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Updated: May 14, 2026

Label-Free Identification of Lymphocyte Subtypes Using Three-Dimensional Quantitative Phase Imaging and Machine Learning
Published on: November 19, 2018
Multiharmonic imaging-based automated recognition of cutaneous T-cell lymphoma
Shayantani Ghosh1, Olesya Pavlova2, Alexandra Latshaw1
1Nonlinear Bioimaging Lab, Department of Applied Physics, University of Geneva, Geneva, Switzerland.
Nonlinear optical microscopy (NLOM) combined with artificial intelligence (AI) aids in diagnosing mycosis fungoides (MF), a type of cutaneous T-cell lymphoma (CTCL). This advanced imaging technique improves early detection of atypical lymphocytes in skin biopsies.
Area of Science:
- Dermatology
- Medical Imaging
- Artificial Intelligence
Background:
- Cutaneous T-cell lymphomas (CTCL), particularly mycosis fungoides (MF), present diagnostic challenges in early stages due to nonspecific clinical and histopathologic findings.
- Delayed diagnosis of MF can lead to significant delays in treatment, impacting patient outcomes.
- Novel diagnostic methods are crucial for improving the diagnostic and therapeutic strategies for CTCL.
Purpose of the Study:
- To evaluate Nonlinear Optical Microscopy (NLOM) for imaging hematoxylin & eosin (H&E) stained skin samples.
- To develop and apply an artificial intelligence (AI) model for detecting atypical epidermotropism and dermal cells in MF skin samples using NLOM.
- To assess the potential of NLOM for in vivo skin imaging of fresh, unstained biopsy samples.
Main Methods:
- Analysis of H&E-stained skin biopsy samples from MF lesions using both brightfield microscopy and NLOM.
- Training a convolutional neural network (CNN) with expert-labeled images to identify skin lymphocytes.
- Application of the AI model to independent datasets from both imaging modalities and fresh, unstained samples.
Main Results:
- NLOM successfully imaged epidermal and dermal structures in H&E-stained MF tissue with sub-cellular resolution.
- The AI model accurately detected lymphocyte epidermotropism and dermal infiltration in analyzed images.
- NLOM demonstrated capability for imaging fresh, unstained biopsies up to 400 µm deep.
Conclusions:
- NLOM coupled with AI effectively detects key features of MF in H&E-stained skin tissue, including lymphocyte epidermotropism and dermal infiltration.
- This combined approach offers a valuable tool for dermatologists to enhance MF-CTCL diagnosis and prognosis.
- The findings suggest potential for more timely and precise therapeutic interventions in MF-CTCL management.
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