Yuan Zhi Liu

Computed optical interferometric tomography for high-speed volumetric cellular imaging

Three-dimensional high-resolution imaging methods are important for cellular-level research. Optical coherence microscopy (OCM) is a low-coherence-based interferometry technology for cellular imaging with both high axial and lateral resolution. Using a high-numerical-aperture objective, OCM normally has a shallow depth of field and requires scanning the focus through the entire region of interest to perform volumetric imaging. With a higher-numerical-aperture objective, the image quality of OCM is affected by and more sensitive to aberrations. Interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO) are computed imaging techniques that overcome the depth-of-field limitation and the effect of optical aberrations in optical coherence tomography (OCT), respectively. In this work we combine OCM with ISAM and CAO to achieve high-speed volumetric cellular imaging. Experimental imaging results of ex vivo human breast tissue, ex vivo mouse brain tissue, in vitro fibroblast cells in 3D scaffolds, and in vivo human skin demonstrate the significant potential of this technique for high-speed volumetric cellular imaging.

Simultaneous determination of intergranular interactions and intrinsic switching field distributions in magnetic materials

We develop a generally applicable method for the accurate measurement of intrinsic switching field distributions and the determination of exchange and dipolar interactions in granular magnetic materials. The method is based on the simultaneous analysis of hysteresis loop and recoil curve data. Its validity and practical implementation are demonstrated by means of computational modeling using a reference function identification scheme. We find the methodology to be numerically accurate in a wide parameter range, far exceeding the previously utilized mean-field interaction regime used in other methodologies.

Stability in computed optical interferometric tomography (Part I): Stability requirements

As imaging systems become more advanced and acquire data at faster rates, increasingly dynamic samples can be imaged without concern of motion artifacts. For optical interferometric techniques such as optical coherence tomography, it often follows that initially, only amplitude-based data are utilized due to unstable or unreliable phase measurements. As systems progress, stable phase maps can also be acquired, enabling more advanced, phase-dependent post-processing techniques. Here we report an investigation of the stability requirements for a class of phase-dependent post-processing techniques - numerical defocus and aberration correction with further extensions to techniques such as Doppler, phase-variance, and optical coherence elastography. Mathematical analyses and numerical simulations over a variety of instabilities are supported by experimental investigations.

Three-dimensional motion correction using speckle and phase for in vivo computed optical interferometric tomography.

Over the years, many computed optical interferometric techniques have been developed to perform high-resolution volumetric tomography. By utilizing the phase and amplitude information provided with interferometric detection, post-acquisition corrections for defocus and optical aberrations can be performed. The introduction of the phase, though, can dramatically increase the sensitivity to motion (most prominently along the optical axis). In this paper, we present two algorithms which, together, can correct for motion in all three dimensions with enough accuracy for defocus and aberration correction in computed optical interferometric tomography. The first algorithm utilizes phase differences within the acquired data to correct for motion along the optical axis. The second algorithm utilizes the addition of a speckle tracking system using temporally- and spatially-coherent illumination to measure motion orthogonal to the optical axis. The use of coherent illumination allows for high-contrast speckle patterns even when imaging apparently uniform samples or when highly aberrated beams cannot be avoided.

Stability in computed optical interferometric tomography (Part II): in vivo stability assessment

Stability is of utmost importance to a wide range of phase-sensitive processing techniques. In Doppler optical coherence tomography and optical coherence elastography, in addition to defocus and aberration correction techniques such as interferometric synthetic aperture microscopy and computational/digital adaptive optics, a precise understanding of the system and sample stability helps to guide the system design and choice of imaging parameters. This article focuses on methods to accurately and quantitatively measure the stability of an imaging configuration in vivo. These methods are capable of partially decoupling axial from transverse motion and are compared against the stability requirements for computed optical interferometric tomography laid out in the first part of this article.

Automated computational aberration correction method for broadband interferometric imaging techniques.

Numerical correction of optical aberrations provides an inexpensive and simpler alternative to the traditionally used hardware-based adaptive optics techniques. In this Letter, we present an automated computational aberration correction method for broadband interferometric imaging techniques. In the proposed method, the process of aberration correction is modeled as a filtering operation on the aberrant image using a phase filter in the Fourier domain. The phase filter is expressed as a linear combination of Zernike polynomials with unknown coefficients, which are estimated through an iterative optimization scheme based on maximizing an image sharpness metric. The method is validated on both simulated data and experimental data obtained from a tissue phantom, an ex vivo tissue sample, and an in vivo photoreceptor layer of the human retina.

Computed Optical Interferometric Imaging: Methods, Achievements, and Challenges

Three-dimensional high-resolution optical imaging systems are generally restricted by the tradeoff between resolution and depth-of-field as well as imperfections in the imaging system or sample. Computed optical interferometric imaging is able to overcome these longstanding limitations using methods such as interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO), which manipulate the complex interferometric data. These techniques correct for limited depth-of-field and optical aberrations without the need for additional hardware. This paper aims to outline these computational methods, making them readily available to the research community. Achievements of the techniques will be highlighted, along with past and present challenges in implementing the techniques. Challenges such as phase instability and determination of the appropriate aberration correction have been largely overcome so that imaging of living tissues using ISAM and CAO is now possible. Computed imaging in optics is becoming a mature technology poised to make a significant impact in medicine and biology.

Automated interferometric synthetic aperture microscopy and computational adaptive optics for improved optical coherence tomography.

In this paper, we introduce an algorithm framework for the automation of interferometric synthetic aperture microscopy (ISAM). Under this framework, common processing steps such as dispersion correction, Fourier domain resampling, and computational adaptive optics aberration correction are carried out as metrics-assisted parameter search problems. We further present the results of this algorithm applied to phantom and biological tissue samples and compare with manually adjusted results. With the automated algorithm, near-optimal ISAM reconstruction can be achieved without manual adjustment. At the same time, the technical barrier for the nonexpert using ISAM imaging is also significantly lowered.

Computational optical coherence tomography [Invited]

Optical coherence tomography (OCT) has become an important imaging modality with numerous biomedical applications. Challenges in high-speed, high-resolution, volumetric OCT imaging include managing dispersion, the trade-off between transverse resolution and depth-of-field, and correcting optical aberrations that are present in both the system and sample. Physics-based computational imaging techniques have proven to provide solutions to these limitations. This review aims to outline these computational imaging techniques within a general mathematical framework, summarize the historical progress, highlight the state-of-the-art achievements, and discuss the present challenges.

A computational approach to high-resolution imaging of the living human retina without hardware adaptive optics

We demonstrate high-resolution imaging of the living human retina by computationally correcting highorder ocular aberrations. These corrections are performed post-acquisition and without the need for a deformable mirror or wavefront sensor that are commonly employed in hardware adaptive optics (HAO) systems. With the introduction of HAO to ophthalmic imaging, high-resolution near diffraction-limited imaging of the living human retina has become possible. The combination of a deformable mirror, wavefront sensor, and supporting hardware/software, though, can more than double the cost of the underlying imaging modality, in addition to significantly increasing the system complexity and sensitivity to misalignment. Optical coherence tomography (OCT) allows 3-D imaging in addition to naturally providing the complex optical field of backscattered light. This is unlike a scanning laser ophthalmoscope which measures only the intensity of the backscattered light. Previously, our group has demonstrated the utility of a technique called computational adaptive optics (CAO) which utilizes the complex field measured with OCT to computationally correct for optical aberrations in a manner similar to HAO. Until now, CAO has been applied to ex vivo imaging and in vivo skin imaging. Here, we demonstrate in vivo imaging of cone photoreceptors using CAO. Additional practical considerations such as imaging speed, and stability are discussed.