Performance of a fully-automated system on a WHO malaria microscopy evaluation slide set.

BACKGROUND: Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. METHODS: The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. RESULTS: The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. CONCLUSIONS: EasyScan GO's expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

Automated microscopy for routine malaria diagnosis: a field comparison on Giemsa-stained blood films in Peru.

BACKGROUND: Microscopic examination of Giemsa-stained blood films remains a major form of diagnosis in malaria case management, and is a reference standard for research. However, as with other visualization-based diagnoses, accuracy depends on individual technician performance, making standardization difficult and reliability poor. Automated image recognition based on machine-learning, utilizing convolutional neural networks, offers potential to overcome these drawbacks. A prototype digital microscope device employing an algorithm based on machine-learning, the Autoscope, was assessed for its potential in malaria microscopy. Autoscope was tested in the Iquitos region of Peru in 2016 at two peripheral health facilities, with routine microscopy and PCR as reference standards. The main outcome measures include sensitivity and specificity of diagnosis of malaria from Giemsa-stained blood films, using PCR as reference. METHODS: A cross-sectional, observational trial was conducted at two peripheral primary health facilities in Peru. 700 participants were enrolled with the criteria: (1) age between 5 and 75 years, (2) history of fever in the last 3 days or elevated temperature on admission, (3) informed consent. The main outcome measures included sensitivity and specificity of diagnosis of malaria from Giemsa-stained blood films, using PCR as reference. RESULTS: At the San Juan clinic, sensitivity of Autoscope for diagnosing malaria was 72% (95% CI 64-80%), and specificity was 85% (95% CI 79-90%). Microscopy performance was similar to Autoscope, with sensitivity 68% (95% CI 59-76%) and specificity 100% (95% CI 98-100%). At San Juan, 85% of prepared slides had a minimum of 600 WBCs imaged, thus meeting Autoscope's design assumptions. At the second clinic, Santa Clara, the sensitivity of Autoscope was 52% (95% CI 44-60%) and specificity was 70% (95% CI 64-76%). Microscopy performance at Santa Clara was 42% (95% CI 34-51) and specificity was 97% (95% CI 94-99). Only 39% of slides from Santa Clara met Autoscope's design assumptions regarding WBCs imaged. CONCLUSIONS: Autoscope's diagnostic performance was on par with routine microscopy when slides had adequate blood volume to meet its design assumptions, as represented by results from the San Juan clinic. Autoscope's diagnostic performance was poorer than routine microscopy on slides from the Santa Clara clinic, which generated slides with lower blood volumes. Results of the study reflect both the potential for artificial intelligence to perform tasks currently conducted by highly-trained experts, and the challenges of replicating the adaptiveness of human thought processes.

Classification of malignant and benign tumors of the lung by infrared spectral histopathology (SHP).

We report results of a study utilizing a novel tissue classification method, based on label-free spectral techniques, for the classification of lung cancer histopathological samples on a tissue microarray. The spectral diagnostic method allows reproducible and objective classification of unstained tissue sections. This is accomplished by acquiring infrared data sets containing thousands of spectra, each collected from tissue pixels ∼6 µm on edge; these pixel spectra contain an encoded snapshot of the entire biochemical composition of the pixel area. The hyperspectral data sets are subsequently decoded by methods of multivariate analysis that reveal changes in the biochemical composition between tissue types, and between various stages and states of disease. In this study, a detailed comparison between classical and spectral histopathology is presented, suggesting that spectral histopathology can achieve levels of diagnostic accuracy that is comparable to that of multipanel immunohistochemistry.

A method for the comparison of multi-platform spectral histopathology (SHP) data sets.

Results of a study comparing infrared imaging data sets collected on different instruments or instrument platforms are reported, along with detailed methods developed to permit such comparisons. It was found that different instrument platforms, although employing different detector technologies and pixel sizes, produce highly similar and reproducible spectral results. However, differences in the absolute intensity values of the reflectance data sets were observed that were caused by heterogeneity of the sample substrate in terms of reflectivity and planarity.

Statistical analysis of a lung cancer spectral histopathology (SHP) data set.

We report results on a statistical analysis of an infrared spectral dataset comprising a total of 388 lung biopsies from 374 patients. The method of correlating classical and spectral results and analyzing the resulting data has been referred to as spectral histopathology (SHP) in the past. Here, we show that standard bio-statistical procedures, such as strict separation of training and blinded test sets, result in a balanced accuracy of better than 95% for the distinction of normal, necrotic and cancerous tissues, and better than 90% balanced accuracy for the classification of small cell, squamous cell and adenocarcinomas. Preliminary results indicate that further sub-classification of adenocarcinomas should be feasible with similar accuracy once sufficiently large datasets have been collected.