In-vivo handheld optoacoustic tomography of the human thyroid.

We interrogated the application and imaging features obtained by non-invasive and handheld optoacoustic imaging of the thyroid in-vivo. Optoacoustics can offer complementary contrast to ultrasound, by resolving optical absorption-based and offering speckle-free imaging. In particular we inquired whether vascular structures could be better resolved using optoacoustics. For this reason we developed a compact handheld version of real-time multispectral optoacoustic tomography (MSOT) using a detector adapted to the dimensions and overall geometry of the human neck. For delivering high-fidelity performance, a curved ultrasound array was employed. The feasibility of handheld thyroid MSOT was assessed on healthy human volunteers at single wavelength. The results were contrasted to ultrasound and Doppler ultrasound images obtained from the same volunteers. Imaging findings demonstrate the overall MSOT utility to accurately retrieve optical features consistent with the thyroid anatomy and the morphology of surrounding structures.

Multispectral opto-acoustic tomography of exercised muscle oxygenation.

Unlike near-infrared spectroscopy, multispectral opto-acoustic tomography (MSOT) has the potential to offer high-resolution imaging assessment of hemodynamics and blood saturation levels in muscle. However motion artifacts impede the real-time applications of the technique. We developed fast-MSOT with motion tracking that reduces motion artifacts. We used this algorithm to follow blood oxygenation level changes associated with muscle exercise in the muscle and the skin of healthy volunteers.

Multispectral optoacoustic tomography at 64, 128, and 256 channels.

Optoacoustic (photoacoustic) imaging has already showcased the capacity to offer high-resolution small animal visualization in vivo in a variety of cancer, cardiovascular, or neuroimaging applications. In particular, multispectral optoacoustic tomography (MSOT) has shown imaging along the spectral and the time dimensions, enabling sensing of multiple molecules over time and, more recently, in real time. Furthermore, cross-sectional imaging of at least 20 mm diameter has been showcased in vivo in animals and humans using 64-element curved transducers placed along a single curved line. Herein, we investigated the imaging improvements gained by utilizing a larger number of detectors and inquired whether more detectors will result in measurable image quality improvements. For this reason, we implemented MSOT using 64-, 128-, and 256-element transducers and imaged the same phantoms and animals under similar conditions. Further, corroborated by numerical simulation analysis, our findings quantify the improvements in resolution and overall image quality for the increasing number of detectors used pointing to significant improvements in image quality for the 256 detector array, over 64 or 128 detectors.

Optoacoustic imaging of blood perfusion: techniques for intraoperative tissue viability assessment.

Reliably assessing tissue viability during surgery is of major importance in surgical procedures. The most basic requirement for viability is sufficient oxygen supply to the tissue. Therefore it is highly desirable to visualize in real-time the dynamic process of blood perfusion up to and within the microvasculature. A modality sensitive to structures in the range of few hundred micrometers and offering high contrast to the embedding tissue is then needed. To this end, a number of methods have been developed, but have had no significant impact on the clinical routine due to various deficiencies. In this paper we demonstrate the applicability of optoacoustic imaging, which combines ultrasonic resolution with strong optical contrast. A method for optoacoustic perfusion assessment, based on a local and repeatable injection of saline, was proposed and assessed ex-vivo on large pig bowels and in-vivo in mouse tails. The obtained dynamic perfusion images highlight the method's potential to enable immediate and quantitative assessment of tissue viability during surgery.

Three-dimensional optoacoustic tomography using a conventional ultrasound linear detector array: whole-body tomographic system for small animals.

PURPOSE: Optoacoustic imaging relies on the detection of ultrasonic waves induced by laser pulse excitations to map optical absorption in biological tissue. A tomographic geometry employing a conventional ultrasound linear detector array for volumetric optoacoustic imaging is reported. The geometry is based on a translate-rotate scanning motion of the detector array, and capitalizes on the geometrical characteristics of the transducer assembly to provide a large solid angular detection aperture. A system for three-dimensional whole-body optoacoustic tomography of small animals is implemented. METHODS: The detection geometry was tested using a 128-element linear array (5.0∕7.0 MHz, Acuson L7, Siemens), moved by steps with a rotation∕translation stage assembly. Translation and rotation range of 13.5 mm and 180°, respectively, were implemented. Optoacoustic emissions were induced in tissue-mimicking phantoms and ex vivo mice using a pulsed laser operating in the near-IR spectral range at 760 nm. Volumetric images were formed using a filtered backprojection algorithm. RESULTS: The resolution of the optoacoustic tomography system was measured to be better than 130 µm in-plane and 330 µm in elevation (full width half maximum), and to be homogenous along a 15 mm diameter cross section due to the translate-rotate scanning geometry. Whole-body volumetric optoacoustic images of mice were performed ex vivo, and imaged organs and blood vessels through the intact abdominal and head regions were correlated to the mouse anatomy. CONCLUSIONS: Overall, the feasibility of three-dimensional and high-resolution whole-body optoacoustic imaging of small animal using a conventional linear array was demonstrated. Furthermore, the scanning geometry may be used for other linear arrays and is therefore expected to be of great interest for optoacoustic tomography at macroscopic and mesoscopic scale. Specifically, conventional detector arrays with higher central frequencies may be investigated.

Non-invasive carotid imaging using optoacoustic tomography.

The high prevalence of atherosclerosis and the corresponding derived morbidity drives the investigation of novel imaging tools for disease diagnosis and assessment. Multi-spectral optoacoustic tomography (MSOT) can resolve structural, hemodynamic and molecular parameters that relate to cardiovascular disease. Similarly to ultrasound imaging, optoacoustic (photoacoustic) imaging can be implemented as a handheld arrangement which further brings dissemination potential to point of care applications. Correspondingly, we experimentally investigate herein the performance of non-invasive optoacoustic scanning developed for carotid imaging, in phantoms and humans. The results demonstrate that traditional transducers employed in ultrasound imaging do not offer optimal MSOT imaging. Instead, feasibility to detect human carotids and carotid-sized vessels in clinically-relevant depths is better demonstrated with curved arrays and tomographic approaches.

Model-based optoacoustic inversions with incomplete projection data.

PURPOSE: Optoacoustic imaging is an emerging noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with diffraction-limited resolution of ultrasound. Yet, quantified reconstruction of tissue absorption maps requires optoacoustic signals to be collected from as many locations around the object as possible. In many tomographic imaging scenarios, however, only limited-view or partial projection data are available, which has been shown to generate image artifacts and overall loss of quantification accuracy. METHODS: In this article, the recently introduced interpolated-matrix-model optoacoustic inversion method is tested in different limited-view scenarios and compared to the standard backprojection algorithm. Both direct (TGSVD) and iterative (PLSQR) regularization methods are proposed to improve the accuracy of image reconstructions with their performance tested on simulated and experimental data. RESULTS: While for full-view tomographic data the model-based inversion has been generally shown to attain higher reconstruction accuracy compared to backprojection algorithms, the incomplete tomographic datasets lead to ill-conditioned forward matrices and, consequently, to error-prone inversions, with strong artifacts following a distinct ripple-type pattern. The proposed regularization techniques are shown to stabilize the inversion and eliminate the artifacts. CONCLUSIONS: Overall, it has been determined that the regularized interpolated-matrix-model-based optoacoustic inversions show higher accuracy than reconstructions with the standard backprojection algorithm. Finally, the combination of model-based inversion with PLSQR or TGSVD regularization methods can lead to an accurate reconstruction of limited-projection angle optoacoustic data and practical systems for optoacoustic imaging in many realistic cases where the full-view dataset is unavailable.

Optoacoustic imaging for clinical applications: devices and methods.

INTRODUCTION: Optoacoustic (photoacoustic) imaging offers visualization of optical contrast in tissues, within several millimeters to centimeters, with resolutions that are typical of ultrasound imaging. This performance can offer a natural extension to widespread optical microscopy approaches, for applications from small animals to humans. AREAS COVERED: An increasing number of optoacoustic approaches are considered for biomedical imaging. Implementations range from handheld and endoscopic operations to fixed scanner set-ups that can address a wide range of preclinical and clinical needs. This article illuminates aspects of the underlying principles of optoacoustic imaging operation and critically reviews the major system trends developed for clinical application. In addition to anatomical imaging, typically performed using single wavelength illumination, multispectral methods are also reviewed as they pertain to functional and molecular imaging. This article also highlights the advantages and limitations as well as the potential of this technology for clinical practice. EXPERT OPINION: Optoacoustic imaging is an emerging and highly promising area of the imaging sciences that can offer high-resolution optical visualization deep within tissues. Therefore, it offers a promising alternative to existing optical systems developed for clinical use, which are generally limited to superficial or low-resolution imaging. These up-and-coming features offer a wider variety of optoacoustic approaches that are likely to be clinically deployed in the near future.

Optoacoustic tomography with varying illumination and non-uniform detection patterns.

Quantification of tissue morphology and biomarker distribution by means of optoacoustic tomography is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to mitigate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by per-projection variations of object's illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are showcased both numerically and experimentally on tissue phantoms and mice.