Manduca, Armando

Brain magnetic resonance elastography (MRE) is an imaging technique capable of accurately and non-invasively measuring the mechanical properties of the living human brain. Recent studies have shown that MRE has potential to provide clinically useful information in patients with intracranial tumors, demyelinating disease, neurodegenerative disease, elevated intracranial pressure, and altered functional states. The objectives of this review are: (1) to give a general overview of the types of measurements that have been obtained with brain MRE in patient populations, (2) to survey the tools currently being used to make these measurements possible, and (3) to highlight brain MRE-based quantitative biomarkers that have the highest potential of being adopted into clinical use within the next 5 to 10 years. The specifics of MRE methodology strategies are described, from wave generation to material parameter estimations. The potential clinical role of MRE for characterizing and planning surgical resection of intracranial tumors and assessing diffuse changes in brain stiffness resulting from diffuse neurological diseases and altered intracranial pressure are described. In addition, the emerging technique of functional MRE, the role of artificial intelligence in MRE, and promising applications of MRE in general neuroscience research are presented.

Magnetic resonance elastography (MRE) is a phase contrast–based MRI technique that can measure displacement due to propagating mechanical waves, from which material properties such as shear modulus can be calculated. Magnetic resonance elastography can be thought of as quantitative, noninvasive palpation. It is increasing in clinical importance, has become widespread in the diagnosis and staging of liver fibrosis, and additional clinical applications are being explored. However, publications have reported MRE results using many different parameters, acquisition techniques, processing methods, and varied nomenclature. The diversity of terminology can lead to confusion (particularly among clinicians) about the meaning of and interpretation of MRE results. This paper was written by the MRE Guidelines Committee, a group formalized at the first meeting of the ISMRM MRE Study Group, to clarify and move toward standardization of MRE nomenclature. The purpose of this paper is to (1) explain MRE terminology and concepts to those not familiar with them, (2) define “good practices” for practitioners of MRE, and (3) identify opportunities to standardize terminology, to avoid confusion.

Abstract Gene-editing experiments commonly elicit the error-prone non-homologous end joining for DNA double-strand break (DSB) repair. Microhomology-mediated end joining (MMEJ) can generate more predictable outcomes for functional genomic and somatic therapeutic applications. We compared three DSB repair prediction algorithms – MENTHU, inDelphi, and Lindel – in identifying MMEJ-repaired, homogeneous genotypes (PreMAs) in an independent dataset of 5,885 distinct Cas9-mediated mouse embryonic stem cell DSB repair events. MENTHU correctly identified 46% of all PreMAs available, a ∼2- and ∼60-fold sensitivity increase compared to inDelphi and Lindel, respectively. In contrast, only Lindel correctly predicted predominant single-base insertions. We report the new algorithm MENdel, a combination of MENTHU and Lindel, that achieves the most predictive coverage of homogeneous out-of-frame mutations in this large dataset. We then estimated the frequency of Cas9-targetable homogeneous frameshift-inducing DSBs in vertebrate coding regions for gene discovery using MENdel. 47 out of 54 genes (87%) contained at least one early frameshift-inducing DSB and 49 out of 54 (91%) did so when also considering Cas12a-mediated deletions. We suggest that the use of MENdel helps researchers use MMEJ at scale for reverse genetics screenings and with sufficient intra-gene density rates to be viable for nearly all loss-of-function based gene editing therapeutic applications.

AbstractObjectivesDefecation requires relaxation of the internal and external anal sphincters. High anal resting pressure is associated with painful constipation, defecatory disorders, and increased healthcare utilization in constipated patients; the mechanisms are unclear. Perhaps patients with a high anal resting pressure have a less distensible canal, which impedes defecation.MethodsIn 50 of 64 participants (33 healthy and 17 constipated women), anal pressures and distensibility were measured, respectively, with manometry and balloon distention combined with magnetic resonance imaging; rectal balloon expulsion time (BET) was also studied.ResultsThe BET (P = .006) was longer, and the mean (SD) rectoanal pressure gradient (−58[40] vs −34[26] mm Hg,P = .03) was more negative in constipated than healthy women; anal resting pressure was not different. During anal distention, the balloon expanded rapidly at an opening pressure of 49 (18) mm Hg, which was lower (P < .0001) than resting pressure (90 [25] mm Hg). The resting pressure was correlated with the opening pressure (r = 0.57,P < .0001) and inversely (r = −0.38,P = .007) with maximum volume but not with anal distensibility (volume‐pressure slope). In healthy women, the difference (opening‐resting pressure) was correlated with anal relaxation during evacuation (r = 0.35,P = .04). Anal distensibility and sensory thresholds were not different between constipated and healthy women.ConclusionsAmong healthy and constipated women, a greater anal resting pressure is correlated with greater opening pressure and lower maximum volume during distention, and, hence, provides a surrogate marker of anal distensibility. The difference (opening‐resting pressure), which reflects anal relaxation during distention, is correlated with anal relaxation during evacuation. Anal resting pressure and distensibility were comparable in healthy and constipated women.

PurposeTo develop a novel magnetic resonance elastography (MRE) acquisition using a hybrid radial EPI readout scheme (TURBINE), and to demonstrate its feasibility to obtain wave images and stiffness maps in a phantom and in vivo brain.MethodThe proposed 3D TURBINE‐MRE is based on a spoiled gradient‐echo MRE sequence with the EPI readout radially rotating about the phase‐encoding axis to sample a full 3D k‐space. A polyvinyl chloride phantom and 6 volunteers were scanned on a compact 3T GE scanner with a 32‐channel head coil at 80 Hz and 60 Hz external vibration, respectively. For comparison, a standard 2D, multislice, spin‐echo (SE) EPI‐MRE acquisition was also performed with the same motion encoding and resolution. The TURBINE‐MRE images were off‐line reconstructed with iterative SENSE algorithm. The regional ROI analysis was performed on the 6 volunteers, and the median stiffness values were compared between SE‐EPI‐MRE and TURBINE‐MRE.ResultsThe 3D wave‐field images and the generated stiffness maps were comparable between TURBINE‐MRE and standard SE‐EPI‐MRE for the phantom and the volunteers. The Bland–Altman plot showed no significant difference in the median regional stiffness values between the two methods. The stiffness measured with the 2 methods had a strong linear relationship with a Pearson correlation coefficient of 0.943.ConclusionWe demonstrated the feasibility of the new TURBINE‐MRE sequence for acquiring the desired 3D wave‐field data and stiffness maps in a phantom and in‐vivo brains. This pilot study encourages further exploration of TURBINE‐MRE for functional MRE, free‐breathing abdominal MRE, and cardiac MRE applications.

ObjectivesThe aim of this study was to perform a whole-brain analysis of alterations in brain mechanical properties due to normal pressure hydrocephalus (NPH).Materials and MethodsMagnetic resonance elastography (MRE) examinations were performed on 85 participants, including 44 cognitively unimpaired controls, 33 with NPH, and 8 who were amyloid-positive with Alzheimer clinical syndrome. A custom neural network inversion was used to estimate stiffness and damping ratio from patches of displacement data, accounting for edges by training the network to estimate the mechanical properties in the presence of missing data. This learned inversion was first compared with a standard analytical approach in simulation experiments and then applied to the in vivo MRE measurements. The effect of NPH on the mechanical properties was then assessed by voxel-wise modeling of the stiffness and damping ratio maps. Finally, a pattern analysis was performed on each individual's mechanical property maps by computing the correlation between each person's maps with the expected NPH effect. These features were used to fit a classifier and assess diagnostic accuracy.ResultsThe voxel-wise analysis of the in vivo mechanical property maps revealed a unique pattern in participants with NPH, including a concentric pattern of stiffening near the dural surface and softening near the ventricles, as well as decreased damping ratio predominantly in superior regions of the white matter (family-wise error correctedP< 0.05 at cluster level). The pattern of viscoelastic changes in each participant predicted NPH status in this cohort, separating participants with NPH from the control and the amyloid-positive with Alzheimer clinical syndrome groups, with areas under the receiver operating characteristic curve of 0.999 and 1, respectively.ConclusionsThis study provides motivation for further development of the neural network inversion framework and demonstrates the potential of MRE as a novel tool to diagnose NPH and provide a window into its pathogenesis.

Magnetic resonance elastography (MRE) is increasingly being applied to thin or small structures in which wave propagation is dominated by waveguide effects, which can substantially bias stiffness results with common processing approaches. The purpose of this work was to investigate the importance of such biases and artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries with one or more dimensions that are small relative to the shear wavelength; and (ii) a realistic cardiac geometry. Finite element models were created using simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry, and simulated displacements acquired by MRE from harmonic excitations from 60 to 220 Hz across a range of frequencies. The displacement wave fields were inverted with direct inversion of the Helmholtz equation with and without the application of bandpass filtering and/or the curl operator to the displacement field. In all geometries considered, and at all frequencies considered, strong biases and artifacts were present in inversion results when the curl operator was not applied. Bandpass filtering without the curl was not sufficient to yield accurate recovery. In the 3D geometries, strong biases and artifacts were present in 2D inversions even when the curl was applied, while only 3D inversions with application of the curl yielded accurate recovery of the complex shear modulus. These results establish that taking the curl of the wave field and performing a full 3D inversion are both necessary steps for accurate estimation of the shear modulus both in simple thin‐walled or small structures and in a realistic cardiac geometry when using simple inversions that neglect the hydrostatic pressure term. In practice, sufficient wave amplitude, signal‐to‐noise ratio, and resolution will be required to achieve accurate results.