Studying Axonal Transport in the Brain by Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

Bearer, Elaine L.; Zhang, Xiaowei; Jacobs, Russell E.

doi:10.1007/978-1-0716-1990-2_6

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…Firstly, in this study, widespread image registration methods were adopted. Especially, by DARTEL algorithm, individual images could be normalized into the template space via a set of tissue probability maps iteratively (Zhang et al, 2022). However, it couldn't be adopted by our previous work, for the lacking of tissue probability maps in individual space.…”

Section: Discussionmentioning

confidence: 99%

“…By tracing the deposition of Mn 2+ , the active neurons would have high voxel intensity in MEMRI images, while other voxels have low intensity. Recently, the MEMRI technique has been widely used in various studies of the rodent brain (Ho et al, 2018 ; Perez et al, 2018 ; Gimenes et al, 2019 ; Yang et al, 2020 ; Bearer et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain

et al. 2022

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AimsTo construct an automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain with high accuracy, which could preserve the inherent voxel intensity and Regions of interest (ROI) morphological characteristics simultaneously.Methods and resultsThe transformation relationship from standardized space to individual space was obtained by firstly normalizing individual image to the Paxinos space and then inversely transformed. On the other hand, all the regions defined in the atlas image were separated and resaved as binary mask images. Then, transforming the mask images into individual space via the inverse transformations and reslicing using the 4th B-spline interpolation algorithm. The boundary of these transformed regions was further refined by image erosion and expansion operator, and finally combined together to generate the individual parcellations. Moreover, two groups of MEMRI images were used for evaluation. We found that the individual parcellations were satisfied, and the inherent image intensity was preserved. The statistical significance of case-control comparisons was further optimized.ConclusionsWe have constructed a new automatic method for individual parcellation of rat brain MEMRI images, which could preserve the inherent voxel intensity and further be beneficial in case-control statistical analyses. This method could also be extended to other imaging modalities, even other experiments species. It would facilitate the accuracy and significance of ROI-based imaging analyses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain

et al. 2022

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“…The amount of dextran amine molecules was 0.08 picomoles or approximately 6.9 x 10 16 molecules. The solution injected into the anterior cingulate area (ACA), with the stereotactic device settings of: x, 0.5 mm right of the midline; y, 1.0 mm anterior to bregma; z, −1.5 deep to the surface of the skull) as previously described (Bearer et al, 2022). Injection proceeded over 5 minutes using a hand-pulled quartz micropipette loaded under direct visualization for precise volume control, guided by computer-assisted stereotactic injector (myNeuroLab.com, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

Harnessing axonal transport to map reward circuitry: Differing brain-wide projections from medial forebrain domains

Bearer,

Medina,

Uselman

et al. 2023

Preprint

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Neurons project long axons that contact other distant neurons. Projections can be mapped by hijacking endogenous membrane trafficking machinery by introducing tracers. To witness functional connections in living animals, we developed a tracer detectible by magnetic resonance imaging (MRI), Mn(II). Mn(II) relies on kinesin-1 and amyloid-precursor protein to travel out axons. Within 24h, projection fields of cortical neurons can be mapped brain-wide with this technology. MnCl2was stereotactically injected either into anterior cingulate area (ACA) or into infralimbic/prelimbic (IL/PL) of medial forebrain (n=10-12). Projections were imaged, first bymanganese-enhancedMRI(MEMRI) live, and then after fixation by microscopy. MR images were collected at 100µm isotropic resolution (∼5 neurons) in 3D at four time points: before and at successive time points after injections. Images were preprocessed by masking non-brain tissue, followed by intensity scaling and spatial alignment. Actual injection locations, measured from post-injection MR images, were found to be 0.06, 0.49 and 0.84mm apart between cohorts, in R-L, A-P, and D-V directions respectively. Mn(II) enhancements arrived in hindbrains by 24h in both cohorts, while co-injected rhodamine dextran was not detectible beyond immediate subcortical projections. Data-driven unbiased voxel-wise statistical maps after ACA injections revealed significant progression of Mn(II) distally into deeper brain regions: globus pallidus, dorsal striatum, amygdala, hypothalamus, substantia nigra, dorsal raphe and locus coeruleus. Accumulation was quantified as a fraction of total volume of each segment containing significantly enhanced voxels (fractional accumulation volumes), and results visualized in column graphs. Unpaired t-tests between groups of brain-wide voxel-wise intensity profiling by either region of interest (ROI) measurements or statistical parametric mapping highlighted distinct differences in distal accumulation between injection sites, with ACA projecting to periaqueductal gray and IL/PL to basolateral amygdala (p<0.001 FDR). Mn(II) distal accumulations differed dramatically between injection groups in subdomains of the hypothalamus, with ACA targeting dorsal medial, periventricular region and mammillary body nuclei, while IL/PL went to anterior hypothalamic areas and lateral hypothalamic nuclei. Given that these hypothalamic subsegments communicate activity in the central nervous system to the body, these observations describing distinct forebrain projection fields will undoubtedly lead to newer insights in mind-body relationships.

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“…Future work will likely pursue these diseases, as MEMRI reports on APP‐dependent transport, and as transgenic mice replicating features of AD promise to provide valuable experimental systems for mechanistic understanding and drug discovery. To assist in future work by investigators new to MEMRI, protocols describing techniques for tract‐tracing are now available 170,171 …”

Section: Applications Of Memri: Tracing Neuronal Projections and Axon...mentioning

confidence: 99%

“…To assist in future work by investigators new to MEMRI, protocols describing techniques for tract-tracing are now available. 170,171…”

Section: Applications Of Memri: Tracing Neuronal Projections and Axon...mentioning

confidence: 99%

Longitudinal manganese‐enhanced magnetic resonance imaging of neural projections and activity

et al. 2022

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Manganese-enhanced magnetic resonance imaging (MEMRI) holds exceptional promise for preclinical studies of brain-wide physiology in awake-behaving animals. The objectives of this review are to update the current information regarding MEMRI and to inform new investigators as to its potential. Mn(II) is a powerful contrast agent for two main reasons: (1) high signal intensity at low doses; and (2) biological interactions, such as projection tracing and neural activity mapping via entry into electrically active neurons in the living brain. High-spin Mn(II) reduces the relaxation time of water protons: at Mn(II) concentrations typically encountered in MEMRI, robust hyperintensity is obtained without adverse effects. By selectively entering neurons through voltagegated calcium channels, Mn(II) highlights active neurons. Safe doses may be repeated over weeks to allow for longitudinal imaging of brain-wide dynamics in the same individual across time. When delivered by stereotactic intracerebral injection, Mn(II) enters active neurons at the injection site and then travels inside axons for long distances, tracing neuronal projection anatomy. Rates of axonal transport within the brain were measured for the first time in "time-lapse" MEMRI. When delivered systemically, Mn(II) enters active neurons throughout the brain via voltage-sensitive calcium channels and clears slowly. Thus behavior can be monitored during Mn(II) uptake and hyperintense signals due to Mn(II) uptake captured retrospectively, allowing pairing of behavior with neural activity maps for the first time. Here we review critical information gained from MEMRI projection mapping about human

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Studying Axonal Transport in the Brain by Manganese-Enhanced Magnetic Resonance Imaging (MEMRI)

Cited by 7 publications

References 44 publications

Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain

Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain

Harnessing axonal transport to map reward circuitry: Differing brain-wide projections from medial forebrain domains

Longitudinal manganese‐enhanced magnetic resonance imaging of neural projections and activity

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