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The use of digital images in pathology.

Digital images are routinely used by the publishing industry, but most diagnostic pathologists are unfamiliar with the technology and its possibilities. This review aims to explain the basic principles of digital image acquisition, storage, manipulation and use, and the possibilities provided not only in research, but also in teaching and in routine diagnostic pathology. Images of natural objects are usually expressed digitally as 'bitmaps'--rectilinear arrays of small dots. The size of each dot can vary, but so can its information content in terms, for example, of colour, greyscale or opacity. Various file formats and compression algorithms are available. Video cameras connected to microscopes are familiar to most pathologists; video images can be converted directly to a digital form by a suitably equipped computer. Digital cameras and scanners are alternative acquisition tools of relevance to pathologists. Once acquired, a digital image can easily be subjected to the digital equivalent of any conventional darkroom manipulation and modern software allows much more flexibility, to such an extent that a new tool for scientific fraud has been created. For research, image enhancement and analysis is an increasingly powerful and affordable tool. Morphometric measurements are, after many predictions, at last beginning to be part of the toolkit of the diagnostic pathologist. In teaching, the potential to create dramatic yet informative presentations is demonstrated daily by the publishing industry; such methods are readily applicable to the classroom. The combination of digital images and the Internet raises many possibilities; for example, instead of seeking one expert diagnostic opinion, one could simultaneously seek the opinion of many, all around the globe. It is inevitable that in the coming years the use of digital images will spread from the laboratory to the medical curriculum and to the whole of diagnostic pathology.

Humans↗

Image processing in forensic pathology.

Image processing applications in forensic pathology are becoming increasingly important. This article introduces basic concepts in image processing as applied to problems in forensic pathology in a non-mathematical context. Discussions of contrast enhancement, digital encoding, compression, deblurring, and other topics are presented.

Forensic Medicine↗

Image cytometric analysis in pathology.

Image cytometry (ICM) is used in surgical pathology to quantify nuclear DNA content, nuclear and cytoplasmic immunostain. DNA aneuploidy is shown to be an independent negative prognostic factor in malignant melanoma, small cell carcinoma of the lung, esophageal, ovarian, endometrial, prostatic, urinary bladder, and papillary thyroid carcinoma. On bladder washings, DNA ploidy by ICM is used as an aid in diagnosis and management of recurrent transitional cell carcinoma of the bladder. Quantitation of nuclear immunostain for proliferation markers by ICM has clinical significance in prognosis and management of solid tumors of bladder, breast and ovary, astrocytoma, lymphoma, and malignant melanoma. Angiogenesis, measured by microvessel density is a predictor of prognosis in breast carcinoma and an independent predictor of metastasis for breast carcinoma, malignant melanoma, non-small cell lung carcinoma, and prostate carcinoma. Quantitated by ICM, angiogenesis is predictive of the presence or subsequent development of regional lymph node metastases in head and neck squamous carcinomas. Future prospects for ICM in pathology include the standardization of ICM techniques; extended clinical use of DNA ploidy for diagnosis, prognosis and as a help with therapeutic decisions; development of neural networks and quantification of fluorescence in situ hybridization to distinguish benign from malignant lesions of low malignant potential, and three-dimensional reconstruction of morphology from two-dimensional sections measured for prognostic parameters.

DNA, Neoplasm↗

Imaging procedures in adrenal pathology.

Imaging plays a vital role in the evaluation of adrenal pathology. The most widely used modalities are computed tomography and magnetic resonance imaging. Alone or in conjunction with appropriate clinical and biochemical data, imaging can provide specific diagnoses that preclude the need for tissue sampling. This article reviews imaging features of normal and diseased adrenals, from both benign and malignant causes.

Adrenal Gland Diseases↗

Analyzing the eye movement of dentists during their reading of CT images.

In order to evaluate the eye movements of dentists when they were interpreting radiographs, ten normal computed tomography (CT) images and ten images with pathologic lesions were shown to eight dentists, and the pattern of their eye movement was qualitatively analyzed. Six fixation point parameters were calculated, including the time required to discriminate between normal and pathologic images (X(1)), the total fixation point count (X(2)), the total travel distance between fixation points (X(3)), the average time spent on each fixation point (X(4)), the total gaze fixation time (X(5)), and the maximum gaze fixation time spent on each image (X(6)). When the subjects were interpreting pathologic images, X(2) and X(4) were shorter; however, when they were viewing normal images, time was spent on observing multiple fixation points before the completion of the interpretive process. While pathologic images were recognized through top-down processing, there was a tendency for normal images to be recognized through bottom-up processing. The results of discriminant analysis, using a linear discriminant function, indicated that the independent variables X(2) and X(4) and the dependent variable X(5) were the only variables that contributed significantly to differentiating between normal and pathologic images. The linear discriminant function was Z = 9.0 x 10(-2) x X(2) + 3.0 x X(4) - 2.1 (discriminant score: Z < 0, pathologic image; Z > or = 0, normal image). When the mean value of each individual's gaze fixation data was substituted into the discriminant formula, the hit rate for normal and pathologic images was discriminated at 94% (15 of 16).

Journal Article↗

A pathologist-designed imaging system for anatomic pathology signout, teaching, and research.

Pathology images are derived from gross surgical specimens, light microscopy, immunofluorescence, electron microscopy, molecular diagnostic gels, flow cytometry, image analysis data, and clinical laboratory data in graphic form. We have implemented a network of desktop personal computers (PCs) that allow us to easily capture, store, and retrieve gross and microscopic, anatomic, and research pathology images. System architecture involves multiple image acquisition and retrieval sites and a central file server for storage. The digitized images are conveyed via a local area network to and from image capture or display stations. Acquisition sites consist of a high-resolution camera connected to a frame grabber card in a 486-type personal computer, equipped with 16 MB (Table 1) RAM, a 1.05-gigabyte hard drive, and a 32-bit ethernet card for access to our anatomic pathology reporting system. We have designed a push-button workstation for acquiring and indexing images that does not significantly interfere with surgical pathology sign-out. Advantages of the system include the following: (1) Improving patient care: the availability of gross images at time of microscopic sign-out, verification of recurrence of malignancy from archived images, monitoring of bone marrow engraftment and immunosuppressive intervention after bone marrow/solid organ transplantation on repeat biopsies, and ability to seek instantaneous consultation with any pathologist on the network; (2) enhancing the teaching environment: building a digital surgical pathology atlas, improving the availability of images for conference support, and sharing cases across the network; (3) enhancing research: case study compilation, metastudy analysis, and availability of digitized images for quantitative analysis and permanent/reusable image records for archival study; and (4) other practical and economic considerations: storing case requisition images and hand-drawn diagrams deters the spread of gross room contaminants and results in considerable cost savings in photographic media for conferences, improved quality assurance by porting control stains across the network, and a multiplicity of other advantages that enhance image and information management in pathology.

Computer Systems↗

[A study of the utility of the MR image for the diagnosis of thymic tumors--imaging and pathologic correlation].

MR imaging was performed in 25 patients with thymic tumors (five with non-invasive thymomas, 15 with invasive thymomas, and five with thymic carcinomas), and the MR imaging appearance was compared with the pathological findings. Non-invasive thymomas showed generally oval or round masses with well-defined margins and homogeneous intensity on T1- and T2-weighted images. Invasive thymomas showed a multinodular appearance in 79% (11/15) of cases, and an internodular difference in signal intensity (IDSI) in 64% (7/11) on T2-weighted images. It was considered that the IDSI on T2-weighted images correlated pathologically with the hemorrhagic and/or necrotic areas and hyalinization. The IDSI seemed to be a characteristic finding of invasive thymomas. The histological findings and MR imaging appearance of thymomas were compared. The predominantly epithelial type showed a low incidence of nodular appearance but showed marked IDSI on T2-weighted images. Therefore, it is more likely that the predominantly epithelial type induced more varied intratumoral changes than other types. Extension of thymic carcinomas was similar to that of invasive thymomas on MR imaging, but thymic carcinomas showed no definite nodular appearance. In conclusion, MR images in thymic tumors were useful for not only determining the morphology of the tumor but also the tissue characteristics. Therefore, MR imaging can be a useful modality to correlate with the histological findings and biological behavior of thymic tumors.

Adult↗

[Normal and pathological twin images of the human body].

The author demonstrates examples of symmetrical images in human pathology. He introduces the subject with arguments of the philosophical and cultural areas. He defines asymmetry and dissymmetry. The symmetrical images are linked to different planes (natural, artificial and mixed). With numerous symmetrical pathological images he demonstrates new teleonomical hypotheses: interchangeable, enantiomorphous, turned, rotated images. The concept of symmetry, asymmetry and dissymmetry leads to the concept of symmetrical thinking in clinical imaging.

Anatomy↗

MR imaging and sonography of early prostatic cancer: pathologic and imaging features that influence identification and diagnosis.

OBJECTIVE: The purpose of this study was to correlate findings at MR imaging and transrectal sonography with histopathologic findings after surgery in patients with prostatic cancer, to identify the pathologic characteristics of prostatic cancer that improved detection with MR imaging and transrectal sonography, and to identify the imaging characteristics that correlated with detection of true cancers. MATERIALS AND METHODS: Data from MR imaging in 320 patients and from transrectal sonography in 343 patients who were enrolled in the Radiological Diagnostic Oncology Group multiinstitutional study of imaging in prostatic cancer were correlated with results of radical prostatectomy. Only cancers 5 mm or greater in at least one dimension were evaluated pathologically. The locations of lesions and the linear dimensions and volumes of individual lesions and the prostate gland were evaluated pathologically and with imaging studies. The appearance of lesion margins on images and the degree of differentiation of lesions seen on pathologic examination were also studied. Univariate and multivariate analysis were performed to determine the pathologic findings associated with imaging detection and the imaging characteristics associated with prostatic cancer. RESULTS: MR imaging and transrectal sonography showed 62% and 64% of cancers, respectively, each with a positive predictive value of 68%. Cancers that were larger, moderately or poorly differentiated, or located in the posterior half of the outer gland were easier to detect (p < .0001). The overall size of the prostate did not effect lesion detection. However, abnormalities identified in the posterior half of the outer gland were more likely to be cancers. On transrectal sonograms, larger abnormalities also were more likely to be malignant tumors. The sharpness of the margins of the imaged abnormalities did not predict pathologic status. CONCLUSION: Detection of prostatic cancer with MR imaging or transrectal sonography is affected by cancer size, differentiation, and location; the odds of an imaged lesion's being malignant are related to location and, for transrectal sonography, size. Knowledge of anatomic/pathologic features that enhance lesion detection may help when using imaging tests to detect prostatic carcinoma. That certain imaging characteristics of lesions are associated with true cancers may assist in the interpretation of MR images and transrectal sonograms of the prostate.

Algorithms↗

Quantitative DNA analysis of fresh solid tumors by flow and image cytometric methods: a comparison using the Roche Pathology Workstation Image Analyzer.

The clinical utility of DNA ploidy and cell cycle parameters as prognostic indicators has been demonstrated for selected malignant tumors. Previous quantitative DNA analysis studies have used various tumor sample preparation methods and analyzers. We undertook a pilot study to compare the results of DNA analysis of fresh solid tumors by flow cytometry with the new Roche Pathology Workstation Image Analyzer. Flow cytometric DNA analysis was done on cell suspensions of fine needle aspirates from fresh tumor specimens and analyzed for ploidy and cell cycle statistics with a Becton-Dickinson FACScan Analyzer, using a rectangular model. Small aliquots from these same aspirates were prepared as direct cytologic smears and Feulgen stained for DNA analysis with the Roche Image Analyzer. Additional smears were stained with Diff-Quik for morphologic correlation with DNA histograms. The study group consisted of 40 malignant neoplasms. There was a high correlation between the flow and image DNA indices (R = 0.93, slope = 1.0036, P < 0.001) but a weaker relationship between the flow and image estimated S-phase fractions (R = 0.57, slope = 0.5401, P < 0.01). DNA ploidy categorization for the two methods was concordant in 30 (75%) cases, discordant in seven (17.5%) cases, and equivocal in three (7.5%) cases. In our experience, quantitative DNA analysis of fresh tumor aspirates by flow and image cytometric methods yielded comparable and/or complementary results, with each method having certain advantages and disadvantages. Proposed reasons for false and true discordances and an approach for evaluation are discussed.

Biopsy, Needle↗

Digital imaging in pathology: the case for standardization.

The process of digital imaging in microscopy is a series of operations, each contributing to the quality of the final image that is displayed on the computer monitor. The operations include sample preparation and staining by histology, optical image formation by the microscope, digital image sampling by the camera sensor, postprocessing and compression, transmission across the network and display on the monitor. There is an extensive literature about digital imaging and each step of the process is fairly well understood. However, the complete process is very hard to standardize or even to understand fully. The important concepts for pathology imaging standards are: (1) systems should be able to share image files, (2) the standards should allow the transmission of information on baseline colours and recommended display parameters, (3) the images should be useful to the pathologist, not necessarily better or worse than direct examination of a slide under the microscope, (4) a mechanism to evaluate image quality objectively should be present, (5) a mechanism to adjust and correct the minor errors of tissue processing should be developed, (6) a public organization should support pathologists in the development of standards.

Image Interpretation, Computer-Assisted↗

Storage and distribution of pathology digital images using integrated web-based viewing systems.

CONTEXT: Health care providers have expressed increasing interest in incorporating digital images of gross pathology specimens and photomicrographs in routine pathology reports. OBJECTIVE: To describe the multiple technical and logistical challenges involved in the integration of the various components needed for the development of a system for integrated Web-based viewing, storage, and distribution of digital images in a large health system. DESIGN: An Oracle version 8.1.6 database was developed to store, index, and deploy pathology digital photographs via our Intranet. The database allows for retrieval of images by patient demographics or by SNOMED code information. SETTING: The Intranet of a large health system accessible from multiple computers located within the medical center and at distant private physician offices. RESULTS: The images can be viewed using any of the workstations of the health system that have authorized access to our Intranet, using a standard browser or a browser configured with an external viewer or inexpensive plug-in software, such as Prizm 2.0. The images can be printed on paper or transferred to film using a digital film recorder. Digital images can also be displayed at pathology conferences by using wireless local area network (LAN) and secure remote technologies. CONCLUSIONS: The standardization of technologies and the adoption of a Web interface for all our computer systems allows us to distribute digital images from a pathology database to a potentially large group of users distributed in multiple locations throughout a large medical center.

Computer Storage Devices↗

Primary malignant rhabdoid tumor of the brain: clinical, imaging, and pathologic findings.

PURPOSE: To describe the imaging and pathologic findings of malignant rhabdoid tumor (MRT), a rare primary brain neoplasm affecting children. METHODS: The CT and/or MR features, pathologic findings, and clinical records of three children with primary MRT of the brain were retrospectively reviewed. RESULTS: The tumors, large, left-sided cerebral masses, were intraventricular in two cases. MR images in one patient showed T1- and T2-weighted signal intensity isointense with gray matter. Multiple necrotic/cystic foci were present in all cases, with two showing a patchy pattern of enhancement on CT and MR. The diagnosis of MRT was documented by ultrastructural and immunohistochemical studies. All patients had normal abdominal CT scans, excluding the possibility of primary renal rhabdoid tumor metastatic to the brain. The disease progressed rapidly in each case, despite surgery, chemotherapy, and craniospinal irradiation, with serial imaging evidence of tumor regrowth at the primary site and the development of metastatic satellite lesions. CONCLUSIONS: The diagnosis of primary MRT of the brain can be made only pathologically; however, the nonspecific imaging findings in these cases suggest that MRT should be considered in the differential diagnosis of large childhood intracranial neoplasms.

Adult↗

Minority report - false negative breast assessment in women recalled for suspicious screening mammography: imaging and pathological features, and associated delay in diagnosis.

AIM: We studied imaging, pathology and diagnostic aspects of false negative assessment (FNA) in women recalled for suspicious screening mammography. METHOD: Subjects were women aged 50-69 years undergoing biennial screening mammography within the Florence District screening programme from January 1992-December 2001 (339,953 consecutive screens). We identified all cancers occurring in women recalled to assessment and ascertained, and reviewed, all cases considered as negative on assessment and subsequently diagnosed with breast cancer. We compared imaging features, tumour histology and stage, and diagnostic testing on assessment for all women with cancer, and presentation and length of delay in women falsely negative on assessment. RESULTS: Eleven thousand six hundred and twenty four women were recalled to diagnostic assessment (recall rate = 3.4%) predominantly for suspicious mammography (9,216 positive screens). Breast cancer was missed in 57 cases: a FNA rate of 0.50% (0.37-0.62%) and comprising 4.1% (3.0-5.1%) of cancers occurring in women recalled after a positive screen. Two types of abnormalities were significantly more frequent in FNA cases than cancers detected at assessment: mass with regular borders (21.1 vs. 5.6%, p = 10(-5)), and asymmetrical density (22.8 vs. 5.4%, p = 10(-5)). On review 56% of FNAs were benign or probably benign BI-RADS categories. FNA occurred in 1.4% of early recalls and in 0.4% of initial assessment (p=0.0001). Significantly fewer tests were performed when assessing missed cancers than detected cancers with the most significant difference noted for FNAC (29.8 vs. 96.0%, p=10(-6)); mammography as the only evaluation on assessment was more frequent in missed cancers (31.5% vs 0.2%, p = 10(-6)). The 57 missed cases were subsequently diagnosed at early recall (2 cases), next biennial screen (11 cases), or as interval breast cancers (44 cases) with a mean delay in diagnosis of 628 days. Tumour histology, size and nodal status did not significantly differ between cancers missed and cancers diagnosed on assessment. CONCLUSION: False negatives on assessment represent a minority group in whom screening has failed. They might be reduced by adopting a more intensive diagnostic approach to assessment. Although there was no evidence of a worse prognosis in cancers missed at assessment, the delay in diagnosis is substantial and may impact long-term outcomes.

Aged↗

Signal analysis and compression performance evaluation of pathological microscopic images.

Digitizing high-quality microscopic images and developing input/output technology for displaying those results is critical to telepathology in which pathological microscopic images are transferred to remote locations where they are diagnosed by specialists. This paper will discuss the results achieved by directly digitizing (nonfilm process) pathological microscopic images at a 2k x 2k resolution, and then using a super-high-definition imaging system to analyze their signals and evaluate compression performance. We will start off by digitizing samples that a pathologist will actually use in making a diagnosis, and then analyze their color distribution and spatial frequencies characteristics by comparing them to general images. This will make it apparent that such pathological images characteristically contain high spatial frequency in their chrominance components. We will also discuss the evaluation results of color differences for L*a*b* space and compression ratios achieved when using JPEG to encode pathological images. We will also present a subjective evaluation of the influence subsampling of chrominance components has on image quality.

Computer Systems↗

Acute encephalopathy with bilateral thalamotegmental involvement in infants and children: imaging and pathology findings.

PURPOSE: To investigate the imaging and pathologic characteristics of acute encephalopathy with bilateral thalamotegmental involvement in infants and children. METHODS: Five Japanese children ranging in age from 11 to 29 months were studied. We performed CT imaging in all patients, 10 MR examinations in four patients, and an autopsy in one patient. RESULTS: The encephalopathy affected the thalami, brain stem tegmenta, and cerebral and cerebellar white matter. The brain of the autopsied case showed fresh necrosis and brain edema without inflammatory cell infiltration. Petechiae and congestion were demonstrated mainly in the thalamus. CT and MR images showed symmetric focal lesions in the same areas in the early phase. These lesions became more demarcated and smaller in the intermediate phase. The ventricles and cortical sulci enlarged. MR images demonstrated T1 shortening in the thalami. The prognosis was generally poor; one patient died, three patients were left with severe sequelae, and only one patient improved. CONCLUSIONS: The encephalopathy might be a postviral or postinfectious brain disorder. T1 shortening in the thalami indicated the presence of petechiae.

Acute Disease↗

Imaging the pathology of Alzheimer's disease: amyloid-imaging with positron emission tomography.

The steep rise in the incidence of Alzheimer's disease (AD) has further added to the considerable public health burden caused by aging of the United States population. Among the most characteristic pathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles. The capability to use positron emission tomography and selective markers for amyloid protein deposition promises to substantially alter the way we diagnosis and manage patients who have AD.

Alzheimer Disease↗