GB2364567A - Determining distribution of chromophores in skin or other epithelial tissue - Google Patents

Abstract

Apparatus for aiding diagnosis of skin disorder includes a hand-held device 103 containing LEDs 203 for illuminating the skin through an aperture 210, and means 213 for detecting light remitted from the skin at selected wavelengths corresponding to known chromophores. Variations in intensity of light emitted from points across lesions in the skin are measured, and the results are processed and interpreted by a microprocessor 205.

Description

2364567 Epithelial Diagnostic Aid

Background of the Invention

5 1. Field of the Invention

The present invention relates to a diagnostic aid for the examination of lesions of epithelial surfaces.

2. Description of the Related Art

10 It is known that epithelial surfaces, such as the skin, comprise a variety of chromophores disposed within the constituent layers of the epithelial tissue. In addition, inhomogeneities in the distribution of specific chromophores within the epithelial tissue can be correlated with specific abnormalities (referred to herein as lesions).

15 In the case of skin, the conventional approach for diagnosing skin ailments involves the examination of the surface characteristics of a lesion.

In addition, and dependant on the skin condition, a proportion or entire area of a skin lesion may be surgically excised for histological examination under a microscope.

20 There are a variety of epithelia[ tissue conditions where the provision of histological information rapidly would be a valuable adjunct to enable the efficient diagnosis of an ailment. In the example of a malignant melanoma of the skin, histological information could be vital to determining the prognosis of the disease. For instance, the ingression of melanocytes into 25 the papillary dermis layer of the skin and, in particular, the depth of ingression into the papillary dermis has been correlated to the prognosis of the disease (Neville, C.D. "Melanoma: Issues of Importance to the clinician", British Journal of Hospital Medicine, 1995). For this reason, a device that could provide histological information about an area of skin rapidly and by a non-invasive technique would be a distinct advantage.

The principal chromophores located in the skin include melanin, 5 haemoglobin, oxy-haemoglobin and collagen. In normal healthy skin, melanin is located exclusively in the epidermis, and haernoglobin and oxy haemoglobin are located primarily in the papillary dermis and to a lesser extent the reticular dermis. Collagen is located throughout the dermis, with the highest concentration residing in the reticular dermis. Abnormalities in 10 the distribution of such chromophores can provide valuable information about the histology of a skin ailment and can be obtained by detecting and interpreting the distribution of different chromophores within the skin.

Our application WO 98/22023 discloses a non-invasive method by which the skin colour co-ordinates and the papillary dermis thickness are determined by 15 the analysis of light remitted from an area of skin following illumination.

Our co-pending United Kingdom patent application numbers 99 12 908 and 99 25 414 relate to advances and improvements in the determination of the concentration and distribution of chromophores within the skin. In particular, United Kingdom patent application number 99 12 908 20 relates to methods and apparatus by which the histology of the skin may be determined and the identification of the presence depth and concentration of chromophores within the skin. United Kingdom patent application number 99 25 414 relates to a method and apparatus for providing the information of the skin structure, more particularly, to mapping the surface of dermal 25 papillae.

Furthermore, our co-pending United Kingdom patent application Number 00 10 888.6 relates to an apparatus and methodology for determining the distribution of chromophores within the histological layers of the skin.

The present invention relates to a simplified apparatus to and methodology for determining the concentration and/or the distribution of 5 chromophores within an epithelial surface.

Brief Summary of the Invention

According to a first aspect of the present invention there is provided a hand-held device for the determination of the concentration and distribution 10 of chromophores within an epithelial surface, comprising illumination means configured to illuminate an area of said epithelial surface; detection means to convert remitted light into an electrical signal; processing means configured to analyse the difference in concentration of one or more of said chromophores; and display means for displaying an output from said 15 processing means.

By chromophore we mean any constituent of the epithelial surface having chemical groups capable of the absorption or scattering of specific wavelengths or wavelength ranges of light.

By epithelial surface we mean any epithelial tissue including, in 20 particular, the skin, nails, the lining of the nose, rectum, vagina, mouth, ear and eye (including the corneal surfaces and retinal tissues).

It is an important feature of the present invention that the device is a portable hand-held device of convenient size and shape to access a number of epithelial tissue areas of varying geometry, e.g. the bridge of the nose, the 25 surfaces of the ear etc. Furthermore a cost-effective device would be a distinct advantage.

According to a second aspect of the invention there is provided a method of interpreting the distribution of chromophores within a lesion of an epithelial tissue, said method comprising the steps of: illuminating the epithelial surface detecting the intensity of light remitted from the skin surface to form a first data set determining the variation in intensity of said remitted 5 light across said lesion, and providing an output corresponding to the significance of the variation between the intensity of light remitted across the lesion.

The image can be obtained at one or more points over a defined distance or over a defined time.

10 According to a third aspect of the present invention there is provided a method of interpreting the distdbution of chromophores within a lesion of an epithelial tissue, said method comprising the steps of: illuminating an epithelial surface; determining the intensity of light remitted from said lesion to form a first data set; illuminating an epithelial surface; obtaining an image 15 of light remitted from said healthy epithelial tissue to form a second data set; and equating variations in remitted light within said first and second data sets, and providing an output corresponding to the extent of variation within or between each data set.

20 Brief Description of the Several Views of the Drawings

How the invention may be carried out will now be described by way of example only and with reference to the accompanying drawings in which:

Figure I illustrates generally how apparatus according to the present invention is used; 25 Figure 2 is a diagrammatic sectional view of one embodiment of the invention using a single point detector and one or more point light sources; Figure 3 is a fragmentary sectional view, but similar to Figure 2, illustrating an alternative single point detector arrangement; Figure 4 is a block diagram illustrating the optical/electronic system incorporated in the embodiment of Figure 2; Figure 5 is a view similar to Figure 2 but illustrating a second 5 embodiment of the invention utilising a multiple detection line array arrangement; Figure 6 is an enlarged perspective fragmentary view illustrating the line array shown in Figure 5; Figure 7 is similar to Figure 3 but illustrating a third embodiment of the 10 present invention utilising a scanning mirror; Figure 8 is a flow chart illustrating the process by which data sets are collected and analysed; Figure 9 is a further flow chart providing more detailed information regarding sections 801, 802, 803/808 and 804/809 of Figure 8; 15 Figure 10 is a schematic representation of a malignant melanoma; Figure I I is a graphical representation of the variations in the concentration of blood across along line 1003 of Figure 10; Figure 12 is a graphical representation of the variations in the concentration of dermal melanin across along line 1003 of Figure 10.

Best Mode for Carrying Out the Invention

A schematic representation of an example of a device according to the present invention is shown in Figure 1. Illustrated in Figure I is a clinician 101 carrying out an examination of a patient 102 using a device 103 according to 25 the present invention.

The device is switched on and positioned by the clinician 101 against the skin of the patient 102 at a locality or localities where the patient's skin has a visibly discernible lesion, such as a mole.

The device 103 is used to provide the clinician with a preliminary indication of whether or not the skin irregularity is likely to be malignant and require treatment or excision. The device 103 is in a form which is akin to that 5 of a pen in that it is small and convenient to hold in the hand of the clinician 101 and is easily portable.

The construction of the device 103 shown in Figure I will now be described in more detail and with reference to various embodiments of that device which are shown in Figures 2 to 7.

10 A schematic representation of a device according to the invention is shown in Figure 2. The device 103 comprises a casing 201 which is adapted to be held in an operators hand and exclude ambient light from the surroundings. Incorporated within the casing is an optical system configured to provide a measure the light remitted from a small area of the skin following 15 illumination. Furthermore, the device is provided with a microprocessor for analysing the remitted light data, interpreting the distribution and concentration of chromophores and presenting the variation in chromophore concentration on a display means.

The casing 201 contains a battery 202 which serves as the power 20 supply for the microprocessor 205 and a series of light emitting diodes (LED's) 203. The battery is activated by depressing the on/off switch 206.

The LED's 203 are arranged in a circular, ring-like conformation.

Furthermore, a series of LED's are present and each series is configured to illuminate the skin with a defined spectral profile of illumination. The selection 25 of the series of LED's illuminated is mediated by multiplexing operation under the control of the microprocessor 205.

Light emitted by the LED's passes through a band pass filter 215 which selects the wavelength/wavelength range of light, which is subsequently directed towards the skin along the optical fibre bundle 208.

Light emitted from the terminal of the optical fibre bundle 208 passes through a first polarisation filter 209 and illuminates the skin through the glass 5 aperture 210.

Light remitted by the skin surface passes through a second polarisation filter mounted such that the angle of polarisation is at ninety degrees to that of the first polarisation filter. The polarisation filters prevent light reflected from within the device or the skin surface from accessing the 10 detector and obscuring the detection of light remitted by the skin surface.

The entire detection system is mounted within a cover 218 to prevent ambient light in the nose cone accessing the detector. Furthermore, the entire nose cone section is isolated from the illumination assembly by an opaque screen 216 to prevent stray light from the LED illumination array 15 accessing the detector 213.

Light traversing the second polarisation filter 214 is focused by a lens 212 and detected by a point detector 213. The detector comprises a silicon photodiode or phototransistor which is configured to convert the intensity of light detected into an electrical signal which is fed into the microprocessor 20 205 for further analysis.

The data collected by the detector 213 is processed by the microprocessor 205, analysed and an appropriate display is presented on the LCD screen 207. In addition, to alert an operator, a coloured light 215 is lighted in response to a significant result obtained.

25 The operative end of the casing 201 carries a thin transparent cover 211 which in use is pressed against the skin of the patient. The part of the nose-cone in line with the window 210 is transparent to the light being emitted by the respective LED's 203 and light entering the device from the skin surface.

The nose cone may optionally comprise a series of homogenous grey scale calibration patches to calibrate the image of remitted light obtained. A 5 detailed description of an example of such a calibration procedure can be found in our co-pending UK Patent Application Number 00 10 888.6. The construction, and alternative constructions for the nose-cone are described in more detail in our co-pending UK Patent application.

In use, the operator identifies the lesion of interest, places the glass 10 aperture directly against the skin surface and initiates the collection of data by depressing the activation switch 206. Depressing the switch 206 activates the microprocessor 205 and initiates a program sequence of obtaining a data sets corresponding to light remitted by the skin at a single point.

The microprocessor program initiates the illumination different LED 15 series, one series at a time, and detecting the light remitted at each illumination step. The microprocessor measures and stores remitted light signal from the detector in the memory.

The device is slowly moved across the lesion and numerous data sets corresponding to the spectral characteristics of remitted light at each point 20 traversed by the device is detected and stored in the memory. The speed of movement of the device should be sufficient to enable data sets to be obtained at each point, although the speed of detection of the data is not thought to be a limiting factor, rendering the speed of traverse less critical.

The process by which the data sets are obtained and converted into a 25 result set are discussed in more detail in reference to Figure 8. The operator can select different results sets for display on the display screen 207 by selectively depressing one of the switches 204a, 204b and 204c.

Figure 3 illustrates an alternative construction of the operative end of a device according to the invention. Light emitted by the LED's 203 is transmitted through the glass aperture 210 via the optical fibre bundles 208 in the conventional manner. No polarisation filters are required in this 5 embodiment as light emitted by the termini of the optical fibre bundles 208 cannot access the detector 213 directly due to the presence of an opaque remitted light channel 301. As no direct access of illuminating light is enabled, light entering the opaque remitted light channel 301 emanates solely from remittance from the skin surface contacted with the nose cone 210.

10 As with the device shown in Figure 3, the data obtained by the detector 213 is transmitted to and processed by the microprocessor 205.

A schematic representation of the essential components of the device are shown in Figure 4. Corresponding reference numerals are used to identify like or corresponding parts.

15 The system is powered by a battery 202 which in turn is controlled by an on/off switch 206. The microprocessor 205 comprises random access memory 216 and read only memory 217 segments as in standard microprocessor units. The microprocessor 205 is activated by the depression of switch 206, which initiates the illumination of the skin by the LED array 20 203. The detector 213 images the intensity of light remitted from the skin surface and, generates a signal that is conveyed to the microprocessor 205.

The data obtained from the detector is stored in the microprocessor memory, subsequently analysed and displayed on the display screen 207.

The devices illustrated in Figures 2 and 3 detect light remitted from a 25 single spot on the patient's skin, the device then having to be moved across the patient's skin in order to build up useful data of the target area.

The embodiment shown in Figures 5 and 6 is basically the same as the embodiment shown in Figures 2 and 3 but with the difference that in the embodiment of Figures 5 and 6 a line detection array 502 is used to record the light remitted from the patient's skin rather than a single spot detector.

The device is shown in cross section in Figure 5 with the line detector 502 5 extending into the paper. The line array may be of any length although the range one to fifty millimetres is preferred with twenty millimetres most preferred.

The detector comprises a series of single point detectors arranged in a line. A linear diffuse LED array 203 is mounted onto the linear detector array.

10 As with previous devices, one or more LED series (each series corresponding to a specific wavelength or wavelength range of illumination) are present, each series configured to provide illumination of a specific wavelength.

The device shown in Figure 5 comprises a series of remitted light 15 channels 501 illustrated in perspective in Figure 6. The light channels are arranged such that there is one light channel per single point detector of the detection array. The detector comprises a silicon base 503 on which LED's 203 are mounted (see Figure 6).

Light emitted by the LED's 203 accesses the skin 102 through the 20 window 210 to produce a line of illumination. Remitted light from the skin 102 accesses the detector 502 through the channels 501. Consequently, each detector detects the intensity of light remitted at a point along the line of illumination.

In this embodiment, and in common with the embodiment shown in 25 Figure 3, there are no polarisation filters as the reflection of light into the detector is excluded by the opaque remitted light channels 501.

With this arrangement the device is placed across a lesion and the intensity of remitted light is dependant on variations in chromophore concentration with distance along the length of the detection array 502.

Alternatively, the detection array 502 is scanned across the patient's skin in the vicinity of the target area to build up an image in which variations in the 5 intensity with time (corresponding to the distance scanned across the lesion) are recorded.

As indicated earlier the device is shown in Figures 2 and 3 it is necessary for the operator/clinician to physically move the operative end of the device across the patient's skin.

10 Figure 7 illustrates a modification to the device which would obviate the necessity to do this by providing a mechanical means by which the point of illumination is scanned across the lesion.

The device illustrated in Figure 7 is essential equivalent to that of Figure 2. The device has a casing 201, a microprocessor 205, LED's 203 that 15 transmit light along optical fibre bundles 208, a detector 213 and first and second polarisation filters 209 and 214. The mechanical scanning of a skin surface is controlled by a rotatable mirror 221. The mirror pivots about a points such that the illumination is scanned across the skin surface 102.

Remitted light from the surface is correspondingly reflected towards the 20 detector 213.

This mirror would be mounted and driven in such a way that its angle to the axes of the device 201 would vary typically between, for example, fifty degrees and forty degrees, the medium position being forty-five degrees.

In use the skin of the subject 102 is placed directly adjacent to the 25 glass aperture 224 of the device. Preferably, the glass aperture 224 is pressed against the skin 102 such that ambient light from the surroundings cannot access the detector. The lesion is then scanned and the data collected and analysed as discussed in reference to Figures 8 and 9.

Various further modifications could be made to the devices previously described with reference to Figures I to 7.

For example instead of simply selecting a single LED to illuminate the 5 patient's skin all the LED's series carried in the device could be energised in turn by a multiplexing arrangement. This would provide a sequential illumination of, for example, red, blue and infrared wavelengths. The precise wavelengths selected will depend on the chromophores within the skin under investigation.

10 In addition, the skin could be illuminated by any suitable means, for example, a light bulb provided with a bandpass filter, to select the wavelength, or diffracted through a prism to enable the selection of wavelength constituents, incandescent lamps with band pass filters, light emitting polymers or other low power fluorescent devices.

15 In the following description of Figures 8 to 12, the term "data set" is used to specify the intensity-time/distance data of the remitted light. The term 6(result set" is used to specify the analysed data sets which provide information regarding the distribution and concentration of chromophores derived from the analysis of the the above defined data sets.

20 The process by which the variation in the concentration of a chromophore within a skin lesion is determined is illustrated in Figure 8. The initial step 801 involves the illumination of the skin with light of the desired wavelength and intensity. The wavelength of light selected will be a specific wavelength or wavelength range. For example, near red or infra-red 25 wavelengths can be used to determine the distribution of collagen within the skin surface and red light wavelengths are required to determine the distribution of haernoglobin (blood) within the skin surface.

The remitted light is detected 802, converted into an electrical signal and the skin re-illuminated at a second wavelength/wavelength range 813 and the intensity of light remitted following the illumination at a second wavelength is detected. The intensity of remitted light recorded is stored by 5 the microprocessor 206 as separate data sets.

The subsequent processing of the data sets obtained will depend on whether a single point detector is used, as described in reference to Figures 2, 3 and 7, or a multiple point image detector is used, as described in reference to Figures 5 and 6 and our co-pending United Kingdom application 10 number 00 10 888.6.

In the case of single point detectors 803, the data set comprises a series of intensity readings obtained over time. The point of illumination and the point of remitted light detection is traversed across the image, preferably by manually moving the device across the lesion or by mechanical means as 15 described in reference to Figure 7. Consequently, variations in the concentration of chromophores across the skin lesion results in corresponding changes in the intensity of light remitted from the skin surface.

Each data set will correspond to intensity time data obtained at a specific wavelengths/wavelength ranges of illumination.

20 An algorithm 812 is applied to the data sets which determines the concentration and distribution of specific chromophore constituents within the skin. The algorithms applied are described in detail in our co-pending patent applications WO 98/22023 and United Kingdom patent application numbers 99 12 908 and 99 25 414. The intensity of the light remitted from the skin 25 over time stored in each data set is used to create a series of results sets using the above mentioned algorithms. Each result set corresponds to the variation in the concentration of each chromophore recorded overtime.

The appropriate results sets are selected 804 which correspond to the particular chromophore distributions under investigation.

Following the selection of the results sets, the variation in the concentration and distribution of the chromophore over time within each 5 result set is individually analysed 805. The extent and significance of the variation is determined 806 and a significance output is displayed on the output display 807.

The output display 807 is designed to signal to an operator whether the variations in concentration of one or more chromophores is sufficiently 10 indicative of an abnormality. The output enables an operator or clinician to contemplate further action necessary, such as the excision of the lesion.

The output display 807 may take a variety of forms. In the simplest embodiment, the output display is a single LED which lights if an abnormality is detected. Alternatively, a series of LED's, whereby the number of which 15 light corresponds to the degree of variation detected could be used. A further alternative is the display of the output as a number presented on the display 207. The value of the number corresponding to the degree of variation within the results set.

In situations were the user wishes to view the mapping of the 20 chromophores over the lesion a graphical representation, such as that illustrated in Figures 11 and 12, could be viewed on the screen 107. The operator will be able to select different chromophores by, for example, depressing buttons such as 204a, 204b and 204c of the device shown in Figure 2. Alternatively all the chromophores may be displayed 25 simultaneously.

A final display option is provision of display relating to the likely structure of the skin as interpreted by the microprocessor following programming to correlate the distribution and concentration of chromophores to specific skin structures.

In the case of a multiple point imaging device 808, where an image is obtained across a lesion, the intensity variations across a section taken 5 through the lesion is used to provide information relating to the concentration and distribution of chromophores as a function of distance across the lesion.

Individual data sets corresponding to images obtained at specific wavelength/wavelength ranges are stored.

As with the single data point intensity-time data sets, an algorithm is 10 applied the intensity-distance data plots to convert the data obtained into the distribution and concentration of specific chromophores within the skin. The resultant chromophore concentration and distribution information is stored as a result set.

The appropriate result sets are selected 809, analysed 810 and the 15 variation in chromophore concentration across the lesion determined 811.

As for the single data point apparatus the variation in chromophore concentration in one or more result sets is displayed on the output display 807.

The selection of remitted light results sets is illustrated in more detail in 20 Figure 9. The skin is illuminated at three wavelengths 901, 902 and 903 respectively. The intensity of the light remitted across the lesion from wavelengths 901, 902 and 903 provides data sets 904, 905 and 906 respectively.

As previously described, an algorithm is applied to the data sets to 25 provide a series of results sets, for example 907, 908 and 909. Each result set relates to the variation in concentration and distribution of a respective chromophore across the lesion. For example, result sets 907 to 909 could correspond to dermal melanin, blood distribution and collagen distribution respectively.

These variations in the concentration of chromophores within an epithelial tissue, such as the skin, is indicative of specific abnormalities.

5 Of the three result sets provided, one or more of these result sets is selected 804 and subsequently analysed for variations in the concentration of a chromophore 805. The selection of results sets is a matter of choice for the clinician or may be predetermined for specific skin conditions.

A schematic representation of a malignant melanoma lesion is shown 10 in Figure 10. The malignant melanoma 1001 is surrounded by normal healthy skin 1002. An image data set is obtained by determining variations in chromophore concentration along line 1003. Line 1003 has sections 1004 which traverse healthy tissue and 1005 which traverses the lesion. In the case of a single point device the point of illumination and detection is moved 15 along line 1003. In the case of a multiple point detector, the data along line 1003 is selected from an image for further analysis.

Alternatively, line 1006 provides a lesion data set which is compared with a second data set obtained at line 1007 which corresponds to healthy skin. A comparison between the data sets corresponding to line 1006 and 20 1007 provides an indication of abnormality within the lesion relative to the normal skin. Concentrating on a single result set obtained along line 1003, an example

of a result set is illustrated graphically in Figure 11. Figure 11 details the variation in concentration of blood along line 1003.

25 It has been found that, in malignant melanomas and other cancers, the blood vessels are excluded from the centre of the tumour and concentrate about the periphery of the lesion. This is known as an erythematous blush. The identification of this feature is hence, indicative of a malignant melanoma.

The graph shown in Figure 11 shows a plot of time/distance (dependant on whether a single point or multiple detection device is used) on 5 the x co-ordinate and blood concentration on the y co-ordinate.

In normal skin sections 1004, the concentration remains relatively constant I 101, which indicative of a homogenous distribution of blood. At the periphery of the lesion 1005, the concentration rises 1102 to a concentration maximum (C,,,,,) at 1103. The intensity falls at 1104 to an concentration 10 minimum (Cmij at 1105. The fall in concentration corresponds to the central regions of the melanoma were blood perfusion is minimal.

As the periphery of the lesion is approached again, the concentration rises at 1106 to a second maximum 1107. The concentration declines at 1108 to the level of normal skin 110 1.

15 As variations in blood concentration of the skin, is indicative of abnormality, the intensity data is used to calculate a variation factor, the value of which relates to the extent of variation within the result set.

Examples of equations by which a suitable variation factor is calculated are also shown in Figure 11. The first equation correlates the variance between 20 the concentration maximum (C,,x) and the mean concentration (C,,.r,) of the result set. Hence, the value of the variation factor is dependant on the difference between the concentration maxima and the mean concentration value. For a given chromophore, a threshold value above which the variation is considered significant is set or alternatively, range values of the variation 25 factor can be defined to provide an indication of the extent of variation within the data set.

A second equation shown in Figure I I works on similar principles and equates the concentration minima (Cmin) with the mean concentration (C,,, n).

A variety of alternative statistical measures could be applied to determine the level and significance of variations.

Figure 12 shows a second result set corresponding to dermal melanin 5 along line 1003 of Figure 10. In malignant melanomas, the presence of melanin that has penetrated into the papillary dermis is a significant prognostic factor. In normal skin the amount of melanin within the dermis is virtually negligible and consequently, the detection of any melanin in the dermis can be an indicator of malignancy.

10 In Figure 12, the dermal melanin concentration, as identified by the remitted light intensity, is virtually negligible in normal skin. However, within the lesion, the concentration of dermal melanin rises at 1202 to a maximum at 1203 and declines at 1204 back to the negligible level 1201.

In this case, a binary equation can be applied as the dermal melanin is 15 either present or absent. Alternatively, a variation factor which equals the concentration maximum can be provided as an indicator of the level of penetration into the dermis.

The discussion of Figures I I and 12 provides an example of two result sets which may be provided by an apparatus of the invention. A single 20 result set or multiple result sets corresponding to numerous chromophores may be obtained and analysed.

In particular, it has been found that, following the assessment of one hundred and thirty eight lesions in a clinical trial using images obtained by a SlAscope device (as described in our co-pending UK Patent Application 25 Number 00 10 888.6), in lesions of diameter of greater than six millimetres, the combination of blood displacement in the form of an erythernatous blush and melanin in the dermis provided a correlation with histological examination. Upon statistical analysis, the sensitivity was found to be 91.3% and the specificity of 77.3%. Consequently, the presence of dermal melanin and blood displacement within a lesion of diameter of greater than six millimetres indicates that the lesion is four times more likely to be a malignant melanoma. Conversely, a lesion of less than six millimetres diameter and with no detectable melanin in the dermis or blood displacement is nine times less likely to be a malignant melanoma.

The actual data of the trail is shown below in Table 1.

Table 1 - the identification of malignant melanoma and non 10 melanomas using a test of three criteria - melanin in the dermis, blood displacement and lesion diameter of less than 6mm Melanoma Non-melanoma Totals Test positive 21 26 47 Test negative 2 89 91 Totals 23 115 138 Alternative chromophores and properties of the skin that can be 15 analysed include the mapping of the dermo-papillary junction, total melanin distribution and keratin.

It will also be appreciated that the present application is not limited to the skin and the distribution of chromophores within any epithelial surface could be determined by the devices and methodology described in the 20 present application and our co-pending United Kingdom patent application numbers 99 12 908, 99 25 414 and 00 10 888.6.

Claims (3)

Claims

1. A hand-held device for the determination of the concentration and distribution of chromophores within an epithelial surface, comprising 5 illumination means configured to illuminate an area of said epithelial surface detection means to convert the intensity of remitted light into an electrical signal processing means configured to analyse the difference in intensity of 10 one or more of said chromophores across a lesion; and display means for displaying an output from said processing means.

2. A method of interpreting the distribution of chromophores within a lesion of an epithelial tissue, said method comprising the steps of 15 illuminating the epithelial surface with a wavelength of light corresponding to a chromophore detecting the intensity of light remitted from the skin surface to form a data set determining the variation in intensity of said remitted light across said 20 lesion, and providing an output corresponding to the significance of the variation in the concentration of said chromophore across the lesion.

3. A method of interpreting the distribution of chromophores within 25 a lesion of an epithelial tissue, said method comprising the steps of illuminating an epithelia[ surface with a wavelength of light corresponding to a chromophore determining the intensity of light remitted from said lesion to form a first data set illuminating an epithelial surface with a wavelength of light corresponding to a second chromophore 5 obtaining an image of light remitted from said epithelial tissue to form a second data set; wherein variations in said first and second data sets are determined and an output corresponding to the degree of variation within each data set generated.