Kristy Tan1, Adam L. Sandler2, Avital Meiri1, Rick Abbott2, James T. Goodrich2, Eric Barnhill3, and Mark E. Wagshul1
1Gruss MRRC, Albert Einstein College of Medicine, Bronx, NY, United States, 2Department of Neurological Surgery, Albert Einstein College of Medicine/Children’s Hospital at Montefiore, Bronx NY, Bronx, NY, United States, 3Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom
Synopsis
Hydrocephalus patients with functioning shunts are often faced with severe headache disorders. This is believed to be due to a change in brain viscoelasticity. MRE uses external mechanical vibrations to induce waves and estimates viscoelasticity from the wave propagation. This study found a significant decrease of brain viscoelasticity in patients (N=14) compared to controls (N=12) (G* white matter, controls: 1407.82 (SD=111.3) Pa vs patients: 1099.33 (SD=262.86) Pa, p =0.0001). Additionally, an inverse correlation between ventricular volume and viscoelasticity in corresponding lobes was found indicating that brain viscoelasticity may play a role in hydrocephalus patient’s symptoms such as headaches.Purpose
Chronic headaches are a well-documented complaint of shunted hydrocephalic patients 1. However, it is also one of the signs of shunt malfunction. The current gold standard for determining shunt efficiency is to place an intracranial pressure monitor into the lateral ventricle, but it is a highly invasive procedure.
Cranial compliance (inverse of viscoelasticity) deficiency may cause headaches in some chronically shunted patients with functioning shunts (often with slit or smaller than normal ventricles) 2-3.This study aims to use a novel, non-invasive imaging technique, Magnetic Resonance Elastography (MRE) 4, to investigate the role of brain viscoelasticity in the pathophysiology and symptoms in pediatric hydrocephalus.
Methods
A total of 14 shunt-dependent patients (age 15-37, median age 23) who developed hydrocephalus as infants and suffer from chronic headaches were selected. Patients with abnormally large ventricles were excluded. Imaging data from volunteers with no medical history of neurological issues were also collected (N=12). T1W images and MRE data were acquired on a 3T Philips MRI. MRE was performed by inducing a mechanical wave at 30Hz, transmitted through the zygomatic arches.
Phase images were unwrapped using a Laplacian-based phase unwrapping algorithm 5 and de-noised using complex dualtree wavelets 6 with overlapping group sparsity thresholding 7. Tissue shear modulus was then measured using Algebraic Helmholtz Inversion 8. Images were motion and distortion corrected using MRE magnitude and field maps respectively. To ensure low vibration amplitude areas were excluded, data was masked > 40% of the maximum amplitude. Image segmentation was performed on high-resolution T1W images to produce CSF, white and gray matter masks using FSL’s FAST tool on brain-extracted images (BET). Using the CSF component, the ventricles were split into frontal, occipital and temporal horns (Fig. 1) and volumetric figures for each segment was calculated. Subjects were then normalized to MNI152 template space using FNIRT. MNI structural atlas masks were used to calculate G* in the frontal, occipital, parietal and temporal lobes (Fig. 2).
All statistical calculations were performed using IBM SPSS statistics package v22. An independent-samples t-test was performed to compare G* values in controls and patients and p-values were FDR corrected for multiple comparisons. Within the patient group, Pearson’s product-moment correlation was calculated to determine the relationship between ventricular volume and G*.
Results
Group comparison between the controls and
patients showed a significant decrease in G* in whole gray matter (1054.2
(SD=89.5) Pa vs 824.6 (SD=212.8) Pa, respectively, p=0.0013) and white matter
(1407.82 (SD=111.3) Pa vs 1099.33 (SD=262.86) Pa, respectively, p
=0.0001) (Fig.4). Similarly for structural lobes, comparisons between
controls and patients showed the patient group had decreased viscoelasticity in
the frontal (p=0.0321), occipital (p =0.0027), parietal (p =0.0002) and
temporal lobes (p=0.0032).
Within the patient group, an inverse
correlation was found between G* and ventricular volume, specifically, the
right parietal lobe G* with right occipital horn volume (p =0.003, R2=0.5369)
(Fig. 5).
Discussion
Few studies have investigated the effect of hydrocephalus
on the viscoelasticity of the brain. A study of normal pressure hydrocephalus
(NPH) patients found viscoelasticity to be reduced by 20% in patients compared
to controls 9. A separate study on NPH patients pre and
post-shunt placement found patients’ brain viscoelasticity to be lower than
healthy controls pre-surgery, but no difference was found within the patient
group pre and post-surgery 10.
This study found patients to have lower
viscoelasticity compared to healthy controls, indicating a marked change in
brain biomechanics within treated chronically shunted
patients. Additionally, an inverse correlation between regional
ventricular volume and viscoelasticity was found, indicating regional effects
of ventricular dilation on regional brain viscoelasticity.
Conclusions
This study demonstrates that viscoelasticity
is altered in hydrocephalus patients and indicates that it may play a role
in clinical symptoms, such as headaches, in chronically shunted patients. MRE
is shown to be an effective, non-invasive tool to determine regional
viscoelastic differences within the brain and may be a powerful diagnostic
tool in hydrocephalus. Further ongoing work includes investigating the
relationship between viscoelasticity and headache severity along with other
imaging methods such as DTI and MRICP. Once developed, these techniques may
assist neurosurgeons in the future to diagnose chronically shunted patients and
for guiding the development of alternative or supplementary therapies in
hydrocephalus.
Acknowledgements
This research was supported by Rudi Schulte Research Institute and Hydrocephalus Association.References
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