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
imaging
1
(SWI) and, more recently, quantitative susceptibility mapping
2 (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).
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