<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation"^^ . "Recording the activity of large neuronal populations is crucial for understanding brain function but is\r\nconstrained by current technologies. Multiphoton microscopy (MPM) with calcium-sensitive\r\nfluorescence sensors offers sub-cellular imaging of neuronal activity but is limited to ~1 mm depth\r\nand a narrow field of view. Functional magnetic resonance imaging (fMRI), despite whole-brain\r\ncoverage, uses blood-oxygenation as a neural activity proxy and suffers from poor spatial (~0.4 mm)\r\nand temporal (~1 sec) resolution.\r\n\r\nPhotoacoustic imaging (PAI) uniquely combines the molecular contrast of light absorbance with\r\nultrasound imaging, thereby achieving ~cm penetration and bridging the scales of MPM and fMRI.\r\nCombined with calcium probes tailored for photoacoustic emission, PAI could enable brain-wide\r\ncalcium imaging, advancing neurobiological research. However, suitable far-red (600–700 nm)\r\ncalcium reporters are currently unavailable.\r\n\r\nThis thesis presents advancements toward whole-brain neuroimaging using photoacoustic methods.\r\nA custom Fabry-Perot-based Photoacoustic Tomography system (FP-PAT) was developed, enabling 3D\r\nbrain tissue imaging with a 15*15*15 mm³ field of view and ~90 μm spatial resolution. System\r\nimprovements in speed and sensitivity are introduced to make it suitable for calcium imaging\r\napplications.\r\n\r\nNovel calcium photoacoustic reporters based on synthetic dyes and HaloTag-based self-labeling\r\nproteins were developed in collaboration with the Deo lab at EMBL. A multimodal spectroscopy\r\nplatform combining photoacoustic, absorption, and fluorescence readouts was designed to screen\r\nand characterize these probes. Selected probes were then tested in tissue-mimicking phantoms with\r\nFP-PAT, demonstrating superior performance in signal intensity, sensitivity, and photostability\r\ncompared to existing calcium sensors.\r\n\r\nNext, we demonstrated successful in vivo labelling and PA imaging of mouse brain slices, thereby\r\nshowing the feasibility of using HaloTag-based probes to label neurons and detect the signal with FP-\r\nPAT. Moreover, preliminary data on a calcium-sensitive version of the probe, HaloCaMP, shows\r\nsuccessfully labeled mouse brain slices with a detectable change in signal after incubation in calcium\r\nbuffer.\r\n\r\nFinally, acute slice preparation and PAI were used to assess calcium sensors in live tissue stimulated\r\nwith high potassium. Proof-of-concept data for the fluorescent calcium indicator jGCaMP8m showed\r\ndetectable PA signal changes upon stimulation. However, the HaloCaMP probe did not yet\r\ndemonstrate calcium-mediated signal changes, likely due to low calcium affinity and brightness of\r\nthis first-generation sensor.\r\n\r\nThis work introduces a novel class of far-red photoacoustic calcium reporters with superior\r\nperformance, providing critical spectroscopic characterization and methods for labeling mouse brain\r\ntissue. While challenges remain for realistic in vivo applications, this research establishes a\r\nfoundation for developing photoacoustic neuroimaging with tailored calcium sensors, paving the way\r\nfor future in vivo brain-wide calcium imaging."^^ . "2026" . . . . . . . "Nikita"^^ . "Kaydanov"^^ . "Nikita Kaydanov"^^ . . . . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (PDF)"^^ . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (Other)"^^ . . . . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (Other)"^^ . . . . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (Other)"^^ . . . . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (Other)"^^ . . . . . . "Towards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation (Other)"^^ . . . . . "HTML Summary of #36518 \n\nTowards photoacoustic neuroimaging in mice: development and validation of novel calcium sensors with tailored photoacoustic instrumentation\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .