Synopsis

MR elastography of the brain is an emerging technique that can noninvasively estimate brain tissue stiffness, which is usually reported as the shear modulus. It relies on using motion-encoding gradients synchronized to an externally applied vibration, to measure shear wave propagation through the brain parenchyma. This data is then analyzed, typically offline, to produce cerebral elastograms – maps of brain stiffness. In recent years, more patient-friendly vibration transducers have been developed, enabling clinical studies in human patient groups. A number of degenerative brain disorders have been observed to be associated with lower brain stiffness, although studies tend to be relatively small, and few have been independently confirmed by other research groups to date. Due to wide variation in the implementations and analysis approaches used in brain MR elastography, users must take care when interpreting brain MRE data. There is a need for large scale multi-site studies using brain MRE in clinical brain disorders.

Highlights

• MR elastography of the brain is an emerging technique that can noninvasively quantify the “stiffness” of the brain, in terms of the shear modulus

• Brain MRE has been applied in several clinical populations, mostly in fairly small samples, but few studies have been replicated, and there are conflicting results between laboratories in some disorders.
• Key challenges in applying MRE to the brain for clinical applications include:

o Patient-friendly transducer design to deliver reliable vibration waves deep into the brain

o Standardising methods for data acquisition and analysis across centres to provide consistent and reproducible results

Target audience

Outcome/Objectives

Upon completion of this course, participants should be able to:

• Describe the technical foundations of MR Elastography;
• Identify key clinical applications where MRE can be used; and
• Compare and contrast MRE to other quantitative MRI techniques.

Purpose

The aims of this module on brain elastography are to: ·

• Outline current approaches used in brain elastography
• Demonstrate applications in brain disorders and compare with other MR modalities
• Outline current challenges for routine clinical use of brain elastography

How is brain MR Elastography performed?

• There are three key components to brain elastography: the transducer hardware that creates shear waves in the brain; the MR sequence and parameters that govern acquisition of the displacement (wave) data; and the reconstruction software that calculates the shear modulus from the displacement data.
• Current designs of transducers used in brain elastography will be reviewed, and the other two discussed with a focus on brain-specific aspects, as technical details of these topics will be covered in another talk in this series.

Clinical applications of brain MR Elastography

Brain MRE has been used to quantify brain stiffness changes in numerous human brain disorders, on the basis that changes in brain tissue microstructure are reflected in altered mechanical properties. The long-term goal is to assist in clinical decision making, on the basis of supplementary information gained from MRE examinations. Examples of studies using MRE in brain disorders include:

• Dementia: Small reductions in brain stiffness have been reported in Alzheimer’s disease in humans¹, frontotemporal dementia ².
• Normal pressure hydrocephalus: Results for NPH patients are conflicting, with one group finding that the brain tissue in NPH patients is less stiff than in controls^3,4, while another finds it to be stiffer⁵.
• Brain tumours: A small number of studies have used brain MRE to examine patient groups with brain tumours. Murphy et al⁶ showed that stiffness of meningiomas estimated using brain MRE correlated better with surgeon-assessed stiffness at operation than T1 or T2 weighted imaging. A follow up study by the same group⁷ has assessed intratumoral consistency in meningiomas. Glioblastomas have been shown to have both stiff and soft regions using multifrequency MRE, but the authors observed lower viscosity in tumours than healthy brain tissue ⁸.
• Inflammation/Demyelination: Fehlner et al ⁹ examined patients with Clinically Isolated Syndrome, observing about a 14% decrease in shear modulus compared to controls. Wuerfel et al ¹⁰ showed a similar magnitude decrease in multiple sclerosis patients.

It is also useful to note that some studies ^11,12 have suggested that the healthy adult brain decreases slightly in stiffness with age, and varies with gender (females have slightly stiffer brains), so baseline healthy reference data being used for comparison in studies of patient groups should be age and gender matched.

There have also been many animal studies where MRE has been used, together with histopathological methods, to evaluate models of brain disorders. These are particularly valuable in understanding how brain MRE findings relate to the underlying pathophysiology.

Potential pitfalls for the clinician and researchers in Brain MR Elastography

As with all new techniques, there is considerable variation in implementations of MRE at different research sites that can influence the results obtained with brain MRE. These include:

• Transducer design – this can affect the magnitude and quality of the shear waves induced in the brain, and thus the imaging data quality. Design also affects patient tolerance and compliance during scans. Major improvements in transducer designs have occurred recently, generally removing the need for invasive methods such as vibrating bite bars.
• Sequences and imaging parameters – Different MRE sequences have different signal to noise profiles and scan times. Key imaging parameters such as vibration frequency have a strong influence on the values of shear modulus obtained, due to the viscoelasticity of brain tissue
• Reconstruction algorithms and pre-and post-processing methods used to filter the data and estimate the shear modulus and calculate values for analysis have different strengths and weaknesses that the user needs to be aware of. This includes issues such as reconstruction software providing potentially unreliable results in areas of low vibration amplitude, larger than usual influence of partial volume effects near tissue boundaries due to calculations relying on multiple pixels and more.

MRE has been used in numerous clinical studies of liver, but it is still developing for use in brain disorders. While there are small numbers of studies in a range of brain disorders, few results have been independently confirmed, and in some disorders, there are conflicting results in the literature, or some variation in the quantitative parameters measured. While MRE is an exciting new technique with great potential, there remains a need for large scale clinical studies of brain disorders to enable more widespread clinical adoption, and harmonization of methods to allow for comparison between approaches.

Conclusions

• Brain Elastography is an exciting new imaging modality that has great potential for clinical use in cancer, neurodegeneration and other brain disorders.
• It provides complementary information to other imaging modalities.
• However, users need to be familiar with differences between approaches used in different implementations, both for data acquisition and analysis, and their effects on the estimates of brain stiffness obtained.

Acknowledgements

References

1 Murphy, M. C. et al. Decreased brain stiffness in Alzheimer's disease determined by magnetic resonance elastography. J. Magn. Reson. Imaging, doi:10.1002/jmri.22707 (2011).

2 Huston, J., 3rd et al. Magnetic resonance elastography of frontotemporal dementia. J. Magn. Reson. Imaging 43, 474-478, doi:10.1002/jmri.24977 (2016).

3 Freimann, F. B. et al. Alteration of brain viscoelasticity after shunt treatment in normal pressure hydrocephalus. Neuroradiology 54, 189-196, doi:10.1007/s00234-011-0871-1 (2012).

4 Streitberger, K.-J. et al. In vivo viscoelastic properties of the brain in normal pressure hydrocephalus. NMR Biomed. 24, 385-392, doi:10.1002/nbm.1602 (2011).

5 Fattahi, N. et al. MR elastography demonstrates increased brain stiffness in normal pressure hydrocephalus. American Journal of Neuroradiology 37, 462-467 (2016).

6 Murphy, M. C. et al. Preoperative assessment of meningioma stiffness using magnetic resonance elastography. J. Neurosurg. 118, 643-648, doi:10.3171/2012.9.jns12519 (2013).

7 Hughes, J. D. et al. Higher-Resolution Magnetic Resonance Elastography in Meningiomas to Determine Intratumoral Consistency. Neurosurgery 77, 653-659, doi:10.1227/neu.0000000000000892 (2015).

8 Streitberger, K. J. et al. High-resolution mechanical imaging of glioblastoma by multifrequency magnetic resonance elastography. PLoS ONE 9, e110588, doi:10.1371/journal.pone.0110588 (2014).

9 Fehlner, A. et al. Higher-resolution MR elastography reveals early mechanical signatures of neuroinflammation in patients with clinically isolated syndrome. J. Magn. Reson. Imaging 44, 51-58, doi:10.1002/jmri.25129 (2016).

10 Wuerfel, J. et al. MR-elastography reveals degradation of tissue integrity in multiple sclerosis. Neuroimage 49, 2520-2525, doi:DOI: 10.1016/j.neuroimage.2009.06.018 (2010).

11 Arani, A. et al. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults. Neuroimage 111, 59-64, doi:10.1016/j.neuroimage.2015.02.016 (2015).

12 Sack, I. et al. The impact of aging and gender on brain viscoelasticity. Neuroimage 46, 652-657 (2009).