In vivo B 1 + enhancement of calf MRI at 7 T via optimized flexible metasurfaces.

PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.

Acute nicotinamide riboside supplementation increases human cerebral NAD+ levels in vivo.

PURPOSE: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD+) levels in the human brain in vivo by means of downfield proton MRS (DF 1H MRS). METHODS: DF 1H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD+ levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg). Additionally, two more baseline scans were performed following the same paradigm to assess test-retest reliability of the NAD+ levels in the absence of NR. RESULTS: NR supplementation increased mean NAD+ concentration compared to the baseline (0.458 ± 0.053 vs. 0.392 ± 0.058 mM; p < 0.001). The additional two baseline scans demonstrated no differences in mean NAD+ concentrations (0.425 ± 0.118 vs. 0.405 ± 0.082 mM; p = 0.45), and no difference from the first baseline scan (F(2, 16) = 0.907; p = 0.424). CONCLUSION: These preliminary results confirm that acute NR supplementation increases cerebral NAD+ levels in healthy human volunteers and shows the promise of DF 1H MRS utility for robust detection of NAD+ in humans in vivo.

A review of recent developments and applications of high-permittivity dielectric shimming in magnetic resonance.

We present a review outlining the basic mechanism, background, recent technical developments, and clinical applications of aqueous dielectric padding in the field of MRI. Originally meant to be a temporary solution, it has gained traction as an effective method for correcting B1 + inhomogeneities due to the unique properties of the calcium titanate and barium titanate perovskites used. Aqueous dielectric pads have used a variety of high-permittivity materials over the years to improve the quality of MRI acquisitions at 1.5 and 3 T and more recently for 7 T neuroimaging applications. The technical development and assessment of these pads have been advanced by an increased use of mathematical modeling and electromagnetic simulations. These tools have allowed for a more complete understanding of the physical interactions between dielectric pads and the RF coil, making testing and safety assessments more accurate. The ease of use and effectiveness that dielectric pads offer have allowed them to become more commonplace in tackling imaging challenges in more clinically focused environments. More recently, they have seen usage not only in anatomical imaging methods but also in specialized metabolic imaging sequences such as GluCEST and NOEMTR . New colossally high-permittivity materials have been proposed; however, practical utilization has been a continued challenge due to unfavorable frequency dependences as well as safety limitations. A new class of metasurfaces has been under development to address the shortcomings of conventional dielectric padding while also providing increased performance in enhancing MRI images.

Repeatability of Lac+ measurements in healthy human brain at 3 T.

PURPOSE: In vivo quantification of lactate has numerous applications in studying the pathology of both cerebral and musculoskeletal systems. Due to its low concentration (~0.5-1 mM), and overlap with lipid signals, traditional 1H MR spectra acquired in vivo using a small voxel and short echo time often result in an inadequate signal to detect and resolve the lactate peak, especially in healthy human volunteers. METHODS: In this study, using a semi-LASER acquisition with long echo time (TE = 288 ms) and large voxel size (80 × 70 × 20 mm3), we clearly visualize the combined signal of lactate and threonine. Therefore, we call the signal at 1.33 ppm Lac+ and quantify Lac+ concentration from water suppressed spectra in healthy human brains in vivo. Four participants (22-37 years old; mean age = 28 ± 5.4; three male, one female) were scanned on four separate days, and on each day four measurements were taken. Intra-day values are calculated for each participant by comparing the four measurements on a single day. Inter-day values were calculated using the mean intra-day measurements. RESULTS: The mean intra-participant Lac+ concentration, standard deviation (SD), and coefficient of variation (CV) ranged from 0.49 to 0.61 mM, 0.02 to 0.07 mM, and 4% to 13%, respectively, across four volunteers. The inter-participant Lac+ concentration, SD, and CV was 0.53 mM, ±0.06 mM, and 11%. CONCLUSION: Repeatability is shown in Lac+ measurement in healthy human brain using a long echo time semi-LASER sequence with a large voxel in about 3.5 min at 3 T.

Quantification of NAD + T 1 and T 2 relaxation times using downfield 1 H MRS at 7 T in human brain in vivo.

Introduction: The purpose of this study was to use a single-slice spectrally-selective sequence to measure T 1 and T 2 relaxation times of NAD + proton resonances in the downfield 1 H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD + quantification. Methods: Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T 2 relaxation, and saturation recovery data were to measure T 1 relaxation. The downfield acquisition used a spectrally-selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially-selective Shinnar-Le Roux refocusing pulse for localization. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation. Results: The mean ± standard deviation of T 1 relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T 2 relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R 2 of the H2 and H6 T 1 fits were 0.98. The mean R 2 of the H4 proton T 1 fit was 0.96. The mean R 2 of the T 2 fits of the H2 and H4 proton resonances were 0.98, while the mean R 2 of the T 2 fits of the H4 proton was 0.93. The relative uncertainty in NAD + concentration due to relaxation time uncertainty was 8.5%-11%. Conclusion: Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD + T 1 and T 2 relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

Optimization of 1H MR spectroscopy methods for large volume acquisition of low concentration downfield resonances at 3T and 7T.

Purpose: This goal of this study was to optimize spectrally selective 1H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan. Methods: Spectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced. Results: Proposed methods were compared qualitatively to previously-reported techniques at 7T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single slice localization allowed shorter TEs with large volumes, enhancing signal, while low bandwidth slice selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High quality brain spectra of NAD+ and tryptophan are shown in four subjects at 3T. Conclusion: Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7T. These methodological improvements allowed for previously unachievable detection of NAD+ and tryptophan in human brain at 3T in under five minutes.

Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

Personalized and muscle-specific OXPHOS measurement with integrated CrCEST MRI and proton MR spectroscopy.

Creatine chemical exchange saturation transfer (CrCEST) MRI is an emerging high resolution and noninvasive method for measuring muscle specific oxidative phosphorylation (OXPHOS). However, CrCEST measurements are sensitive to changes in muscle pH, which might confound the measurement and interpretation of creatine recovery time (τCr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τCr is expected to vary between individuals. To address this issue, a method to measure pH pre- and post-exercise and its impact on CrCEST MRI with high temporal resolution is needed. In this work, we integrate carnosine 1H- magnetic resonance spectroscopy (MRS) and 3D CrCEST to establish "mild" and "moderate/intense" exercise stimuli. We then test the dependence of CrCEST recovery time on pH using different exercise stimuli. This comprehensive metabolic imaging protocol will enable personalized, muscle specific OXPHOS measurements in both healthy aging and myriad other disease states impacting muscle mitochondria.

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle.

INTRODUCTION: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS: Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS: Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS: Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.