The feasibility of monitoring exogenous dye uptake in tissue in vivo using pulsed photothermal radiometry.
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Animals↗
Biomedical subjects
B C Wilson
Publications and source records attributed to B C Wilson.
Magnetic resonance imaging of interstitial laser photocoagulation in brain.
Magnetic resonance (MR) imaging can be used to monitor the development of thermal lesions induced in tissue using interstitial laser photocoagulation (ILP). A potential application for ILP is the treatment of surgically inaccessible brain tumors. For the successful clinical application of MR-monitored ILP, it is necessary to relate MR images of ILP lesions to the actual induced lesions. In this preliminary study we performed ILP in the normal brains of anesthetized cats by delivering interstitially 1.0, 1.5, and 2.0 W of continuous-wave Nd:YAG laser energy (1,064 nm) for 1,000 s via a plane-cut 400 microns core optical fiber. At 48 h post-irradiation the lesions consisted of four sharply demarcated concentric zones of thermal damage. Lesion diameter increased linearly with delivered power. T2-weighted proton spin-echo images acquired during ILP showed a region of complete or near signal loss that underestimated the actual lesion at 48 h. Gadolinium-enhanced T1-weighted spin-echo images acquired immediately post-irradiation showed the actual lesion precisely.
Animals↗
Optical properties of Intralipid: a phantom medium for light propagation studies.
Intralipid is an intravenous nutrient consisting of an emulsion of phospholipid micelles and water. Because Intralipid is turbid and has no strong absorption bands in the visible region of the electromagnetic spectrum, and is readily available and relatively inexpensive, it is often used as a tissue simulating phantom medium in light dosimetry experiments. In order to assist investigators requiring a controllable medium that over a finite range of wavelengths is optically equivalent to tissue, we have compiled previously published values of the optical interaction coefficients of Intralipid, most of which were measured at a wavelength of 633 nm. We have extended the measurements of the absorption and reduced scattering coefficients from 460 to 690 nm and the total attenuation coefficient from 500 to 890 nm. These measurements show that, for stock 10% Intralipid, the absorption coefficient varies from 0.015 to 0.001 cm-1 between 460 and 690 nm, the reduced scattering coefficient varies from 92 to 50 cm-1 between 460 and 690 nm, the total attenuation coefficient varies from 575 to 150 cm-1 between 500 and 890 nm, and the average cosine of scatter varies from 0.87 to 0.82 between 460 and 690 nm. With these data, we discuss the design of an optically tissue-equivalent phantom consisting of Intralipid and black India ink.
Absorption↗
Interstitial laser photocoagulation: Nd:YAG 1064 nm optical fiber source compared to point heat source.
Interstitial laser photocoagulation (ILP) was performed in vitro in lean bovine and chicken muscle by delivering 1.6 W of continuous-wave Nd:YAG laser energy (1064 nm) from a 400-microns core optical fiber for 300s. The resulting thermal coagulation lesion was consistently larger when the delivered energy was deposited into a small steel sphere than when it was delivered freely into the tissue. Mathematical modelling confirms this result. This preliminary study suggests that a point heat source produces a larger volume of thermal coagulation than a point optical source (1064 nm) delivering the same power.
Animals↗
The use of a neural network to determine tissue optical properties from spatially resolved diffuse reflectance measurements.
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Light↗
The use of India ink as an optical absorber in tissue-simulating phantoms.
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Absorption↗
Determination of optical properties of turbid media using pulsed photothermal radiometry.
Pulsed photothermal radiometry (PPTR) measures blackbody radiation emitted by a sample after absorption of an optical pulse. Three techniques for obtaining the absorption coefficient of absorbing-only, semi-infinite samples are examined and shown to give comparable results. An analytic theory for the time dependence of the PPTR signal in semi-infinite scattering and absorbing media has been derived and tested in a series of controlled gel phantoms. This theory, based on the diffusion approximation of the radiative transport equation, is shown to model the time course of the detected signal accurately. Furthermore, when the incident fluence is known, the theory can be used in a non-linear, two-parameter fitting algorithm to determine the absorption and reduced scattering coefficients of a turbid sample with an accuracy of 10-15% for transport albedos ranging from 0.42-0.88.
Algorithms↗
Sonographic changes during hepatic interstitial laser photocoagulation. An investigation of three optical fiber tips.
RATIONALE AND OBJECTIVES: Interstitial laser photocoagulation (ILP) destroys tumors thermally, using laser energy delivered from implanted optical fibers. The objectives of the study are to identify a fiber tip/delivered energy combination which produces lesions of useful size, visible on ultrasound (US) during ILP, and to compare ILP lesions and their US images. METHODS: Hepatic ILP was performed at laparotomy in six pigs, using three different fiber tips (cylindrical diffusing, spherical diffusing, plane-cut). US images were obtained during ILP, immediately after ("early" images), and before the animals were killed (2-2.5 hours, "late" images). Actual lesions were assessed histopathologically. RESULTS: Few US changes were seen around cylindrical diffusing and spherical diffusing tips until tip destruction. Plane-cut tips, at 1.5 to 2.0 W, produced prominent US images of the 1- to 2-cm thermal lesions. Early images tended to overestimate necrosis. Late images approximated necrosis. CONCLUSION: For US-controlled ILP, plane-cut tips are better than currently available cylindrical diffusing or spherical diffusing tips. Lesion image growth periods might enable control of lesion size. Further studies are needed to determine the consistency of the described relationship between lesion images and actual lesions.
Animals↗
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↗
Use of photodynamic therapy in the palliation of massive advanced rectal cancer. Phase I/II study.
Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm2). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications.
Adenocarcinoma↗
A control method for a nonlinear multivariable system: application to interstitial laser hyperthermia.
An original adaptive control method is presented for controlling a nonlinear multivariable system. The method, which could be described as a modified quasi-linear approach, involves dividing the source excitation into a series of pulsing rounds and is implemented as a control algorithm on a computer. The theory underlying the method is developed with reference to an application involving temperature control in interstitial laser hyperthermia. In this application, the method is both successful and necessary to achieve optimally uniform elevated temperatures in a ground beef phantom. Apart from variable and parameter definitions, the method is otherwise general and might be useful for controlling a nonlinear system in which no prior exact characterization of the system is possible. Simulations were conducted to assess the effectiveness of the method in systems for which the unit excitation response changes by factors ranging from zero to three over the total period of excitation. In each case the method has proven stable.
Algorithms↗
Resistance to photodynamic therapy in radiation induced fibrosarcoma-1 and Chinese hamster ovary-multi-drug resistant. Cells in vitro.
A degree of resistance to photodynamic therapy (PDT) has been induced in radiation-induced fibrosarcoma-1 (RIF-1) tumor cells by repeated photodynamic treatment with Photofrin (4 or 18 h incubation) in vitro to the 0.1-1% survival level, followed by regrowth from single surviving colonies. The resistance is shown as increased cell survival in the strain designated RIF-8A, compared to the wild-type RIF-1 cells, when exposed to increasing Photofrin concentration for 18 h incubation and fixed light exposure. No difference was found between RIF-1 and RIF-8A in the uptake of Photofrin per unit cell volume at 18 h incubation. Resistance to PDT was also observed in Chinese hamster ovary-multi-drug resistant (CHO-MDR) cells compared to the wild-type CHO cells, possibly associated with decreased cellular concentration of Photofrin in the former. By contrast, the PDT-resistant RIF-8A cells did not show any cross-resistance to Adriamycin, nor was there any significant drug concentration difference between RIF-1 and RIF-8A. These findings suggest that different mechanisms are responsible for PDT-induced resistance and multi-drug resistance.
Animals↗
Current and future trends in laser medicine.
In this overview, a number of the major current, and possible future developments in laser medicine are explored. In therapeutic applications, particular emphasis is given to obtaining selectivity in tissue targets and interaction mechanisms in order to achieve specific biological effects. This includes spatial confinement of thermal damage by pulsed laser irradiation and targetting by exogenous photothermal or photochemical chromophores. The potential for diagnostic applications of lasers in medicine is illustrated primarily by various in vivo spectroscopic techniques. Both therapeutic and diagnostic applications will rely increasingly on the development of total systems in which lasers will form only one, albeit an essential, part. Numerous scientific and technical problems need to be solved in order to realize the full clinical potential of the many new concepts in laser medicine. The impetus for such progress will come from integrated, multidisciplinary collaborations between medical, scientific and industrial groups.
Cornea↗
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↗
Photodynamic therapy of malignant brain tumours.
Fifty patients with malignant supratentorial tumours were treated with intra-operative photodynamic therapy (PDT); in 33 cases the tumour was recurrent. In 45 patients the tumour was a cerebral glioma and in 5 cases a solitary cerebral metastasis. All patients received a porphyrin photosensitizer 18-24 hours pre-operatively. Photoillumination was carried out at 630 nm to a tumour cavity created by radical tumour resection and/or tumour cyst drainage. The light energy density ranged from 8 to 175 J/cm2. In 8 patients additional interstitial light was administered. The operative mortality was 4%. Follow up has ranged from 1 to 30 months. The median survival for the 45 primary malignant tumours was 8.6 months with a 1 and 2 year actuarial survival rate of 32% and 18%, respectively. In 12 patients a complete or near complete CT scan response was identified post PDT. These patients tended to have a tumour geometry (eg. cystic) that allowed complete or near complete light distribution to the tumour. The median survival for this group was 17.1 months with a 1 and 2 year actuarial survival of 62% and 38%, respectively. In the 33 cases who did not have a complete response the median survival was 6.5 months with a 1 and 2 year actuarial survival of 22% and 11%, respectively. Photodynamic therapy of malignant brain tumours can be carried out with acceptable risk. Good responses appear to be related to adequate light delivery to the tumour.
Adolescent↗
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↗
Photodynamic therapy: light delivery and dosage for second-generation photosensitizers.
With the development of new photosensitizers that have enhanced photoactivation at longer wavelengths than haematoporphyrin derivative, new considerations arise in the light source and delivery systems and in the techniques for physical dosimetry and in vivo optical measurements in photodynamic therapy. The limitations and future potential of solid-state laser sources are presented. The relationships between photosensitizer photoactivation characteristics and the effective photodynamic treatment volume are developed and discussed quantitatively. The problems in defining and measuring the photodynamic dose are examined, and potential techniques for measuring the factors involved in this are evaluated with emphasis on noninvasive approaches which may be used clinically.
Humans↗