Optical coherence tomography (OCT) is one of the most innovative and successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.^1,2 OCT is a non-invasive optical analog to ultrasound (US) with significantly higher resolution ($<1\mu \mathrm{m}$) enabling three- and four-dimensional high-speed (>millions of A-scans/s) imaging with tissue penetration of up to 2 mm, closely matching that of conventional histopathology. The year 2021 marks not only the 30th birthday of OCT (assuming its initiation with the Science paper by Huang et al.³ in 1991) but also the 35th birthday of low-coherence interferometry and optical ranging in biological systems.^4,5 In the last three decades, more than 75,000 OCT related papers have been published (about two thirds in ophthalmology) with continuous yearly increases of published articles.⁶ Breaking through the 1000 publications/year barrier was initiated in 2005/2006 with the introduction of spectral domain OCT (SD OCT). In 2020, the OCT-related scientific output was more than 7800 papers, resulting in nearly one paper every single hour on every single day of the year. Extrapolating this publishing performance, a saturation of yearly publication output at about 9500 can be expected around 2030. After 30 years, it is interesting and important to benchmark this performance with other medical imaging techniques:⁶ multiphoton microscopy (MPM) [including second harmonic generation (SHG) and third harmonic generation (THG)], developed about three decades before OCT,^7,8 has about 50,000 publications so far; photoacoustic imaging (PAI), established in the 1970s,^9,10 has about 15,000 papers; and confocal microscopy, developed in the 1940s,^11,12 has about 145,000. Developed in the 1940s,¹³ US imaging has contributed to about 160,000 papers; positron emission tomography (PET), initiated in the 1970s,^14,15 has about 175,000; computed tomography (CT), developed in the 1930s,¹⁶ has about 750,000; and magnetic resonance imaging (MRI), developed in the late 1940s,¹⁷ has close to 1,000,000 publications. This dominance in publications of radiology and nuclear medicine imaging technologies is also one of the reasons why medical imaging is, in general, associated with MRI, CT, PET, or US. It is important to note, though, that from a medical imaging market perspective, optical imaging technologies dominate with 66% versus 34% for radiology and nuclear medicine imaging technologies. In addition, in the United States alone, about 450,000 physicians use primarily optical imaging techniques; 60,000 use primarily radiologic imaging; and about 130,000 use both.¹⁸

We present measurements of total retinal blood flow in healthy volunteers using a three beam Doppler optical coherence tomography (D-OCT) technique. This technology has the advantage of a precise determination of the flow vector without the use of any a-priori information on the vessel geometry. Circular D-OCT scans around the optic disc were recorded and venous as well as arterial total blood flow was determined and compared for each subject. The reproducibility of the method was assessed in 6 subjects by repeated measurements. Only small deviations of around 6% between the measurements were found which indicates the high precision of the proposed method.

We present a newly developed single mode fiber based swept source polarization sensitive optical coherence tomography system using a single input state at 1040 nm. Two non-polarizing fiber based beam splitters are combined to form a Mach-Zehnder interferometer, while two polarizing beam splitters are used to obtain a polarization sensitive detection. Both types of beam splitters solely feature conventional single mode fibers. Polarization control paddles are used to set and maintain the polarization states in the fibers of the interferometer and detection unit. By use of a special paddle alignment scheme we are able to eliminate any bulk optic wave plates and polarization maintaining fibers in the interferometer and detection paths while preserving the advantages of a single input state system that illuminates the sample with circularly polarized light. To demonstrate the capabilities of our system, we performed retinal measurements on healthy human volunteers.

We present a dual modality functional optical coherence tomography and photoacoustic microscopy (OCT-PAM) system. The photoacoustic modality employs an akinetic optical sensor with a large imaging window. This imaging window enables direct reflection mode operation, and a seamless integration of optical coherence tomography (OCT) as a second imaging modality. Functional extensions to the OCT-PAM system include Doppler OCT (DOCT) and spectroscopic PAM (sPAM). This functional and non-invasive imaging system is applied to image zebrafish larvae, demonstrating its capability to extract both morphological and hemodynamic parameters in vivo in small animals, which are essential and critical in preclinical imaging for physiological, pathophysiological and drug response studies.

Conventional imaging of the human cornea with optical coherence tomography (OCT) relies on telecentric scanning optics with sampling beams that are parallel to the optical axis of the eye. Because of the shape of the cornea, the beams have in some areas considerable inclination to the corneal surface which is accompanied by low signal intensities in these areas and thus an inhomogeneous appearance of corneal structures. In addition, alterations in the polarization state of the probing light depend on the angle between the imaging beam and the birefringent axis of the sample. Therefore, changes in the polarization state observed with polarization-sensitive (PS-) OCT originate mainly from the shape of the cornea. In order to minimize the effects of the corneal shape on intensity and polarization-sensitive based data, we developed a conical scanning optics design. This design provides imaging beams that are essentially orthogonal to the corneal surface. Thus, high signal intensity throughout the entire imaged volume is obtained and the influence of the corneal shape on polarization-sensitive data is greatly reduced. We demonstrate the benefit of the concept by comparing PS-OCT imaging results of the human cornea in healthy volunteers using both scanning schemes.

Objective: 3D optical coherence tomography (OCT) is used for analyses of human placenta organoids in situ without sample preparation. Methods: The trophoblast organoids analyzed were derived from primary human trophoblast. In this study a custom made ultra-high-resolution spectral domain OCT system with uniform spatial and axial resolution of 2.48 m in organoid tissue was used. The obtained OCT results align to differentiation status tested via quantitative polymerase chain reaction, Western blot analyses, immunohistochemistry, and immunofluorescence of histological sections. Results: 3D OCT enables a more detailed placenta organoid monitoring compared to brightfield microscopy. Inner architecture with light scattering bridges surrounding cavities were visualized and quantified in situ for the first time. The formation of these bridges and cavities is congruent to differentiated trophoblast organoids having developed syncytiotrophoblasts. Conclusion: Using 3D OCT in living placenta organoids is a fast tool to assess the differentiation status and resolve internal structures in situ, which is not possible with standard live cell imaging modality. Significance: Only recently human placenta-derived organoids were established, allowing to have a highly reproducible and stable in vitro model to investigate not only developmental but also physiological and pathophysiological processes during early pregnancy. To our knowledge, this work is the first to analyze living human placenta organoids using 3D OCT. Thereby, the rapid and especially non- endpoint OCT qualitative analyses align to the differentiation stage of organoids, which will aid future advancement in this field.