Comparative Analysis by Magnetic Resonance Imaging of Extracellular Space Diffusion and Interstitial Fluid Flow in the Rat Striatum and Thalamus

Zuo, Long; Li, Kai; Han, Hongbin

doi:10.1007/s00723-015-0670-7

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Interestingly, the expression of Versican is also located at the boundary between the caudate nucleus and thalamus. Because the boundary seems to exert barrier functions hindering cross-regional transportation [ 41 ], Versican or its related tissues can restrict the diffusion of substances in the ECS.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Visualization of Dynamic Tracer Transportation in the Extracellular Space of Deep Brain Regions Using Tracer-Based Magnetic Resonance Imaging

et al. 2017

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BackgroundThis study assessed an innovative tracer-based magnetic resonance imaging (MRI) system to visualize the dynamic transportation of tracers in regions of deep brain extracellular space (ECS) and to measure transportation ability and ECS structure.Material/MethodsGadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) was the chosen tracer and was injected into the caudate nucleus and thalamus. Real-time dynamic transportation of Gd-DTPA in ECS was observed and the results were verified by laser scanning confocal microscopy. Using Transwell assay across the blood-brain barrier, a modified diffusion equation was further simplified. Effective diffusion coefficient D* and tortuosity λ were calculated. Immunohistochemical staining and Western blot analysis were used to investigate the extracellular matrix contributing to ECS structure.ResultsTracers injected into the caudate nucleus were transported to the ipsilateral frontal and temporal cortices away from the injection points, while both of them injected into the thalamus were only distributed on site. Although the caudate nucleus was closely adjacent to the thalamus, tracer transportation between partitions was not observed. In addition, D* and the λ showed statistically significant differences between partitions. ECS was shown to be a physiologically partitioned system, and its division is characterized by the unique distribution territory and transportation ability of substances located in it. Versican and Tenascin R are possible contributors to the tortuosity of ECS.ConclusionsTracer-based MRI will improve our understanding of the brain microenvironment, improve the techniques for local delivery of drugs, and highlight brain tissue engineering fields in the future.

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Section: Discussionmentioning

confidence: 99%

Quantitative Visualization of Dynamic Tracer Transportation in the Extracellular Space of Deep Brain Regions Using Tracer-Based Magnetic Resonance Imaging

et al. 2017

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“…The advantage of the Gd‐DTPA tracer‐based MRI method is that it is unique in detecting and imaging the brain ECS on a whole brain scale, especially for investigations of the ECS in the deep center of the brain (Zuo and Han, 2015; Han et al, 2014). The brain ECS provides the extrasynaptic transfer channel among neurons, axons and glial cells (Sykova and Nicholson, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, a direct linear relationship between signal enhancement and Gd‐DTPA concentration was identified under the same conditions as used here (Xu et al, 2011). Based on previous research from Li et al (2013) and Zuo and Han (2015), the following diffusion parameters within the ECS were calculated: free diffusion coefficient (D), effective diffusion coefficient (D*), tortuosity (λ), and clearance rate constant (k'). The maximal volume fraction of distribution (Vd max %) was also determined (Zuo and Han, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…Based on previous research from Li et al (2013) and Zuo and Han (2015), the following diffusion parameters within the ECS were calculated: free diffusion coefficient (D), effective diffusion coefficient (D*), tortuosity (λ), and clearance rate constant (k'). The maximal volume fraction of distribution (Vd max %) was also determined (Zuo and Han, 2015). The free diffusion coefficient (D) of Gd‐DTPA was calculated as 5.18 × 10 −4 mm 2 /s in 0.3% agar gel at 37 °C (Li et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

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Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging

Yang

Wang

et al. 2016

Intl J of Devlp Neuroscience

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The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real-time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways.

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“…Anesthesia was performed as described above and rats were scanned using a 3.0-T MRI system (Verio, Siemens Medical Solutions, Erlangen, Germany) with an eight-channel coil. Brain images were obtained with a high-resolution T1-weighted 3-dimensional magnetization-prepared rapid-acquisition with gradient echo (T1 3DMP-RAGE) sequence with the parameters specified by Han and Zuo (Han et al, 2014 ; Zuo et al, 2015 ). A 2-μl volume of 10 mmol/L Gd-DTPA solution (Magnevist; Bayer Schering Pharma AG, Berlin, Germany) was injected directly into the SN as described above (see Section Surgical Procedure).…”

Section: Methodsmentioning

confidence: 99%

Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

et al. 2017

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The relationship between extracellular space (ECS) diffusion parameters and brain drug clearance is not well-studied, especially in the context of Parkinson's disease (PD). Therefore, we used a rodent model of PD to explore the distribution and clearance of a magnetic resonance tracer. Forty male Sprague Dawley rats were randomized into four different groups: a PD group, a Madopar group (PD + Madopar treatment), a sham group, and a control group. All rats received an injection of the extracellular tracer gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) directly into the substantia nigra (SN). ECS diffusion parameters including the effective diffusion coefficient (D*), clearance coefficient (k'), ratio of the maximum distribution volume of the tracer (Vd-max%), and half-life (t1/2) were measured. We found that all parameters were significantly increased in the PD group compared to the other three groups (D*: F = 5.774, p = 0.0025; k': F = 20.00, P < 0.0001; Vd-max%: F = 12.81, P < 0.0001; and t1/2: F = 23.35, P < 0.0001). In conclusion, the PD group exhibited a wider distribution and lower clearance of the tracer compared to the other groups. Moreover, k' was more sensitive than D* for monitoring morphological and functional changes in the ECS in a rodent model of PD.

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Comparative Analysis by Magnetic Resonance Imaging of Extracellular Space Diffusion and Interstitial Fluid Flow in the Rat Striatum and Thalamus

Cited by 9 publications

References 35 publications

Quantitative Visualization of Dynamic Tracer Transportation in the Extracellular Space of Deep Brain Regions Using Tracer-Based Magnetic Resonance Imaging

Quantitative Visualization of Dynamic Tracer Transportation in the Extracellular Space of Deep Brain Regions Using Tracer-Based Magnetic Resonance Imaging

Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging

Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

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