Early Detection of Uveal Melanoma Using Electrical Impedance Spectroscopy

Academic Background

Uveal Melanoma (UM) is the most common primary intraocular malignancy in adults, characterized by high aggressiveness, which can lead to vision loss and even life-threatening outcomes. Early detection and timely treatment are crucial for preserving vision and reducing mortality rates. However, many UM patients do not exhibit noticeable symptoms until the tumor has grown significantly, making early diagnosis highly challenging. Existing diagnostic methods, such as fundus examination and ultrasound imaging, while effective, require specialized equipment and expertise and are not suitable for large-scale screening. Therefore, developing a simple, non-invasive method for early detection is of great significance.

Electrical Impedance Spectroscopy (EIS) is a technique that distinguishes healthy tissues from pathological ones by measuring the electrical properties of biological tissues. Previous studies have shown that cancerous tissues exhibit significant differences in electrical properties (e.g., cell surface charge, transmembrane potential, ion concentration, and cell membrane permeability) compared to healthy tissues. EIS has been successfully applied in the detection of cutaneous melanoma, but its application in intraocular tumor detection has not been thoroughly explored.

Source of the Paper

This paper was co-authored by Vaibhav B. Yadav, Enosh Lim, Alison H. Skalet, and Mohammad J. Moghimi, affiliated with Northern Illinois University, Wake Forest University School of Medicine, Casey Eye Institute, and Knight Cancer Institute, among other institutions. The paper was published in 2024 in the journal npj Biosensing, titled “Evaluation of Electrical Impedance Spectroscopy of Bovine Eyes for Early Detection of Uveal Melanoma.”

Research Process and Results

1. Research Objectives and Methods

The study aimed to evaluate the potential of EIS technology in detecting simulated uveal melanoma in bovine eye models for early diagnosis. The research was divided into two main parts: Finite Element Analysis (FEA) and ex vivo experiments.

a) Finite Element Analysis (FEA)

The researchers used COMSOL Multiphysics® software to construct a bovine eye model, simulating the effects of different electrode configurations (e.g., flat electrodes and needle electrodes on the cornea) on current density and impedance. The model included intraocular structures such as the sclera, choroid, retina, and vitreous humor. By injecting a current of 188 µA, the current distribution in healthy eyes and eye models containing simulated tumors was simulated.

b) Ex Vivo Experiments

The researchers conducted experiments using bovine eyes, measuring impedance and current distribution at various frequencies (50 Hz to 500 kHz). In the experiments, incisions were made in the sclera of bovine eyes, and muscle tissue (5×5×5 mm) simulating a tumor was inserted to assess the impact of the tumor on electrical properties. The experiments also compared the impedance differences between fresh and preserved bovine eyes.

2. Key Results

a) FEA Results

The FEA results showed that the presence of simulated tumors significantly altered the current density distribution in the eye models. For example, in the presence of a 0.6 mm diameter tumor in the ciliary body, the maximum current density shifted from the center of the eye to the tumor region, increasing by 40%. Additionally, flat electrodes (contact lenses) injected lower current density into the tumor compared to needle electrodes but were more suitable for non-invasive measurements.

b) Ex Vivo Experimental Results

The experimental results demonstrated that inserting simulated tumor muscle tissue significantly reduced the impedance of bovine eyes. For instance, at a frequency of 100 kHz, the impedance of an intact bovine eye was 250 Ω, which decreased by 100 Ω after tumor insertion. Furthermore, the presence of an incision increased impedance, but inserting the tumor further reduced it. The experiments also revealed that the impedance of fresh bovine eyes was significantly lower than that of preserved eyes, likely due to the higher conductivity of water and ions in fresh tissues.

3. Conclusions and Significance

Through FEA and ex vivo experiments, this study demonstrated the potential of EIS technology in detecting intraocular tumors. The results indicated that the presence of simulated tumors significantly altered the current distribution and impedance characteristics within the eye, and EIS technology was capable of detecting tumors as small as 5 mm. These findings provide a theoretical basis for developing a non-invasive, simple method for early UM detection.

4. Research Highlights

• Innovative Approach: The first application of EIS technology for intraocular tumor detection, offering a new perspective for early diagnosis.
• High Sensitivity: Experiments showed that EIS technology could detect tumors as small as 5 mm, with a sensitivity of 7.75 kΩ/mm³.
• Non-Invasive Potential: The design of flat electrodes (contact lenses) lays the foundation for future non-invasive detection devices.

5. Future Prospects

The researchers plan to conduct further animal model and human trials to validate the effectiveness of EIS technology in living organisms. Additionally, they aim to use artificial intelligence (AI) models to analyze EIS data from patients with various eye diseases to improve diagnostic accuracy.

Summary

This study, through FEA and ex vivo experiments, validated the potential of EIS technology in the early detection of uveal melanoma. The research results provide important evidence for developing a non-invasive, highly sensitive method for intraocular tumor detection, with significant clinical application value.