Christoph J. Engelbrecht

Bio: Christoph J. Engelbrecht is an academic researcher from University of Zurich. The author has contributed to research in topics: Microscopy & Optical fiber. The author has an hindex of 5, co-authored 5 publications receiving 867 citations. Previous affiliations of Christoph J. Engelbrecht include Novartis & École Polytechnique Fédérale de Lausanne.

Scanning fiber endoscopy with highly flexible, 1 mm catheterscopes for wide-field, full-color imaging

Abstract: In modern endoscopy, wide field of view and full color are considered necessary for navigating inside the body, inspecting tissue for disease and guiding interventions such as biopsy or surgery. Current flexible endoscope technologies suffer from reduced resolution when device diameter shrinks. Endoscopic procedures today, using coherent fiber-bundle technology on the scale of 1 mm, are performed with such poor image quality that the clinician's vision meets the criteria for legal blindness. Here, we review a new and versatile scanning fiber-imaging technology and describe its implementation for ultrathin and flexible endoscopy. This scanning fiber endoscope (SFE) or catheterscope enables high-quality, laser-based, video imaging for ultrathin clinical applications, while also providing new options for in vivo biological research of subsurface tissue and high resolution fluorescence imaging.

Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo

Abstract: We present a small, lightweight two-photon fiberscope and demonstrate its suitability for functional imaging in the intact brain. Our device consists of a hollow-core photonic crystal fiber for efficient delivery of near-IR femtosecond laser pulses, a spiral fiber-scanner for resonant beam steering, and a gradient-index lens system for fluorescence excitation, dichroic beam splitting, and signal collection. Fluorescence light is remotely detected using a standard photomultiplier tube. All optical components have 1 mm dimensions and the microscope’s headpiece weighs only 0.6 grams. The instrument achieves micrometer resolution at frame rates of typically 25 Hz with a field-of-view of up to 200 microns. We demonstrate functional imaging of calcium signals in Purkinje cell dendrites in the cerebellum of anesthetized rats. The microscope will be easily portable by a rat or mouse and thus should enable functional imaging in freely behaving animals.

Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex.

Abstract: Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast is widely used for probing brain activity, but its relationship to underlying neural activity remains elusive. Here, we combined fMRI with fiber-optic recordings of fluorescent calcium indicator signals to investigate this relationship in rat somatosensory cortex. Electrical forepaw stimulation (1-10 Hz) evoked fast calcium signals of neuronal origin that showed frequency-dependent adaptation. Additionally, slower calcium signals occurred in astrocyte networks, as verified by astrocyte-specific staining and two-photon microscopy. Without apparent glia activation, we could predict BOLD responses well from simultaneously recorded fiber-optic signals, assuming an impulse response function and taking into account neuronal adaptation. In cases with glia activation, we uncovered additional prolonged BOLD signal components. Our findings highlight the complexity of fMRI BOLD signals, involving both neuronal and glial activity. Combined fMRI and fiber-optic recordings should help to clarify cellular mechanisms underlying BOLD signals.

Miniaturized selective plane illumination microscopy for high-contrast in vivo fluorescence imaging

Abstract: Light-sheet-based fluorescence imaging techniques rely on simultaneous excitation of a single optical plane and thus permit high-contrast optically sectioned imaging of extended tissue samples. Here, we introduce a miniaturized fiber-optic implementation of a selective plane-illumination microscope (miniSPIM). The excitation light was delivered through a single-mode optical fiber, and a light-sheet was created with a cylindrical gradient-index lens and a right-angle microprism. Fluorescence emission was collected orthogonally to the light-sheet through a gradient-index lens assembly and a coherent fiber bundle. The end face of the fiber bundle was imaged onto a charge-coupled device camera. The spatial resolutions of the miniSPIM were 3.2 μm laterally and 5.1 μm axially. Images of fluorescent beads and neurons in mouse neocortex exhibited superior axial resolution and contrast in the miniSPIM-mode compared to images recorded in epi-illumination mode. The miniSPIM may thus enable novel in vivo imaging approaches.

Enhanced fluorescence signal in nonlinear microscopy through supplementary fiber-optic light collection

Abstract: Nonlinear microscopy techniques crucially rely on efficient signal detection. Here, we present a ring of large-core optical fibers for epi-collection of fluorescence photons that are not transmitted through the objective and thus normally wasted. Theoretical treatments indicated that such a supplementary fiber-optic light collection system (SUFICS) can provide an up to 4-fold signal gain. In typical in vivo imaging experiments, the fiber-ring channel was brighter than the objective channel down to 800 μm depth, thus providing a gain >2. Moreover, SUFICS reduced noise levels in calcium imaging experiments by about 23%. We recommend SUFICS as a generally applicable, effective add-on to nonlinear microscopes for enhancing fluorescence signals.

Miniaturized integration of a fluorescence microscope

Abstract: The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

Astrocyte Calcium Signaling: The Third Wave

Abstract: The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function.

Exploiting multimode waveguides for pure fibre-based imaging

Abstract: technology. This has been necessitated by the need to access hostile or difficult environments in situ and in vivo. strategies to date have included the use of specialist fibres and miniaturized scanning systems accompanied by ingenious microfabricated lenses. Here we present a novel approach for this field by utilizing disordered light within a standard multimode optical fibre for lensless microscopy and optical mode conversion. We demonstrate the modalities of bright- and dark-field imaging and scanning fluorescence microscopy at acquisition rates that allow observation of dynamic processes such as Brownian motion of mesoscopic particles. Furthermore, we show how such control can realize a new form of mode converter and generate various types of advanced light fields such as propagation-invariant beams and optical vortices. These may be useful for future fibre-based implementations of super-resolution or light-sheet microscopy.