The Spatial Distribution of Water Components with Similar T2 May Provide Insight into Pathways for Large Molecule Transportation in the Brain

Abstract

Purpose: Although there is no lymphatic system in the central nervous system (CNS), there seems to be a mechanism to remove macro molecules from the brain. Cerebrospinal fluid (CSF) and interstitial fluid (ISF) are thought to be parts of this pathway, but the details are not known. In this study, MR signal of the extracellular water was decomposed into components with distinct T₂'s, to obtain some information about distribution of waste material in the brain.

Methods: Images were acquired using a Curr, Purcell, Meiboom, Gill (CPMG) imaging sequence. In order to reduce T₁ contamination and the signal oscillation, hard pulses were used as refocusing pulses. The signal was then decomposed into many T₂ components using non-negative least squares (NNLS) in pixel-by-pixel basis. Finally, a color map was generated by assigning different color for each T₂ component, then adding them together.

Results: From the multi-echo images, it was possible to decompose the decaying signal into separate T₂ components. By adjusting the color table to create the color map, it is possible to visualize the extracellular water distribution, as well as their T₂ values. Several observation points include: (1) CSF inside ventricles has very long T₂ (~2 s), and seems to be relatively homogeneous, (2) subarachnoid CSF also have long T₂, but there are short T₂ component at the brain surface, at the surface of dura, at the blood vessels in the subarachnoid space, etc., (3) in the brain parenchyma, short T₂ components (longer than intracellular component but shorter than CSF) exists along the white matter, in the choroid plexus, etc. These can be considered as distribution of macromolecules (waste materials) in the brain.

Conclusion: From T₂ component analysis it is possible to obtain some insight into pathways for the transport of large molecules in the CNS, where no lymphatic system is present.

Keywords: cerebrospinal fluid; glymphatic; interstitial fluid; lymphatic; neurofluid.

Fig. 1

Typical color maps. Pixels are roughly divided into three groups: intracellular (black), extracellular (red), and the CSF (blue). The extracellular water is distributed in the white matter, the brain surface, dural side of subarachnoid space or possibly in the subdural space, choroid plexus, etc. The T₂ of the fat tissue is close to that of extracellular water, and it is sometimes difficult to distinguish these. This ambiguity can be eliminated by applying fat saturation pulse. The lower right image is an axial slice at the top of the head (magnified). In this image, fat saturation was turned on.

Fig. 2

This shows the acquired multi-TE images (a) and result of T₂ decomposition (b). Images were acquired by a CPMG imaging sequence with echo interval of 40 ms, echo train length of 25. These images were decomposed into 25 T₂ components, ranging from 60 to 2000 ms. On the figure, TE or T₂ increases from left to right, then top to bottom. CPMG, Curr, Purcell, Meiboom, Gill.

Fig. 3

Example of the result of decomposition with brain images. Three pixels were selected as the example. In many pixels, T₂ values are clustered into two or three groups.

Fig. 4

This shows the results of numerical simulation of NNLS decomposition. Top row: without noise. Bottom row: Gaussian noise with SD of 1% of peak signal. From left to right: one, two, and three T₂ components. Within each image, horizontal axis corresponds to pixel position, longitudinal axis corresponds to T₂ value. Actual T₂ values for each index are: 0 → 60.0, 5 → 124.6, 10 → 258.6, 15 → 537.0, 20 → 1114.9, 24 → 2000.0 (ms). NNLS, non-negative least squares.