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T H Foster

Publications and source records attributed to T H Foster.

At least 37 records · Page 2Linked to original sources
PubMed1994

Oxygen diffusion and reaction kinetics in the photodynamic therapy of multicell tumour spheroids.

Effects of oxygen diffusion and reaction kinetics in photodynamic therapy are considered in the context of a multicell tumour spheroid model. Steady-state measurements of oxygen made with a Clark-style microelectrode (4 microm diameter tip) enable us to determine the rate of metabolic oxygen consumption and the oxygen diffusion coefficient in 500 microm diameter EMT6/Ro spheroids. These values are 5.77 micromol 1(-1) s(-1) and 1460 microm2 s(-1), respectively. Time-dependent electrode measurements of oxygen concentration during laser irradiation of individual Photofrin-sensitized spheroids are fitted to numerical solutions of a pair of diffusion-with-reaction equations. The analysis yields the rate of photodynamic oxygen consumption and a parameter that governs the oxygen sensitivity of photodynamic therapy. These experimentally derived quantities are used to calculate the temporal and spatial distributions of oxygen and the rate of oxygen consumption in a spheroid during irradiation at several fluence rates. The spatial distribution of photodynamic oxygen consumption is strongly fluence rate dependent. Using the experimental and theoretical results developed in this report, previously published survival data are analysed. The analysis indicates that the threshold dose of reacting singlet oxygen in the EMT6/Ro spheroid is 323 +/- 38 micromol 1(-1) (mean +/- SEM).

Animals↗
PubMed1993

Fluence rate effects in photodynamic therapy of multicell tumor spheroids.

EMT6/Ro spheroids approximately 500 microns in diameter were subjected to photodynamic therapy administered at various incident radiation fluence rates. Following 24 h incubation with 10 micrograms/ml Photofrin, groups of spheroids were irradiated at 630 nm with an identical fluence of 60 J/cm2, delivered at fluence rates ranging from 25 to 200 mW/cm2. After treatment, spheroids were dissociated, cell yields were determined, and surviving cells were assayed for their colony-forming ability. A surviving fraction was calculated for each treatment group by computing the product of the fractional cell yield and the plating efficiency. The results exhibit a strong dependence on the fluence rate, with surviving fractions decreasing from approximately 0.5 to 0.07 as the incident fluence rate was lowered from 200 to 25 mW/cm2. These data were analyzed using a mathematical model of photochemical oxygen consumption in spheroids undergoing photodynamic therapy. Calculations showed that therapy-induced oxygen consumption creates hypoxic volumes within which cells would be protected from singlet oxygen-mediated damage and that the magnitude of these hypoxic volumes depends on the radiation fluence rate. The fluence rate dependence of the spheroid cell survival was consistent with such an interpretation.

Animals↗
PubMed1992

Photofrin and light induces microtubule depolymerization in cultured human endothelial cells.

Endothelial cells were cultured from human umbilical veins and incubated with Photofrin (1 microgram/ml). Cells were then exposed to light, and cytoplasmic microtubule (MT) status was monitored by immunofluorescence microscopy using alpha-tubulin antibody. As early as 15 min following irradiation, a light dose-dependent depolymerization of MT was observed. At sublethal light doses, this effect was transient, with MT repolymerizing within 2-3 h. Cellular ATP levels were monitored to determine whether diminished ATP levels were correlated with MT depolymerization. No correlation was found, since ATP levels remained at a constant value near 50% of unirradiated controls during a time interval in which transient MT depolymerization was observed. Cell viability was monitored by trypan blue exclusion. Transient MT depolymerization occurred at photodynamic doses that produced essentially no decrease in cell viability, while at higher doses, irreversible MT depolymerization was observed prior to loss of viability. Since MT are unstable at intracellular calcium levels greater than 1 microM, we postulate that MT depolymerization results from increases in intracellular calcium caused by photodynamic insult. MT are important in maintaining cell shape. Disruption of MT in endothelial cells due to photodynamic therapy could result in or contribute to exposure of the thrombogenic subendothelium or could alter vascular permeability in the treatment area.

Adenosine Triphosphate↗
PubMed1992

Dosimetry in photodynamic therapy: oxygen and the critical importance of capillary density.

Recently published results of tumor response to various photoradiation protocols in photodynamic therapy appear to contradict accepted definitions of photodynamic dose. In this report, the failure of standard dosimetry models to predict therapeutic outcome is interpreted on the basis of PDT-induced oxygen consumption in tumors with relatively low capillary densities. Calculated estimates of oxygen consumption in photodynamic therapy are combined with the Krogh cylinder model of oxygen diffusion. It is shown that, for tissue volumes in which the intercapillary spacing is less than a specific critical distance, oxygen may be considered constant and unaffected by the therapy. Under these conditions, the 1O2 delivered to a given volume of tissue is spatially uniform and proportional to the number of photons absorbed by the sensitizer. When the intercapillary spacing exceeds the critical distance, the dose of 1O2 varies with radial distance from the capillary wall. In this situation, dose may no longer be considered simply in terms of the product of the photon fluence and the sensitizer absorption coefficient. Since fractionation will increase the 1O2 dose only to cells relatively remote from the capillary wall, the analysis further suggests that fractionating the radiation dose should result in an improved therapeutic ratio for photodynamic therapy.

Capillaries↗
PubMed1991

Photosensitized release of von Willebrand factor from cultured human endothelial cells.

Cultured endothelial cells from the human umbilical vein were incubated with low concentrations (1 microgram/ml) of the photosensitizer Photofrin II. Following a sublethal light exposure, a light dose-dependent release of von Willebrand factor (vWf) into the culture medium was observed. Analysis of the multimeric composition of the released protein indicated that it originated from the intracellular pool of large vWf multimers stored in the Weibel-Palade bodies. This release was detected as early as 1 h postirradiation. Release was inhibited at low temperature and was dependent upon the presence of extracellular calcium. Photosensitization resulted in an influx of calcium whose time course paralleled vWf release from the cells. Since vWf mediates platelet adhesion to the vascular subendothelium, it is possible that its photochemically stimulated release in vivo could contribute to platelet thrombus formation observed in tissue following photodynamic therapy.

Cysteine↗
PubMed1991

Oxygen consumption and diffusion effects in photodynamic therapy.

Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of 50 mW/cm2 may consume 3O2 at rates as high as 6-9 microM s-1. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize 1O2-mediated damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with 360 J/cm2 delivered at 50 mW/cm2 compared to the same light dose delivered at 200 mW/cm2. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.

Animals↗
PubMed1990

Diagnosis of femoropopliteal venous thrombosis with MR imaging: a comparison of four MR pulse sequences.

In a prospective study, MR images were evaluated in seven patients with femoropopliteal venous thrombosis with symptoms of less than 5 days duration. T1-weighted (600/25 [TR/TE]), intermediate (2000/30), and T2-weighted (2000/100) spin-echo series and a gradient-recalled acquisition in the steady state (GRASS) series were compared. Using venography as the standard for diagnosis, we found GRASS to be the most sensitive of the MR techniques, showing thrombi in all patients. It provided good contrast between the low-intensity thrombus and high-intensity flowing blood and also between thrombus and intermediate- or high-intensity perivascular tissues. The T1-weighted series was the least sensitive technique. All thrombi showed heterogeneity in the transaxial image with differences in signal between the peripheral and central regions. A higher intensity signal in the center than in the periphery at some level of the thrombus was found in six of seven T2-weighted or GRASS images. Heterogeneity in the signal intensity was more frequent in distal portions of thrombi, whereas the most proximal extent was homogeneous in appearance in six of seven cases. The heterogeneous appearance may be related to the greater age of the distal thrombus, because deep venous thrombi are known to begin in the calf and extend proximally over time. We conclude, on the basis of our experience with a small number of patients, that the GRASS MR technique is more sensitive for detecting acute deep venous thrombosis than T1-weighted, intermediate, and T2-weighted MR images.

Adult↗
PubMed1989

Reduced-bandwidth MR imaging of the head at 1.5 T1.

A decrease in the magnetic resonance (MR) imaging bandwidth can be used to increase the signal-to-noise ratio (S/N) at constant imaging time or to maintain the S/N for reduction of imaging time. The effect of bandwidth reduction from the default value of 16 kHz to 8 kHz was evaluated prospectively in 50 patients referred for MR imaging of the head. On intermediate (2,000/30 [repetition time msec/echo time msec]) and more T2-weighted (2,000/90) studies, there were no definite missed diagnoses and no diagnostically important changes in lesion characteristics when the reduced-bandwidth technique was used to obtain half- or quarter-time studies, excluding differences attributable to unintentional changes in patient position between image acquisitions. Chemical shift misregistration artifacts associated with reduced bandwidth are easily recognized with experience and do not interfere with diagnosis, as the artifacts occur in characteristic locations and diminish in most anatomic locations with increasing echo time. This study suggests the feasibility of reduced-bandwidth techniques in clinical MR imaging of the head at high field strength to achieve an increased S/N, to decrease imaging time, or to obtain images in additional projections.

Brain↗
PubMed1986

NMR imaging shows water distribution and transport in plant root systems in situ.

Images of Vicia faba L. root systems at 0.6-mm resolution, undisturbed and within the soil medium in which they were grown, have been obtained by using a 1.5-Tesla proton ((1)H) NMR medical imaging research system. Images of root systems in seven soil media (Cahaba soil, vermiculite, sand, perlite, fritted clay, potting soil, and peatlite) exhibited variable but useful quality owing to a diversity of magnetic properties of the soils. Root structure and pathology in the form of partial decay of hypogeal cotyledons were easily discernible. Water transport in roots with light-stressed foliage was demonstrated by using water doped with a paramagnetic NMR contrast agent, and the process of plant-wilt and recovery was monitored in situ. Images of germinated seeds within soil media indicated that dynamic observations of germination and growth are possible. The results suggest that NMR imaging can be an effective noninvasive tool for studying plants in situ.

Journal Article↗
PubMed1986

Normal and abnormal temporomandibular joint: MR imaging with surface coil.

The normal temporomandibular joint (TMJ) was evaluated using magnetic resonance (MR) imaging with a surface coil in five subjects and compared with the abnormal joint in 37 patients (aged 14-59 years; total joints studied, 76). Multisection 3-mm-thick sagittal, coronal, and axial images were obtained with a 1.5-T MR system and 6.5-cm-diameter surface coil using both partial saturation and spin-echo sequences (TR = 1,000 msec, TE = 20 or 25 msec). A comparison with arthrography (n = 13 joints), computed tomography (CT) (n = 11), and surgical (n = 5) findings demonstrated that MR imaging with a surface coil provided an accurate depiction of both normal and abnormal TMJs. MR provided information about meniscal position, morphology, and histology that was not available with either arthrography or CT alone. The imaging potential of MR and its noninvasive characteristics warrant priority for further examination of MR as a useful modality in the diagnosis of TMJ pain and dysfunction.

Adolescent↗
PubMed1986

High resolution magnetic resonance imaging using surface coils.

There is, of course, an intense activity directed at the improvement of MR imaging capabilities. Surface-coil techniques offer the possibility of improving the SNR sufficiently to permit the reduction of pixel sizes to values that would not be possible with conventional head and body coils. The successful application of surface-coil techniques to MR imaging suggests that this technique will be widely used in future MR imaging systems. This provides a fertile field for new research. This includes opportunities for mathematical and physical research into optimizing coil design. It also includes many opportunities for clinical research into the utilization of surface coils and high resolution MR imaging.

Equipment Design↗
PubMed1985

Orbital magnetic resonance imaging.

Magnetic resonance images of the eye and orbit performed with surface coils at 1.5 tesla showed anatomic details superior to those of conventional third- and fourth-generation computed tomography.

Anterior Chamber↗
PubMed1985

In vivo solvent-suppressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism?

Solvent-suppression NMR techniques are combined with a pulsed magnetic field gradient and surface coil detection method of spatial localization. The result is a technique that enables observation of metabolites in the hydrogen (1H) NMR chemical-shift spectra from preselected disk-shaped volumes of biological tissue in vivo. Localized spectra are recorded from the normal human brain and forearm and from a dog in acquisition periods of 2 s using a 1.5-T imaging/spectroscopy system. This is several hundred-fold faster than acquiring similar state-of-the-art 31P NMR spectra of brain metabolites in vivo. Spectroscopy experiments are followed by conventional surface coil imaging sequences to precisely define the selected volume. Contamination of spectra by lipid resonances is a problem.

Animals↗
PubMed1985

Ocular and orbital lesions: surface coil MR imaging.

Nine lesions, four ocular (three melanomas, one hemangioma) and five orbital (two perioptic meningiomas, one hemangioma, one pseudotumor, one mucocele), were evaluated by magnetic resonance surface coil imaging at 1.5 T. Small ocular lesions with 3.9-4.5-mm-elevation were demonstrated. The use of two different pulse sequences resulted in separation of melanoma from adjacent retinal detachment. Contrast obtained between orbital lesions and the adjacent normal structures was better than that demonstrated with high-resolution computed tomography.

Adolescent↗
PubMed1985

Improved MR imaging of the orbit at 1.5 T with surface coils.

A method for obtaining localized high-resolution magnetic resonance (MR) images of the eye and orbit is demonstrated. The method uses modified surface receiver coils placed immediately adjacent to the anatomy to detect the MR signal. Surface coils provide enhanced sensitivity for imaging voxels close to the surface of the body while limiting the received patient-generated noise. The resulting improvement in signal-to-noise ratio allows for a reduction in the imaging voxel size to about 0.5 X 0.5 X 5 mm in scan times of 3.4-5 min. At this level of resolution, anatomic detail in the orbital region previously unobservable in MR images is seen.

Eye↗