PubMed Health⌕ Search

Biomedical subjects

M S Patterson

Publications and source records attributed to M S Patterson.

At least 37 records · Page 2Linked to original sources

Effects of light beam size on fluence distribution and depth of necrosis in superficially applied photodynamic therapy of normal rat brain.

The light fluence distributions of 632.8 nm light incident on the exposed surface of normal rat brain in vivo have been measured using an interstitial, stereotactically-mounted optical fiber detector with isotropic response. The dependence of the relative fluence rate on depth and the spatial distribution of fluence were compared for incident beam diameters of 3 and 5 mm. The fluence rate at depth of 1-6 mm along the optical axis within the brain tissue was approximately 70% greater for a 5 mm diameter beam than for a 3 mm beam, at the same incident fluence rate, although the plots of the relative fluence rate vs depth were parallel over the depth range 1-6 mm. The depths of necrosis resulting from photodynamic treatment of brain tissue using the photosensitizer Photofrin and irradiation by 632 nm light with 3 and 5 mm incident beams were also measured. The observed difference in necrosis depths was consistent with the measured difference in fluence. The importance of beam size in photodynamic treatment with small diameter incident light fields is discussed.

Animals↗

The effect of light fluence rate in photodynamic therapy of normal rat brain.

This paper reports the effect of incident light fluence rate on the depth to which necrotic lesions are produced by photodynamic therapy (PDT) in the brains of normal Fisher rats. The rats were injected intraperitoneally with Photofrin (12.5 mg kg-1) 48 h prior to PDT with a fixed incident fluence of 35 J cm-2. The treatment was performed at 10, 50, 100, and 200 mW cm-2 and also in a periodic manner (30 s "on" at 100 mW cm-2, 30 s "off"). The depth to which necrosis occurred was determined 24 h after treatment by microscopic examination of tissue sections. No differences were found in the depth to which necrosis was produced by any of the five irradiation schedules. This finding is discussed in the context of other published dose-rate experiments.

Animals↗

Experimental tests of the feasibility of singlet oxygen luminescence monitoring in vivo during photodynamic therapy.

Singlet oxygen (1O2) is thought to be the cytotoxic agent in photodynamic therapy (PDT) with current photosensitizers. Direct monitoring of 1O2 concentration in vivo would be a valuable tool in studying biological response. Attempts were made to measure 1O2 IR luminescence during PDT of cell suspensions and two murine tumour models using the photosensitizers Photofrin II and aluminium chlorosulphonated phthalocyanine. Instrumentation was virtually identical to that devised by Parker in the one positive report of in vivo luminescence detection in the literature. Despite the fact that our treatments caused cell killing and tissue necrosis, we were unable to observe 1O2 emission under any conditions. We attribute this negative result to a reduction in 1O2 lifetime in the cellular environment. Quantitative calibration of our system allowed us to estimate that the singlet oxygen lifetime in tissue is less than 0.5 microsecond. Some technical improvements are suggested which would improve detector performance and perhaps make such measurements feasible.

Humans↗

Optical properties of normal and diseased human breast tissues in the visible and near infrared.

The optical absorption and scattering coefficients have been determined for specimens of normal and diseased human breast tissues over the range of wavelengths from 500 to 1100 nm. Total attenuation coefficients were measured for thin slices of tissue cut on a microtome. The diffuse reflectance and transmittance were measured for 1.0 mm thick samples of these tissues, using standard integrating sphere techniques. Monte Carlo simulations were performed to derive the scattering and absorption coefficients, as well as the mean cosine of the scattering angle. The results indicate that scatter exceeds absorption by at least two orders of magnitude. Absorption is most significant at wavelengths below 600 nm. The scattering coefficients lie in the range 30-90 mm-1 at 500 nm, and fall smoothly with increasing wavelength to between 10 and 50 mm-1 at 1100 nm. The scattering coefficient for adipose tissue differs, in that it is invariant with wavelength over this spectral range. For all tissues examined, the scattered light is highly forward peaked, with the mean cosine of the scattering angle in the range 0.945-0.985. Systematic differences between the optical properties of some tissue types are demonstrated.

Breast↗

In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine.

In its simplest form, the photodynamic therapy (PDT) threshold dose model states that tissue necrosis due to PDT will occur if the number of photons absorbed by the photosensitizer per unit volume of tissue exceeds a critical value. This threshold is given by the product of photon fluence, photosensitizer concentration and specific absorption coefficient. To test the validity of this concept for PDT of normal rat liver sensitized with aluminum chlorosulphonated phthalocyanine (AISPC), all three of these parameters were varied by changing the injected AISPC dose, the wavelength of excitation and the irradiation geometry. The extent of necrosis caused by the treatment was consistent with the threshold model, except when the concentration of AISPC in the liver exceeded 20 micrograms g-1. For this animal model, we estimate the threshold to be (3.8 +/- 0.2) x 10(19) photons cm-3.

Animals↗

Monte Carlo modeling of light propagation in highly scattering tissues--II: Comparison with measurements in phantoms.

Measurements of the fluence-depth distributions and of the diffuse reflectance of 633 nm light have been made in liquid media with optical properties similar to soft tissues. The results are compared with predictions of Monte Carlo computer calculations in order to test the adequacy of Monte Carlo modeling of light transport in tissue. Except at extremely high albedo, the experimental data and the Monte Carlo results agree well for the depth dependence of the fluence as a function of incident light beam diameter and optical absorption and scattering, and for the dependence of the diffuse reflectance on the albedo. The absolute experimental values for the fluence must be renormalized by a factor which varies with the albedo in order to match the model values, and the possible sources of this discrepancy are discussed.

Connective Tissue↗

Monte Carlo modeling of light propagation in highly scattering tissue--I: Model predictions and comparison with diffusion theory.

Using optical interaction coefficients typical of mammalian soft tissues in the red and near infrared regions of the spectrum, calculations of fluence-depth distributions, effective penetration depths and diffuse reflectance from two models of radiative transfer, diffusion theory, and Monte Carlo simulation are compared for a semi-infinite medium. The predictions from diffusion theory are shown to be increasingly inaccurate as the albedo tends to zero and/or the average cosine of scatter tends to unity.

Light↗

Quantitative contrast measurements in B-mode images comparison between experiment and theory.

Quantitative measurements of image contrast were carried out for B-mode images of anechoic spheres (cysts) embedded in a random scattering medium. Four transducer geometries were used: (a) f/5.7 spherical transducer in pulse echo mode, (b) f/2.4 spherical transducer in pulse echo mode, (c) f/2.4, 30 degrees cone (hybrid transducer), (d) f/5.7, 30 degrees cone (hybrid transducer). The image contrast was also calculated via two methods; (i) a three-dimensional computer simulation and (ii) a relatively simple numerical convolution which relates the image of a small point-like scatterer [point spread function (PSF)] to image contrast. Generally, good agreement was found between the experimental measurements and the values calculated via both theoretical methods. The results indicate that image contrast is not determined solely by the full width at half maximum (FWHM) of the PSF. In particular, the results demonstrate the importance of far off-axis contributions of the ultrasound beam to the significant degradation of contrast in images obtained with high resolution (low f-number) axicons.

Computers↗

Speckle reduction in pulse echo imaging using phase insensitive and phase sensitive signal processing techniques.

In conventional B-scan imaging, speckle often distorts the true representation of small structures and lesions and hence reduces the diagnostic potential of the technique. Considerable speckle reduction has been achieved with an f/2.4, cone hybrid system by cutting the large aperture transducers into sectors, and using either phase insensitive sector addition (PISA), phase insensitive sector multiplication (PISM), or an rf multiplicative processing technique. We have compared two modes of operation with the hybrid system. In the first, the cone acts as transmitter, and each sector of the f/2.4 spherical aperture is a receiver. In the second mode, the f/2.4 sphere acts as transmitter, and each sector of the cone is a receiver. Quantitative assessment using the contrast to speckle ratio developed by Patterson et al, indicates that processing under both modes results in reduced speckle noise and improved image quality, with the cone sector receive (rx) geometry offering the greatest improvement.

Breast↗

The improvement and quantitative assessment of B-mode images produced by an annular array/cone hybrid.

Hybrid ultrasound imaging systems, which combine spherical focusing on transmit with axicon focusing on receive, provide excellent resolution over a useful depth of field. This paper presents a new hybrid design with improved sensitivity, in which the axicon focusing is achieved by two conical mirrors and a PZT 5A disk out into 8 sectors. We have investigated two methods of processing the signals from the 8 sectors. In the first, phase insensitive sector addition (PISA), the B-scan is formed from the sum of the 8 demodulated signals. In the second, multiplicative processing (MP), the 8 rf waveforms are multiplied and the resultant is demodulated to form the image. Both techniques result in smoothed speckle but degraded lateral resolution. As well, MP decreases the off-axis sensitivity of the system and artifacts characteristic of axicon focusing. Quantitative assessment of the effects of PISA and MP was performed using a new approach called contrast-to-speckle ratio (CSR). The CSR data, which is a measure of the image contrast of cylindrical voids in a random scattering medium relative to contrast fluctuations due to speckle, shows the superiority of PISA and MP. This conclusion is supported by images of in vitro human breast tissue.

Breast↗

Computer simulations of speckle in B-scan images.

The granularity or speckle in medical ultrasound images tends to mask the presence of small lesions. As well, artifactual filling in of anechoic regions such as cysts, reduces the diagnostic potential of the images. These effects depend not only on the acoustic properties of the tissue but also are strongly influenced by the imaging system, especially the transducer geometry. To study the effect of the transducer on the final B-scan image, a computer model has been developed simulating the interaction of ultrasound with a simple scattering medium. This model, incorporating the position dependence of the point response of the transducer, is based on single scattering from a collection of points positioned randomly in a three-dimensional volume. Using this approach, B-scan images showing speckle have been generated for different transducer geometries. Inclusion of a 2.6 mm void mimicking a cyst within the three-dimensional scattering volume has allowed us to predict the cyst contrast in the image for the different transducer systems. Experimental B-scan images of a scattering phantom were obtained using the different pulse echo systems. Quantitative assessment using first and second order statistics of the images shows good agreement between experiment and theory.

Acoustics↗

Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity.

On analysis of in vitro assays of human natural killer (NK) cell function the inadequacy of commonly used methods of expressing lytic activity was apparent. A comparison was made of the data obtained using modifications of two equations-the simple exponential fit and the von Krogh equations. Both of these equations were found to satisfy the following essential criteria for use in these assays. First, the majority of the results obtained in the chromium-release assay could be used in data reduction; second, the resultant "dose-response" curve was reduced to linearity; and third, a single numerical expression was obtained which was directly proportional to the cytotoxic activity. Of the two methods the more conventional exponential fit was found to be the simpler to use. The closeness of fit of the experimentally derived data to the ideal curves did not support the possibility that normal lymphocyte preparations contain suppressor cells capable of inhibiting NK activity. Data have also been presented showing that NK-sensitive targets could be categorized with respect to their susceptibility by comparing the slopes of the target cell survival curves obtained using the exponential fit equation. These observations are relevant to the accurate assessment of NK activity in patient populations and to the determination of the effects of disease and its treatment on this activity.

Animals↗