It has been shown that light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) provides marginal brain sensitivity for CBFi in adult humans, new techniques have recently emerged to improve diffuse light throughput and thus, brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to number of independent channels, camera duty cycle and full well capacity, incident power, noise and artifact mitigation, and data processing.
View Article and Find Full Text PDFShort-pulsed solid-state lasers (SSLs) are the most commonly employed light sources in optoacoustic imaging applications. However, their bulky size hinders compact and portable system implementations. Here we developed a compact laser diode (LD)-based optoacoustic mesoscopy (CoLD-OAM) scanner that employs a fiber-coupled laser diode source with 46 × 43 × 11 mm dimensions.
View Article and Find Full Text PDFAcoustic waves provide a biocompatible and deep-tissue-penetrating tool suitable for contactless manipulation in in vivo environments. Despite the prevalence of dynamic fluids within the body, previous studies have primarily focused on static fluids, and manipulatable agents in dynamic fluids are limited to gaseous core-shell particles. However, these gas-filled particles face challenges in fast-flow manipulation, complex setups, design versatility, and practical medical imaging, underscoring the need for effective alternatives.
View Article and Find Full Text PDFSignificance: An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses.
Aim: Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses.
Monitoring brain responses to ultrasonic interventions is becoming an important pillar of a growing number of applications employing acoustic waves to actuate and cure the brain. Optical interrogation of living tissues provides a unique means for retrieving functional and molecular information related to brain activity and disease-specific biomarkers. The hybrid optoacoustic imaging methods have further enabled deep-tissue imaging with optical contrast at high spatial and temporal resolution.
View Article and Find Full Text PDFOptoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In principle, image reconstruction performance could be enhanced by simulating the optoacoustic signal generation, propagation, and detection path.
View Article and Find Full Text PDFSkull bone is the main obstacle for transcranial ultrasound therapy and imaging applications. Most efforts in characterizing ultrasonic properties of the skull have been limited to a narrow frequency range and normal incidence. On the other hand, acoustic guided waves in plates have been used in non-destructive evaluation of materials and also to assess the strength of long bones.
View Article and Find Full Text PDFSkull bone development is a dynamic and well-coordinated process playing a key role in maturation and maintenance of the bone marrow (BM), fracture healing, and progression of diseases such as osteoarthritis or osteoporosis. At present, dynamic transformation of the growing bone (osteogenesis) as well as its vascularization (angiogenesis) remain largely unexplored due to the lack of suitable in vivo imaging techniques capable of noninvasive visualization of the whole developing calvaria at capillary-level resolution. We present a longitudinal study on skull bone development using ultrasound-aided large-scale optoacoustic microscopy (U-LSOM).
View Article and Find Full Text PDFBackground: Intestinal fibrosis is a serious complication of Crohn's disease. Numerous cell types including intestinal epithelial and mesenchymal cells are implicated in this process, yet studies are hampered by the lack of personalized in vitro models. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain these cell types, and our goal was to determine the feasibility of utilizing these to develop a personalized intestinal fibrosis model.
View Article and Find Full Text PDFMicroenvironmental factors modulating age-related DNA damage are unclear. Non-pituitary growth hormone (npGH) is induced in human colon, non-transformed human colon cells, and fibroblasts, and in 3-dimensional intestinal organoids with age-associated DNA damage. Autocrine/paracrine npGH suppresses p53 and attenuates DNA damage response (DDR) by inducing TRIM29 and reducing ATM phosphorylation, leading to reduced DNA repair and DNA damage accumulation.
View Article and Find Full Text PDFUnderstanding the physiological impact of transcranial ultrasound in rodent brains may offer an important preclinical model for human scale magnetic resonance–guided focused ultrasound methods. However, precision tools for high-resolution transcranial ultrasound targeting and real-time in vivo tracking of its effects at the mouse brain scale are currently lacking. We report a versatile bidirectional hybrid fluorescence-ultrasound (FLUS) system incorporating a 0.
View Article and Find Full Text PDFIEEE Trans Ultrason Ferroelectr Freq Control
January 2021
Ultrasound can be delivered transcranially to ablate brain tissue, open the blood-brain barrier, or affect neural activity. Transcranial focused ultrasound in small rodents is typically done with low-frequency single-element transducers, which results in unspecific targeting and impedes the concurrent use of fast neuroimaging methods. In this article, we devised a wide-angle spherical array bidirectional interface for high-resolution parallelized optoacoustic imaging and transcranial ultrasound (POTUS) delivery in the same target regions.
View Article and Find Full Text PDFOptoacoustic microscopy (OAM) can image intrinsic optical absorption contrast at depths of several millimeters where state-of-the-art optical microscopy techniques fail due to intense light scattering in living tissues. Yet, wide adoption of OAM in biology and medicine is hindered by slow image acquisition speed, small field of view (FOV), and/or lack of spectral differentiation capacity of common system implementations. We report on a rapid acquisition functional optoacoustic micro-angiography approach that employs a burst-mode laser triggering scheme to simultaneously acquire multi-wavelength 3D images over an extended FOV covering ${50}\;{\rm mm} \times {50}\;{\rm mm}$50mm×50mm in a single mechanical overfly scan, attaining 28 µm and 14 µm resolution in lateral and axial dimensions, respectively.
View Article and Find Full Text PDFBone microvasculature plays a paramount role in bone marrow maintenance, development, and hematopoiesis. Studies of calvarian vascular patterns within living mammalian skull with the available intravital microscopy techniques are limited to small scale observations. We developed an optical-resolution optoacoustic microscopy method combined with ultrasound biomicroscopy in order to reveal and discern the intricate networks of calvarian and cerebral vasculature over large fields of view covering majority of the murine calvaria.
View Article and Find Full Text PDFIn inflammatory bowel disease (IBD), the intestinal epithelium is characterized by increased permeability both in active disease and remission states. The genetic underpinnings of this increased intestinal permeability are largely unstudied, in part due to a lack of appropriate modelling systems. Our aim is to develop an model of intestinal permeability using induced pluripotent stem cell (iPSC)-derived human intestinal organoids (HIOs) and human colonic organoids (HCOs) to study barrier dysfunction.
View Article and Find Full Text PDFAngiogenesis is critical in bone development and growth. Dense, large-scale, and multi-layered vascular networks formed by thin-walled sinusoidal vessels perfuse the plate bones and play an important role in bone repair. Yet, the intricate functional morphology of skull microvasculature remains poorly understood as it is difficult to visualize using existing intravital microscopy techniques.
View Article and Find Full Text PDFFunctional optoacoustic (OA) imaging assisted with genetically encoded calcium ion indicators (GECIs) holds promise for imaging large-scale neuronal activity at depths and spatiotemporal resolutions not attainable with existing optical microscopic techniques. However, currently available GECIs optimized for fluorescence (FL) imaging lack sufficient contrast for OA imaging and respond at wavelengths having limited penetration into the mammalian brain. Here we present an imaging platform capable of rapid assessment and cross-validation between OA and FL responses of sensor proteins expressed in Escherichia coli colonies.
View Article and Find Full Text PDFHuman skull poses a significant barrier for the propagation of ultrasound waves. Development of methods enabling more efficient ultrasound transmission into and from the brain is therefore critical for the advancement of ultrasound-mediated transcranial imaging or actuation techniques. We report on the first observation of guided acoustic waves in the near field of an ex vivo human skull specimen in the frequency range between 0.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
December 2017
Background And Aims: Human intestinal organoids derived from induced pluripotent stem cells have tremendous potential to elucidate the intestinal epithelium's role in health and disease, but it is difficult to directly assay these complex structures. This study sought to make this technology more amenable for study by obtaining epithelial cells from induced pluripotent stem cell-derived human intestinal organoids and incorporating them into small microengineered Chips. We then investigated if these cells within the Chip were polarized, had the 4 major intestinal epithelial subtypes, and were biologically responsive to exogenous stimuli.
View Article and Find Full Text PDFA critical link exists between pathological changes of cerebral vasculature and diseases affecting brain function. Microscopic techniques have played an indispensable role in the study of neurovascular anatomy and functions. Yet, investigations are often hindered by suboptimal trade-offs between the spatiotemporal resolution, field-of-view (FOV) and type of contrast offered by the existing optical microscopy techniques.
View Article and Find Full Text PDFUltrasound-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.
View Article and Find Full Text PDFUltrasound 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.
View Article and Find Full Text PDFThe mechanisms to communicate emotions have dramatically changed in the last 10 years with social networks, where users massively communicate their emotional states by using the Internet. However, people with socialization problems have difficulty expressing their emotions verbally or interpreting the environment and providing an appropriate emotional response. In this paper, a novel solution called the Emotion-Bracelet is presented that combines a hardware device and a software system.
View Article and Find Full Text PDFIt 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.
View Article and Find Full Text PDFThe recently demonstrated control over light distribution through turbid media based on real-time three-dimensional optoacoustic feedback has offered promising prospects to interferometrically focus light within scattering objects. Nevertheless, the focusing capacity of the feedback-based approach is strongly conditioned by the number of optical modes (speckle grains) enclosed in the volume that can be resolved with the optoacoustic imaging system. In this Letter, we experimentally tested the light intensity enhancement achieved with optoacoustic feedback measurements from different sizes of absorbing microparticles.
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