Venous metrics in a large cohort of healthy elderly individuals from susceptibility-weighted images and quantitative susceptibility maps
Phillip G. D. Ward1,2, Parnesh Raniga1, Nicholas J. Ferris1,3, David G. Barnes2,4, David L. Dowe2, Elsdon Storey5, Robyn L. Woods6, and Gary F. Egan1,7

1Monash Biomedical Imaging, Monash University, Clayton, Australia, 2Faculty of Information Technology, Monash University, Clayton, Australia, 3Monash Imaging, Monash Health, Clayton, Australia, 4Monash eResearch Centre, Monash University, Clayton, Australia, 5Department of Neurology, Monash University, Clayton, Australia, 6Department of Epidemiology & Preventative Medicine, Monash University, Melbourne, Australia, 7ARC Centre of Excellence for Integrative Brain Function, Melbourne, Australia

Synopsis

In this study we examine venous characteristics of elderly individuals in a large healthy population. Venograms were generated from susceptibility-weighted images and quantitative susceptibility maps using state-of-the-art automated venography. Venous density and oxygen extraction fraction were calculated in different brain regions. The pattern of metabolic demand (oxygen extraction fraction) is found to be consistent with rest and passive observation. Additionally, our results suggest that venous density may be a potential biomarker.

Introduction

The magnetic properties of venous blood allow veins to be directly imaged with MRI, without an extrinsic contrast agent, using susceptibility-weighted imaging1 (SWI) and, more recently, quantitative susceptibility mapping2 (QSM). These techniques are sensitive to both small and large veins, and are minimally invasive, making them suitable for studies in healthy and diseased populations. Automated venography methods for processing these scans are advancing, reducing the resources required to analyse these images in large populations. With large populations, sophisticated imaging, and automated processing methods, it is possible to characterise the venous physiology and, with longitudinal data, identify biomarkers of prognostic and diagnostic value. In this study we take the first steps towards these goals by reporting vein density and venous blood deoxygenation in a healthy elderly population.

Method

150 healthy elderly subjects (age > 70 years) were recruited, as part of the ASPREE NEURO sub-study, and scanned on a 3T Siemens Skyra with a 32-channel head and neck coil. A single echo, fully flow compensated, GRE sequence was used (TE=20ms, TR=30ms, Voxel=0.9x0.9x1.8mm3, Matrix=256x232x72, FA=15). Standard SWI images were obtained directly from the Siemens console (IDEA version VD13A), and raw k-space data was saved.

Laplacian unwrapping and V-SHARP were used for background field removal and phase unwrapping on individual coil images3. Coil images were combined using a sensitivity-weighted sum. QSM was calculated using STI Suite. Whole brain vein segmentation (example in Figure 1) was performed using a shape-based Markov Random Field (ShMRF) technique4, which combines both SWI and QSM using an anatomic prior.

Brain regions were extracted by running the freesurfer recon_all pipeline and combining sub-regions into lobes5. Venous density was calculated for each region as the sum of venous voxels divided by the sum of all voxels in the region. Oxygen-extraction fraction (OEF) was calculated using Equation [1] where $$$\Delta\chi_{tissue-vein}$$$ is the maximum venous QSM in the region, $$$Hct$$$ is hematocrit and $$$\chi_{do}$$$ is the magnetic susceptibility of fully deoxygenated haemoglobin. Published values6 were used for $$$Hct$$$ (0.4) and $$$\chi_{do}$$$ (0.264ppm).

$$OEF = \Delta\chi_{tissue-vein} \cdot 4 \pi \cdot \chi_{do} \cdot Hct \>\>\>\>\>\>\>\>\>[1]$$

Results

The venous density (Figure 2, Table 1) was found to be different across many anatomic areas. In the cortical region, the frontal and parietal lobes were found to have consistently lower venous density (mean 4.25% and 4.06% respectively) than the temporal lobe, occipital lobe and cingulate cortex (9.06%, 9.02% and 7.39% respectively). There was no significant difference found between the left and right hemispheres. In the sub-cortical region the values were far less orderly, with lower volume resulting in higher standard deviations.

OEF was found to be significantly higher in the caudate, thalamus and occipital cortex, and lower in the frontal lobe, parietal lobe and putamen (Figure 3, Table 1). OEF was higher for brain regions, which are known to be active (occipital lobe, thalamus) when the brain is at rest or the subject is observing passively.

Discussion

Venous density measurements and oxygen extraction fraction derived from magnetic susceptibility imaging have been recently proposed as imaging biomarkers. Our results indicate that while the venous density can be variable across the brain and across subjects, it may potentially be useful as a biomarker for neurovascular disease.

TheOEF results are also consistent with what is expected in regards to oxygen consumption in different parts of the brain when it is at rest. Additionally, OEF measurements normalised for red blood cell volume to account for physiological differences may provide increased sensitivity to detect neurovascular changes in disease.

Acknowledgements

We acknowledge all of the investigators of the ASPREE principal study and the ASPREE-NEURO sub-study for the coordination, recruitment and all study measurements including 3 Tesla brain MRI. We also thank all of the subjects for their time and willingness to participate.

The Alzheimer’s Australia Dementia Research Foundation (AADRF), the Victorian Life Sciences Computation Initiative (VLSCI), and the Multi-model Australian ScienceS Imaging and Visualisation Environment (MASSIVE) supported this work. The National Health and Medical Research Council (NHMRC) also supported this work (NHMRC Grant APP1086188, NHMRC ASPREE-NEURO grant).

References

1. Haacke, E.M., Xu, Y., Cheng, Y.-C.N., Reichenbach, J.R., 2004. Susceptibility weighted imaging (SWI). Magn Reson Med 52, 612–8. doi:10.1002/mrm.20198.

2. Schweser, F., Deistung, A., Lehr, B.W., Reichenbach, J.R., 2011. Quantitative imaging of intrinsic magnetic tissue properties using {MRI} signal phase: An approach to in vivo brain iron metabolism? NeuroImage 54, 2789 – 2807. doi:10.1016/j.neuroimage.2010.10.070.

3. Li, W., Wu, B., Batrachenko, A., Bancroft-Wu, V., Morey, R.A., Shashi, V., Langkammer, C., De Bellis, M.D., Ropele, S., Song, A.W., Liu, C., 2014. Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan. Human Brain Mapping 35, 2698–2713. doi:10.1002/hbm.22360.

4. Ward, P.G.D., Ferris, N.J., Ng, A.C.L., Barnes, D.G., Dowe, D.L., Egan, G.F., Raniga, P., 2015. Venous segmentation using Gaussian mixture models and Markov random fields, in: Proceedings of the International Society for Magnetic Resonance in Medicine 23rd Annual Meeting, Toronto, Canada.

5. Fischl, B., 2012. FreeSurfer. Neuroimage 62, 774–781. doi:10.1016/j.neuroimage.2012.01.021.

6. Spees, W.M., Yablonskiy, D.A., Oswood, M.C., Ackerman, J.J., 2001. Water proton MR properties of human blood at 1.5 Tesla: Magnetic susceptibility, T1, T2, T*2, and non-Lorentzian signal behavior. Magnetic resonance in medicine 45, 533–542.

Figures

Figure 1: A typical example from one subject of an axially projected venogram shaded to qualitatively reflect OEF (highly deoxygenated veins are yellow, oxygenated veins are red).

Figure 2: Boxplots for the venous density in cortical regions: frontal, parietal, temporal and occipital lobes, the cingulate cortex, left hemisphere, and right hemisphere, and in sub-cortical structures: thalamus, caudate, putamen, hippocampus and amygdala. Numeric values are reported in Table 1.

Figure 3: Boxplots for the venous oxygen-extraction fraction (OEF) in cortical regions: frontal, parietal, temporal and occipital lobes, the cingulate cortex, left hemisphere, and right hemisphere, and in sub-cortical structures: thalamus, caudate, putamen, hippocampus and amygdala. Numeric values are reported in Table 1.

Table 1: Regional venous density (column 2) and OEF measurements (column 3) for each region (column 1).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0329