Johannes Rebling

Effects of the murine skull in optoacoustic brain microscopy

Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments.

Broadband acoustic properties of a murine skull.

It has been well recognized that the presence of a skull imposes harsh restrictions on the use of ultrasound and optoacoustic techniques in the study, treatment and modulation of the brain function. We propose a rigorous modeling and experimental methodology for estimating the insertion loss and the elastic constants of the skull over a wide range of frequencies and incidence angles. A point-source-like excitation of ultrawideband acoustic radiation was induced via the absorption of nanosecond duration laser pulses by a 20 μm diameter microsphere. The acoustic waves transmitted through the skull are recorded by a broadband, spherically focused ultrasound transducer. A coregistered pulse-echo ultrasound scan is subsequently performed to provide accurate skull geometry to be fed into an acoustic transmission model represented in an angular spectrum domain. The modeling predictions were validated by measurements taken from a glass cover-slip and ex vivo adult mouse skulls. The flexible semi-analytical formulation of the model allows for seamless extension to other transducer geometries and diverse experimental scenarios involving broadband acoustic transmission through locally flat solid structures. It is anticipated that accurate quantification and modeling of the skull transmission effects would ultimately allow for skull aberration correction in a broad variety of applications employing transcranial detection or transmission of high frequency ultrasound.

Experimental evaluation of cMUT and PZT transducers in receive only mode for photoacoustic imaging

In photoacoustic imaging, the angular reception performance of ultrasonic transducers is a critical parameter to be considered for system designers. The quantitative comparison between cMUT and PZT emphasizes the difference between the transducer requirements and specifications between conventional ultrasound and photoacoustic imaging. In this present work, we show significant benefits of cMUT based array transducers over conventional PZT arrays for the improvement of quality in photoacoustic imaging systems.

Optoacoustic characterization of broadband directivity patterns of capacitive micromachined ultrasonic transducers

Abstract. Frequency characteristics of ultrasound detectors used in optoacoustic tomography have a major impact on imaging performance. It is common practice to select transducers based on their sensitivity at the central frequency and under normal incidence. However, the bandwidth and angular sensitivity play an equally important role in establishing the quality and accuracy of the reconstructed images. Here, we developed a calibrated optoacoustic characterization method specifically tailored for broadband measurements of the angular transducer sensitivity (directivity). Ultrawideband omnidirectional optoacoustic responses were generated by uniformly illuminating thin absorbing sutures with nanosecond laser pulses and characterized with a needle hydrophone. This calibrated optoacoustic source was used to characterize the frequency dependence of the angular response by a conventional piezoelectric transducer (PZT) and a capacitive micromachined ultrasonic transducer (cMUT) with similar size and central frequency. Furthermore, both transducers had no preamplification electronics directly attached to the detection elements. While the PZT presented a 7.8 dB sensitivity advantage at normal incidence, it was able to provide detectable signal-to-noise levels only at incidence angles of up to 20 deg whereas the cMUT maintained reasonable sensitivity levels and broadband response at incidence angles of 40 deg and beyond. We further experimentally showcase a reduction in the limited-view image artifacts resulting from the broader acceptance angle of the cMUT.

Optical imaging of post-embryonic zebrafish using multi orientation raster scan optoacoustic mesoscopy

Whole-body optical imaging of post-embryonic stage model organisms is a challenging and long sought-after goal. It requires a combination of high-resolution performance and high-penetration depth. Optoacoustic (photoacoustic) mesoscopy holds great promise, as it penetrates deeper than optical and optoacoustic microscopy while providing high-spatial resolution. However, optoacoustic mesoscopic techniques only offer partial visibility of oriented structures, such as blood vessels, due to a limited angular detection aperture or the use of ultrasound frequencies that yield insufficient resolution. We introduce 360° multi orientation (multi-projection) raster scan optoacoustic mesoscopy (MORSOM) based on detecting an ultra-wide frequency bandwidth (up to 160 MHz) and weighted deconvolution to synthetically enlarge the angular aperture. We report unprecedented isotropic in-plane resolution at the 9–17 μm range and improved signal to noise ratio in phantoms and opaque 21-day-old Zebrafish. We find that MORSOM performance defines a new operational specification for optoacoustic mesoscopy of adult organisms, with possible applications in the developmental biology of adulthood and aging.

Virtual craniotomy for high-resolution optoacoustic brain microscopy

Ultrasound-mediated transcranial images of the brain often suffer from acoustic distortions produced by the skull bone. In high-resolution optoacoustic microscopy, the skull-induced acoustic aberrations are known to impair image resolution and contrast, further skewing the location and intensity of the different absorbing structures. We present a virtual craniotomy deconvolution algorithm based on an ultrasound wave propagation model that corrects for the skull-induced distortions in optically-resolved optoacoustic transcranial microscopy data. The method takes advantage of the geometrical and spectral information of a pulse-echo ultrasound image of the skull simultaneously acquired by our multimodal imaging system. Transcranial mouse brain imaging experiments confirmed the ability to accurately account for the signal amplitude decay, temporal delay and pulse broadening introduced by the rodent’s skull. Our study is the first to demonstrate skull-corrected transcranial optoacoustic imaging in vivo.

Broadband optoacoustic characterization of cMUT and PZT transducer directivity in receive mode

Optoacoustic imaging is a rapidly developing area of biomedical imaging due its combination of rich optical contrast and ultrasound depth penetration. Just like conventional pulse-echo ultrasound imaging, optoacoustic tomography relies on the use of ultrasound detector arrays with a large number of elements. The precise knowledge of the transducer’s sensitivity is crucial for the prediction of its performance for a given imaging task. Sensitivity characteristics such as the central frequency and bandwidth are routinely characterized. However, this characterization is typically performed solely under normal incidence since the measurement of the angle and frequency depended sensitivity (directivity) is difficult and time consuming with existing ultrasound characterization methods. We present a simple and fast characterization method for broadband directivity measurements of the angular transducer sensitivity based on the optoacoustic effect. The method utilizes a thin absorbing suture in order to generate omnidirectional and broadband optoacoustic signals, which are calibrated using a needle hydrophone. We applied this method to characterize and compare the directivity of a conventional piezoelectric (PZT) transducer to the directivity of a capacitive micromachined ultrasonic (cMUT) transducer. Both technologies showed a similar broadband response at normal incidence and the PZT transducer displayed a more than two times larger signal to noise ratio at normal incidence. However, the cMUT transducer’s sensitivity was significantly less angle-depended and outperformed the PZT’s sensitivity for angles larger than 20°.

Prediction and near-field observation of skull-guided acoustic waves

Ultrasound waves propagating in water or soft biological tissue are strongly reflected when encountering the skull, which limits the use of ultrasound-based techniques in transcranial imaging and therapeutic applications. Current knowledge on the acoustic properties of the cranial bone is restricted to far-field observations, leaving its near-field unexplored. We report on the existence of skull-guided acoustic waves, which was herein confirmed by near-field measurements of optoacoustically-induced responses in ex-vivo murine skulls immersed in water. Dispersion of the guided waves was found to reasonably agree with the prediction of a multilayered flat plate model. We observed a skull-guided wave propagation over a lateral distance of at least 3 mm, with a half-decay length in the direction perpendicular to the skull ranging from 35 to 300 μm at 6 and 0.5 MHz, respectively. Propagation losses are mostly attributed to the heterogenous acoustic properties of the skull. It is generally anticipated that our findings may facilitate and broaden the application of ultrasound-mediated techniques in brain diagnostics and therapy.

In-vivo assessment of radiation-induced cerebrovascular damage in mice by hybrid optoacoustic-ultrasound bio-microscopy (Conference Presentation)

Radiation-induced brain damage could arise as a side effect in radiotherapy of brain tumors. We present evidence of radiation-induced damage to the skull and brain vasculature of mice as revealed by transcranial optoacoustic and ultrasound bio-microscopy in-vivo. The three-dimensional nature of the acquired optoacoustic images combined with a clear anatomical reference of the pulse-echo ultrasound data allowed clear differentiation of the skull vasculature from the superficial brain vasculature. The irradiation was selectively applied to one brain hemisphere and the effects of the ionizing radiation were evident without introduction of extrinsic labeling, owing to the strong haemoglobin contrast of optoacoustics.

A new catheter design for combined radiofrequency ablation and optoacoustic treatment monitoring using copper-coated light-guides

Electrosurgery, i.e. the application of radiofrequency current for tissue ablation, is a frequently used treatment for many cardiac arrhythmias. Electrophysiological and anatomic mapping, as well as careful radiofrequency power control typically guide the radiofrequency ablation procedure. Despite its widespread application, accurate monitoring of the lesion formation with sufficient spatio-temporal resolution remains challenging with the existing imaging techniques. We present a novel integrated catheter for simultaneous radiofrequency ablation and optoacoustic monitoring of the lesion formation in real time and 3D. The design combines the delivery of both electric current and optoacoustic excitation beam in a single catheter consisting of copper-coated multimode light-guides and its manufacturing is described in detail. The electrical current causes coagulation and desiccation while the excitation light is locally absorbed, generating OA responses from the entire treated volume. The combined ablation-monitoring capabilities were verified using ex-vivo bovine tissue. The formed ablation lesions showed a homogenous coagulation while the ablation was monitored in realtime with a volumetric frame rate of 10 Hz over 150 seconds.