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Single exposure phototesting and assessment of pigmented skin lesions: quantitative methods in terms of blood perfusion estimates
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis concerns the development of quantitative phototesting for the investigation of individual skin sensitivity to ultraviolet (UV) radiation, and the assessment of pigmented skin lesions (PSL) in terms of blood perfusion estimates. In both cases, laser Doppler perfusion imaging (LDPI) was used to quantify the perfusion.

The proposed phototesting method is based on a single exposure to a divergent UVB beam, which produces a continuous, radially attenuating dose field covering an area with a diameter of 4.5 cm. In order to meet the demands posed by this approach, two-dimensional dosimetry was developed, the entire dose field was adapted to the standard erythemal action spectrum for humans, and a spatially resolving technique (LDPI) was used for objective quantification of the skin response. Data analysis methods were developed, enabling the determination of minimal erythemal dose (MED) and the extraction of dose-response information. The method was evaluated on a normal material (20 subjects), proving a good reproducibility of the MED and enhanced possibilities to extract individual dose-response information. In the study of anti-inflammatory effects (16 subjects) of topically applied substances, linear curve-fitting (0.89 ≤ R2 ≤ 0.98) was shown to adequately describe the relationship between dose and response in the dose range immediately above the MED. The gradient of the derived post MED-lines was used as a measure of the response aggressiveness. The results are promising and warrant further evaluation, e.g. in the investigation of patients with suspected photodermatoses.

This thesis also presents a method for the extraction and presentation of blood perfusion data of pigmented skin lesions in conjunction with optical information on the lesions' spatial extent. The boundaries of pigmented lesions could successfully be delineated, using standard image processing steps, in the total light intensity images given by LDPI. Classical blood perfusion measures such as mean perfusion and perfusion quotients was confined to the ROI, making relevant comparison to corresponding values of neighbouring healthy tissue possible. This data analysis approach was used on a pooled group of PSL showing promising results. The method may prove to be a useful adjunct in the discriminative assessment of pigmented skin lesions.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2003. , 68 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 839
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24502Local ID: 6626ISBN: 91-7373-722-4 (print)OAI: oai:DiVA.org:liu-24502DiVA: diva2:244823
Public defence
2003-09-19, Viktoriasalen, Universitetssjukhuset, Linköping, 09:15 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-01-02
List of papers
1. Single exposure phototesting utilizing a divergent ultraviolet beam
Open this publication in new window or tab >>Single exposure phototesting utilizing a divergent ultraviolet beam
1999 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 5, no 4, 255-259 p.Article in journal (Refereed) Published
Abstract [en]

Background/aims: Confident diagnosis of photosensitivity in patients with light dermatoses requires skin exposure to well determined ultraviolet (UV) light doses, most often from a solar simulator. The traditional test procedure results in a rough classification of skin sensitivity based on the minimal erythema dose (MED) found for each patient. The limited number of constant irradiance doses used during phototesting decreases the precision of the MED value. In the present study we aimed at developing the technical system for the determination of MED by using a single, centrifugally attenuating, UVB provocation.

Methods: A divergent UV beam was achieved with the help of an optic lens. To investigate the irradiance profile, an irradiance acquisition system was built that produced three-dimensional intensity maps. In addition, a laser Doppler perfusion imaging (LDPI) system was introduced in the evaluation of the skin response along with visual readings of the same exposed areas, in order to add a quantitative aspect to the assessment of erythema. The procedure was used on one test subject.

Results: The divergent UV beam showed the desired profile. With the current setup 20 different UV-dose levels could be discriminated. Relevant UV-dose levels were determined and tested on a subject, which in practice gave results in the form of visual assessment as well as LDPI-images. The visual or LDPI diameter gave the MED. Within the skin reaction, irradiance and the laser Doppler values could be compared mm for mm.

Conclusions: A more accurate MED determination with a single UV exposure seems to be feasible by using the proposed method. Though further investigation is required, the technique appears to offer new possibilities for the association of dose to response. In addition LDPI is possibly a useful complement to the visual readings of the skin responses, since the method gives a quantification of the grade of erythema, as opposed to visual (+, ++, +++) readings that are subjective and at best semiquantitative.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-30206 (URN)10.1111/j.1600-0846.1999.tb00138.x (DOI)15700 (Local ID)15700 (Archive number)15700 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2016-05-04
2. Phototesting based on a divergent beam: a study on normal subjects
Open this publication in new window or tab >>Phototesting based on a divergent beam: a study on normal subjects
2001 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 17, no 4, 189-196 p.Article in journal (Refereed) Published
Abstract [en]

In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-12817 (URN)10.1034/j.1600-0781.2001.170409.x (DOI)
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2016-05-04
3. Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
Open this publication in new window or tab >>Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
2003 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, 195-202 p.Article in journal (Refereed) Published
Abstract [en]

Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2003
Keyword
acetone, anti-inflammatory effects, clobetasol diproprionate, erythema, gel vehicle, laser Doppler perfusion imaging, phototesting.
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-12819 (URN)10.1034/j.1600-0781.2003.00037.x (DOI)000184575000006 ()2-s2.0-0042925506 (Scopus ID)
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-02-22Bibliographically approved
4. Single exposure phototesting: an adaptation to the CIE erythema action spectrum
Open this publication in new window or tab >>Single exposure phototesting: an adaptation to the CIE erythema action spectrum
2002 (English)In: Proceedings on the 2nd European Medical and Biological Conference, 2002, 964-967 p.Conference paper, Published paper (Refereed)
Abstract [en]

In single exposure, divergent beam phototesting, an originally collimated ultraviolet beam is diverged by an optkal lens to give a circular ultraviolet light field with attenuating irradiance towards its periphery. The chromatic aberration, caused by the lens, and its influence on the erythemal effectiveness of the field has been investigated. Spectral measurements (250-400 nm) were performed along the 20 mm radius of the field in steps of 1 mm. The corresponding erythemal effectiveness was calculated after adjustment of the spectral irradiance according to the erythema action spectrum recommended by the Commission Internationale de l' Éclairage (CIE). The erythemal effectiveness of the irradiance field attenuated towards the periphery and stabilized at about 80% of the maximum value at the centre. Knowledge of this is important for dosimetry in skin photobiology and data interpretation. The divergent beam method was used in parallel with the traditional method on three volunteers.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24527 (URN)6659 (Local ID)6659 (Archive number)6659 (OAI)
Conference
2nd European Medical and Biological Engineering Conference EMBEC'02, Vienna (Austria): Dec. 04 - 08, 2002
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2016-05-04
5. Assessment of pigmented skin lesions in terms of blood perfusion estimates
Open this publication in new window or tab >>Assessment of pigmented skin lesions in terms of blood perfusion estimates
Show others...
2004 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 10, no 1, 43-49 p.Article in journal (Refereed) Published
Abstract [en]

Background/aims: Cutaneous malignant melanoma is a disease of increasing clinical and economical importance. The prognosis is good with early diagnosis. The chief differential diagnosis is benign melanocytic naevus, a common lesion in Caucasians. Attempts have been made to use bioengineering techniques to aid in the initial diagnosis. The present study proposes a method of extracting possibly discriminative blood perfusion properties in pigmented skin lesions by combining information on the lesions' blood perfusion with optical or visual information of their spatial extent.

Methods: A total of 46 blood perfusion measurements were performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three histologically proven malignant melanomas, four histologically proven benign naevi and fifteen naevi assessed by two specialist dermatologists as being benign. Laser Doppler perfusion imaging gave two different types of two-dimensional data sets (64×64 pixels), one representing the total backscattered light intensity at each measurement point (TLI image) and the second corresponding to perfusion values. The boundaries of each examined lesion were derived from the TLI image employing greyscale thresholding, thus resulting in an estimated region of interest (ROI) approximating the optical extent of the lesion. The ROI was superimposed on the perfusion image and extraction of perfusion features was then performed.

Results: The processing of the TLI images was successful in delineating the lesions' boundaries. The first hypothesis that the mean perfusion quotients in MM and benign naevi are equal could not be rejected at the chosen 5% level of significance. The second hypothesis that the mean percent-age of elevated perfusion values (image pixels) within the ROI shows no difference between MM and benign naevi could be rejected at a 5% level of significance.

Conclusions: This study has presented a method of extracting blood perfusion parameters of pigmented skin lesions by combining blood perfusion information with information on the lesion's optical extent. The proposed method of presenting data could prove to be a useful discriminative adjunct in the assessment of pigmented skin lesions.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2004
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-22106 (URN)10.1111/j.1600-0846.2004.00052.x (DOI)000188305400007 ()2-s2.0-1042269518 (Scopus ID)1202 (Local ID)1202 (Archive number)1202 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-02-22Bibliographically approved

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