Opto-electrical transvaginal imaging probe for preinvasive cervical cancer diagnosis.

Background: Cervical cancer is the fourth highest cause of mortality around the world. However, cervical cancer progression is slow, and takes about ten years before fully developing. The current techniques, such as cytology which gives very high accuracy, are costly and requires highly skilled workforce. The colposcopy used as triage to locate the high-grade lesion involves using acetic acid, which is corrosive, resulting in patients’ pain during the procedure and needs an expert pathologist to interpret the colposcopy guided biopsies. Recommended screening with HPV DNA is far-fetched due to the cost.

Scientific Rationale: Due to the reduced activity of the ferrochelatase enzyme during the heme cycle, there is a buildup of porphyrin and lower total haemoglobin within the cancer cells. The proposed transvaginal probe estimates the cancer biomarkers, such as protein, glycogen, PpIX, HbO2, and Hb, on the tissue surfaces to differentiate the cancerous tissues from adjacent normal. The proposed transvaginal imaging probe uses autofluorescence and multispectral diffuse reflectance spectroscopy modalities to do so. The probe detects the increase in porphyrin by shining the light at 405 nm and detecting the image from the tissue surface at about 540 nm. The probe also houses LEDs operating at 545 nm and 575 nm to target the two isosbestic points for HbO2 and Hb and 610 nm, where the absorption coefficient of Hb is about ten times more than HbO2. The camera captures images of the tissue surface by shining the light with 545 nm, 575 nm, and 610 nm, one after the other. The ratio R610/R545, R610/R575, and autofluorescence differentiate the cancerous region from the adjacent normal tissues.

Moreover, the cervical epithelium is a structured tissue undergoing significant changes as it advances from normal epithelium to high-grade Cervical Intraepithelial Neoplasia (CIN). These changes involve a decrease in stratification, an increase in the nuclear-cytoplasmic ratio, and an increase in the extracellular space. Electrical impedance spectroscopy (EIS) has been used as an adjunct to colposcopy for cervical cancer diagnosis for many years. Also, based on the prior work by Prof. Pandya’s lab at IISc, it was found that electrical impedance and associated electrical analogy model parameters can be potentially used for tumour diagnosis and delineation. Electrical impedance tomography (EIT) is a non-invasive imaging method that uses low-frequency electrical signals to produce images of the electrical properties of tissues within a body. Although the EIT approach has existed for nearly two decades, the application of EIT has been limited due to the challenges in the positioning of electrodes and modelling the electrode location, low resolution, and inaccuracy of the images for imaging tissue regions far from the electrodes. The proposed transvaginal imaging probe incorporates a novel approach of EIT with a unique combination of electrode design and electronic data acquisition unit that enables miniaturization into the size of a probe

Novelty and Indigenization:

• The novelty of this project is the application of bi-modal (optical and electrical) for diagnosis of preinvasive lesions in cervix.

• The label-free transvaginal imaging probe housing multiple narrow bandwidth LEDs, subminiaturized high-resolution CMOS camera, and the development of the electronic chip to perform diffused reflectance imaging and electrical impedance tomography is to be indigenously fabricated in the lab.

Expected Outcome:

The objective of the project is to design and develop an at-community digitally connected imaging probe which can be used to capture images of the cervix and share with the clinician in remote location using WiFi or mobile internet. The images can yield rapid assessment with the help of Artificial Intelligence (AI) in identifying preinvasive cancer.

We expect the probe to identify the high-grade lesion with diagnostic accuracy as good as standard colposcopy performed by the physician. With this expectation we can in future offer point of care screen and treat at community.