Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.

Modeling and measurement of lead tip heating and resonant length for implanted, insulated wires.

PURPOSE: To study implant lead tip heating because of the RF power deposition by developing mathematical models and comparing them with measurements acquired at 1.5 T and 3 T, especially to predict resonant length. THEORY AND METHODS: A simple exponential model and an adapted transmission line model for the electric field transfer function were developed. A set of wavenumbers, including that calculated from insulated antenna theory (King wavenumber) and that of the embedding medium were considered. Experiments on insulated, capped wires of varying lengths were performed to determine maximum temperature rise under RF exposure. The results are compared with model predictions from analytical expressions derived under the assumption of a constant electric field, and with those numerically calculated from spatially varying, simulated electric fields from body coil transmission. Simple expressions for the resonant length bounded between one-quarter and one-half wavelength are developed based on the roots of transcendental equations. RESULTS: The King wavenumber for both models more closely matched the experimental data with a maximum root mean square error of 9.81°C at 1.5 T and 5.71°C at 3 T compared to other wavenumbers with a maximum root mean square error of 27.52°C at 1.5 T and 22.01°C for 3 T. Resonant length was more accurately predicted compared to values solely based on the embedding medium. CONCLUSION: Analytical expressions were developed for implanted lead heating and resonant lengths under specific assumptions. The value of the wavenumber has a strong effect on the model predictions. Our work could be used to better manage implanted device lead tip heating.

Improved Resting-State Functional MRI Using Multi-Echo Echo-Planar Imaging on a Compact 3T MRI Scanner with High-Performance Gradients.

In blood-oxygen-level-dependent (BOLD)-based resting-state functional (RS-fMRI) studies, usage of multi-echo echo-planar-imaging (ME-EPI) is limited due to unacceptable late echo times when high spatial resolution is used. Equipped with high-performance gradients, the compact 3T MRI system (C3T) enables a three-echo whole-brain ME-EPI protocol with smaller than 2.5 mm isotropic voxel and shorter than 1 s repetition time, as required in landmark fMRI studies. The performance of the ME-EPI was comprehensively evaluated with signal variance reduction and region-of-interest-, seed- and independent-component-analysis-based functional connectivity analyses and compared with a counterpart of single-echo EPI with the shortest TR possible. Through the multi-echo combination, the thermal noise level is reduced. Functional connectivity, as well as signal intensity, are recovered in the medial orbital sulcus and anterior transverse collateral sulcus in ME-EPI. It is demonstrated that ME-EPI provides superior sensitivity and accuracy for detecting functional connectivity and/or brain networks in comparison with single-echo EPI. In conclusion, the high-performance gradient enabled high-spatial-temporal resolution ME-EPI would be the method of choice for RS-fMRI study on the C3T.

Improved Brain MR Imaging from a Compact, Lightweight 3T Scanner with High-Performance Gradients.

BACKGROUND: A low-cryogen, compact 3T (C3T) MRI scanner with high-performance gradients capable of simultaneously achieving 80 mT/m gradient amplitude and 700 T/m/second slew rate has been in use to study research patients since March 2016 but has not been implemented in the clinical practice. PURPOSE: To compare head MRI examinations obtained with the C3T system and a conventional whole-body 3T (WB3T) scanner in seven parameters across five commonly used brain imaging sequences. STUDY TYPE: Prospective. SUBJECTS: Thirty patients with a clinically indicated head MRI. SEQUENCE: 3T; T1 FLAIR, T1 MP-RAGE, 3D T2 FLAIR, T2 FSE, and DWI. ASSESSMENT: All patients tolerated the scans well. Three board-certified neuroradiologists scored the comparative quality of C3T and WB3T images in blinded fashion using a five-point Likert scale in terms of: signal-to-noise ratio, lesion conspicuity, motion artifact, gray/white matter contrast, cerebellar folia, susceptibility artifact, and overall quality. STATISTICAL TEST: Left-sided, right-sided, and two-sided Wilcoxon signed rank test; Fisher's method. A P value <0.05 was considered statistically significant. RESULTS: The C3T system performed better than the WB3T in virtually all comparisons, except for motion artifacts for the T1 FLAIR and T1 MP-RAGE sequences, where the WB3T system was deemed better. When combining all sequences together, the C3T system outperformed the WB3T system in all image quality parameters evaluated, except for motion artifact (P = 0.13). DATA CONCLUSION: The C3T scanner provided better overall image quality for all sequences, and performed better in all individual categories, except for motion artifact on the T1 FLAIR and T1 MP-RAGE. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

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.

Evaluation of hearing loss in young adults after exposure to 3.0T MRI with standard hearing protection.

Standard clinical protocols require hearing protection during magnetic resonance imaging (MRI) for patient safety. This investigation prospectively evaluated the auditory function impact of acoustic noise exposure during a 3.0T MRI in healthy adults. Twenty-nine participants with normal hearing underwent a comprehensive audiologic assessment before and immediately following a clinically indicated head MRI. Appropriate hearing protection with earplugs (and pads) was used per standard of practice. To characterize noise hazards, current sound monitoring tools were used to measure levels of pulse sequences measured. A third audiologic test was performed if a significant threshold shift (STS) was identified at the second test, within 30 days post MRI. Some sequences produced high levels (up to 114.5 dBA; 129 dB peak SPL) that required hearing protection but did not exceed 100% daily noise dose. One participant exhibited an STS in the frequency region most highly associated with noise-induced hearing loss. No participants experienced OSHA-defined STS in either ear. Overall, OAE measures did not show evidence of changes in cochlear function after MRI. In conclusion, hearing threshold shifts associated with hearing loss or OAE level shifts reflecting underlying cochlear damage were not detected in any of the 3.0T MRI study participants who used the current recommended hearing protection.

Linearity and Bias of Proton Density Fat Fraction as a Quantitative Imaging Biomarker: A Multicenter, Multiplatform, Multivendor Phantom Study.

Background Proton density fat fraction (PDFF) estimated by using chemical shift-encoded (CSE) MRI is an accepted imaging biomarker of hepatic steatosis. This work aims to promote standardized use of CSE MRI to estimate PDFF. Purpose To assess the accuracy of CSE MRI methods for estimating PDFF by determining the linearity and range of bias observed in a phantom. Materials and Methods In this prospective study, a commercial phantom with 12 vials of known PDFF values were shipped across nine U.S. centers. The phantom underwent 160 independent MRI examinations on 27 1.5-T and 3.0-T systems from three vendors. Two three-dimensional CSE MRI protocols with minimal T1 bias were included: vendor and standardized. Each vendor's confounder-corrected complex or hybrid magnitude-complex based reconstruction algorithm was used to generate PDFF maps in both protocols. The Siemens reconstruction required a configuration change to correct for water-fat swaps in the phantom. The MRI PDFF values were compared with the known PDFF values by using linear regression with mixed-effects modeling. The 95% CIs were calculated for the regression slope (ie, proportional bias) and intercept (ie, constant bias) and compared with the null hypothesis (slope = 1, intercept = 0). Results Pooled regression slope for estimated PDFF values versus phantom-derived reference PDFF values was 0.97 (95% CI: 0.96, 0.98) in the biologically relevant 0%-47.5% PDFF range. The corresponding pooled intercept was -0.27% (95% CI: -0.50%, -0.05%). Across vendors, slope ranges were 0.86-1.02 (vendor protocols) and 0.97-1.0 (standardized protocol) at 1.5 T and 0.91-1.01 (vendor protocols) and 0.87-1.01 (standardized protocol) at 3.0 T. The intercept ranges (absolute PDFF percentage) were -0.65% to 0.18% (vendor protocols) and -0.69% to -0.17% (standardized protocol) at 1.5 T and -0.48% to 0.10% (vendor protocols) and -0.78% to -0.21% (standardized protocol) at 3.0 T. Conclusion Proton density fat fraction estimation derived from three-dimensional chemical shift-encoded MRI in a commercial phantom was accurate across vendors, imaging centers, and field strengths, with use of the vendors' product acquisition and reconstruction software. © RSNA, 2021 See also the editorial by Dyke in this issue.

Temperature-corrected proton density fat fraction estimation using chemical shift-encoded MRI in phantoms.

PURPOSE: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. THEORY AND METHODS: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. RESULTS: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. CONCLUSION: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

The effect of spiral trajectory correction on pseudo-continuous arterial spin labeling with high-performance gradients on a compact 3T scanner.

PURPOSE: To demonstrate the feasibility of pseudo-continuous arterial-spin-labeled (pCASL) imaging with 3D fast-spin-echo stack-of-spirals on a compact 3T scanner (C3T), to perform trajectory correction for eddy-current-induced deviations in the spiral readout of pCASL imaging, and to assess the correction effect on perfusion-related images with high-performance gradients (80 mT/m, 700T/m/s) of the C3T. METHODS: To track eddy-current-induced artifacts with Archimedean spiral readout, the spiral readout in pCASL imaging was performed with 5 different peak gradient slew rate (Smax ) values ranging from 70 to 500 T/m/s. The trajectory for each Smax was measured using a dynamic field camera and applied in a density-compensated gridding image reconstruction in addition to the nominal trajectory. The effect of the trajectory correction was assessed with perfusion-weighted (ΔM) images and proton-density-weighted images as well as cerebral blood flow (CBF) maps, obtained from 10 healthy volunteers. RESULTS: Blurring artifact on ΔM images was mitigated by the trajectory correction. CBF values on the left and right calcarine cortices showed no significant difference after correction. Also, the signal-to-noise ratio of ΔM images improved, on average, by 7.6% after correction (P < .001). The greatest improvement of 12.1% on ΔM images was achieved with a spiral readout using Smax of 300~400 T/m/s. CONCLUSION: Eddy currents can cause spiral trajectory deviation, which leads to deformation of the CBF map even in cases of low value Smax . The trajectory correction for spiral-readout-based pCASL produces more reliable results for perfusion imaging. These results suggest that pCASL is feasible on C3T with high-performance gradients.