# Diffusion-Weighted Imaging of the Macaque Brain Using Diffusion-Prepared Turbo Spin Echo in MRI
## 4 Discussion  
The present study has demonstrated an optimal TSE-based method for distortion-free, high-resolution, high-SNR and time-efficient brain dMRI over an anesthetized and well-stabilized macaque. The original and ultimate attempts of our implemented sequence were to achieve distortion-free, submillimeter-scale dMRI across species with improved SNR and time efficiency, which is heavily demanded in the early diagnosis and individualized treatment of brain diseases. We encountered some challenges during our preliminary experiments over human subjects, the most vital of which was in motion artifacts such as spontaneous head movements or respiratory motions, whereas the experiments with motion-free subjects as melons produced high-definition structures [10]. Apart from common technique of employing EPI-based sequences with a number of average scans to enhance signals and using post-reconstructions to blur noise or correct distortions, the conventional compensation approach was to use motion-insensitive TSE-based sequences as readouts (e.g., the PROPELLER technique), although this requires scan time at least twice as high as the resolution increases. Instead of adding other redundant parts, we have proposed and implemented the DP-TSE approach for NHP brain dMRI in vivo.  
The dMRI study with an anesthetized macaque can contribute largely to mesoscale (submillimeter-scale) brain research such as white-matter-related disease. During the experiment, we used a 3D-printed stereotaxic head frame to stabilize the macaque skull and place the coil close enough to the brain, in order to eliminate motion-induced artifacts as  
Figure 4: (**a**) ADC maps from DP-TSE with \(b=1500\) and \(2000\) s/mm\({}^{2}\). (**b**) The ADC fitting of two protocols with TR = 1500 ms, \(b=100\), 300, 600, and \(900\) s/mm\({}^{2}\). (**c**) Comparison of scan time and image quality with parallel acceleration ON/OFF in DP-TSE, \(b=500\) s/mm\({}^{2}\).  
much as possible. In addition, with TSE-based acquisition embedded, the dMRI suffered almost no extra distortion induced by the EPI readout other than the inherent inhomogeneous B\({}_{0}\), whereas the diffusion preparation module suffered fewer high-order diffusion moments with spoilers applied. The multi-shot DW-EPI and DW-rsEPI sequences had similar advantages to address these issues by dividing EPI readouts into several segments, which have commonly been used for high-resolution dMRI and are ideal for control groups for this study; however, such fat effects caused by the wide bandwidth of RF pulses in DW-rsEPI for a shorter TE will not appear in DP-TSE instead, which therefor eliminates the signal loss by the RF inversion of fat saturation in DW-rsEPI.  
In this study, we simply pushed the resolution to 1 mm in-plane and a 2 mm thickness to demonstrate the fair differences between EPI-based and TSE-based sequences without image correction at 3 T; promising results suggest that the TSE-based approach has promising potential in achieving submillimeter-scale resolution at 3 T or even higher field strengths of the MR system. Moreover, without disturbing effects from EPI, TSE-based dMRI could be expected to provide for more complex fiber geometries such as fiber crossings at the whole brain level. The results in Figures 3 and 4 demonstrate that the implemented DP-TSE sequence is suitable for anesthetic macaque brain dMRI and is able to reveal the superiority of high image quality, especially with high \(b\)-values, which paves the way to submillimeter dMRI study in NHPs. In additional, features such as no repetition scans and a parallel imaging capability may incite more possibilities for further research.