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. Author manuscript; available in PMC: 2024 Jun 1.
Published in final edited form as: Nat Photonics. 2023 Nov 16;17(12):1031–1041. doi: 10.1038/s41566-023-01299-6

Table 1.

Summary of key performance characteristics of major label-free biomedical imaging approaches

Method Spatial resolution Imaging depth Speed Main source of contrast Main applications System complexity and cost In vivo? Clinically widely avaialble?
PhM Sub μm Tens of μm **** Refractive index Cell structure * No Yes
PolM Sub μm Tens of μm **** Birefringence Cell and tissue structure (membranes and filament arrays, e.g., collagen fibers; cell spindle) * Yes (togther with other methods) Yes
OCT Several μm Several mm **** Refractive index, speckle/phase variance, Doppler, strain and shear stress Tissue structure; blood circulation; biomechanics ** Yes Yes
HGM Sub μm Sub mm *** High-order nonlinear susceptibility Cell and tissue structure SHG: Non-centrosymmetric structures and fibrillar structures, such as collagen or elastin in connective tissues, or myosin and microtubules in muscle fibers THG: Interfaces and optical heterogeneities, such as lipid-based biological membranes **** Yes No
aFM Sub μm Sub mm *** Endogenous fluorochromes Cell and tissue structure, NAD(P)H, FAD, keratin and elastin; redox; metabolic dynamics *** Yes No
IRAM Several μm Sub mm **** Absorption Endogenous tissue chromophores (hemoglobin, melanin, water and collagen) ** Yes No
RM Sub μm Sub mm * (linear)
*** (nonlinear)
Raman scattering of molecular vibrations Selective macro-molecular vibrations of lipids, proteins, DNA, etc. ** (linear)
**** (nonlinear)
Yes No
PAT Scalable: sub μm – tens of μm Scalable: Sub mm – tens of mm **** Absorption Cell and tissue structure; vasculature **** Yes No

PhM: Phase microscopy; PolM: Polarization microscopy; OCT: optical coherence tomography; HGM: Harmonic-generation microscopy; SHG: Second-harmonic generation; THG: Third-harmonic generation; aFM: Auto-fluorescence microscopy; IRAM: IR-absorption microscopy; RM: Raman microscopy; PAT: photoacoustic tomography. Rapid acquisition speed (****) refers to obtaining more than ten Mega-voxel/s in reasonable, clinical attainable resources.

Note: the table refers to the common version of each method.