Advances in Tissue-Clearing and Volumetric Imaging: A Technical Framework Toward Three-Dimensional Pathology

Area of Science:

• Pathology
• Biotechnology
• Medical Imaging

Background:

• Conventional slide-based pathology limits evaluation to 2D sections.
• Three-dimensional (3D) pathological diagnosis using tissue-clearing technology enables volumetric assessment of intact specimens.
• Significant advancements in 3D pathology have occurred between 2020 and 2026.

Purpose of the Study:

• To review recent progress in 3D pathological diagnosis.
• To highlight key developments in tissue-clearing methodologies, fluorescence labeling, imaging, data processing, and applications.
• To identify challenges and future directions for clinical implementation of 3D pathology.

Main Methods:

• Review of literature and technological advancements from 2020-2026.
• Focus on tissue-clearing techniques, fluorescence labeling strategies, and volumetric imaging modalities.
• Analysis of artificial intelligence (AI)-enabled data processing, including reconstruction, segmentation, and virtual staining.

Main Results:

• Improvements in clearing speed, deep labeling, imaging throughput, and computational analysis.
• Shift from 2D sections to continuous 3D tissue volumes for pathological observation.
• Successful preclinical applications in complex tissues and emerging clinical studies demonstrating diagnostic relevance and workflow compatibility.

Conclusions:

• 3D pathology shows promise for enhanced diagnostic capabilities, moving towards continuous volumetric interpretation.
• AI integration and advanced imaging platforms are accelerating the transition to interpretable 3D pathology.
• Standardization, accessibility, and clinical validation remain critical for widespread adoption of 3D pathology as a diagnostic tool.