Development of a Whole Slide Imaging System on Smartphones and Evaluation With Frozen Section Samples

Abstract

BackgroundThe aim was to develop scalable Whole Slide Imaging (sWSI), a WSI system based on mainstream smartphones coupled with regular optical microscopes. This ultra-low-cost solution should offer diagnostic-ready imaging quality on par with standalone scanners, supporting both oil and dry objective lenses of different magnifications, and reasonably high throughput. These performance metrics should be evaluated by expert pathologists and match those of high-end scanners.ObjectiveThe aim was to develop scalable Whole Slide Imaging (sWSI), a whole slide imaging system based on smartphones coupled with optical microscopes. This ultra-low-cost solution should offer diagnostic-ready imaging quality on par with standalone scanners, supporting both oil and dry object lens of different magnification. All performance metrics should be evaluated by expert pathologists and match those of high-end scanners.MethodsIn the sWSI design, the digitization process is split asynchronously between light-weight clients on smartphones and powerful cloud servers. The client apps automatically capture FoVs at up to 12-megapixel resolution and process them in real-time to track the operation of users, then give instant feedback of guidance. The servers first restitch each pair of FoVs, then automatically correct the unknown nonlinear distortion introduced by the lens of the smartphone on the fly, based on pair-wise stitching, before finally combining all FoVs into one gigapixel VS for each scan. These VSs can be viewed using Internet browsers anywhere. In the evaluation experiment, 100 frozen section slides from patients randomly selected among in-patients of the participating hospital were scanned by both a high-end Leica scanner and sWSI. All VSs were examined by senior pathologists whose diagnoses were compared against those made using optical microscopy as ground truth to evaluate the image quality.ResultsThe sWSI system is developed for both Android and iPhone smartphones and is currently being offered to the public. The image quality is reliable and throughput is approximately 1 FoV per second, yielding a 15-by-15 mm slide under 20X object lens in approximately 30-35 minutes, with little training required for the operator. The expected cost for setup is approximately US $100 and scanning each slide costs between US $1 and $10, making sWSI highly cost-effective for infrequent or low-throughput usage. In the clinical evaluation of sample-wise diagnostic reliability, average accuracy scores achieved by sWSI-scan-based diagnoses were as follows: 0.78 for breast, 0.88 for uterine corpus, 0.68 for thyroid, and 0.50 for lung samples. The respective low-sensitivity rates were 0.05, 0.05, 0.13, and 0.25 while the respective low-specificity rates were 0.18, 0.08, 0.20, and 0.25. The participating pathologists agreed that the overall quality of sWSI was generally on par with that produced by high-end scanners, and did not affect diagnosis in most cases. Pathologists confirmed that sWSI is reliable enough for standard diagnoses of most tissue...

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“…Utilization of free web-based teleconferencing software such as Skype, Google Hangouts, GoToMeetings, Windows Live Messenger, Fuze, and Webex, can provide a low-cost alternative to commercial live view microscopy systems [ 60 , 74 , 75 , 76 ]. Yu et al described the newly realized capacity of smartphones to power whole-slide imaging systems via software which splits the image digitalization process between smartphone applications and remote cloud servers [ 77 ]. An android or iOS smartphone mounted on the eyepiece of a standard optical microscope has the ability to scan whole-slide images into a virtual slide with a resulting image quality comparable to high end commercial slide-scanning systems [ 77 , 78 ].…”

“…Yu et al described the newly realized capacity of smartphones to power whole-slide imaging systems via software which splits the image digitalization process between smartphone applications and remote cloud servers [ 77 ]. An android or iOS smartphone mounted on the eyepiece of a standard optical microscope has the ability to scan whole-slide images into a virtual slide with a resulting image quality comparable to high end commercial slide-scanning systems [ 77 , 78 ]. This innovative smartphone technology offers the potential to bring slide scanning technology to more widespread settings in LMICs.…”

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“…Ideally, utilizing tools that have been previously available to pathologists would reduce the cost of accessing WSI to its lowest and not require much operational training. Previously, we reported the development and clinical evaluation with frozen section samples of one such solution named scalable whole slide imaging (sWSI), a WSI system on smartphones [ 15 ]. With a mainstream smartphone mounted on the eyepiece of any optical microscope, a pathologist can scan the whole slide into a virtual copy by simply operating the microscope following this normal examination procedure.…”