Time-resolved Optical Imaging Research Articles

금속 마이크로입자 및 압밀 시편의 펄스레이저 어블레이션에 의한 나노입자 합성

This paper describes the process of nanoparticle synthesis by laser ablation of microparticles and consolidated sample. We have generated nanoparticles by high-power pulsed laser ablation of AI, Cu and Ag microparticles using a Q-switched Nd:YAG laser (wavelength 355nm, FWHM 6ns, fluence O.8-2.0J/cm²). Microparticles of mean diameter 18~80μm are ablated in the ambient air. The generated nanoparticles are collected on a glass substrate and the size distribution and morphology are examined using a scanning electron microscope and a transmission electron microscope. The effect of laser fluence, collector position and compacting pressure on the distribution of particle size is investigated. To better understand the process of laser ablation of microparticle(LAM), we investigated the Nd: Y AG laser-induced breakdown of Cu microparticle using time-resolved optical shadow images. Nanosecond time-resolved images of the ablation process are also obtained by laser flash shadowgraphy. Based on the experimental results, discussions are made on the dynamics of ablation plume.

Time-resolved optical imaging through turbid media using a fast data acquisition system based on a gated CCD camera

In this paper, we propose a novel approach for the acquisition of time-resolved data for optical tomography. A fast gated CCD has been used as a parallel detector to acquire in one shot the light intensity exiting a phantom within a very short time slice. By using a pulsed illumination and repeating the acquisition at different delays, the time behaviour of the diffused transmittance can be recorded very quickly. Scattering inclusions embedded in a 5 cm thick phantom have been revealed by fitting a set of 120 images, delayed 50 ps from one another, with a mathematical model based on the random walk theory. Moreover, absorption inclusions have been detected in time-gated images taken at suitable delays.

Assessment of an in situ temporal calibration method for time-resolved optical tomography.

A 32-channel time-resolved optical imaging device is developed at University College London to produce functional images of the neonatal brain and the female breast. Reconstruction of images using time-resolved measurements of transmitted light requires careful calibration of the temporal characteristics of the measurement system. Since they can often vary over a period of time, it is desirable to evaluate these characteristics immediately after, or prior to, the acquisition of image data. A calibration technique is investigated that is based on the measurement of light back-reflected from the surface of the object being imaged. This is facilitated by coupling each detector channel with an individual source fiber. A Monte Carlo model is employed to investigate the influence of the optical properties of the object on the back-reflected signal. The results of simulations indicate that their influence may be small enough to be ignored in some cases, or could be largely accounted for by a small adjustment to the calibrated data. The effectiveness of the method is briefly demonstrated by imaging a solid object with tissue-equivalent optical properties.

Spatial resolution in fast time-resolved transillumination imaging: an indeterministic Monte Carlo approach

The spatial resolution achievable in time-resolved optical transillumination imaging through a turbid (scattering and absorbing) medium has been reassessed theoretically. The temporal point spread function was constructed assuming a delta function input pulse, a ∼50 mm thick medium and a small detector with zero risetime. Temporal profiles were derived from an indeterministic Monte Carlo simulation for different time scales. From the temporal point spread function (TPSF), an analytic edge response function from which the spatial resolution was determined was derived. Previous analytical methods for determining the spatial resolution are approximations for very short flight times (sub-100 ps time region). The results show that a spatial resolution of about two millimetres is possible under ideal signal-to-noise ratio conditions and with detector gate times of the order of ten picoseconds. If this predicted spatial resolution can be achieved in an imaging system, it may be possible to improve the diagnosis of breast tumours.

Quantitative optical imaging of brain activity—human and animal studies

In order to overcome the problems associated with near-infrared optical imaging (NIR-imaging) such as the lack of the quantification and poor spatial resolution, we developed a 64-channel time-resolved optical imaging system, by which we could obtain quantitative functional images of human brain activity. Reflectance tomographic images of the changes in oxy-hemoglobin [oxy-Hb], deoxy-hemoglobin [deoxy-Hb], and total-hemoglobin [t-Hb] associated with neural activation were obtained, and given as absolute concentration changes. Then, the obtained optical functional images were superimposed on 3-D images of the subject's brain reconstructed from MRI, on which fMRI images were also superimposed. Very interestingly, but curiously, we found that the activation maps of [oxy-Hb] rather than [deoxy-Hb] were very reasonable and similar to those of the fMRI. The maximum increase in [oxy-Hb] due to finger tapping was about 1 μM, whereas in several cognitive tasks such as the digit span task, the increase was much larger, at 3–8 μM. The optical imaging system employed here can be applied to the subjects of all ages and be used at the bedside as well. By simplifying and miniaturizing the imaging system, we could construct a conventional single channel oxygen monitor for clinical use, by which we could quantify the changes of [oxy-, deoxy- and total Hb] during neuronal activation in each subject and, therefore, statistical analysis became possible.

Maps of optical differential pathlength factor of human adult forehead, somatosensory motor and occipital regions at multi-wavelengths in NIR

The optical differential pathlength factor (DPF) is an important parameter for physiological measurement using near infrared spectroscopy, but for the human adult head it has been available only for the forehead. Here we report measured DPF results for the forehead, somatosensory motor and occipital regions from measurements on 11 adult volunteers using a time-resolved optical imaging system. The optode separation was about 30 mm and the wavelengths used were 759 nm, 799 nm and 834 nm. Measured DPFs were 7.25 for the central forehead and 6.25 for the temple region at 799 nm. For the central somatosensory and occipital areas (10 mm above the inion), DPFs at 799 nm are 7.5 and 8.75, respectively. Less than 10% decreases of DPF for all these regions were observed when the wavelength increased from 759 nm to 834 nm. To compare these DPF maps with the anatomical structure of the head, a Monte Carlo simulation was carried out to calculate DPF for these regions by using a two-layered semi-infinite model and assuming the thickness of the upper layer to be the sum of the thicknesses of scalp and skull, which was measured from MRI images of a subject's head. The DPF data will be useful for quantitative monitoring of the haemodynamic changes occurring in adult heads.

Near-Infrared Optical Imaging by Time-Resolved Spectroscopy.

Near-infrared spectroscopy (NIRS) measures changes in the hemoglobin oxygenation state in the human brain. NIRS has recently started to be used for neuroimaging as well as for clinical monitoring. CW-type NIRS instruments have high temporal resolution and allow prolonged-time and continuous measurements, but they do not provide absolute values of changes in hemoglobin concentrations. In contrast, time-resolved spectroscopy (TRS), which uses short-pulse laser diodes as light sources, makes quantification possible. Quantification is necessary for imaging of brain activity. Recently, a 64-channel time-resolved optical tomographical imaging system (optical CT) and a single-channel TRS instrument have been developed. By the use of this optical CT or combining the single-channel TRS instrument with the multichannel CW-type NIRS instrument, we can obtain topographical images. NIRS is completely noninvasive and does not require strict motion restriction during measurements, unlike PET and fMRI. NIRS will provide a new direction for functional mapping studies.

Dynamics of laser ablation of microparticles prior to nanoparticle generation

To better understand the process of nanoparticle formation when microspheres are ablated by a high-energy laser pulse, we investigated the Nd:YAG laser-induced breakdown of 20 μm glass microspheres using time-resolved optical shadow images and Schlieren images. Time-resolved imaging showed the location of the initial breakdown and the shockwave motion over its first 300 μm of expansion. From these measurements, we determined the shockwave velocity dependence on laser fluence. Measured shockwave velocities were in the range of 1–10 km/s. We also developed a numerical model that simulated breakdown in the glass microsphere and the propagation of this disturbance through the edge of the sphere where it could launch an air shock. Our objective was to simulate the shockwave velocity dependence on laser fluence and to generate glass density, temperature, and mass velocity profiles after breakdown. The simulation and experimental data compared favorably.

Time resolved optical tomography of the human forearm

A 32-channel time-resolved optical imaging instrument has been developedprincipally to study functional parameters of the new-born infant brain. As aprelude to studies on infants, the device and image reconstruction methodologyhave been evaluated on the adult human forearm. Cross-sectional images weregenerated using time-resolved measurements of transmitted light at twowavelengths. All data were acquired using a fully automatedcomputer-controlled protocol. Images representing the internal scattering andabsorbing properties of the arm are presented, as well as images that revealphysiological changes during a simple finger flexion exercise. The resultspresented in this paper represent the first simultaneous tomographicreconstruction of the internal scattering and absorbing properties of aclinical subject using purely temporal data, with additional co-registereddifference images showing repeatable absorption changes at two wavelengths inresponse to exercise.

Interaction of wide band gap single crystals with 248 nm excimer laser irradiation. VII. Localized plasma formation on NaCl single crystal surfaces

Wide band gap insulators containing defects exposed to nanosecond pulses of UV laser radiation at fluences close to the damage threshold often display highly localized flashes of light. In this work, we show that flashes observed during irradiation of cleaved, single crystal NaCl at relatively low fluences are due to localized plume fluorescence. By comparing time-resolved optical images of this fluorescence with subsequent scanning electron microscope images of surface topography, we show that these flashes are often associated with micron-dimension surface and near-surface damage, typically associated with cleavage steps. With continued laser irradiation, plume fluorescence at previously damaged regions usually grows stronger from pulse to pulse. In some cases, weak plume fluorescence disappears after one laser pulse, and may or may not reappear with continued irradiation. We interpret these results in terms of localized laser absorption by deformation-induced defects generated during cleavage. Deliberately deformed material, produced by indentation, is damaged at considerably lower laser fluences, consistent with this interpretation. We suggest that mobile excitations produced by laser absorption preferentially decay along dislocation cores, which strongly localizes laser-induced thermal stresses and damage.

Polarization-dependent characteristics and polarization gating in time-resolved optical imaging of skeletal muscle tissues

The comparisons of the time-resolved transmitted intensity profiles and imaging results based on the polarization gating method between the samples of diluted milk, chicken breast tissue, and chopped chicken breast tissue revealed that the anisotropic structure of chicken breast tissue resulted in coherent coupling between the two inherent polarization directions and difficulty of using the polarization gating method for optical imaging through skeletal muscle tissues. To explore the polarization-dependent optical properties of chicken breast tissues, we calibrated the extinction coefficients of the polarization components parallel with and perpendicular to tissue filaments and the cross-polarized intensity-coupling coefficients between the two polarization components, based on the measured snake-photon intensity data. The calibrated values of these coefficients were quite consistent with previously reported. The extinction coefficient in the polarization along tissue filaments was significantly higher than that of the other polarization. Also, the cross-polarized coupling coefficient of the coupling from the polarization of tissue filaments into the other was stronger than that of inverse coupling.

Visuospatial imagery is a fruitful strategy for the digit span backward task: a study with near-infrared optical tomography

Our newly developed 64-channel time-resolved optical tomographic imaging system using near-infrared light enables us to obtain a quantitative image of hemoglobin concentration changes associated with neuronal activation in the human brain [H. Eda, I. Oda, Y. Ito, Y. Wada, Y. Oikawa, Y. Tsunazawa, M. Takada, Y. Tsuchiya, Y. Yamashita, M. Oda, A. Sassaroll, Y. Yamada, M. Tamura, Multi-channel time-resolved optical tomographic imaging system, Rev. Sci. Instrum., 70 (1999) 3595–3602]. Here, we used this optical imaging system to demonstrate that the backward digit span (DB) task activated the dorsolateral prefrontal cortex (DLPFC) of each hemisphere more than the forward digit span (DF) task in healthy adult volunteers, and higher performance of the DB task was closely related to the activation of the right DLPFC. These results suggest that visuospatial imagery is a useful strategy for the DB task. Optical tomography described here is a new modality of neuropsychological studies.

Multichannel time-resolved optical tomographic imaging system

A time-resolved optical imaging system using near-infrared light has been developed. The system had three pulsed light sources and total 64 channels of detection, working simultaneously for acquisition of the time-resolved data of the pulsed light transmitted through scattering media like biological tissues. The light sources were provided by high power picosecond pulsed diode lasers, and optical switches directed one of the light sources to the object through an optical fiber. The light signals reemitted from the surface of the object were collected by optical fibers, and transmitted to a time-resolved detecting system. Each of the detecting channels consisted of an optical attenuator, a fast photomultiplier, and a time-correlated single photon counting circuit which contained a miniaturized constant fraction discriminator/time-to-amplitude converter module, and a signal acquisition unit with an A/D converter. The performance and potentiality of the imaging system have been examined by the image reconstruction from the measured data using solid phantoms.

Computer simulation of time-resolved optical imaging of objects hidden in turbid media

We review research on time-resolved optical imaging of objects hidden in strongly scattering media, with emphasis on the application to breast cancer detection. A method is presented to simulate the propagation of light in turbid media. Based on a numerical algorithm to solve the time-dependent diffusion equation, the method takes into account spatial variations of the reduced scattering and absorption factors of the medium due to the presence of objects as well as random fluctuations of these factors. It is shown that the simulation method reproduces, without fitting, experimental results on tissue-like phantoms. Using experimental and simulation results, an assessment is made of the reliability for extracting the reduced scattering and absorption coefficients of the medium from time-resolved reflection and transillumination data. The simulation technique is employed to study the conditions for locating mm-sized objects immersed in a turbid medium, by direct, time-resolved imaging. We discuss a simple method to enhance the imaging power of the time-resolved technique. The mathematical justification of the method, as well as some applications to simple problems, is given. The simulation technique is employed to demonstrate the effectiveness of the data processing technique. Results of time-resolved reflection experiments and simulations are presented, showing that the use of the latter allow us to locate 1 mm diameter objects under conditions which would prevent detection otherwise. Our results demonstrate that the combination of simulation and the appropriate processing of the diffusive part of the time-resolved reflected or transmitted light intensity may substantially increase the potential of the time-resolved near-infrared diffusive light imaging technique as a diagnostic tool for breast cancer detection.

The forward and inverse models in time-resolved optical tomography imaging and their finite-element method solutions

Time-resolved optical computerized tomographic imaging has gained widespread attention in biomedical research recently because of its non-invasiveness and non-destructiveness to biological and several attempts, aimed at implementing a practical system, have been made for eliminating the obstacles arising from multiple light scattering of biological tissue. In this paper the basic principle of time-resolved optical absorption and scattering tomography is first presented. The diffusion approximation-based photon transport model in a highly scattering tissue, which offers an advantage in speed in comparison vath other stochastic models, and the procedure for solving this forward model by using the finite-element method (FEM) are then accessed. Theoretically, a commonly used iterative steepest descent algorithm for solving the inverse problem is introduced based on the FEM solution of Jacobian of the forward operator. Owing to the ill-posed Jacobian matrix of the forward operator caused by scatter-dominated photon propagation and unavoidable influence of the noise from the measurement process, a Tikhonov–Miller regularization method is applied to the inverse problem in order to provide an acceptable approximation to its solution. A universal strategy for the FEM solution to the optical tomography problem several numerically simulated images of absorbers and scatters embedded in a homogeneous tissue sample are reconstructed from either mean-time-of-flight or integrated intensity data for the verification of the approach.

Evaluation of spatial resolution as a function of thickness for time-resolved optical imaging of highly scattering media.

Previous experimental and theoretical investigations of the utility of time-resolved methods as a means of optical imaging through the human breast have indicated that a spatial resolution of approximately 1 cm is achievable by isolating the shortest path length photons which propagate through the tissue. Studies have also shown that resolution may be improved further by extrapolating the measured distribution using an appropriate model of photon transport. The experiments described here were performed in order to observe the relationship between achievable spatial resolution and the thickness of the medium. For a given time gate, an improvement in the spatial resolution was observed as the object thickness was reduced. Overall, the results indicate that a breast compression of about 1 cm may improve the limiting spatial resolution by as much as 7 mm. Less encouraging is the implication that temporal extrapolation over several orders of magnitude in intensity is required to achieve a comparable improvement in spatial resolution.

Convolution picture of the boundary conditions in photon migration and its implications in time-resolved optical imaging of biological tissues.

To model the effect of a tissue-air boundary on time-resolved optical measurements, a convolution picture is presented based on the photon migration picture. It is demonstrated that the boundary conditions (either index matched or index mismatched) can be formulated as a spatiotemporal convolution of two terms, with the first being identical to the solution in the infinite medium and the second being independent of the original light source. The conditions under which the spatial convolution part in the second term becomes negligible are also determined thus permitting the complete separation of the two terms by use of a temporal Laplace or Fourier transformation. This result is promising, since it, suggests a method of removing the effect of the boundary conditions in the applications of time-resolved optical imaging (in both the time domain and the frequency domain) in biological tissues.

Time-resolved optical imaging of a solid tissue-equivalent phantom

A solid plastic phantom has been developed with optical properties that closely match those of human breast tissue at near-IR wavelengths. The phantom is a 54-mm-thick slab containing four small cylinders of contrasting scatter and absorption. A detailed description of the phantom is followed by an account of an attempt to image the phantom by a time-resolved imaging technique. Images generated with transmitted light with the shortest flight times revealed the embedded cylinders with greater visibility than images obtained with continuous light transillumination. However, images corresponding to flight times of less than ~700 ps were severely degraded from a lack of detected photons. An attempt was made to overcome this degradation by extrapolating the measured temporal distributions with an analytic model of photon transport. Results suggest that subcentimeter resolution imaging of low-contrast tumors in the breast is scientifically possible. Our phantom is available to any other research groups wishing to evaluate their systems.

The spatial resolution performance of a time-resolved optical imaging system using temporal extrapolation

Optical imaging methods are being explored as a potential means of screening for breast cancer. Previous investigations of time-resolved imaging techniques have suggested that due to the lack of photons with sufficiently small pathlengths, the spatial resolution achievable through a human breast would be unlikely to be better than a centimeter. Experimental results presented here indicate, however, that higher resolution may be achieved by extrapolating the measured temporal distribution of transmitted photons. This is performed using a least-squares fit between data and an analytic model of photon transport. The spatial resolution of a time-resolved imaging system was evaluated by measuring the edge response produced by an opaque mask embedded in the center of a 51-mm-thick, very highly scattering medium. The limiting spatial resolution was improved from about 13 mm to about 5 mm.

Tomographic time-of-flight optical imaging device.

Time-resolved optical imaging has been used to image phantoms, animals, and humans, and offers the potential for the production of functional images of human tissues, such as the oxygenation of brain during stroke. We had previously reported a transmission scanner, and now give an early report on conversion to a rotational tomographic scanner with a non-parallel ray geometry similar to early CAT scanners. Initial scans show that 1) spatial imaging in turbid media using time-of-flight measurements, non-recursive algorithms, and standard tomographic geometry is possible, 2) separation of absorbance and scattering as an image is attainable, a key step in performing spatially-resolved chemometric analysis, 3) imaging of multiple objects buried within scattering material is feasible, demonstrating that equations derived for homogeneous media can be applied in at least some cases to inhomogeneous media such as tissue-like phantoms, and 4) imaging of brain pathology produces recognizable images with sufficient resolution for diagnostic decisions. We conclude that optical tomography is feasible for clinical use and that conversion of the present mechanically scanning device to a clinical scanner should be possible with retention of the current processing algorithms. Such a clinical scanner should ultimately be able to generate images in a few minutes with centimeter resolution at the center of living human brain.