EP1567050A1 - Methodes et dispositif de mesure histologique - Google Patents

Methodes et dispositif de mesure histologique

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Publication number
EP1567050A1
EP1567050A1 EP03809780A EP03809780A EP1567050A1 EP 1567050 A1 EP1567050 A1 EP 1567050A1 EP 03809780 A EP03809780 A EP 03809780A EP 03809780 A EP03809780 A EP 03809780A EP 1567050 A1 EP1567050 A1 EP 1567050A1
Authority
EP
European Patent Office
Prior art keywords
melanin
measurement
dermal
dermal melanin
texture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03809780A
Other languages
German (de)
English (en)
Inventor
Symon D'oyly Cotton
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Astron Clinica Ltd
Original Assignee
Astron Clinica Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Astron Clinica Ltd filed Critical Astron Clinica Ltd
Publication of EP1567050A1 publication Critical patent/EP1567050A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/444—Evaluating skin marks, e.g. mole, nevi, tumour, scar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/445—Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore

Definitions

  • This invention relates to methods and apparatus for the non invasive measurement of epithelial tissue histology and is particularly, but not exclusively, concerned with measuring skin histology.
  • epithelial tissues include the respiratory tract, the genital tract, the gastrointestinal tract and the retina of the eye.
  • the present invention is considered to be potentially useful for the preliminary screening of patients to identify those who should be referred to an appropriate clinician for diagnosis and further to assist the clinician in diagnosis.
  • chromophores within these tissues and their lesions is considered to be potentially useful information for the screening of patients to identify those who should be referred to an appropriate clinician for further diagnosis through tissue biopsy, or other conventional tests.
  • Devices to detect these distributions with non invasive techniques are therefore beneficial. Further, the simplification of such devices and the automation of the diagnostic process will make such devices available to wider populations.
  • FIG. 11 shows a cross section of skin.
  • the major structural layers are well known, cornified layer 45, epidermis 46, dermo-epidermal junction 47, papillary dermis 48, recticular dermis 49.
  • melanocytes 50 the cells responsible for the production of the pigment melanin, lie in the epidermis.
  • some benign skin lesions such as the compound nevus melanocytes can exist in a characteristic pattern in both the epidermis and the papillary dermis.
  • the melanocytes can be asymmetrically distributed in both the epidermis and papillary dermis.
  • the present invention provides additional information on the distribution of the pigment melanin in the papillary dermis, and includes a method for analysing this data. This method is also applicable to other epithelial tissues with similar layered structures with differing optical properties.
  • melanin existing up to the dermo-epidermal junction is facilitated by allowing the thickness of layer 1 to be zero and likewise melanin can exist up to the papillary-reticular dermis boundary by setting the thickness of layer 4 to be zero.
  • ⁇ ( ⁇ ,p, ⁇ ) can be shown to be the sum of iv ( ⁇ ), ⁇ b ( ⁇ ) and ⁇ m ( ⁇ ), where ⁇ m( ⁇ ) is the absorption coefficient of melanin. From the above it is possible to calculate R and T (diffuse radiation and transmission respectively) . For simplicity of notation it is helpful to consider Rl and Tl where,
  • Two-layer systems can be combined to produce the total remitted and transmitted light for the dermis resulting in an equation which can be simplified using the geometric series
  • T Uotal can be shown to be
  • This system of equations can therefore compute the total remitted and transmitted light from an n layered system of arbitrary complexity provided that the thickness and composition of the layers is specified.
  • This equation can then be used to generate the expected coloration of human skin exhibiting dermal descent of melanin.
  • Equation 1 may be modified to suit other tissues and chromophores and in the following description the terms 'skin' and 'melanin' represent a particular example application of this method.
  • the technique is particularly applicable to the chromophore haemoglobin in the skin where this method can be readily applied.
  • a method of non-invasively analysing skin structure comprising the steps of: (i) irradiating a plurality of locations over an area of tissue under investigation and detecting the light remitted at each location;
  • step (iii) comparing the measurement for the dermal melanin obtained in step (ii) with the measurement for the total melanin obtained in step (ii) ; and (iv) using the comparison obtained in step (iii) to investigate the skin.
  • An advantage of this method is that it facilitates the investigation of the skin histology and/or the condition of the skin.
  • This method is generally for analysing epithelial tissue histology and comprises irradiating a plurality of locations in an area of tissue under investigation with light and detecting light remitted at each of the plurality of locations to provide a spectral measurement over said plurality of locations.
  • the method comprises mapping each spectral measurement into a two dimensional colour space, the two primaries arranged such that variations in blood concentration in the tissue have substantially no effect in that space.
  • more than two dimensions may be used. The skilled person will appreciate that the use of two dimensions compared to using further dimensions reduces the processing required to perform the method.
  • the method may for example use 3, 4, 5, 6, 7, 8, 9, 10 or more dimensions.
  • the method may further comprise, for each spectral measurement calculating:
  • ⁇ is the density of melanin.
  • the method may further comprise plotting S(p ud ,p ld ,d ud ,d ld ,d l2 ,d l , ⁇ ,d m ) in that space to provide a series of contours of increasing dermal melanin concentration at the papillary dermis depth.
  • the plotting of contours in this manner provides a convenient way of assessing the function.
  • Point 1 is the position of infinite melanin concentration in any position in the skin
  • point 2 is the point of non melanin in the skin.
  • the line 5 connects points of increasing melanin concentration in the epidermis 45.
  • a machine readable medium containing instructions which when read onto a machine cause that machine to perform the method of the first aspect of the invention.
  • the machine readable medium of any of the aspects of the invention may be any one or more of the following: a floppy disk; a CDROM/RAM; a DVD ROM /RAM (including +R/RW,-R/RW); any form of magneto optical disk; a hard drive; a memory; a transmitted signal (including an internet download, file transfer, or the like) ; a wire; or any other form of medium.
  • Figure 1 shows a graph of a function of dermal melanin depth, dermal melanin concentration and epidermal melanin concentration assuming a constant dermal melanin concentration
  • Figure 2 shows the graph of Figure 1 repeated for a range of dermal melanin concentrations
  • Figure 3 shows a graph of a function of dermal melanin depth, dermal melanin concentration and epidermal melanin concentration assuming a constant dermal melanin depth
  • Figure 4 shows the graph of Figure 3 repeated for a range of dermal melanin depths
  • Figure 5 shows a graph showing areas of similar value of a fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration);
  • Figure 6 shows a diagram of a typical skin lesion viewed from above;
  • Figure 7 to 9 show embodiments of devices that may be used for performing methods described herein;
  • Figure 10 shows a flowchart outlining steps in a method used in one embodiment of the invention
  • Figure 11 shows a cross section of skin
  • FIG. 12 shows a flowchart outlining steps in the methods described herein.
  • Figure 11 shows that that there are three variables of interest that define the distribution of melanin in the skin.
  • concentration of melanin in the epidermis the concentration of melanin in the papillary dermis and the location of melanin in the papillary dermis.
  • Two simplified cases are considered, the first where the concentration of melanin in the papillary dermis is assumed to be uniform, and secondly that the depth of dermal melanin is either zero or the depth of the papillary dermis itself.
  • point 3 is a point of chosen melanin concentration in the epidermis. As dermal melanin depth is increased (at standard concentration) the line 6 is generated. Point 4 represents the maximum possible depth that is the depth of the papillary dermis itself. This depth may have been standardised by the data calibration steps described in GB 9624003.1 but briefly which are as follows:
  • an image of the area of skin under investigation is represented in the same colour space as for the normal skin reference colour co-ordinate range.
  • the skin colour coordinates are acquired from an image using the same lighting conditions and a CCD camera calibrated in the same way as that used to produce the healthy skin reference colour co-ordinate range.
  • a white standard or other appropriate correction factor can be used to allow calibration of the image within the software.
  • a colour image can be acquired using a colour photographic film which is then digitised. This can be performed using either exactly the same lighting conditions and a calibrated set-up or again with the inclusion of a white standard or other appropriate correction factor.
  • Figure 2 shows the effect of repeating line 6 with different amounts of dermal melanin.
  • Lines 5,10,11,12 are then plotted joining points on these lines where the same dermal melanin depth is used.
  • Lines 5,10,11,12 define areas 7,8,9 that represent areas where colours of shallow, medium and deep dermal melanin depth will lie.
  • Figure 3 shows the same axes, curve 5 with end points 1 & 2 as described above.
  • a point of epidermal melanin concentration is chosen 13 and two lines of low and high dermal melanin concentration are plotted with increasing depth 17, 16.
  • the points at which the maximum dermal melanin depth is reached (papillary dermis depth) on these lines are 14 and 15.
  • Figure 4 shows these points 14, 15 joined to form lines of constant dermal melanin concentration at maximum depth 18, 19,20. These lines bound areas 21,22,23 that represent areas where colours of low, medium and high dermal melanin concentration will lie, assuming dermal melanin exists and its maximum possible depth.
  • Areas 21 ( Figure 4) and 9 ( Figure 2) represent tissue with either deep, low concentration melanin, or shallow high concentration melanin (approximating to tissue with a low 'dermal melanin volume'). Whereas areas 23 ( Figure 4) and 7 ( Figure 2) represent tissue with deep, high concentrations of dermal melanin (approximating to tissue with high 'dermal melanin volume'). Line 20 represents the spectral response of tissue where significant melanin has penetrated the papillary dermis.
  • 'Dermal melanin volume' is clinically significant because in a typical melanoma lesion the melanin producing cells, melanocytes, are similar because they are all produced by reproduction from a single mutated cell, and therefore changes in melanin concatenation are likely to be small compared to changes in the location of these cells. Therefore in such lesions areas with increased 'dermal melanin volume' areas with increased dermal melanin depth. Dermal melanin depth is a well-known diagnostic and prognostic indicator in melanoma.
  • 'dermal melanin volume' is measured at an array of points across an area of skin, the measurements can be mapped to colours and displayed as a visualisation approximating to a map of dermal melanin depth across the lesion. This can assists the clinician is determining the degree of chaos in the distribution of melanocytes within the lesion.
  • a particular technique to make measurements of fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration) or 'dermal melanin volume' is as follows.
  • a spectral measurement is made using a device as described in Figures 7,8 and 9 or devices described in PCT/GB01/01986 or PCT/GB01/03011, and the measurements plotted on a graph indicating the areas of similar values of fn(Dermal melanin depth, Dermal melanin concentration, Epidermal melanin concentration) as shown in Figure 5. This measurement can then be categorised by fn(Dermal melanin depth, Dermal melanin concentration, Epidermal melanin concentration).
  • the method comprises mapping each spectral measurement into a two dimensional colour space, the two primaries arranged such that variations in blood concentration in the tissue have substantially no effect in that space.
  • the mapping may be performed by projecting the a surface onto the two dimensional co-ordinate system.
  • the skilled person will appreciate that other techniques are equally possible for mapping the measurement onto the two dimensional colour space.
  • a second particular technique to make measurements of fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration) or 'dermal melanin volume' is as follows.
  • a spectral measurement is made using a device as described in Figures 7,8 & 9 or devices described in PCT/GB01/01986 or PCT/GB01/03011 and plotted on the graph shown in Figure 4.
  • This measurement is compared to lines of changing dermal melanin concentration with constant dermal melanin depth.
  • the line that intersects the measurement point provides a value of dermal melanin concentration which can be used as an approximation to the value of fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration).
  • Figure 12 describes this process.
  • these measurements are taken over a series of adjacent 15 micron square pixels over a 10 mm area, and the spectral measurements are made are the percentage remittance of light from the tissue at three separate primary wavebands with peaks at roughly 450nm 550nm and 650nm, each with a roughly 80nm bandwidth.
  • the skilled person will appreciate that in other embodiments other wavelengths for the peaks may be suitable.
  • peaks centered at roughly any of the following may be suitable: 400nm, 410nm, 420nm, 430 nm, 440 nm, 460nm, 470nm, 480nm, 490nm, 500nm, 510nm, 520nm, 530nm, 540nm, 560nm, 570nm, 580nm, 590nm, 600nm, 610nm, 620nm, 630nm, 640nm, 660nm, 670nm, 680nm, 690nm, 700nm or any value in between these values.
  • the bandwidth of the peak may be varied and may be roughly 50nm, 60nm, 70nm, 90nm, lOOnm, llOnm, 120nm, 130nm, or any value between these values.
  • the measured point could be plotted on Figure 2 where the measurement is compared to lines of changing dermal melanin depth with constant dermal melanin concentration.
  • the line that intersects the point provides a value of dermal melanin depth which can be used as an approximation to the value of fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration).
  • point 3 would represent a zero value, and point 4 a maximum value.
  • the approximate value of fh(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration) obtained from the above methods can be further analysed to enable suspicious lesion to be differentiated from benign ones.
  • the following analysis technique can also be applied to arrays of other measurements made spatially across a tissue sample.
  • the measurements may be of blood or collagen concentration.
  • malignant skin lesions often contain the pigment melanin in the papillary dermis of the skin.
  • a device that detects the presence of dermal melanin is effective at detecting malignant lesions and such devices are described in our patent applications GB0016690.0 and GB0112501.2.
  • these devices suffer from false positives generated by benign lesions which also contain dermal melanin.
  • dermal melanin including the compound nevus and blue nevus. Therefore to increase the specificity of a device to detect malignant lesions a method of differentiating benign lesions containing dermal melanin for malignant lesions is beneficial.
  • Embodiments of this invention provide a method of automatically measuring the chaotic growth of the lesion.
  • Figure 6 shows a diagram of a typical skin lesion viewed from above.
  • the skin 26 contains a malanocytic lesion 25, containing epidermal melanin as well as a region containing both epidermal and dermal melanin 27.
  • two data arrays are created to describe the lesion derived from spectral measurements using the techniques described in the text above and our previous patents which are also detailed above and incorporated herein by reference.
  • one array contains values proportional to the total amount of melanin in the skin, and a second with values approximating to fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration). Where no dermal melanin exists this second array has zero values.
  • a well-known property of skin lesions is they have characteristic patterns in the distribution of melanin. Benign lesions have a variety of patterns, but these patterns are similar in both the epidermis and papillary dermis as melanocytes slowly descend from the dermal/epidermal junction into the papillary dermis. These melanocytes can also cease melanin production limiting dermal melanin to a shallow even layer in the papillary dermis. Malignant lesions characteristically grow chaotically in three dimensions so the patterns of melanin distribution are significantly different in the epidermis and papillary dermis. This invention detects these differences through a mathematical process.
  • Figure 10 describes this process. In a particular implementation it operates on two arrays of data generated from spectral measurements taken over an area of skin.
  • One array is of measurements of total melanin calculated using the method described in GB9624003.1 and PCT/GB00/02124, and the second is an array of values of fn(dermal melanin depth, dermal melanin concentration, epidermal melanin concentration) or 'dermal melanin volume' calculated from the process described in Figure 12.
  • the two arrays may provide images of the total melanin and the dermal melanin volume respectively.
  • step 1 of Figure 10 the lesion is identified by applying a threshold to values of total melanin TM(x,y).
  • step 2 the texture of the total melanin array within the lesion is measured i.e. the apparent texture of the image represented by the array is determined.
  • the standard deviation SD is used to determine the texture, but other well known statistical measures could also be used such as range or fractal dimension.
  • the numbers within the array are taken as a series and the standard deviation of these using known mathematical methods is taken.
  • step 3 areas inside the lesion where dermal melanin is present are identified as those coordinates where the 'dermal melanin volume' DMN(x.y) is not zero.
  • step 4 the same texture measurement is made of DMN(x,y).
  • the standard deviation SD is used again in order to determine the texture of the image, but other well known statistical measures could also be used such as range or fractal dimension.
  • step 5 a ratio of the two texture measurements is made and in step 6 this is threshold is applied to determine malignancy. Calculating the ratio in this manner may be thought of as comparing the roughness of the texture of the images. It has been found that if the dermal melanin has a rougher texture than the 'dermal melanin volume' then the likelihood of a malignancy increases.
  • An improvement to this sequence is to add a preliminary step which detects elements in the array where hairs are present on the skin and marks them to be excluded from the calculation process. Erroneous data from the presence of hair has been found to disrupt this algorithm and provide unreliable results.
  • This device consists of a light tight housing 30 containing a transparent optical window 29 which is placed in contact with the skin 28.
  • Light of a specific wavelength band is generated by light emitting diodes mounted on a ring 33.
  • This ring may contain a number of groups of LED's each with it's own emission waveband. In one particular embodiment there are four groups of LED's, each group containing between 8 and 24 individual LED dies, this number depends on the brightness of the individual devices, where relatively dim devices are used in larger numbers to approximately equalise the iUiimination intensity across wave bands.
  • the wavebands of each group of LED's span between 400nm and lOOOnm.
  • an additional reflector is mounted beside each LED to ensure a majority of the emitted light is reflected onto the window 19.
  • an additional filter is added over one or more of the LED groups to eliminate unwanted emissions in the infra-red region of the spectrum. This ring 33 is covered by a polarising filter 32.
  • a feature of the design of the LED system is that the LED's are evenly spaced relative to the window 29 to ensure even illumination of the skin 28.
  • the LED iUuminator is controlled by an electronic driver system 38 which receives control signals from the processing means 39.
  • the electronic driver system responds to signals received from the processing means and switches the LED groups on and off in sequence as required to synchronise with the camera system 35 and 37.
  • the driver system can deliver different currents to each LED group, these currents can be generated according to data passed from the processing means 39 to the LED control system 38.
  • the driver system can deliver different currents to each LED to compensate for the differences in efficiency of each device.
  • Light remitted from the skin 28 passes through a second polarisation filter 31 mounted such that its polarisation axis is at 90 degrees relative to the polarisation axis of filter 32. This light then passes into the lens 34, and is focused onto a CCD sensor array 35 .
  • the lens 34 is designed to focus affectively over a wide waveband corresponding to the wavebands emitted by the LED illuminator 33.
  • this waveband is from 400 nm to 1000 nm
  • the CCD sensor is controlled by an electronic system 37 which converts the light intensity on each array element into a digital pixel value in an image array which is passed to the processing means 39.
  • the processing means can control the exposure time and gain of the CCD array 35.
  • the complete device is controlled by a control program implemented by the processing means 39. This program provides for a sequence of images to be acquired, each with a different illumination spectrum provided by the LED light source 33 and a corresponding exposure time.
  • eight individual images are recorded, one with each of four wavelength bands with exposures set such that normal skin can be recorded.
  • the eighth image is taken with no illumination to determine the black values for each picture element.
  • the image acquisition cycle is triggered by switch 36.
  • the image data is then processed using algorithms described above.
  • the process data is displayed on a screen 40.
  • FIG 8 One particular embodiment of this device is illustrated in Figure 8, in which items 29 to 3 8 are contained within a handset 41 and the processing means and display means are provided by a laptop computer 42. This provides a compact and portable implementation of this device.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Measuring And Recording Apparatus For Diagnosis (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne une méthode d'analyse non effractive de la structure cutanée, dont les étapes consistent à irradier une pluralité d'emplacements répartis dans une zone de tissu examinée et à détecter la lumière renvoyée par chaque emplacement. Ces étapes peuvent être suivies d'une analyse de la lumière renvoyée par chaque emplacement, et d'une mesure représentant la quantité totale de mélanine et la mélanine dermique contenues dans le tissu examiné. La mesure de la mélanine dermique peut ensuite être comparée à une mesure antérieure de la mélanine totale. Cette comparaison est alors utilisée pour effectuer une analyse histologique de la peau.
EP03809780A 2002-10-29 2003-10-29 Methodes et dispositif de mesure histologique Withdrawn EP1567050A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0225060A GB0225060D0 (en) 2002-10-29 2002-10-29 Methods and apparatus for measuring tissue histology
GB0225060 2002-10-29
PCT/GB2003/004672 WO2004039255A1 (fr) 2002-10-29 2003-10-29 Methodes et dispositif de mesure histologique

Publications (1)

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EP1567050A1 true EP1567050A1 (fr) 2005-08-31

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EP03809780A Withdrawn EP1567050A1 (fr) 2002-10-29 2003-10-29 Methodes et dispositif de mesure histologique

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EP (1) EP1567050A1 (fr)
AU (1) AU2003276422A1 (fr)
CA (1) CA2504191A1 (fr)
GB (2) GB0225060D0 (fr)
WO (1) WO2004039255A1 (fr)

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Publication number Priority date Publication date Assignee Title
GB2443389A (en) * 2006-11-03 2008-05-07 Astron Clinica Ltd Method and apparatus for obtaining a measurement of sun damage
DE102008041971A1 (de) 2007-09-13 2010-03-11 Beiersdorf Ag Verfahren zur Reduktion von Altersflecken
DE102008041972A1 (de) 2007-09-13 2010-03-11 Beiersdorf Ag Verfahren zur Faltenreduktion
WO2016099099A1 (fr) 2014-12-15 2016-06-23 Samsung Electronics Co., Ltd. Dispositif de capture d'images et dispositif de protection de détection
RU2601678C2 (ru) * 2014-12-15 2016-11-10 Самсунг Электроникс Ко., Лтд. Портативное устройство для измерения хромофоров в коже и способ применения устройства

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Publication number Priority date Publication date Assignee Title
GB2218802A (en) * 1988-03-10 1989-11-22 Glyn Alyn Edwards An opto-electrical device
GB9624003D0 (en) * 1996-11-19 1997-01-08 Univ Birmingham Method and apparatus for measurement of skin histology
US7054674B2 (en) * 1996-11-19 2006-05-30 Astron Clinica Limited Method of and apparatus for investigating tissue histology
FR2822671A1 (fr) * 2001-03-29 2002-10-04 Medick S A Appareil optoelectronique permettant une exposition solaire controlee et son procede de mise en oeuvre
ITFI20010181A1 (it) * 2001-10-05 2003-04-05 Flyby S R L Metodo e dispositivo per la determinazione della dose minima eritemica relativa ad esposizione della cute umana a radiazione ultravioletta

Non-Patent Citations (1)

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Title
See references of WO2004039255A1 *

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Publication number Publication date
GB2411721A (en) 2005-09-07
GB0225060D0 (en) 2002-12-04
CA2504191A1 (fr) 2004-05-13
GB0510959D0 (en) 2005-07-06
AU2003276422A1 (en) 2004-05-25
WO2004039255A1 (fr) 2004-05-13

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