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Functional imaging of visual cortical layers and subplate in awake mice with optimized three-photon microscopy
摘要： Two-photon microscopy is used to image neuronal activity, but has severe limitations for studying deeper cortical layers. Here, we developed a custom three-photon microscope optimized to image a vertical column of the cerebral cortex > 1 mm in depth in awake mice with low (<20 mW) average laser power. Our measurements of physiological responses and tissue-damage thresholds define pulse parameters and safety limits for damage-free three-photon imaging. We image functional visual responses of neurons expressing GCaMP6s across all layers of the primary visual cortex (V1) and in the subplate. These recordings reveal diverse visual selectivity in deep layers: layer 5 neurons are more broadly tuned to visual stimuli, whereas mean orientation selectivity of layer 6 neurons is slightly sharper, compared to neurons in other layers. Subplate neurons, located in the white matter below cortical layer 6 and characterized here for the first time, show low visual responsivity and broad orientation selectivity.
关键词： subplate neurons,deep brain imaging,visual cortex,neuronal activity,three-photon microscopy,GCaMP6s
更新于2025-09-23 15:23:52
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Design study of dedicated brain PET with polyhedron geometry
摘要： BACKGROUND: Despite being the conventional choice, whole body PET cameras with a 76 cm diameter ring are not the optimal means of human brain imaging. OBJECTIVE: In fact, a dedicated brain PET with a better geometrical structure has the potential to achieve a higher sensitivity, a higher signal-to-noise ratio, and a better imaging performance. METHODS: In this study, a polyhedron geometrical dedicated brain PET (a dodecahedron design) is compared to three other candidates via their geometrical ef?ciencies by calculating the Solid Angle Fractions (SAF); the three other candidates include a spherical cap design, a cylindrical design, and the conventional whole body PET. RESULTS: The spherical cap and the dodecahedron have an identical SAF that is 58.4% higher than that of a 30 cm diameter cylinder and 5.44 times higher than that of a 76 cm diameter cylinder. The conceptual polygon-shape detectors (including pentagon and hexagon detectors based on the PMT-light-sharing scheme instead of the conventional square-shaped block detector module) are presented for the polyhedron PET design. Monte Carlo simulations are performed in order to validate the detector decoding. CONCLUSIONS: The results show that crystals in a pentagon-shape detector can be successfully decoded by Anger Logic. The new detector designs support the polyhedron PET investigation.
关键词： polyhedron geometry,Positron emission tomography (PET),brain imaging
更新于2025-09-23 15:22:29
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Brain imaging with near-infrared fluorophores
摘要： As the centralized control system of the body, the brain is a complex organ of the utmost importance that even the most minor disorder and trauma can cause inestimable harm. There has always been an unmet clinical need for non-invasive high-resolution imaging techniques without a craniotomy to assist neurosurgeons gain anatomical and functional information for brain examination. Compared to the traditional methods, near-infrared (NIR) imaging (window I, 700–900 nm; window II, 1000–1700 nm) provides an innovative strategy for non-radioactive inspection with high tempo-spatial resolution. In particular, NIR-II imaging shows longer tissue penetration depths and ultralow tissue backgrounds due to drastically decreased photon scattering and tissue autofluorescence. In the current review, we highlight recent advances in NIR fluorophores, especially their rational design and application in NIR fluorescence imaging of the brain, sorted through brain tumors, traumatic brain injuries and bleeding diseases, as well as neurodegenerative disorders like Alzheimer’s and Huntington’s diseases. This state-of-the-art, non-invasive and non-radioactive optical imaging modality shows a promising prospect in understanding the fundamental pathophysiology of neurological diseases and is envisioned for potential clinical translation.
关键词： Fluorophores,Brain imaging,Near-infrared
更新于2025-09-23 15:21:01
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Dual layer doI detector modules for a dedicated mouse brain PET/MRI
摘要： This work discusses two system geometries including their associated block detectors. Both configurations were based on a dual layer offset structure with small crystals sizes, in the order of 1×1×4/6 mm3, to provide discrete depth of interaction information. The detector for configuration “A” was based on a 4×4 silicon photomultiplier (SiPM) array attached to an optical diffusor, and a 12×12 as well as a 9×11 LSO crystal array, to achieve optimal system sensitivity. This configuration was evaluated by a double layer of 12×12 crystals. Configuration “B” was composed of three 2×2 SiPM arrays equipped with a 1 mm diffusor to read out an LSO stack of 20×6 and 19×5 individual crystals. The average peak-to-valley ratio of the inner/outer layer was 3.5/3.6 for detector “A”, and 3.4/2.8 for detector “B”. The average full width at half maximum (FWHM) energy resolution of the block detectors were 22.24±3.36% for “A” and 30.67±5.37% for “B”. The FWHM of the full block timing resolution of the inner/outer layer was 1.4 ns/1.2 ns for detector “A” and 1.8 ns/1.4 ns for “B”. The performance of the crystal position profile, the energy, and timing resolution indicate that configuration “A” is more appropriate for a mouse brain PET/MRI system.
关键词： PET/MRI,Depth of interaction,brain,small animal brain imaging,PET/RF,integrated MRI-coil,preclinical imaging,PET
更新于2025-09-19 17:15:36
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First prototyping of a dedicated PET system with the hemisphere detector arrangement
摘要： A strong demand is expected for high-sensitivity, high-resolution, and low-cost brain positron emission tomography (PET) imaging for early diagnosis of dementia as well as for general neuroscience studies. Therefore, we have proposed novel geometries of a hemisphere detector arrangement for high-sensitivity brain imaging, in which an add-on detector at the chin position or neck position helps in sensitivity uniformity improvement. In this study, we developed the first prototype system for proof-of-concept using 4-layer depth-of-interaction detectors, each of which consisted of 16×16×4 Zr-doped GSO crystals with dimensions of 2.8×2.8×7.5 mm3 and a high-sensitivity 64-channel flat-panel photomultiplier tube. We used 47 detectors to form a hemisphere detector with a hemisphere shape of 25 cm inner diameter and 50 cm outer diameter, and we used seven detectors for each of the add-on detectors. The hemisphere detector was realized by multiple rings having different numbers of detectors and a cross-shaped top detector unit covering the top. Performance evaluation showed uniform spatial resolutions of 3-4 mm by the filtered back-projection method. Peak sensitivity was measured as more than 10% at a region near the top of the head, which was achieved with the help of the top detector unit. In addition, using the prototype system, we performed the first FDG clinical test with a healthy volunteer. The results showed that the proposed geometries had high potential for realizing high-sensitivity, high-resolution, and low-cost brain PET imaging. As for the add-on detector position, it was shown that the neck position resulted in higher sensitivity and wider field of view (FOV) than the chin position because the add-on detector at the neck position can be placed continuously to the hemisphere detector and close to the FOV.
关键词： brain imaging,helmet-type PET,dementia,positron emission tomography,brain PET,depth-of-interaction
更新于2025-09-19 17:15:36
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Quantum dot cellular uptake and toxicity in the developing brain: implications for use as imaging probes
摘要： Nanometer-sized luminescent semiconductor quantum dots (QDs) have been utilized as imaging and therapeutic agents in a variety of disease settings, including diseases of the central nervous system. QDs have several advantages over traditional fluorescent probes including their small size (5–10 nm), tunable excitation and emission spectra, tailorable surface functionality, efficient photoluminescence, and robust photostability, which are ideal characteristics for in vivo imaging. Although QDs are promising imaging agents in brain-related applications, no systematic evaluation of QD behavior in brain-relevant conditions has yet been done. Therefore, we sought to investigate QD colloidal stability, cellular uptake, and toxicity in vitro, ex vivo, and in vivo in the brain environment. We found that QD behavior is highly dependent on surface functionality and that treatment of cultured organotypic whole hemisphere (OWH) slices with QDs results in dose-dependent toxicity and metallothionein increase, but no subsequent mRNA expression level changes in inflammatory cytokines or other oxidative stress. QDs coated with poly(ethylene glycol) (PEG) were protected from aggregation in neurophysiologically relevant fluids and allowed for greater penetration in tissue. Importantly, QD behavior differed in cultured slices as compared to monolayer cell cultures, and behavior in cultured slices aligned more closely with that seen in vivo. Irrespective of surface chemistry and brain-relevant platform, non-aggregated QDs were primarily internalized by microglia in a region-dependent manner both in slices and in vivo upon systemic administration. This knowledge will help guide further engineering of candidate QD-based imaging probes for neurological application.
关键词： brain,imaging probes,quantum dots,colloidal stability,cellular uptake,toxicity
更新于2025-09-11 14:15:04
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Optimized image acquisition for dopamine transporter imaging with ultra-high resolution clinical pinhole SPECT
摘要： SPECT can be used to image dopamine transporter (DaT) availability in the human striatum, e.g. for diagnosis of Parkinson’s disease (PD). As traditional SPECT provides limited resolution and sensitivity, we proposed a full ring focusing multi-pinhole SPECT system (G-SPECT-I (Beekman 2015 Eur. J. Nucl. Med. Mol. Imaging 42 S209)) which demonstrated a 2.5 mm reconstructed resolution in phantom scans. G-SPECT-I achieves data completeness in the scan region of interest by translating the patient bed with an xyz-stage and combining projections from all bed positions into image reconstruction using a scanning focus method (SFM). This paper aims to develop dedicated SFM parameters for performing a DaTscan with high effective sensitivity and appropriate sampling. To this end, the axial scanning length was restricted and transaxial bed trajectories with a reduced number of positions based on a convex hull data-completeness model were tested. Quantitative accuracy was assessed using full G-SPECT-I simulations of an Alderson phantom based on measured system matrices. For each sampling strategy, the specific binding ratio (SBR) and asymmetry index (AI) in the left and right striatum, as well as the Localized SBR (L-SBR) and the Localized AI (L-AI) in eight striatal sub-regions were calculated and compared to those of the reference scan which performs full brain oversampling using 112 bed positions. Results show that structures essential for PD diagnosis were visually and quantitatively barely affected even when using the lowest number of bed translations (i.e. 4). The maximum deviation from the reference was only 1.5%, 1.5%, 5.5% and 7.0% for the SBR, AI, L-SBR and L-AI, respectively, when 4 positions were used. Thus, it is possible to perform an accurate DaTscan with a confined axial scan region and a limited number of focused bed positions. This enables protocols for extremely fast dynamic SPECT scans with less than half-minute time frames, which can be useful for motion correction.
关键词： sampling,pinhole collimator,brain imaging,high resolution SPECT,DaTscan,high sensitivity SPECT,clinical SPECT
更新于2025-09-10 09:29:36
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Optical coherence tomography imaging of the basal ganglia: feasibility and brief review
摘要： Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures.
关键词： Basal ganglia,Optical coherence tomography (OCT),Rat brain,Histology,Thalamus,Brain imaging
更新于2025-09-04 15:30:14