Characterizing Protein Concentration in Cerebrospinal Fluid with T2 Component Analysis

Magn Reson Med Sci. 2024 Sep 26. doi: 10.2463/mrms.mp.2023-0157. Online ahead of print.

Abstract

Purpose: T2 values are hypothesized to be reduced where protein accumulates in the cerebrospinal fluid (CSF). We aimed to verify the accuracy of Carr-Purcell-Meiboom-Gil (CPMG) pulses and non-negative least squares (NNLS) analysis in visualizing protein concentrations by mapping the T2 values.

Methods: We first dissolved 1.2g of bovine serum albumin powder in 4 mL of artificial CSF to purify an albumin solution with a concentration of 4.5 mM. Artificial CSF was added thereto, and eight types of albumin solutions, with concentrations of 0.002-4.5 mM, were purified. We acquired this albumin solution with CPMG pulses and NNLS, decomposed the T2 values per pixel, and derived 25 T2 component values of 60-2000 ms. We assessed the change of T2 values by the difference in albumin concentration of a single voxel. Finally, we used the method to assess T2 values from two patients, one with a subdural hematoma and one with a suprasellar cystic tumor. T2 component values were plotted graphically, presented individually, and created in color maps.

Results: T2 component values for albumin concentrations ranging from 0.056 to 4.55 mM showed different T2 peaks, whereas, for concentrations 0.002 to 0.019 mM, the peaks were similar heights and overlapped. Peak width was similar for all concentrations. The color maps successfully reflected the changes in T2 values across both RGB color patterns. T2 components for albumin samples with 2.5 mM and 6.1 mM concentrations within a single voxel were represented separately and reflected the ratio of the two samples in nine different regions of interest within one slice. In the clinical cases, the T2 component map imaged differences in albumin concentrations, similar to those observed in the albumin samples.

Conclusion: The present method with CPMG sequences and NNLS provide adequate images to differentiate accumulating protein concentrations in the CSF, even at the level of a single pixel.

Keywords: Carr-Purcell-Meiboom-Gil; T2 map; cerebrospinal fluid; glymphatic system; non-negative least squares.