scholarly journals Minimally invasive deep-brain imaging through a 50 μm-core multimode fibre

2018 ◽  
Author(s):  
Sebastian A. Vasquez-Lopez ◽  
Vadim Koren ◽  
Martin Plöschner ◽  
Zahid Padamsey ◽  
Tomáš Čižmár ◽  
...  

AbstractAchieving optical access to deep-brain structures represents an important step towards the goal of understanding the mammalian central nervous system. The complex refractive index distribution within brain tissue introduces severe aberrations to long-distance light propagation thereby prohibiting image reconstruction using currently available non-invasive techniques. In an attempt to overcome this challenge endoscopic approaches have been adopted, principally in the form of fibre bundles or GRIN-lens based endoscopes. Unfortunately, these approaches create substantial mechanical lesions of the tissue precipitating neuropathological responses that include inflammation and gliosis. Together, lesions and the associated neuropathology may compromise neural circuit performance. By replacing Fourier-based image relay with a holographic approach, we have been able to reduce the volume of tissue lesion by more than 100-fold, while preserving diffraction-limited imaging performance. Here we demonstrate high-resolution fluorescence imaging of neuronal structures, dendrites and synaptic specialisations, in deep-brain regions of living mice. These results represent a major breakthrough in the compromise between high-resolution imaging and tissue damage, heralding new possibilities for deep-brain imaging in vivo.

2020 ◽  
Vol 6 (40) ◽  
pp. eabc6521 ◽  
Author(s):  
Zhongya Qin ◽  
Congping Chen ◽  
Sicong He ◽  
Ye Wang ◽  
Kam Fai Tam ◽  
...  

Optical deep-brain imaging in vivo at high resolution has remained a great challenge over the decades. Two-photon endomicroscopy provides a minimally invasive approach to image buried brain structures, once it is integrated with a gradient refractive index (GRIN) lens embedded in the brain. However, its imaging resolution and field of view are compromised by the intrinsic aberrations of the GRIN lens. Here, we develop a two-photon endomicroscopy by adding adaptive optics based on direct wavefront sensing, which enables recovery of diffraction-limited resolution in deep-brain imaging. A new precompensation strategy plays a critical role to correct aberrations over large volumes and achieve rapid random-access multiplane imaging. We investigate the neuronal plasticity in the hippocampus, a critical deep brain structure, and reveal the relationship between the somatic and dendritic activity of pyramidal neurons.


2020 ◽  
Author(s):  
Zhongya Qin ◽  
Congping Chen ◽  
Sicong He ◽  
Ye Wang ◽  
Kam Fai Tam ◽  
...  

AbstractOptical deep brain imaging in vivo at high resolution has remained a great challenge over the decades. Two-photon endomicroscopy provides a minimally invasive approach to image buried brain structures, once it is integrated with a gradient refractive index (GRIN) lens embedded in the brain. However, its imaging resolution and field of view are compromised by the intrinsic aberrations of the GRIN lens. Here, we develop a two-photon endomicroscopy by adding adaptive optics based on the direct wavefront sensing, which enables recovery of diffraction-limited resolution in deep brain imaging. A new precompensation strategy plays a critical role to correct aberrations over large volumes and achieve rapid random-access multiplane imaging. We investigate the neuronal plasticity in the hippocampus, a critical deep brain structure, and reveal the relationship between the somatic and dendritic activity of pyramidal neurons.


Author(s):  
Congping Chen ◽  
Zhongya Qin ◽  
Sicong He ◽  
Wanjie Wu ◽  
Ye Wang ◽  
...  

2012 ◽  
Vol 107 (10) ◽  
pp. 2853-2865 ◽  
Author(s):  
Ji-Wei He ◽  
Fenghua Tian ◽  
Hanli Liu ◽  
Yuan Bo Peng

While near-infrared (NIR) spectroscopy has been increasingly used to detect stimulated brain activities with an advantage of dissociating regional oxy- and deoxyhemoglobin concentrations simultaneously, it has not been utilized much in pain research. Here, we investigated and demonstrated the feasibility of using this technique to obtain whole brain hemodynamics in rats and speculated on the functional relevance of the NIR-based hemodynamic signals during pain processing. NIR signals were emitted and collected using a 26-optodes array on rat's dorsal skull surface after the removal of skin. Following the subcutaneous injection of formalin (50 μl, 3%) into a hindpaw, several isolable brain regions showed hemodynamic changes, including the anterior cingulate cortex, primary/secondary somatosensory cortexes, thalamus, and periaqueductal gray ( n = 6). Time courses of hemodynamic changes in respective regions matched with the well-documented biphasic excitatory response. Surprisingly, an atypical pattern (i.e., a decrease in oxyhemoglobin concentration with a concomitant increase in deoxyhemoglobin concentration) was seen in phase II. In a separate group of rats with innocuous brush and noxious pinch of the same area ( n = 11), results confirmed that the atypical pattern occurred more likely in the presence of nociception than nonpainful stimulation, suggesting it as a physiological substrate when the brain processes pain. In conclusion, the NIR whole brain imaging provides a useful alternative to study pain in vivo using small-animal models. Our results support the notion that neurovascular response patterns depend on stimuli, bringing attention to the interpretation of vascular-based neuroimaging data in studies of pain.


Author(s):  
Sebastiano Lucerna ◽  
Francesco M. Salpietro ◽  
Concetta Alafaci ◽  
Francesco Tomasello
Keyword(s):  

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Shai Berman ◽  
Roey Schurr ◽  
Gal Atlan ◽  
Ami Citri ◽  
Aviv A Mezer

Abstract The claustrum is a thin sheet of neurons enclosed by white matter and situated between the insula and the putamen. It is highly interconnected with sensory, frontal, and subcortical regions. The deep location of the claustrum, with its fine structure, has limited the degree to which it could be studied in vivo. Particularly in humans, identifying the claustrum using magnetic resonance imaging (MRI) is extremely challenging, even manually. Therefore, automatic segmentation of the claustrum is an invaluable step toward enabling extensive and reproducible research of the anatomy and function of the human claustrum. In this study, we developed an automatic algorithm for segmenting the human dorsal claustrum in vivo using high-resolution MRI. Using this algorithm, we segmented the dorsal claustrum bilaterally in 1068 subjects of the Human Connectome Project Young Adult dataset, a publicly available high-resolution MRI dataset. We found good agreement between the automatic and manual segmentations performed by 2 observers in 10 subjects. We demonstrate the use of the segmentation in analyzing the covariation of the dorsal claustrum with other brain regions, in terms of macro- and microstructure. We identified several covariance networks associated with the dorsal claustrum. We provide an online repository of 1068 bilateral dorsal claustrum segmentations.


Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 372 ◽  
Author(s):  
Priyanka Reddy ◽  
Aaron Elkins ◽  
Joanne Hemsworth ◽  
Kathryn Guthridge ◽  
Simone Vassiliadis ◽  
...  

Lolitrem B is the most potent indole-diterpene mycotoxin produced by Epichloë festucae var. lolii (termed LpTG-1), with severe intoxication cases reported in livestock. To date, there are no in vivo metabolism studies conducted for the mycotoxin. A mouse model assay established for assessing toxicity of indole-diterpenes was used to investigate metabolic products of lolitrem B. Mice were administered lolitrem B at 0.5 and 2.0 mg/kg body weight (b.wt) intraperitoneally before body and brain tissues were collected at 6 h and 24 h post-treatment. Samples were cryoground and subjected to a biphasic or monophasic extraction. The aqueous and lipophilic phases were analysed using liquid chromatography high-resolution mass spectrometry (LC–HRMS); data analysis was performed with Compound Discoverer™ software. A total of 10 novel phase I metabolic products were identified in the lipophilic phase and their distribution in the liver, kidney and various brain regions are described. The biotransformation products of lolitrem B were found to be present in low levels in the brain. Based on structure–activity postulations, six of these may contribute towards the protracted tremors exhibited by lolitrem B-exposed animals.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Seulki Yoo ◽  
Joo-won Kim ◽  
John F. Schenck ◽  
Seung-Kyun Lee

Abstract The habenula plays an important role in brain reward circuitry and psychiatric conditions. While much work has been done on the function and structure of the habenula in animal models, in vivo imaging studies of the human habenula have been relatively scarce due to its small size, deep brain location, and lack of clear biomarkers for its heterogeneous substructure. In this paper, we report high-resolution (0.5 × 0.5 × 0.8 mm3) MRI of the human habenula with quantitative susceptibility mapping (QSM) at 3 T. By analyzing 48 scan datasets collected from 21 healthy subjects, we found that magnetic susceptibility contrast is highly non-uniform within the habenula and across the subjects. In particular, we observed high prevalence of elevated susceptibility in the posterior subregion of the habenula. Correlation analysis between the susceptibility and the effective transverse relaxation rate (R2*) indicated that localized susceptibility enhancement in the habenula is more associated with increased paramagnetic (such as iron) rather than decreased diamagnetic (such as myelin) sources. Our results suggest that high-resolution QSM could make a potentially useful tool for substructure-resolved in vivo habenula imaging, and provide a groundwork for the future development of magnetic susceptibility as a quantitative biomarker for human habenula studies.


2012 ◽  
Vol 32 (3) ◽  
pp. 425-436 ◽  
Author(s):  
Manon Brundel ◽  
Jeroen de Bresser ◽  
Jeroen J van Dillen ◽  
L Jaap Kappelle ◽  
Geert Jan Biessels

Vascular cognitive impairment is an umbrella term for cognitive dysfunction associated with and presumed to be caused by vascular brain damage. Autopsy studies have identified microinfarcts as an important neuropathological correlate of vascular cognitive impairment that escapes detection by conventional magnetic resonance imaging (MRI). As a frame of reference for future high-resolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors, cognitive decline and dementia. We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer's disease (43%), and demented patients with both Alzheimer-type and cerebrovascular pathology (33%) compared with nondemented older individuals (24%). In many patients, multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor, or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 μm to a few mm, which is within the detection limit of current high-resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular cognitive impairment.


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