# Beyond the Nucleus: Cytoplasmic Dominance in Follicular Thyroid Carcinoma Detection Using Single-Cell Raman Imaging Across Multiple Devices

## TL;DR

This study shows that cytoplasmic biochemical signals detected by single-cell Raman imaging are more effective than nuclear signals in diagnosing follicular thyroid carcinoma, with high accuracy across multiple devices.

## Contribution

It reveals the dominant role of cytoplasmic features over nuclear features in FTC detection using Raman imaging, emphasizing organelle-specific diagnostic information.

## Key findings

- Cytoplasmic Raman spectra distinguish FTC from normal cells with 84% accuracy.
- Nuclear spectra only achieve 53% accuracy in classification.
- Raman-based diagnosis is robust across different imaging devices.

## Abstract

Cytological diagnosis of follicular thyroid carcinoma (FTC) is one of major challenges in the field of endocrine oncology due to absence of evident morphological indicators. Morphological abnormalities in the nucleus are typically key indicators in cancer cytopathology and are attributed to a range of biochemical alterations in nuclear components. Consequently, Raman spectroscopy has been widely used to detect cancer in various cytological samples, often identifying biochemical changes prior to observable morphological alterations. However, in the case of FTC, cytoplasmic features such as carotenoids, cytochromes, and lipid droplets have shown greater diagnostic relevance compared to nuclear features. This study leverages single-cell Raman imaging to explore the spatial origin of diagnostic signals in FTC and normal thyroid (NT) cells, assessing the contributions of the nucleus and cytoplasm independently. Our results demonstrate that Raman spectra from the cytoplasmic region can distinguish between FTC and NT cells with an accuracy of 84% under co-culture conditions, maintaining robustness across multiple devices. In contrast, classification based on nuclear spectra achieved only 53% accuracy, suggesting that biochemical alterations in the cytoplasm play a more significant role in FTC detection than those in the nucleus. Our work elevates the promise of Raman-based cytopathology by providing complementary organelle-dependent information to traditional diagnostic methods and demonstrating transferability across different devices.