Super-resolution photoacoustic imaging via flow induced absorption fluctuations

In deep tissue photoacoustic imaging the spatial resolution is inherently limited by the acoustic wavelength. We present an approach for surpassing the acoustic diffraction limit by exploiting temporal fluctuations in the sample absorption distribution, such as those induced by flowing particles. In addition to enhanced resolution, our approach inherently provides background reduction, and can be implemented with any conventional photoacoustic imaging system. The considerable resolution increase is made possible by adapting notions from super-resolution optical fluctuations imaging (SOFI) developed for blinking fluorescent molecules, to flowing acoustic emitters. By generalizing SOFI mathematical analysis to complex valued signals, we demonstrate super-resolved photoacoustic images that are free from oscillations caused by band-limited detection. The presented technique holds potential for contrast-agent free micro-vessels imaging, as red blood cells provide a strong endogenous source of naturally fluctuating absorption

Ultrasound localization microscopy to image and assess microvasculature in a rat kidney.

The recent development of ultrasound localization microscopy, where individual microbubbles (contrast agents) are detected and tracked within the vasculature, provides new opportunities for imaging the vasculature of entire organs with a spatial resolution below the diffraction limit. In stationary tissue, recent studies have demonstrated a theoretical resolution on the order of microns. In this work, single microbubbles were localized in vivo in a rat kidney using a dedicated high frame rate imaging sequence. Organ motion was tracked by assuming rigid motion (translation and rotation) and appropriate correction was applied. In contrast to previous work, coherence-based non-linear phase inversion processing was used to reject tissue echoes while maintaining echoes from very slowly moving microbubbles. Blood velocity in the small vessels was estimated by tracking microbubbles, demonstrating the potential of this technique to improve vascular characterization. Previous optical studies of microbubbles in vessels of approximately 20 microns have shown that expansion is constrained, suggesting that microbubble echoes would be difficult to detect in such regions. We therefore utilized the echoes from individual MBs as microscopic sensors of slow flow associated with such vessels and demonstrate that highly correlated, wideband echoes are detected from individual microbubbles in vessels with flow rates below 2 mm/s

Ultrasensitive plano-concave optical microresonators for ultrasound sensing

Highly sensitive broadband ultrasound detectors are needed to expand the capabilities of biomedical ultrasound, photoacoustic imaging and industrial ultrasonic non-destructive testing techniques. Here, a generic optical ultrasound sensing concept based on a novel plano-concave polymer microresonator is described. This achieves strong optical confinement (Q-factors > 105) resulting in very high sensitivity with excellent broadband acoustic frequency response and wide directivity. The concept is highly scalable in terms of bandwidth and sensitivity. To illustrate this, a family of microresonator sensors with broadband acoustic responses up to 40 MHz and noise-equivalent pressures as low as 1.6 mPa per √Hz have been fabricated and comprehensively characterized in terms of their acoustic performance. In addition, their practical application to high-resolution photoacoustic and ultrasound imaging is demonstrated. The favourable acoustic performance and design flexibility of the technology offers new opportunities to advance biomedical and industrial ultrasound-based techniques

Quantum metrology and its application in biology

Quantum metrology provides a route to overcome practical limits in sensing devices. It holds particular relevance to biology, where sensitivity and resolution constraints restrict applications both in fundamental biophysics and in medicine. Here, we review quantum metrology from this biological context, focusing on optical techniques due to their particular relevance for biological imaging, sensing, and stimulation. Our understanding of quantum mechanics has already enabled important applications in biology, including positron emission tomography (PET) with entangled photons, magnetic resonance imaging (MRI) using nuclear magnetic resonance, and bio-magnetic imaging with superconducting quantum interference devices (SQUIDs). In quantum metrology an even greater range of applications arise from the ability to not just understand, but to engineer, coherence and correlations at the quantum level. In the past few years, quite dramatic progress has been seen in applying these ideas into biological systems. Capabilities that have been demonstrated include enhanced sensitivity and resolution, immunity to imaging artifacts and technical noise, and characterization of the biological response to light at the single-photon level. New quantum measurement techniques offer even greater promise, raising the prospect for improved multi-photon microscopy and magnetic imaging, among many other possible applications. Realization of this potential will require cross-disciplinary input from researchers in both biology and quantum physics. In this review we seek to communicate the developments of quantum metrology in a way that is accessible to biologists and biophysicists, while providing sufficient detail to allow the interested reader to obtain a solid understanding of the field. We further seek to introduce quantum physicists to some of the central challenges of optical measurements in biological science.Comment: Submitted review article, comments and suggestions welcom

Medical Imaging of Microrobots: Toward In Vivo Applications

Medical microrobots (MRs) have been demonstrated for a variety of non-invasive biomedical applications, such as tissue engineering, drug delivery, and assisted fertilization, among others. However, most of these demonstrations have been carried out in in vitro settings and under optical microscopy, being significantly different from the clinical practice. Thus, medical imaging techniques are required for localizing and tracking such tiny therapeutic machines when used in medical-relevant applications. This review aims at analyzing the state of the art of microrobots imaging by critically discussing the potentialities and limitations of the techniques employed in this field. Moreover, the physics and the working principle behind each analyzed imaging strategy, the spatiotemporal resolution, and the penetration depth are thoroughly discussed. The paper deals with the suitability of each imaging technique for tracking single or swarms of MRs and discusses the scenarios where contrast or imaging agent's inclusion is required, either to absorb, emit, or reflect a determined physical signal detected by an external system. Finally, the review highlights the existing challenges and perspective solutions which could be promising for future in vivo applications

Non-Destructive Evaluation of Aerospace Composites

Five methods of non-destructive material evaluation (NDE) were used to inspect various forms of damage commonly found in aerospace fiberglass composites: voids, edge and sub-surface delaminations, surface burning, and cracking. The images produced by X-ray, X-ray Computed Tomography, terahertz (THz) imaging, ultrasound, and flash IR thermography were analyzed for the detection of defects. Test results and analysis of each NDE method\u27s capabilities provide a comparison study of conventional techniques versus the emerging technology of THz imaging for the non-destructive evaluation of aerospace composite materials. A comparison guide to the five methods\u27 damage detection effectiveness for fiberglass composites is provided by defect type

Investigation of ultrasonic properties of MAGIC gels for pulse-echo gel dosimetry

This thesis describes investigations into the design and evaluation of novel ultrasonic methods for 3-dimensional ionising radiation dose verification. Pulse-echo ultrasound methods were investigated for the measurement and analysis of complex radiation therapy dose delivery.The physical properties of MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper) polymer gel dosimeters have been characterized. The variations of speed of sound, ultrasonic attenuation coefficient and density of MAGIC gel with radiation dose and temperature have been quantified. This extends work that has previously been reported for the properties of this gel to the effect of measurement temperature on the results. The facilities to perform these measurements were specified, constructed and evaluated as part of the project.The measurement of radiation dose using ultrasound back scatter from an interface between the polymer gel dosimeter and an inert reflector is demonstrated. To enable the measurement of radiation dose using pulse-echo ultrasound methods a novel inert material has been specified, manufactured and characterised. This material is matched to the acoustic impedance of MAGIC gel to produce the most dose-sensitive reflections.The reflections from the interface between the inert reflector and dose-dependent MAGIC gel have been analysed using both a single element transducer and a commercial ultrasound scanner. Both measurement systems demonstrate the same dose and temperature dependence of the ultrasonic reflection. A methodology has been developed to relate pixel values from the ultrasound scanner to the amplitude of the reflected ultrasound signal. A phantom consisting of an array of threads formed from the inert backscattering material has been designed and constructed and a method of extracting pixel data from images of the array acquired using a commercial ultrasound scanner has been developed, so that multiple imaging positions could be used to perform a 3-dimensional assessment of radiation dose distributions.It has been demonstrated that a pulse-echo technique using a commercial ultrasound scanner shows promise for radiation gel dosimetry. Further investigation and alternative polymer gel and inert reflector combinations may improve these techniques

Randomized benchmarking of atomic qubits in an optical lattice

We perform randomized benchmarking on neutral atomic quantum bits (qubits) confined in an optical lattice. Single qubit gates are implemented using microwaves, resulting in a measured error per randomized computational gate of 1.4(1) x 10^-4 that is dominated by the system T2 relaxation time. The results demonstrate the robustness of the system, and its viability for more advanced quantum information protocols.Comment: 11 pages, 4 figure

New methods for deep tissue imaging

Microscopes play vital role biological science and medicine. For single photon microscopies, the scattering of photons makes regions of interest located a few hundred microns beneath the surface inaccessible. Multi-photon microscopes are widely used for minimally invasive in vivo brain imaging due to their increased imaging depth. However, multi-photon microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. In the first part of the thesis, I present a solution to vastly improve the dynamic range of a multi-photon microscope while limiting potential photodamage. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications. In the second section of the thesis work, I explore a completely different approach towards deep tissue imaging by changing the type of radiation from light to ultrasound. Inspired by an optical phase contrast technique invented in the lab, I developed an unprecedented ultrasound imaging system that can visualize the ultrasound phase contrast in the sample. The ultrasound phase contrast technique is able to visualize local sound speed variations instead of local reflectivity. Compared with existing sound speed tomography systems, our technique eliminates the cumbersome sound speed reconstruction process. The research work in this section contains three parts. In the first part, we designed a low-cost single element scanning system as proof of concept. In the second part, we implemented the ultrasound phase contrast imaging system on a commercial linear phased transducer array and an imaging apparatus designed for samples with finite thickness. In the third part, we studied the feasibility of ultrasound phase contrast imaging in arbitrarily thick tissue. We presented a complete workflow of theoretical study, simulation, prototyping and experimental testing for all three parts.2020-02-28T00:00:00