In the last 25 years, optical coherence tomography (OCT) has advanced to be one of the most innovative and most successful translational optical imaging techniques, achieving substantial economic impact as well as clinical acceptance. This is largely owing to the resolution improvements by a factor of 10 to the submicron regime and to the imaging speed increase by more than half a million times to more than 5 million A-scans per second, with the latter one accomplished by the state-of-the-art swept source laser technologies that are reviewed in this article. In addition, parallelization of OCT detection, such as line-field and full-field OCT, has shortened the acquisition time even further by establishing quasi-akinetic scanning. Besides the technical improvements, several functional and contrast-enhancing OCT applications have been investigated, among which the label-free angiography shows great potential for future studies. Finally, various multimodal imaging modalities with OCT incorporated are reviewed, in that these multimodal implementations can synergistically compensate for the fundamental limitations of OCT when it is used alone.

A novel all-optical akinetic ultrasound sensor, consisting of a rigid, fiber-coupled Fabry-Pérot etalon with a transparent central opening is presented. The sensing principle relies exclusively on the detection of pressure-induced changes of the refractive index in the fluid filling the Fabry-Pérot cavity. This enables resonance-free, inherently linear signal detection over a broad bandwidth. We demonstrate that the sensor achieves a exceptionally low peak noise equivalent pressure (NEP) values of 2 Pa over a 20 MHz measurement bandwidth (without signal averaging), while maintaining a flat frequency response, and a detection bandwidth up to 22.5 MHz (−6 dB). The measured large full field of view of the sensor is 2.7 mm × 1.3 mm and the dynamic range is $137\text{dB}/\sqrt{\text{Hz}}$ or 63 dB at 20 MHz bandwidth. For different required amplitude ranges the upper amplitude detection limit can be customized from at least 2 kPa to 2 MPa by using cavity mirrors with a lower optical reflectivity. Imaging tests on a resolution target and on biological tissue show the excellent suitability of the akinetic sensor for optical resolution photoacoustic microscopy (OR-PAM) applications.

Ultrasound-mediated neuromodulation is emerging as a key technology for targeted noninvasive brain stimulation, but key insights into its effects and dose-response characteristics are still missing. The purpose of this study is to systematically evaluate the effect of low-intensity transcranial ultrasound stimulation (TUS) on complementary aspects of cerebral hemodynamic. We simultaneously record the EMG signal, local field potential (LFP) and cortical blood flow (CBF) using electrophysiological recording and laser speckle contrast imaging under ultrasound stimulation to simultaneously monitor motor responses, neural activities and hemodynamic changes during the application of low-intensity TUS in mouse motor cortex, using excitation pulses which caused whisker and tail movement. Our experimental results demonstrate interdependent TUS-induced motor, neural activity and hemodynamic responses that peak approximately 0.55s, 1.05s and 2.5s after TUS onset, respectively, and show a linear coupling relationship between their respective varying response amplitudes to repeated stimuli. We also found monotonic dose-response parametric relations of the CBF peak value increase as a function of stimulation intensity and duration, while stimulus duty-cycle had only a weak effect on peak responses. These findings demonstrate that TUS induces a change in cortical hemodynamics and LSCI provide a high temporal resolution view of these changes.

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

The cutaneous vasculature is involved in many diseases. Current clinical examination techniques, however, cannot resolve the human vasculature with all plexus in a non-invasive manner. By combining an optical coherence tomography system with angiography extension and an all optical photoacoustic tomography system, we can resolve in 3D the blood vessels in human skin for all plexus non-invasively. With a customized imaging unit that permits access to various parts of patients’ bodies, we applied our multimodality imaging system to investigate several different types of skin conditions. Quantitative vascular analysis is given for each of the dermatological conditions to show the potential diagnostic value of our system in non-invasive examination of diseases and physiological processes. Improved performance of our system over its previous generation is also demonstrated with an updated characterization.

Optical coherence tomography angiography (OCTA) is a relatively novel functional extension of the widely accepted ophthalmic imaging tool named optical coherence tomography (OCT). Since OCTA's debut in ophthalmology, researchers have also been trying to expand its translational application in dermatology. The ability of OCTA to resolve microvasculature has shown promising results in imaging skin diseases. Meanwhile, photoacoustic imaging (PAI), which uses laser pulse induced ultrasound waves as the signal, has been studied to differentiate human skin layers and to help in skin disease diagnosis. This perspective article gives a short review of OCTA and PAI in the field of photodermatology. After an introduction to the principles of OCTA and PAI, we describe the most updated results of skin disease imaging using these two optical imaging modalities. We also place emphasis on dual modality imaging combining OCTA and photoacoustic tomography (PAT) for dermatological applications. In the end, the challenges and prospects of these two imaging modalities in dermatology are discussed.