Faculty Bibliography

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.

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.

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.

The hippocampus is one of the most challenging brain regions for proton MR spectroscopy (MRS) applications. Moreover, quantification of J-coupled species such as myo-inositol (m-Ins) and glutamate + glutamine (Glx) is affected by the presence of macromolecular background. While long echo time (TE) MRS eliminates the macromolecules, it also decreases the m-Ins and Glx signal and, as a result, these metabolites are studied mainly with short TE. Here, we investigate the feasibility of reproducibly measuring their concentrations at a long TE of 120 ms, using a semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence, as this sequence was recently recommended as a standard for clinical MRS. Gradient offset-independent adiabatic refocusing pulses were implemented, and an optimal long TE for the detection of m-Ins and Glx was determined using the T₂ relaxation times of macromolecules. Metabolite concentrations and their coefficients of variation (CVs) were obtained for a 3.4-mL voxel centered on the left hippocampus on 3-T MR systems at two different sites with three healthy subjects (aged 32.5 ± 10.2 years [mean ± standard deviation]) per site, with each subject scanned over two sessions, and with each session comprising three scans. Concentrations of m-Ins, choline, creatine, Glx and N-acetyl-aspartate were 5.4 ± 1.5, 1.7 ± 0.2, 5.8 ± 0.3, 11.6 ± 1.2 and 5.9 ± 0.4 mM (mean ± standard deviation), respectively. Their respective mean within-session CVs were 14.5% ± 5.9%, 6.5% ± 5.3%, 6.0% ± 3.4%, 10.6% ± 6.2% and 3.5% ± 1.4%, and their mean within-subject CVs were 17.8% ± 18.2%, 7.5% ± 6.3%, 7.4% ± 6.4%, 12.4% ± 5.3% and 4.8% ± 3.0%. The between-subject CVs were 25.0%, 12.3%, 5.3%, 10.7% and 6.4%, respectively. Hippocampal long-TE sLASER single voxel spectroscopy can provide macromolecule-independent assessment of all major metabolites including Glx and m-Ins.

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.

The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ([Formula: see text]H) and sodium ([Formula: see text]) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intracellular sodium concentration ([Formula: see text]), extracellular volume fraction (ECV) and the water fraction (WF) based on a three-compartment model of the tissue. TSC is measured from [Formula: see text] MRI, ECV is calculated from baseline and post-contrast [Formula: see text]H [Formula: see text] maps, while WF is measured with a [Formula: see text]H chemical shift technique. [Formula: see text] is then extrapolated from the model. Proof-of-concept was demonstrated in three healthy subjects and two patients with triple negative breast cancer. In both patients, TSC was two to threefold higher in the tumor than in normal tissue. This alteration mainly resulted from increased [Formula: see text] ([Formula: see text] 30 mM), which was [Formula: see text] 130% greater than in healthy conditions (10-15 mM) while the ECV was within the expected range of physiological values (0.2-0.25). Multinuclear MRI shows promise for disentangling [Formula: see text] and ECV by taking advantage of complementary [Formula: see text]H and [Formula: see text] measurements.

PURPOSE/OBJECTIVE:Resting state functional magnetic resonance imaging (rsfMRI) is an emerging tool to explore the functional connectivity of different brain regions. We aimed to assess the disruption of functional connectivity of the Default Mode Network (DMN), Dorsal Attention Network(DAN) and Fronto-Parietal Network (FPN) in patients with glial tumors. METHODS:rsfMRI data acquired on 3T-MR of treatment-naive glioma patients prospectively recruited (2015-2019) and matched controls from the 1000 functional-connectomes-project were analyzed using the CONN functional toolbox. Seed-Based Connectivity Analysis (SBCA) and Independent Component Analysis (ICA, with 10 to 100 components) were performed to study reliably the three networks of interest. RESULTS:). For the FPN, increased connectivity was noted in the precuneus, posterior cingulate gyrus, and frontal cortex. No difference in the connectivity of the networks of interest was demonstrated between low- and high-grade gliomas, as well as when stratified by their IDH1-R132H (isocitrate dehydrogenase) mutation status. CONCLUSION/CONCLUSIONS:Altered functional connectivity is reliably found with SBCA and ICA in the DMN, DAN, and FPN in glioma patients, possibly explained by decreased connectivity between the cerebral hemispheres across the corpus callosum due to disruption of the connections.

INTRODUCTION:In numerous countries, large population testing is impossible due to the limited availability of RT-PCR kits and CT-scans. This study aimed to determine a pre-test probability score for SARS-CoV-2 infection. METHODS:This multicenter retrospective study (4 University Hospitals) included patients with clinical suspicion of SARS-CoV-2 infection. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. A pre-test probability score was derived from univariate analyses of clinical and biological variables between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. RESULTS:605 patients were included between March 10th and April 30th, 2020 (200 patients for the training cohort, 405 consecutive patients for the validation cohort). In the multivariate analysis, lymphocyte (<1.3 G/L), eosinophil (<0.06 G/L), basophil (<0.04 G/L) and neutrophil counts (<5 G/L) were associated with high probability of SARS-CoV-2 infection but no clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC = 0.918 (CI: [0.891-0.946]; STD = 0.014) with a Positive Predictive Value of high-probability score of 93% (95%CI: [0.89-0.96]). Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 98% (95%CI: [0.93-0.99]). The performance of the score was stable even during the last period of the study (15-30th April) with more controls than infected patients. CONCLUSIONS:The PARIS score has a good performance to categorize the pre-test probability of SARS-CoV-2 infection based on complete white blood cell count. It could help clinicians adapt testing and for rapid triage of patients before test results.