Abstract:
Apparatus for diagnosis of a skin disease site using spectral analysis includes a light source for generating light to illuminate the disease site and a probe unit optically connected to the light source for exposing the disease site to light to generate fluorescence and reflectance light. The probe unit also collects the generated fluorescence and reflectance light and transmits this light to a spectrometer to be analysed. The spectrometer generates and displays spectral measurements of the fluorescence light and the reflectance light which in together assist the user in diagnosing the disease site. The apparatus makes use of a conventional personal computer using a plug-in spectrometer card to provide a compact and low cost system. The system performs combined fluorescence and reflectance spectral analysis in a quick and efficient manner to provide a powerful tool for dermatologic diagnosis.

Description:
FIELD OF THE INVENTION 
     This invention relates to an apparatus for assisting in diagnosis of skin disease by making spectral measurements of fluorescence and reflectance light from the skin disease site. 
     BACKGROUND OF THE INVENTION 
     Currently, clinical diagnosis of skin disease is generally accomplished by visual inspection under white light illumination. In this process, the reflectance light of a skin lesion is examined. Visual diagnosis alone may not be particularly accurate for early detection of skin cancer since many skin conditions have a similar appearance under white light. Therefore, when a suspect lesion is identified by visual examination, a biopsy is often performed for a definitive diagnosis. Not only is it crucial to diagnose skin pre-cancer or skin cancer at an early stage when it is curable, but it is also important to improve the clinical diagnosis of suspected skin lesions so as to avoid unnecessary skin biopsies. 
     Several approaches have been tried to improve dermatologic diagnosis. Digital processing of reflectance images has been extensively investigated recently. Although reflectance imaging has led to improvements in the registration, recording, and documentation of skin lesions, there has been little improvement in the diagnostic accuracy. The foregoing approach does not provide any additional data to the physician making the visual assessment because it is still based on the reflectance pattern of a lesion under white light illumination which is essentially the same pattern a human observer sees. 
     An alternative approach is ultraviolet (UV) or infrared (IR) photography which does extend visual perception of a physician to the UV or IR reflectance patterns. However, the inconvenience due to delays in processing of film images renders this technique impractical for everyday use. 
     A further alternative approach that is already in widespread medical use involves a &#34;Wood&#39;s lamp&#34; which consists of a mercury discharge lamp associated with a filter that transmits UVA light with a 365 nanometer peak while absorbing visible light. When this device is used to assist in skin diagnosis, the eye serves as both the detector and the long pass filter. The eye is not sensitive to UV light, but is sensitive to visible fluorescence light when the &#34;Wood&#39;s lamp&#34; is used in a darkened room, where the physician sees an image of a fluorescing disease site. The &#34;Wood&#39;s lamp&#34; is useful for the diagnosis of some skin conditions such as tinea capitis, tinea versicolor, erythrasma, and some pseudomonas infections, as well as aiding in the detection and diagnosis of hypopigmented skin. It is of no value in conditions where the fluorescence is not in the visible spectrum. 
     SUMMARY OF THE INVENTION 
     The apparatus and method of the present invention use spectral measurements of both fluorescence light and reflectance light from a disease site to aid in the medical assessment of skin conditions and the diagnosis of cutaneous diseases. 
     Accordingly, the apparatus of the present invention provides apparatus for diagnosis of a skin disease site using spectral analysis comprising: 
     a light source for generating light to illuminate the disease site; 
     a probe means to conduct the illumination light from the light source to the disease site and to collect the reflected and fluorescence light and conduct said light to be analysed; and 
     spectral analysis means optically connected to the probe means for generating and displaying spectral measurements of the fluorescence light and the reflectance light to assist the user in diagnosing the disease site. 
     In a further aspect, the present invention provides a method for diagnosis of a skin disease site using spectral analysis comprising the steps of: 
     illuminating the disease site with a light source to generate fluorescence and reflectance light at the disease site; 
     collecting the generated fluorescence and reflectance light; 
     conducting a spectral analysis of the collected light using a spectrometer; 
     displaying spectral measurements of the fluorescence light and the reflectance light; and 
     analysing the measured fluorescence and reflectance spectra together to make a diagnosis of the disease site. 
     In a preferred embodiment, the apparatus of the present invention includes a compact spectrometer connected to a personal computer, a fluorescence excitation light source with a shutter, a white light source with a shutter, a bifurcated fibre bundle, a light coupler, a skin probe, and controlling electronics. The system is designed to automatically switch between the fluorescence excitation light and the white light sources and complete fluorescence and reflectance spectral measurements of a skin disease site sequentially in a few seconds. The system exploits the spectral differences of different skin diseases to aid in the dermatologic diagnosis. In particular, the apparatus provides a low cost, compact system that is capable of quickly and efficiently performing combined fluorescence and reflectance spectral analysis. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Aspects of the present invention are illustrated, merely by way of example, in the accompanying drawings in which: 
     FIG. 1 is a schematic diagram showing an embodiment of the apparatus of the present invention; 
     FIG. 2 is a detail view of light coupler arrangement of the present invention that connects a white light source and a laser light source; 
     FIG. 3 is a detail section view of the probe member according to a preferred embodiment of the present invention; 
     FIG. 4a to 4h are fluorescence and reflectance spectral measurements of various skin diseases that illustrate how viewing both spectral measurements together assists a user in identifying a particular skin disease; 
     FIG. 5 is a fluorescence spectrum of a psoriasis lesion; 
     FIG. 6 is a fluorescence spectrum of a squamous cell carcinoma (SCC); 
     FIG. 7a shows the fluorescence spectra of normal skin and seborrheic keratosis; 
     FIG. 7b shows the fluorescence ratio spectrum equal to the seborrheic keratosis fluorescence spectrum divided by the normal skin fluorescence spectrum; 
     FIGS. 7c and 7d show the reflectance spectra and reflectance ratio spectrum, respectively, of seborrheic keratosis and normal skin; 
     FIG. 8a shows the fluorescence spectra of spider angioma and normal skin; 
     FIG. 8b shows the fluorescence ratio spectrum equal to the angioma fluorescence spectrum divided by the normal skin fluorescence spectrum; and 
     FIGS. 8c and 8d show the reflectance spectra and reflectance ratio spectrum, respectively, of spider angioma and normal skin. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring to FIG. 1, there is a schematic view of the apparatus of the present invention for diagnosing skin diseases. In essence, the apparatus includes a light source 4 and a probe 6 optically connected via optical fibre 7 to light source 4 for exposing a skin disease site 8 to light. The light from source 4 generates fluorescence and reflectance light at disease site 8 that is collected by probe 6 and transmitted by optical fibre 10 via light filter 12 to spectral analysis means in the form of a spectrometer 14. Spectrometer 14 generates and displays spectral measurements of the fluorescence and reflectance light on the monitor 18 of a computer 16 for viewing by a user to assist in the diagnosis of the disease site. 
     In a preferred embodiment of the present invention, the fluorescence and reflectance light is acquired and analysed sequentially. In order to accomplish this, light source 4 preferably comprises a white light source 20 for reflectance measurements and an excitation light source 22 for fluorescence measurements as best shown in FIG. 2. Excitation light source 22 can be a Helium-Cadmium (442 nm) laser and white light source 20 can be a quartz tungsten halogen lamp. 
     The two light sources 20 and 22 are joined together by an optical coupler 24 that allows light from either source to be transmitted via the same optical fibre bundle 7. Optical coupler 24 comprises a sealed enclosure 26 housing an angled reflecting surface or mirror 28 having a small aperture 29. A laser light port 30 is formed in enclosure 26 to admit laser light from laser light source 22. Port 30 is aligned with aperture 29 to permit passage of laser light directly through mirror 28 to a light exit port 32 which is connectable to optical fibre bundle 7 and probe unit 6. A white light port 34 is formed in enclosure 26 and positioned with respect to mirror 28 such that white light is reflected through an angle to be incident upon light exit port 32. White light port 34 is optically connectable to white light source 20 via a short length of optical fibre 36. Lenses 38 and 40 are also provided within enclosure 26 to collimate white light from port 34 onto the mirror surface and to focus reflected light from the mirror onto light exit port 32. 
     Associated with each light source are shutter systems 41 and 42 to permit switching between excitation laser light source 22 and white light source 20, respectively, such that the disease site is illuminated sequentially by only one of the light sources at a time. Shutter systems 41 and 42 are preferably electronic and controlled by computer 16 (FIG. 1). Computer 16 is programmed to close shutter 41 while shutter 42 is open to obtain reflectance light measurements of the disease site and vice versa to obtain fluorescence light measurements. 
     FIG. 3 is a detailed view of the probe unit 6 used to illuminate disease site 8 with light from the light sources and collect fluorescence and reflectance light from the site to transmit to spectrometer 14. Probe unit 6 comprises a generally cylindrical member 50 housing combined optical fibre bundles 7 and 10 that extend to a distal end 52 of the cylindrical member. An opaque sleeve member 55 is telescopically mounted on cylindrical member 50 for slidable movement. The overlap of sleeve member 55 with distal end 52 of cylindrical member 50 defines a chamber 56 that is positionable over skin disease site 8 of interest. Fibre bundles 7 communicate with chamber 56 to transmit illumination light into the chamber and fibre bundle 10 communicates with the chamber to transmit fluorescence or reflectance light from the chamber to the spectrometer 14. Slidable movement of sleeve member 55 with respect to cylindrical member 50 adjusts the length of chamber 56 and hence the distance between the fibre bundles at distal end 52 to vary the size of the illumination spot at disease site 8. By adjusting the length of chamber 56, different sizes and areas of disease sites can be examined and diagnosed. 
     Free end 62 of sleeve member 56 is preferably cut at a 45 degree angle to the longitudinal axis of the sleeve. This avoids the collection of specular reflected light from the skin surface. In addition, sleeve member 55 is preferably formed with a window 58 to allow observation inside the chamber when positioned over a disease site to ensure proper positioning. There is a slidable cover 60 to seal the window when the apparatus is in use. The design of probe unit 6 is such that the apparatus of the present invention can be used in a normally lighted room since no ambient light is able to enter chamber 56 and interfere with spectral measurement when chamber 56 is positioned over a disease site and cover 60 is closed over window 58. 
     The small cross-sectional area of sleeve member 55 is all that actually contacts the skin at disease site 8 in order to minimise the pressure on the disease site. Any excessive pressure on the skin at the disease site will affect the blood content in the skin tissue at the disease site which will affect the resulting spectral measurements. 
     Fluorescence light and reflectance light from the disease site is transmitted via optical fibre 10 to spectrometer 14. When shutter 41 is open to transmit excitation laser light to the disease site, filter 12 is used to pass fluorescence light to the spectrometer and block any reflected excitation light. For example, if a He-Cd laser is used to generate an excitation light of 442 nm wavelength, a 470 nm long pass filter 12 will pass fluorescence light with wavelengths larger than 470 nm but will block reflected excitation light. 
     Preferably, spectrometer 14 is a computer interface card installable in an interface slot of computer 16 which is preferably a standard personal computer (PC) having an I/O bus appropriate to receive the interface card. Such a PC based plug-in spectrometer is available from Ocean Optics, Inc. (Dunedin, Fla.) under the name Model PC 1000. The plug-in spectrometer is adapted to connect to optic fibre 10 and includes a miniature monochromalor, a CCD linear array detector, and all data acquisition and controlling electronics on the interface card. A spectrometer version for laptop computers using a PCMCIA port may also be used. 
     As previously described, computer 16 controls shutter systems 41 and 42. Computer 16 also controls spectrometer 14 in order to acquire spectral measurements of the fluorescence and reflectance light from the disease site. In prototype testing, the necessary spectral measurements of fluorescence and reflectance light were accomplished in a few seconds. 
     FIGS. 4a to 4h illustrate typical fluorescence and reflectance spectra of particular skin diseases acquired using the apparatus and method of the present invention. Using reflectance spectra alone or visual inspection of white light illumination, it can be difficult to differentiate between various skin conditions such as seborrheic keratosis (FIG. 4f) and compound nevus (FIG. 4h), or between actinic keratosis (FIG. 4b) and basal cell carcinoma (FIG. 4d) since each pair of skin diseases have similar reflectance spectra. However, when a user also considers the corresponding fluorescence spectrum for the particular skin disease, it is possible to differentiate between seborrheic keratosis (FIG. 4e) with a fluorescence intensity higher than normal skin and compound nevus (FIG. 4g) with a fluorescence intensity much lower than normal skin. In a similar manner, it is possible to use fluorescence spectra to differentiate between actinic keratosis (FIG. 4a) with a fluorescence intensity higher than normal skin and basal cell carcinoma (FIG. 4c) having a fluorescence intensity lower than normal skin. 
     It is important to note that the apparatus and method of the present invention rely on using both reflectance and fluorescence spectral measurements in combination to assist in diagnosis. In general, comparing only one type of spectral measurements results in difficulties in distinguishing between certain skin diseases. For example, using only fluorescence spectra for each skin disease makes it difficult to distinguish between actinic keratosis (FIG. 4a) and seborrheic keratosis (FIG. 4e) or between basal cell carcinoma (FIG. 4c) and compound nevus (FIG. 4g) as each of these particular pairs of skin diseases have similar fluorescence spectra. The fact that the above pairs of skin diseases have different reflectance spectra allow them to be distinguished clearly from each other. 
     By way of a simplified example, the following chart shows the manner in which the fluorescence spectrum and the reflectance spectrum can be analysed to distinguish between the various skin diseases. 
     
                       TABLE 1______________________________________Distinguishing between skin conditions by consideringFluorescence and Reflectance Spectral Characteristics______________________________________ ##STR1##______________________________________ 
    
     More sample spectra are shown in FIGS. 5-8. FIG. 5 is the fluorescence spectrum of a psoriasis lesion, showing a unique spectral peak at around 635 nm, allowing psoriasis to be easily differentiated from other skin lesions. FIG. 6 shows fluorescence spectra of a squamous cell carcinoma (SCC). The fluorescence intensity over a SCC lesion is not uniformly distributed. As shown, in some places within the lesion, the fluorescence intensity is higher than normal skin, while in other locations, the fluorescence intensity is lower than normal. This feature for SCC lesions is different from that of basal cell carcinomas (BCC), where the fluorescence intensity is uniformly lower than found in surrounding normal skin. 
     It is important to compare lesional spectra to the spectra of the surrounding normal skin in order to assess the spectral features of diseased skin. This comparison compensates for the regional variations in skin optical properties and spectral features. It also adjusts for intersubject variability. 
     To further standardise the method of the present invention, we have developed a ratio technique to aid spectra interpretation. In the ratio analysis technique, lesional spectra (reflectance or fluorescence) are divided by the corresponding spectra of the surrounding normal skin. In this way, the relative spectral intensity changes are quantified, and the spectral shape changes are enhanced and more easily visualised on the spectral curves. 
     FIGS. 7a to 7d show the original spectra and the ratio spectra of a seborrheic keratosis. FIG. 7a is the original fluorescence spectra, the lesion has higher fluorescence intensity than the normal, but the shape of the two curves are visually about the same. FIG. 7b is the fluorescence ratio spectrum which equals the lesion fluorescence spectrum divided by the normal fluorescence spectrum. The absolute value of the ratio spectrum is larger than 1, indicating that the lesion has higher fluorescence intensity than the normal and it indicates quantitatively how many times higher is the lesion signal than the normal at each wavelengths. Interestingly, a valley around 510 nm is shown on the ratio spectrum curve, which is unique to seborrheic keratosis and which cannot be discerned by only looking at the original spectra shown in FIG. 7a. Therefore, using the ratio technique, new spectral features have been revealed from the original spectra and new diagnostic information has been obtained. 
     FIG. 7c is the reflectance spectra of the same seborrheic keratosis lesion and its surrounding normal skin. FIG. 7d is the reflectance ratio spectrum which equals the lesion reflectance spectrum divided by the normal reflectance spectrum. The reflectance ratio spectrum of seborrheic keratosis shows lower values at short wavelengths and higher values at longer wavelengths and is a quantitative representation of the slope changes described in table 1. 
     FIG. 8a is the fluorescence spectra of a spider angioma and its surrounding normal skin. The lesion has lower fluorescence intensity than normal skin. FIG. 8b is the fluorescence ratio spectrum of the same lesion. The ratios with values less than 1 indicate that the lesional fluorescence intensity is lower than its surrounding normal skin while the numerical ratio values quantify this difference as a function of wavelength. FIG. 8c shows the reflectance spectra of the same spider angioma, and FIG. 8d the reflectance ratio spectrum. The reflectance ratio spectra of spider angiomas have a unique &#34;saw-tooth&#34; shape with a minimum at around 600 nm. This unique spectral feature can be used to easily differentiate spider angioma from other skin lesions. 
     Although the present invention has been described in some detail by way of example for purposes of clarity and understanding, it will be apparent that certain changes and modifications may be practised within the scope of the appended claims.