Enhancing spatiotemporal focusing of light deep inside scattering media with time-gated reflection matrix

Enhancing spatiotemporal focusing of light deep inside scattering media with time-gated reflection matrix

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ABSTRACT Time-gated reflection matrix (RM) has been successfully used for optical imaging deep inside scattering media. Recently, this method was extended to enhance the spatiotemporal focusing of light ultra-deep inside scattering media. This is achieved by calibrating the decomposition of the RM with the Tikhonov regularization parameter to convert multiply scattered photons that share the same time of flight with the singly scattered photons into singly scattered photons. Such a capability suggests a reshaping to the interaction mechanism between light and scattering media, which may benefit or inspire wide optical applications that desire enhanced spatiotemporal focusing of light at depths inside scattering media. Light is playing an increasingly important role in biomedicine from imaging, sensing, therapy, stimulation, to manipulation. The applications, however, have seen limitations at depths in biological tissue and tissue-like scattering media, where photons experience multiple scattering events due to the spatial inhomogeneities of refractive index. It is possible to exploit multiply scattered (MS) photons for imaging in some techniques, such as diffuse optical tomography1, ultrasound-modulated optical tomography2, and photoacoustic tomography3, albeit with compromised resolution. To achieve a high resolution, singly scattered (SS) photons (also known as ballistic photons) that only probe the in situ target need to be screened out from the predominant MS photons4. Endeavors to this purpose can be divided into two categories. In the first category, SS photons are spatially filtered out from MS photons, and the representative technology is confocal microscopy where a small pinhole aperture only allows fluorescence emission from the desired focal plane to pass through5. In the second category, SS photons are temporally filtered out from MS photons, as demonstrated in optical coherence tomography (OCT) based on time-gating technique6. For both categories, the imaging depth are still restricted to ~1 mm beneath tissue surface because the number of SS photons decreases exponentially with optical thickness7. Inspired by the transmission matrix approach8 and random matrix model in ultrasound imaging through strongly scattering media9, a time-gated reflection matrix (RM)-based method called “Smart OCT” was proposed to enhance the imaging depth10,11. In this implementation, a singular value decomposition of the RM was used to screen out most of the MS photons. Despite of that, MS photons with the same time of flight as the SS photons were still dominant for targets located deeper than a few scattering mean free paths (SMFP). The common wisdom is that the residual MS photons have impeded the imaging quality and hence in order to yield high resolution, they need to be removed or suppressed through methods such as iteration12 or a spatial input–output correlation11. Most recently, in _Light: Science & Applications_, Cao et al. suggest that the part of MS photons that share the same time of flight as the SS photons can be utilized and converted into SS photons to enhance in situ optical energy delivery spatially and temporally13. In this work, the main goal is to retrieve singular values of the part of MS photons with the same time of flight as the SS photons. First, a coherent gating is created inside the scattering medium using an ultra-short pulse beam. The back-reflected photons from the scattering medium can be divided into three types: SS photons (ξSS), MS2 photons (ξMS2) sharing the same time of flight as the SS photons, and other remaining MS photons (ξMS1). After the construction of RM, a singular value decomposition (also termed as “time reversal operator”) is applied to the RM (R): \(R = U\Sigma V^{\rm T}\), where _T_ represents transpose, Σ is a diagonal matrix containing the real positive singular values in a descending order \(\sigma _1 \,>\, \sigma _2 \,>\, \cdots \,>\, \sigma _N\) (_N_ is the number of the singular values in Σ), _U_ and _V_ are two unitary matrices whose columns correspond to the input and output mode, respectively. Singular values in the diagonal matrix corresponding to the SS, MS2, and MS1 photons are also in a descending order. Practically, Σ is not actually a standard diagonal matrix and it cannot be used to filter out the MS2 photons. Thus, matrix\(R^{\dagger} R = USV^T\)(\({\dagger}\) represents conjugate transpose) that has a more standard diagonal matrix will be taken into consideration in the inversion process. As a result, _S_ is a diagonal matrix containing the square of the singular values (\(\sigma _i^2\)) of the diagonal matrix Σ. Note that however, this operator is very labile in ultra-deep position due to the noise and there are a lot of non-zero elements at adjacent positions of diagonal line of the diagonal matrix. To reduce the influence of noise, the Tikhonov regularization parameter14 is introduced to create a calibration matrix to optimize the reversal results in the inversion process. The calibrated matrix is \(C = UFSV^T\), where _F_ is a diagonal matrix with diagonal elements \(\alpha _i = \sigma _i^2{{{\mathrm{/}}}}\left( {\sigma _i^2 + \lambda ^2} \right)\) (_λ_ is a variance ranging from 10−8 to 108 for different penetration depths). During the selection of _λ_, there is a tradeoff between the retrieval number of eigenstates and the retrieval accuracy rate of each eigenstate. In the optimization process, the target is to make the output field from calibrated matrix close to the measured output field. After successfully retrieving singular values of the SS and MS2 photons, the desired wavefront can be acquired, and the corresponding phase pattern will be loaded on the spatial light modulator. At last, the optical energy delivery can be enhanced by a magnitude at an ultra-deep (~14.4 SMFP) position. As demonstrated in this study, the optical energy delivery can be enhanced by shaping some part of the MS photons into SS photons, it can be potentially used to increase the signal-to-noise ratio (SNR) or the imaging depth of “Smart OCT”. Fundamentally, optical scattering arises from the interaction between photons and matter. Therefore, shaping MS photons into SS photons suggests that the light-matter interaction for the particular photons is changed and furtherly, the underlying physical mechanism can be reshaped from the conventional realm. This method may also benefit or inspire other optical applications that desire enhanced spatiotemporal focusing of light at depths inside scattering media, such as selective optogenetics15 and laser microsurgery16, etc. REFERENCES * Boas, D. A. et al. Imaging the body with diffuse optical tomography. _IEEE Signal Process. Mag._ 18, 57–75 (2001). Article  ADS  Google Scholar  * Lai, P. X., Xu, X. & Wang, L. V. Ultrasound-modulated optical tomography at new depth. _J. Biomed. Opt._ 17, 066006 (2012). Article  ADS  Google Scholar  * Wang, L. V. & Yao, J. J. A practical guide to photoacoustic tomography in the life sciences. _Nat. Methods_ 13, 627–638 (2016). Article  Google Scholar  * Park, J. H. et al. Perspective: wavefront shaping techniques for controlling multiple light scattering in biological tissues: toward in vivo applications. _APL Photonics_ 3, 100901 (2018). Article  ADS  Google Scholar  * Pawley, J. Handbook of biological confocal microscopy (Springer Science & Business Media, 2006). * Schuman, J. S. et al. Optical coherence tomography: a new tool for glaucoma diagnosis. _Curr. Opin. Ophthalmol._ 6, 89–95 (1995). Article  Google Scholar  * Wang, L. V. & Wu, H. I. Biomedical optics: principles and imaging (John Wiley & Sons, 2012). * Popoff, S. M. et al. Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media. _Phys. Rev. Lett._ 104, 100601 (2010). Article  ADS  Google Scholar  * Aubry, A. & Derode, A. Random matrix theory applied to acoustic backscattering and imaging in complex media. _Phys. Rev. Lett._ 102, 084301 (2009). Article  ADS  Google Scholar  * Badon, A. et al. Smart optical coherence tomography for ultra-deep imaging through highly scattering media. _Sci. Adv._ 2, e1600370 (2016). Article  ADS  Google Scholar  * Kang, S. et al. Imaging deep within a scattering medium using collective accumulation of single-scattered waves. _Nat. Photonics_ 9, 253–258 (2015). Article  ADS  Google Scholar  * Popoff, S. M. et al. Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis. _Phys. Rev. Lett._ 107, 263901 (2011). Article  ADS  Google Scholar  * Cao, J. et al. Enhance the delivery of light energy ultra-deep into turbid medium by controlling multiple scattering photons to travel in open channels. _Light Sci. Appl._ 11, 108 (2022). Article  ADS  Google Scholar  * Tikhonov, A. N. Solution of incorrectly formulated problems and the regularization method. _Sov. Math. Dokl._ 4, 1035–1038 (1963). MATH  Google Scholar  * Zhong, T. T. et al. Optically selective neuron stimulation with a wavefront shaping-empowered multimode fiber. _Adv. Photonics Res._ 3, 2100231 (2022). Article  Google Scholar  * Poorten, V. V. et al. Current indications for adjuvant treatment following transoral laser microsurgery of early and intermediate laryngeal cancer. _Curr. Opin. Otolaryngol. Head Neck Surg._ 29, 79–85 (2021). Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China Zhipeng Yu, Huanhao Li, Tianting Zhong & Puxiang Lai * Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen, China Zhipeng Yu, Huanhao Li, Tianting Zhong & Puxiang Lai * Photonics Research Institute, The Hong Kong Polytechnic University, Hong Kong SAR, China Puxiang Lai Authors * Zhipeng Yu View author publications You can also search for this author inPubMed Google Scholar * Huanhao Li View author publications You can also search for this author inPubMed Google Scholar * Tianting Zhong View author publications You can also search for this author inPubMed Google Scholar * Puxiang Lai View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Puxiang Lai. RIGHTS AND PERMISSIONS OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yu, Z., Li, H., Zhong, T. _et al._ Enhancing spatiotemporal focusing of light deep inside scattering media with Time-Gated Reflection Matrix. _Light Sci Appl_ 11, 167 (2022). https://doi.org/10.1038/s41377-022-00858-w Download citation * Published: 01 June 2022 * DOI: https://doi.org/10.1038/s41377-022-00858-w SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT Time-gated reflection matrix (RM) has been successfully used for optical imaging deep inside scattering media. Recently, this method was extended to enhance the spatiotemporal


focusing of light ultra-deep inside scattering media. This is achieved by calibrating the decomposition of the RM with the Tikhonov regularization parameter to convert multiply scattered


photons that share the same time of flight with the singly scattered photons into singly scattered photons. Such a capability suggests a reshaping to the interaction mechanism between light


and scattering media, which may benefit or inspire wide optical applications that desire enhanced spatiotemporal focusing of light at depths inside scattering media. Light is playing an


increasingly important role in biomedicine from imaging, sensing, therapy, stimulation, to manipulation. The applications, however, have seen limitations at depths in biological tissue and


tissue-like scattering media, where photons experience multiple scattering events due to the spatial inhomogeneities of refractive index. It is possible to exploit multiply scattered (MS)


photons for imaging in some techniques, such as diffuse optical tomography1, ultrasound-modulated optical tomography2, and photoacoustic tomography3, albeit with compromised resolution. To


achieve a high resolution, singly scattered (SS) photons (also known as ballistic photons) that only probe the in situ target need to be screened out from the predominant MS photons4.


Endeavors to this purpose can be divided into two categories. In the first category, SS photons are spatially filtered out from MS photons, and the representative technology is confocal


microscopy where a small pinhole aperture only allows fluorescence emission from the desired focal plane to pass through5. In the second category, SS photons are temporally filtered out from


MS photons, as demonstrated in optical coherence tomography (OCT) based on time-gating technique6. For both categories, the imaging depth are still restricted to ~1 mm beneath tissue


surface because the number of SS photons decreases exponentially with optical thickness7. Inspired by the transmission matrix approach8 and random matrix model in ultrasound imaging through


strongly scattering media9, a time-gated reflection matrix (RM)-based method called “Smart OCT” was proposed to enhance the imaging depth10,11. In this implementation, a singular value


decomposition of the RM was used to screen out most of the MS photons. Despite of that, MS photons with the same time of flight as the SS photons were still dominant for targets located


deeper than a few scattering mean free paths (SMFP). The common wisdom is that the residual MS photons have impeded the imaging quality and hence in order to yield high resolution, they need


to be removed or suppressed through methods such as iteration12 or a spatial input–output correlation11. Most recently, in _Light: Science & Applications_, Cao et al. suggest that the


part of MS photons that share the same time of flight as the SS photons can be utilized and converted into SS photons to enhance in situ optical energy delivery spatially and temporally13.


In this work, the main goal is to retrieve singular values of the part of MS photons with the same time of flight as the SS photons. First, a coherent gating is created inside the scattering


medium using an ultra-short pulse beam. The back-reflected photons from the scattering medium can be divided into three types: SS photons (ξSS), MS2 photons (ξMS2) sharing the same time of


flight as the SS photons, and other remaining MS photons (ξMS1). After the construction of RM, a singular value decomposition (also termed as “time reversal operator”) is applied to the RM


(R): \(R = U\Sigma V^{\rm T}\), where _T_ represents transpose, Σ is a diagonal matrix containing the real positive singular values in a descending order \(\sigma _1 \,>\, \sigma _2


\,>\, \cdots \,>\, \sigma _N\) (_N_ is the number of the singular values in Σ), _U_ and _V_ are two unitary matrices whose columns correspond to the input and output mode,


respectively. Singular values in the diagonal matrix corresponding to the SS, MS2, and MS1 photons are also in a descending order. Practically, Σ is not actually a standard diagonal matrix


and it cannot be used to filter out the MS2 photons. Thus, matrix\(R^{\dagger} R = USV^T\)(\({\dagger}\) represents conjugate transpose) that has a more standard diagonal matrix will be


taken into consideration in the inversion process. As a result, _S_ is a diagonal matrix containing the square of the singular values (\(\sigma _i^2\)) of the diagonal matrix Σ. Note that


however, this operator is very labile in ultra-deep position due to the noise and there are a lot of non-zero elements at adjacent positions of diagonal line of the diagonal matrix. To


reduce the influence of noise, the Tikhonov regularization parameter14 is introduced to create a calibration matrix to optimize the reversal results in the inversion process. The calibrated


matrix is \(C = UFSV^T\), where _F_ is a diagonal matrix with diagonal elements \(\alpha _i = \sigma _i^2{{{\mathrm{/}}}}\left( {\sigma _i^2 + \lambda ^2} \right)\) (_λ_ is a variance


ranging from 10−8 to 108 for different penetration depths). During the selection of _λ_, there is a tradeoff between the retrieval number of eigenstates and the retrieval accuracy rate of


each eigenstate. In the optimization process, the target is to make the output field from calibrated matrix close to the measured output field. After successfully retrieving singular values


of the SS and MS2 photons, the desired wavefront can be acquired, and the corresponding phase pattern will be loaded on the spatial light modulator. At last, the optical energy delivery can


be enhanced by a magnitude at an ultra-deep (~14.4 SMFP) position. As demonstrated in this study, the optical energy delivery can be enhanced by shaping some part of the MS photons into SS


photons, it can be potentially used to increase the signal-to-noise ratio (SNR) or the imaging depth of “Smart OCT”. Fundamentally, optical scattering arises from the interaction between


photons and matter. Therefore, shaping MS photons into SS photons suggests that the light-matter interaction for the particular photons is changed and furtherly, the underlying physical


mechanism can be reshaped from the conventional realm. This method may also benefit or inspire other optical applications that desire enhanced spatiotemporal focusing of light at depths


inside scattering media, such as selective optogenetics15 and laser microsurgery16, etc. REFERENCES * Boas, D. A. et al. Imaging the body with diffuse optical tomography. _IEEE Signal


Process. Mag._ 18, 57–75 (2001). Article  ADS  Google Scholar  * Lai, P. X., Xu, X. & Wang, L. V. Ultrasound-modulated optical tomography at new depth. _J. Biomed. Opt._ 17, 066006


(2012). Article  ADS  Google Scholar  * Wang, L. V. & Yao, J. J. A practical guide to photoacoustic tomography in the life sciences. _Nat. Methods_ 13, 627–638 (2016). Article  Google


Scholar  * Park, J. H. et al. Perspective: wavefront shaping techniques for controlling multiple light scattering in biological tissues: toward in vivo applications. _APL Photonics_ 3,


100901 (2018). Article  ADS  Google Scholar  * Pawley, J. Handbook of biological confocal microscopy (Springer Science & Business Media, 2006). * Schuman, J. S. et al. Optical coherence


tomography: a new tool for glaucoma diagnosis. _Curr. Opin. Ophthalmol._ 6, 89–95 (1995). Article  Google Scholar  * Wang, L. V. & Wu, H. I. Biomedical optics: principles and imaging


(John Wiley & Sons, 2012). * Popoff, S. M. et al. Measuring the transmission matrix in optics: an approach to the study and control of light propagation in disordered media. _Phys. Rev.


Lett._ 104, 100601 (2010). Article  ADS  Google Scholar  * Aubry, A. & Derode, A. Random matrix theory applied to acoustic backscattering and imaging in complex media. _Phys. Rev. Lett._


102, 084301 (2009). Article  ADS  Google Scholar  * Badon, A. et al. Smart optical coherence tomography for ultra-deep imaging through highly scattering media. _Sci. Adv._ 2, e1600370


(2016). Article  ADS  Google Scholar  * Kang, S. et al. Imaging deep within a scattering medium using collective accumulation of single-scattered waves. _Nat. Photonics_ 9, 253–258 (2015).


Article  ADS  Google Scholar  * Popoff, S. M. et al. Exploiting the time-reversal operator for adaptive optics, selective focusing, and scattering pattern analysis. _Phys. Rev. Lett._ 107,


263901 (2011). Article  ADS  Google Scholar  * Cao, J. et al. Enhance the delivery of light energy ultra-deep into turbid medium by controlling multiple scattering photons to travel in open


channels. _Light Sci. Appl._ 11, 108 (2022). Article  ADS  Google Scholar  * Tikhonov, A. N. Solution of incorrectly formulated problems and the regularization method. _Sov. Math. Dokl._ 4,


1035–1038 (1963). MATH  Google Scholar  * Zhong, T. T. et al. Optically selective neuron stimulation with a wavefront shaping-empowered multimode fiber. _Adv. Photonics Res._ 3, 2100231


(2022). Article  Google Scholar  * Poorten, V. V. et al. Current indications for adjuvant treatment following transoral laser microsurgery of early and intermediate laryngeal cancer. _Curr.


Opin. Otolaryngol. Head Neck Surg._ 29, 79–85 (2021). Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomedical Engineering, The


Hong Kong Polytechnic University, Hong Kong SAR, China Zhipeng Yu, Huanhao Li, Tianting Zhong & Puxiang Lai * Shenzhen Research Institute, The Hong Kong Polytechnic University, Shenzhen,


China Zhipeng Yu, Huanhao Li, Tianting Zhong & Puxiang Lai * Photonics Research Institute, The Hong Kong Polytechnic University, Hong Kong SAR, China Puxiang Lai Authors * Zhipeng Yu


View author publications You can also search for this author inPubMed Google Scholar * Huanhao Li View author publications You can also search for this author inPubMed Google Scholar *


Tianting Zhong View author publications You can also search for this author inPubMed Google Scholar * Puxiang Lai View author publications You can also search for this author inPubMed Google


Scholar CORRESPONDING AUTHOR Correspondence to Puxiang Lai. RIGHTS AND PERMISSIONS OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License, which


permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to


the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless


indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or


exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Reprints


and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yu, Z., Li, H., Zhong, T. _et al._ Enhancing spatiotemporal focusing of light deep inside scattering media with Time-Gated Reflection


Matrix. _Light Sci Appl_ 11, 167 (2022). https://doi.org/10.1038/s41377-022-00858-w Download citation * Published: 01 June 2022 * DOI: https://doi.org/10.1038/s41377-022-00858-w SHARE THIS


ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard


Provided by the Springer Nature SharedIt content-sharing initiative