An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study

The University of Arizona, Tucson, Arizona, United States
Human Pathlogy (Impact Factor: 2.77). 12/2004; 35(11):1303-14. DOI: 10.1016/j.humpath.2004.09.002
Source: PubMed


This paper describes the design and fabrication of a novel array microscope for the first ultrarapid virtual slide processor (DMetrix DX-40 digital slide scanner). The array microscope optics consists of a stack of three 80-element 10 x 8-lenslet arrays, constituting a "lenslet array ensemble." The lenslet array ensemble is positioned over a glass slide. Uniquely shaped lenses in each of the lenslet arrays, arranged perpendicular to the glass slide constitute a single "miniaturized microscope." A high-pixel-density image sensor is attached to the top of the lenslet array ensemble. In operation, the lenslet array ensemble is transported by a motorized mechanism relative to the long axis of a glass slide. Each of the 80 miniaturized microscopes has a lateral field of view of 250 microns. The microscopes of each row of the array are offset from the microscopes in other rows. Scanning a glass slide with the array microscope produces seamless two-dimensional image data of the entire slide, that is, a virtual slide. The optical system has a numerical aperture of N.A.= 0.65, scans slides at a rate of 3 mm per second, and accrues up to 3,000 images per second from each of the 80 miniaturized microscopes. In the ultrarapid virtual slide processing cycle, the time for image acquisition takes 58 seconds for a 2.25 cm2 tissue section. An automatic slide loader enables the scanner to process up to 40 slides per hour without operator intervention. Slide scanning and image processing are done concurrently so that post-scan processing is eliminated. A virtual slide can be viewed over the Internet immediately after the scanning is complete. A validation study compared the diagnostic accuracy of pathologist case readers using array microscopy (with images viewed as virtual slides) and conventional light microscopy. Four senior pathologists diagnosed 30 breast surgical pathology cases each using both imaging modes, but on separate occasions. Of 120 case reads by array microscopy, there were 3 incorrect diagnoses, all of which were made on difficult cases with equivocal diagnoses by light microscopy. There was a strong correlation between array microscopy vs. "truth" diagnoses based on surgical pathology reports. The kappa statistic for the array microscopy vs. truth was 0.96, which is highly significant (z=10.33, p <0.001). There was no statistically significant difference between rates of agreement with truth between array microscopy and light microscopy (z=0.134, p >0.05). Array microscopy and light microscopy did not differ significantly with respect to the number/percent of correct decisions rendered (t=0.552, p=0.6376) or equivocal decisions rendered (t=2.449, p=0.0917). Pathologists rated 95.8% of array microscopy virtual slide images as good or excellent. None were rated as poor. The mean viewing time for a DMetrix virtual slide was 1.16 minutes. The DMetrix virtual slide processor has been found to reduce the virtual slide processing cycle more than 10 fold, as compared with other virtual slide systems reported to date. The virtual slide images are of high quality and suitable for diagnostic pathology, second opinions, expert opinions, clinical trials, education, and research.

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    • "The application of telediagnosis in the field of pathology is relatively advanced, and significant contributions to the development of telepathology have been made by Weinstein et al. in the USA beginning in the early 1980s [23-25], Kaiser et al. in Europe [26,27], and by Sawai et al. in Japan from the early 1990s [28]. Along with the shift from static to robotic images and from analog to digital lines, recent developments in IT led to the emergence of the worldwide use of VS, especially in the fields of diagnosis and education [29,30], followed by diagnostic developments such as automated diagnosis of histological screening via the Internet [31]. "
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    ABSTRACT: BackgroundAn online consultation system using virtual slides (whole slide images; WSI) has been developed for pathological diagnosis, and could help compensate for the shortage of pathologists, especially in the field of dermatopathology and in other fields dealing with difficult cases. This study focused on the performance and future potential of the system.MethodIn our system, histological specimens on slide glasses are digitalized by a virtual slide instrument, converted into web data, and up-loaded to an open server. Using our own purpose-built online system, we then input patient details such as age, gender, affected region, clinical data, past history and other related items. We next select up to ten consultants. Finally we send an e-mail to all consultants simultaneously through a single command. The consultant receives an e-mail containing an ID and password which is used to access the open server and inspect the images and other data associated with the case. The consultant makes a diagnosis, which is sent to us along with comments.Because this was a pilot study, we also conducted several questionnaires with consultants concerning the quality of images, operability, usability, and other issues.ResultsWe solicited consultations for 36 cases, including cases of tumor, and involving one to eight consultants in the field of dermatopathology. No problems were noted concerning the images or the functioning of the system on the sender or receiver sides. The quickest diagnosis was received only 18 minutes after sending our data. This is much faster than in conventional consultation using glass slides. There were no major problems relating to the diagnosis, although there were some minor differences of opinion between consultants. The results of questionnaires answered by many consultants confirmed the usability of this system for pathological consultation. (16 out of 23 consultants.)ConclusionWe have developed a novel teledermatopathological consultation system using virtual slides, and investigated the usefulness of the system. The results demonstrate that our system can be a useful tool for international medical work, and we anticipate its wider application in the future.Virtual slidesThe virtual slides for this article can be found here:
    Diagnostic Pathology 12/2012; 7(1):177. DOI:10.1186/1746-1596-7-177 · 2.60 Impact Factor
    • "Some scanners create even larger images[9] (especially emerging scanners with z-axis capabilities[3] that create a series of images) and there is concern in the DICOM (Digital Imaging and Communications in Medicine) Pathology Working Group (WG-26) that DICOM cannot handle images larger than 64,000 pixels and 2 GB total size.[10] Compression is one way to deal with this massive amount of data, but it is difficult to define a single acceptable level of compression (hence image quality) for use across all clinical questions.[811] "
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    ABSTRACT: We aim to determine to what degree whole-slide images (WSI) can be compressed without impacting the ability of the pathologist to distinguish benign from malignant tissues. An underlying goal is to demonstrate the utility of a visual discrimination model (VDM) for predicting observer performance. A total of 100 regions of interest (ROIs) from a breast biopsy whole-slide images at five levels of JPEG 2000 compression (8:1, 16:1, 32:1, 64:1, and 128:1) plus the uncompressed version were shown to six pathologists to determine benign versus malignant status. There was a significant decrease in performance as a function of compression ratio (F = 14.58, P < 0.0001). The visibility of compression artifacts in the test images was predicted using a VDM. Just-noticeable difference (JND) metrics were computed for each image, including the mean, median, ≥90th percentiles, and maximum values. For comparison, PSNR (peak signal-to-noise ratio) and Structural Similarity (SSIM) were also computed. Image distortion metrics were computed as a function of compression ratio and averaged across test images. All of the JND metrics were found to be highly correlated and differed primarily in magnitude. Both PSNR and SSIM decreased with bit rate, correctly reflecting a loss of image fidelity with increasing compression. Observer performance as measured by the Receiver Operating Characteristic area under the curve (ROC Az) was nearly constant up to a compression ratio of 32:1, then decreased significantly for 64:1 and 128:1 compression levels. The initial decline in Az occurred around a mean JND of 3, Minkowski JND of 4, and 99th percentile JND of 6.5. Whole-slide images may be compressible to relatively high levels before impacting WSI interpretation performance. The VDM metrics correlated well with artifact conspicuity and human performance.
    04/2012; 3:17. DOI:10.4103/2153-3539.95129
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    • "In addition to robotic and gripping systems these setup always include at least one microscope based imaging system whose images enable either the tracking and recognition of objects or the control of the systems. (Weinstein et al., 2004), (Potsaid et al., 2005) and (Bert et al., 2006) use an image mosaicing NVS to create virtual views that can be used in the manipulation of MEMS or bioMEMS parts. Several high resolution local images of the work scene are dynamically stitched to give a mosaic image representing a global view of the scene. "
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    ABSTRACT: The paper deals with the problem of imaging at the microscale. The trifocal transfer based novel view synthesis approach is developed and applied to the images from two photon microscopes mounted in a stereoscopic configuration and observing vertically the work scene. The final result is a lateral virtual microscope working up to 6 frames per second with a resolution up to that of the real microscopes. Visual feedback, accurate measurements and control have been performed with, showing it ability to be used for robotic manipulation of MEMS parts. Keywords: Novel view synthesis, trifocal tensor, photon microscope, microassembly, micromanipulation, MEMS.
    International Journal of Optomechatronics 11/2010; 4(4). DOI:10.1080/15599612.2010.522759 · 0.48 Impact Factor
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