Arvin Arani1, Paul Min1, Nikoo Fattahi1, Nicholas M Wetjen1, Clifford Jack1, Kendall H Lee1, Richard L Ehman1, and John Huston III1
1Mayo Clinic, Rochester, MN, United States
Synopsis
Hydrocephalus
is a common medical condition that results from obstruction to the flow of
cerebral spinal fluid (CSF) or resorption of CSF. No non-invasive method offers
direct measurement of intracranial pressure (ICP). Magnetic resonance
elastography (MRE) is capable of non-invasively measuring brain tissue
stiffness in-vivo, and may act as a surrogate
to ICP. The objective of this study was to investigate the impact of ICP on
brain stiffness using MRE in a porcine model. This study shows that MRE brain stiffness
changes directly correspond to changes in ICP, motivating future investigation
into shunt-therapy monitoring in a patient population.Purpose
Hydrocephalus
is a common medical condition that results from obstruction to the flow of
cerebral spinal fluid (CSF) or resorption of CSF. The clinical symptoms can be
confused with many other medical conditions and no noninvasive method offers
direct measurement of intracranial pressure (ICP). Shunt tube placement has
been shown to be an effective therapy in many cases. This procedure involves
improving CSF drainage, in turn reducing ICP. A non-invasive measurement or
surrogate to ICP may help with predicting patient requiring shunting and monitoring
shunt-therapy outcomes. Magnetic
resonance elastography (MRE) is a non-invasive imaging technique capable of
measuring brain tissue stiffness, and may act as a surrogate to ICP (1). The objective of this study was to investigate
the impact of ICP on brain stiffness using MRE in a porcine model.
Methods
Two
pediatric catheters were implanted in the left and right lateral ventricles of
3 pigs using a previously described intra-parenchymal drug delivery system
technique (2) for targeting (Figure 1). The CSF was drained post-surgery
and a saline line was connected to one catheter and a pressure monitor was
connected to the second catheter. The pressure in the ventricles was
systematically increased by raising the saline bag a certain distance above the
pig’s head. MRE was conducted post-surgery at 60Hz, 90Hz, 120Hz, and 150Hz at different
ICP values ranging between 0-55 mmHg for each pig. To establish a baseline stiffness value, MRE
was conducted pre-surgery at the same vibration frequencies. Image acquisition
included a modified spin-echo echo planar imaging sequence to acquire MRE data
with the following imaging parameters: TR/TE = 3600-3800/46-62 ms; FOV = 24 cm;
72x72; 35 contiguous 3-mm-thick axial slices; vibration frequency matched
motion-encoding gradient; motion-encoding in all 3 directions; and 8 phase
offsets. MRE post-processing involved: 1) Applying a [5x5x5] cubic smoothing
filter, 2) calculating the curl of the displacement images, 3) calculating the
stiffness (direct inversion). The mean
and median magnitude of the complex shear modulus |G*| was reported.
Results
The
anatomical change in ventricular size with increased pressure has been shown in
Figure 2 for pig #1. The apparent change in the mean and median of |G*| over
the entire brain volume post-surgery and after CSF drainage is shown in Figure
3, for all vibration frequencies tested. For pigs 1 and 2 the ICP was reduced
to 0 mmHg, which resulted in decrease in |G*|, which is especially noticeable
at higher frequencies. The mean and median |G*| over the entire brain volume
has been plotted in Figure 4, as a function of ICP and vibration frequency. Sample elastograms illustrating the observed
changes in brain stiffness over the span of the experiment for all three pigs
has been shown in Figure 5.
Discussion
This
study demonstrated that changes in brain stiffness correspond with variations
in ICP in a porcine model. In the first two pigs, drainage of CSF was shown to
decrease the mean brain stiffness by 1.2-1.7 kPa at a vibration frequency of
150Hz. Proper drainage of CSF in pig #3 was not possible due to surgical
complications. This resulted in a baseline ICP of 26 mmHg instead of 0 mmHg, showing
no apparent change in |G*| between pre-surgical and post-surgical scans. From
Figure 4 it appears that there is a threshold over which brain stiffness does
not increase with elevated ICP. In this
small sample size this appears to be between 20-24 mmHg. Once, past this
threshold the brain seems to stiffen with increased ICP. From a mechanical
standpoint, increases in tissue stiffness result when a tissue is compressed
such that the relationship between stress and strain becomes non-linear causing
a rise in stiffness. The 20-24 mmHg range may represent this transition in the
porcine brain. Alternatively, from Figure 5 it becomes clear that the
distribution of stiffness is not uniform throughout the entire brain, which may
indicate that only small regions of tissue are increasing in stiffness with
acute changes in pressure and that these do not become significant enough to affect
the entire brain volume until higher ICP values are reached.
Conclusion
Brain MRE is
able to measure changes in total stiffness across the entire brain volume both
due to CSF drainage and with increased ICP. This study motivates future
investigation into the changes in brain stiffness at different time points (pre
and post shunt), and in different brain regions, in order to evaluate the
potential role of brain MRE for therapy monitoring.
Acknowledgements
This research was
supported by Theodore W. Batterman Family Foundation and R01 grants EB001981.References
1. Hatt
A et al. AJNR American journal of neuroradiology 2015;36(10):1971-1977.
2. Kim I et al. J Neurosci Methods
2014;227:29-34.