Faculty Bibliography

PURPOSE/OBJECTIVE:The purpose of this work was to design and build a coil for quadri-nuclear MRI of the human brain at 7 T. METHODS: RESULTS: CONCLUSION/CONCLUSIONS:While the SNR of the quadruple tuned coil was significantly lower than dual- and single-tuned reference coils, it represents a step toward truly simultaneous quadri-nuclear measurements.

In this work, we introduce a super-resolution method that generates a high-resolution (HR) sodium (²³ Na) image from simultaneously acquired low-resolution (LR) ²³ Na density-weighted MRI and HR proton density, T₁ , and T₂ maps from proton (¹ H) MR fingerprinting in the brain at 7 T. The core of our method is a partial least squares regression between the HR (¹ H) images and the LR (²³ Na) image. An iterative loop and deconvolution with the point spread function of each acquired image were included in the algorithm to generate a final HR ²³ Na image without losing features from the LR ²³ Na image. The method was applied to simultaneously acquired HR proton and LR sodium data with in-plane resolution ratios between sodium and proton data of 3.8 and 1.9 and the same slice thickness. Four volunteers were scanned to evaluate the method's performance. For the data with a resolution ratio of 3.8, the mean absolute difference between the generated and ground truth HR ²³ Na images was in the range of 1.5%-7.2% of the ground truth with a multiscale structural similarity index (M-SSIM) of 0.93 ± 0.03. For the data with a resolution ratio of 1.9, the mean absolute difference was in the range of 4.8%-6.3% with an M-SSIM of 0.95 ± 0.01.

PURPOSE/OBJECTIVE:H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients' putamen (H7). METHODS:26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen's d). RESULTS:Patients' occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls', respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients' occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 - 0.37; Cr, d = 0.27 - 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 - 0.34; Cr, d = 0.16 - 0.51). CONCLUSIONS:H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

Nuclear magnetic resonance relaxometry represents a powerful tool for extracting dynamic information. Yet, obtaining links to molecular motion is challenging for many ions that relax through the quadrupolar mechanism, which is mediated by electric field gradient fluctuations and lacks a detailed microscopic description. For sodium ions in aqueous electrolytes, we combine ab initio calculations to account for electron cloud effects with classical molecular dynamics to sample long-time fluctuations, and obtain relaxation rates in good agreement with experiments over broad concentration and temperature ranges. We demonstrate that quadrupolar nuclear relaxation is sensitive to subpicosecond dynamics not captured by previous models based on water reorientation or cluster rotation. While ions affect the overall water retardation, experimental trends are mainly explained by dynamics in the first two solvation shells of sodium, which contain mostly water. This work thus paves the way to the quantitative understanding of quadrupolar relaxation in electrolyte and bioelectrolyte systems.

Proton MRI can provide detailed morphological images, but it reveals little information about cell homeostasis. On the other hand, sodium MRI can provide metabolic information but cannot resolve fine structures. The complementary nature of proton and sodium MRI raises the prospect of their combined use in a single experiment. In this work, we assessed the repeatability of normalized proton density (PD), T₁, T₂, and normalized sodium density-weighted quantification measured with simultaneous 3D ¹H MRF/²³Na MRI in the brain at 7 T, from ten healthy volunteers who were scanned three times each. The coefficients of variation (CV) and the intra-class correlation (ICC) were calculated for the mean and standard deviation (SD) of these 4 parameters in grey matter, white matter, and cerebrospinal fluid. As result, the CVs were lower than 3.3% for the mean values and lower than 6.9% for the SD values. The ICCs were higher than 0.61 in all 24 measurements. We conclude that the measurements of normalized PD, T₁, T₂, and normalized sodium density-weighted from simultaneous 3D ¹H MRF/²³Na MRI in the brain at 7 T showed high repeatability. We estimate that changes > 6.6% (> 2 CVs) in mean values of both ¹H and ²³Na metrics could be detectable with this method.

PURPOSE/OBJECTIVE:, and proton density) and sodium density weighted images over the whole brain. METHODS:were evaluated in phantoms. Finally, in vivo application of the method was demonstrated in five healthy subjects. RESULTS:values measured using our method were lower than the results measured by other conventional techniques. CONCLUSIONS:

OBJECTIVES/OBJECTIVE:To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. METHODS:from MRF were compared in 12 gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. RESULTS:, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). CONCLUSION/CONCLUSIONS:, FA, and ADC for predicting 3-month outcome after mTBI. KEY POINTS/CONCLUSIONS:, and FA.

In patients with Friedreich ataxia, structural MRI is typically used to detect abnormalities primarily in the brainstem, cerebellum, and spinal cord. The aim of the present study was to additionally investigate possible metabolic changes in Friedreich ataxia using in vivo sodium MRI that may precede macroanatomical alterations, and to explore potential associations with clinical parameters of disease progression. Tissue sodium concentration across the whole brain was estimated from sodium MRI maps acquired at 3 T and compared between 24 patients with Friedreich ataxia (21-57 years old, 13 females) and 23 controls (21-60 years old, 12 females). Tensor-based morphometry was used to assess volumetric changes. Total sodium concentrations and volumetric data in brainstem and cerebellum were correlated with clinical parameters, such as severity of ataxia, activity of daily living and disability stage, age, age at onset, and disease duration. Compared to controls, patients showed reduced brain volume in the right cerebellar lobules I-V (difference in means: -0.039% of total intracranial volume [TICV]; Cohen's d = 0.83), cerebellar white matter (WM) (-0.105%TICV; d = 1.16), and brainstem (-0.167%TICV; d = 1.22), including pons (-0.102%TICV; d = 1.00), medulla (-0.036%TICV; d = 1.72), and midbrain (-0.028%TICV; d = 1.05). Increased sodium concentration was additionally detected in the total cerebellum (difference in means: 2.865 mmol; d = 0.68), and in several subregions with highest effect sizes in left (5.284 mmol; d = 1.01) and right cerebellar lobules I-V (5.456 mmol; d = 1.00), followed by increases in the vermis (4.261 mmol; d = 0.72), and in left (2.988 mmol; d = 0.67) and right lobules VI-VII (2.816 mmol; d = 0.68). In addition, sodium increases were also detected in all brainstem areas (3.807 mmol; d = 0.71 to 5.42 mmol; d = 1.19). After controlling for age, elevated total sodium concentrations in right cerebellar lobules IV were associated with younger age at onset (r = -0.43) and accordingly with longer disease duration in patients (r = 0.43). Our findings support the potential of in vivo sodium MRI to detect metabolic changes of increased total sodium concentration in the cerebellum and brainstem, the key regions in Friedreich ataxia. In addition to structural changes, sodium changes were present in cerebellar hemispheres and vermis without concomitant significant atrophy. Given the association with age at disease onset or disease duration, metabolic changes should be further investigated longitudinally and in larger cohorts of early disease stages to determine the usefulness of sodium MRI as a biomarker for early neuropathological changes in Friedreich ataxia and efficacy measure for future clinical trials.

The objective of the current study was to design and build a dual-tuned coil array for simultaneous ²³ Na/¹ H MRI of the human brain at 7 T. Quality factor, experimental B₁ ⁺ measurements, and electromagnetic simulations in prototypes showed that setups consisting of geometrically interleaved ¹ H and ²³ Na loops performed better than or similar to ¹ H or ²³ Na loops in isolation. Based on these preliminary findings, we built a transmit/receive eight-channel ²³ Na loop array that was geometrically interleaved with a transmit/receive eight-channel ¹ H loop array. We assessed the performance of the manufactured array with mononuclear signal-to-noise ratio (SNR) and B₁ ⁺ measurements, along with multinuclear magnetic resonance fingerprinting maps and images. The ²³ Na array within the developed dual-tuned device provided more than 50% gain in peripheral SNR and similar B₁ ⁺ uniformity and coverage as a reference birdcage coil of similar size. The ¹ H array provided good B₁ ⁺ uniformity in the brain, excluding the cerebellum and brain stem. The integrated ²³ Na and ¹ H arrays were used to demonstrate truly simultaneous quantitative ¹ H mapping and ²³ Na imaging.