaging systems, Filtering (signal processing), Interference (communication)
In this paper we present a novel application of digital detection and data-acquisition techniques to a prototype
dynamic optical tomography system. The core component is a digital signal processor (DSP) that is responsible for
collecting and processing the digitized data set. Utilizing the processing power of the DSP, real-time data rates for
this 16-source, 32-detector system, can be achieved at rates as high as 140Hz per tomographic frame. Many of the
synchronously-timed processes are controlled by a complex programmable logic device (CPLD) that is used in
conjunction with the DSP to orchestrate data flow. The operation of the instrument is managed through a
comprehensive graphical user interface, which was designed using the LabVIEW software package. Performance
analysis demonstrates very low system noise (~.60pW RMS noise equivalent power) and excellent signal precision
(<0.1%) for most practical cases. First experiments on tissue phantoms show that dynamic behavior can be
accurately captured using this system.
In this report we present a brief outline of our technological approaches to developing a comprehensive imaging platform suitable for the investigation of the dynamics of the hemoglobin signal in large tissue structures using NIRS imaging techniques. Our approach includes a combined hardware and software development effort that provides for i) hardware integration, ii) system calibration, iii) data integrity checks, iv) image recovery, v) image enhancement and vi) signal processing. Presented are representative results obtained from human subjects that explore the sensitivity and other capabilities of the measuring system to detect focal hemodynamic responses in the head, breast and limb of volunteers. Results obtained support the contention that time-series NIRS imaging is a powerful and sensitive technique for exploring the hemodynamics of healthy and diseased tissues.
We have introduced working technology that provides for time-series imaging of the hemoglobin signal in large tissue structures. In this study we have explored our ability to detect aberrant time-frequency responses of breast vasculature for subjects with Stage II breast cancer at rest and in response to simple provocations. The hypothesis being explored is that time-series imaging will be sensitive to the known structural and functional malformations of the tumor vasculature. Mammographic studies were conducted using an adjustable hemisheric measuring head containing 21 source and 21 detector locations (441 source-detector pairs). Simultaneous dual-wavelength studies were performed at 760 and 830 nm at a framing rate of ~2.7 Hz. Optical measures were performed on women lying prone with the breast hanging in a pendant position. Two class of measures were performed: (1) 20- minute baseline measure wherein the subject was at rest; (2) provocation studies wherein the subject was asked to perform some simple breathing maneuvers. Collected data were analyzed to identify the time-frequency structure and central tendencies of the detector responses and those of the image time series. Imaging data were generated using the Normalized Difference Method (Pei et al., Appl. Opt. 40, 5755-5769, 2001). Results obtained clearly document three classes of anomalies when compared to the normal contralateral breast. 1) Breast tumors exhibit altered oxygen supply/demand imbalance in response to an oxidative challenge (breath hold). 2) The vasomotor response of the tumor vasculature is mainly depressed and exhibits an altered modulation. 3) The affected area of the breast wherein the altered vasomotor signature is seen extends well beyond the limits of the tumor itself.
We report on the first three-dimensional, volumetric, tomographic localization of changes in the concentration of oxyhemoglobin and deoxyhemoglobin in the brain. To this end we have developed a model-based iterative image reconstruction scheme that employs adjoint differentiation methods to minimize the difference between measured and predicted data. To illustrate the performance of the technique, the three-dimensional distribution of changes in the concentration of oxyhemoglobin and deoxyhemoglobin during a Valsalva maneuver are visualized. The observed results are consistent with previously reported effects concerning optical responses to hemodynamic perturbations.
Presented are the operating characteristics of an integrated CW-near infrared tomographic imaging system capable of fast data collection and producing 2D/3D images of optical contrast features that exhibit dynamic behavior in tissue and other highly scattering media in real time. Results of preliminary in vivo studies on healthy and cancerous breast tissue are shown.
We describe the design rationale, performance features, and operating characteristics of a newly constructed CW-NIR tomographic imaging system that is capable of continuous, real-time imaging of large tissue structures. Results from phantom and clinical studies are presented and discussed.
Vascular disease is a significant source of mortality and morbidity for many patient populations. While substantial strides in surgical therapeutics have been made in the past decade, our limited understanding of the microvascular processes, which are invisible to conventional imaging modalities and beyond the scope of our current physiologic paradigms, has slowed the advancement of medical therapeutic interventions. In this report we present data in support of an emerging body of work demonstrating that the method of dynamic optical tomography can yield critical insights into the underpinnings of microvascular pathophysiology in large tissue structures.
We report on the first three dimensional tomographic localization of vascular reactivity in the brain. Using a model-based iterative image reconstruction algorithm we show volumetric spatial changes in the absorption coefficient caused by changes in blood volume. Unlike currently available topographic reconstruction techniques, volumetric reconstruction schemes promise to be capable of spatially distinguishing between signals originating in the cerebral cortex from those originating in the overlying vascular tissues.
Dynamic processes in biology are often controlled by multiple parameters that interact in a complex nonlinear fashion. Increasingly, evidence has accumulated that such behavior exhibits the property of sensitivity to initial conditions, a feature exhibited by chaotic systems. One such system is the vasculature. In this report, we present what we believe is the first experimental demonstration ever of imaging chaotic behavior of the vasculature in a large tissue structure (i.e., the human forearm). Supporting these findings are results from numerical simulation demonstrating our ability to image and correctly characterize complex dynamic behavior in dense scattering media that experience spatiotemporally coincident variations in hemodynamic states.
Representative results from simulated, laboratory and physiological studies are presented, demonstrating the ability to extract important features of dynamic behavior from dense scattering media. These results were obtained by analyzing a time series of image data. Investigations on the human forearm clearly reveal the ability to identify and correctly locate principal features of the vasculature. Characterization of these features using linear and nonlinear time-series analysis methods can produce a wealth of information regarding the spatio-temporal features of the dynamics of vascular reactivity.
These studies are directed towards an on-line monitoring of tissue optical properties during medical laser diagnostics and therapy. The method of detection is based upon photoacoustic measurements. The detection of the laser induced acoustic transients was realized by means of piezoelectric transducers. Results concerning the optical properties of layered tissue- like samples are presented for two experimental configurations, i.e. transmission mode and reflection mode. The corresponding transients are calculated analytically and account for different influences which contribute to the signal, such as the laser parameters. Especially the effect of optoacoustic diffraction was investigated experimentally and verified theoretically. Its influence could be eliminated by applying fitting functions to the detected transients which take into account the distorting effect of diffraction.
Pulsed photothermal radiometry (PPTR) is a contact free nondestructive method of material inspection. It also is a promising tool for in vivo tissue spectroscopy and on-line dosimetry. For this approach, one has to consider light scattering and thus a complicated signal interpretation. Different models of light propagation in scattering media are compared, such as Monte Carlo simulation (MCS) and various approaches of diffusion theory. Simulated PPTR signals with these calculations are compared. The validity of the different models in order to describe PPTR measurements correctly is discussed.
KEYWORDS: Tissue optics, Photoacoustic spectroscopy, Signal detection, Acoustics, Pulsed laser operation, Transducers, Signal processing, Signal attenuation, Near field optics, Optical properties
Tissue optical properties are determined by an interpretation of pressure transients generated by irradiation with pulsed laser light. These pressure signals are detected using piezoelectric transducers. The signals are influenced by numerous processes during generation, propagation and detection. To study each process in particular, specific experiments were performed using biological tissue in vitro as well as different substances with various absorption and scattering properties. Especially acoustical diffraction effects cause a strong distortion of the shape and spatial oscillations in the amplitude of the transients. These phenomenons were investigated experimentally and verified theoretically.
The knowledge of laser tissue interaction, the light propagation in tissue and thus its optical properties are of fundamental importance for both laser treatment and diagnostics. We use the method of pulsed photothermal radiometry (PPTR) to evaluate optical or thermal properties of tissue-like phantoms. Because its a non-destructive and non-contact technique its a promising tool for tissue optics in vivo. As phantoms we used gelatine of known optical properties with ink added as absorber. Once the thermal features are known, one can determine the optical properties of the sample and vice versa. PPTR investigations of absorption coefficients were compared to other methods such as time resolved stress detection and optical transmission measurements. PPTR is a suitable tool to perform spectroscopy under conditions of high pressure and/or temperature and can therefore be used to investigate the ablation process.
For most applications in laser medicine suitable delivery systems are required. We developed fiber optic based diffusing tips especially for photodynamic therapy (PDT) and laser induced thermotherapy (LITT). To realize an adequate emitting cylindrical diffuser the fiber core was abraded by a precision cutter. Hence, the use of scattering media such as TiO2-doped polymers is avoided. Because the diffuser size is mainly determined by the manipulated fiber and a surrounding glass capillary, one can realize small diameters ((phi) approximately equals 3 mm). The laser light is distributed mainly by surface scattering and total reflection at the fiber air boundary. Because the use of absorbing media is avoided, it is possible to apply high laser power as necessary in LITT and pulsed PDT. We produced diffusing tips with lengths of several centimeters and typical diameters of 3 mm. By controlling the fiber-shaping process, a homogeneous intensity profile or even special designs can be achieved. The control is done by either on-line camera surveillance or calculated predictions. A delivery system especially for the photodynamical treatment of female cervix dysplasia has been designed.
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