WO2016157010A1 - Digital parasitology - Google Patents
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- WO2016157010A1 WO2016157010A1 PCT/IB2016/051468 IB2016051468W WO2016157010A1 WO 2016157010 A1 WO2016157010 A1 WO 2016157010A1 IB 2016051468 W IB2016051468 W IB 2016051468W WO 2016157010 A1 WO2016157010 A1 WO 2016157010A1
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- G—PHYSICS
- G06—COMPUTING OR CALCULATING; COUNTING
- G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
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- G06V20/60—Type of objects
- G06V20/69—Microscopic objects, e.g. biological cells or cellular parts
- G06V20/698—Matching; Classification
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- the following relates to diagnosis and epidemiological monitoring of parasitic infections due to etiological agents such as nematode worms of various types, or amoebic infections.
- STH infections are a serious medical problem, especially in developing regions.
- some common nematode species of human soil-transmitted helminth (STH) infections also known as geohelminths, include: Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), Ancylostoma duodenale and Necator americanus (hookworms).
- STH infections are most prevalent in tropical and sub-tropical regions of the developing world where adequate water and sanitation are lacking, with estimates suggesting that people numbering in the hundreds of millions may be infected.
- Large numbers of STH infections occur in sub-Saharan Africa, East Asia, China, India and South America. Children in particular are significantly impacted, and can experience long-term debilitation such as stunted growth, diminished physical fitness, and impaired memory and cognition.
- the World Health Organization has engaged in eradication programs for several parasitic infections, using preventative chemotherapy. Epidemiological data and disease surveillance are important components of these programs. Thus, there is a need for innovative diagnostic tools that will make this possible.
- a stool i.e. feces
- urine sample depending on the parasite
- a sample slide is prepared and inspected under a microscope via which eggs and/or worms are observed.
- a quantitative count is made, especially for epidemiology. This is typically done by a specialist, for example, a parasitologist.
- a related problem is that, due to the time constraints, a parasitologist may not count the eggs, so that the diagnosis is limited to the type of parasite (if any) being identified on the microscope slide. While this may be sufficient to initiate deworming treatment, it reduces the data available for epidemiological monitoring. Quantitative count data allows for better targeting of deworming programs, such as the STH eradication programs being implemented by the WHO. Indeed, where eradication efforts are effective, epidemiological monitoring becomes more valuable as a tool for early detection of new outbreaks and targeted deworming of those (now fewer) individuals actually infected with the parasite.
- a medical parasitology system includes: a digital microscope configured to acquire a digital microscope image; a parasitology workstation including a computer and an electronic display device, the parasitology workstation programmed to perform a medical parasitology method including displaying the digital microscope image on the electronic display device; and a wireless communication link configured to transmit the digital microscope image from the digital microscope to the parasitology workstation.
- a medical parasitology method includes: acquiring a digital microscope image of a biological sample suspected to indicate a parasite infection using a digital microscope; sending the digital microscope image to a parasitology workstation; displaying the digital microscope image on an electronic display device of the parasitology workstation; and analyzing, using the parasitology workstation, the digital microscope image to determine a diagnosis of a parasite infection.
- a system for diagnosing a parasite infection includes: a digital microscope configured to acquire a digital microscope image of a biological sample; and a medical parasitology workstation, comprising: an electronic display configured to display the digital microscope image; and a computer programmed to perform an auto-count process that scans the digital microscope image using a parasite template image in order to generate a parasite count for the digital microscope image.
- a system for diagnosing a parasite infection includes: a digital microscope configured to acquire a digital microscope image of a sample; a medical parasitology workstation, comprising: an electronic display; and one or more processors configured to: cause the electronic display to display the acquired digital microscope image; obtain parasite template images from a library of parasite template images; and suggest, via the electronic display, at least one parasitic infection based on a comparison between the obtained parasite template images and the acquired digital microscope image.
- One advantage resides in requiring fewer parasitologists in a parasitic infection diagnosing program. Put another way, one parasitologist may diagnose more infections in a shorter amount of time using the systems and methods described herein.
- Another advantage resides in a reduced need for "fixing" chemicals.
- Another advantage resides in more accurate data collection of an amount of eggs in a sample.
- Another advantage resides in that parasite count data are more likely to be collected than in previous systems.
- Another advantage resides in a diagnostic system that is easier for a parasitologist to use, due to an improved user interface and more automated interface functionality, than previous systems.
- Another advantage resides in a low cost diagnostic tool.
- Another advantage resides in the effective utilization of volunteers who are not fully trained as parasitologists.
- the invention may take form in various components and arrangements of components, and in various steps and arrangements of steps.
- the drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention.
- FIGURE 1 diagrammatically shows a medical parasitology system for diagnosing a parasitic infection and/or performing epidemiological monitoring.
- FIGURE 2 shows a in illustrative example of a display generated on the electronic display device of the medical parasitology system of FIGURE 1.
- Various systems and methods described herein relate to a mobile (or in-the- field) digital microscope constructed as a scanner or as a large-FOV (field of view) digital microscope for acquiring relatively large-area images so as to enable parasite counts, and a wireless communication link to a centralized parasitology laboratory equipped with medical parasitology workstation(s) and staffed by parasitologist(s).
- a mobile digital microscope constructed as a scanner or as a large-FOV (field of view) digital microscope for acquiring relatively large-area images so as to enable parasite counts, and a wireless communication link to a centralized parasitology laboratory equipped with medical parasitology workstation(s) and staffed by parasitologist(s).
- samples can be collected, imaged by the mobile digital microscope, and the digital microscope images sent to the central lab for diagnosis. This improves the efficiency of the parasitologists who no longer need to travel to perform on-site microscopic inspections.
- the microscope may attach to a mobile phone, and may be battery operated. Any acquired image may be displayed on a mobile phone or tablet and/or on a display in a laboratory. In some embodiments, to save cost and improve portability the portable microscope has no electronic display.
- a biological sample 2 (e.g. stool or urine or blood) is acquired from a human subject who is to be diagnosed for possible parasite infection.
- the biological sample 2 may optionally be processed for microscopic inspection, for example by placement on a microscope slide, optional chemical staining or other chemical processing, sieving, or so forth.
- the Kato-Katz sample preparation technique is applied to prepare the sample 2, although other or variant preparation techniques are contemplated.
- the sample is loaded into and scanned by a digital microscope.
- the microscope 4 is preferably designed to be low cost and simple to operate - accordingly, it is typically an optical (i.e. "light") microscope.
- the magnification is chosen to comport with the (average) size of parasites that are expected to be observed if the subject is infected.
- the parasite may be microscopically observed in any stage of its life cycle that is present in the biological sample, including its motile phase (e.g. the motile worm phase of a nematode) and/or its embryotic stage (e.g. nematode eggs may be observed).
- the field of view should be large enough to provide a statistically significant parasite count - to this end, the microscope 4 may be a scanning microscope in which the sample stage is translatable (manually or automatically), or may be designed with an aperture large enough to acquire the entire desired field of view without scanning.
- the microscope 4 is preferably sufficiently simple to operate that it does not require a trained clinician (e.g. parasitologist) to operate, and accordingly may be operated by a local volunteer or other non-expert.
- the non-expert is not expected to have the expertise to analyze the microscope image in order to diagnose whether the subject has a parasite infection.
- the microscope 4 is a digital microscope which acquires an electronic, i.e. digital, microscope image, for example comprising a two-dimensional array of pixels each having a greyscale value, and the acquired digital microscope image is conveyed via a wireless communication link 6 to a parasitology laboratory 8, and more particularly to a medical parasitology workstation 10 housed in or accessible at the laboratory 8 (e.g. accessed via a dumb terminal at the laboratory 8).
- the wireless communication link 6 may, for example, comprise a mobile telecommunication link of the type commonly used for cellular telephone communication, such as a wireless 3G or 4G link. Alternatively, the wireless communication link 6 may be a dedicated satellite link. To accommodate possibly limited bandwidth, it is contemplated to perform image compression before the wireless transmission, and/or to store and transfer the digital microscope image in a compressed format such as JPEG.
- the parasitology workstation 10 provides functionality to display the acquired digital microscope image, and optionally to perform an auto-count process 12 in order to generate a parasite count, that is, a count of parasites observed in the image in motile (e.g. worm) form and/or in embryonic (e.g. egg) form.
- the medical parasitology workstation 10 includes an electronic processor 16 (for example, in the form of a computer) and an electronic display device 20 such as an LCD display device, an organic LED (OLED) display device, a plasma display device, a cathode ray tube (CRT) display device, or so forth.
- the illustrative processor 16 is embodied as a computer which also includes or is operatively connected with the display device 20.
- the processor 16 and display 20 may be embodied as a desktop computer or tower computer with separate display, or as a notebook computer with integral display, or so forth. It is also contemplated for the processor 16 to be implemented as a cloud computing resource, accessed via a "dumb" terminal that includes the display device 20.
- a health worker may obtain manually prepare the biological sample 2 on a microscope slide (e.g. using the Kato Katz method).
- the slide may or may not be stained or otherwise prepared.
- the microscope 4 is used to acquire a digital microscope image of the biological sample 2.
- the microscope 4 may in some embodiments be a scanning optical microscope in which the sample stage scanning is operated by hand. For example, images may be repeatedly captured and then combined to construct an image of the entire sample, or the microscope may use a line light source and associated linear array of optical sensors, and the sample 2 is scanned in the direction transverse to the line light source while acquiring data from the optical sensors to generate a two-dimensional digital microscope image.
- an automated sample stage driven by a small electromotor and optional gearing, e.g. if scanning is performed in two orthogonal directions
- the scanner is used only to center the sample under the microscope (or is omitted entirely and the slide 2 is manually centered on a stationary sample stage).
- the aperture of the microscope is selected to be large enough such that the entire sample may be imaged at once to generate the digital microscope image. This leads to the advantage that, during capturing of the sample, no scanning is needed.
- the microscope 4 may have a stationary sample stage and a light beam (e.g. linear) may be optically scanned over the sample using an optical train with tilting mirrors or the like.
- the digital microscope 4 is portable, so that it can be transported from village to village in order to acquire digital microscope images for analysis from a large number of persons, for example as part of a regional epidemiological study.
- the digital microscope 4 is battery powered to facilitate portability.
- the digital microscope 4 omits any electronic display device to facilitate portability.
- the digital microscope 4 may include a USB port, Bluetooth wireless connectivity, or the like in order to enable the digital microscope 4 to connect with a cellular telephone or other wireless mobile device.
- the digital image may be transferred to the mobile device and displayed using the mobile device display.
- the mobile device may also provide (i.e. embody) the wireless communication link 6, for example by loading a suitable mobile device application ("app" onto the mobile device that programs the mobile device to connect with the microscope 4, receive the digital microscope image, and wirelessly communicate the image to the parasitology workstation 10.
- the components 4, 6 enable the biological sample 2 to be imaged and to transfer the digital microscope image (rather than the biological sample itself) to the parasitology laboratory 8 for analysis.
- This enables one or more medically trained clinicians, e.g. parasitologists, to analyze incoming digital microscope images at the laboratory 8, using the parasitology workstation 10, rather than spending time physically visiting remote locations to perform sample acquisition.
- sample preparation may be simplified. If sufficient laboratory facilities are available, it might also be possible to clean off and re-use microscope slides, further reducing cost.
- the single illustrative digital microscope 4 is illustrated, in general there may be many such digital microscopes acquiring digital microscope images of samples acquired from human subjects in different villages or other different locales, all of which may send microscope images to the centralized parasitology lab 8.
- the digital microscope 4 (or an intermediate device such as a cellular telephone or other mobile device) suitably annotates each microscope image with identifying information such as subject name (except possibly in epidemiological studies in which donor anonymity is maintained), geographical location, subject demographic information, or so forth.
- parasitology workstation 10 In larger-scale laboratory operations staffed by more than one parasitologist, there may also be more than one parasitology workstation 10 (e.g. one workstation per parasitologist), and a central image storage may be provided for the laboratory from which individual workstations can retrieve images for analysis.
- the microscope 4 is portable, it is also contemplated for the microscope to be non-portable - for example, the disclosed benefits can be substantially obtained by deploying a fleet of non-portable microscopes at various (possibly temporary) locations, for example covering a geographical region that is the subject of epidemiological monitoring.
- the digital microscope image is displayed on the electronic display device 20.
- the parasitologist performs the analysis of the displayed image manually, by visually identifying parasites in the image based on his or her medical expertise, and optionally performing a count of the visually observed parasites (where again a parasite may be in motile form and/or embryotic form, e.g. imaged parasite eggs).
- a parasite may be in motile form and/or embryotic form, e.g. imaged parasite eggs.
- there may be many images to analyze at least one for each human subject undergoing diagnosis. Accordingly, in some embodiments further efficiency is gained by improving the diagnostic processing performed using the parasitology workstation 10.
- FIGURE 2 in one assistive approach, a library 22 of parasite template images is provided.
- the library 22 is stored on a non-transitory storage medium (e.g. hard disk of the computer 16, or a remote network-accessed server storage, or so forth) that is included with or accessible by the workstation 10.
- images 30 of known parasites retrieved from the library 22 are shown side-by-side (or at least on the same screen as) the display 32 of the digital microscope image, so that the parasitologist can easily compare the image features with known (template) parasite images 30.
- the optional automated or semi-automated counting process 12 may be invoked to generate a parasite count.
- the parasite count may be variously represented, such as a count of the field of view of the image, or normalized based on area (e.g. count/square millimeter), or normalized based on a sample weight (e.g. a per gram count of the sample).
- the parasite count preferably follows some standardized set of counting rules, such as being for a standard area or sample weight, counting only parasites in embryotic form (i.e. an "egg count"), etc.
- Illustrative FIGURE 2 shows a count window or dialog 34 which displays count results for two types of parasites observed in the digital microscope image 32, namely for the trichuris trichiura parasite and for the ascans lumbricoides parasite.
- the optional automated counting process 12 greatly increases a parasitologist's workflow efficiency. Furthermore, without automation, a parasitologist may be tempted to limit the diagnosis to identification of the type of parasite (if any), without performing a parasite count. The count data is useful for programs such as eradication programs or other epidemiology.
- template matching is employed to perform the automated counting, using a parasite template image for the matching.
- the match at a location in the microscope image denoted (Xi, 0 > yi,o) may be computed as ⁇ TM Q * 1 ⁇ yTM c 1
- /() denotes a pixel of the microscope image
- TQ denotes a pixel of the parasite template image.
- smaller values for the double summation indicate a closer match between the microscope image at the location (Xi i0 , yi,o) and the parasite template image - thus, a match may be defined as the value of the double summation being below some chosen threshold value.
- the count then sums the number of matches as the parasite template image is scanned across the microscope image.
- the threshold may be chosen, for example, so as to match the output of the template matching with manual counts by a parasitologist for a few "training" images. For circular eggs or other circular parasites, the foregoing can be applied directly.
- the scan may be repeated for several different rotations of the parasite template image to accommodate the different possible orientations of the non-circular parasite instances. This is merely an illustrative example, and more generally any template matching algorithm may be employed.
- Some contemplated template matching algorithms may be feature-based - for example, if it is determined that the parasite image exhibits a maximum pixel intensity, maximum contrast, or so forth that is characteristic of the parasite, these parasite template image features may be used for the template matching process.
- the parasite image template may be obtained from the library 22.
- this approach could be problematic when used in conjunction with images acquired by the disclosed in the field microscope imagers because image quality may vary due to equipment limitations, wireless bandwidth limitations, the use of relatively untrained volunteers for acquiring the images, and so forth.
- the parasitologist manually identifies and tags one or a few instances of a parasite signature in the actual digital microscope image being analyzed, and the instance(s) are then used to generate the template image.
- the parasitology workstation 10 is provided with a user input pointing device via which a user can identify a parasite image in the display 32 of the digital microscope image shown on the electronic display device 20.
- the user input pointing device may, for example, be a mouse, trackball, trackpad, or the like, or the user input pointing device may be the electronic display device 20 if the electronic display device 20 includes a touch-sensitive screen.
- the parasitologist identifies a single instance of the parasite in the microscope image, then that image may be used as the parasite template image. If the parasitologist identifies more than one parasite (of a given type) in the microscope image, the parasite template may be derived from these by, for example, averaging the images (after suitable rotations in the case of a non-circular parasite). In the case of feature-based template matching, the value(s) of the template image feature(s) used in the template matching are suitably chosen as an average of the feature values for the parasite instances identified by the parasitologist.
- Automated parasite counting performed by the auto-count process 12 is generally faster than manual counting performed by the parasitologist. However, still further efficiency can be gained by executing the auto-count process 12 as a background process running on the computer 16.
- the parasitologist's time is efficiently used to identify just one or a few parasite instances per microscope image, and the counting is thereafter performed as a background process (optionally using the identified parasite instances as the parasite image template) while the parasitologist moves on to viewing the next microscope image.
- the display will show an image of a new sample to the parasitologist while a processor 16 performs parasite counting on the previous microscope image. This advantageously increases efficiency of a parasitologist's time, for example, because the parasitologist may move on to identifying parasites in a different image while the processor performs counting in the background.
- the process may be further automated by automating the identification of the type of parasite(s) in the microscope image.
- an algorithm may access the library 22 of parasite template images.
- the algorithm suitably compares the parasite template images with the slide image information to make suggestions to the parasitologist.
- One way to do this is to perform the template matching process for each parasite template image in the library 22, and suggest any parasite whose template image produces a threshold number of matches.
- the algorithm may display an image 30 of a suggested parasite alongside the actual slide image. This approach is advantageous because it increases efficiency of the parasitologist's time. For example, in this approach, the parasitologist ideally will spend less time digging through information from a library of parasite information, and spend less time making a diagnosis.
- the algorithm may determine the suggestions by finding similarities between the slide image and information from the library of parasite infection information.
- the parasitologist may use the display to access more information about specific parasites. This more automated approach further reduces potential for errors because, with the information so easily available to the parasitologist, the parasitologist is more likely to access the information rather than relying on his memory.
- the process may be even more automated. Specifically, computerized analysis may be done before a parasitologist sees the sample. For example, an algorithm may look for similar features in a digital image of the sample, and count the number of occurrences of these features. Template matching may be employed in this sub-variant approach as well.
- the automated counting is sufficiently efficient (and uses stored parasite template images), then it is contemplated to perform the diagnosis and counting locally using an on-board microscope scanner microprocessor. This may be done without any on-board display component, except perhaps an alphanumeric readout to identify the parasite type(s) and count(s).
- Information on the parasite count may be collected into, for example, a centralized database, and used for purposes such as more efficient and better allocation of parasite eradication resources.
- any other kind of information may be collected and recored. For example, a time and geographic location information may be collected.
- diagnosis and data collection techniques disclosed herein may be embodied by a non-transitory storage medium storing instructions readable and executable by an electronic data processing device to perform the disclosed techniques.
- a non-transitory storage medium may comprise a hard drive or other magnetic storage medium, an optical disk or other optical storage medium, a cloud-based storage medium such as a RAID disk array, flash memory or other non-volatile electronic storage medium, or so forth.
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Abstract
The following relates to diagnosis and epidemiological monitoring of parasitic infections due to etiological agents such as nematode worms of various types, or amoebic infections. In a remote location, a sample of stool or urine may be collected and placed onto a slide. A mobile (or in-the-field) digital microscope scanner or large-FOV (field of view) digital microscope may be used to acquire an image(s) of the sample. The image(s) may be transmitted to a remote location (e.g. a parasitology lab) for analysis (e.g. by a parasitologist). Computer algorithms may aide in the diagnosis. For example, a computer algorithm may count a number of eggs in the sample, or provide suggestions to a parasitologist about what parasite(s) might be present in a sample.
Description
DIGITAL PARASITOLOGY
BACKGROUND
The following relates to diagnosis and epidemiological monitoring of parasitic infections due to etiological agents such as nematode worms of various types, or amoebic infections.
Parasitic infections are a serious medical problem, especially in developing regions. For example, some common nematode species of human soil-transmitted helminth (STH) infections, also known as geohelminths, include: Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), Ancylostoma duodenale and Necator americanus (hookworms). These infections are most prevalent in tropical and sub-tropical regions of the developing world where adequate water and sanitation are lacking, with estimates suggesting that people numbering in the hundreds of millions may be infected. Large numbers of STH infections occur in sub-Saharan Africa, East Asia, China, India and South America. Children in particular are significantly impacted, and can experience long-term debilitation such as stunted growth, diminished physical fitness, and impaired memory and cognition.
The World Health Organization (WHO) has engaged in eradication programs for several parasitic infections, using preventative chemotherapy. Epidemiological data and disease surveillance are important components of these programs. Thus, there is a need for innovative diagnostic tools that will make this possible.
In a conventional tool to diagnose STH infections, a stool (i.e. feces) or urine sample (depending on the parasite) is collected, and a sample slide is prepared and inspected under a microscope via which eggs and/or worms are observed. Ideally, a quantitative count is made, especially for epidemiology. This is typically done by a specialist, for example, a parasitologist.
However, there are far too few parasitologists available who are qualified to perform the microscopic inspection/diagnosis. These parasitologists are dispatched in the field, where their effectiveness is further hampered by difficulties in travel and limited access to electricity and other infrastructure. An alternative approach is to send samples to a central parasitology laboratory for analysis, but this approach requires preserving the samples (e.g. stool or urine samples) prior to transporting the samples to the parasitology laboratory because the samples degrade quickly. Thus, this approach requires the availability of slide
"fixing" chemicals in the field to preserve the samples, which are not always readily available. Furthermore, this approach is also hampered by travel limitations.
A related problem is that, due to the time constraints, a parasitologist may not count the eggs, so that the diagnosis is limited to the type of parasite (if any) being identified on the microscope slide. While this may be sufficient to initiate deworming treatment, it reduces the data available for epidemiological monitoring. Quantitative count data allows for better targeting of deworming programs, such as the STH eradication programs being implemented by the WHO. Indeed, where eradication efforts are effective, epidemiological monitoring becomes more valuable as a tool for early detection of new outbreaks and targeted deworming of those (now fewer) individuals actually infected with the parasite.
SUMMARY
In accordance with one aspect, a medical parasitology system includes: a digital microscope configured to acquire a digital microscope image; a parasitology workstation including a computer and an electronic display device, the parasitology workstation programmed to perform a medical parasitology method including displaying the digital microscope image on the electronic display device; and a wireless communication link configured to transmit the digital microscope image from the digital microscope to the parasitology workstation.
In accordance with another aspect, a medical parasitology method includes: acquiring a digital microscope image of a biological sample suspected to indicate a parasite infection using a digital microscope; sending the digital microscope image to a parasitology workstation; displaying the digital microscope image on an electronic display device of the parasitology workstation; and analyzing, using the parasitology workstation, the digital microscope image to determine a diagnosis of a parasite infection.
In accordance with yet another aspect, a system for diagnosing a parasite infection includes: a digital microscope configured to acquire a digital microscope image of a biological sample; and a medical parasitology workstation, comprising: an electronic display configured to display the digital microscope image; and a computer programmed to perform an auto-count process that scans the digital microscope image using a parasite template image in order to generate a parasite count for the digital microscope image.
In accordance with yet another aspect, a system for diagnosing a parasite infection includes: a digital microscope configured to acquire a digital microscope image of a sample; a medical parasitology workstation, comprising: an electronic display; and one or
more processors configured to: cause the electronic display to display the acquired digital microscope image; obtain parasite template images from a library of parasite template images; and suggest, via the electronic display, at least one parasitic infection based on a comparison between the obtained parasite template images and the acquired digital microscope image.
One advantage resides in requiring fewer parasitologists in a parasitic infection diagnosing program. Put another way, one parasitologist may diagnose more infections in a shorter amount of time using the systems and methods described herein.
Another advantage resides in a reduced need for "fixing" chemicals.
Another advantage resides in more accurate data collection of an amount of eggs in a sample.
Another advantage resides in that parasite count data are more likely to be collected than in previous systems.
Another advantage resides in a diagnostic system that is easier for a parasitologist to use, due to an improved user interface and more automated interface functionality, than previous systems.
Another advantage resides in a low cost diagnostic tool.
Another advantage resides in the effective utilization of volunteers who are not fully trained as parasitologists.
Other advantages will become apparent to one of ordinary skill in the art upon reading and understanding this disclosure.
The invention may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention.
FIGURE 1 diagrammatically shows a medical parasitology system for diagnosing a parasitic infection and/or performing epidemiological monitoring.
FIGURE 2 shows a in illustrative example of a display generated on the electronic display device of the medical parasitology system of FIGURE 1.
DETAILED DESCRIPTION
Various systems and methods described herein relate to a mobile (or in-the- field) digital microscope constructed as a scanner or as a large-FOV (field of view) digital microscope for acquiring relatively large-area images so as to enable parasite counts, and a wireless communication link to a centralized parasitology laboratory equipped with medical
parasitology workstation(s) and staffed by parasitologist(s). In this way, samples can be collected, imaged by the mobile digital microscope, and the digital microscope images sent to the central lab for diagnosis. This improves the efficiency of the parasitologists who no longer need to travel to perform on-site microscopic inspections. Instead of a wireless link, it is also contemplated to store the images on an on-scanner memory or on a USB thumb drive or other portable non-transitory storage medium, and manually transport the images to the lab where the USB thumb drive is connected with the workstation in order to copy the image to the workstation. The microscope may attach to a mobile phone, and may be battery operated. Any acquired image may be displayed on a mobile phone or tablet and/or on a display in a laboratory. In some embodiments, to save cost and improve portability the portable microscope has no electronic display.
With reference to FIGURE 1, a medical parasitology system is described for diagnosing a parasitic infection and/or performing epidemiological monitoring. A biological sample 2 (e.g. stool or urine or blood) is acquired from a human subject who is to be diagnosed for possible parasite infection. The biological sample 2 may optionally be processed for microscopic inspection, for example by placement on a microscope slide, optional chemical staining or other chemical processing, sieving, or so forth. In some contemplated embodiments, the Kato-Katz sample preparation technique is applied to prepare the sample 2, although other or variant preparation techniques are contemplated. The sample is loaded into and scanned by a digital microscope. The microscope 4 is preferably designed to be low cost and simple to operate - accordingly, it is typically an optical (i.e. "light") microscope. The magnification is chosen to comport with the (average) size of parasites that are expected to be observed if the subject is infected. In general, the parasite may be microscopically observed in any stage of its life cycle that is present in the biological sample, including its motile phase (e.g. the motile worm phase of a nematode) and/or its embryotic stage (e.g. nematode eggs may be observed). The field of view should be large enough to provide a statistically significant parasite count - to this end, the microscope 4 may be a scanning microscope in which the sample stage is translatable (manually or automatically), or may be designed with an aperture large enough to acquire the entire desired field of view without scanning. The microscope 4 is preferably sufficiently simple to operate that it does not require a trained clinician (e.g. parasitologist) to operate, and accordingly may be operated by a local volunteer or other non-expert. However, the non-expert is not expected to have the expertise to analyze the microscope image in order to diagnose whether the subject has a parasite infection. Rather, the microscope 4 is a digital
microscope which acquires an electronic, i.e. digital, microscope image, for example comprising a two-dimensional array of pixels each having a greyscale value, and the acquired digital microscope image is conveyed via a wireless communication link 6 to a parasitology laboratory 8, and more particularly to a medical parasitology workstation 10 housed in or accessible at the laboratory 8 (e.g. accessed via a dumb terminal at the laboratory 8). The wireless communication link 6 may, for example, comprise a mobile telecommunication link of the type commonly used for cellular telephone communication, such as a wireless 3G or 4G link. Alternatively, the wireless communication link 6 may be a dedicated satellite link. To accommodate possibly limited bandwidth, it is contemplated to perform image compression before the wireless transmission, and/or to store and transfer the digital microscope image in a compressed format such as JPEG. The parasitology workstation 10 provides functionality to display the acquired digital microscope image, and optionally to perform an auto-count process 12 in order to generate a parasite count, that is, a count of parasites observed in the image in motile (e.g. worm) form and/or in embryonic (e.g. egg) form. To this end, the medical parasitology workstation 10 includes an electronic processor 16 (for example, in the form of a computer) and an electronic display device 20 such as an LCD display device, an organic LED (OLED) display device, a plasma display device, a cathode ray tube (CRT) display device, or so forth. The illustrative processor 16 is embodied as a computer which also includes or is operatively connected with the display device 20. For example, the processor 16 and display 20 may be embodied as a desktop computer or tower computer with separate display, or as a notebook computer with integral display, or so forth. It is also contemplated for the processor 16 to be implemented as a cloud computing resource, accessed via a "dumb" terminal that includes the display device 20.
In the following, a parasite infection diagnosis process suitably performed by the medical parasitology system of FIGURE 1, possibly as part of or in conjunction with epidemiological monitoring, is described.
Initially, to collect the samples, a health worker may obtain manually prepare the biological sample 2 on a microscope slide (e.g. using the Kato Katz method). The slide may or may not be stained or otherwise prepared.
Once the slide is prepared, the portable microscope 4 is used to acquire a digital microscope image of the biological sample 2. The microscope 4 may in some embodiments be a scanning optical microscope in which the sample stage scanning is operated by hand. For example, images may be repeatedly captured and then combined to construct an image of the entire sample, or the microscope may use a line light source and
associated linear array of optical sensors, and the sample 2 is scanned in the direction transverse to the line light source while acquiring data from the optical sensors to generate a two-dimensional digital microscope image. Instead of a manual sample stage, an automated sample stage driven by a small electromotor (and optional gearing, e.g. if scanning is performed in two orthogonal directions) may move the sample under the microscope to record the entire image.
In another alternative, the scanner is used only to center the sample under the microscope (or is omitted entirely and the slide 2 is manually centered on a stationary sample stage). In this approach, the aperture of the microscope is selected to be large enough such that the entire sample may be imaged at once to generate the digital microscope image. This leads to the advantage that, during capturing of the sample, no scanning is needed. As still yet another contemplated alternative, the microscope 4 may have a stationary sample stage and a light beam (e.g. linear) may be optically scanned over the sample using an optical train with tilting mirrors or the like.
In some embodiments, the digital microscope 4 is portable, so that it can be transported from village to village in order to acquire digital microscope images for analysis from a large number of persons, for example as part of a regional epidemiological study. In some embodiments, the digital microscope 4 is battery powered to facilitate portability. In some embodiments, the digital microscope 4 omits any electronic display device to facilitate portability. It is further contemplated for the digital microscope 4 to include a USB port, Bluetooth wireless connectivity, or the like in order to enable the digital microscope 4 to connect with a cellular telephone or other wireless mobile device. In such embodiments, the digital image may be transferred to the mobile device and displayed using the mobile device display. In such embodiments, the mobile device may also provide (i.e. embody) the wireless communication link 6, for example by loading a suitable mobile device application ("app" onto the mobile device that programs the mobile device to connect with the microscope 4, receive the digital microscope image, and wirelessly communicate the image to the parasitology workstation 10.
It will be appreciated that the components 4, 6 enable the biological sample 2 to be imaged and to transfer the digital microscope image (rather than the biological sample itself) to the parasitology laboratory 8 for analysis. This enables one or more medically trained clinicians, e.g. parasitologists, to analyze incoming digital microscope images at the laboratory 8, using the parasitology workstation 10, rather than spending time physically visiting remote locations to perform sample acquisition. Furthermore, since the biological
sample 2 is not physically transported to the laboratory 8, sample preparation may be simplified. If sufficient laboratory facilities are available, it might also be possible to clean off and re-use microscope slides, further reducing cost.
It should also be noted that while the single illustrative digital microscope 4 is illustrated, in general there may be many such digital microscopes acquiring digital microscope images of samples acquired from human subjects in different villages or other different locales, all of which may send microscope images to the centralized parasitology lab 8. The digital microscope 4 (or an intermediate device such as a cellular telephone or other mobile device) suitably annotates each microscope image with identifying information such as subject name (except possibly in epidemiological studies in which donor anonymity is maintained), geographical location, subject demographic information, or so forth.
In larger-scale laboratory operations staffed by more than one parasitologist, there may also be more than one parasitology workstation 10 (e.g. one workstation per parasitologist), and a central image storage may be provided for the laboratory from which individual workstations can retrieve images for analysis.
While in the illustrative example the microscope 4 is portable, it is also contemplated for the microscope to be non-portable - for example, the disclosed benefits can be substantially obtained by deploying a fleet of non-portable microscopes at various (possibly temporary) locations, for example covering a geographical region that is the subject of epidemiological monitoring.
After receipt at the workstation 10, the digital microscope image is displayed on the electronic display device 20. In one approach, the parasitologist performs the analysis of the displayed image manually, by visually identifying parasites in the image based on his or her medical expertise, and optionally performing a count of the visually observed parasites (where again a parasite may be in motile form and/or embryotic form, e.g. imaged parasite eggs). However, in an epidemiological study, or when dealing with a rapidly spreading parasite outbreak, there may be many images to analyze (at least one for each human subject undergoing diagnosis). Accordingly, in some embodiments further efficiency is gained by improving the diagnostic processing performed using the parasitology workstation 10.
With continuing reference to FIGURE 1 and with further reference to
FIGURE 2, in one assistive approach, a library 22 of parasite template images is provided. The library 22 is stored on a non-transitory storage medium (e.g. hard disk of the computer 16, or a remote network-accessed server storage, or so forth) that is included with or accessible by the workstation 10. As shown in FIGURE 2, images 30 of known parasites
retrieved from the library 22 are shown side-by-side (or at least on the same screen as) the display 32 of the digital microscope image, so that the parasitologist can easily compare the image features with known (template) parasite images 30. In addition or in the alternative, in some embodiments the optional automated or semi-automated counting process 12 may be invoked to generate a parasite count. The parasite count may be variously represented, such as a count of the field of view of the image, or normalized based on area (e.g. count/square millimeter), or normalized based on a sample weight (e.g. a per gram count of the sample). The parasite count preferably follows some standardized set of counting rules, such as being for a standard area or sample weight, counting only parasites in embryotic form (i.e. an "egg count"), etc. Illustrative FIGURE 2 shows a count window or dialog 34 which displays count results for two types of parasites observed in the digital microscope image 32, namely for the trichuris trichiura parasite and for the ascans lumbricoides parasite.
The optional automated counting process 12 greatly increases a parasitologist's workflow efficiency. Furthermore, without automation, a parasitologist may be tempted to limit the diagnosis to identification of the type of parasite (if any), without performing a parasite count. The count data is useful for programs such as eradication programs or other epidemiology.
In one suitable automated counting approach, template matching is employed to perform the automated counting, using a parasite template image for the matching. In this approach, the parasite template image is scanned across the image, and at each location the "match" between the parasite template image and the region of the image at that location is quantitatively compared. For example, denoting without loss of generality the pixel positions along one (x) image direction as x = (0, xmax— 1) and along the orthogonal (y) direction as = (0, ... , ymax— 1) , the match at a location in the microscope image denoted (Xi,0 > yi,o) may be computed as∑ ™Q* 1∑y™ c 1| i,o + χ> Υί,ο+γ) ~ T(x, y) \ where /() denotes a pixel of the microscope image and TQ denotes a pixel of the parasite template image. In this formulation, smaller values for the double summation indicate a closer match between the microscope image at the location (Xii0, yi,o) and the parasite template image - thus, a match may be defined as the value of the double summation being below some chosen threshold value. The count then sums the number of matches as the parasite template image is scanned across the microscope image. The threshold may be chosen, for example, so as to match the output of the template matching with manual counts by a parasitologist for a few "training" images.
For circular eggs or other circular parasites, the foregoing can be applied directly. On the other hand, if the parasite is non-circular, then the scan may be repeated for several different rotations of the parasite template image to accommodate the different possible orientations of the non-circular parasite instances. This is merely an illustrative example, and more generally any template matching algorithm may be employed. Some contemplated template matching algorithms may be feature-based - for example, if it is determined that the parasite image exhibits a maximum pixel intensity, maximum contrast, or so forth that is characteristic of the parasite, these parasite template image features may be used for the template matching process.
Accuracy of the parasite count generated by the template matching is contingent on how well the parasite image template matches the parasites imaged in the digital microscope image. In some embodiments, the parasite image template may be obtained from the library 22. However, this approach could be problematic when used in conjunction with images acquired by the disclosed in the field microscope imagers because image quality may vary due to equipment limitations, wireless bandwidth limitations, the use of relatively untrained volunteers for acquiring the images, and so forth.
In another way of generating the parasite template image for the template matching process, the parasitologist manually identifies and tags one or a few instances of a parasite signature in the actual digital microscope image being analyzed, and the instance(s) are then used to generate the template image. To this end, the parasitology workstation 10 is provided with a user input pointing device via which a user can identify a parasite image in the display 32 of the digital microscope image shown on the electronic display device 20. The user input pointing device may, for example, be a mouse, trackball, trackpad, or the like, or the user input pointing device may be the electronic display device 20 if the electronic display device 20 includes a touch-sensitive screen. If the parasitologist identifies a single instance of the parasite in the microscope image, then that image may be used as the parasite template image. If the parasitologist identifies more than one parasite (of a given type) in the microscope image, the parasite template may be derived from these by, for example, averaging the images (after suitable rotations in the case of a non-circular parasite). In the case of feature-based template matching, the value(s) of the template image feature(s) used in the template matching are suitably chosen as an average of the feature values for the parasite instances identified by the parasitologist.
Automated parasite counting performed by the auto-count process 12 is generally faster than manual counting performed by the parasitologist. However, still further
efficiency can be gained by executing the auto-count process 12 as a background process running on the computer 16. Here, the parasitologist's time is efficiently used to identify just one or a few parasite instances per microscope image, and the counting is thereafter performed as a background process (optionally using the identified parasite instances as the parasite image template) while the parasitologist moves on to viewing the next microscope image. In other words, the display will show an image of a new sample to the parasitologist while a processor 16 performs parasite counting on the previous microscope image. This advantageously increases efficiency of a parasitologist's time, for example, because the parasitologist may move on to identifying parasites in a different image while the processor performs counting in the background.
In another variant approach, the process may be further automated by automating the identification of the type of parasite(s) in the microscope image. In one appraoch, an algorithm may access the library 22 of parasite template images. The algorithm suitably compares the parasite template images with the slide image information to make suggestions to the parasitologist. One way to do this is to perform the template matching process for each parasite template image in the library 22, and suggest any parasite whose template image produces a threshold number of matches. The algorithm may display an image 30 of a suggested parasite alongside the actual slide image. This approach is advantageous because it increases efficiency of the parasitologist's time. For example, in this approach, the parasitologist ideally will spend less time digging through information from a library of parasite information, and spend less time making a diagnosis. The algorithm may determine the suggestions by finding similarities between the slide image and information from the library of parasite infection information.
Once the suggestion is provided to the parasitologist, if the parasitologist desires, the parasitologist may use the display to access more information about specific parasites. This more automated approach further reduces potential for errors because, with the information so easily available to the parasitologist, the parasitologist is more likely to access the information rather than relying on his memory.
In another sub-variant to the approach, the process may be even more automated. Specifically, computerized analysis may be done before a parasitologist sees the sample. For example, an algorithm may look for similar features in a digital image of the sample, and count the number of occurrences of these features. Template matching may be employed in this sub-variant approach as well.
In a variant embodiment, if the automated counting is sufficiently efficient (and uses stored parasite template images), then it is contemplated to perform the diagnosis and counting locally using an on-board microscope scanner microprocessor. This may be done without any on-board display component, except perhaps an alphanumeric readout to identify the parasite type(s) and count(s).
Information on the parasite count may be collected into, for example, a centralized database, and used for purposes such as more efficient and better allocation of parasite eradication resources. Along with the parasite count, any other kind of information may be collected and recored. For example, a time and geographic location information may be collected.
It will be further appreciated that the diagnosis and data collection techniques disclosed herein may be embodied by a non-transitory storage medium storing instructions readable and executable by an electronic data processing device to perform the disclosed techniques. Such a non-transitory storage medium may comprise a hard drive or other magnetic storage medium, an optical disk or other optical storage medium, a cloud-based storage medium such as a RAID disk array, flash memory or other non-volatile electronic storage medium, or so forth.
Of course, modifications and alterations will occur to others upon reading and understanding the preceding description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims
1. A medical parasitology system comprising:
a digital microscope (4) configured to acquire a digital microscope image;
a parasitology workstation (10) including a computer (16) and an electronic display device (20), the parasitology workstation (10) programmed to perform a medical parasitology method including displaying the digital microscope image on the electronic display device (20); and
a wireless communication link (6) configured to transmit the digital microscope image from the digital microscope to the parasitology workstation (10).
2. The medical parasitology system of claim 1 wherein the digital microscope (4) is a battery-powered portable digital microscope (4).
3. The medical parasitology system of any one of claims 1-2 wherein the digital microscope (4) does not include an electronic display device capable of displaying the digital microscope image.
4. The medical parasitology system of any one of claims 1-3 wherein the medical parasitology workstation (10) further includes:
a non-transitory storage medium storing a library of parasite template images (22); wherein the medical parasitology method performed by the parasitology workstation (10) further includes displaying, on the electronic display (20) device and together with the display of the digital microscope image, parasite template images (30) retrieved from the library of parasite template images (22).
5. The medical parasitology system of any one of claims 1-4 wherein the medical parasitology method performed by the parasitology workstation (10) further includes:
generating a parasite count for the digital microscope image by performing template matching on the digital microscope image using a parasite template image (30).
6. The medical parasitology system of claim 5 wherein the parasitology workstation (10) further includes:
a non-transitory storage medium storing a library of parasite template images (22);
wherein the medical parasitology method performed by the parasitology workstation (10) further includes retrieving the parasite template image (30) used in the template matching from the library of parasite template images (22).
7. The medical parasitology system of claim 5 wherein the parasitology workstation (10) further includes:
a user input pointing device via which a user can identify a parasite image in the digital microscope image displayed on the electronic display device (20);
wherein the parasite template image (30) used in the template matching comprises or is generated from one or more parasite images identified in the digital microscope image displayed on the electronic display (20) device by a user via the user input pointing device.
8. The medical parasitology system of claim 7 wherein a second digital microscope image is acquired by the digital microscope and transmitted via the wireless communication link (6) from the digital microscope (4) to the parasitology workstation (10), and the medical parasitology method performed by the parasitology workstation (10) further includes:
(i) displaying the second digital microscope image on the electronic display device (20) so as to replace the displayed digital microscope image with the displayed second digital microscope image; and
(ii) enabling user interaction with the displayed second digital microscope image via the user input pointing device;
wherein the parasitology workstation (10) is configured to perform the template matching on the digital microscope image as a background process while concurrently performing the operations (i) and (ii) on the second digital microscope image.
9. A medical parasitology method, comprising:
acquiring a digital microscope image of a biological sample suspected to indicate a parasite infection using a digital microscope (4);
sending the digital microscope image to a parasitology workstation (10);
displaying the digital microscope image on an electronic display device (20) of the parasitology workstation (10); and
analyzing, using the parasitology workstation (10), the digital microscope image to determine a diagnosis of a parasite infection.
10. The medical parasitology method of claim 9, further comprising: retrieving parasite template images (30) from a library of parasite template images (22) stored on a non-transitory storage medium; and
displaying the retrieved parasite template images (30) on the electronic display device (20) of the parasitology workstation (10) together with the displayed microscope image.
11. The medical parasitology method of claim 10, wherein the parasite template images (30) comprise images of parasites or parasite eggs.
12. The medical parasitology method of any of claims 9-11 wherein the analyzing comprises:
performing template matching on the digital microscope image using a parasite template image (30) to generate the diagnosis of a parasite infection comprising a parasite count for the digital microscope image, the template matching being performed by a computer (16) of the parasitology workstation (10).
13. The medical parasitology method of claim 12 further comprising:
performing the template matching as a background process on the computer (16) of the parasitology workstation (10) while simultaneously displaying a new digital microscope image on the electronic display device (20) of the parasitology workstation (10).
14. The method of any of claims 9-13 wherein the sending comprises one of:
(A) transmitting the digital microscope image from the digital microscope (4) to the parasitology workstation (10) via a wireless communication link (6); or
(B) storing the digital microscope image on a portable non-transitory storage medium disposed with the digital microscope (4), transporting the portable non-transitory storage medium to the parasitology workstation (10), connecting the portable non-transitory storage medium to the parasitology workstation (10), and copying the digital microscope image from the portable non-transitory storage medium to the parasitology workstation (10).
15. A system for diagnosing a parasite infection, comprising:
a digital microscope (4) configured to acquire a digital microscope image of a biological sample; and
a medical parasitology workstation (10), comprising:
an electronic display (20) configured to display the digital
microscope image; and
a computer (16) programmed to perform an auto-count process
(12) that scans the digital microscope image using a parasite template image
(30) in order to generate a parasite count for the digital microscope image.
16. The system of claim 15 wherein:
the auto-count process (12) is performed as a background process; and
the computer (16) executes a foreground process that causes the electronic display (20) to display successive digital microscope images.
17. A system for diagnosing a parasite infection, comprising:
a digital microscope (4) configured to acquire a digital microscope image of a sample; a medical parasitology workstation (10), comprising:
an electronic display (20); and
one or more processors configured to:
cause the electronic display (20) to display the acquired digital microscope image;
obtain parasite template images (30) from a library of parasite template images (22); and
suggest, via the electronic display (20), at least one parasitic infection based on a comparison between the obtained parasite template images (30) and the acquired digital microscope image.
18. The system of claim 17, wherein the processors are further configured to: receive, from a user, an identification of a parasite in the digital microscope image; and
based on the identification, estimate a parasite count for the sample by performing template matching on the acquired digital microscope image using the identified parasite in the digital microscope image as a template image (30) for the template matching.
19. The system of claim 18, wherein the processors are further configured to: perform the template matching as a background process; and
display a next digital microscope image acquired by the digital microscope (4).
20. The system of any one of claims 17-19, wherein the digital microscope (4) comprises one of:
a scanning optical microscope including a manual sample slide translation mechanism;
a scanning optical microscope including an automatic slide translation mechanism; and
an optical microscope having a field-of-view encompassing the area of the acquired digital image.
21. The system of any one of claims 17-20, wherein the digital microscope (4) comprises a plurality of digital microscopes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562139019P | 2015-03-27 | 2015-03-27 | |
| US62/139,019 | 2015-03-27 |
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| WO2016157010A1 true WO2016157010A1 (en) | 2016-10-06 |
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| Application Number | Title | Priority Date | Filing Date |
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| PCT/IB2016/051468 Ceased WO2016157010A1 (en) | 2015-03-27 | 2016-03-16 | Digital parasitology |
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| WO (1) | WO2016157010A1 (en) |
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2016
- 2016-03-16 WO PCT/IB2016/051468 patent/WO2016157010A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| HALIM S ET AL: "Estimating Malaria Parasitaemia from Blood Smear Images", CONTROL, AUTOMATION, ROBOTICS AND VISION, 2006. ICARCV '06. 9TH INTERN ATIONAL CONFERENCE ON, IEEE, PI, 5 December 2006 (2006-12-05), pages 1 - 6, XP031334099, ISBN: 978-1-4244-0341-7 * |
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