Imaging Subcortical White Matter by High Resolution 7 T MRI in vivo: Towards Potential U-Fiber Density Mapping in Humans
Evgeniya Kirilina1,2, Juliane Dinse1, Pierre-Louise Bazin1, Carsten Stueber3,4, Stefan Geyer1, Robert Trample1, Andreas Deistung5, Juergen R Reichenbach5, and Nikolaus Weiskopf1,6

1Neurophysics, Max Plank Institute for Human Cognitive and Brain Science, Leipzig, Germany, 2Neurocomputation and Neuroimaging Unit, Department of Educational Science and Psychology, Free University Berlin, Berlin, Germany, 3Department of Radiology, Weill Cornell Medical College, New York, NY, United States, 4Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, United States, 5Medical Physics Group, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, 6Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom

Synopsis

Subcortical white matter (SWM) incorporates U-fibers, the intra-hemispheric connections between adjacent gyri. Despite their importance for cortical connectivity little is known about the U-fiber distribution in humans due to the lack of appropriate imaging methods. Herein we investigate SWM using high-resolution in-vivo MRI at 7T. A clear-cut discrimination of SWM from the adjacent brain regions was obtained based on higher qR2*, qR2 and susceptibility in-vivo. These new findings may pave the way for future in-vivo segmentation strategies for this crucial brain region as well as potential U-fiber density mapping in humans.

PURPOSE

Subcortical white matter (SWM) is a thin layer of white matter (WM) residing just below the cortical sheet. Its structure, metabolism and function differ substantially from deep WM. Importantly, SWM incorporates short association fibers, the intra-hemispheric connections between adjacent gyri, referred to as U-fibers. Despite their importance for cortico-cortical connectivity little is known about the density and distribution of U-fiber in humans1 mainly due to the lack of appropriate imaging methods. In humans invasive tracer studies are not applicable and DTI-based tractography does not yield satisfactory results in SWM2. Several SWM contrasts has been demonstrated with structural MRI ex-vivo at 1.5T3 and 7T4 and in-vivo at 7T5, but no study has fully explored the potential of high-resolution ultra-high field structural SWM mapping in-vivo yet. Thus, we investigate four contrasts in SWM ((i) quantitative transverse and (ii) effective transverse relaxation rates (qR2 and qR2*), (iii) longitudinal relaxation rate (qR1) and (iv) quantitative susceptibility maps (QSM)) using high-resolution in-vivo MRI at 7T. We show that SWM qR2*, qR2 and QSM exhibit strong contrast to both grey matter (GM) and deep WM. Iron and iron reach cells were identified as the intrinsic contrast agents by comparing the in-vivo data with ex-vivo MR imaging and quantitative iron maps acquired with proton induced X-ray emission (PIXE).

METHODS

MR measurements were performed on a whole body 7 T Siemens MRI scanner. qR2* and qR1 maps with an isotropic resolution of 0.5 mm were sourced from a recently published repository and analysed6. qR1 maps were co-registered in the coordinate space of the qR2* maps using 0.6 mm resolution R2* and T1-weighted images, acquired in a separate session. WM and GM regions were segmented based on the co-registered qR1 maps7. For two participants QSM were reconstructed with the HEIDI algorithm8 employing phase images of an additional multi-echo gradient-echo (GRE) acquisition (0.5 mm isotropic). For one volunteer an additional multi-echo spin-echo data set (0.5 in plane resolution, 1 mm slices) has been acquired and used for calculating transverse relaxation rate (qR2) maps. To better understand the in-vivo maps, post mortem tissue samples were additionally investigated with T2*-weighted imaging (FLASH, 80 μm isotropic resolution) and qR1 mapping (MP2RAGE, 200 μm resolution, occipital pole, 92 y, f, postmortem time before fixation 22 hours) as well as quantitative iron mapping with PIXE (primary motor and sensory cortex, 82 y, f, postmortem time before fixation 8 h)9.

RESULTS

High-resolution in-vivo 7T MRI revealed a thin (0.5-2 mm) hyperintense layer below the GM-WM border on qR2, qR2*, and QSM maps (see Figs.1 and 2), indicating SWM. qR2 (ΔR2=8±3 s-1), qR2* (ΔR2*=15±5 s-1), and magnetic susceptibility (Δχ=25±5 ppb) values in this layer were significantly higher than in deep WM. Interestingly, the increase in qR2, qR2*, QSM was found to be more prominent in sulcal fundi and walls as compared to the gyral crowns. Similar findings were observed on the ex-vivo tissue sample, where SWM again exhibited as a thin contrast-rich layer with decreased signal intensities on T2*-weighted images and hyperintense in qR1 (ΔR1=0.4±0.1 10-3 s-1) maps (see Fig. 3), below the GM-WM border. Contrast between SWM and deep WM was found to be stronger, than the intra-cortical contrast in both T2*-weighted and qR1 images. Iron quantification yielded increased iron levels within a 1 mm thick SWM layer below the GM-WM boarder, whereas iron content has been determined to be 355 ± 30 μg, 255 ± 50 μg, 92 ± 30 μg per g dry brain tissue in SWM, GM, and WM, respectively.

CONCLUSION

Utilizing the superior resolution provided by 7 T MRI we were able to image SWM in in-vivo and in post-mortem brain tissue samples at the WM-GM interface. A clear-cut discrimination of SWM from the adjacent brain regions was obtained based on higher qR2*, qR2 and susceptibility in in-vivo tissue and higher qR2* and qR1 in ex-vivo tissue as compared to both GM and deep WM. We found the SWM contrast to be even higher than the GM-WM contrast as well as intra-cortical grey matter contrast. The higher R2, R2*, and susceptibility values indicate iron complexes and iron reach cells in SWM as dominating biophysical contrast source and is further supported by the elevated iron concentrations in SWM measured with PIXE. These new findings are of paramount importance and may pave the way for future in-vivo segmentation strategies for this crucial brain region as well as potential U-fiber density mapping in humans.

Acknowledgements

No acknowledgement found.

References

1. Oishi K et al. Superficially Located White Matter Structures Commonly Seen in the Human and the Macaque Brain with Diffusion Tensor Imaging. Brain Connect. 2011;1:37–47

2. Reveley C et al. Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography. PNAS. 2015;112:2820–2828.

3. Curnes J et al. MR imaging of compact white matter pathways. Am J Neuroradiol, 1988; 9:1061–1068.

4. Bagnato F et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011; 134:3602–3615.

5. Deistun A. et al. Toward in vivo histology: a comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2*-imaging at ultra-high magnetic field strength. Neuroimage 2013;65:299–314.

6. Tardif C et al. Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain. Neuroimage. 2015;doi:10.1016/j.neuroimage.2015.08.042

7. Bazin P-L et al. A computational framework for ultra-high resolution cortical segmentation at 7Tesla. Neuroimage. 2014; 93(2):201–209.

8. Schweser F. et al. Quantitative susceptibility mapping for investigating subtle susceptibility variations in the human brain. Neuroimage. 2012;62:2083–2100.

9. Stüber C et al. Myelin and iron concentration in the human brain: A quantitative study of MRI contrast. NeuroImage. 2014;93(1):95–106.

Figures

QR2* (left) and QSM (right) maps of a representative participant overlaid with GM mask (light red). Arrows show SWM visible in both contrasts.

QR2* (left) and R2 (right) maps of a single participant. Arrows shows SWM visible in both contrasts.

T2*w image (left) and quantitative R1 maps (right) of a post-mortem occipital pole tissue sample. White arrows show SWM visible in both contrasts, red arrows indicate the Stria of Gennari visible in both contrasts.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0502