Search PubMed⌕ Search

Biomedical subjects

H J Sterenborg

Publications and source records attributed to H J Sterenborg.

At least 37 records · Page 2Linked to original sources

The optical properties of lung as a function of respiration.

Lung consists of alveoli enclosed by tissue and both structures contribute to volume-dependent scattering of light. It is the purpose of this paper to determine the volume-dependent optical properties of lung. In vivo interstitial fibre measurements of the effective attenuation coefficient mu eff at 632.8 nm differed during inspiration (mu eff = 2.5 +/- 0.5 cm-1) from that during expiration (mu eff = 3.2 +/- 0.6 cm-1). In vitro measurements on a piglet lung insufflated with oxygen from 50 to 150 ml showed the effective attenuation coefficient at 632.8 nm decreases as a function of oxygen volume in the lung (at 50 ml mu eff = 2.97 +/- 0.11 cm-1, at 100 ml mu eff = 1.50 +/- 0.07 cm-1, and at 150 ml mu eff = 1.36 +/- 0.15 cm-1). This was explained by combining scattering of alveoli (Mie theory) with optical properties of collapsed lung tissue using integrating sphere measurements. Theory and measured in vitro values showed good agreement (deviation < or = 15%). Combination of these data yields the absorption coefficient and scattering parameters of lung tissue as a function of lung volume. We conclude that the light fluence rate in lung tissue should be estimated using optical properties that include scattering by the alveoli.

Absorption↗

Performance of a light applicator for photodynamic therapy in the oral cavity: calculations and measurements.

Photodynamic therapy (PDT) is an experimental therapy for the treatment of superficial cancer using laser light. In PDT a uniform light distribution is usually required for an optimal therapeutic effect. To irradiate part of the oral cavity uniformly for PDT, two prototype applicators were built, each for a different lower jaw. The applicators made use of the light transmitted through the wall of a cavity of diffusely reflecting material. The radiant exitance of the applicators was measured at 632.8 nm. For the radiant exitance of M of the two applicators, a uniformity ratio, UR = Mmax/Mmin < 2 was found, which was considered reasonable for clinical applications. Calculations predict that the UR can be improved by decreasing the thickness of the cavity wall.

Biophysical Phenomena↗

Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals.

The observed decrease in the fluorescence signal during photodynamic therapy (PDT) may contain dosimetric information as this photobleaching provides direct information on the photodynamic processes occurring in the tissue. A correct interpretation of the photobleaching signal, however, is crucial for its use in dosimetry. In this study the influence of scattering and absorption phenomena in tissue on the emitted fluorescence signal are described mathematically. Analytical solutions of the resulting expression show a difference from the single-decaying-exponential function generally used for describing photobleaching signals. The solutions are a function of the fluence rate at the inner side of tissue boundary psi(0*), the photobleaching dose constant beta, the incident irradiation power I0 and time. The accuracy of the results was investigated by comparison of the analytic solutions with numerical calculations using fluence rate profiles and escape functions obtained by Monte Carlo (MC) simulations. Good resemblance is observed when the value for psi(0*) calculated by the MC simulations is used in the analytical solutions. Experimental results in this study indicate the photobleaching dose constant of ALA-induced PpIX to be 33 +/- 3 J cm-2. Determination of beta for different types of photosensitizer and the development of an accurate method to determine psi(0*) can make monitoring of photobleaching during PDT valuable for dosimetry.

Aminolevulinic Acid↗

Evaluation of spectral correction techniques for fluorescence measurements on pigmented lesions in vivo.

Recently, the use of optical spectroscopy for non-invasive diagnosis of malignant melanoma has been suggested. The reliability of such optical measurements can be seriously compromised by spatial variations in the optical properties of the tissue that are not related to malignancy. In the present paper we report a novel approach to fluorescence spectroscopy which allows for elimination of spatial variations in the optical properties of the tissue investigated. To test this concept we performed fluorescence and color measurements on moles and unpigmented control skin in human volunteers before and after topical application of delta-aminolevulinic acid (ALA). Two types of fluorescence data analysis were investigated; a single ratio technique based on the ratio of the red to the yellow fluorescence (660-750 nm to 550-600 nm) at 405 nm excitation and a double-ratio technique, the red-to-yellow ratio at 405 nm excitation divided by the red-to-yellow ratio at 435 nm excitation. The two excitation wavelengths were selected to be located close to the maximum and at some distance from the Soret excitation band of the porphyrins. The single ratio showed a significant correlation between fluorescence and color. The double ratio was independent of the color of the lesion. These findings indicate that the double-ratio technique is suitable for in-vivo detection of local differences in concentration of fluorescent tumor-localizing drugs in pigmented lesions. This enables in-vivo studies of the pharmacokinetics of tumor-localizing agents in pigmented lesions and may significantly contribute to the development of a non-invasive diagnostic tool for malignant melanoma.

Adult↗

Photodynamic therapy with pulsed light sources: a theoretical analysis.

The effectiveness of photodynamic therapy using pulsed sources was evaluated using a mathematical model describing the time-dependent excitation and de-excitation of the photosensitizer molecule. Using the various numerical data available in the literature on haematoporphyrin we calculated that the effectiveness of pulsed excitation in PDT is identical to that of CW excitation for peak fluence rates below 4 x 10(8) W m-2. Above this threshold the effectiveness drops significantly. In practice this effect will occur with sources with high pulse energy and low repetition frequency. The commonly used dye lasers pumped by either a Cu vapour laser or a frequency doubled Nd:YAG laser have a PDT effectiveness identical to that of a CW source of the same wavelength and the same average fluence rate.

Biophysical Phenomena↗

Fluorescence localization in tumour and normal brain after intratumoral injection of haematoporphyrin derivative into rat brain tumour.

In the intracerebral 9L rat gliosarcoma, the spatial distribution of the photosensitizer haematoporphyrin derivative (HpD) was studied after intratumoral injection. The fluorescence volume was measured in histological sections from 10 min up to 5 days after injection. Complete sensitization of the tumours could not be achieved by slow stereotactical injection of 4 mm3 HpD (mean HpD fluorescence volume, 13 +/- 11 mm3). Larger parts of the tumour could be loaded with HpD (39 +/- 23 mm3, p = 0.0001) by increasing the injection velocity and the volume to 50 mm3. Again, complete sensitization of the tumours was not achieved during a time scale of 5 days after intratumoral injection. Although the fluorescence volume did not change significantly with time, it was influenced by the injection site within the tumour. Injection of HpD within 1 mm from the tumour border resulted in significantly smaller fluorescence volumes in the tumour than injection into the tumour centre. Large injection volumes caused an increased leakage of HpD to normal brain, leading to the loss of selectivity of photosensitizer content and the occurrence of dark toxicity of normal brain while the tumours still appeared vital.

Animals↗

In vivo autofluorescence of an unpigmented melanoma in mice. Correlation of spectroscopic properties to microscopic structure.

Recently, fluorescence spectroscopy and imaging have been under investigation for in vivo diagnosis of several types of superficial cancer, including primary melanomas of the skin. Here we report on a detailed investigation of the autofluorescence properties of a K1735P melanoma implanted intradermally in the ears of syngeneic C3H/HeN mice. Although this tumour can produce melanin in some cases, it appeared as an unpigmented lesion in our experiments. Excitation-emission maps in the wavelength range of 360-700 nm were recorded from tumours and normal ears. The control ears and the tumour-bearing ears showed fluorescence in a broad range of excitation and emission wavelengths. Valleys of decreased fluorescence were observed in the 385-425 nm range and could be related to absorption of the excitation light by haemoglobin, oxyhaemoglobin and a third unknown absorber. The spectroscopic differences between the malignant melanoma and the control skin could be related to either differences in blood oxygenation or the tissue dimensions. However, no spectroscopic features were detected reflecting intrinsic differences between the melanoma and normal tissue.

Animals↗

Local neurotoxicity of hematoporphyrin derivative following intracerebral injection.

The present study reports on toxicity of hematoporphyrin derivative (HpD) for normal brain tissue in vivo without the addition of light. Hematoporphyrin derivative was injected by slow infusion in rat brains. Histological examination was carried out for intervals after HpD administration, ranging from 0 h to 15 days. Ultrastructural changes were examined with transmission electron microscopy. The extent of the necrosis was determined for different HpD concentrations and compared with control animals infused with 0.9% saline. Leukocytic infiltration was observed at day 5. Transmission electron microscopy showed that nuclei of neurons were completely disintegrated 4 h after HpD administration. Furthermore disruption of myelin sheaths was observed. The extent of the necrosis decreased with lower HpD doses. Injection of 2 micrograms HpD in a volume of 4 microL (0.5 mg/mL) resulted in a virtually equal extension of the tissue damage, as compared to the mechanical damage in the control animals caused by the infusion procedure.

Animals↗

Tumor growth delay by laser-generated shock waves.

The antiproliferative effect of laser-generated shock waves (L-SW) was investigated on a human renal cell carcinoma, RC-8, grown subcutaneously in the nu/nu mouse. The RC-8 is characterized by the syndrome of humoral hypercalcemia of malignancy (HHM) associated with profound cachexia, increase of serum Ca level, hypophosphatemia, and an enhancement of serum parathyroid-like peptides. In this model system, the effects on cachexia and tumor growth were studied after a series of pulses (3-200) generated by a Candela LFDL/3 equipped pulsed-dye laser with optical fiber guided through a hypodermic needle with a 45 degrees angle bended tip, stuck through the skin of the mouse, and positioned directly below the tumor. The antitumor effect, expressed as a delay of tumor growth, was found to be dependent on number of pulses applied, tumor size, and growth rate (alpha). Treatment of RC-8 with alpha = 0.21 was effective only after 200 pulses combined with a tumor volume smaller than 100 mm3. Under these conditions a growth delay of approximately 8 days was observed, paralleled by delay of animal weight loss (cachexia). Under conditions of a decreased growth rate of RC-8 (alpha = 0.13), the susceptibility toward L-SW was found to be increased, expressed by a suppression of tumor growth after 100 pulses. However, no L-SW-associated delay of cachexia was observed under these latter conditions.

Animals↗

Wavelength dependence of skin cancer induction by ultraviolet irradiation of albino hairless mice.

Information on the variation in carcinogenicity with wavelength is crucial in risk assessments for skin cancers induced by UV radiation. Until recently the wavelength (lambda) dependencies of other detrimental UV effects, such as sunburn, have been used as substitutes. Direct information on the lambda dependency can only be obtained from animal experiments. To this end we accumulated a large data set on skin tumors induced by chronic UV exposure of albino SKH:HR1 mice (14 different broadband UV sources and about 1100 mice); the data come from the Photobiology Unit of the former Skin and Cancer Hospital in Philadelphia and from the Department of Dermatology of the University of Utrecht. The lambda dependency was extracted from this data set (a statistically satisfactory description with chi 2 = 13.4, df = 7) and represented by the Skin Cancer Utrecht-Philadelphia action spectrum, i.e., a set of factors to weight the exposures at different wavelengths according to their respective effectiveness (inversely proportional to the daily exposure required for a median tumor induction time of 300 days). The fits obtained with other already available action spectra proved to be poor (chi 2 > 60, df = 11). The maximum effectiveness was found at 293 nm, and above 340 nm the effectiveness showed a shoulder at about 10(-4) of the maximum. A sensitivity analysis of the final solution for the lambda dependency showed a large margin of uncertainty above 340 nm and an information gap below 280 nm. The large variation in tumor responses in the present data set can be transformed to a coherent, common dose-response relationship by proper spectral weighting with this single action spectrum.

Animals↗

[The use of lasers in the treatment of urolithiasis].

The treatment of calculi in the urinary tract has been subject to major changes over the last few years. Since extracorporeal shockwave lithotripsy (ESWL) is the first choice of treatment, there appears to be little need for endoscopic and surgical techniques. In case ESWL treatment is unsuccessful or inadequate, laser lithotripsy is a good alternative. In most cases, laser lithotripsy causes a good disintegration with use of very thin and flexible instrumentation. Hence, the risk of damage to the urinary tract is much less than with other endoscopic techniques such as ultrasonic and electrohydraulic lithotripsy. Our first results with 21 bladder and 18 ureter calculi in 25 patients were a successful disintegration of 84% of bladder calculi and a 70% success for ureter calculi. Only one complication of the ureteroscopic manipulation was observed. Disadvantages of laser lithotripsy are the high price of the equipment and the fact that not all calculi can be fragmented with one type of laser.

Adult↗

High-speed photographic evaluation of endoscopic lithotripsy devices.

Shock-wave generation and bubble formation occurring during endoscopic lithotripsy were studied using high-speed photography for various devices: a pulsed-dye laser, a Q-switched Nd:YAG laser and an electrohydraulic (EHL) apparatus. The three devices investigated generated gas bubbles that rapidly expanded and decayed. The maximal size of these bubbles was 5-8 mm for the pulsed-dye laser, 6 mm for the Q-switched Nd:YAG laser and up to 14 mm for the EHL device. The bubble size appeared to be governed mainly by the energy per pulse delivered by the lithotripsy device. The shock-wave pattern depended strongly on the type of device used; the 25-ns Q-switched Nd:YAG laser pulse generated a single pressure step, whereas the 1.5-microseconds pulsed-dye laser produced a train of shock fronts.

Humans↗

Photodynamic therapy of malignant glioma. A review of literature.

Photodynamic therapy is a new form of cancer treatment which can serve as an adjuvant therapy for malignant glioma. It is based on the selective retention of a photosensitive dye in tumour tissue. Subsequent exposure of the tumour to light of an appropriate wavelength causes selective destruction of tumour tissue. Experimental data indicates that the blood-brain barrier plays an important role in the delivery of the photosensitizer to a brain tumour and that intratumoral injection of the photosensitizer may be advantageous as compared to intravenous administration. A limited group of patients have entered clinical trials. Treatment protocols varied too much and the number of patients was too small to draw any conclusions on the efficiency of PDT of gliomas.

Animals↗

Evaluation of skin cancer risk resulting from long term occupational exposure to radiation from ultraviolet lasers in the range from 190 to 400 nm.

The relative risk of occupational exposure to radiation from UV lasers was estimated using a mathematical model based on both epidemiological data and animal experiments. Calculations were performed for the 193 nm ArF excimer laser cornea shaping, the 308 nm XeCl excimer laser for coronary angioplasty, and other UV lasers in a laboratory environment. The model included the effects of direct exposure and exposure to scattered radiation. The results show that for the two medical applications the increase in the relative risk is comparable to that of one additional day of sunbathing per year. For subjects exposed to UV lasers in a laboratory setting, the relative risk may increase to a value comparable to that of people with an outdoor profession.

Erythema↗

Tumorigenesis by a long wavelength UV-A source.

Albino hairless mice (Skh-hr1) were exposed daily to radiation from a high-power long wavelength UV-A source (wavelengths longer than 340 nm). The irradiations lasted 2 h per day. The daily dose was 220 kJ/m2. Heavy scratching marks were observed in 13 out of 48 animals. However during the experiment 31 of the animals developed tumors of 1 mm or larger before any scratching was observed. The median induction time was 265 days for 1 mm tumors.

Animals↗

Skin optics.

Quantitative dosimetry in the treatment of skin disorders with (laser) light requires information on propagation of light in the skin related to the optical properties of the individual skin layers. This involves the solution of the integro-differential equation of radiative transfer in a model representing skin geometry, as well as experimental methods to determine the optical properties of each skin layer. These activities are unified under the name skin optics. This paper first reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Then, previously published data as well as some current unpublished data on (human) stratum corneum, epidermis and dermis, have been collected and/or (re)analyzed in terms of absorption coefficient, scattering coefficient, and anisotropy factor of scattering. The results are that the individual skin layers show strongly forward scattering (anisotropy factors between 0.7 and 0.9). The absorption and scattering data show that for all wavelengths considered scattering is much more important than absorption. Under such circumstances, solutions to the transport equation for a multilayer skin model and finite beam laser irradiation are currently not yet available. Hence, any quantitative dosimetry for skin treated with (laser) light is currently lacking.

Absorption↗

The dose-response relationship for tumourigenesis by UV radiation in the region 311-312 nm.

Groups of hairless mice were irradiated daily with Philips TL01 UVB sources. This type of lamp has become available recently and was developed for UVB phototherapy of psoriasis. The TL01 emits radiation in a narrow band around 311-312 nm. Tumours developed on all animals. The dose-response relationship had practically the same shape as that found in a similar experiment with Westinghouse FS40 sunlamps; the tumour induction time appeared to be proportional to the daily dose to a power of -0.58. An additional experiment was performed with a TL01 from which the shorter wavelengths were filtered away. This reduced the carcinogenic effectiveness by a factor of 2.3. The potential of the filtered lamp for phototherapy of psoriasis is discussed.

Animals↗