Mobile microscopy as a screening tool for oral cancer in India: A pilot study

Abstract

Oral cancer is the most common type of cancer among men in India and other countries in South Asia. Late diagnosis contributes significantly to this mortality, highlighting the need for effective and specific point-of-care diagnostic tools. The same regions with high prevalence of oral cancer have seen extensive growth in mobile phone infrastructure, which enables widespread access to telemedicine services. In this work, we describe the evaluation of an automated tablet-based mobile microscope as an adjunct for telemedicine-based oral cancer screening in India. Brush biopsy, a minimally invasive sampling technique was combined with a simplified staining protocol and a tablet-based mobile microscope to facilitate local collection of digital images and remote evaluation of the images by clinicians. The tablet-based mobile microscope (CellScope device) combines an iPad Mini with collection optics, LED illumination and Bluetooth-controlled motors to scan a slide specimen and capture high-resolution images of stained brush biopsy samples. Researchers at the Mazumdar Shaw Medical Foundation (MSMF) in Bangalore, India used the instrument to collect and send randomly selected images of each slide for telepathology review. Evaluation of the concordance between gold standard histology, conventional microscopy cytology, and remote pathologist review of the images was performed as part of a pilot study of mobile microscopy as a screening tool for oral cancer. Results indicated that the instrument successfully collected images of sufficient quality to enable remote diagnoses that show concordance with existing techniques. Further studies will evaluate the effectiveness of oral cancer screening with mobile microscopy by minimally trained technicians in low-resource settings.

Fig 1. Overview of the automated CellScope device and system for mobile screening.

(A) An automated image acquisition system capable of auto-focusing and scanning of a sample slide. (B) Representative image of H&E stained cells acquired with a 20X/0.4NA objective on the automated scanning CellScope. Scale bar represents 100 μm. (C) Schematic to explain the overall workflow of the telemicroscopy process.

Fig 2. Screenshots of the iPad mobile app user interface.

(A) The login page on the iPad app showing the password protected secure system for the technician. (B) Another screenshot on the iPad app showing options to enter patient date of birth, sample ID, gender and additional comments.

Fig 3. Screenshots of the CellScope server user interface.

(A) Screenshot of the CellScope server (web portal interface) showing the list of patients whose diagnosis has been carried out. Color-coding of records was used to indicate the status of the samples (i.e. diagnostic result provided, awaiting review, sample rejected, etc.) (B) Screenshot of server interface showing CellScope images acquired from a patient sample. Note the thumbnail panel on the left showing thumbnails of all images captured for that patient sample and a magnified image of the selected image in the center/right. Selected regions of interest (indicated by light blue rectangles which could be drawn by the pathologists using tools provided in the interface) are overlaid on the image. (C) Screenshot of the server interface showing a pop-up window containing various cellular features which could be used by the pathologist to annotate the selected region of interest. A free-text box in this window allowed the pathologists to enter additional comments, if necessary.

Fig 4. Workflow of sample acquisition and analysis for the study.

Fig 5. Process for encoding/decoding of patient information and samples.

Fig 6. Data security for the CellScope system.

Fig 7. The automated mobile microscope is capable of capturing images representative of relevant disease features.

(A) Morphologically normal cells from a brush biopsy preparation. (A’) Zoom-in of cells in A showing normal morphology. (B) Abnormal cells from a patient with confirmed malignancy, including cells with high nucleus to cytoplasm ratio and hyperchromatic nucleus indicated with red arrows. (B’) Zoom-in of suspicious cells in B showing morphological changes. (C) Suspicious cells imaged from a patient with confirmed leukoplakia. The red arrow indicates a high nucleus: cytoplasm ratio indicating a suspicious cell. Note the paucity of cells leading to difficulty with the auto-focusing algorithm for this sample preparation. (C’) Zoom-in of suspicious cell in C showing high nucleus-to-cytoplasm ratio. All scale bars represent 100 μm.