Improving Ki67 assessment concordance by the use of an artificial intelligence-empowered microscope: a multi-institutional ring study.

AIMS: The nuclear proliferation biomarker Ki67 plays potential prognostic and predictive roles in breast cancer treatment. However, the lack of interpathologist consistency in Ki67 assessment limits the clinical use of Ki67. The aim of this article was to report a solution utilising an artificial intelligence (AI)-empowered microscope to improve Ki67 scoring concordance. METHODS AND RESULTS: We developed an AI-empowered microscope in which the conventional microscope was equipped with AI algorithms, and AI results were provided to pathologists in real time through augmented reality. We recruited 30 pathologists with various experience levels from five institutes to assess the Ki67 labelling index on 100 Ki67-stained slides from invasive breast cancer patients. In the first round, pathologists conducted visual assessment on a conventional microscope; in the second round, they were assisted with reference cards; and in the third round, they were assisted with an AI-empowered microscope. Experienced pathologists had better reproducibility and accuracy [intraclass correlation coefficient (ICC) = 0.864, mean error = 8.25%] than inexperienced pathologists (ICC = 0.807, mean error = 11.0%) in visual assessment. Moreover, with reference cards, inexperienced pathologists (ICC = 0.836, mean error = 10.7%) and experienced pathologists (ICC = 0.875, mean error = 7.56%) improved their reproducibility and accuracy. Finally, both experienced pathologists (ICC = 0.937, mean error = 4.36%) and inexperienced pathologists (ICC = 0.923, mean error = 4.71%) improved the reproducibility and accuracy significantly with the AI-empowered microscope. CONCLUSION: The AI-empowered microscope allows seamless integration of the AI solution into the clinical workflow, and helps pathologists to obtain higher consistency and accuracy for Ki67 assessment.

Validation of Whole-Slide Imaging for Histolopathogical Diagnosis: Current State.

Rapid advances in informatics and technological improvements have led to the development of high-throughput whole-slide imaging (WSI) scanners able to produce high-quality digital images, which allow achieving a correct diagnosis of the biopsies using virtual viewers. This technology is currently prepared to be introduced in the departments of pathology for routine diagnosis. The aim of this review is to analyze the current evidence regarding the use of WSI in primary or routine diagnosis in the different subspecialties of pathology. An increasing number of studies have shown almost perfect inter- and intraobserver agreement between the diagnoses obtained with WSI and the classical diagnoses based on conventional light microscopy. The only exception seems to be cytology, which still requires some technological development. Although validation studies are needed in some areas of pathology, growing evidence indicates that WSI is a reliable tool for routine diagnosis. Pathologists have a positive perception of the ergonomics of the workstations, the low magnification of WSI and the possibility of making annotations and measurements. WSI can be used from any device and anywhere, thereby providing great opportunities for teleconsultation. New technologies such as the recognition of histopathology patterns using image analysis may facilitate diagnosis and improve the reproducibility among pathologists in the future.

Wide-field computational imaging of pathology slides using lens-free on-chip microscopy.

Optical examination of microscale features in pathology slides is one of the gold standards to diagnose disease. However, the use of conventional light microscopes is partially limited owing to their relatively high cost, bulkiness of lens-based optics, small field of view (FOV), and requirements for lateral scanning and three-dimensional (3D) focus adjustment. We illustrate the performance of a computational lens-free, holographic on-chip microscope that uses the transport-of-intensity equation, multi-height iterative phase retrieval, and rotational field transformations to perform wide-FOV imaging of pathology samples with comparable image quality to a traditional transmission lens-based microscope. The holographically reconstructed image can be digitally focused at any depth within the object FOV (after image capture) without the need for mechanical focus adjustment and is also digitally corrected for artifacts arising from uncontrolled tilting and height variations between the sample and sensor planes. Using this lens-free on-chip microscope, we successfully imaged invasive carcinoma cells within human breast sections, Papanicolaou smears revealing a high-grade squamous intraepithelial lesion, and sickle cell anemia blood smears over a FOV of 20.5 mm(2). The resulting wide-field lens-free images had sufficient image resolution and contrast for clinical evaluation, as demonstrated by a pathologist's blinded diagnosis of breast cancer tissue samples, achieving an overall accuracy of ~99%. By providing high-resolution images of large-area pathology samples with 3D digital focus adjustment, lens-free on-chip microscopy can be useful in resource-limited and point-of-care settings.

[Rational choice of technologies and equipment in the logistic support of a pathomorphology laboratory].

The purpose of the present communication is to provide specialists with the comparative characteristics of the most important user qualities of the major histological labware by the world's leading manufacturers introduced on the market. These are comparatively estimated solely from technologically significant criteria on the basis of the materials of open references, general public technical documents, and the authors' experience. Fabric processors, embedding complexes, microtomes, autostainers, and coverslippers are comparatively characterized from the viewpoint of a practical user. The presented materials may be useful to specialties to take decisions on logistics and re-equipment of morphological laboratories.

Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.

BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device. METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups. RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC. CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.

Digital pathology in drug discovery and development: multisite integration.

Digital pathology is an emerging technology that provides an image-based environment for managing and interpreting the information generated from a digitized glass slide, offering substantial improvements in pharmaceutical drug development across discovery, preclinical GLP pathology and oncology clinical trials. Digital pathology is transforming global pharmaceutical research by enabling data sharing to integrate dispersed pharma pathology labs around the world. This article reviews the stages of multisite digital pathology integration in large pharmaceutical companies, offering suggestions for success and highlighting challenges.

The design of a health technology assessment system in telepathology.

Up to a few years ago, the management of the information on the slides (virtual slides) in telepathology applications was principally based on the design and construction of a few identical and expensive platforms with microscope units and software tools for the display and for electronic control (zooming, moving, and cutting of images). The development of information technology tools allows the diffusion of new visualization strategies and the availability of low cost or free visualization proprietary tools. New competitive systems such as client-server architectures are available in telepathology today. The investigation of the new technologies for telepathology is a basic and core aspect in telemedicine technology assessment. A new interactive environment to investigate the health technology assessment of a telepathology system has been studied. In particular, in consideration of previous experience the methodology focused both on the senior pathologist and younger student pathologist. Two interactive forms were created by a working group: a feedback form and a diagnostic form. The first was designed to investigate the technology characteristics and acceptance of the telepathology systems. The second tool was designed to investigate the diagnostic accuracy on a significant sample of virtual slides by two different groups of pathologists (senior and younger students). The acceptance of the methodology was very high.

[Budget management in anatomical pathology: health technology assessment of new methodologies]. / Budget in anatomia patologica: il controllo di gestione per la valutazione di nuova tecnologia.

The author's experience in heath technology assessment of new methodologies for routine diagnosis at the Department of Anatomical Pathology at the Trento Hospital is presented. The workload of the department together with the annual budget trends (from 2000 to 2006) of the various costs is analysed. Budget analysis also allows evaluation of expenses relative to the introduction of new tests, which are increasingly requested in order to personalise therapy accordingly to the biological profile of individual patients. Health Technology Assessment permits in-depth analysis of the efficacy, safety, costs, benefits and feasibility in addition to providing a measurement of the contribution to improving the quality of work and life. This is an important tool in decision-making processes for pathologists, especially in consideration of the limited resources available in healthcare.

Evaluation of a centrifuge method and thin-layer preparation in urine cytology.

OBJECTIVE: To evaluate and compare the quality and cost of urine cytology using the Cytospin method (Shandon, ThermoElectron Corporation, Waltham, Massachusetts, U.S.A.) and the AutoCyte PREP (TriPath Imaging, Burlington, North Carolina, U.S.A.) in a general laboratory. STUDY DESIGN: A study of differences between the Cytospin method and AutoCyte PREP in the areas of specimen preparation, staining, number and quality of diagnostic cells, background, screener preference, and cost was undertaken over a 3-month period in 2000. Sixty fresh voided urine samples from 25 patients with known transitional cell carcinoma were prepared by the Cytospin method and the AutoCyte PREP according to the manufacturers' instructions. RESULTS: The Cytospin method had longer preparation time but shorter screening time than the AutoCyte PREP. The number of diagnostic cells was higher in the Cytospin method. Fixation quality and staining clarity were better in the Cytospin method. Qualitative assessment of cell arrangements, cell and nuclear size and shape, nuclear/cytoplasmic ratio and nuclear membrane irregularity showed no significant differences between the 2 methods. Cellular details and nuclear chromatin patterns were clearer and better preserved in the Cytospin method, but the AutoCyte PREP showed less blood and inflammatory cells and debris. CONCLUSION: In the majority of cases the screeners preferred the Cytospin method due to its better overall cytologic quality. However, the amount of blood, inflammation and debris was much lower in the AutoCyte PREP. This reduced the need to make a second, diluted specimen and made turnaround time faster. The AutoCyte PREP was 7 times more expensive than the Cytospin method.

Application of virtual microscopy in clinical cytopathology.

Virtual microscopy (VM) refers to the use of an automated microscope and digital imaging technology to scan, store, and view glass slides. VM systems allow the user to view a scanned image of the entire slide at multiple magnifications on a computer screen. We tested VM to evaluate its possible utility in diagnostic cytopathology. Ten cervical-vaginal monolayered preparations (AutoCyte preparation) were scanned using a BLISS (Bacus Laboratories Inc. Slide Scanner) system. Approximately 20-30% of the cellular area of each slide was imaged. The cases were randomly chosen to include examples ranging from benign cellular changes (BCC) to high-grade squamous intraepithelial lesions (HSIL). The computer performed image tiling and fusing of multiple JPEG images to create a high-quality VM slide. Six examiners (two each of cytopathologists, senior residents, and cytotechnologists) blindly evaluated the VM slides using an image server program (WebSlide Browser thin client software). The cytopathologic diagnoses made on the VM slide were then compared to the original glass slide diagnoses. BLISS took 36-100 min (avg. 58.4 min) to scan the selected fields in a glass slide with file sizes ranging from 23.1-83.6 MB. Time taken by the examiners to render a diagnosis ranged from 1-15 min (avg. 4.1 min) per case. The combined diagnostic accuracy was 98.3%. Only one case of LSIL was missed by one examiner. VM is a promising new tool, which gives a user the feel and simulated experience of an actual microscopic examination and provides a useful alternative to a glass slide in diagnostic cytopathology. Possible applications include: 1) second opinion consultation without transporting the glass slide, 2) education, 3) VM proficiency tests / board exams, and 4) telepathology. Shortcomings include 1) expensive initial setup, 2) inability to maintain an adequate focus in a thick smear with multiple levels, 3) large storage size of the VM slide, and 4) relatively long time needed to scan a slide.

Selection and implementation for coagulation instruments/reagents in a multiple hospital/clinic network.

Selection, standardization, and implementation of instrumentation and reagents throughout a health care facility network can often be a difficult process. However, in today's ever-changing health care setting, it is often mandated. The Veteran's Integrated Systems Network 16 (VISN 16) was faced with such a task early in 1999, with the targeted area being its coagulation laboratories. The plan outlined in this paper was drafted to help facilitate the selection, standardization and implementation of coagulation systems for 17 health care facilities that make up the VISN 16 network. The VISN, encompassing 170,000 square miles, has 10 tertiary care hospitals, six of which have close relationships with affiliate universities. There are 299,733 patients enrolled in this health delivery system. The facilities range from large institutions performing both tertiary and outpatient care to small outpatient clinics. Because of the plan's detailed, comprehensive content, which included analyses of a large number of performance parameters as well as cost-efficiency, the selection process was carried out using a checklist that could be helpful to other organizations selecting equipment and reagents for coagulation studies. An implementation process was devised, resulting in coagulation standardization across the Integrated Health Network.

Constructing a local district telepathology network in Japan. Diagnosis of intraoperative frozen sections via telepathology over an integrated service digital network and the National Television Standard Committee System.

OBJECTIVE: To construct a local telepathology network between the Department of Pathology, Tohoku University Hospital, and Koritu Kesennuma Hospital, about 150 km away. STUDY DESIGN: Tohoku University Hospital is connected with Koritu Kesennuma Hospital by an integrated service digital network for telepathology using the National Television Standard Committee system. The cases submitted for telepathology were limited to those in which a rapid intraoperative diagnosis was made on frozen sections. RESULTS: At this writing, more than 200 cases were diagnosed during a period of 2.5 years. The cases submitted increased with time, amounting to 150 in 1996. In some cases the use of telepathology proved to be fairly advantageous. For example, in one case a radical operation was avoided because of a diagnosis on intraoperative frozen sections. DISCUSSION: There are problems to be solved before telepathology becomes available for practical use: (1) misdiagnosis due to poor quality of instruments, including the transmission cable and pictures; (2) cost-benefit ratio, (3) protection of patients' privacy, and (4) overwork for pathologists. The Japanese government will officially accept telepathology as a means of medical examination in the future. Despite some problems left, telepathology is a promising technology.

Selection and implementation of a laboratory computer system.

The process of selection of a pathology computer system has become increasingly complex as there are an increasing number of facilities that must be provided and stringent performance requirements under heavy computing loads from both human users and machine inputs. Furthermore, the continuing advances in software and hardware technology provide more options and innovative new ways of tackling problems. These factors taken together pose a difficult and complex set of decisions and choices for the system analyst and designer. The selection process followed by the Microbiology Department at Heidelberg Repatriation Hospital included examination of existing systems, development of a functional specification followed by a formal tender process. The successful tenderer was then selected using predefined evaluation criteria. The successful tenderer was a software development company that developed and supplied a system based on a distributed network using a SUN computer as the main processor. The software was written using Informix running on the UNIX operating system. This represents one of the first microbiology systems developed using a commercial relational database and fourth generation language. The advantages of this approach are discussed.

The effect of allowing clinical discretion in ordering biochemical tests. Evaluation by complementary methods.

We describe the effects on costs, working patterns, and clinical behavior of installing a DAX "discretionary" biochemistry analyzer. Use of the new analyzer encouraged doctors to be more specific in requesting biochemical tests, which substantially reduced the number of tests requested and slightly reduced overall costs. Doctors preferred being able to order tests in this more specific way.

The evaluation of a portable clinical analyzer in the emergency department.

A recently available portable clinical analyzer (PCA), which examines sodium, potassium, chloride, glucose, urea nitrogen, and hematocrit levels on 60 microL of blood and calculates hemoglobin and osmolality levels within 2 minutes, was evaluated. Blood from 574 patients was drawn by emergency department staff, who immediately tested the samples with the PCA and transported them for plasma analysis on a reference analyzer in the clinical laboratory. Correlations between the PCA and the reference analyzer were as follows: R2 = 0.987 for urea nitrogen; R2 = 0.97, glucose; R2 = 0.937, K;R2 = 0.79, hematocrit; R2 = 0.751, sodium; and R2 = 0.689 for chloride. With its rapid turnaround, small sample requirement, and ease of operation, the PCA is most useful in an emergency department setting, where immediate access to clinically relevant laboratory testing is required in support of urgent clinical decision-making.