wavefront measurement using computational adaptive...

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Wavefront measurement using computational adaptive optics FREDRICK A. SOUTH, 1,2 YUAN-ZHI LIU, 1,2 ANDREW J. BOWER, 1,2 YANG XU, 1,2 P. SCOTT CARNEY , 3 AND STEPHEN A. BOPPART 1,2,4,5, * 1 Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA 2 Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA 3 The Institute of Optics, University of Rochester, Rochester, New York 14627, USA 4 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA 5 Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA *Corresponding author: [email protected] Received 3 October 2017; revised 23 January 2018; accepted 25 January 2018; posted 25 January 2018 (Doc. ID 308342); published 28 February 2018 In many optical imaging applications, it is necessary to correct for aberrations to obtain high quality images. Optical coherence tomography (OCT) provides access to the amplitude and phase of the backscattered optical field for three-dimensional (3D) imaging samples. Computational adaptive optics (CAO) modifies the phase of the OCT data in the spatial frequency domain to correct optical aberrations without using a deformable mirror, as is commonly done in hardware-based adaptive optics (AO). This provides improvement of image quality through- out the 3D volume, enabling imaging across greater depth ranges and in highly aberrated samples. However, the CAO aberration correction has a complicated relation to the imaging pupil and is not a direct measurement of the pupil aberrations. Here we present new methods for recovering the wavefront aberrations directly from the OCT data without the use of hardware adaptive optics. This enables both computational measurement and correction of optical aberrations. © 2018 Optical Society of America OCIS codes: (100.5090) Phase-only filters; (110.3175) Interferometric imaging; (110.3200) Inverse scattering; (110.4500) Optical coherence tomography; (110.1758) Computational imaging. https://doi.org/10.1364/JOSAA.35.000466 1. INTRODUCTION Measurement and correction of aberrations is often an important step in obtaining high-resolution images in optical microscopy [1]. In some cases the imaging optics may be imperfect due to physical limitations or design constraints. Additionally, imaging below the surface of biological tissue is complicated by sample- induced aberrations, which arise from the spatially varying refrac- tive index of the tissue. In the case of living or dynamic samples, these aberrations can also be time varying. Therefore, it is nec- essary to devise a strategy to determine and compensate for the wavefront aberrations to obtain a diffraction-limited image. Typically this is done using adaptive optics (AO) compo- nents, such as a wavefront sensor and deformable mirror, to measure and correct the aberrated optical wavefront. However, these additional hardware components can be expen- sive and difficult to align and maintain. The hardware aberra- tion correction is only optimized for a particular location within the 3D imaging volume, and calibration error, fitting error, measurement error, and bandwidth error all contribute to the presence of uncorrected aberrations [2]. Alternatively, interferometric detection provides access to both the amplitude and the phase of the backscattered light. Access to this phase information provides computational control of the full complex wavefront, allowing computational image formation based upon models of the imaging experi- ment. In this way, aberrations can be corrected postacquisition without the need for adaptive optics hardware. Optical coherence tomography (OCT) measures a broadband interferometric signal to reconstruct the three-dimensional struc- ture of scattering samples from backscattered light [3]. Since its invention, OCT has become an invaluable tool in medicine and biology. It is now the standard of care for retinal imaging and has been applied in various other clinical settings, as well as in non- biological materials imaging [4]. Computational adaptive optics (CAO) is a computational imaging method that modifies the spatial frequency content of the OCT data to correct for optical aberrations [57]. CAO has primarily been used for aberration correction, and it has been demonstrated for imaging of tissues such as in vivo skin and ex vivo brain [8], as well as the living human retina [911]. 466 Vol. 35, No. 3 / March 2018 / Journal of the Optical Society of America A Research Article 1084-7529/18/030466-08 Journal © 2018 Optical Society of America

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Page 1: Wavefront measurement using computational adaptive opticsbiophotonics.illinois.edu/sites/default/files/josaa-35-3-466_0.pdfWavefront measurement using computational adaptive optics

Wavefront measurement using computationaladaptive opticsFREDRICK A. SOUTH,1,2 YUAN-ZHI LIU,1,2 ANDREW J. BOWER,1,2 YANG XU,1,2 P. SCOTT CARNEY,3

AND STEPHEN A. BOPPART1,2,4,5,*1Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA2Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA3The Institute of Optics, University of Rochester, Rochester, New York 14627, USA4Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA5Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA*Corresponding author: [email protected]

Received 3 October 2017; revised 23 January 2018; accepted 25 January 2018; posted 25 January 2018 (Doc. ID 308342);published 28 February 2018

In many optical imaging applications, it is necessary to correct for aberrations to obtain high quality images.Optical coherence tomography (OCT) provides access to the amplitude and phase of the backscattered opticalfield for three-dimensional (3D) imaging samples. Computational adaptive optics (CAO) modifies the phase ofthe OCT data in the spatial frequency domain to correct optical aberrations without using a deformable mirror, asis commonly done in hardware-based adaptive optics (AO). This provides improvement of image quality through-out the 3D volume, enabling imaging across greater depth ranges and in highly aberrated samples. However, theCAO aberration correction has a complicated relation to the imaging pupil and is not a direct measurement of thepupil aberrations. Here we present new methods for recovering the wavefront aberrations directly from the OCTdata without the use of hardware adaptive optics. This enables both computational measurement and correctionof optical aberrations. © 2018 Optical Society of America

OCIS codes: (100.5090) Phase-only filters; (110.3175) Interferometric imaging; (110.3200) Inverse scattering; (110.4500) Optical

coherence tomography; (110.1758) Computational imaging.

https://doi.org/10.1364/JOSAA.35.000466

1. INTRODUCTION

Measurement and correction of aberrations is often an importantstep in obtaining high-resolution images in optical microscopy[1]. In some cases the imaging optics may be imperfect due tophysical limitations or design constraints. Additionally, imagingbelow the surface of biological tissue is complicated by sample-induced aberrations, which arise from the spatially varying refrac-tive index of the tissue. In the case of living or dynamic samples,these aberrations can also be time varying. Therefore, it is nec-essary to devise a strategy to determine and compensate for thewavefront aberrations to obtain a diffraction-limited image.

Typically this is done using adaptive optics (AO) compo-nents, such as a wavefront sensor and deformable mirror,to measure and correct the aberrated optical wavefront.However, these additional hardware components can be expen-sive and difficult to align and maintain. The hardware aberra-tion correction is only optimized for a particular location withinthe 3D imaging volume, and calibration error, fitting error,measurement error, and bandwidth error all contribute tothe presence of uncorrected aberrations [2].

Alternatively, interferometric detection provides access toboth the amplitude and the phase of the backscattered light.Access to this phase information provides computationalcontrol of the full complex wavefront, allowing computationalimage formation based upon models of the imaging experi-ment. In this way, aberrations can be corrected postacquisitionwithout the need for adaptive optics hardware.

Optical coherence tomography (OCT)measures a broadbandinterferometric signal to reconstruct the three-dimensional struc-ture of scattering samples from backscattered light [3]. Since itsinvention, OCT has become an invaluable tool in medicine andbiology. It is now the standard of care for retinal imaging and hasbeen applied in various other clinical settings, as well as in non-biological materials imaging [4]. Computational adaptive optics(CAO) is a computational imaging method that modifies thespatial frequency content of the OCT data to correct for opticalaberrations [5–7]. CAO has primarily been used for aberrationcorrection, and it has been demonstrated for imaging of tissuessuch as in vivo skin and ex vivo brain [8], as well as the livinghuman retina [9–11].

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In some cases, it may also be desirable to perform computa-tional aberration measurements. For example, aberration mea-surements can be used to determine the flaws in an imagingsystem design, and three-dimensional mapping of aberrationsin biological tissue can be used to optimize system parameters[12]. Wavefront measurement can also be medically relevant, asin aberrometry of the human eye [2], and sample-inducedaberrations may prove to be a source of contrast for varioustissue types.

CAO acts on OCT data in the Fourier domain by a phase-only filter. However, due to the double-pass nature of the OCTimaging experiment, this CAO correction filter does notdirectly correspond to the aberrations of the imaging pupil.Previous work has attempted to directly compare the CAO cor-rection filter with the true wavefront measurement acquiredwith a Shack–Hartmann wavefront sensor [13]. However, thecomplicated relationship between the pupil wavefront and theCAO correction filter was only explored for defocus, leavingaberrations unaddressed.

We have developed new methods for recovering the wave-front aberrations directly from the OCT data itself, without theneed for a wavefront sensor or deformable mirror. These meth-ods have been tested in simulation to determine sensitivity toinduced aberrations, as well as with cross talk between aberra-tions. The results are shown to compare favorably with previ-ously published hardware adaptive optics wavefront sensingmeasurements.

2. COMPUTATIONAL ADAPTIVE OPTICS MODEL

A. OCT Signal Acquisition

The OCT signal is obtained through interference of backscat-tered light from the sample with a coherent reference beam,providing complex-valued data for each point within the im-aged volume. An illustration of the imaging setup is givenin Fig. 1. Detailed derivations can be found in [14,15] andare followed closely here. The complex-valued spectral domainOCT signal is acquired as a function of wavenumber, k, ateach transverse scan location, �x; y� � �rk�. The focus remainsfixed at a particular depth, z0. The signal S�rk; k� can then bewritten as

S�rk; k� �ZZ

h�r 0k − rk; z 0 − z0; k�η�r 0k; z 0�d2r 0kdz 0; (1)

which is the convolution of the system point spread function,h�rk; z; k�, with the sample susceptibility, η�rk; z�.

The system point spread function is given as

h�rk; z; k� � k2jP�k�j2f �−rk; z; k�g�−rk; z; k�; (2)

which is the multiplication of the input and output beam pro-files, f �rk; z; k� and g�rk; z; k�, along with the power spectrumof the laser source, jP�k�j2. In a standard OCT imaging system,the input and output imaging pupils are the same. The beamprofile can be described by a plane wave representation,G�qk; k�. Therefore, both the input and output beam profilesare given by

g�rk; z; k� �Z

G�qk; k�eiqk·rkeikz �qk ;k�zd2qk; (3)

where kz�qk; k� �ffiffiffiffiffiffiffiffiffiffiffiffiffiffik2 − qk

q. At the focus z � 0, the beam

profile is given by the Fourier transform of the imaging pupilG�qk; k�.

The signal representation in Eq. (1) can be simplified bytransforming to the spatial frequency domain,

S�qk; k� �Z

h�qk; z 0 − z0; k�η�qk; z 0�dz 0; (4)

where the (∼) denotes the two-dimensional Fourier transformover the lateral scanning dimension. The transfer function isthen given as the transverse convolution, denoted as �k, ofthe input and output pupil functions in the spatial frequencydomain,

h�qk; z; k� � k2jP�k�j2g�−qk; z; k� �k g�−qk; z; k�: (5)

The spatial frequency domain representation of the pupilfunction is

g�qk; z; k� � G�qk; k�eikz �qk ;k�z ; (6)

which is the imaging pupil G�qk; k� propagated a distance zaway from the focus. Aberrations are modeled as phase varia-tions in the imaging pupil, G�qk; k�. This leads to an aberratedsystem transfer function via the autoconvolution operation, asindicated in Eq. (5).

B. Aberration Correction

In computational adaptive optics, the aberrated system transferfunction is corrected by multiplication with a phase-only filterin the spatial frequency domain,

SAC�qk; k� � HAC�qk; k�SA�qk; k�; (7)

where

HAC�qk; k� � e−iϕh�qk ;k�; (8)

and where subscript A indicates the aberrated data, and sub-script AC indicates the aberration correction filter and aberra-tion corrected data. The phase term ϕh�qk; k� corresponds tothe phase of the aberrated system transfer function. Under theassumption that the deviation from the central wavenumber isnot too large, meaning �Δk∕kc�2 is negligible [7], the aberra-tion correction filter can be evaluated at the central wavelengthand applied at each depth plane, zi, as

SAC�qk; zi� � HAC�qk; zi�SA�qk; zi�; (9)

where

Fig. 1. Illustration of the OCT imaging setup. The imaging beampasses through the pupil G�qk; k� and illuminates the sample withfield g�rk; z; k�. The light is backscattered from the sample η�rk; z�and is collected through the same imaging pupil.

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HAC�qk; zi� � e−iϕh�qk ;zi�: (10)

This filter can be determined through a variety of proce-dures including image sharpness optimization, the guide-starmethod, and the split-aperture method [5,16,17]. These areanalogous to sensorless AO, guide-star optimization, and theShack–Hartmann wavefront sensor in hardware AO. In anycase, the filter corresponds to the double-pass system transferfunction.

3. METHODS FOR WAVEFRONTMEASUREMENT

A generic pupil function has both amplitude and phase,

G�qk; zi� � jG�qk; zi�jeiϕg �qk ;zi�; (11)

where the goal of wavefront measurement is to determine thephase aberrations of the imaging pupil, ϕg . Through the CAOaberration correction procedure, the phase ϕh is obtained. Therelationship between the pupil and system transfer function is,to within a constant,

H �qk; zi� � G�qk; zi� � G�qk; zi�; (12)

where the propagation away from focus in Eq. (6) has beenabsorbed into the function G�qk; zi�. The following sectionsoutline methods for estimating the aberrations of the pupilphase. While the first two methods attempt to estimate ϕggiven ϕh, the final method estimates ϕg directly.

A. Asymptotic Method

A computational method termed interferometric syntheticaperture microscopy (ISAM) solves the OCT inverse problemthrough asymptotic approximations taken near and far fromthe focus [14,18]. Although these approximations were per-formed with an unaberrated imaging pupil, it is possible thatthey may hold for small wavefront aberrations. The asymptoticapproximations taken in ISAM allow the complex autoconvo-lution to be represented as a multiplication of stretched pupilfunctions,

H �qk; zi� ≈ G�qk∕2; zi� × G�qk∕2; zi�: (13)

For the generic pupil function of Equation (11), the corre-sponding transfer function under the asymptotic approxima-tion is

H �qk; zi� ≈ jG�qk∕2; zi�j2ei2ϕg �qk∕2;zi�: (14)

The relationship between the strength of aberrations is thensimply a factor of two.

The phase aberrations are often represented as a weightedsum of Zernike polynomials (see Appendix A). The pupil phasecan then be represented by

ϕg�qk; zi� �Xncn�zi�Zn�sk�; (15)

where cn is the root-mean-square (RMS) variation of each cor-responding Zernike aberration at depth zi. Note that for thecurrent model, the pupil aberrations are depth independent,and the propagation away from focus can be approximated us-ing the defocus term Z 4. Therefore the depth dependence of cnwill be left unnoted for convenience. Also note that the Zernike

polynomials exist over the unit circle. Therefore the coordinatesare normalized to extend over the limiting pupil defined by thenumerical aperture (NA),

sk ��

qkkcNA

�: (16)

The transfer function phase determined using CAO withZernike weights dn can be similarly represented as

ϕh�qk; zi� �Xn

d nZ n�sk∕2� ≈Xn

2cnZ n�sk∕2�: (17)

An estimate of the Zernike weights for the pupil aberrationscan then be easily obtained as

cn �dn

2: (18)

This provides a simple relationship between the Zernikeweights of the CAO phase filter and the imaging pupil.

B. Autoconvolution Method

Instead of relying upon the asymptotic approximations ofISAM, it is possible to retrieve the pupil phase via inverse au-toconvolution. In this case, the autoconvolution relationship ofEq. (12) still holds. However, the inverse autoconvolution iscomplicated by the fact that ϕh is influenced by both the am-plitude and phase of G�qk�. Therefore, it is necessary includethe pupil function amplitude. Gaussian beam illumination istypical for a point scanned OCT system and will be assumedhere, although other amplitude profiles could be used. Passing aGaussian beam through a limiting circular aperture results inthe complex pupil function

G�qk� � circ�sk� exp�−s2k � i

Xn

cnZ n�sk��; (19)

where circ�sk� is defined as unity for jskj ≤ 1 and zeroelsewhere.

Given the phase ϕh from the CAO correction and a modelfor jG�qk�j, we can perform an optimization procedure tosearch for the corresponding pupil phase [19]. The estimatedZernike polynomial weights are calculated as

cn � argminϕg�

Pn

cnZn

kG�qk� � G�qk� − jG�qk� � G�qk�jeiϕhk2kG�qk� � G�qk�k2

:

(20)

This finds a pupil function whose autoconvolution has aphase profile that matches the CAO filter.

C. Forward-Model Method

The previous two methods estimate the pupil aberrations fromthe phase obtained by the CAO image correction; that is to say,ϕg is estimated from ϕh. Alternatively, the pupil aberrations ϕgcan be estimated directly by incorporating the forward modelinto the CAO procedure. In the absence of aberrations, a groupof image metrics known as image sharpness are maximized[20–22]. Stated another way, aberrations can only decrease theimage sharpness. Therefore, it is possible to determine the ap-propriate CAO phase filter by maximizing the image sharpness.Here we define the image sharpness operator as

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I�S�x; y�� �Xx;y

�S�x; y�S��x; y��2; (21)

where (*) indicates the complex conjugate. This operator cal-culates the sum of the intensity squared across the image.

Typically, the image sharpness is optimized by searchingover possible phases ϕh, in accordance with Eqs. (9) and (10).However, it is possible to generate the CAO phase filter via theforward model as

HAC�qk� � exp�−i arg�G�qk� � G�qk���: (22)

The image sharpness optimization can then be performed bysearching over possible phases ϕg , providing a direct estimate ofthe imaging pupil phase

cn � argmaxϕg�

PncnZn

I�F −1�SAC�qk���; (23)

where F −1� � indicates the inverse Fourier transform to thespatial domain.

4. SIMULATION AND RESULTS

To determine the effectiveness of each method, OCT data wassimulated, allowing for the introduction of arbitrary aberrationsinto the imaging pupil. The data used here were generated us-ing the more exact model of Eqs. (21) and (29) from [14].Simulated data were generated on a densely spaced 3D grid,then resampled by a noninteger multiple to a coarser grid tomimic data acquisition. The simulated OCT experimentsused a Gaussian spectrum with 1 μm central wavelength and100 nm bandwidth, and the transverse imaging area was128 μm × 128 μm acquired with a 1 μm step size. The NAwas 0.1, matching that of previous computational OCT experi-ments [5,23]. The imaging pupil was constructed followingEq. (19), with aberrations introduced into the pupil phaseusing weighted Zernike polynomial functions,

ϕg�qk; k� � kXn

c�μm�n Z n�qk∕�kNA��: (24)

Here cn was defined in units of micrometers (μm) corre-sponding to optical path length, and the variation in wavenum-ber was explicitly accounted for in the simulation. The imagesharpness optimization and inverse autoconvolution proce-dures were performed on an Intel Core i7-5960X with 32 GBof RAM using the MATLAB 2016a Optimization Toolbox.The optimization time was approximately 0.59, 3.75, and2.07 s for the asymptotic, autoconvolution, and forward modelmethods, respectively.

The following sections outline a series of simulated experi-ments in which the sensitivity, cross talk, and other character-istics of the above methods are determined.

A. Sensitivity and Cross Talk

To determine the sensitivity to each aberration term, as well asthe cross talk between terms, single aberrations were applied inthe imaging pupil with increasing RMS. The imaging sampleconsisted of in-focus point-scatterers with unit susceptibility,such that the induced polarization was equal to the incidentfield (see [24], Section 2.3). Aberrations up to 4th order wereapplied (excluding tip/tilt and defocus) with RMS increasing

from zero to 0.6 rad at the central wavelength. The appliedaberrations were then estimated from the OCT data using eachof the three methods detailed in Section 3.

For the asymptotic and forward model methods, the wave-front was estimated by correcting up to 4th order Zernike terms(excluding tip/tilt). However, as a result of the autoconvolutionoperation, the phase of the system transfer function is more rap-idly varying than that of the imaging pupil. This means thatwhile ϕg is described accurately by Zernike terms up to 4th or-der, ϕh may not be. The transfer function phase is representedmore accurately as more Zernike modes are used. It was exper-imentally determined that the CAO optimization performed asthe first step in the autoconvolution method must include up toat least 6th order Zernike modes. This provides an approxima-tion of ϕh that is sufficiently accurate for performing theinverse autoconvolution operation to 4th order imaging pupilaberrations, and that was used for the results presented here.

The sensitivity was defined as the slope of the linear least-squares fit between the estimated weights, cn, corresponding toapplied weights, cn. The cross talk was defined as the normal-ized RMS variation in all aberration terms other than theapplied term, �P

mc2m≠n

�1∕2

cn; (25)

evaluated at the maximum applied aberration. A perfect esti-mate would result in sensitivity equal to one and cross talkequal to zero [25].

Aberration estimates obtained using the asymptotic approxi-mation are shown in Fig. 2. In Figs. 2(a)–2(c), the estimatedweights are given for 2nd, 3rd, and 4th orders, respectively. Anideal estimate is indicated by the dashed line for reference.Notice that certain Zernike modes are nearly identical, differingonly in their rotation (e.g., astigmatism terms n � 3; 5).Therefore the estimates for these terms are very close to oneanother. The sensitivity and cross talk for each applied termare shown in Fig. 2(d). There is reasonable performance onlyfor 2nd order aberrations, indicating that the asymptoticapproximation is not valid at higher orders. This is not unex-pected, as the approximations used in this method were devel-oped in the absence of phase aberrations.

The inverse autoconvolution method showed superior sen-sitivity at all orders when compared with the asymptoticmethod. The aberration estimates and corresponding metricsare given in Fig. 3. The sensitivity at 2nd order was 0.95and remained greater than 0.5 through 4th order. For coma(terms n � 7; 8), the method overestimated the appliedaberration, but the sensitivity remained within 0.25 of theideal case.

Of the three proposed methods, the forward model methodhad the most consistent performance across all orders asdemonstrated in Fig. 4. Additionally, the method did not over-estimate any aberrations. The average sensitivity across all termswas 0.81, while the average cross talk was 0.04.

B. Impact of Signal-to-Noise Ratio

In a realistic imaging scenario, the data will be corrupted bynoise. For OCT, this can be modeled by additive complex

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white Gaussian noise [14,26]. The simulations and measure-ments of the previous section were repeated with peak signal-to-noise ratio (SNR) varying from 50 dB down to 20 dB, wherethe peak SNR was defined as

SNRpeak � 10 log10

�max jS�rk�j2

σ2noise

�: (26)

The resulting sensitivity and cross talk for the autoconvolu-tion and forward model methods are shown in Fig. 5. As theasymptotic method is not sensitive to higher orders, the resultsare not included. Although the computational wavefront mea-surement fails below a certain SNR threshold, it is important tonote that the computational image correction still succeeds.This is in accordance with previous results [27].

At high SNR, both methods performed similarly to thenoise free case. However, as the SNR decreases, the tails andsidelobes of the point spread function became buried in thenoise. Therefore, much of the point spread function shapecan be obscured. The performance of the autoconvolutionmethod began to suffer with peak SNR of 30 dB, where crosstalk approached the sensitivity for several aberration terms. At20 dB, the results became unstable with estimated RMS farbeyond that which was applied.

The performance of the forward model method remainedstrong down to 25 dB peak SNR. Here the average sensitivitywas 0.81, and average cross talk was 0.29. A comparisonbetween the average sensitivity and cross talk for the autocon-volution and forward model methods is given in Fig. 6. Acomparable experiment was previously performed using a

(a) (b)

(c) (d)

CrosstalkSensi�vity

2nd order ( = 3, 5) 3rd order ( = 6 to 9)

4th order ( = 10 to 14)

Fig. 3. Measurement of single aberrations using the autoconvolu-tion method. (a)–(c) The applied and estimated Zernike weightsare shown for 2nd, 3rd, and 4th order aberrations, respectively.The dotted line corresponds to a perfect estimate. All Zernike weightsare in radians. (d) The sensitivity and cross talk were calculated foreach applied Zernike term.

(a) (b)

(c) (d)

Fig. 4. Measurement of single aberrations using the forward modelmethod. (a)–(c) The applied and estimated Zernike weights are shownfor 2nd, 3rd, and 4th order aberrations, respectively. The dotted linecorresponds to a perfect estimate. All Zernike weights are in radians.(d) The sensitivity and cross talk were calculated for each appliedZernike term.

(a) (b)

(c) (d)

Fig. 2. Measurement of single aberrations using the asymptoticmethod. (a)–(c) The applied and estimated Zernike weights are shownfor 2nd, 3rd, and 4th order aberrations, respectively. The dotted linecorresponds to a perfect estimate. All Zernike weights are in radians.(d) The sensitivity and cross talk were calculated for each appliedZernike term.

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deformable mirror and Shack–Hartmann wavefront sensor[25]. The average sensitivity and cross talk were 0.71 and 0.32,respectively, and only included aberrations up to 3rd order.Considering this, the performance of the forward modelmethod was comparable or superior to that of direct hardwaremeasurement.

C. Multiple Simultaneous Aberrations

Additional simulated experiments were performed with multi-ple aberrations applied simultaneously in the pupil plane.The aberration weights were randomly generated to have a total

wavefront RMS of zero, 0.2, 0.4, and 0.6 rad, with lower orderZernike terms allowed to take on greater weights. This wasdone to mimic common imaging scenarios where the magni-tude of lower order aberrations is significantly greater than thatof higher order aberrations, such as imaging the human retina[28,29]. The total wavefront RMS is defined as

σ ��X

nc2n

�1∕2

: (27)

A total of 10 random wavefronts were generated at eachRMS, and OCT data were simulated for each wavefront.The noise level was set to 50 dB peak SNR. Due to its con-sistent performance across all orders and resilience to noise, the

Autoconvolution method Forward model methodBd 05

Bd 04Bd 03

B d 52Bd 02

Fig. 5. Performance of the autoconvolution and forward modelmethods at each Zernike mode for decreasing peak SNR. The forwardmodel method shows superior performance in noisy conditions.

Peak SNR (dB)

20 30 40 500

0.2

0.4

0.6

0.8

1

Sensitivity (Autoconvolution)

Cross-talk (Autoconvolution)

Sensitivity (Forward model)

Cross-talk (Forward model)

Fig. 6. Average sensitivity and cross talk versus peak SNR for theautoconvolution and forward model methods. While the methodshave similar average sensitivity, the cross talk for the forward modelmethod is notably superior at low SNR.

(a) (b)

(c) (d)

Fig. 7. Measurement of multiple simultaneous aberrations usingthe forward model method. (a)–(c) The applied and measuredZernike weights are shown for a randomly generated wavefront at0.2, 0.4, and 0.6 radians RMS, respectively. (d) Average wavefrontRMS measured over 10 randomly generated wavefronts. Thecorresponding sensitivity to total wavefront RMS was 0.85.

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forward model method was used to estimate the appliedwavefronts.

Example wavefronts and the corresponding computationalmeasurements are shown in Fig. 7. As seen in Figs. 7(a)–7(c),the measurement closely tracked the applied wavefront. Foreach wavefront, the total RMS of the measured aberrationswas calculated. The average measured RMS across each setof 10 wavefronts is shown in Fig. 7(d). The sensitivity was0.85, calculated as the least squares slope of the total measuredRMS as a function of applied RMS.

As a demonstration of volumetric aberration measurementand correction, a 3D OCT dataset was generated with 50 ran-domly located point scatterers. The pupil aberrations weregiven by a randomly generated wavefront of 0.6 rad total RMS.The forward model method was used to estimate and correctthe aberrations throughout the imaging volume. Volume ren-derings of the aberrated OCT data and CAO corrected data areshown in Fig. 8(a), along with corresponding en face imagestaken 150 μm below focus shown in Fig. 8(b). The CAO imagedemonstrates correction of the point spread function with in-creased signal amplitude and resolution, and 3.9 times im-provement in image sharpness [see Eq. (21)]. While onlyfour points are resolved the OCT image, a previously obscuredfifth point is revealed following wavefront correction (whitearrow). The applied and measured aberration weights are givenin Fig. 8(c), showing the mean and standard deviation of thewavefront measurement across all 50 scatterers. The averagesensitivity to the total wavefront RMS was 0.89, giving anapproximate Strehl ratio of 0.94 [30].

5. CONCLUSIONS

Using the proposed methods, aberrations can be both measuredand corrected computationally directly from the OCT datawithout the use of hardware adaptive optics components.Our methods were tested in simulation, and the performancecompares favorably to that of previously published wavefrontsensor measurements in optical microscopy. Based on its sim-plicity, consistency, and robustness to noise, the forward modelmethod is recommended for use in future experiments.

The results presented here only considered pupil aberra-tions. However, these methods could also be used to determinethe local aberrations introduced by the imaged sample.This could provide aberration corrected images as well as a3D aberration map, revealing the effect of the tissue on theimaging beam. This is interesting from a scientific perspective,since the mapping of optical aberrations can be used to opti-mize imaging system parameters such as choice of optics orscanning region. For biomedical applications, aberrationmeasurement could be used as a new form of image contrastbetween tissue types that may otherwise appear similar underOCT imaging. In general, where hardware wavefront measure-ment has found useful application, CAO is a computationalalternative for simultaneous wavefront measurement andcorrection.

APPENDIX A: TABLE OF ZERNIKEPOLYNOMIALS

A list of the Zernike polynomial indices used in this publicationis included in Table 1 to aid the reader. The polynomialsare indexed according to the ANSI Z80.28 standard [31].The functions are given here in polar coordinates but can also

(a) (c)OCT CAO (b)

CAO

OCT

Fig. 8. Measurement and correction of multiple aberrations in a 3D imaging volume. (a) Volume rendering of aberrated (OCT) and corrected(CAO) data. The dimensions of the volume are 128 μm × 128 μm × 640 μm. (b) En face images are taken from 150 μm below focus. FollowingCAO, the point spread function is improved and a previously obscured fifth point is revealed (white arrow). (c) Applied and measured aberrations ateach point scatterer throughout the volume. The error bars correspond to the standard deviation across all 50 measurements. Zernike weights are inradians.

Table 1. Zernike Polynomial Indices, RMSNormalizationFactors, and Common Names

n Zn�r;θ� RMS Name

2nd order3 r2 sin�2θ�

ffiffiffi6

pastigmatism

4 2r2 − 1ffiffiffi3

pdefocus

5 r2 cos�2θ�ffiffiffi6

pastigmatism

3rd order

6 r3 sin�3θ� 2ffiffiffi2

ptrefoil

7 �3r3 − 2r� sin�θ� 2ffiffiffi2

pcoma

8 �3r3 − 2r� cos�θ� 2ffiffiffi2

pcoma

9 r3 sin�3θ� 2ffiffiffi2

ptrefoil

4th order

10 r4 sin�4θ� ffiffiffiffiffi10

pquadrafoil

11 �4r4 − 3r2� sin�2θ� ffiffiffiffiffi10

psecondary astigmatism

12 6r4 − 6r2 � 1ffiffiffi5

pspherical

13 �4r4 − 3r2� cos�2θ� ffiffiffiffiffi10

psecondary astigmatism

14 r4 cos�4θ� ffiffiffiffiffi10

pquatrefoil

472 Vol. 35, No. 3 / March 2018 / Journal of the Optical Society of America A Research Article

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be written in rectangular coordinates [32]. Each polynomialwas normalized by its RMS to satisfy the conditionZ

1

0

Z2π

0

Zn�r; θ�Zm�r; θ�rdrdθ∕Z

1

0

Z2π

0

rdrdθ � δnm:

(A1)

Funding. National Institutes of Health (NIH) (R01CA213149, R01 EB013723, R01 EB023232); Air ForceOffice of Scientific Research (AFOSR) (FA9550-17-1-0387);Beckman Institute for Advanced Science and Technology,University of Illinois, Urbana-Champaign; University ofIllinois at Urbana-Champaign (UIUC).

Acknowledgment. The authors thank Darold Spillmanfor technical support. F. A. S. was supported in part by an ECEYang Fellowship, and A. J. B. was supported in part by aBeckman Graduate Fellowship. Additional information canbe found at http://biophotonics.illinois.edu.

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Research Article Vol. 35, No. 3 / March 2018 / Journal of the Optical Society of America A 473