TY - JOUR AB - Parkinson's disease is a devastating neurodegenerative disorder characterized by loss of neuromelanin-containing dopaminergic neurons. Novel 3D culture systems like human midbrain-like organoids (hMOs) enable new research avenues for patient-specific therapies, but cannot reach their full potential unless rapid optical imaging of entire organoids is enabled. Currently, hMOs have to undergo tissue clearing processes before imaging to overcome light scattering. Since tissue clearing is a lengthy chemical procedure, large ensemble studies and pharmacological longitudinal studies, which require live cultures, are impossible. To address this obstacle, raster scanning optoacoustic mesoscopy (RSOM) is considered for imaging intact hMOs. RSOM is an optical imaging technique that leverages the optoacoustic effect to overcome the need of tissue clearing. Moreover, by using tomographic principles, large specimens can be imaged within minutes. The results confirm that RSOM can image the neuromelanin distribution in complete hMOs at a single-cell resolution. Whole hMO volumes of standard size can be imaged in 4 min. Comparison with bright-field microscopy and histology confirms the ground truth of the RSOM images. This work opens several research opportunities regarding neuromelanin in hMOs with potential to boost research in Parkinson disease. AU - Englert, L. AU - Lacalle-Aurioles, M.* AU - Mohamed, N.V.* AU - Lépine, P.* AU - Mathur, M.* AU - Ntziachristos, V. AU - Durcan, T.M.* AU - Aguirre Bueno, J. C1 - 68410 C2 - 53648 CY - Postfach 101161, 69451 Weinheim, Germany TI - Fast 3D optoacoustic mesoscopy of neuromelanin through entire human midbrain organoids at single-cell resolution. JO - Laser Photon. Rev. VL - 17 IS - 8 PB - Wiley-v C H Verlag Gmbh PY - 2023 SN - 1863-8880 ER - TY - JOUR AB - The development of fluorophores with photoemission beyond 1000 nm provides the opportunity to develop novel fluorescence microscopes sensitive to those wavelengths. Imaging at wavelengths beyond the visible spectrum enables imaging depths of hundreds of microns in intact tissue, making this attractive for volumetric imaging applications. Here, a novel shortwave-infrared line-scan confocal microscope is presented that is capable of deep imaging of biological specimens, as demonstrated by visualization of labeled glomeruli in a fixed uncleared kidney at depths beyond 400 µm. Imaging of brain vasculature labeled with the near-infrared organic dye indocyanine green, the shortwave-infrared organic dye Chrom7, and rare earth-doped nanoparticles is also shown, thus encompassing the entire spectrum detectable by a typical shortwave-infrared sensitive InGaAs detector. AU - Lingg, J.G.P. AU - Bischof, T.S. AU - Arus, B.A. AU - Cosco, E. AU - Sletten, E.M.* AU - Rowlands, C.J.* AU - Bruns, O.T. AU - Chmyrov, A. C1 - 68303 C2 - 53627 CY - Postfach 101161, 69451 Weinheim, Germany TI - Shortwave-infrared line-scan confocal microscope for deep tissue imaging in intact organs. JO - Laser Photon. Rev. VL - 17 IS - 11 PB - Wiley-v C H Verlag Gmbh PY - 2023 SN - 1863-8880 ER - TY - JOUR AB - Zebrafish are common model organisms in developmental biology, but have recently emerged as imaging targets of research in cancer, tissue regeneration, metabolic disorders, functional genomics, and phenotype-based drug discovery. Conventionally, zebrafish are studied during the first few days of development using optical microscopy methods. However, optical methods are not suited for imaging at later stages, since the fish become opaque. To address needs to visualize beyond the first days of development, a novel multimodality system for observing zebrafish from larval stage to adulthood is developed. Using a hybrid platform for concurrent selective plane illumination microscopy (SPIM) and optoacoustic mesoscopy, fish (ex vivo) at stages of development up to 47 days at a similar object size-to-resolution ratio are imaged. Using multiple wavelength illumination over the visible and short-wavelength infrared regions, it is demonstrated that the optoacoustic method can follow GFP-based contrast used in SPIM, enabling molecular imaging interrogation in adult fish. Moreover, the optoacoustic modality reveals zebrafish features based on optical contrast absent in SPIM, including contrast from endogenous blood, water, and lipids. It is discussed how the hybrid system method can enable the study of zebrafish in a wider range of applications and over time-scales not possible currently when using optical microscopy. AU - Vetschera, P. AU - Koberstein-Schwarz, B. AU - Schmitt-Manderbach, T.* AU - Dietrich, C.* AU - Hellmich, W.* AU - Chekkoury, A. AU - Symvoulidis, P. AU - Reber, J. AU - Westmeyer, G.G. AU - López-Schier, H. AU - Omar, M. AU - Ntziachristos, V. C1 - 68169 C2 - 53613 CY - Postfach 101161, 69451 Weinheim, Germany TI - Beyond early development: Observing Zebrafish over 6 weeks with hybrid optical and optoacoustic imaging. JO - Laser Photon. Rev. VL - 17 IS - 7 PB - Wiley-v C H Verlag Gmbh PY - 2023 SN - 1863-8880 ER - TY - JOUR AB - Tracking of biodynamics across entire living organisms is essential for understanding complex biology and disease progression. The presently available small-animal functional and molecular imaging modalities remain constrained by factors including long image acquisition times, low spatial resolution, limited penetration or poor contrast. Here flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high-speed imaging of fast kinetics and biodistribution of optical contrast agents in whole mice that simultaneously provides reference images of vascular and organ anatomy with unrivaled fidelity and contrast, is presented. The imaging protocol employs continuous overfly scanning of a spherical matrix array transducer, accomplishing a 200 µm resolution 3D scan of the whole mouse body within 45 s without relying on signal averaging. This corresponds to an imaging speed gain of more than an order of magnitude compared with existing state-of-the-art implementations of comparable resolution performance. Volumetric tracking and quantification of gold nanoagent and near infrared (NIR)-II dye kinetics and their differential uptake in various organs are demonstrated. fSVOT thus offers unprecedented capabilities for multiscale imaging of pharmacokinetics and biodistribution with high contrast, resolution, and speed. AU - Ron, A.* AU - Kalva, S.K.* AU - Periyasamy, V. AU - Deán-Ben, X.L.* AU - Razansky, D. C1 - 61379 C2 - 50204 CY - Postfach 101161, 69451 Weinheim, Germany TI - Flash scanning volumetric optoacoustic tomography for high resolution whole-body tracking of nanoagent kinetics and biodistribution. JO - Laser Photon. Rev. VL - 15 IS - 3 PB - Wiley-v C H Verlag Gmbh PY - 2021 SN - 1863-8880 ER - TY - JOUR AB - Scanning optical microscopy techniques are commonly restricted to a sub-millimeter field-of-view (FOV) or otherwise employ slow mechanical translation, limiting their applicability for imaging fast biological dynamics occurring over large areas. A rapid scanning large-field multifocal illumination (LMI) fluorescence microscopy technique is devised based on a beam-splitting grating and an acousto-optic deflector synchronized with a high-speed camera to attain real-time fluorescence microscopy over a centimeter-scale FOV. Owing to its large depth of focus, the approach allows noninvasive visualization of perfusion across the entire mouse cerebral cortex, not achievable with conventional wide-field fluorescence microscopy methods. The new concept can readily be incorporated into conventional wide-field microscopes to mitigate image blur due to tissue scattering and attain optimal trade-off between spatial resolution and FOV. It further establishes a bridge between conventional wide-field macroscopy and laser scanning confocal microscopy, thus it is anticipated to find broad applicability in functional neuroimaging, in vivo cell tracking, and other applications looking at large-scale fluorescent-based biodynamics. AU - Chen, Z.* AU - Mc Larney, B. AU - Rebling, J.* AU - Dean-Ben, X.L.* AU - Zhou, Q.* AU - Gottschalk, S. AU - Razansky, D. C1 - 57736 C2 - 47884 CY - Postfach 101161, 69451 Weinheim, Germany TI - High-speed large-field Multifocal illumination fluorescence microscopy. JO - Laser Photon. Rev. VL - 14 IS - 2 PB - Wiley-v C H Verlag Gmbh PY - 2020 SN - 1863-8880 ER - TY - JOUR AB - Intravital imaging of large specimens is intrinsically challenging for postembryonic studies. Selective plane illumination microscopy (SPIM) has been introduced to volumetrically visualize organisms used in developmental biology and experimental genetics. Ideally suited for imaging transparent samples, SPIM can offer high frame rate imaging with optical microscopy resolutions and low phototoxicity. However, its performance quickly deteriorates when applied to opaque tissues. To overcome this limitation, SPIM optics were merged with optical and optoacoustic (photoacoustic) readouts. The performance of this hybrid imaging system was characterized using various phantoms and by imaging a highly scattering ex vivo juvenile zebrafish. The results revealed the system's enhanced capability over that of conventional SPIM for high-resolution imaging over extended depths of scattering content. The approach described here may enable future visualization of organisms throughout their entire development, encompassing regimes in which the tissue may become opaque. AU - Lin, H.-C. AU - Chekkoury, A. AU - Omar, M. AU - Schmitt-Manderbach, T.* AU - Koberstein-Schwarz, B. AU - Mappes, T.* AU - López-Schier, H. AU - Razansky, D. AU - Ntziachristos, V. C1 - 46800 C2 - 37847 SP - L29-L34 TI - Selective plane illumination optical and optoacoustic microscopy for postembryonic imaging. JO - Laser Photon. Rev. VL - 9 IS - 5 PY - 2015 SN - 1863-8880 ER - TY - JOUR AB - Miniaturized optical detectors of ultrasound represent a promising alternative to piezoelectric technology and may enable new minimally invasive clinical applications, particularly in the field of optoacoustic imaging. However, the use of such detectors has so far been limited to controlled lab environments, and has not been demonstrated in the presence of mechanical disturbances, common in clinical imaging scenarios. Additionally, detection sensitivity has been inherently limited by laser noise, which hindered the use of sensing elements such as optical fibers, which exhibit a weak response to ultrasound. In this work, coherence-restored pulse interferometry (CRPI) is introduced – a new paradigm for interferometric sensing in which shot-noise limited sensitivity may be achieved alongside robust operation. CRPI is implemented with a fiber-based resonator, demonstrating over an order of magnitude higher sensitivity than that of conventional 15 MHz intravascular ultrasound probes. The performance of the optical detector is showcased in a miniaturized all-optical optoacoustic imaging catheter. AU - Rosenthal, A. AU - Kellnberger, S. AU - Bozhko, D. AU - Chekkoury, A. AU - Omar, M. AU - Razansky, D. AU - Ntziachristos, V. C1 - 31571 C2 - 34555 CY - Weinheim SP - 450-457 TI - Sensitive interferometric detection of ultrasound for minimally invasive clinical imaging applications. JO - Laser Photon. Rev. VL - 8 IS - 3 PB - Wiley-v C H Verlag Gmbh PY - 2014 SN - 1863-8880 ER -