# Ten Years of Gabor-Domain Optical Coherence Microscopy
## 2 Strategies for Cellular-Resolution Imaging  
Noninvasive imaging techniques, which include ultrasound, optical coherence tomography (OCT), and confocal microscopy, are routinely used in clinical applications for providing insight on tissue structural morphology. These methods face a tradeoff between spatial resolution and depth of imaging, as depicted in Figure 1, in which the application space is shown in log-scale for the two key parameters of transverse resolution and imaging depth. These two parameters determine what kind of features can be imaged--including cellular and subcellular--and at what depth inside of the tissue. With typical cellular structures having a size of 10-20 \(\upmu\)m, a resolution \(<\)5 \(\upmu\)m is desired to visualize the cellular morphology. A depth of imaging of \(\sim\)1 mm or more is advantageous to track cellular changes in tissue induced by various diseases. OCT is an optical imaging technique based on low-coherence interferometry with an axial resolution on the micrometer-scale and lateral resolution limited to tens of micrometers [2]. OCT produces cross-sectional views of tissue up to a depth of several millimeters. In OCT, transverse and axial resolutions are decoupled. OCT--in particular spectral domain OCT (SD-OCT)--is widely used in ophthalmic and cardiovascular applications [2; 3]. Confocal microscopy, with micron or submicron lateral resolution, has depth of imaging limited to tens of micrometers [4]. Optical imaging systems, including OCT and confocal microscopy, face a trade-off between lateral resolution and depth of imaging. To increase the lateral resolution \(\Delta x\), the numerical aperture (NA) is increased, resulting in shallower depth of focus (DOF), as illustrated in Figure 2.  
Optical coherence microscopy (OCM) was introduced as a variant of OCT to achieve micrometer-scale resolution [5]. OCM uses a higher NA objective (i.e., \(\sim\)0.2) than conventional OCT (i.e., \(\sim\)0.04), and can produce cellular imaging at the expense of a reduction in depth of focus (100-200 \(\upmu\)m). OCM variants include point-scanning OCM and full-field OCM [6; 7; 8]. In full-field OCM, more often referred to as full-field OCT (FF-OCT), en face images are acquired. Computational approaches for extending the depth of focus in OCM have been proposed successfully [9; 10]. Figure 1: Noninvasive imaging techniques (adapted from [1]). Ultrasound and optical coherence tomography suffer from insufficient lateral resolution for cellular imaging, while confocal microscopy and optical coherence microscopy suffer from limited imaging depth in tissue. Gabor-domain optical coherence microscopy was introduced to overcome the tradeoff between transverse resolution and depth of focus. Figure 2: Tradeoff between lateral resolution (\(\Delta x\)) and depth of focus (DOF) in an optical imaging system. NA: Numerical aperture. The choice of the light source in OCT and OCM has direct impact on both transverse and axial resolutions, as well as on imaging depth, since transverse resolution is linearly proportional to the central wavelength, axial resolution is inversely proportional to the bandwidth, and longer wavelengths penetrate deeper into tissue. Superluminescent diodes (SLDs) [11] are broadly used in OCT due to availability in the 800, 1300, and 1500 nm spectral bands, relatively large bandwidth (typically 50-100 nm), affordability, and increased brightness (at the expense of bandwidth) over thermal sources [12]. An advantage of fluorescence-based sources, which have been employed in FF-OCT in conjunction with pulsed illumination to reduce motion artifacts, is the smoothness of the spectrum, yet their applicability is limited due to cost and requirement of a high-power laser excitation source [13]. Light-emitting diodes (LEDs), have been described to produce submicron axial resolution in FF-OCT with spatial resolution and sensitivity equivalent to those obtained with halogen sources [14].