In Vivo Detection of Short T2* Lipid 1H in Mouse Brain with a ZTE/UTE Subtraction Method (ZUS)
Yaotang Wu1,2, Michael Marcotrigiano3, Hui Xue1,2,4, Robert V Mulkern1,2, and Jeffrey Neil2,5

1Department of Radiology, Boston Children's Hospital, Boston, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Department of Research, Boston Children's Hospital, Boston, MA, United States, 4Sichuan University, Chengdu, China, People's Republic of, 5Department of Neurology, Boston Children's Hospital, Boston, MA, United States


A new method, ZUS, utilizes ZTE to detect all signals with T2* as short as a few hundred microseconds, including myelin proton signals, and UTE to selectively detect signals with longer T2* values, considered to be tissue water components. The difference of these two types of images is used to visualize signals from lipid 1H. In this study, the feasibility of ZUS was demonstrated on a cholesterol phantom (the major component of myelin) and on a live mouse. ZUS images highlighted lipid, particularly myelin in the corpus callosum, of mouse brain in vivo.


Lipid plays an important role in brain white matter function, particularly for myelin, and quantitative assessment of myelin with MRI has many applications. However, the T2* of MR signals from the lipid components of myelin are shorter than 1 ms (1), making it very difficult to detect myelin proton signals. Recently, Ultra Short TE (UTE) has been applied to explore the detection of myelin (1, 2). Based on our earlier study of short T2 imaging (3), we developed a new method, which takes advantage of both Zero TE (ZTE) and UTE, to positively visualize myelin protons from mouse brain in vivo.


Cholesterol, which constitutes approximately 40 Mol % of myelin lipid and 30 Mol % of grey matter lipid (4), was selected to demonstrate feasibility of ZUS for direct myelin proton detection. Powdered cholesterol (Sigma, St. Louis, MO) was placed into a plastic tube of 1.5 cm diameter to form column with density of 1.83 mMol cm-3 (Cholesterol tube). A saline filled plastic tube of 1.5 cm diameter (Saline tube) was attached to the Cholesterol tube by Teflon tape (Phantom, Fig.1A). Mice (C3H/HeNCrl, Charles River Laboratories, Wilmington, MA) were used as subjects for in vivo MRI. Animals were anesthetized by inhalation of isoflurane through a nose cone for the duration of the study.

ZTE/UTE Subtraction (ZSU)

The major differences between ZTE and UTE are the timing of the excitation pulses and sampling of FID data. With ZTE, the projection gradient is ramped up and stabilized. Subsequently a short, hard RF pulse is issued with the gradient on. After a receiver dead time delay, the FID is sampled under the constant gradient. With UTE, a non-selective or selective pulse is issued. After a short time delay (TE), the projection gradient is ramped up, and the FID is sampled under the rising gradient ramp and the following constant gradient. With ZTE, signals with T2* as short as a few hundred microseconds, limited by the receiver dead time and signal acquisition time, can be detected. With UTE, signals with T2* as short as those detected by ZTE are not detected, but UTE selectively excites signals within a limited range of resonance frequencies and with longer T2* values. Subtraction of UTE from ZTE thus provides an image from signals with only the shortest T2* values detected by ZTE. MR imaging was performed on a Bruker BioSpec 70/30 scanner using a FOV = 35 mm and a digital resolution = 0.137 mm for the animal study and a 50 mm FOV and 0.195 mm digital resolution for the phantom study. ZTE was acquired with a bandwidth = 250 kHz, excitation pulse = 5 µs (5°), number of average = 1 and TR = 10 ms. UTE was acquired with bandwidth = 250 kHz, TE = 9 µs, excitation pulse 5 µs (5°) (UTE1) or with bandwidth = 100 kHz, TE = 1.5 ms and excitation pulse 1 ms (5°) (UTE2). Scan time for either ZTE or UTE was about 35 min.


The ZTE image of the phantom shows both cholesterol and saline (Fig. 1B). Both UTE1 and UTE2 show saline only (UTE2 shown in Fig. 1C). The subtraction shows cholesterol only (Fig. 1D). ZTE, UTE2, and ZUS images of the brain of a live mouse are provided in Fig. 2 A, B, and C, respectively. ZUS allowed visualization of the skull (arrow) and brain. Note that the white matter of the corpus callosum (arrowhead) has higher lipid signal than surrounding grey matter.


ZUS images may be optimized to visualize signals with a limited range of short T2* values by adjusting the pulse length of UTE, which excites the unwanted signals to be eliminated in ZUS. UTE2 was selected in this study, eliminating T2* signals longer than 500 μs in the ZUS image. T1 weighting was minimized by the use of a 5° excitation angle and a TR of 10 ms. The direct visualization of only solid state signals from powdered cholesterol sample and the higher signal from the mouse corpus callosum in vivo in the ZUS images support our contention that ZUS provides information from myelin protons with possibly some contamination from water associated myelin in vivo. The intensity of solid skull bone also visualized in ZUS may serve as an index for quantitative assessment of lipids in the brain.


Mark Mattingly and Gang Zhu of Bruker Biospin (Billerica, MA) provided considerable assistance with probe and sequences technical issues.


1. Wilhelm MJ, et al. Direct magnetic resonance detection of myelin and prospects for quantitative imaging of myelin density. Proc Nat Acad Sci USA 2012;109:9605-9610. 2. Waldman A, et al. MRI of the brain with ultra-short echo-time pulse sequences. Neuroradiology 2003;45:887–892. 3. Wu Y, et al. Multinuclear solid-state three-dimensional MRI of bone and synthetic calcium phosphates. Proc Nat Acad Sci USA 1999;96:1574–1578. 4. O’Brien and Sampson. Lipid composition of the normal human brain: Grey matter, white matter, and myelin. J Lipid Res 1965;6:537-544.


Fig. 1. MR images and photo of the phantom. A: Photo of the phantom. B: ZTE image of the phantom shows both cholesterol and saline. C: UTE2 shows saline only. D: ZUS (B-C), shows cholesterol only.

Fig. 2. MR images of a mouse brain. A: ZTE. B: UTE2. C: ZUS (A-B). ZUS positively visualized the skull bone (arrow) and white matter of the corpus callosum (arrowhead).

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)