Showing papers by "Roger J. Zemp published in 2017"

Non-interferometric photoacoustic remote sensing microscopy

Abstract: Elasto-optical refractive index modulation due to photoacoustic initial pressure transients produced significant reflection of a probe beam when the absorbing interface had an appreciable refractive index difference This effect was harnessed in a new form of non-contact optical resolution photoacoustic microscopy called photoacoustic remote sensing microscopy A non-interferometric system architecture with a low-coherence probe beam precludes detection of surface oscillations and other phase-modulation phenomenon The probe beam was confocal with a scanned excitation beam to ensure detection of initial pressure-induced intensity reflections at the subsurface origin where pressures are largest Phantom studies confirmed signal dependence on optical absorption, index contrast and excitation fluence In vivo imaging of superficial microvasculature and melanoma tumors was demonstrated with ~27±05 μm lateral resolution A new design for a photoacoustic microscope capable of high-quality, real-time in vivo imaging has been developed by scientists in Canada Parsin Hajireza and co-workers from the University of Alberta and the company Illumisonics report that, unlike other designs, their approach does not rely on interferometric detection of photoacoustic stress, which can be problematic Instead, it involves making time-varying intensity measurements of the reflection of a probe beam from the sample A high signal-to-noise ratio and a working distance of 25 centimetres between the sample and the system's objective lens are achievable The researchers demonstrate the potential of their scheme for biomedical applications by using to perform in vivo imaging of microvasculature and melanoma tumours in chicken embryos with a spatial resolution of 27 micrometres

Multifrequency Interlaced CMUTs for Photoacoustic Imaging.

Abstract: Multifrequency capacitive micromachined ultrasound transducers (CMUTs) are introduced consisting of interlaced 82- [Formula: see text] (low frequency) and 36- [Formula: see text] (high frequency) membranes. The membranes have been interlaced on a scale smaller than the shortest wavelength of operation allowing several advantages over other multifrequency transducer designs including aligned beam profiles, optimal imaging resolution, and minimal grating lobes. The low- and high-frequency CMUTs operate at 1.74 and 5.04 MHz in immersion, respectively. Multifrequency transducers have applications in wideband photoacoustic (PA) imaging where multifrequency transducers are better able to detect both high- and low-frequency PA frequency content. The PA frequency content is target size dependent, which means traditional high-frequency transducers have less sensitivity to larger objects such as diffuse contrast agents. We demonstrate that the low-frequency subarrays are able to better visualize diffuse agent distributions, while the high-frequency subarrays offer fine-resolution imaging important for microvascular imaging and structural navigation. Spectroscopically unmixed images superimpose high sensitivity images of agent concentrations (acquired using low-frequency subarrays) onto high-resolution images of microvessel-mimicking phantoms (acquired using high-frequency subarrays).

Photoacoustic imaging of lymphatic pumping.

Abstract: The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system.

Fast Orthogonal Row–Column Electronic Scanning With Top-Orthogonal-to-Bottom Electrode Arrays

Abstract: Recently, top-orthogonal-to-bottom electrode 2-D arrays were introduced as a practical design for 3-D ultrasound imaging without requiring the wiring of a 2-D grid of elements. However, previously proposed imaging schemes suffered from speed or image-quality limitations. Here, we propose a new imaging scheme which we call Fast Orthogonal Row–Column Electronic Scanning (FORCES). This new approach takes advantage of bias sensitivity to enable high-quality and fast B-scan imaging. We compare this imaging scheme with an equivalent linear array, a previously proposed row–column imaging scheme, as well as with the Explososcan imaging scheme for 2-D arrays through simulations. In a point phantom simulation, the lateral (azimuthal) resolution of a $64 \times 64$ element 6.67-MHz $\lambda $ /2-pitch array using the FORCES imaging scheme with an f-number of 1.7 was 0.52 mm with similar in-plane image quality to an equivalent linear array but with improved and electronically steerable elevational resolution. When compared with other 3-D imaging schemes in point phantom simulations, the FORCES imaging scheme showed an azimuthal resolution improvement of 54% compared with Explososcan. Compared with a previously introduced row–column method, the FORCES imaging scheme had similar resolution but a 25-dB decrease in sidelobe amplitude, significantly impacting contrast to noise in scattering phantoms.

Temporal evolution of low-coherence reflectrometry signals in photoacoustic remote sensing microscopy.

Abstract: Recently, a new noncontact reflection-mode imaging modality called photoacoustic remote sensing (PARS) microscopy was introduced providing optical absorption contrast. Unlike previous modalities, which rely on interferometric detection of a probe beam to measure surface oscillations, the PARS technique detects photoacoustic initial pressures induced by a pulsed laser at their origin by monitoring intensity modulations of a reflected probe beam. In this paper, a model describing the temporal evolution from a finite excitation pulse is developed with consideration given to the coherence length of the interrogation beam. Analytical models are compared with approximations, finite-difference time-domain (FDTD) simulations, and experiments with good agreement.

Fabrication of Linear Array and Top-Orthogonal-to-Bottom Electrode CMUT Arrays With a Sacrificial Release Process

Abstract: The microfabrication processes for sacrificial-release-based capacitive micromachined ultrasound transducer arrays are provided with an emphasis on top-orthogonal-to-bottom electrode 2-D arrays. These arrays have significant promise for high-quality 3-D imaging with reduced wiring complexity compared with fully wired arrays. The protocols and best practices are outlined in significant detail along with design considerations and notes of caution for pitfalls and factors impacting yield.

Enhanced Detection of Cancer Biomarkers in Blood-Borne Extracellular Vesicles Using Nanodroplets and Focused Ultrasound

Abstract: The feasibility of personalized medicine approaches will be greatly improved by the development of noninvasive methods to interrogate tumor biology Extracellular vesicles shed by solid tumors into the bloodstream have been under recent investigation as a source of tumor-derived biomarkers such as proteins and nucleic acids We report here an approach using submicrometer perfluorobutane nanodroplets and focused ultrasound to enhance the release of extracellular vesicles from specific locations in tumors into the blood The released extracellular vesicles were enumerated and characterized using micro flow cytometry Only in the presence of nanodroplets could ultrasound release appreciable levels of tumor-derived vesicles into the blood Sonication of HT1080-GFP tumors did not increase the number of circulating tumor cells or the metastatic burden in the tumor-bearing embryos A variety of biological molecules were successfully detected in tumor-derived extracellular vesicles, including cancer-associated proteins, mRNAs, and miRNAs Sonication of xenograft HT1080 fibrosarcoma tumors released extracellular vesicles that contained detectable RAC1 mRNA with the highly tumorigenic N92I mutation known to exist in HT1080 cells Deep sequencing serum samples of embryos with sonicated tumors allowed the identification of an additional 13 known heterozygous mutations in HT1080 cells Applying ultrasound to HT1080 tumors increased tumor-derived DNA in the serum by two orders of magnitude This work is the first demonstration of enhanced extracellular vesicle release by ultrasound stimulation and suggests that nanodroplets/ultrasound offers promise for genetic profiling of tumor phenotype and aggressiveness by stimulating the release of extracellular vesicles Cancer Res; 77(1); 3-13 ©2016 AACR

Non-interferometric photoacoustic remote sensing (NI-PARS)

Abstract: A photoacoustic remote sensing system (NI-PARS) for imaging a subsurface structure in a sample, has an excitation beam configured to generate ultrasonic signals in the sample at an excitation location; an interrogation beam incident on the sample at the excitation location, a portion of the interrogation beam returning from the sample that is indicative of the generated ultrasonic signals; an optical system that focuses at least one of the excitation beam and the interrogation beam with a focal point that is below the surface of the sample; and a detector that detects the returning portion of the interrogation beam.

Photoacoustic–Ultrasound Tomography With S-Sequence Aperture Encoding

Abstract: A combined photoacoustic–ultrasound (PAUS) tomography system is introduced using ring-array and novel aperture encoding schemes. The ultrasound subsystem is able to achieve diffraction limited half-wavelength isotropic in-plane spatial resolution unlike previous systems. S-sequence aperture encoding improves signal-to-noise ratio (SNR) for the ultrasound tomography (UST) subsystem. We measured an average resolution of $139 \pm 44~\mu \text{m}$ for S-sequence UST and a resolution of $180 \pm 32~\mu \text{m}$ for photoacoustic tomography. We were able to measure SNR improvement using S-sequence spatial encoding using tissue-mimicking phantoms, and we displayed a composite PAUS phantom image.

Large-Scale Nonlinear Lumped and Integrated Field Simulations of Top-Orthogonal-to-Bottom-Electrode CMUT Architectures

Abstract: Capacitive micromachined ultrasonic transducers (CMUTs) promise many advantages over traditional piezoelectric transducers such as the potential to construct large, cost-effective 2-D arrays. To avoid wiring congestion issues associated with fully wired arrays, top-orthogonal-to-bottom electrode (TOBE) CMUT array architectures have proven to be a more practical alternative, using only $2N$ wires for an $N \times N$ array. Optimally designing a TOBE CMUT array is a significant challenge due to the range of parameters from the device level up to the operating conditions of the entire array. Since testing many design variations can be prohibitively expensive, a simulation approach accounting for both the small and large-scale array characteristics of TOBE arrays is essential. In this paper, we demonstrate large-scale TOBE CMUT array simulations using a nonlinear CMUT lumped-circuit model. We investigate the performance of the array with different CMUT design parameters and array operating conditions. These simulated results are then compared with measurements of TOBE arrays fabricated using a sacrificial release process.

Fabrication and performance of a 128-element crossed-electrode relaxor array, for a novel 3D imaging approach

Abstract: 3D Ultrasound systems present several technical challenges, particularly the large number of elements in a 2D array, high electrical impedance, and image acquisition time. Crossed electrode arrays address some of these issues, especially the huge reduction in number of elements. However, creating a two-way focused 3D image in real-time is difficult with these arrays because azimuth and elevation dimensions cannot be beamformed at the same time. This typically forces one to use a synthetic aperture approach which is inherently slow and requires increased beamforming complexity over a 1D array. We have developed a new, fast and simple 3D imaging approach referred to as Simultaneous Azimuth and Fresnel Elevation (SAFE) compounding. The principle behind this technique is to perform conventional plane wave compounding with the top set of electrodes, while implementing a reconfigurable Fresnel elevation lens with the bottom electrodes. While a Fresnel lens would usually result in unacceptable secondary lobe levels, these lobes can be suppressed by compounding different Fresnel patterns. Since plane wave imaging already compounds the same slice repeatedly, the elevation Fresnel lens can be simultaneously compounded to increase the beam quality, resulting in no loss in frame rate. In this study, the design, fabrication, and characterization of a crossed electrode array based on an electrostrictive ceramic (eg. Pulse polarity depends on a DC bias) is presented.

Multi-frequency CMUT imaging arrays for multi-scale imaging and imaging-therapy applications

Abstract: Large and small CMUT membranes were fabricated in an interlaced fashion to create a multi-frequency array using a modified standard silicon-nitride sacrificial release process on a scale smaller than the wavelength to ensure the minimization of grating lobes. A 7 mm by 7 mm multi-frequency array with 20 elements was fabricated and wire-bonded to custom printed circuit boards (PCBs) mounted onto a custom interfacing circuitry with voltage protected pre-amplifiers, connected to a Verasonics programmable ultrasound platform. This system enabled real-time imaging and programmable control over low- and/or high-frequency transmission and reception. To demonstrate multi-band ultrasound imaging, three wire targets with the separation of 0.7 cm were imaged in an oil immersion medium. The low-frequency elements showed better signal to noise ratio (SNR) for the targets far from the transducer while high-frequency elements proved better resolution for shallower depths.

Non-interferometric deep optical resolution photoacoustic remote sensing microscopy (Conference Presentation)

Abstract: A novel all-optical non-contact photoacoustic microscopy system is introduced. The confocal configuration is used to ensure detection of initial pressure shock wave-induced intensity reflections at the subsurface origin where pressures are largest. Phantom studies confirm signal dependence on optical absorption, index-contrast, and excitation fluence. Taking advantage of a focused1310 nm interrogation beam, the penetration depth of the system is improved to ~ 2mm for an optical resolution system. High signal-to-noise ratios (>60dB) with ~ 2.5 cm working distance from the objective lens to the sample is achieved. Real-time in-vivo imaging of microvasculature and melanoma tumors are demonstrated.

Ultrasound Scattering Anisotropy Visualization With Ultrasound Tomography.

Abstract: An ultrasound tomography (UST) system was used to image ultrasound scattering anisotropy in phantom experiments. This anisotropy was visualized as vector fields with arrows corresponding to the principal scattering angle of each pixel. UST with a ring-array system allows for a large range of transmit and receive angle combinations, producing real-time acquisition anisotropy maps unachievable with previous single element and linear array studies. Resolution was measured to be [Formula: see text], averaged over seven different placements within the transducer's field-of-view. Vector field images of iron filings aligned to a magnetic field were reconstructed and characterized for validation.

A nonlinear large signal equivalent circuit model for a square CMUT cell

Abstract: Using analytical calculations, a precise large signal equivalent circuit model of square CMUT dynamics was developed. The model predicts many intrinsic properties of a square CMUT cell including resonance frequency, phase and magnitude of the membrane displacement, membrane velocity, electrical conductance, collapse voltage, etc. ANSYS 3D finite element analysis (FEA) was used to validate the equivalent circuit model predictions by performing static, pre-stressed harmonic and nonlinear transient analysis. The model was designed and implemented in a circuit simulator and then compared with finite element methods (FEM) and experimental results. The results were compared with circular CMUT cells when the half-side-length of the square CMUT is assumed to be equal to the radii of the circular CMUT cell. A silicon-nitride standard sacrificial release process was used to fabricate the square CMUT cells. The experimental results obtained by a laser vibrometer were compared with circuit simulations and the results showed excellent agreements.

Compression-tracking photoacoustic perfusion and microvascular pressure measurements

Abstract: We propose a method to measure blood pressure of small vessels non-invasively and in-vivo : by combining PA imaging with compression US. Using this method, we have shown pressure-lumen area tracking, as well as estimation of the internal vessel pressure, located 2 mm deep in tissue. Additionally, reperfusion can be tracked by measuring the total PA signal within a region of interest (ROI) after compression has been released. The ROI is updated using cross-correlation based displacement tracking 1 . The change in subcutaneous perfusion rates can be seen when the temperature of the hand of a human subject drops below the normal.

Optimization strategies and neighbour-pair complementary codes for massively parallel focal-zone ultrafast ultrasound

Abstract: Plane wave methods for ultrafast ultrasound imaging suffer from a low signal to noise ratio (SNR) and a limited field of view at greater imaging depths. Imaging using multiple focused coded beams in parallel is one strategy for high speed imaging that may improve on these limitations. However, the SNR and resolution of this strategy are degraded by the interference between the beams transmitted in parallel. We aim to reduce this interference while retaining acceptable axial resolution by careful design of the coded beams. To ensure good axial resolution and to increase flexibility of code design, we use two transmit events to form each set of lines in the image. This implies an increase in imaging speed of approximately K=2, where K is the number of beams fired in parallel. To decode channel data we use a matched filter, summing cross-correlation results over each pair of transmit events. As a result, the interference between two beams fired in parallel is dictated by the magnitude of the sum of cross-correlations between parallel beam encoding patterns. We have constructed a metric based on this idea, and optimized coded beams for this metric using the sequential quadratic programming capabilities of MATLAB's nonlinear optimization toolbox. Using our optimization framework, we have generated codes that allow for very low interference between two simultaneously transmitted parallel beams. Our optimization framework also enables generation of lowerinterference codes for many simultaneous parallel focal zones, compared to randomly selected codes. In simulation, we found that using optimized codes reduces the clutter associated with parallel transmission, and that the optimized coded imaging strategy is capable of generating images with higher contrast than those acquired at the same frame rate by plane wave imaging.

Photoacoustic remote sensing microscopy with lock-in amplification

Abstract: High sensitive detection with lock-in amplification can provide high signal noise ratio even when noise is in orders of magnitude higher than the signal. Here we report to combine lock-in amplification with a novel photoacoustic remote sensing (PARS) technology to achieve high resolution, high contrast, all optical non-contact photoacoustic imaging at depth beyond optical scattering limitation. We demonstrate phantom measurements from PARS with lock-in technology were several orders of magnitude more sensitive than those from PARS with the broadband detection techniques.

Non-invasive spinal vibration testing using ultrafast ultrasound imaging: A new way to measure spine function

Abstract: The extremely high frame-rate of ultrafast ultrasound imaging has enabled the possibility to image extremely fast events on the order of thousands of frames/sec. With the success of ultrafast imaging across a wide variety of disciplines, we now explore the ability of ultrafast imaging to capture spinal vibrations for non-invasive spinal testing in living subjects. Previously, we have shown that accelerometer-based vibration testing in cadaveric models can reveal the presence, location and magnitude of spinal pathology. However, this process remains an invasive procedure as current non-invasive sensors are inadequate. In this experiment, we investigate the ability of non-invasive ultrafast ultrasound to quantify in-vivo vertebral vibration response across a broad range of frequencies (10-100 Hz) in an anesthetized pig model.