Myelin Imaging in Human Brain Using a Short Repetition Time Adiabatic Inversion Recovery Prepared Ultrashort Echo Time (STAIR-UTE) MRI Sequence in Multiple Sclerosis

Abstract

Background Water signal contamination is a major challenge for direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the signals detected in white matter. Purpose To validate a new short repetition time (TR) adiabatic inversion recovery (STAIR) prepared UTE (STAIR-UTE) sequence designed to suppress water signals and to allow imaging of ultrashort T2 protons of myelin in white matter using a clinical 3-T scanner. Materials and Methods In this prospective study, an optimization framework was used to obtain the optimal inversion time for nulling water signals using STAIR-UTE imaging at different TRs. Numeric simulation and phantom studies were performed. Healthy volunteers and participants with multiple sclerosis (MS) underwent MRI between November 2018 and October 2019 to compare STAIR-UTE and a clinical T2-weighted fluid-attenuated inversion recovery sequence for assessment of MS lesions. UTE measures of myelin were also performed to allow comparison of signals in lesions and with those in normal-appearing white matter (NAWM) in patients with MS and in normal white matter (NWM) in healthy volunteers. Results Simulation and phantom studies both suggest that the proposed STAIR-UTE technique can effectively suppress long T2 tissues with a broad range of T1s. Ten healthy volunteers (mean age, 33 years ± 8 [standard deviation]; six women) and 10 patients with MS (mean age, 51 years ± 16; seven women) were evaluated. The three-dimensional STAIR-UTE sequence effectively suppressed water components in white matter and selectively imaged myelin, which had a measured T2* value of 0.21 msec ± 0.04 in the volunteer study. A much lower mean UTE measure of myelin proton density was found in MS lesions (3.8 mol/L ± 1.5), and a slightly lower mean UTE measure was found in NAWM (7.2 mol/L ± 0.8) compared with that in NWM (8.0 mol/L ± 0.8) in the healthy volunteers (P < .001 for both comparisons). Conclusion The short repetition time adiabatic inversion recovery-prepared ultrashort echo time sequence provided efficient water signal suppression for volumetric imaging of myelin in the brain and showed excellent myelin signal contrast as well as marked ultrashort echo time signal reduction in multiple sclerosis lesions and a smaller reduction in normal-appearing white matter compared with normal white matter in volunteers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Messina and Port in this issue.

Graphical abstract

Figure 1:

A, Diagram shows how three-dimensional short repetition time (TR) adiabatic inversion recovery (IR) (STAIR) prepared ultrashort echo time (STAIR-UTE) sequence employs an adiabatic full passage (AFP) pulse to invert the longitudinal magnetization of long T2 components, followed by equally separated (with a time interval of τ) multispoke three-dimensional UTE-cones data acquisitions. N_sp = number of spokes. B, Diagram shows how basic three-dimensional UTE-cones sequence employs a short rectangular pulse for signal excitation and three-dimensional spiral sampling following conical view ordering. DAW = data acquisition window, FID = free induction decay, G_x,y,z = gradients in x, y, and z axes, RF = radiofrequency, TE = echo time. C, Diagram shows how longitudinal magnetization (y-axis) of the long T2 component is inverted by the AFP pulse, whereas magnetization of the ultrashort T2 myelin component is not inverted but largely saturated because of its fast transverse magnetization decay during the relatively long AFP pulse. This leads to selective imaging of the myelin component around a specific inversion time where long T2 signals are very largely nulled.

Figure 2:

Graphs show numeric simulation used to investigate the effect of repetition time (TR) and flip angle on suppression of, A, long T2 signals; B, C, and E, contrast-to-noise (CNR) efficiency; and, D, specific absorption ratio performance in short TR adiabatic inversion recovery (STAIR) prepared ultrashort echo time (STAIR-UTE) imaging. For the investigation of the signal suppression performance with different TRs (ie, 50, 100, 150, 200, 250, 500, and 800 msec), a wide range of T1s (ie, 20–2500 msec) are shown imaged with STAIR-UTE (A). Better visual comparison is shown in the zoomed curves in A, with T1s ranging from 300 to 2000 msec. CNR efficiency is defined by signal intensity difference between short and long T2 components normalized to TR. Higher CNR efficiency and mean CNR efficiency (calculated by averaging CNR efficiency of T1s between 300 and 1500 msec) are achieved when a shorter TR is used with STAIR-UTE sequence (B and C). Radiofrequency (RF) power is calculated by the sum of the squares of RF waveforms used in the sequence normalized to TR. This increases significantly with a shorter TR (D). Mean CNR efficiency also changes with excitation flip angle (E). Higher mean CNR efficiency is achieved when a flip angle between 20° and 40° are used with a TR less than 250 msec. B and E use the same color coding for TR-T1 combinations as in A.

Figure 3:

Results of phantom study to investigate signal suppression of long T2 signal with three-dimensional short repetition time (TR) adiabatic inversion recovery–prepared ultrashort echo time imaging using different TRs (ie, 50, 100, 150, 200, 250, 500 and 800 msec). A, Nine 5-mL water phantoms were prepared with MnCl2˙4H2O concentrations of 0.0055, 0.01, 0.015, 0.0195, 0.0265, 0.0375, 0.085, 0.18, and 1.4828 g/L. Phantoms were then placed in parallel in a cylinder container filled with 1% agarose. Corresponding T1s of these nine phantoms were 2012, 1520, 1195, 1002, 801, 609, 299, 148, and 18 msec, respectively. B, Graph shows signal intensity curves measured in all phantoms with different TR and inversion time (TI) combinations. a.u. = arbitrary units.

Figure 4:

Representative short repetition time (TR) adiabatic inversion recovery–prepared ultrashort echo time brain images (TR = 140 msec) in a healthy volunteer (29-year-old woman) with echo times (TEs) of, A, 0.032 msec, B, 0.1 msec, C, 0.3 msec, and, D, 2.2 msec. The magnitude and real and imaginary parts of mean signal intensity with different TEs of a region of interest (green oval in A) are plotted in E. F, Exponential fitting of magnitude signals at different TEs shows a short T2* of 0.22 ± 0.01 msec in this region of white matter. G, Linear fitting of phase signals with TE (R² = 0.98) clearly demonstrates a chemical shift of detected myelin signals. a.u. = arbitrary units.

Figure 5:

Representative three-dimensional short repetition time (TR) adiabatic inversion recovery prepared ultrashort echo time images in same volunteer as in Figure 4 with TR of 140 msec and inversion time of 61 msec demonstrate volumetric myelin imaging of whole brain.

Figure 6:

A–E, Selective T2-weighted fluid-attenuated inversion recovery (FLAIR) (repetition time [TR] msec/echo time msec, 7600/117), and, F–J, short TR adiabatic inversion recovery (STAIR) prepared ultrashort echo time (UTE) (TR = 140 msec) images in three representative participants with multiple sclerosis (MS). A, B, F, and G were obtained in a 35-year-old man; C, D, H, and I were obtained in a 69-year-old woman; E and J were obtained in a 48-year-old man. Arrows indicate MS lesions. Hyperintense lesions detected on T2-FLAIR images show signal loss on corresponding STAIR-UTE images, consistent with demyelination.

Figure 7:

Image shows correlation of T2 fluid-attenuated inversion recovery (T2-FLAIR) and short repetition time adiabatic inversion recovery–prepared ultrashort echo time (UTE) measurements in multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) in 10 participants with MS and signal intensities in normal white matter (NWM) in 10 healthy volunteers. A moderate correlation exists between T2-FLAIR and UTE measurements in the MS lesions (r = –0.43; P = .04). Low correlation exists between the two measurements for NAWM and NWM. These did not reach a statistically significant difference (NAWM: r = –0.09, P = .14; NWM: r = 0.04, P = .84). a.u. = arbitrary units.

Figure 8:

Boxplots show results of statistical analysis for measurements of normal white matter (NWM), normal-appearing white matter (NAWM), and multiple sclerosis (MS) lesions with, A, T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) and, B, short repetition time adiabatic inversion recovery (STAIR) prepared ultrashort echo time (STAIR-UTE) measures. Both the T2-FLAIR and STAIR-UTE sequences show signal intensity differences in MS lesions compared with NWM in healthy volunteers and NAWM in participants with MS (P < .001). The STAIR-UTE measurements show a significant difference between NWM in healthy volunteers and NAWM in participants with MS (P < .001), which is not observed in corresponding T2-FLAIR data (P = .82). The red line in each boxplot indicates the median. The bottom and top edges of each box indicate the 25th and 75th percentiles, respectively. + = outliers. a.u. = arbitrary units.