Optoacoustic imaging in endocrinology and metabolism.

Imaging is an essential tool in research, diagnostics and the management of endocrine disorders. Ultrasonography, nuclear medicine techniques, MRI, CT and optical methods are already used for applications in endocrinology. Optoacoustic imaging, also termed photoacoustic imaging, is emerging as a method for visualizing endocrine physiology and disease at different scales of detail: microscopic, mesoscopic and macroscopic. Optoacoustic contrast arises from endogenous light absorbers, such as oxygenated and deoxygenated haemoglobin, lipids and water, or exogenous contrast agents, and reveals tissue vasculature, perfusion, oxygenation, metabolic activity and inflammation. The development of high-performance optoacoustic scanners for use in humans has given rise to a variety of clinical investigations, which complement the use of the technology in preclinical research. Here, we review key progress with optoacoustic imaging technology as it relates to applications in endocrinology; for example, to visualize thyroid morphology and function, and the microvasculature in diabetes mellitus or adipose tissue metabolism, with particular focus on multispectral optoacoustic tomography and raster-scan optoacoustic mesoscopy. We explain the merits of optoacoustic microscopy and focus on mid-infrared optoacoustic microscopy, which enables label-free imaging of metabolites in cells and tissues. We showcase current optoacoustic applications within endocrinology and discuss the potential of these technologies to advance research and clinical practice.

Ultrasound nanotheranostics in fighting cancer: Advances and prospects.

The intrinsic limits of conventional ultrasound microbubble contrast agent greatly promoted the development and application of various nanomaterials for more efficient cancer ultrasound theranostics. Considerable successes have been achieved in the field of ultrasound molecular imaging and targeted therapy for tumor based on nanoparticulate theranostic agents. This review summarizes and discusses the emerging development on exploring organic and inorganic nanomaterials for ultrasound-based tumor diagnositic applications, and as synergistic agents for ultrasound targeted therapy in fighting cancer. The relationship between structure/composition and functionality of nanomaterials for ultrasound theranostic is discussed and revealed in detail. Finally, the further development and challenges facing clinical implementation of ultrasound nanomedicine are discussed. As a highly promising and valuable tumor-specific theranostic methodology, it is believed that ultrasound nanomedicine would pave a novel but efficient way for combating cancer.

Photoacoustic-based visual servoing of a needle tip.

In intraoperative settings, the presence of acoustic clutter and reflection artifacts from metallic surgical tools often reduces the effectiveness of ultrasound imaging and complicates the localization of surgical tool tips. We propose an alternative approach for tool tracking and navigation in these challenging acoustic environments by augmenting ultrasound systems with a light source (to perform photoacoustic imaging) and a robot (to autonomously and robustly follow a surgical tool regardless of the tissue medium). The robotically controlled ultrasound probe continuously visualizes the location of the tool tip by segmenting and tracking photoacoustic signals generated from an optical fiber inside the tool. System validation in the presence of fat, muscle, brain, skull, and liver tissue with and without the presence of an additional clutter layer resulted in mean signal tracking errors <2 mm, mean probe centering errors <1 mm, and successful recovery from ultrasound perturbations, representing either patient motion or switching from photoacoustic images to ultrasound images to search for a target of interest. A detailed analysis of channel SNR in controlled experiments with and without significant acoustic clutter revealed that the detection of a needle tip is possible with photoacoustic imaging, particularly in cases where ultrasound imaging traditionally fails. Results show promise for guiding surgeries and procedures in acoustically challenging environments with this novel robotic and photoacoustic system combination.

Photoacoustic Probes for Molecular Detection: Recent Advances and Perspectives.

Photoacoustic (PA) imaging (PAI) is a noninvasive and nonionizing biomedical imaging modality that combines the advantages of optical imaging and ultrasound imaging. Based on PAI, photoacoustic detection (PAD) is an emerging approach that is involved with the interaction between PA probes and analytes resulting in the changes of photoacoustic signals for molecular detection with rich contrast, high resolution, and deep tissue penetration. This Review focuses on the recent development of PA probes in PAD. The following contents will be discussed in detail: 1) the construction of PA probes; 2) the applications and mechanisms of PAD to different types of analytes, including microenvironments, small biomolecules, or metal ions; 3) the challenges and perspectives of PA probes in PAD.

A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast Masses: A New Evaluation Tool for Radiologists.

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.

A new look at the heart-novel imaging techniques.

The development and successful implementation of cutting-edge imaging technologies to visualise cardiac anatomy and function is a key component of effective diagnostic efforts in cardiology. Here, we describe a number of recent exciting advances in the field of cardiology spanning from macro- to micro- to nano-scales of observation, including magnetic resonance imaging, computed tomography, optical mapping, photoacoustic imaging, and electron tomography. The methodologies discussed are currently making the transition from scientific research to routine clinical use, albeit at different paces. We discuss the most likely trajectory of this transition into clinical research and standard diagnostics, and highlight the key challenges and opportunities associated with each of the methodologies.

Pushing the Boundaries of Neuroimaging with Optoacoustics.

With the central ability to visualize a variety of endogenous chromophores and biomarkers or exogenous contrast agents, optoacoustic (photoacoustic) imaging empowers new experimental capabilities for investigating brain mechanisms and functions. Here, the operational principles of optoacoustic neuroimaging are reviewed in conjunction with recent advances enabling high-resolution and real-time observation, which extend beyond the reach of optical imaging methods. Multiple implementations of optoacoustics for monitoring hemodynamics and neuro-vascular responses in the brain are showcased. The unique capabilities of optoacoustic imaging for multi-spectral cellular and molecular sensing are discussed with reference to recent application for visualizing healthy and diseased brains. Outstanding challenges in the field are considered in the context of current and future applications of optoacoustic neuroimaging for basic and translational neuroscience research. In pushing the boundaries of brain imaging, optoacoustic methods afford major insights into the neuronal mechanisms of brain functions and organization of behavior.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

[Development of Molecular Probes for Spatio-temporal Analysis of in Vivo Tumor with Photoacoustic Imaging].

Photoacoustic imaging (PA imaging or PAI) has been focused on as a new technique to provide images of high spatial resolution, at depths of up to 5 cm, and the development of novel PAI probes for tumor imaging is of marked interest. Although nanomaterials such as gold nanorods have been reported as PAI probes, dyes are required to aid their ease of preparation, cost-effectiveness, and safety. However, because PAI has relatively low intrinsic sensitivity compared to optical imaging, and requires high-energy laser pulse exposure, an appropriate probe design, high tumor accumulation, and photostability are required for PAI probes. We developed some dyes and evaluated their usefulness as PAI probes. We first developed a high tumor-accumulation dye probe, IC7-1-Bu, which utilizes serum albumin as a tumor-targeting carrier to deliver an adequate PA signal at the tumor. Although IC7-1-Bu showed strong tumor targeting ability and a sufficient PA signal at the tumor in in vivo studies, IC7-1-Bu lacks photostability against multiple laser irradiations of PAI. In order to improve dye photostablity, we focused on the effect of singlet oxygen ((1)O2) generated by excited PAI probes on probe degeneration, and developed a triplet-state quencher conjugated dye probe, IC-5-T. IC-5-T reduced (1)O2 generation and improved photostability against multiple irradiations compared to IC7-1-Bu. IC-5-T also showed a sufficient PA signal at the tumor, and 1.5-fold higher photostabillity compared to IC7-1-Bu in sequential in vivo PAI studies. These results suggest that IC-5-T is a potential PAI probe for tumor imaging.

Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications Towards Early-Stage Theranostics.

Photoacoustic imaging (PAI) has ushered in a new era of observational biotechnology and has facilitated the exploration of fundamental biological mechanisms and clinical translational applications, which has attracted tremendous attention in recent years. By converting laser into ultrasound emission, PAI combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. This evolutional technique enables multiscale and multicontrast visualization from cells to organs, anatomy to function, and molecules to metabolism with high sensitivity and specificity. The state-of-the-art developments and applications of PAI are described in this review. Future prospects for clinical use are also highlighted. Collectively, PAI holds great promise to drive biomedical applications towards early-stage theranostics.

[Optoacoustic imaging]. / Optoakustische Bildgebung.

CLINICAL/METHODICAL ISSUE: Imaging modalities play an increasing role in today's medical diagnostics. Among them, ultrasound (US) is one the most widespread techniques although it has relatively poor soft tissue contrast. Furthermore, US is poorly suited as a modality for molecular imaging (MI). STANDARD RADIOLOGICAL METHODS: Methods such as Doppler and contrast-enhanced US (CEUS) allow functional imaging of the vasculature; however, ultrasound-based MI remains limited to the vascular network due to the size of available contrast agents. METHODICAL INNOVATIONS: Optoacoustic imaging combines the benefits of optics (high contrast) with those of acoustics (low scattering and high resolution). In this technique, signals are generated in tissue with high contrast depending on the local optical absorption coefficient and detected with an acoustic procedure. PERFORMANCE: Optoacoustic imaging can intrinsically be scaled in terms of resolution and is therefore usable in various applications from in vitro microscopy, to preclinical small animal imaging up to clinical imaging. With a resolution in the range of clinical ultrasound systems (100-400 µm), highly scattering tissue can be imaged up to several centimeters in depth. ACHIEVEMENTS: In contrast to conventional ultrasound imaging, optoacoustic techniques are highly suitable for MI. Various contrast agents as well as different technical implementations of the approach have already been preclinically evaluated. The technique is currently close to being transferred to clinical implementation and the first studies have already been started. PRACTICAL RECOMMENDATIONS: Clinical studies are ongoing with respect to early diagnosis of breast cancer and arthritis. Furthermore, the suitability of the technique for skin imaging is currently being investigated.

Optical innovations in surgery.

BACKGROUND: In the past decade, there has been a major drive towards clinical translation of optical and, in particular, fluorescence imaging in surgery. In surgical oncology, radical surgery is characterized by the absence of positive resection margins, a critical factor in improving prognosis. Fluorescence imaging provides the surgeon with reliable and real-time intraoperative feedback to identify surgical targets, including positive tumour margins. It also may enable decisions on the possibility of intraoperative adjuvant treatment, such as brachytherapy, chemotherapy or emerging targeted photodynamic therapy (photoimmunotherapy). METHODS: This article reviews the use of optical imaging for intraoperative guidance and decision-making. RESULTS: Image-guided cancer surgery has the potential to be a powerful tool in guiding future surgical care. Photoimmunotherapy is a theranostic concept (simultaneous diagnosis and treatment) on the verge of clinical translation, and is highlighted as an effective combination of image-guided surgery and intraoperative treatment of residual disease. Multispectral optoacoustic tomography, a technique complementary to optical image-guided surgery, is currently being tested in humans and is anticipated to have great potential for perioperative and postoperative application in surgery. CONCLUSION: Significant advances have been achieved in real-time optical imaging strategies for intraoperative tumour detection and margin assessment. Optical imaging holds promise in achieving the highest percentage of negative surgical margins and in early detection of micrometastastic disease over the next decade.

Ultrasound-guided photoacoustic imaging: current state and future development.

Photoacoustic imaging, frequently coregistered with ultrasonic imaging, can provide functional and cellular/molecular information about tissue within the anatomical landmarks of an imaged region. This review details the fundamentals of photoacoustic imaging and its most promising imaging applications. Particular attention is paid to photoacoustic imaging's relationship with ultrasound, focusing on distinct differences and similarities between the two modalities and highlighting the mutual benefit of using both concurrently in certain preclinical and clinical applications. Much like its origins as an imaging modality were intertwined with ultrasonic imaging (namely, its acoustic transducers and hardware), the future of photoacoustic imaging-particularly in the clinical arena-similarly depends on ultrasound and its time-tested ability to provide real-time visualization of soft tissue.

The 'nanobig rod' class of gold nanorods: optimized dimensions for improved in vivo therapeutic and imaging efficacy.

Currently, gold nanorods can be synthesized in a wide range of sizes. However, for the intended biological applications gold nanorods with approximate dimensions 50 nm × 15 nm are used. We investigate by computer simulation the effect of particle dimensions on the optical and thermal properties in the context of the specific applications of photoacoustic imaging. In addition we discuss the influence of particle size in overcoming the following biophysical barriers when administrated in vivo: extravasation, avoidance of uptake by organs of the reticuloendothelial system, penetration through the interstitium, binding capability and uptake by the target cells. Although more complex biological influences can be introduced in future analysis, the present work illustrates that larger gold nanorods, designated by us as 'nanobig rods', may perform better at meeting the requirements for successful in vivo applications compared to their smaller counterparts, which are conventionally used.

Medical imaging: just what the doctor (and the researcher) ordered: new applications for medical imaging technology.

Medical imaging has come a long way in the past decade. From the gold standards of ultrasound, magnetic resonance (MR), and computed tomography (CT) to new and combined technologies, medical imaging is yielding extreme close-up views of the fine details of tissues and revealing the dynamics of cellular and molecular biology, often in real time. With this in-depth information, researchers are unraveling the how and why of diseases so they can work toward developing novel drugs and other treatment options as well as earlier disease detection and prevention. At the same time, clinicians are beginning to employ the advanced imaging modalities to determine more accurately the stage of disease in patients, and to personalize therapy to provide the best possible outcome for individuals with cancer or other illnesses.

Photoacoustic imaging: a potential tool to detect early indicators of metastasis.

The metastasis of cancer is a multistage process involving complex biological interactions and difficult to predict outcomes. Accurate assessment of the extent of metastasis is critical for clinical practice; unfortunately, medical imaging methods capable of identifying the early stages of invasion and metastasis are lacking. Photoacoustic imaging is capable of providing noninvasive, real-time imaging of significant anatomical and physiological changes. indicating the progression of cancer invasion and metastasis. Preclinically, photoacoustic methods have been used to image lymphatic anatomy, including the sentinel lymph nodes, to identify circulating tumor cells within vasculature and to detect micrometastases. Progress has begun toward the development of clinically applicable photoacoustic imaging systems to assist with the determination of cancer stage and likelihood of metastatic invasion.

Recent advances in colloidal gold nanobeacons for molecular photoacoustic imaging.

Photoacoustic imaging (PAI) represents a hybrid, nonionizing modality, which has been of particular interest because of its satisfactory spatial resolution and high soft tissue contrast. PAI has the potential to provide both functional and molecular imaging in vivo since optical absorption is sensitive to physiological parameters. In this review we summarize our effort to advance molecular PAI with colloidal gold nanobeacons (GNB). GNB represents a robust nanoparticle platform that entraps multiple copies of tiny gold nanoparticles (2-4 nm) within a larger colloidal particle encapsulated by biocompatible synthetic or natural amphilines. The utilization of numerous small gold particles greatly amplifies the signal without exceeding the renal elimination threshold size. With fibrin-targeted GNB, the robust detection of microthrombus formed over a ruptured atherosclerotic plaque has been achieved, which offers an important opportunity to recognize patients with moderate lumen stenosis but high risk of stroke. With the use of second-generation smaller GNBs, the potential to improve sentinel lymph node assessment and biopsy was advanced with respect to rapidity and sensitivity of detection in mice. Finally, for angiogenesis, an essential microanatomical biomarker of tumor and cardiovascular disease progression, integrin-targeted GNBs allowed visualization of numerous angiogenic sprouts and bridges that were otherwise undetectable from inherent blood signal alone, offering sensitive and specific discrimination and quantification of angiogenesis in vivo.

Gold nanorods as molecular contrast agents in photoacoustic imaging: the promises and the caveats.

Rod-shaped gold nanoparticles exhibit intense and narrow absorption peaks for light in the far-red and near-infrared wavelength regions, owing to the excitation of longitudinal plasmons. Light absorption is followed predominantly by non radiative de-excitation, and the released heat and subsequent temperature rise cause strong photoacoustic (optoacoustic) signals to be produced. This feature combined with the relative inertness of gold, and its favorable surface chemistry, which permits affinity biomolecule coupling, has seen gold nanorods (AuNR) attracting much attention as contrast agents and molecular probes for photoacoustic imaging. In this article we provide an short overview of the current status of the use of AuNR in molecular imaging using photoacoustics. We further examine the state of the art in various chemical, physical and biochemical phenomena that have implications for the future photoacoustic applications of these particles. We cover the route through fine-tuning of AuNR synthetic procedures, toxicity reduction by appropriate coatings, in vitro cellular interactions of AuNRs, attachment of targeting antibodies, in vivo fate of the particles and the effects of certain light interactions with the AuNR.

Photoacoustic tomography: fundamentals, advances and prospects.

Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges.

[Means and methods of acoustic protection in aviation: current status and outlook for development].

Analysis of the current status of acoustic protection in aviation shows that despite the material progress in the field, risk of professional pathologies in flying and technical personnel is still high. The situation is dramatized by the lack of effective personal and crew acoustic protectors. The authors speculate on applicability of innovative materials and technologies, ingenious designs of earphones and modular prefabricated demountable structures. Tests of proposed personal protectors demonstrated their competitiveness with foreign analogs. Prospective lines of development, e.g. incorporation of active sound absorption systems in existing passive protectors are discussed.