Distinct brain iron profiles associated with logopenic progressive aphasia and posterior cortical atrophy.

Quantitative susceptibility mapping (QSM) can detect iron distribution in the brain by estimating local tissue magnetic susceptibility properties at every voxel. Iron deposition patterns are well studied in typical Alzheimer's disease (tAD), but little is known about these patterns in atypical clinical presentations of AD such as logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA). Seventeen PCA patients and eight LPA patients were recruited by the Neurodegenerative Research Group at Mayo Clinic, Rochester, MN, and underwent MRI that included a five-echo gradient echo sequence for calculation of QSM. Mean QSM signal was extracted from gray and white matter for regions-of-interest across the brain using the Mayo Clinic Adult Lifespan Template. Bayesian hierarchical models were fit per-region and per-hemisphere to compare PCA, LPA, 63 healthy controls, and 20 tAD patients. Strong evidence (posterior probability > 0.99) was observed for greater susceptibility in the middle occipital gyrus and amygdala in both LPA and PCA, and in the right inferior parietal, inferior temporal, and angular gyri in PCA and the caudate and substantia nigra in LPA compared to controls. Moderate evidence for greater susceptibility (posterior probability > 0.90) was also observed in the inferior occipital gyrus, precuneus, putamen and entorhinal cortex in both LPA and PCA, along with superior frontal gyrus in PCA and inferior temporal gyri, insula and basal ganglia in LPA, when compared to controls. Between phenotypic comparisons, LPA had greater susceptibility in the caudate, hippocampus, and posterior cingulate compared to PCA, while PCA showed greater susceptibility in the right superior frontal and middle temporal gyri compared to LPA. Both LPA and PCA showed moderate and strong evidence for greater susceptibility than tAD, particularly in medial and lateral parietal regions, while tAD showed greater susceptibility in the hippocampus and basal ganglia. This study proposes the possibility of unique iron profiles existing between LPA and PCA within cortical and subcortical structures. These changes match well with the disease-related changes of the clinical phenotypes, suggesting that QSM could be an informative candidate marker to study iron deposition in these patients.

Magnetic resonance elastography of the prostate in patients with lower urinary tract symptoms: feasibility of the modified driver at high multi-frequencies.

PURPOSE: To demonstrate the feasibility and diagnostic value of high-frequency magnetic resonance elastography (MRE) for evaluation of prostatic disease in patients with lower urinary tract symptoms (LUTS). METHODS: 41 patients who underwent preoperative prostate MRI and MRE with a modified driver were enrolled retrospectively from May 2016 to September 2021. All were included in the assessment of MRE image quality, using a qualitative visual inspection and a quantitative confidence map. 35 patients (prostate cancer (PCa), n = 13; non-PCa, n = 22) undergoing prostatectomy or biopsy were evaluated for the diagnostic performance of stiffness values. The confidence values and the stiffness values were analyzed by one-way analysis of variance (ANOVA) and independent samples T test, respectively. Area under the receiver operating characteristic (AUROC) analysis was performed. RESULTS: Through the qualitative analysis, all MRE acquisitions were successful at 60, 90, 120 and 150 Hz. The quantitative confidence values were significantly lower at 60 Hz (0.683 ± 0.055) and 90 Hz (0.762 ± 0.048) than that at 120 Hz (0.814 ± 0.049) and 150 Hz (0.840 ± 0.049), all P < 0.001. The stiffness of PCa was higher than non-PCa at 90 Hz (P = 0.008), 120 Hz (P < 0.001) and 150 Hz (P < 0.001). The AUCs were 0.773, 0.881 and 0.944, respectively. CONCLUSION: Prostate MRE using the modified driver is feasible at 60-150 Hz and image quality is better at higher frequencies. Prostate MRE may be useful and helpful to evaluate prostate diseases in patients with LUTS at higher frequencies; however, further study may be warranted with larger population in future.

Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer.

PURPOSE: To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS: The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0 T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram. RESULTS: PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60 Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90 Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60 Hz]; 0.975 vs. 0.904, P = 0.060 [90 Hz], respectively). CONCLUSIONS: MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

Harnessing brain waves: a review of brain magnetic resonance elastography for clinicians and scientists entering the field.

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.

Artificial neural networks for magnetic resonance elastography stiffness estimation in inhomogeneous materials.

PURPOSE: To test the hypothesis that removing the assumption of material homogeneity will improve the spatial accuracy of stiffness estimates made by Magnetic Resonance Elastography (MRE). METHODS: An artificial neural network was trained using synthetic wave data computed using a coupled harmonic oscillator model. Material properties were allowed to vary in a piecewise smooth pattern. This neural network inversion (Inhomogeneous Learned Inversion (ILI)) was compared against a previous homogeneous neural network inversion (Homogeneous Learned Inversion (HLI)) and conventional direct inversion (DI) in simulation, phantom, and in-vivo experiments. RESULTS: In simulation experiments, ILI was more accurate than HLI and DI in predicting the stiffness of an inclusion in noise-free, low-noise, and high-noise data. In the phantom experiment, ILI delineated inclusions ≤ 2.25 cm in diameter more clearly than HLI and DI, and provided a higher contrast-to-noise ratio for all inclusions. In a series of stiff brain tumors, ILI shows sharper stiffness transitions at the edges of tumors than the other inversions evaluated. CONCLUSION: ILI is an artificial neural network based framework for MRE inversion that does not assume homogeneity in material stiffness. Preliminary results suggest that it provides more accurate stiffness estimates and better contrast in small inclusions and at large stiffness gradients than existing algorithms that assume local homogeneity. These results support the need for continued exploration of learning-based approaches to MRE inversion, particularly for applications where high resolution is required.

MRI feature tracking strain is prognostic for all-cause mortality in AL amyloidosis.

OBJECTIVES: Cardiac involvement is a major determinate of mortality in light chain (AL) amyloidosis. Cardiac magnetic resonance imaging (MRI) feature tracking (FT) strain is a new method for measuring myocardial strain. This study retrospectively evaluated the association of MRI FT strain with all-cause mortality in AL amyloidosis. MATERIALS AND METHODS: Seventy-six patients with newly diagnosed AL amyloidosis underwent cardiac MRI. 75 had images suitable for MRI FT strain analysis. MRI delayed enhancement, morphologic and functional evaluation, cardiac biomarker staging and transthoracic echocardiography were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. RESULTS: There were 52 deaths. Median follow-up of surviving patients was 1.7 years. In univariate analysis, global radial (Hazard Ratio (HR) = 0.95, p <.01), circumferential (HR = 1.09, p < .01) and longitudinal (HR = 1.08, p < .01) strain were associated with all-cause mortality. In separate multivariate models, radial (HR = 0.96, p = .02), circumferential (HR = 1.09, p = .03) and longitudinal strain (HR = 1.07, p = .04) remained prognostic when combined with presence of biomarker stage 3. CONCLUSIONS: MRI FT strain is associated with all-cause mortality in patients with AL amyloidosis.

Air embolism: diagnosis and management.

Air embolism is an uncommon, but potentially life-threatening event for which prompt diagnosis and management can result in significantly improved patient outcomes. Most air emboli are iatrogenic. Arterial air emboli may occur as a complication from lung biopsy, arterial catheterization or cardiopulmonary bypass. Immediate management includes placing the patient on high-flow oxygen and in the right lateral decubitus position. Venous air emboli may occur during pressurized venous infusions, or catheter manipulation. Immediate management includes placement of the patient on high-flow oxygen and in the left lateral decubitus and/or Trendelenburg position. Hyperbaric oxygen therapy is the definitive treatment which may decrease the size of air emboli by facilitating gas reabsorption, while also improving tissue oxygenation and reducing ischemic reperfusion injury.

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.

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.

Higher-Resolution Magnetic Resonance Elastography in Meningiomas to Determine Intratumoral Consistency.

BACKGROUND: Magnetic resonance elastography (MRE) analyzes shear wave movement through tissue to determine stiffness. In a prior study, measurements with first-generation brain MRE techniques correlated with intraoperative observations of overall meningioma stiffness. OBJECTIVE: To evaluate the diagnostic accuracy of a higher-resolution MRE technique to preoperatively detect intratumoral variations compared with surgeon assessment. METHODS: Fifteen meningiomas in 14 patients underwent MRE. Tumors with regions of distinctly different stiffness were considered heterogeneous. Intratumoral portions were considered hard if there was a significant area ≥6 kPa. A 5-point scale graded intraoperative consistency. A durometer semiquantitatively measured surgical specimen hardness. Statistics included χ, sensitivity, specificity, positive and negative predicative values, and Spearman rank correlation coefficient. RESULTS: For MRE and surgery, 9 (60%) and 7 (47%) tumors were homogeneous, 6 (40%) and 8 (53%) tumors were heterogeneous, 6 (40%) and 10 (67%) tumors had hard portions, and 14 (93%) and 12 (80%) tumors had soft portions, respectively. MRE sensitivity, specificity, and positive and negative predictive values were as follows: for heterogeneity, 75%, 100%, 100%, and 87%; for hardness, 60%, 100%, 100%, and 56%; and for softness, 100%, 33%, 86%, and 100%. Overall, 10 tumors (67%) matched well with MRE and intraoperative consistency and correlated between intraoperative observations (P = .02) and durometer readings (P = .03). Tumor size ≤3.5 cm or vascular tumors were more likely to be inconsistent (P < .05). CONCLUSION: MRE was excellent at ruling in heterogeneity with hard portions but less effective in ruling out heterogeneity and hard portions, particularly in tumors more vascular or <3.5 cm. MRE is the first technology capable of prospectively evaluating intratumoral stiffness and, with further refinement, will likely prove useful in preoperative planning.

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.

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.

The feasibility of endorectal MR elastography for prostate cancer localization.

The objectives of this study were to evaluate the feasibility of using a rigid radio-frequency receiver endorectal coil for intracavitary prostate magnetic resonance elastography (MRE) and to demonstrate the capability of this technique for generating stiffness maps over a typical prostate volume. An endorectal coil is currently used to help improve the signal-to-noise ratio of images acquired with multiparametric magnetic resonance imaging. We propose that this same coil could also serve to generate shear waves in the prostate gland during imaging, opening up the possibility of incorporating prostate stiffness characterization into multiparametric magnetic resonance imaging. Prostate cancer has been shown to change the elasticity of tissue, suggesting that stiffness imaging (elastography) may provide supplementary diagnostic information. A rigid endorectal coil was mechanically coupled to a piezoceramic actuator and used to investigate full volume (27 slices, 2-mm thick) endorectal MRE in a prostate mimicking phantom. The low-amplitude vibrations (± 8-38 µm displacements) necessary to perform endorectal MRE did not affect the signal-to noise ratio of the coil and endorectal MRE was capable of resolving 0.1 cc (0.6 cm diameter) spherical inclusion volumes. Therefore, the results of this study, in combination with current clinical practice, motivate clinical evaluation of endorectal MRE in patients.

Transurethral prostate magnetic resonance elastography: prospective imaging requirements.

Tissue stiffness is known to undergo alterations when affected by prostate cancer and may serve as an indicator of the disease. Stiffness measurements can be made with magnetic resonance elastography performed using a transurethral actuator to generate shear waves in the prostate gland. The goal of this study was to help determine the imaging requirements of transurethral magnetic resonance elastography and to evaluate whether the spatial and stiffness resolution of this technique overlapped with the requirements for prostate cancer detection. Through the use of prostate-mimicking gelatin phantoms, frequencies of at least 400 Hz were necessary to obtain accurate stiffness measurements of 10 mm diameter inclusions, but the detection of inclusions with diameters as small as 4.75 mm was possible at 200 Hz. The shear wave attenuation coefficient was measured in vivo in the canine prostate gland, and was used to predict the detectable penetration depth of shear waves in prostate tissue. These results suggested that frequencies below 200 Hz could propagate to the prostate boundary with a signal to noise ratio (SNR) of 60 and an actuator capable of producing 60 µm displacements. These requirements are achievable with current imaging and actuator technologies, and motivate further investigation of magnetic resonance elastography for the targeting of prostate cancer.