The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.

A face-off of MRI research sequences by their need for de-facing.

It is now widely known that research brain MRI, CT, and PET images may potentially be re-identified using face recognition, and this potential can be reduced by applying face-deidentification ("de-facing") software. However, for research MRI sequences beyond T1-weighted (T1-w) and T2-FLAIR structural images, the potential for re-identification and quantitative effects of de-facing are both unknown, and the effects of de-facing T2-FLAIR are also unknown. In this work we examine these questions (where applicable) for T1-w, T2-w, T2*-w, T2-FLAIR, diffusion MRI (dMRI), functional MRI (fMRI), and arterial spin labelling (ASL) sequences. Among current-generation, vendor-product research-grade sequences, we found that 3D T1-w, T2-w, and T2-FLAIR were highly re-identifiable (96-98%). 2D T2-FLAIR and 3D multi-echo GRE (ME-GRE) were also moderately re-identifiable (44-45%), and our derived T2* from ME-GRE (comparable to a typical 2D T2*) matched at only 10%. Finally, diffusion, functional and ASL images were each minimally re-identifiable (0-8%). Applying de-facing with mri_reface version 0.3 reduced successful re-identification to ≤8%, while differential effects on popular quantitative pipelines for cortical volumes and thickness, white matter hyperintensities (WMH), and quantitative susceptibility mapping (QSM) measurements were all either comparable with or smaller than scan-rescan estimates. Consequently, high-quality de-facing software can greatly reduce the risk of re-identification for identifiable MRI sequences with only negligible effects on automated intracranial measurements. The current-generation echo-planar and spiral sequences (dMRI, fMRI, and ASL) each had minimal match rates, suggesting that they have a low risk of re-identification and can be shared without de-facing, but this conclusion should be re-evaluated if they are acquired without fat suppression, with a full-face scan coverage, or if newer developments reduce the current levels of artifacts and distortion around the face.

Magnetic Susceptibility in Progressive Supranuclear Palsy Variants, Parkinson's Disease, and Corticobasal Syndrome.

BACKGROUND: Previous studies have shown that magnetic susceptibility is increased in several subcortical regions in progressive supranuclear palsy (PSP). However, it is still unclear how subcortical and cortical susceptibilities vary across different PSP variants, Parkinson's disease (PD), and corticobasal syndrome (CBS). OBJECTIVE: This study aims to clarify the susceptibility profiles in the subcortical and cortical regions in different PSP variants, PD, and CBS. METHODS: Sixty-four patients, 20 PSP-Richardson syndrome (PSP-RS), 9 PSP-parkinsonism (PSP-P), 7 PSP-progressive gait freezing, 4 PSP-postural instability, 11 PD, and 13 CBS, and 20 cognitively normal control subjects underwent a 3-Tesla magnetic resonance imaging scan to reconstruct quantitative susceptibility maps. Region-of-interest analysis was performed to obtain susceptibility in several subcortical and cortical regions. Bayesian linear mixed effect models were used to estimate susceptibility within group and differences between groups. RESULTS: In the subcortical regions, patients with PSP-RS and PSP-P showed greater susceptibility than control subjects in the pallidum, substantia nigra, red nucleus, and cerebellar dentate (P < 0.05). Patients with PSP-RS also showed greater susceptibility than patients with PSP-progressive gait freezing, PD, and CBS in the red nucleus and cerebellar dentate, and patients with PSP-P showed greater susceptibility than PD in the red nucleus. Patients with PSP-postural instability and CBS showed greater susceptibility than control subjects in the pallidum and substantia nigra. No significant differences were observed in any cortical region. CONCLUSIONS: The PSP variants and CBS had different patterns of magnetic susceptibility in the subcortical regions. The findings will contribute to our understanding about iron profiles and pathophysiology of PSP and may provide a potential biomarker to differentiate PSP variants, PD, and CBS. © 2023 International Parkinson and Movement Disorder Society.

Left-Right Intensity Asymmetries Vary Depending on Scanner Model for FLAIR and T1 Weighted MRI Images.

BACKGROUND: Localized 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. PURPOSE: To investigate whether systematic LRIA exist for a range of scanner models and to determine if LRIA can introduce diagnostic uncertainty. STUDY TYPE: A retrospective study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data base. SUBJECTS: One thousand seven hundred fifty-three (median age: 72, males/females: 878/875) unique participants with longitudinal data were included. FIELD STRENGTH: 3T. SEQUENCES: T1 -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. ASSESSMENT: LRIA 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 T1 m and original T1 -w images were made. STATISTICAL TESTS: For 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. RESULTS: LRIA 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 CONCLUSION: LRIA is system specific, systematic, creates diagnostic uncertainty, and impacts IR-SPGR, MP-RAGE, and LT-FSE-IR product sequences. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3.

Associations of quantitative susceptibility mapping with Alzheimer's disease clinical and imaging markers.

Altered iron metabolism has been hypothesized to be associated with Alzheimer's disease pathology, and prior work has shown associations between iron load and beta amyloid plaques. Quantitative susceptibility mapping (QSM) is a recently popularized MR technique to infer local tissue susceptibility secondary to the presence of iron as well as other minerals. Greater QSM values imply greater iron concentration in tissue. QSM has been used to study relationships between cerebral iron load and established markers of Alzheimer's disease, however relationships remain unclear. In this work we study QSM signal characteristics and associations between susceptibility measured on QSM and established clinical and imaging markers of Alzheimer's disease. The study included 421 participants (234 male, median age 70 years, range 34-97 years) from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center; 296 (70%) had a diagnosis of cognitively unimpaired, 69 (16%) mild cognitive impairment, and 56 (13%) amnestic dementia. All participants had multi-echo gradient recalled echo imaging, PiB amyloid PET, and Tauvid tau PET. Variance components analysis showed that variation in cortical susceptibility across participants was low. Linear regression models were fit to assess associations with regional susceptibility. Expected increases in susceptibility were found with older age and cognitive impairment in the deep and inferior gray nuclei (pallidum, putamen, substantia nigra, subthalamic nucleus) (betas: 0.0017 to 0.0053 ppm for a 10 year increase in age, p = 0.03 to <0.001; betas: 0.0021 to 0.0058 ppm for a 5 point decrease in Short Test of Mental Status, p = 0.003 to p<0.001). Effect sizes in cortical regions were smaller, and the age associations were generally negative. Higher susceptibility was significantly associated with higher amyloid PET SUVR in the pallidum and putamen (betas: 0.0029 and 0.0012 ppm for a 20% increase in amyloid PET, p = 0.05 and 0.02, respectively), higher tau PET in the basal ganglia with the largest effect size in the pallidum (0.0082 ppm for a 20% increase in tau PET, p<0.001), and with lower cortical gray matter volume in the medial temporal lobe (0.0006 ppm for a 20% decrease in volume, p = 0.03). Overall, these findings suggest that susceptibility in the deep and inferior gray nuclei, particularly the pallidum and putamen, may be a marker of cognitive decline, amyloid deposition, and off-target binding of the tau ligand. Although iron has been demonstrated in amyloid plaques and in association with neurodegeneration, it is of insufficient quantity to be reliably detected in the cortex using this implementation of QSM.

TURBINE-MRE: A 3D hybrid radial-Cartesian EPI acquisition for MR elastography.

PURPOSE: To 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. METHOD: The 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. RESULTS: The 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. CONCLUSION: We 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.

Across-vendor standardization of semi-LASER for single-voxel MRS at 3T.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 µT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 µT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.

Acute pressure changes in the brain are correlated with MR elastography stiffness measurements: initial feasibility in an in vivo large animal model.

PURPOSE: The homeostasis of intracranial pressure (ICP) is of paramount importance for maintaining normal brain function. A noninvasive technique capable of making direct measurements of ICP currently does not exist. MR elastography (MRE) is capable of noninvasively measuring brain tissue stiffness in vivo, and may act as a surrogate to measure ICP. The objective of this study was to investigate the impact of changing ICP on brain stiffness using MRE in a swine model. METHODS: Baseline MRE measurements were obtained, and then catheters were surgically placed into the left and right lateral ventricles of three animals. ICP was systematically increased over the range of 0 to 55 millimeters mercury (mmHg), and stiffness measurements were made using brain MRE at vibration frequencies of 60 hertz (Hz), 90 Hz, 120 Hz, and 150 Hz. RESULTS: A significant linear correlation between stiffness and ICP in the cross-subject comparison was observed for all tested vibrational frequencies (P ≤ 0.01). The 120 Hz (0.030 ± 0.004 kilopascal (kPa)/mmHg, P < 0.0001) and 150 Hz (0.031 ± 0.008 kPa/mmHg, P = 0.01) vibrational frequencies had nearly identical slopes, which were approximately two- to three-fold higher than the 90 Hz (0.017 ± 0.002 kPa/mmHg, P < 0.0001) and 60 Hz (0.009 ± 0.002 kPa/mmHg, P = 0.001) slopes, respectively. CONCLUSION: In this study, MRE demonstrated the potential for noninvasive measurement of changes in ICP. Magn Reson Med 79:1043-1051, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cardiac MR elastography using reduced-FOV, single-shot, spin-echo EPI.

PURPOSE: To implement a reduced field of view (rFOV) technique for cardiac MR elastography (MRE) and to demonstrate the improvement in image quality of both magnitude images and post-processed MRE stiffness maps compared to the conventional full field of view (full-FOV) acquisition. METHODS: With Institutional Review Board approval, 17 healthy volunteers underwent both full-FOV and rFOV cardiac MRE scans using 140-Hz vibrations. Two cardiac radiologists blindly compared the magnitude images and stiffness maps and graded the images based on several image quality attributes using a 5-point ordinal scale. Fisher's combined probability test was performed to assess the overall evaluation. The octahedral shear strain-based signal-to-noise ratio (OSS-SNR) and median stiffness over the left ventricular myocardium were also compared. RESULTS: One volunteer was excluded because of an inconsistent imaging resolution during the exam. In the remaining 16 volunteers (9 males, 7 females), the rFOV scans outperformed the full-FOV scans in terms of subjective image quality and ghosting artifacts in the magnitude images and stiffness maps, as well as the overall preference. The quantitative measurements showed that rFOV had significantly higher OSS-SNR (median: 1.4 [95% confidence interval (CI): 1.2-1.5] vs. 2.1 [95% CI: 1.8-2.4]), P < 0.05) compared to full-FOV. Although no significant change was found in the median myocardial stiffness between the 2 scans, we observed a decrease in the stiffness variation within the myocardium from 2.1 kPa (95% CI: [1.9, 2.3]) to 1.9 kPa (95% CI: [1.7, 2.0]) for full-FOV and rFOV, respectively (P < 0.05) in a subgroup of 7 subjects with ghosting present in the myocardium. CONCLUSION: This pilot volunteer study demonstrated that rFOV cardiac MRE has the capability to reduce ghosting and to improve image quality in both MRE magnitude images and stiffness maps. Magn Reson Med 80:231-238, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Regional assessment of in vivo myocardial stiffness using 3D magnetic resonance elastography in a porcine model of myocardial infarction.

PURPOSE: The stiffness of a myocardial infarct affects the left ventricular pump function and remodeling. Magnetic resonance elastography (MRE) is a noninvasive imaging technique for measuring soft-tissue stiffness in vivo. The purpose of this study was to investigate the feasibility of assessing in vivo regional myocardial stiffness with high-frequency 3D cardiac MRE in a porcine model of myocardial infarction, and compare the results with ex vivo uniaxial tensile testing. METHODS: Myocardial infarct was induced in a porcine model by embolizing the left circumflex artery. Fourteen days postinfarction, MRE imaging was performed in diastole using an echocardiogram-gated spin-echo echo-planar-imaging sequence with 140-Hz vibrations and 3D MRE processing. The MRE stiffness and tensile modulus from uniaxial testing were compared between the remote and infarcted myocardium. RESULTS: Myocardial infarcts showed increased in vivo MRE stiffness compared with remote myocardium (4.6 ± 0.7 kPa versus 3.0 ± 0.6 kPa, P = 0.02) within the same pig. Ex vivo uniaxial mechanical testing confirmed the in vivo MRE results, showing that myocardial infarcts were stiffer than remote myocardium (650 ± 80 kPa versus 110 ± 20 kPa, P = 0.01). CONCLUSIONS: These results demonstrate the feasibility of assessing in vivo regional myocardial stiffness with high-frequency 3D cardiac MRE. Magn Reson Med 79:361-369, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative 3D magnetic resonance elastography: Comparison with dynamic mechanical analysis.

PURPOSE: Magnetic resonance elastography (MRE) is a rapidly growing noninvasive imaging technique for measuring tissue mechanical properties in vivo. Previous studies have compared two-dimensional MRE measurements with material properties from dynamic mechanical analysis (DMA) devices that were limited in frequency range. Advanced DMA technology now allows broad frequency range testing, and three-dimensional (3D) MRE is increasingly common. The purpose of this study was to compare 3D MRE stiffness measurements with those of DMA over a wide range of frequencies and shear stiffnesses. METHODS: 3D MRE and DMA were performed on eight different polyvinyl chloride samples over 20-205 Hz with stiffness between 3 and 23 kPa. Driving frequencies were chosen to create 1.1, 2.2, 3.3, 4.4, 5.5, and 6.6 effective wavelengths across the diameter of the cylindrical phantoms. Wave images were analyzed using direct inversion and local frequency estimation algorithm with the curl operator and compared with DMA measurements at each corresponding frequency. Samples with sufficient spatial resolution and with an octahedral shear strain signal-to-noise ratio > 3 were compared. RESULTS: Consistency between the two techniques was measured with the intraclass correlation coefficient (ICC) and was excellent with an overall ICC of 0.99. CONCLUSIONS: 3D MRE and DMA showed excellent consistency over a wide range of frequencies and stiffnesses. Magn Reson Med 77:1184-1192, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

In vivo, high-frequency three-dimensional cardiac MR elastography: Feasibility in normal volunteers.

PURPOSE: Noninvasive stiffness imaging techniques (elastography) can image myocardial tissue biomechanics in vivo. For cardiac MR elastography (MRE) techniques, the optimal vibration frequency for in vivo experiments is unknown. Furthermore, the accuracy of cardiac MRE has never been evaluated in a geometrically accurate phantom. Therefore, the purpose of this study was to determine the necessary driving frequency to obtain accurate three-dimensional (3D) cardiac MRE stiffness estimates in a geometrically accurate diastolic cardiac phantom and to determine the optimal vibration frequency that can be introduced in healthy volunteers. METHODS: The 3D cardiac MRE was performed on eight healthy volunteers using 80 Hz, 100 Hz, 140 Hz, 180 Hz, and 220 Hz vibration frequencies. These frequencies were tested in a geometrically accurate diastolic heart phantom and compared with dynamic mechanical analysis (DMA). RESULTS: The 3D Cardiac MRE was shown to be feasible in volunteers at frequencies as high as 180 Hz. MRE and DMA agreed within 5% at frequencies greater than 180 Hz in the cardiac phantom. However, octahedral shear strain signal to noise ratios and myocardial coverage was shown to be highest at a frequency of 140 Hz across all subjects. CONCLUSION: This study motivates future evaluation of high-frequency 3D MRE in patient populations. Magn Reson Med 77:351-360, 2017. © 2016 Wiley Periodicals, Inc.

Cardiac MR elastography for quantitative assessment of elevated myocardial stiffness in cardiac amyloidosis.

PURPOSE: To evaluate if cardiac magnetic resonance elastography (MRE) can measure increased stiffness in patients with cardiac amyloidosis. Myocardial tissue stiffness plays an important role in cardiac function. A noninvasive quantitative imaging technique capable of measuring myocardial stiffness could aid in disease diagnosis, therapy monitoring, and disease prognostic strategies. We recently developed a high-frequency cardiac MRE technique capable of making noninvasive stiffness measurements. MATERIALS AND METHODS: In all, 16 volunteers and 22 patients with cardiac amyloidosis were enrolled in this study after Institutional Review Board approval and obtaining formal written consent. All subjects were imaged head-first in the supine position in a 1.5T closed-bore MR imager. 3D MRE was performed using 5 mm isotropic resolution oblique short-axis slices and a vibration frequency of 140 Hz to obtain global quantitative in vivo left ventricular stiffness measurements. The median stiffness was compared between the two cohorts. An octahedral shear strain signal-to-noise ratio (OSS-SNR) threshold of 1.17 was used to exclude exams with insufficient motion amplitude. RESULTS: Five volunteers and six patients had to be excluded from the study because they fell below the 1.17 OSS-SNR threshold. The myocardial stiffness of cardiac amyloid patients (median: 11.4 kPa, min: 9.2, max: 15.7) was significantly higher (P = 0.0008) than normal controls (median: 8.2 kPa, min: 7.2, max: 11.8). CONCLUSION: This study demonstrates the feasibility of 3D high-frequency cardiac MRE as a contrast-agent-free diagnostic imaging technique for cardiac amyloidosis. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1361-1367.

MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias.

OBJECTIVE: The purpose of this study was to investigate age-corrected brain MR elastography (MRE) findings in four dementia cohorts (Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia, and normal pressure hydrocephalus) and determine the potential use as a differentiating biomarker in dementia subtypes. SUBJECTS AND METHODS: Institutional review board approval and written informed consent were obtained to perform MRE on 84 subjects: 20 patients with normal pressure hydrocephalus, eight with Alzheimer disease, five with dementia with Lewy bodies, five with frontotemporal dementia, and 46 cognitively normal control subjects. Shear waves of 60-Hz vibration frequency were transmitted into the brain using a pillowlike passive driver, and brain stiffness was determined in eight different regions (cerebrum, frontal, occipital, parietal, temporal, deep gray matter-white matter, sensorimotor cortex, and cerebellum). All stiffness values were age-corrected and compared with control subjects. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: Regional stiffness patterns unique to each dementing disorder were observed. Patients with Alzheimer disease and frontotemporal dementia showed decreased cerebral stiffness (p = 0.001 and p = 0.002, respectively) with regional softening of the frontal and temporal lobes. Patients with Alzheimer disease additionally showed parietal lobe and sensorimotor region softening (p = 0.039 and p = 0.018, respectively). Patients with normal pressure hydrocephalus showed stiffening of the parietal, occipital, and sensorimotor regions (p = 0.007, p < 0.001, and p < 0.0001, respectively). Patients with dementia with Lewy bodies did not show significant stiffness changes in any of the regions. CONCLUSION: Quantitative MRE of changes in brain viscoelastic structure shows unique regional brain stiffness patterns between common dementia subtypes.

Magnetic resonance elastography of frontotemporal dementia.

PURPOSE: To investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease. MATERIALS AND METHODS: We examined five male subjects with bvFTD and nine cognitively normal age-matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre- and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre- and postcentral gyri). RESULTS: Significantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD. CONCLUSION: Future studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD.

Magnetic resonance elastography detects tumoral consistency in pituitary macroadenomas.

INTRODUCTION: Most pituitary macroadenomas (PMA) are soft and suckable allowing transsphenoidal resection. A small percentage of PMA are firm, which significantly alters the time, technical difficulty, and effectiveness of transsphenoidal surgery. No current imaging technology can reliably assess PMA viscoelastic consistency in preparation for surgery. Magnetic resonance elastography (MRE) is an MRI-based technique that measures the propagation of mechanically induced shear waves through tissue to calculate stiffness. We prospectively evaluated MRE in 10 patients undergoing transsphenoidal resection of PMA to determine feasibility and potential usefulness. METHODS: 10 patients with PMA > 2.0 cm in maximum diameter were prospectively imaged with MRE prior to transsphenoidal surgery. Mean patient age was 59.5 ± 16.2 (22-78) years. Five were female and five male. MRE was performed with a modified single-shot spin-echo echo-planar-imaging pulse sequence on a 3T MRI. MRE values were independently calculated. The surgeon, blinded to the MRE results, graded tumor consistency at surgery as soft, intermediate, or firm. Chi-squared test compared surgical grading and MRE stiffness values. RESULTS: MRE was accomplished in all patients with excellent resolution. By surgical categorization, six tumors were soft and four intermediate. The mean MRE value for soft tumors was 1.38 ± 0.36 (1.08-1.87) kPa, while for intermediate tumors it was 1.94 ± 0.26 (1.72-2.32) kPa (p = 0.020). CONCLUSION: Determination of PMA stiffness is feasible with MRE. There was a statistically significant difference in MRE values between soft and intermediate PMAs. Further study in a larger series is ongoing to determine whether MRE will prove useful in preoperative planning for PMA.

Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults.

Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011 ± 0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56 ± 0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 kPa and 0.09 kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and temporal lobes.

Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Incorporating endorectal MR elastography into multi-parametric MRI for prostate cancer imaging: Initial feasibility in volunteers.

PURPOSE: To investigate the tolerability and technical feasibility of performing endorectal MR elastography (eMRE) in human volunteers within the representative age group commonly affected by prostate cancer. MATERIALS AND METHODS: Endorectal MRE was conducted on seven volunteers in a 1.5 Tesla (T) MR imager using a rigid endorectal coil. Another five volunteers were imaged on a 3T MR imager using an inflatable balloon type endorectal coil. Tolerability was accessed for vibration amplitudes of ±1-50 µm and for frequencies of 100-300 Hz. RESULTS: All 12 volunteers tolerated the displacements necessary to successfully perform eMRE. Shear waves with frequencies up to 300 Hz could propagate across the entire prostate using both coil designs. CONCLUSION: The results of this study motivate further investigation of eMRE in prostate cancer patients to help determine if there is an added value of integrating eMRE into existing multi-parametric prostate MRI exams.