Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2 O exchange study

Abstract

Inversion recovery ultrashort echo time (IR-UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR-UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂ * signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂ O exchange model and explored the potential of IR-UTE imaging for the quantification of ultrashort T₂ * signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂ O. Long T₂ MR signals were measured using a clinical proton density-weighted fast spin echo (PD-FSE) sequence. IR-UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null ). Then, at this TI_null , images with echo times (TEs) of 0.01-4 ms were acquired to measure the T₂ * values of STCs. The PD-FSE signal dropped to near zero after 24 h of immersion in D₂ O. A wide range of TI_null values were used at different time points (240-330 ms for white matter and 320-350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂ * values of STCs were 200-300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂ O or H₂ O), and showed minimal changes after sequential immersion. The ultrashort T₂ * signals seen on IR-UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂ O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.

Keywords: T2*; gray matter; inversion recovery ultrashort echo time imaging; inversion time; myelin; white matter.

Figure 1

(A) Diagram of the 2D adiabatic inversion recovery ultrashort echo time (IR-UTE) pulse sequence with a minimum nominal TE of 10 μs. (B–C) Expected magnetization changes of WM and GM ultrashort T₂ and long T₂ components (WM_S, GM_S, WM_L and GM_L), with an inversion time (TI) that is chosen to null the WM_L, and GM_L respectively. The adiabatic inversion recovery pulse provides robust inversion of the longitudinal magnetization (M_z) of long T₂ components. M_z of the ultrashort T₂ components experience significant relaxation on the transverse plane during the long adiabatic inversion process, and are not inverted but partially saturated. At the time when UTE acquisition starts (TE = 10 μs, i.e. TE_10μs) and with TI chosen to null WM_L (Fig. B), GM_L have negative and GM_S have positive magnetization, leading to a smaller magnitude of the GM net magnetization. At a relatively longer TE (e.g. TE = 0.6 ms, i.e. TE_0.6ms), the magnitude of GM_L signal is essentially the same as that at TE_10μs, while WM_S and GM_S signals decay to zero or near zero. Subtraction of the magnitude signals seen in the image acquired at a longer TE from those seen on TE_10μs image provides positive contrast for WM and negative contrast for GM, enabling exclusive visualization of WM_S. With a TI chosen to null GM_L (Fig. C), both WM_L and WM_S have positive signals at TE_10μs, and the subtraction image provides positive contrast for both WM and GM, with WM generally showing higher signal.

Figure 2

(A) Longitudinal magnetizations (M_z) of WM and GM long T₂ components (i.e., WM_L and GM_L) plotted against inversion time (TI) in the IR-UTE sequence. (B) 2D IR-UTE images of one cerebral specimen (no. 1) acquired with different TIs before exchange with D₂O (TR/TE = 1000/2.2 ms). Note that at TE = 2.2 ms, the signals of WM and GM ultrashort T₂ components (WM_S and GM_S) become negligible due to their ultrashort T2*s. At shorter TIs (TI = 20 ms and 100 ms), there is little or no contrast between WM and GM. With TI increased to 300 ms, WM_L signals were largely suppressed and GM_L signals were moderately suppressed, as evidenced by the near zero signals in the WM and dramatic signal reduction in the GM. Further increase in TI resulted in signal increase in both WM and GM, with WM showing higher signal than GM. (C) T₁ map calculated from images in Figure (B). The three purple boxes represent three regions of interest (ROIs) defined in the WM for quantification of the average WM_L T₁. (D) T₁ fitting curves of a WM ROI (left, red box) and a GM ROI (right, red box) shows that with TR = 1000 ms, the TI for optimal nulling long T₂ signals (TI_null) was ~300 ms for WM_L and ~377 ms for GM_L, respectively.

Figure 3

(A) IR-UTE images from one cerebral specimen (no.1) acquired before exchange with D₂O with the inversion time (300 ms) chosen to null WM long T₂ components (TR = 1000 ms). T₂* values of the WM ultrashort T₂ components were 200 to 300 μs as shown on the T₂* map (lower panel, right corner). (B) The magnitude subtraction image (TE_10μs – TE_0.6ms) provides positive signal for WM and negative signal form GM. (C) Mono-exponential fitting of the IR-UTE images in Figure A showed a T₂* value of 206 μs in a WM ROI (yellow box, Fig. B).

Figure 4

(A) PD-FSE images of one cerebral hemisphere specimen (no.1) acquired before (0 min) and after sequential immersion in D₂O for 90 min, 150 min and 24 hrs. PD signals progressively decreased with increasing immersion time. (B) Corresponding IR-UTE images (TE = 10 μs) of the same specimen acquired with an inversion time that was chosen to null WM long T₂ components. (C) Quantitative sequential signal intensity changes of the PD-FSE images in Figure A, as measured in three regions of interests (ROIs) in WM (small yellow boxes inside the tissue area, 0-min PD-FSE and IR-UTE images). (D) Corresponding average T₁ changes in these WM ROIs. (E) Relatively constant T₂* values were obtained from these ROIs at corresponding time points. Signal-to-noise ratio (SNR) of the PD-FSE image was 166 and 11.3 for a WM ROI (the small yellow box labeled with a red star in the 0-min PD-FSE and IR-UTE images) before and after exchange, respectively. SNR of the corresponding IR-UTE image was 20.5 and 21.4 before and after exchange, respectively (TE = 10 μs). White arrowheads show the margin (sealed by 3M Micropore^® surgical tape) of the 2.5-inch plastic dish containing the samples. The margin of the plastic dish was immediately next to the 3-inch surface coil. The ROI representing background noise was placed outside of the coil area (Figs. A&B, the large yellow boxes on the top right corner labeled with red stars).

Figure 5

PD-FSE (TR/TE = 8000/13.5 ms) and UTE (TR/TE = 1000/0.01 ms) images, as well as UTE bi-component T₂* fitting results of one cerebral hemisphere specimen (no.5) before (top panel) and after (bottom panel) it was immersed in D₂O for 24 hrs. f_S stands for fraction of ultrashort T₂ components, _ST₂* stands for T₂* of the ultrashort T₂ components, and _LT₂* stands for T₂* of the long T₂ components. Inserts in the bi-component T₂* fitting plots (Fig. C and Fig. F) are IR-UTE images (TR/TE = 1000/0.01 ms) before and after exchange with D₂O, with long T₂ signals from GM being suppressed by the adiabatic inversion pulse. The red circle in the top insert (Fig. C) shows the definition of the region of interest (ROI) in WM for T₂* fitting at both time points.

Figure 6

(A) PD-FSE image of the cerebellar specimen before exchange with D₂O. (B) Selected IR-UTE images of the same specimen before exchange acquired at TR = 1000 ms with two different TIs and variable TEs. At TI = 260 ms (top panel), the magnitude subtraction image (TE_10μs – TE_0.6ms) highlights WM ultrashort T₂ components (WM_S). At TI = 350 ms, the subtraction image highlights both WM_S and GM ultrashort T₂ components, with WM_S showing higher signal. (C) T₂* fitting curves in a WM region of interest (ROI) (TI = 260 ms, red box) and a GM ROI (TI = 350 ms, yellow circle). (D) Sequential changes of average PD-FSE signal intensity, T₁s of WM and GM long T₂ components, and T₂*s of WM and GM ultrashort T₂ components in the defined ROIs in Figure C after immersion in D₂O. White arrowheads show the margin (sealed by 3M Micropore^® surgical tape) of the 2.5-inch plastic dish containing the samples.