Table S1. Summary of the multiphoton biomarkers for breast cancer based on the individual multiphoton imaging modalities, as well as the carcinogenic events cross-validated by multiple multiphoton imaging modalities.
| Modality | Biomarker | Biological relevance | Reference |
|---|---|---|---|
| Signatures observed by individual modality | |||
| 2PF, 3PF | Cellular FAD fluorescence | Oxidative phosphorylation | (12,13,16,24), this study |
| Increased FAD fluorescence lifetime | Metabolic shift | 13 | |
| Cellular NAD(P)H fluorescence | Aerobic glycolysis | (14-16)*, this study | |
| Decreased NAD(P)H fluorescence lifetime | Metabolic shift | (14) | |
| Increased redox ratio | Metabolic shift | (15,16)* | |
| Elastin organization | Elastic lamella synthesis in angiogenesis, fibrocystic tissue | (34)#, this study | |
| Angiogenesis-associated 3PF-sensitive microvesicle (AA3V) | Upregulated NAD(P)H in angiogenesis | This study | |
| SHG | Collagen organization (also observed by THG): TACS-1: locally dense collagen; TACS-2: straightened collagen tumor boundary; TACS-3: radially aligned collagen to TACS-2; TACS-4: locally reduced collagen; TACS-5: tubularly aligned collagen | Small tumorigenic region; increased tumor volume; invasive and metastatic growth; disruption and degradation of connective tissue; collagen enclosure in angiogenesis | (12,13,22), this study |
| THG | Tumor-associated THG-sensitive microvesicle (TATV) | Carcinogenesis, signaling molecule | (21)#, this study |
| Stellate structure (also observed by CARS) | Lipid degradation, lipolysis | This study | |
| THG-sensitive cell | Intracellular heterogeneity | This study | |
| Disrupted axon fiber (also observed by CARS) | Caused by other tumorigenic events | This study | |
| Small lipid droplet, lipid vesicle (also observed by CARS) | Signaling lipid vesicle, lipid metabolism | This study | |
| CARS, SRS | Regulated lipid composition (CH2 stretching): increased lipid content; decreased lipid content; deformed lipid deposit; increased cholesterol content | Excessive lipid, lipogenesis; lipid degradation, lipolysis; lipid degradation, lipolysis; carcinogenesis, increased hormone level | (17-19,25,47)#, this study |
| Increased protein content (CH aromatic stretching, CH3 stretching) | Carcinogenesis | (19,39)*, this study | |
| Water content (OH stretching) | Water co-localized with protein | (39)*, this study | |
| Mammary duct (also observed by 2PF, 3PF, THG) | Mammary duct formation | (23), this study | |
| Events revealed by multiple modalities | |||
| 2PF, SHG, 3PF, THG, CARS | Cellular FAD fluorescence; elastin organization; TACS-1,2,3,4,5; cellular NAD(P)H fluorescence; AA3V; TATV; decreased lipid content (CH2 stretching); increased protein content (CH aromatic stretching); water content (OH stretching) | Local invasion | (12,13,21)#, this study |
| 2PF, SHG, THG | Cellular FAD fluorescence; elastin organization; TACS-1 | Fibrocystic tissue | (24), this study |
| 2PF, SHG, 3PF, CARS | Cellular FAD fluorescence; elastin organization; TACS-4,5; AA3V; increased lipid content (CH2 stretching) | Angiogenesis | (34)#, this study |
| 2PF, SHG, THG, CARS | Cellular FAD fluorescence; elastin organization; TACS-1; TATV; increased lipid content (CH2 stretching); increased protein content (CH aromatic stretching) | Lipogenesis | (17,18), this study |
| 2PF, 3PF, THG, CARS | FAD fluorescent lipid; NAD(P)H fluorescent lipid; TACS-4; decreased lipid content (CH2 stretching); increased protein content (CH aromatic stretching); water content (OH stretching) | Lipolysis, β-oxidation | This study |
| SHG, CARS | High SHG response; lipid content (CH2 stretching) | Cholesterol crystallization | (48)#, this study |
*, non-multiphoton; #, non-breast cancer.