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Mapping human brain capillary water lifetime: high ‐ resolution metabolic neuroimaging

View Article: PubMed Central - PubMed

ABSTRACT

Shutter‐speed analysis of dynamic‐contrast‐agent (CA)‐enhanced normal, multiple sclerosis (MS), and glioblastoma (GBM) human brain data gives the mean capillary water molecule lifetime (τb) and blood volume fraction (vb; capillary density–volume product (ρ†V)) in a high‐resolution 1H2O MRI voxel (40 μL) or ROI. The equilibrium water extravasation rate constant, kpo (τb−1), averages 3.2 and 2.9 s−1 in resting‐state normal white matter (NWM) and gray matter (NGM), respectively (n = 6). The results (italicized) lead to three major conclusions. (A) kpo differences are dominated by capillary water permeability (PW†), not size, differences. NWM and NGM voxel kpoand vb values are independent. Quantitative analyses of concomitant population‐averaged kpo, vb variations in normal and normal‐appearing MS brain ROIs confirm PW†dominance. (B) PW† is dominated (>95%) by a trans(endothelial)cellular pathway, not the PCA† paracellular route. In MS lesions and GBM tumors, PCA†increases but PW†decreases. (C) kpo tracks steady‐state ATP production/consumption flux per capillary. In normal, MS, and GBM brain, regional kpocorrelates with literature MRSI ATP (positively) and Na+ (negatively) tissue concentrations. This suggests that the PW†pathway is metabolically active. Excellent agreement of the relative NGM/NWM kpovb product ratio with the literature 31PMRSI‐MT CMRoxphos ratio confirms the flux property. We have previously shown that the cellular water molecule efflux rate constant (kio) is proportional to plasma membrane P‐type ATPase turnover, likely due to active trans‐membrane water cycling. With synaptic proximities and synergistic metabolic cooperativities, polar brain endothelial, neuroglial, and neuronal cells form “gliovascular units.” We hypothesize that a chain of water cycling processes transmits brain metabolic activity to kpo, letting it report neurogliovascular unit Na+,K+‐ATPase activity. Cerebral kpo maps represent metabolic (functional) neuroimages. The NGM 2.9 s−1kpo means an equilibrium unidirectional water efflux of ~1015 H2O molecules s−1 per capillary (in 1 μL tissue): consistent with the known ATP consumption rate and water co‐transporting membrane symporter stoichiometries. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

No MeSH data available.


Related in: MedlinePlus

Normal parametric maps. SSP maps for the healthy control subject of Figure 1. (a) R1exv (intrinsic, extravascular R1), (b) vb (blood volume fraction), and (c) kpo (τb−1) (τb is the mean capillary water molecule lifetime). The kpo rate constant map displays ongoing resting‐state metabolic activity.
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nbm3294-fig-0002: Normal parametric maps. SSP maps for the healthy control subject of Figure 1. (a) R1exv (intrinsic, extravascular R1), (b) vb (blood volume fraction), and (c) kpo (τb−1) (τb is the mean capillary water molecule lifetime). The kpo rate constant map displays ongoing resting‐state metabolic activity.

Mentions: Figure 2 displays axial voxel‐by‐voxel parametric maps for the subject of Figure 1. The biomarkers are (a) R1exv, (b) vb, and (c) kpo (τb−1). As expected, R1exv is greater in NWM than in normal gray matter (NGM), and the vb map exhibits greater NGM (0.03) than NWM (0.01) values. The latter approximate rather well absolute CBV fractions, not relative values. Though such maps are quite important, they exhibit the natures of the R1exv and vb properties. The larger NWM R1exv values reflect the greater macromolecular volume fractions of NWM 74 and the larger NGM vb values reflect the well‐known greater NGM vascularity. As far as we are aware, Figure 2(c) is the first kpo map. As discussed above, τb is a supra‐intensive parameter. It is very interesting that the kpo map (Fig. 2(c)) exhibits greater intensity in NWM, averaging 3.0 s−1, than in NGM, 2.5 s−1.


Mapping human brain capillary water lifetime: high ‐ resolution metabolic neuroimaging
Normal parametric maps. SSP maps for the healthy control subject of Figure 1. (a) R1exv (intrinsic, extravascular R1), (b) vb (blood volume fraction), and (c) kpo (τb−1) (τb is the mean capillary water molecule lifetime). The kpo rate constant map displays ongoing resting‐state metabolic activity.
© Copyright Policy - creativeCommonsBy-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920360&req=5

nbm3294-fig-0002: Normal parametric maps. SSP maps for the healthy control subject of Figure 1. (a) R1exv (intrinsic, extravascular R1), (b) vb (blood volume fraction), and (c) kpo (τb−1) (τb is the mean capillary water molecule lifetime). The kpo rate constant map displays ongoing resting‐state metabolic activity.
Mentions: Figure 2 displays axial voxel‐by‐voxel parametric maps for the subject of Figure 1. The biomarkers are (a) R1exv, (b) vb, and (c) kpo (τb−1). As expected, R1exv is greater in NWM than in normal gray matter (NGM), and the vb map exhibits greater NGM (0.03) than NWM (0.01) values. The latter approximate rather well absolute CBV fractions, not relative values. Though such maps are quite important, they exhibit the natures of the R1exv and vb properties. The larger NWM R1exv values reflect the greater macromolecular volume fractions of NWM 74 and the larger NGM vb values reflect the well‐known greater NGM vascularity. As far as we are aware, Figure 2(c) is the first kpo map. As discussed above, τb is a supra‐intensive parameter. It is very interesting that the kpo map (Fig. 2(c)) exhibits greater intensity in NWM, averaging 3.0 s−1, than in NGM, 2.5 s−1.

View Article: PubMed Central - PubMed

ABSTRACT

Shutter‐speed analysis of dynamic‐contrast‐agent (CA)‐enhanced normal, multiple sclerosis (MS), and glioblastoma (GBM) human brain data gives the mean capillary water molecule lifetime (τb) and blood volume fraction (vb; capillary density–volume product (ρ†V)) in a high‐resolution 1H2O MRI voxel (40 μL) or ROI. The equilibrium water extravasation rate constant, kpo (τb−1), averages 3.2 and 2.9 s−1 in resting‐state normal white matter (NWM) and gray matter (NGM), respectively (n = 6). The results (italicized) lead to three major conclusions. (A) kpo differences are dominated by capillary water permeability (PW†), not size, differences. NWM and NGM voxel kpoand vb values are independent. Quantitative analyses of concomitant population‐averaged kpo, vb variations in normal and normal‐appearing MS brain ROIs confirm PW†dominance. (B) PW† is dominated (>95%) by a trans(endothelial)cellular pathway, not the PCA† paracellular route. In MS lesions and GBM tumors, PCA†increases but PW†decreases. (C) kpo tracks steady‐state ATP production/consumption flux per capillary. In normal, MS, and GBM brain, regional kpocorrelates with literature MRSI ATP (positively) and Na+ (negatively) tissue concentrations. This suggests that the PW†pathway is metabolically active. Excellent agreement of the relative NGM/NWM kpovb product ratio with the literature 31PMRSI‐MT CMRoxphos ratio confirms the flux property. We have previously shown that the cellular water molecule efflux rate constant (kio) is proportional to plasma membrane P‐type ATPase turnover, likely due to active trans‐membrane water cycling. With synaptic proximities and synergistic metabolic cooperativities, polar brain endothelial, neuroglial, and neuronal cells form “gliovascular units.” We hypothesize that a chain of water cycling processes transmits brain metabolic activity to kpo, letting it report neurogliovascular unit Na+,K+‐ATPase activity. Cerebral kpo maps represent metabolic (functional) neuroimages. The NGM 2.9 s−1kpo means an equilibrium unidirectional water efflux of ~1015 H2O molecules s−1 per capillary (in 1 μL tissue): consistent with the known ATP consumption rate and water co‐transporting membrane symporter stoichiometries. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

No MeSH data available.


Related in: MedlinePlus