Bio

Bio


Tali Ilovitsh is a postdoctoral fellow in Prof. Katherine Ferrara laboratory at the Department of Radiology, School of Medicine, Stanford University. She received her B.Sc. (2010), M.Sc. in a direct track (2011), and Ph.D. (2016) degrees in electrical engineering from Bar Ilan University, Israel. Her Ph.D. research in the field of optical imaging was focused on the development of super-resolution techniques for microscopy. Since joining the Ferrara lab in 2016 she has been working in the fields of ultrasound therapy and imaging. Her research is focused on the development of medical ultrasound technologies that provide non-invasive, cost effective, real-time and safe monitoring, diagnostics and therapy for clinically relevant problems. Currently, she uses low frequency focused ultrasound as a mean to open the blood brain barrier and facilitate drug delivery. Additionally, she develops an ultrasound beam shaping technology that allows to image tissues beyond ultrasonically-impenetrable obstacles, and is also used for label-free ultrasound super-resolution.

Professional Education


  • Bachelor of Science, Bar-Ilan University (2012)
  • Master of Science, Bar-Ilan University (2013)
  • Doctor of Philosophy, Bar-Ilan University (2017)

Stanford Advisors


Publications

All Publications


  • Simultaneous Axial Multifocal Imaging Using a Single Acoustical Transmission: A Practical Implementation IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Ilovitsh, A., Ilovitsh, T., Foiret, J., Stephens, D. N., Ferrara, K. W. 2019; 66 (2): 273–84

    Abstract

    Standard ultrasound imaging techniques rely on sweeping a focused beam across a field of view; however, outside the transmission focal depth, image resolution and contrast are degraded. High-quality deep tissue in vivo imaging requires focusing the emitted field at multiple depths, yielding high-resolution and high-contrast ultrasound images but at the expense of a loss in frame rate. Recent developments in ultrasound technologies have led to user-programmable systems, which enable real-time dynamic control over the phase and apodization of each individual element in the imaging array. In this paper, we present a practical implementation of a method to achieve simultaneous axial multifoci using a single acoustical transmission. Our practical approach relies on the superposition of axial multifoci waveforms in a single transmission. The delay in transmission between different elements is set such that pulses constructively interfere at multiple focal depths. The proposed method achieves lateral resolution similar to successive focusing, but with an enhanced frame rate. The proposed method uses standard dynamic receive beamforming, identical to two-way focusing, and does not require additional postprocessing. Thus, the method can be implemented in real time on programmable ultrasound systems that allow different excitation signals for each element. The proposed method is described analytically and validated by laboratory experiments in phantoms and ex vivo biological samples.

    View details for DOI 10.1109/TUFFC.2018.2885080

    View details for Web of Science ID 000458775800003

    View details for PubMedID 30530361

    View details for PubMedCentralID PMC6375789

  • Enhanced microbubble contrast agent oscillation following 250kHz insonation. Scientific reports Ilovitsh, T., Ilovitsh, A., Foiret, J., Caskey, C. F., Kusunose, J., Fite, B. Z., Zhang, H., Mahakian, L. M., Tam, S., Butts-Pauly, K., Qin, S., Ferrara, K. W. 2018; 8 (1): 16347

    Abstract

    Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuationcompared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents). In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicated that microbubble expansion was enhanced for 250kHz transmission as compared with the 1MHz center frequency. Following 250kHz insonation, microbubble expansion increased nonlinearly with increasing ultrasonic pressure, and was accurately predicted by either the modified Rayleigh-Plesset equation for a clean bubble or the Marmottant model of a lipid-shelledmicrobubble. The expansion ratio reached 30-fold with 250kHz at a peak negative pressure of 400kPa, as compared to a measured expansion ratio of 1.6 fold for 1MHz transmission at a similar peak negative pressure. Further, the range of peak negative pressure yielding stable cavitation in vitro was narrow (~100kPa) for the 250kHz transmission frequency. Blood brain barrier opening using in vivo transcranial ultrasound in mice followed the same trend as the in vitro experiments, and the pressure range for safe and effective treatment was 75-150kPa. For pressures above 150kPa, inertial cavitation and hemorrhage occurred. Therefore, we conclude that (1) at this low frequency, and for the large oscillations, lipid-shelled microbubbles can be approximately modeled as clean gas microbubbles and (2) the development of safe and successful protocols for therapeutic delivery to the brain utilizing 250kHz or a similar center frequency requires consideration of the narrow pressure window between stable and inertial cavitation.

    View details for DOI 10.1038/s41598-018-34494-5

    View details for PubMedID 30397280

  • Imaging beyond ultrasonically-impenetrable objects SCIENTIFIC REPORTS Ilovitsh, T., Ilovitsh, A., Foiret, J., Ferrara, K. W. 2018; 8: 5759

    Abstract

    Ultrasound images are severely degraded by the presence of obstacles such as bones and air gaps along the beam path. This paper describes a method for imaging structures that are distal to obstacles that are otherwise impenetrable to ultrasound. The method uses an optically-inspired holographic algorithm to beam-shape the emitted ultrasound field in order to bypass the obstacle and place the beam focus beyond the obstruction. The resulting performance depends on the transducer aperture, the size and position of the obstacle, and the position of the target. Improvement compared to standard ultrasound imaging is significant for obstacles for which the width is larger than one fourth of the transducer aperture and the depth is within a few centimeters of the transducer. For such cases, the improvement in focal intensity at the location of the target reaches 30-fold, and the improvement in peak-to-side-lobe ratio reaches 3-fold. The method can be implemented in conventional ultrasound systems, and the entire process can be performed in real time. This method has applications in the fields of cancer detection, abdominal imaging, imaging of vertebral structure and ultrasound tomography. Here, its effectiveness is demonstrated using wire targets, tissue mimicking phantoms and an ex vivo biological sample.

    View details for DOI 10.1038/s41598-018-23776-7

    View details for Web of Science ID 000429679900039

    View details for PubMedID 29636513

    View details for PubMedCentralID PMC5893560

  • Acoustical structured illumination for super-resolution ultrasound imaging. Communications biology Ilovitsh, T., Ilovitsh, A., Foiret, J., Fite, B. Z., Ferrara, K. W. 2018; 1

    Abstract

    Structured illumination microscopy is an optical method to increase the spatial resolution of wide-field fluorescence imaging beyond the diffraction limit by applying a spatially structured illumination light. Here, we extend this concept to facilitate super-resolution ultrasound imaging by manipulating the transmitted sound field to encode the high spatial frequencies into the observed image through aliasing. Post processing is applied to precisely shift the spectral components to their proper positions in k-space and effectively double the spatial resolution of the reconstructed image compared to one-way focusing. The method has broad application, including the detection of small lesions for early cancer diagnosis, improving the detection of the borders of organs and tumors, and enhancing visualization of vascular features. The method can be implemented with conventional ultrasound systems, without the need for additional components. The resulting image enhancement is demonstrated with both test objects and ex vivo rat metacarpals and phalanges.

    View details for DOI 10.1038/s42003-017-0003-5

    View details for PubMedID 29888748

  • Superresolved nanoscopy using Brownian motion of fluorescently labeled gold nanoparticles APPLIED OPTICS Ilovitsh, T., Ilovitsh, A., Wagner, O., Zalevsky, Z. 2017; 56 (5): 1365–69
  • Three dimensional imaging of gold-nanoparticles tagged samples using phase retrieval with two focus planes SCIENTIFIC REPORTS Ilovitsh, T., Ilovitsh, A., Weiss, A., Meir, R., Zalevsky, Z. 2015; 5: 15473

    Abstract

    Optical sectioning microscopy can provide highly detailed three dimensional (3D) images of biological samples. However, it requires acquisition of many images per volume, and is therefore time consuming, and may not be suitable for live cell 3D imaging. We propose the use of the modified Gerchberg-Saxton phase retrieval algorithm to enable full 3D imaging of gold-particle tagged samples using only two images. The reconstructed field is free space propagated to all other focus planes using post processing, and the 2D z-stack is merged to create a 3D image of the sample with high fidelity. Because we propose to apply the phase retrieving on nano particles, the regular ambiguities typical to the Gerchberg-Saxton algorithm, are eliminated. The proposed concept is presented and validated both on simulated data as well as experimentally.

    View details for DOI 10.1038/srep15473

    View details for Web of Science ID 000363395100001

    View details for PubMedID 26498517

    View details for PubMedCentralID PMC4620448

  • Cellular superresolved imaging of multiple markers using temporally flickering nanoparticles SCIENTIFIC REPORTS Ilovitsh, T., Danan, Y., Meir, R., Meiri, A., Zalevsky, Z. 2015; 5: 10965

    Abstract

    In this paper we present a technique aimed for simultaneous detection of multiple types of gold nanoparticles (GNPs) within a biological sample, using lock-in detection. We image the sample using a number of modulated laser beams that correspond to the number of GNP species that label a given sample. The final image where the GNPs are spatially separated is obtained computationally. The proposed method enables the simultaneous superresolved imaging of different areas of interest within biological sample and also the spatial separation of GNPs at sub-diffraction distances, making it a useful tool in the study of intracellular trafficking pathways in living cells.

    View details for DOI 10.1038/srep10965

    View details for Web of Science ID 000355548400001

    View details for PubMedID 26020693

    View details for PubMedCentralID PMC4447069

  • Cellular imaging using temporally flickering nanoparticles Scientific Reports Ilovitsh, T., Danan, Y., Meir, R., Meiri, A., Zalevsky, Z. 2015; 5: 8244

    Abstract

    Utilizing the surface plasmon resonance effect in gold nanoparticles enables their use as contrast agents in a variety of applications for compound cellular imaging. However, most techniques suffer from poor signal to noise ratio (SNR) statistics due to high shot noise that is associated with low photon count in addition to high background noise. We demonstrate an effective way to improve the SNR, in particular when the inspected signal is indistinguishable in the given noisy environment. We excite the temporal flickering of the scattered light from gold nanoparticle that labels a biological sample. By preforming temporal spectral analysis of the received spatial image and by inspecting the proper spectral component corresponding to the modulation frequency, we separate the signal from the wide spread spectral noise (lock-in amplification).

    View details for DOI 10.1038/srep08244

    View details for Web of Science ID 000348768100016

    View details for PubMedID 25650019

    View details for PubMedCentralID PMC4316156

  • Phase stretch transform for super-resolution localization microscopy BIOMEDICAL OPTICS EXPRESS Ilovitsh, T., Jalali, B., Asghari, M. H., Zalevsky, Z. 2016; 7 (10): 4198–4209

    Abstract

    Super-resolution localization microscopy has revolutionized the observation of living structures at the cellular scale, by achieving a spatial resolution that is improved by more than an order of magnitude compared to the diffraction limit. These methods localize single events from isolated sources in repeated cycles in order to achieve super-resolution. The requirement for sparse distribution of simultaneously activated sources in the field of view dictates the acquisition of thousands of frames in order to construct the full super-resolution image. As a result, these methods have slow temporal resolution which is a major limitation when investigating live-cell dynamics. In this paper we present the use of a phase stretch transform for high-density super-resolution localization microscopy. This is a nonlinear frequency dependent transform that emulates the propagation of light through a physical medium with a specific warped diffractive property and applies a 2D phase function to the image in the frequency domain. By choosing properly the transform parameters and the phase kernel profile, the point spread function of each emitter can be sharpened and narrowed. This enables the localization of overlapping emitters, thus allowing a higher density of activated emitters as well as shorter data collection acquisition rates. The method is validated by numerical simulations and by experimental data obtained using a microtubule sample.

    View details for DOI 10.1364/BOE.7.004198

    View details for Web of Science ID 000385418200031

    View details for PubMedID 27867725

    View details for PubMedCentralID PMC5102550

  • K-factor image deshadowing for three-dimensional fluorescence microscopy SCIENTIFIC REPORTS Ilovitsh, T., Weiss, A., Meiri, A., Ebeling, C. G., Amiel, A., Katz, H., Mannasse-Green, B., Zalevsky, Z. 2015; 5: 13724

    Abstract

    The ability to track single fluorescent particles within a three dimensional (3D) cellular environment can provide valuable insights into cellular processes. In this paper, we present a modified nonlinear image decomposition technique called K-factor that reshapes the 3D point spread function (PSF) of an XYZ image stack into a narrow Gaussian profile. The method increases localization accuracy by ~60% with compare to regular Gaussian fitting, and improves minimal resolvable distance between overlapping PSFs by ~50%. The algorithm was tested both on simulated data and experimentally.

    View details for DOI 10.1038/srep13724

    View details for Web of Science ID 000360536500001

    View details for PubMedID 26333693

    View details for PubMedCentralID PMC4558540

  • Superresolved labeling nanoscopy based on temporally flickering nanoparticles and the K-factor image deshadowing BIOMEDICAL OPTICS EXPRESS Ilovitsh, T., Danan, Y., Ilovitsh, A., Meiri, A., Meir, R., Zalevsky, Z. 2015; 6 (4): 1262–72

    Abstract

    Localization microscopy provides valuable insights into cellular structures and is a rapidly developing field. The precision is mainly limited by additive noise and the requirement for single molecule imaging that dictates a low density of activated emitters in the field of view. In this paper we present a technique aimed for noise reduction and improved localization accuracy. The method has two steps; the first is the imaging of gold nanoparticles that labels targets of interest inside biological cells using a lock-in technique that enables the separation of the signal from the wide spread spectral noise. The second step is the application of the K-factor nonlinear image decomposition algorithm on the obtained image, which improves the localization accuracy that can reach 5nm and enables the localization of overlapping particles at minimal distances that are closer by 65% than conventional methods.

    View details for DOI 10.1364/BOE.6.001262

    View details for Web of Science ID 000352228400014

    View details for PubMedID 25909010

    View details for PubMedCentralID PMC4399665

  • Optical realization of the radon transform OPTICS EXPRESS Ilovitsh, T., Ilovitsh, A., Sheridan, J., Zalevsky, Z. 2014; 22 (26): 32301–7

    Abstract

    This paper presents a novel optical system for the realization of the Radon transform in a single frame. The optical system is simple, fast and accurate and consists of a 4F system, where in the 2F plane a vortex like optical element is placed. This optical element performs the rotation of the object, which replaces the need for mechanically rotating it, as is done in other common optical realization techniques of the Radon transform. This optical element is realized using a spatial light modulator (SLM) and an amplitude slide. The obtained Radon transform is given in Cartesian coordinates, which can subsequently be transformed using a computer to a polar set. The proposed concept is supported mathematically, numerically and experimentally.

    View details for DOI 10.1364/OE.22.032301

    View details for Web of Science ID 000347179300066

    View details for PubMedID 25607195

  • Improved localization accuracy in stochastic super-resolution fluorescence microscopy by K-factor image deshadowing BIOMEDICAL OPTICS EXPRESS Ilovitsh, T., Meiri, A., Ebeling, C. G., Menon, R., Gerton, J. M., Jorgensen, E. M., Zalevsky, Z. 2014; 5 (1): 244–58

    Abstract

    Localization of a single fluorescent particle with sub-diffraction-limit accuracy is a key merit in localization microscopy. Existing methods such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) achieve localization accuracies of single emitters that can reach an order of magnitude lower than the conventional resolving capabilities of optical microscopy. However, these techniques require a sparse distribution of simultaneously activated fluorophores in the field of view, resulting in larger time needed for the construction of the full image. In this paper we present the use of a nonlinear image decomposition algorithm termed K-factor, which reduces an image into a nonlinear set of contrast-ordered decompositions whose joint product reassembles the original image. The K-factor technique, when implemented on raw data prior to localization, can improve the localization accuracy of standard existing methods, and also enable the localization of overlapping particles, allowing the use of increased fluorophore activation density, and thereby increased data collection speed. Numerical simulations of fluorescence data with random probe positions, and especially at high densities of activated fluorophores, demonstrate an improvement of up to 85% in the localization precision compared to single fitting techniques. Implementing the proposed concept on experimental data of cellular structures yielded a 37% improvement in resolution for the same super-resolution image acquisition time, and a decrease of 42% in the collection time of super-resolution data with the same resolution.

    View details for DOI 10.1364/BOE.5.5.000244

    View details for Web of Science ID 000329225500021

    View details for PubMedID 24466491

    View details for PubMedCentralID PMC3891336