Author: dborycki@ichf.edu.pl

28.08.2023

Diffuse optics and interferometry

Diffuse optics offers a noninvasive portable approach for examining biological tissues, including the human brain, in vivo [1]. Near-infrared spectroscopy (NIRS) [2] and diffuse correlation spectroscopy (DCS) are the primary diffuse optical modalities [3, 4]. In both approaches, the light illuminates the tissue, and diffusively scattered photons are collected at some distance from the emitter (typically 2-3 cm). NIRS uses the detected signal to estimate optical properties (absorption and scattering), while DCS quantifies the blood flow from temporal changes of the remitted light intensity. Although these methods have been applied to monitor brain oxygenation and blood flow, their most widely adopted versions rely on continuous wavelength (CW) lasers, precluding absolute measures of the optical and dynamical tissue properties [5].

Time-domain NIRS (TD-NIRS) enables quantification of the optical properties through the sample’s photon time-of-flight distribution (TOF distribution) [9-12]. This capability can also be combined with correlation spectroscopy to achieve TOF- (or photon path-length-) resolved blood flow information. So, we could better distinguish photons traversing superficial layers (short TOFs) from photons traveling deep into the brain (long TOFs). Also, given the TOF distribution, we could estimate the optical properties to achieve the absolute blood flow index (BFI), effectively combining the capabilities of TD-NIRS with DCS into a single modality. Such an approach is called time-domain diffuse correlation spectroscopy (TD-DCS) [6, 7].

Though TD-DCS is a powerful technique even applied in clinics, it relies only on light intensity. Therefore, TD-DCS does not enable the detection of the optical phase [8]. The optical phase is accessible in interferometric near-infrared spectroscopy (iNIRS) [9].

Interferometry in brain monitoring

Image: Interferometry in brain monitoring.

The optical phase is accessible in interferometric near-infrared spectroscopy (iNIRS). The iNIRS approach uses interferometry based on a temporally coherent tunable laser to achieve TOF resolution. Specifically, iNIRS supplements the conventional NIRS configuration with the tunable light source and the reference arm. The field remitted from the sample is recombined with the reference field. The beat frequency of the signal encodes photon path lengths (or times-of-flight). Short paths produce lower beat frequencies than long paths. Consequently, the photon time-of-flight distribution can be achieved by inverse-Fourier transforming the recorded signal. However, iNIRS provides much more information through the two-dimensional autocorrelation function (ACF) of the reemitted optical field. In iNIRS, the ACF is measured as a function of time lag with TOF resolution. This two-dimensional measurement (figure below) encodes information about the sample’s absorption, scattering, and blood flow index (BFI).

iNIRS was validated in in liquid phantoms [9], mouse brain [10], and human brain in vivo [11]. However, the original iNIRS (as DCS and TD-DCS) uses single-mode fibers for light collection, requiring integration times of 0.5-1 second. This time frame is too long, precluding the ability to detect rapid blood flow changes in the human brain that could be linked to neural signals.

To overcome those limitations, we recently proposed parallel interferometric near-infrared spectroscopy (πNIRS). In πNIRS we use multi-mode fibers for light collection and a high-speed, two-dimensional camera for light detection. Each camera pixel acts effectively as a single iNIRS channel. So, the processed signals from each pixel are spatially averaged to reduce the overall integration time. Moreover, interferometric detection provides us with the unique capability of accessing complex information (amplitude and phase) about the light remitted from the sample, which with more than 8000 parallel channels, enabled us to sense the cerebral blood flow with only a 10 msec integration time (∼100x faster than conventional iNIRS). We used such an approach to monitor the pulsatile blood flow in a human forearm in vivo. Also, we demonstrated that this approach could monitor the activation of the prefrontal cortex by recording the change in blood flow in the forehead of the subject while he was reading an unknown text [12].

Text: Dawid Borycki, PhD habil.

Team:

Dawid Borycki, PhD habil.

Michał Dąbrowski, PhD

Klaudia Nowacka, MEng

References:

  1. S. Samaei, P. Sawosz, M. Kacprzak, Z. Pastuszak, D. Borycki, and A. Liebert, “Time-domain diffuse correlation spectroscopy (TD-DCS) for noninvasive, depth-dependent blood flow quantification in human tissue in vivo,” Sci Rep 11, 1817 (2021).
  2. D. Borycki, O. Kholiqov, and V. J. Srinivasan, “Interferometric near-infrared spectroscopy directly quantifies optical field dynamics in turbid media,” Optica 3, 1471-1476 (2016).
  3. D. Borycki, O. Kholiqov, S. P. Chong, and V. J. Srinivasan, “Interferometric Near-Infrared Spectroscopy (iNIRS) for determination of optical and dynamical properties of turbid media,” Opt Express 24, 329-354 (2016).
  4. D. Borycki, O. Kholiqov, and V. J. Srinivasan, “Reflectance-mode interferometric near-infrared spectroscopy quantifies brain absorption, scattering, and blood flow index in vivo,” Opt Lett 42, 591-594 (2017).
  5. S. Samaei, K. Nowacka, A. Gerega, Z. Pastuszak, and D. Borycki, “Continuous-wave parallel interferometric near-infrared spectroscopy (CW piNIRS) with a fast two-dimensional camera,” Biomed Opt Express 13, 5753-5774 (2022).
17.01.2023

Spatio-Temporal Optical Coherence Tomography (STOC-T) imaging

Conventional scanning OCT combines time- with confocal gating enabling high-speed, high-resolution cross-sectional imaging of the human retina. Classic OCT, however, does not provide high-resolution en face images of the outer retinal layers due to eye aberrations and the fundamental tradeoff between imaging depth and transverse resolution.

This tradeoff is reduced by a full-field OCT (FF-OCT) method that uses a two-dimensional camera instead of a single-element photodiode. However, an attempt to boost the FF-OCT imaging speed by Fourier-domain (FD) detection resulted in another severe limitation – spatial coherence of the laser generates coherent artifacts, which reduces the spatial resolution and, as shown below, precludes visualization of deep retina layers.

To solve this problem, we developed a new way of controlling the optical phase called STOC (Spatio-Temporal Optical Coherence). Application of STOC to Fourier-domain full-field optical coherence tomography (FD-FF-OCT) is called STOC tomography (STOC-T) or STOC imaging and enabled obtaining in vivo high-resolution, volumetric images of human skin, retina, and cornea at unprecedented speeds.

In STOC imaging, we have extended FD-FF-OCT with a spatial phase modulator (SPM). The SPM dynamically modulates the phase of incident light by generating time-varying transverse mode (TEM) patterns. This is accomplished through the use of active modulators or long multimode optical fiber. The resulting signals are processed and averaged to produce noise-free volume images of the sample. Phase modulation acts here as an additional optical gating mechanism that isolates the signal used to create images. The result is improved images of the sample.

However, the en face images (XY projections) are distorted by eye or sample-induced aberrations. We overcome them in post-processing using the computational aberration correction (CAC). The CAC algorithm proceeds as sketched in the figure. Specifically, we iteratively (in the computer) correct the phase of the spatial spectrum until we optimize the image sharpness metric:

To achieve wide-field retina images, we perform measurements at different locations and then stitch resulting volumes together to render high-resolution, high-fidelity retinal images at different depths (indicated earlier). Specifically, we render the choroid, which was impossible with conventional Fourier-domain FF-OCT (without phase modulation).

Text: Dawid Borycki, PhD

Team:

Egidijus Auksorius

Dawid Borycki

Piotr Węgrzyn

Kamil Liżewski

Sławomir Tomczewski

Maciej Wojtkowski

References:

  1. M. Wojtkowski, P. Stremplewski, E. Auksorius, and D. Borycki, “Spatio-Temporal Optical Coherence Imaging – a new tool for in vivo microscopy,” Photonics Letters of Poland 11, 45-50 (2019). https://photonics.pl/PLP/index.php/letters/article/view/11-15
  2. Borycki, D. et al., Control of the optical field coherence by spatiotemporal light modulation, Opt. Lett., 2013 38(22): p. 4817-4820.
  3. Borycki, D., et al., Spatiotemporal optical coherence (STOC) manipulation suppresses coherent cross-talk in full-field swept-source optical coherence tomography. Biomed Opt Express, 2019. 10(4): p. 2032-2054.
  4. Stremplewski, P., et al., In vivo volumetric imaging by crosstalk-free full-field OCT. Optica, 2019. 6(5): p. 608-617.
  5. Auksorius, E., et al., Crosstalk-free volumetric in vivo imaging of a human retina with Fourier-domain full-field optical coherence tomography. Biomed Opt Express, 2019. 10(12): p. 6390-6407.
  6. Auksorius, E., et al., In vivo imaging of the human cornea with high-speed and high-resolution Fourier-domain full-field optical coherence tomography. Biomed Opt Express, 2020. 11(5): p. 2849-2865.
  7. Borycki, D., et al., Computational aberration correction in spatiotemporal optical coherence (STOC) imaging. Opt Lett, 2020. 45(6): p. 1293-1296.
  8. Egidijus Auksorius, Dawid Borycki, Maciej Wojtkowski, Multimode fiber enables control of spatial coherence in Fourier-domain full-field optical coherence tomography for in vivo corneal imaging, Opt Lett, 2021. 46(6): p. 1413-1416.
  9. Auksorius E., et al., Spatio-Temporal Optical Coherence Tomography provides advanced imaging of the human retina and choroid, arXiv preprint arXiv:2107.10672 (2021).
  10. Auksorius E., Fourier-domain full-field optical coherence tomography with real-time axial imaging, Opt Lett, 2021., Vol. 46(18): p. 4478-4481.
  11. Auksorius E., et al., Multimode fiber as a tool to reduce cross talk in Fourier-domain full-field optical coherence tomography. Opt Lett, 2022. 47(4): p. 838-841.
  12. Tomczewski S., et al., Light-adapted flicker optoretinograms captured with a spatio-temporal optical coherence-tomography (STOC-T) system. Biomed Opt Express, 2022 13(4): p. 2186-2201.
  13. Auksorius, E., et al., Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex. iScience, 2022 25(12) 105513.

18.07.2022

Maestro project funded by NCN: discovering a new STOC-T method for imaging

In this project, we proposed a new approach to control the coherence of light used in imaging. This novel idea, which we verified experimentally, was used to image the skin, cornea and retina of the human eye in vivo. As a result, we created a new method for imaging biological objects, which we called spatio-temporal optical coherence tomography (STOC-T).

In our work, we carried out basic research by introducing a specific model of light scattering using the statistical properties of light (spatial and temporal coherence). We proposed experiments to verify the correctness of the introduced model. A laboratory set-up was also created based on the experimental setup demonstrating the capabilities of the new method in biomedical imaging. We demonstrated the feasibility of the new method for in vivo imaging, which confirmed the validity of the theses put forth in this project. 

We demonstrated the practical effects of our research by imaging the human eye. For corneal imaging, with STOC-T we were able to significantly increase the exposure time without exposing the deeper, delicate retina. At the same time, it allows us to maintain a high power density of light so that we can see very little backscatter from the cornea. In addition, the volumetric nature of the collected data allowed us to optically “flatten” the curvature of the cornea and obtain exceptionally sharp images of all the layers that make up the cornea across the entire cross-section. This is not an easy art, because the transparency of the cornea, although it allows one to look inside the eye, does not at all facilitate the examination of the eye itself.

In the case of retinal imaging, we have shown that we can penetrate deeper into areas under the retina that previously could not be imaged. In particular, using STOC-T for retinal imaging has allowed us to reconstruct the morphology of the cones in the human eye. In addition, by using a super-fast camera that captures tens of thousands of frames per second, we can capture images instantly.  Our STOC-T method allows us to capture the retina in a fraction of a second and record all its depth in extremely high, unprecedented resolution. The patient doesn’t even have time to blink, and his eye is already imaged, and with an accuracy that allows us to see even individual cells. And even if the subject were to move his or her eye, the device, or rather the computer, would compensate for the movement, still producing a sharp image. In addition, our camera has no moving parts, and thanks to the phase modulation of the laser beam, we can use higher powers without harming the deeper tissues of the eye.

Text: prof. Maciej Wojtkowski and dr Dawid Borycki