Murphy, Matthew C.

Increasing concerns have been raised about the long-term negative effects of subconcussive repeated head impact (RHI). To elucidate RHI injury mechanisms, many efforts have studied how head impacts affect the skull-brain biomechanics and have found that mechanical interactions at the skull-brain interface dampen and isolate brain motions by decoupling the brain from the skull. Despite intense interest, in vivo quantification of the functional state of the skull-brain interface remains difficult. This study developed a magnetic resonance elastography (MRE) based technique to non-invasively assess skull-brain mechanical interactions (i.e., motion transmission and isolation function) under dynamic loading. The full MRE displacement data were separated into rigid body motion and wave motion. The rigid body motion was used to calculate the brain-to-skull rotational motion transmission ratio ( R tr ) to quantify skull-brain motion transmissibility, and the wave motion was used to calculate the cortical normalized octahedral shear strain ( NOSS ) (calculated based on a partial derivative computing neural network) to evaluate the isolation capability of the skull-brain interface. Forty-seven healthy volunteers were recruited to investigate the effects of age/sex on R tr and cortical NOSS , and 17 of 47 volunteers received multiple scans to test the repeatability of the proposed techniques under different strain conditions. The results showed that both R tr and NOSS were robust to MRE driver variations and had good repeatability, with intraclass correlation coefficient (ICC) values between 0.68 and 0.97 (fair to excellent). No age or sex dependence were observed with R tr , whereas a significant positive correlation between age and NOSS was found in the cerebrum, frontal, temporal, and parietal lobes (all p < 0.05), but not in the occipital lobe ( p = 0.99). The greatest change in NOSS with age was found in the frontal lobe, one of the most frequent locations of traumatic brain injury (TBI). Except for the temporal lobe ( p = 0.0087), there was no significant difference in NOSS between men and women. This work provides motivation for utilizing MRE as a non-invasive tool for quantifying the biomechanics of the skull-brain interface. It evaluated the age and sex dependence and may lead to a better understanding of the protective role and mechanisms of the skull-brain interface in RHI and TBI, as well as improve the accuracy of computational models in simulating the skull-brain interface.

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) present a major health burden to society. Changes in brain structure and cognition are generally only observed at the late stage of the disease. Although advanced magnetic resonance imaging (MRI) techniques such as diffusion imaging may allow identification of biomarkers at earlier stages of neurodegeneration, early diagnosis is still challenging. Magnetic resonance elastography (MRE) is a noninvasive MRI technique for studying the mechanical properties of tissues by measuring the wave propagation induced in the tissues using a purpose‐built actuator. Here, we present a systematic review of preclinical and clinical studies in which MRE has been applied to study neurodegenerative diseases. Actuator systems for data acquisition, inversion algorithms for data analysis, and sample demographics are described and tissue stiffness measures obtained for the whole brain and internal structures are summarized. A total of six animal studies and eight human studies have been published. The animal studies refer to 123 experimental animals (68 AD and 55 PD) and 121 wild‐type animals, while the human studies refer to 142 patients with neurodegenerative disease (including 56 AD and 17 PD) and 166 controls. The animal studies are consistent in the reporting of decreased stiffness of the hippocampal region in AD mice. However, in terms of disease progression, although consistent decreases in either storage modulus or shear modulus magnitude are reported for whole brain, there is variation in the results reported for the hippocampal region. The clinical studies are consistent in reports of a significant decrease in either whole brain storage modulus or shear modulus magnitude, in both AD and PD and with different brain structures affected in different neurodegenerative diseases. MRE studies of neurodegenerative diseases are still in their infancy, and in future it will be interesting to investigate potential relationships between brain mechanical properties and clinical measures, which may help elucidate the mechanisms underlying onset and progression of neurodegenerative diseases.Evidence Level1.Technical EfficacyStage 2.

Abstract Plasticity in the brain is impacted by an individual’s age at the onset of the blindness. However, what drives the varying degrees of plasticity remains largely unclear. One possible explanation attributes the mechanisms for the differing levels of plasticity to the cholinergic signals originating in the nucleus basalis of Meynert. This explanation is based on the fact that the nucleus basalis of Meynert can modulate cortical processes such as plasticity and sensory encoding through its widespread cholinergic projections. Nevertheless, there is no direct evidence indicating that the nucleus basalis of Meynert undergoes plastic changes following blindness. Therefore, using multiparametric magnetic resonance imaging, we examined if the structural and functional properties of the nucleus basalis of Meynert differ between early blind, late blind and sighted individuals. We observed that early and late blind individuals had a preserved volumetric size and cerebrovascular reactivity in the nucleus basalis of Meynert. However, we observed a reduction in the directionality of water diffusion in both early and late blind individuals compared to sighted individuals. Notably, the nucleus basalis of Meynert presented diverging patterns of functional connectivity between early and late blind individuals. This functional connectivity was enhanced at both global and local (visual, language and default-mode networks) levels in the early blind individuals, but there were little-to-no changes in the late blind individuals when compared to sighted controls. Furthermore, the age at onset of blindness predicted both global and local functional connectivity. These results suggest that upon reduced directionality of water diffusion in the nucleus basalis of Meynert, cholinergic influence may be stronger for the early blind compared to the late blind individuals. Our findings are important to unravelling why early blind individuals present stronger and more widespread cross-modal plasticity compared to late blind individuals.

BackgroundFocally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid‐space hydrocephalus (DESH), and should be differentiated from atrophy.PurposeTo evaluate for change in FES size and pituitary height after shunt placement in iNPH.Study typeRetrospective.SubjectsA total of 125 iNPH patients who underwent shunt surgery and 40 age‐matched controls.Field Strength/Sequence1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w.AssessmentFES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls.Statistical testsWilcoxon signed‐rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05.ResultsFifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI.Data ConclusionDecrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less‐well recognized feature of altered CSF dynamics.Evidence Level3Technical EfficacyStage 2

PurposeInversion algorithms used to convert acquired MR elastography wave data into material property estimates often assume that the underlying materials are locally homogeneous. Here we evaluate the impact of that assumption on stiffness estimates in gray‐matter regions of interest in brain MR elastography.MethodsWe describe an updated neural network inversion framework using finite‐difference model–derived data to train convolutional neural network inversion algorithms. Neural network inversions trained on homogeneous simulations (homogeneous learned inversions [HLIs]) or inhomogeneous simulations (inhomogeneous learned inversions [ILIs]) are generated with a variety of kernel sizes. These inversions are evaluated in a brain MR elastography simulation experiment and in vivo in a test–retest repeatability experiment including 10 healthy volunteers.ResultsIn simulation and in vivo, HLI and ILI with small kernels produce similar results. As kernel size increases, the assumption of homogeneity has a larger effect, and HLI and ILI stiffness estimates show larger differences. At each inversion's optimal kernel size in simulation (7 × 7 × 7 for HLI, 11 × 11 × 11 for ILI), ILI is more sensitive to true changes in stiffness in gray‐matter regions of interest in simulation. In vivo, there is no difference in the region‐level repeatability of stiffness estimates between the inversions, although ILI appears to better maintain the stiffness map structure as kernel size increases, while decreasing the spatial variance in stiffness estimates.ConclusionsThis study suggests that inhomogeneous inversions provide small but significant benefits even when large stiffness gradients are absent.

BackgroundLocalized regions of left–right image intensity asymmetry (LRIA) were incidentally observed on T2‐weighted (T2‐w) and T1‐weighted (T1‐w) diagnostic magnetic resonance imaging (MRI) images. Suspicion of herpes encephalitis resulted in unnecessary follow‐up imaging. A nonbiological imaging artifact that can lead to diagnostic uncertainty was identified.PurposeTo investigate whether systematic LRIA exist for a range of scanner models and to determine if LRIA can introduce diagnostic uncertainty.Study TypeA retrospective study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data base.SubjectsOne thousand seven hundred fifty‐three (median age: 72, males/females: 878/875) unique participants with longitudinal data were included.Field Strength3T.SequencesT1‐w three‐dimensional inversion‐recovery spoiled gradient‐echo (IR‐SPGR) or magnetization‐prepared rapid gradient‐echo (MP‐RAGE) and T2‐w fluid‐attenuated inversion recovery (FLAIR) long tau fast spin echo inversion recovery (LT‐FSE‐IR). Only General Electric, Philips, and Siemens' product sequences were used.AssessmentLRIA was calculated as the left–right percent difference with respect to the mean intensity from automated anatomical atlas segmented regions. Three neuroradiologists with 37 (**), 32 (**), and 3 (**) years of experience rated the clinical impact of 30 T2‐w three‐dimensional FLAIR exams with LRIA to determine the diagnostic uncertainty. Statistical comparisons between retrospective intensity normalized T1m and original T1‐w images were made.Statistical TestsFor each image type, a linear mixed effects model was fit using LRIA scores from all scanners, regions, and participants as the outcome and age and sex as predictors. Statistical significance was defined as having a P‐value <0.05.ResultsLRIA scores were significantly different from zero on most scanners. All clinicians were uncertain or recommended definite diagnostic follow‐up in 62.5% of cases with LRIA >10%. Individuals with acute brain pathology or focal neurologic deficits are not enrolled in ADNI; therefore, focal signal abnormalities were considered false positives.Data ConclusionLRIA is system specific, systematic, creates diagnostic uncertainty, and impacts IR‐SPGR, MP‐RAGE, and LT‐FSE‐IR product sequences.Level of Evidence: 2Technical Efficacy Stage: 3