Laboratories

Translational Optoacoustics

Hybrid optoacoustic and multiphoton imaging of a mouse ear and a zebrafish larva ex-vivo. 1. Mouse ear. The Raster-Scan Optoacoustic Mesoscopy (RSOM) scan of an extended region of the ear shows blood vessels of different sizes. A multi-frequency reconstruction (red color: full bandwidth, cyan color: high frequencies) enhances small vessels and features. The white box indicates the region of hybrid microscopy scans. Optoacoustic Microscopy (OM, red color) visualizes blood vessels, Second-Harmonic Generation Microscopy (SHG, blue color) reveals collagen in the extracellular matrix and Third-Harmonic Generation Microscopy (THG, green color) shows keratinocytes of the epidermis and hair follicles. A Brightfield Microscopy (BF) scan was performed for reference. 2. Zebrafish larva: The RSOM scan shows melanophores, eyes and inner organs of the entire specimen. The microscopy scans simultaneously visualize single melanocytes (OM), muscles (SHG) and connective tissue (THG) of the fish tail.
Figure: CBI

Multimodal optoacoustic and multiphoton microscopy (MPOM) of human carotid atheroma. Coarse OAM scan and widefield BF observation enable ROI selection for subsequent MPOM imaging. Overlay of OAM (red), SHG (green), THG (blue), and TPEF (white) demonstrates an unscathed condition of the connective tissue (e.g. collagen and elastin), no large inclusions or fissures, and a negligible amount of embedded blood residues at the shoulder region. Analogous examination indicates a coarse alternating pattern of moieties as well as a slightly disturbed morphology at the cap region, whereas a fine interleaving structure along with an advanced degradation of cell morphology is revealed at the lipid core. Image courtesy of Markus Seeger and Angelos Karlas. M. Seeger, et al., Photoacoustics, 2016.
Figure: CBI

Our group focuses on developing technology and applications on the combination of optical and optoacoustic microscopy in order to deliver contrast and imaging abilities not available in optical microscopes today. While optical fluorescence microscopy is able to achieve sub-microns resolution even below the diffraction limit in living biological specimens, it is restricted by light scattering to superficial investigations at shallow depths. Optoacoustic microscopy offers absorption contrast, which complements fluorescence signals. Importantly it can be implemented to resolve the origin of ultrasound waves generated in response to short nanosecond-range light pulses propagating through tissue, essentially ‘listening’ to the molecules absorbing light. Acoustic signals scatters less than light in tissues and can enable high resolution imaging at larger depths. Our goal is to merge the advantages of optical and acoustical methods, achieving high resolution imaging at greater depths.

Relevant publications

Pleitez M. A., Khan A. A., Soldá A., Chmyrov A., Reber J., Gasparin F., Seeger M., Schätz B., Scheideler M., Herzig S., Ntziachristos V., Label-free metabolic imaging by mid-infrared optoacoustic microscopy in living cells, Nat Biotechnol 2020, 38. 293-296.

Ntziachristos V., Pleitez M. A., Aime S., Brindle K., Emerging Technologies to Image Tissue Metabolism, Cell Metab 2019, 29, 518.

Wissmeyer G., Pleitez M. A., Rosenthal A., Ntziachristos V., Looking at sound: optoacoustics with all optical ultrasound detection, Light: Sci & App 2018, 7, 53.

Karlas A., Pleitez M.A., Aguirre J., Ntziachristos V. Optoacoustic imaging in endocrinology, Nature Reviews Endocrinology 2021, 17, 323-335.

Wong T. T. W., Zhang R., Hai P., Zhang C., Pleitez M. A., Aft R. L., Novack D. V., Wang L. V., Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy, Sci Adv 2017, 3, e1602168.

Pleitez M. A., Hertzberg O., Bauer A., Lieblein T., Glasmacher M., Tholl H., Mäntele W., Infrared reflectometry of skin: Analysis of backscattered light from different skin layers, Spectrochim Acta A 2017, 184, 220-227.

Pleitez M. A., Hertzberg O., Bauer A., Seeger M., Lieblein T., von Lilienfeld-Toal H., Mäntele W., Photothermal deflectometry enhanced by total internal reflection enables non-invasive glucose monitoring in human epidermis, Analyst 2015, 140, 483-488.

Pleitez M. A., Lieblein T., Bauer A., Hertzberg O., von Lilienfeld-Toal H., Mäntele W., In vivo noninvasive monitoring of glucose concentration in human epidermis by mid-infrared pulsed photoacoustic spectroscopy, Anal Chem 2013, 85, 1013-1020.