Spatial frequency domain correlation mapping optical coherence tomography for nanoscale structural characterization

Abstract

Most of the fundamental pathological processes in living tissues exhibit changes at the nanoscale. Noninvasive, label-free detection of structural changes in biological samples pose a significant challenge to both researchers and healthcare professionals. It is highly desirable to be able to resolve these structural changes, during physiological processes, both spatially and temporally. Modern nanoscopy largely requires labeling, is limited to superficial 2D imaging, and is generally not suitable for in vivo applications. Furthermore, it is becoming increasingly evident that 2D biology often does not translate into the real 3D situation. Here, we present a method, spatial frequency domain correlation mapping optical coherence tomography (sf-cmOCT), for detection of depth resolved nanoscale structural changes noninvasively. Our approach is based on detection and correlation of the depth resolved spectra of axial spatial frequencies of the object which are extremely sensitive to structural alterations. The presented work describes the principles of this approach and demonstrates its feasibility by monitoring internal structural changes within objects, including human skin in vivo. Structural changes can be visualized at each point in the sample in space from a single image or over time using two or more images. These experimental results demonstrate possibilities for the study of nanoscale structural changes, without the need for biomarkers or labels. Thus, sf-cmOCT offers exciting and far-reaching opportunities for early disease diagnosis and treatment response monitoring, as well as a myriad of applications for researchers.

Characterization of nanosensitive multifractality in submicron scale tissue morphology and its alteration in tumor progression

“…In our recent publications, 20 , 34 we have experimentally and numerically demonstrated the implementation of nsOCT to image a commercially fabricated sample with 431.56 nm axial periodic structures. In Ref.…”

“…Recently, we have numerically and experimentally validated nsOCT approach on synthetic submicron axial structure with few nanometer accuracy. 20 Here we have numerically validated our proposed nanosensitive multifractal analysis approach in combination of nsOCT simulation and multifractal analysis in a tissue-like randomized synthetic phantom. This approach demonstrated its applicability to measure depth-resolved nanosensitive multifractality in submicron structure in biological tissue.…”

“…In this regard, our research group actively engaged to develop nanosensitive optical coherence tomography (nsOCT) to detect depth-resolved submicron scale structure with few nanometer accuracy. 16 – 18 We have recently demonstrated label-free nsOCT-based imaging technique to visualize few nanometer structural changes 19 , 20 and its application in cornea crosslinking, 21 and wound healing study. 22 There is a recently demonstrated application of nsOCT for in vivo detection of nanosensitive changes of the human tympanic membrane in otitis media.…”

Noninvasive detection of nanoscale structural changes in cornea associated with cross‐linking treatment

“…Later nsOCT has been used for the study of the nanometer‐scale structural changes of the human tympanic membrane in otitis media . Recently a version of the nsOCT based on the correlation between axial spatial frequency profiles has been published . In this study, oversampling is used to increase the number of points in the reconstructed axial spatial frequency/period profiles.…”

Nanosensitive optical coherence tomography to assess wound healing within the cornea

“…However, sensitivity to structural alterations in time and in space is at nanoscale, as it was shown in references [15,16,23]. Also, spatial frequency domain correlation mapping optical coherence tomography has been described recently [25] , for detection of depth resolved nanoscale structural changes non-invasively based on the principles of nano-sensitive OCT.…”