Diffusion Kurtosis at varying diffusion times in the normal and injured mouse brains
Dan Wu1, Frances J Northington2, and Jiangyang Zhang1,3

1Radiology, Johns Hopkins University School of Medicine, BALTIMORE, MD, United States, 2Pediatrics, Johns Hopkins University School of Medicine, BALTIMORE, MD, United States, 3Radiology, New York University School of Medicine, New Yourk, NY, United States

Synopsis

To investigate the diffusion time dependence of diffusion kurtosis, we measured kurtosis at varying diffusion times using pulsed and oscillating gradients. The results showed reduced kurtosis as diffusion time decreased from 25 ms to 2.5 ms in the normal adult mouse brains, and the differences were higher in the gray matter than the white matter regions. Results from neonatal mice with severe hypoxic-ischemic injury showed that both kurtosis measurements at short and long diffusion times elevated in the edema region, and the changes were heterogeneous in the hippocampus, which may be correlated with long-term outcome.

Introduction

Diffusion kurtosis imaging (DKI) is a useful tool to examine tissue microstructures based on measurements acquired at multiple b-values1,2. On the other hand, recent studies suggested that diffusion MRI measurements acquired at multiple diffusion times can provide additional information on microstructural properties3,4. Combining the two approaches may lead to more comprehensive understanding of microstructural organization, however, the relationships between the two approaches are not well understood. In this study, we measured diffusion kurtosis at varying diffusion times using pulsed and oscillating gradients, and attempted to characterize the diffusion time dependence of DKI in the normal and hypoxia-ischemia injured mouse brains.

Methods

In vivo diffusion MRI were performed on a horizontal 11.7 Tesla scanner with a 72 mm volume transmitter and a 15 mm planar surface coil. Normal adult C57BL/6 mice (n = 7) were scanned using a pulsed gradient spin-echo (PGSE) sequence with δ/Δ = 4/20 ms and a cosine-trapezoid5 oscillating gradient spin-echo (OGSE) sequence with an oscillating frequency of 100Hz (equivalent diffusion time = 2.5 ms). The sequences were calibrated using a gel phantom. Images were acquired with a four-segment EPI readout, TE/TR = 55/3000 ms, NA = 4, 30 diffusion directions, b = 1000 and 2000 s/mm2, in-plane resolution of 0.17 x 0.17 mm2, and slice-thickness of 0.8 mm. Neonatal C57BL/6 mice (n = 5) at postnatal day 10 were subjected to unilateral hypoxia-ischemia (HI) using the Vannucci model6 and imaged at 24 hrs after injury with similar imaging parameters as the adult mice except in-plane resolution = 0.2 x 0.2 mm2, slice-thickness = 1 mm, and NA = 2. Follow-up scans were performed at 3, 10, and 17 days after the injury with T2-weighted and DTI scans. The mean diffusivity (MD), mean kurtosis (MK), axial and radial kurtosis (K// and K⊥) were obtained using the Diffusional Kurtosis Estimator software7.

Results

In the normal adult mouse brain, MKOGSE measured at 2.5 ms diffusion time was significantly lower than that MKPGSE measured at 20 ms diffusion time (Fig. 1). The differences between PGSE and OGSE MKs (ΔMK= MKPGSE - MKOGSE, Fig. 1B) were greater in the cortex and hippocampus (77.8±3.5% and 41.2±6.3%, respectively) than in the corpus callosum and cerebral peduncle (33.7±3.4% and 23.8±4.4%, respectively) (Fig. 2A). In these white matter structures, the differences between PGSE and OGSE K// were less than the differences in K⊥ (Fig. 2B-C).

In neonatal mouse brains that had severe edema (with hyper-intense T2 and reduced MD) at 24hrs after HI injury, both PGSE and OGSE MK were drastically elevated in the edema region (Fig. 3A). The ipsilateral cortical MK increased to more than three folds of the contralateral side (Table 1). Both PGSE and OGSE MK maps showed marked heterogeneity within the edema region. In addition, ΔMK was higher in the edema region than the contralateral side (Fig. 3B). Compared to other edema region, the dorsal hippocampus (indicated by the red arrows) had relatively normal PGSE/OGSE MK and ΔMK values (Table1), and this region was mostly spared at 17 days after injury without developing into cyst (Fig. 3C).

Discussion and conclusion

The reductions in MK when the diffusion time decreased from 20 ms to 2.5 ms agree with previous tissue diffusion modelling results at relatively short diffusion times8. It is likely that water diffusion becomes less restricted as diffusion time decreases, resulting in reduced non-Gaussianity. The change in diffusion kurtosis with diffusion time may reflect the spatial scale of microstructural barriers that cause the non-Gaussianity. For example, the greater ΔMK values in the cortex than the corpus callosum suggest a larger amount of water diffusion in the cortex turns less non-Gaussian as the diffusion distance shortens from 10 to 3 μm, given the diffusion time from 20 to 2.5 ms.

The investigation of diffusion kurtosis at varying diffusion time may offer additional information about the microstructural changes under pathological conditions. Recent studies showed the DKI has higher sensitivity than DWI in detecting brain injury9,10,11, and the heterogeneity in kurtosis measurements may reflect the heterogeneity of injury. In the HI injured mouse brain, heterogeneity was observed in the PGSE and OGSE MK as well ΔMK images (Fig. 3), implying the involvement of microstructural changes at multiple spatial scales. The heterogeneity in the hippocampal region is worth investigating, and it may correlate with the long-term outcomes.

Acknowledgements

No acknowledgement found.

References

1. Jensen J, Helpern J, Ramani A, et al. Diffusional kurtosis imaging: the quantification of non-Gaussian water diffusion by means of MRI. Magn Reson Med. 2005;53:1432-1440.

2. Wu E, Cheung M. MR diffusion kurtosis imaging for neural tissue characterization. NMR Biomed. 2010; 23:836-848.

3. Parsons EC Jr, Does MD, Gore JC. Temporal diffusion spectroscopy:theory and implementation in restricted systems using oscillating gradients. Magn Reson Med. 2006;55:75–84.

4. Does MD, Parsons EC, Gore JC. Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain. Magn Reson Med. 2003;49:206–215.

5. Van AT, Holdsworth SJ, Bammer R. In vivo investigation of restricted diffusion in the human brain with optimized oscillating diffusion gradient encoding. Magn Reson Med. 2014;71:83–94.

6. Rice JE III, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981;9:131–141.

7. Tabesh A, Jensen JH, Ardekani BA, Helpern JA. Estimation of tensors and tensor-derived measures in diffusional kurtosis imaging. Magn Reson Med. 2011; 65:823-836.

8. Jensen JH, Helpern JA, MRI quantification of non-Gaussian water diffusion by kurtosis analysis. NMR Biomed. 2010;23:698-710.

9. Hui S, Fieremans E, Jensen H, et al. Stroke assessment with diffusional kurtosis imaging. Stroke. 2012;43(11):2968-73.

10. Umesh Rudrapatna S, Wieloch T, Beirup K, et al. Can diffusion kurtosis imaging improve the sensitivity and specificity of detecting microstructural alterations in brain tissue chronically after experimental stroke? Comparisons with diffusion tensor imaging and histology. Neuroimage. 2014;97:363-73.

11. Weber A, Hui S, Jensen H, et al. Diffusional kurtosis and diffusion tensor imaging reveal different time-sensitive stroke-induced microstructural changes. Stroke. 2015;46(2):545-50.

Figures

Fig. 1: (A) Maps of mean kurtosis (MK), axial and radial kurtosis (K// and K⊥) acquired from a normal adult mouse brain showed reduced diffusion kurtosis when diffusion time reduced from 20ms (PGSE) to 2.5ms (OGSE). (B) The ΔMK map showed higher MK difference in the cortex (CX) and hippocampus (HP), compared to the corpus callosum (cc) and cerebral peduncle (cp).

Fig. 2: MK, K// and K⊥ measured at 20 ms (PGSE) and 2.5 ms (OGSE) in the several gray and white matter structures. Structural abbreviations are the same as in Fig. 1. The data were represented as mean ± standard deviation (n = 7). * p < 0.01 by paired Student t-test.

Fig. 3: (A) MK and MD maps of a representative neonatal mouse brain with severe edema at 24 hrs after hypoxia-ischemia, acquired using PGSE and OGSE diffusion MRI. (B) The ΔMK and ΔMD images at the same level. (C) T2-weighted MRI of the same mouse brain scanned at 24hrs, 3days, 10days, and 17days after injury.

Table 1: MK, ΔMK, MD, and ΔMD values measured in neonatal mouse brains with severe edema (n=5) at 24hrs after hypoxia-ischemia using PGSE and OGSE diffusion MRI. Values from the ipsilateral and contralateral cortex, dorsal hippocampus (corresponds to the red arrows in Fig. 3), and ventral hippocampus (rest of the hippocampus) regions are listed.



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