Myelin water quantification in multiple sclerosis using short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) imaging

Abstract

Background: Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions.

Method: Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison.

Results: The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM.

Conclusions: The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies.

Keywords: Myelin water (MW); fast spin echo (FSE); multiple sclerosis (MS); short repetition time adiabatic inversion recovery (STAIR).

Figure 1

Sequence diagram for STAIR-FSE sequence. Inversion of longitudinal magnetization is achieved using the AFP pulse. TI is the time between the center of the AFP pulse and the center of the excitation pulse, while ST represents the time interval between the center of the excitation pulse and the center of the last refocusing pulse. The STAIR-FSE sequence employs a short TR and an optimized TI to effectively suppress long T₂ water components with a wide range of long T_1S. The FSE sequence enables rapid data acquisition of the MW signals. AFP, adiabatic full passage; TI, inversion time; ST, saturation time; FSE, fast spin echo; TR, repetition time; STAIR-FSE, short repetition time adiabatic inversion recovery prepared-fast spin echo; MW, myelin water.

Figure 2

Representative whole brain STAIR-FSE images acquired from a 31-year-old healthy male volunteer. STAIR-FSE, short repetition time adiabatic inversion recovery prepared-fast spin echo.

Figure 3

Representative STAIR-FSE and PD-FSE images as well as corresponding aMWF maps from a 31-year-old healthy male volunteer. White matter regions have much higher aMWF values than gray matter regions. STAIR-FSE, short repetition time adiabatic inversion recovery prepared-fast spin echo; PD-FSE; proton density-weighted FSE; aMWF, apparent myelin water fraction.

Figure 4

Representative T₂-FLAIR (first column), STAIR-FSE (second column), PD-FSE (third column), and aMWF (fourth column) images from three patients with MS. Patient #1 was a 57-year-old female, Patient #2 was a 58-year-year-old female, and Patient #3 was a 67-year-old female. Hyperintense lesions detected on T₂-FLAIR images show a signal loss on the STAIR-FSE images and decreased values in the corresponding aMWF maps. MS lesions are indicated by yellow arrows. T₂-FLAIR, T₂-fluid attenuated inversion recovery; STAIR-FSE, short repetition time adiabatic inversion recovery prepared-fast spin echo; PD-FSE, proton density-weighted FSE; aMWF, apparent myelin water fraction; MS, multiple sclerosis.

Figure 5

Paired comparisons of the STAIR-FSE-measured aMWFs between MS lesions, NAWM, and NWM for the first (A) and second (B) type analysis. For the first type analysis, significant differences in aMWF measures were found between MS and NAWM and between MS and NWM. Though NAWM had a lower aMWF value than NWM, no significant difference was found for the aMWF measurements between them (P=0.4). For the second type of data analysis, significant differences were found for aMWF measures between MS and NAWM, between MS and NWM, and between NAWM and NWM (“***” indicates P<0.001, “**” indicates P<0.05, and “^▲” indicates P>0.05). MS, multiple sclerosis; NAWM, normal-appearing white matter; NWM, normal white matter; aMWF, apparent myelin water fraction; STAIR-FSE, short repetition time adiabatic inversion recovery prepared-fast spin echo.