Eric Barnhill

Magnetic resonance elastography (MRE) of the human brain: Technique, findings and clinical applications

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms-at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

Real‐time 4D phase unwrapping applied to magnetic resonance elastography

Phase amplitude is a source of signal in magnetic resonance elastography (MRE) experiments but its exploitation in experimental design has been limited due to the challenges of phase wrap. This study addressed this aspect of MRE through new developments in algorithms, heuristic strategy, and user interface.

Tomoelastography by multifrequency wave number recovery from time-harmonic propagating shear waves.

Palpation is one of the most sensitive, effective diagnostic practices, motivating the quantitative and spatially resolved determination of soft tissue elasticity parameters by medical ultrasound or MRI. However, this so-called elastography often suffers from limited anatomical resolution due to noise and insufficient elastic deformation, currently precluding its use as a tomographic modality on its own. We here introduce an efficient way of processing wave images acquired by multifrequency magnetic resonance elastography (MMRE), which relies on wave number reconstruction at different harmonic frequencies followed by their amplitude-weighted averaging prior to inversion. This results in compound maps of wave speed, which reveal variations in tissue elasticity in a tomographic fashion, i.e. an unmasked, slice-wise display of anatomical details at pixel-wise resolution. The method is demonstrated using MMRE data from the literature including abdominal and pelvic organs such as the liver, spleen, uterus body and uterus cervix. Even in small regions with low wave amplitudes, such as nucleus pulposus and spinal cord, elastic parameters consistent with literature values were obtained. Overall, the proposed method provides a simple and noise-robust strategy of in-plane wave analysis of MMRE data, with a pixel-wise resolution producing superior detail to MRE direct inversion methods.

Perfusion alters stiffness of deep gray matter

Viscoelastic properties of the brain reflect tissue architecture at multiple length scales. However, little is known about the relation between vital tissue functions, such as perfusion, and the macroscopic mechanical properties of cerebral tissue. In this study, arterial spin labelling is paired with magnetic resonance elastography to investigate the relationship between tissue stiffness and cerebral blood flow (CBF) in the in vivo human brain. The viscoelastic modulus, |G*|, and CBF were studied in deep gray matter (DGM) of 14 healthy male volunteers in the following sub-regions: putamen, nucleus accumbens, hippocampus, thalamus, globus pallidus, and amygdala. CBF was further normalized by vessel area data to obtain the flux rate q which is proportional to the perfusion pressure gradient. The striatum (represented by putamen and nucleus accumbens) was distinct from the other DGM regions by displaying markedly higher stiffness and perfusion values. q was a predictive marker for DGM stiffness as analyzed by linear regression |G*| = q·(4.2 ± 0.6)kPa·s + (0.80 ± 0.06)kPa (R2 = 0.92, P = 0.006). These results suggest a high sensitivity of MRE in DGM to perfusion pressure. The distinct mechano-vascular properties of striatum tissue, as compared to the rest of DGM, may reflect elevated perfusion pressure, which could explain the well-known susceptibility of the putamen to hemorrhages.

Nonlinear multiscale regularisation in MR elastography: Towards fine feature mapping

&NA; Fine‐featured elastograms may provide additional information of radiological interest in the context of in vivo elastography. Here a new image processing pipeline called ESP (Elastography Software Pipeline) is developed to create Magnetic Resonance Elastography (MRE) maps of viscoelastic parameters (complex modulus magnitude |G*| and loss angle ø) that preserve fine‐scale information through nonlinear, multi‐scale extensions of typical MRE post‐processing techniques. Methods: A new MRE image processing pipeline was developed that incorporates wavelet‐domain denoising, image‐driven noise estimation, and feature detection. ESP was first validated using simulated data, including viscoelastic Finite Element Method (FEM) simulations, at multiple noise levels. ESP images were compared with MDEV pipeline images, both in the FEM models and in three ten‐subject cohorts of brain, thigh, and liver acquisitions. ESP and MDEV mean values were compared to 2D local frequency estimation (LFE) mean values for the same cohorts as a benchmark. Finally, the proportion of spectral energy at fine frequencies was quantified using the Reduced Energy Ratio (RER) for both ESP and MDEV. Results: Blind estimates of added noise (&sgr;) were within 5.3% ± 2.6% of prescribed, and the same technique estimated &sgr; in the in vivo cohorts at 1.7 ± 0.8%. A 5 × 5 × 5 truncated Gabor filter bank effectively detects local spatial frequencies at wavelengths &lgr; ≤ 10px. For FEM inversions, mean |G*| of hard target, soft target, and background remained within 8% of prescribed up to Symbol and mean ø results were within 10%, excepting hard target ø, which required redrawing around a ring artefact to achieve similar accuracy. Inspection of FEM |G*| images showed some spatial distortion around hard target boundaries and inspection of ø images showed ring artefacts around the same target. For the in vivo cohorts, ESP results showed mean correlation of Symbol with MDEV and liver stiffness estimates within 7% of 2D‐LFE results. Finally, ESP showed statistically significant increase in fine feature spectral energy as measured with RER for both |G*| (Symbol) and ø (Symbol). Conclusion: Information at finer frequencies can be recovered in ESP elastograms in typical experimental conditions, however scatter‐ and boundary‐related artefacts may cause the fine features to have inaccurate values. In in vivo cohorts, ESP delivers an increase in fine feature spectral energy, and better performance with longer wavelengths, than MDEV while showing similar stability and robustness. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. HighlightsNew Magnetic Resonance Elastography (MRE) software pipeline incorporating wavelet‐based denoising and feature‐detection techniques.Systematic noise testing with new Finite Element Method (FEM)–based simulations.Results robust to noise and show new levels of detail for MRE elastograms. Graphical abstract Figure. No caption available.

Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions

To improve the resolution of elasticity maps by adapting motion and distortion correction methods for phase‐based magnetic resonance imaging (MRI) contrasts such as magnetic resonance elastography (MRE), a technique for measuring mechanical tissue properties in vivo.

MR elastography measurement of the effect of passive warmup prior to eccentric exercise on thigh muscle mechanical properties (Forthcoming/Available Online)

To investigate the effect of warmup by application of the thermal agent Deep Heat (DH) on muscle mechanical properties using magnetic resonance elastography (MRE) at 3T before and after exercise‐induced muscle damage (EIMD).

MR elastography measurement of the effect of passive warmup prior to eccentric exercise on thigh muscle mechanical properties

To investigate the effect of warmup by application of the thermal agent Deep Heat (DH) on muscle mechanical properties using magnetic resonance elastography (MRE) at 3T before and after exercise‐induced muscle damage (EIMD).

Neural connectivity, music, and movement: a response to Pat Amos

Pat Amos documents the power of therhythmic moment in autism, connectsit to current thinking in developmentalpsychology, and draws practical lessonsfortherapeuticintervention.Onequestiontherapists in practice may struggle with isconvincing some parents and other pro-fessionals of the potential power of thesetypes ofinterventions. Asamovementandmusic therapist I recall a mother tellingme about her recent visit to a prominentpediatricneuropsychiatrist.Theneuropsy-chiatrist was once again recommending aregimen of heavy medication and behav-ioral therapy. The mother told her thatshe felt her son was making great progressthroughworkwithrhythmandmove-ment. “That won’t hold,” said the neu-ropsychiatrist.Will it hold? Can a movement basedintervention compete with a pharmaceu-tical one? The idea can meet with greatskepticism. However, there is a strongargument to be made from neurobiolog-ical theory that a rhythmic interventionholds the potential to be at least as pow-erful as a chemical intervention, and thebroaderone’sinvestigationintoneurobiol-ogy, the more the arguments for this viewaccumulate.

Heterogeneous multifrequency direct inversion (HMDI) for magnetic resonance elastography with application to a clinical brain exam

HIGHLIGHTSA novel, homogeneity accommodating direct inversion method for elastographic wave inversion (HMDI) is introduced and applied to Magnetic Resonance Elastography (MRE) data.Multifrequency MRE is combined with SPM in a fully automated processing pipeline to obtain whole brain and white matter model‐free stiffness and dispersion estimates.The automatic elastograms show sharp boundaries and spatially resolved brain features without masking, median filtering or smoothing.Two multifrequency MRE methods (HMDI and MDEV) are compared on a prospective 48‐subject data set.Both methods are sensitive to known age effects and internally consistent across frequencies. ABSTRACT A new viscoelastic wave inversion method for MRE, called Heterogeneous Multifrequency Direct Inversion (HMDI), was developed which accommodates heterogeneous elasticity within a direct inversion (DI) by incorporating first‐order gradients and combining results from a narrow band of multiple frequencies. The method is compared with a Helmholtz‐type DI, Multifrequency Dual Elasto‐Visco inversion (MDEV), both on ground‐truth Finite Element Method simulations at varied noise levels and a prospective in vivo brain cohort of 48 subjects ages 18–65. In simulated data, MDEV recovered background material within 5% and HMDI within 1% of prescribed up to SNR of 20 dB. In vivo HMDI and MDEV were then combined with segmentation from SPM to create a fully automated “brain palpation” exam for both whole brain (WB), and brain white matter (WM), measuring two parameters, the complex modulus magnitude |G*|, which measures tissue “stiffness”, and the slope of |G*| values across frequencies, a measure of viscous dispersion. |G*| values for MDEV and HMDI were comparable to the literature (for a 3‐frequency set centered at 50 Hz, WB means were 2.17 and 2.15 kPa respectively, and WM means were 2.47 and 2.49 kPa respectively). Both methods showed moderate correlation to age in both WB and WM, for both |G*| and |G*| slope, with Pearsons r≥0.4 in the most sensitive frequency sets. In comparison to MDEV, HMDI showed better preservation of recovered target shapes, more noise‐robustness, and stabler recovery values in regions with rapid property change, however summary statistics for both methods were quite similar. By eliminating homogeneity assumptions within a fast, fully automatic, regularization‐free direct inversion, HMDI appears to be a worthwhile addition to the MRE image reconstruction repertoire. In addition to supporting the literature showing decrease in brain viscoelasticity with age, our work supports a wide range of inter‐individual variation in brain MRE results.