Yet more evidence that myelin protons can be directly imaged with UTE sequences on a clinical 3T scanner: Bicomponent T2* analysis of native and deuterated ovine brain specimens

Abstract

Purpose: UTE sequences with a minimal nominal TE of 8 µs have shown promise for direct imaging of myelin protons (T₂ , < 1 ms). However, there is still debate about the efficiency of 2D slice-selective UTE sequences in exciting myelin protons because the half excitation pulses used in these sequences have a relatively long duration (e.g., 0.3-0.6 ms). Here, we compared UTE and inversion-recovery (IR) UTE sequences used with either hard or half excitation pulses (durations 32 µs or 472 µs, respectively) for imaging myelin in native and deuterated ovine brain at 3T.

Methods: Freshly frozen ovine brains were dissected into ∼2 mm-thick pure white matter and ∼3 to 8 mm-thick cerebral hemisphere specimens, which were imaged before and/or after different immersion time in deuterium oxide.

Results: Bicomponent T2* analysis of UTE signals obtained with hard excitation pulses detected an ultrashort T₂ component (STC) fraction (f_S ) of 0% to 10% in native specimens, and up to ∼86% in heavily deuterated specimens. f_S values were significantly affected by the TIs used in IR-UTE sequences with either hard or half excitation pulses in native specimens but not in heavily deuterated specimens. The STC T2* was in the range of 150 to 400 µs in all UTE and IR-UTE measurements obtained with either hard or half excitation pulses.

Conclusion: Our results further support myelin protons as the major source of the ultrashort T2* signals seen on IR-UTE images and demonstrate the potential of IR-UTE sequences with half excitation pulses for directly imaging myelin using clinical scanners. Magn Reson Med 80:538-547, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: T2*; UTE; bicomponent; inversion recovery; myelin; white matter.

Figure 1

Diagrams of the 2D IR-UTE pulse sequences with a TE of 10 µs used with (A) a short hard excitation pulse (rectangular shape, duration 32 µs, bandwidth = 8.2 kHz) followed by 2D radial ramp sampling, and (B) a half excitation pulse (duration 472 µs, bandwidth = 2.7 kHz) followed by 2D radial ramp sampling. (C) Illustration of the contrast mechanism for imaging ultrashort T₂ components in white matter (WM_S) using IR-UTE with the inversion time (TI) set for nulling of signals from the long T₂ components (WM_L), with the TI termed as WM_L TI_null. In magnitude IR-UTE images, the signal in white matter quickly decays to zero with increasing TE, while the signal in grey matter is still high at TE = 2.2 ms because it is dominated by long T₂ components (GM_L). (D) M_Z of WM_L and WM_S plotted against different TIs at the time UTE acquisition starts. At TI_c, signals from WM_L are nulled. At TI_a, which is much shorter than TI_c, signal in the image is dominated by WM_L. At TI_b, which is only slightly shorter than TI_c, signal from WM_S is cancelled out by that from WM_L. At TI_d and TI_e, signals from WM_S and WM_L coexist in the image but with different fractions. Note that the time parameters in the diagrams were not proportionally illustrated.

Figure 2

Representative magnitude images (acquired with hard excitation pulses) of one native WM short block. (A) Images obtained with varying inversion times (TIs) at TE = 2.2 ms. (B) T₁ map calculated from the images in (A) showing a relatively homogeneous center and a rim with a slightly longer T₁. The black box shows the region of interest (ROI) used for quantitative T₂* analyses. (C) Images obtained with different TEs and without inversion recovery preparation (labeled as ‘TI/NA (not applicable)’). (D-F) Images obtained with different TEs and varying TIs. There was an obvious signal intensity decrease with the increase of TE in the images at TIs = 270 ms and 275 ms, but not at TI = 295 ms.

Figure 3

Representative bi-component T₂* fitting curves of one native WM short block. (A) Measurement with hard excitation pulses and no IR preparation. (B-D) Measurements with hard excitation pulses and varying TIs. All measurements provided different ultrashort T₂ component fractions (f_S) but similar T₂* (T_2S*) values.

Figure 4

Bi-component T₂* analysis of images acquired with hard excitation pulse and no IR preparation from a WM short block after a 27-hr 4-pass D₂O exchange, showing a much higher ultrashort T₂ component fraction with similar T₂* (i.e., f_S and T_2S*) compared with a native WM short block shown as in Fig.3A. Inserts are the images of the WM short block after 27-hr D₂O exchange which showed fast signal decay with the increase in TE.

Figure 5

T₂* fitting results from the ~8-mm thick hemisphere slab imaged using both hard and half excitation pulse sequences (A–C) and the average results from three pure white matter short blocks imaged using hard excitation pulse sequence (D–F). IR-UTE images were acquired with TI = WM_L TI_null (labeled as TI_c, equivalent to that in Fig. 1D, on the x-axes of the figures) and 5-70 ms longer. The ultrashort T₂ component fraction (f_S) was very low when measured with UTE (<10%), much higher when measured with IR-UTE at WM_L TI_null, and decreased as TI increased from WM_L TI_null. The UTE sequence used with half pulse excitation did not detect the ultrashort T₂ component in this native specimen. f_S was consistently lower when measured with half pulse excitation than with hard pulse excitation at various TIs greater than WM_L TI_null (A&D). The ultrashort T₂ component T₂* (T_2S*) values were all in the range of 150 – 250 µs (B&E), and the long T₂ component T₂* (T_2L*) changed significantly with the increase in TI when hard pulse excitation was used (C&F). At WM_L TI_null, the T₂* signal followed a single component decay (R² > 0.99) (F). These results demonstrated the efficiency of the half pulse UTE and IR-UTE sequences in measuring T_2S* and detecting f_S changes in the presence of different proportions of LTC signals.

Figure 6

T₂* fitting curves of UTE and IR-UTE signals (all half excitation pulses) from three pure white matter long segments that were subject to 1-hr (left column, No.1), 2-hr (middle column, No.2) and 27-hr (right column, No.3) exchange with D₂O, respectively. (A) The UTE sequence detected an increase of f_S from ~9.5% to ~47.1% with D₂O exchange time in specimens No.1 to No.3. (B) The IR-UTE images obtained at WM_L TI_null showed single component T₂* signal decay, which changed little with D₂O exchange time. (C) The IR-UTE images obtained at 85 ms longer than WM_L TI_null (labled as “WM_L TI_null + 85 ms” in figure) showed bi-component T₂* signal decays in specimens after 1-hr and 2-hr D₂O exchange, and single component T₂* signal decay in the specimen after 27-hr D₂O exchange. f_S, ultrashort T₂ component fraction; T_2S*, ultrashort T₂ component T₂*.