Proton Free Induction Decay MRSI at 7T in the Human Brain Using an Egg-Shaped Modified Rosette K-Space Trajectory.

Purpose: 1.1 Proton ( 1 H)-MRSI via spatial-spectral encoding poses high demands on gradient hardware at ultra-high fields and high-resolutions. Rosette trajectories help alleviate these problems, but at reduced SNR-efficiency due to their k-space densities not matching any desired k-space filter. We propose modified rosette trajectories, which more closely match a Hamming filter, and thereby improve SNR performance while still staying within gradient hardware limitations and without prolonging scan time. Methods: 1.2Analytical and synthetic simulations were validated with phantom and in vivo measurements at 7 T. The rosette and modified rosette trajectories were measured in five healthy volunteers in six minutes in a 2D slice in the brain. A 3D sequence was measured in one volunteer within 19 minutes. The SNR, linewidth, CRLBs, lipid contamination and data quality of the proposed modified rosette trajectory were compared to the rosette trajectory. Results: 1.3Using the modified rosette trajectories, an improved k-space weighting function was achieved resulting in an increase of up to 12% in SNR compared to rosette's dependent on the two additional trajectory parameters. Similar results were achieved for the theoretical SNR calculation based on k-space densities, as well as when using the pseudo-replica method for simulated, in-vivo and phantom data. The CRLBs improved slightly, but non-significantly for the modified rosette trajectories, while the linewidths and lipid contamination remained similar. Conclusion: 1.4By improving the rosette trajectory's shape, modified rosette trajectories achieved higher SNR at the same scan time and data quality.

A Comparison of 7 Tesla MR Spectroscopic Imaging and 3 Tesla MR Fingerprinting for Tumor Localization in Glioma Patients.

This paper investigated the correlation between magnetic resonance spectroscopic imaging (MRSI) and magnetic resonance fingerprinting (MRF) in glioma patients by comparing neuro-oncological markers obtained from MRSI to T1/T2 maps from MRF. Data from 12 consenting patients with gliomas were analyzed by defining hotspots for T1, T2, and various metabolic ratios, and comparing them using Sørensen-Dice similarity coefficients (DSCs) and the distances between their centers of intensity (COIDs). The median DSCs between MRF and the tumor segmentation were 0.73 (T1) and 0.79 (T2). The DSCs between MRSI and MRF were the highest for Gln/tNAA (T1: 0.75, T2: 0.80, tumor: 0.78), followed by Gly/tNAA (T1: 0.57, T2: 0.62, tumor: 0.54) and tCho/tNAA (T1: 0.61, T2: 0.58, tumor: 0.45). The median values in the tumor hotspot were T1 = 1724 ms, T2 = 86 ms, Gln/tNAA = 0.61, Gly/tNAA = 0.28, Ins/tNAA = 1.15, and tCho/tNAA = 0.48, and, in the peritumoral region, were T1 = 1756 ms, T2 = 102 ms, Gln/tNAA = 0.38, Gly/tNAA = 0.20, Ins/tNAA = 1.06, and tCho/tNAA = 0.38, and, in the NAWM, were T1 = 950 ms, T2 = 43 ms, Gln/tNAA = 0.16, Gly/tNAA = 0.07, Ins/tNAA = 0.54, and tCho/tNAA = 0.20. The results of this study constitute the first comparison of 7T MRSI and 3T MRF, showing a good correspondence between these methods.

Predicting dynamic, motion-related changes in B0 field in the brain at a 7T MRI using a subject-specific fine-trained U-net.

PURPOSE: Subject movement during the MR examination is inevitable and causes not only image artifacts but also deteriorates the homogeneity of the main magnetic field (B0 ), which is a prerequisite for high quality data. Thus, characterization of changes to B0 , for example induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. METHODS: We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo gradient-echo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-trained the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. RESULTS: Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. CONCLUSION: It is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of MR acquisitions without the use of navigators.

Implementation of a 7T Epilepsy Task Force consensus imaging protocol for routine presurgical epilepsy work-up: effect on diagnostic yield and lesion delineation.

OBJECTIVE: Recently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy. METHODS: The 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI. RESULTS: Of 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T. CONCLUSIONS: The diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.

Current Aspects of Intraoperative High-Field (3T) Magnetic Resonance Imaging in Pediatric Neurosurgery: Experiences from a Recently Launched Unit at a Tertiary Referral Center.

OBJECTIVE: To evaluate the neurosurgical and economic effectiveness of a newly launched intraoperative high-field (3T) magnetic resonance imaging (MRI) suite for pediatric tumor and epilepsy neurosurgery. METHODS: Altogether, 148 procedures for 124 pediatric patients (mean age, 8.7 years; range, 0-18 years) within a 2.5-year period were undertaken in a 2-room intraoperative MRI (iopMRI) suite. Surgery was performed mainly for intractable epilepsy (n = 81; 55%) or pediatric brain tumors (n = 65; 44%) in the supine (n = 113; 76%) and prone (n = 35; 24%) positions. The mean time of iopMRI from draping to re-surgery was 50 minutes. RESULTS: IopMRI was applied not in all but in 64 of 148 procedures (43%); in 45 procedures (31%), iopMRI was estimated unnecessary at the end of surgery based on the leading surgeon's decision. In the remaining 39 procedures (26%), ultra-early postoperative MRI was carried out after closure with the patient still sterile in the head coil. Of the 64 procedures with iopMRI, second-look surgery was performed in 26% (in epilepsy surgery in 17%, in tumor surgery in 9%). We did not encounter any infections, wound revisions, or position-related or anesthesiology-related complications. CONCLUSIONS: We used iopMRI in less than half of pediatric tumor and epilepsy surgery for which it was scheduled initially. Therefore, high costs argue against its routine use in pediatric neurosurgery, although it optimized surgical results in one quarter of patients and met high safety standards.

Metabolic Insights into Iron Deposition in Relapsing-Remitting Multiple Sclerosis via 7 T Magnetic Resonance Spectroscopic Imaging.

OBJECTIVE: To investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis (MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesions in vivo according to iron deposition. METHODS: 7 T MR spectroscopic imaging and susceptibility-weighted imaging was performed in 31 patients with relapsing-remitting MS (16 female/15 male; mean age, 36.9 ± 10.3 years). Mean metabolic ratios of four neuro-metabolites were calculated for regions of interest (ROI) of normal appearing white matter (NAWM), "non-iron" (lesion without iron accumulation on SWI), and three distinct types of iron-laden lesions ("rim": distinct rim-shaped iron accumulation; "area": iron deposition across the entire lesions; "transition": transition between "area" and "rim" accumulation shape), and for lesion layers of "non-iron" and "rim" lesions. Furthermore, newly emerging "non-iron" and "iron" lesions were compared longitudinally, as measured before their appearance and one year later. RESULTS: Thirty-nine of 75 iron-containing lesions showed no distinct paramagnetic rim. Of these, "area" lesions exhibited a 65% higher mIns/tNAA (p = 0.035) than "rim" lesions. Comparing lesion layers of both "non-iron" and "rim" lesions, a steeper metabolic gradient of mIns/tNAA ("non-iron" +15%, "rim" +40%) and tNAA/tCr ("non-iron" -15%, "rim" -35%) was found in "iron" lesions, with the lesion core showing +22% higher mIns/tNAA (p = 0.005) and -23% lower tNAA/tCr (p = 0.048) in "iron" compared to "non-iron" lesions. In newly emerging lesions, 18 of 39 showed iron accumulation, with the drop in tNAA/tCr after lesion formation remaining significantly lower compared to pre-lesional tissue over time in "iron" lesions (year 0: p = 0.013, year 1: p = 0.041) as opposed to "non-iron" lesions (year 0: p = 0.022, year 1: p = 0.231). CONCLUSION: 7 T MRSI allows in vivo characterization of different iron accumulation types each presenting with a distinct metabolic profile. Furthermore, the larger extent of neuronal damage in lesions with a distinct iron rim was reconfirmed via reduced tNAA/tCr concentrations, but with metabolic differences in lesion development between (non)-iron-containing lesions. This highlights the ability of MRSI to further investigate different types of iron accumulation and suggests possible implications for disease monitoring.

Ultrahigh-field MRI: where it really makes a difference.

BACKGROUND: Currently, two major magnetic resonance (MR) vendors provide commercial 7­T scanners that are approved by the Food and Drug Administration (FDA) for clinical application. There is growing interest in ultrahigh-field MRI because of the improved clinical results in terms of morphological detail, as well as functional and metabolic imaging capabilities. MATERIALS AND METHODS: The 7­T systems benefit from a higher signal-to-noise ratio, which scales supralinearly with field strength, a supralinear increase in the blood oxygenation level dependent (BOLD) contrast for functional MRI and susceptibility weighted imaging (SWI), and the chemical shift increases linearly with field strength with consequently higher spectral resolution. RESULTS: In multiple sclerosis (MS), 7­T imaging enables visualization of cortical lesions, the central vein sign, and paramagnetic rim lesions, which may be beneficial for the differential diagnosis between MS and other neuroinflammatory diseases in challenging and inconclusive clinical presentations and are seen as promising biomarkers for prognosis and treatment monitoring. The recent development of high-resolution proton MR spectroscopic imaging in clinically reasonable scan times has provided new insights into tumor metabolism and tumor grading as well as into early metabolic changes that may precede inflammatory processes in MS. This technique also improves the detection of epileptogenic foci in the brain. Multi-nuclear clinical applications, such as sodium imaging, have shown great potential for the evaluation of repair tissue quality after cartilage transplantation and in the monitoring of newly developed cartilage regenerative drugs for osteoarthritis. CONCLUSION: For special clinical applications, such as SWI in MS, MR spectroscopic imaging in tumors, MS and epilepsy, and sodium imaging in cartilage repair, 7T may become a new standard.

Technical Note: Advantages of a 2-Room Intraoperative 3-Tesla Magnetic Resonance Imaging Operating Suite for Performing Laser Interstitial Thermal Therapy in Pediatric Epilepsy and Tumor Surgery.

OBJECTIVE: Magnetic resonance thermography-guided laser interstitial thermal therapy (LITT) provides a minimally invasive treatment option in children with central nervous system tumors or medically intractable epilepsy. However, transporting anesthetized children between an operating room (OR) and a radiologic suite creates logistical challenges. Thus we describe advantages of using a 2-room intraoperative magnetic resonance imaging (MRI) concept for LITT. METHODS: Patients were pinned in a head frame that doubles as the lower part of the MRI head coil. Preoperative MRI was performed for accurate neuronavigation, after which laser fibers were stereotactically implanted. Transport between OR and MRI was achieved by sliding the top of the OR table onto a trolly. RESULTS: We performed 12 procedures in 11 children, mean age 7.1 years (range: 2 to 14 years). Ten children suffered from medically intractable epilepsy, and 1 child had a pilocytic midbrain astrocytoma. Two fibers were placed in 8 and 1 fiber in 4 procedures. Mean entry point and target errors were 2.8 mm and 3.4 mm, respectively. Average transfer time from OR to MRI and vice versa was 9 minutes (±1 minute, 40 seconds). Altogether, 50% of the seizure patients were seizure free (Engel grade I) at 22 months' follow-up time. One hemorrhagic event, which could be managed nonoperatively, occurred. We recorded no surgical site or intracranial infections. CONCLUSIONS: All LITT procedures were successfully carried out with head frame in the sterile environment. The intraoperative MRI suite proved to be advantageous for minimally invasive procedures, especially in young children resulting in short transports while maintaining high accuracy and safety.

Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct (2H) and indirect (1H) detection of deuterium labeled compounds at 7T and clinical 3T.

INTRODUCTION: Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6'-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2H MRSI (DMI) and 1H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. METHODS: Five volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6'-2H2]-glucose administration using time-resolved 3D 2H FID-MRSI with elliptical phase encoding at 7T and 3D 1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. RESULTS: One hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2H DMI and 3T 1H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2H and 1H data points a weak to moderate negative correlation was observed for Glx4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc6 data GM (r=-0.61, p<0.001) and WM (r=-0.70, p<0.001). CONCLUSION: This study demonstrates that indirect detection of deuterium labeled compounds using 1H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.

Evaluation of Gliomas with Magnetic Resonance Fingerprinting with PET Correlation-A Comparative Study.

OBJECTIVES: Advanced MR imaging of brain tumors is still mainly based on qualitative imaging. PET imaging offers additive metabolic information, and MR fingerprinting (MRF) offers a novel approach to quantitative data acquisition. The purpose of this study was to evaluate the ability of MRF to predict tumor regions and grading in combination with PET. METHODS: Seventeen patients with histologically verified infiltrating gliomas and available amino-acid PET data were enrolled. ROIs for solid tumor parts (SPo), perifocal edema (ED1), and normal-appearing white matter (NAWM) were selected on conventional MRI sequences and aligned to the MRF and PET images. The predictability of gliomas by region and grading as well as intermodal correlations were assessed. RESULTS: For MRF, we calculated an overall predictability by region (SPo, ED1, and NAWM) for all of the MRF parameters of 76.5%, 47.1%, and 94.1%, respectively. The overall ability to distinguish low- from high-grade gliomas using MRF was 88.9% for LGG and 75% for HGG, with an accuracy of 82.4%, a ppV of 85.71%, and an npV of 80%. PET positivity was found in 13/17 patients for solid tumor parts, and in 3/17 patients for the edema region. However, there was no significant difference in region-specific MRF values between PET positive and PET negative patients. CONCLUSIONS: MRF and PET provide quantitative measurements of the tumor tissue characteristics of gliomas, with good predictability. Nonetheless, the results are dissimilar, reflecting the different underlying mechanisms of each method.

Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct ( 2 H) and indirect ( 1 H) detection of deuterium labeled compounds at 7T and clinical 3T.

Introduction: Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6'- 2 H 2 ]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2 H MRSI (DMI) and 1 H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. Methods: Five volunteers (4m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8g/kg oral [6,6'- 2 H 2 ]-glucose administration using time-resolved 3D 2 H FID-MRSI with elliptical phase encoding at 7T and 3D 1 H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. Results: One hour after oral tracer administration regionally averaged deuterium labeled Glx 4 concentrations and the dynamics were not significantly different over all participants between 7T 2 H DMI and 3T 1 H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc 6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2 H and 1 H data points a weak to moderate negative correlation was observed for Glx 4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc 6 data GM (r=- 0.61, p<0.001) and WM (r=-0.70, p<0.001). Conclusion: This study demonstrates that indirect detection of deuterium labeled compounds using 1 H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2 H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.

1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain.

Impaired glucose metabolism in the brain has been linked to several neurological disorders. Positron emission tomography and carbon-13 magnetic resonance spectroscopic imaging (MRSI) can be used to quantify the metabolism of glucose, but these methods involve exposure to radiation, cannot quantify downstream metabolism, or have poor spatial resolution. Deuterium MRSI (2H-MRSI) is a non-invasive and safe alternative for the quantification of the metabolism of 2H-labelled substrates such as glucose and their downstream metabolic products, yet it can only measure a limited number of deuterated compounds and requires specialized hardware. Here we show that proton MRSI (1H-MRSI) at 7 T has higher sensitivity, chemical specificity and spatiotemporal resolution than 2H-MRSI. We used 1H-MRSI in five volunteers to differentiate glutamate, glutamine, γ-aminobutyric acid and glucose deuterated at specific molecular positions, and to simultaneously map deuterated and non-deuterated metabolites. 1H-MRSI, which is amenable to clinically available magnetic-resonance hardware, may facilitate the study of glucose metabolism in the brain and its potential roles in neurological disorders.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Noninvasive 3-Dimensional 1 H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T : Feasibility and Interscanner Reproducibility.

OBJECTIVES: Noninvasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies, for example, cancer, dementia, and depression. A novel approach to map glucose metabolism noninvasively in the human brain has been presented recently on ultrahigh-field magnetic resonance (MR) scanners (≥7T) using indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine, and lactate. The aim of this study was to demonstrate the feasibility to noninvasively detect deuterium-labeled downstream glucose metabolites indirectly in the human brain via 3-dimensional (3D) proton ( 1 H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. MATERIALS AND METHODS: This prospective, institutional review board-approved study was performed in 7 healthy volunteers (mean age, 31 ± 4 years, 5 men/2 women) after obtaining written informed consent. After overnight fasting and oral deuterium-labeled glucose administration, 3D metabolic maps were acquired every ∼4 minutes with ∼0.24 mL isotropic spatial resolution using real-time motion-, shim-, and frequency-corrected echo-less 3D 1 H-MR spectroscopic Imaging on a clinical routine 3T MR system. To test the interscanner reproducibility of the method, subjects were remeasured on a similar 3T MR system. Time courses were analyzed using linear regression and nonparametric statistical tests. Deuterium-labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1 H MR spectra due to exchange of labeled and unlabeled molecules. RESULTS: Sixty-five minutes after deuterium-labeled glucose administration, glutamate + glutamine (Glx) signal intensities decreased in gray/white matter (GM/WM) by -1.63 ± 0.3/-1.0 ± 0.3 mM (-13% ± 3%, P = 0.02/-11% ± 3%, P = 0.02), respectively. A moderate to strong negative correlation between Glx and time was observed in GM/WM ( r = -0.64, P < 0.001/ r = -0.54, P < 0.001), with 60% ± 18% ( P = 0.02) steeper slopes in GM versus WM, indicating faster metabolic activity. Other nonlabeled metabolites showed no significant changes. Excellent intrasubject repeatability was observed across scanners for static results at the beginning of the measurement (coefficient of variation 4% ± 4%), whereas differences were observed in individual Glx dynamics, presumably owing to physiological variation of glucose metabolism. CONCLUSION: Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware, offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for noninvasive imaging of glucose and neurotransmitter metabolism in the human brain.

Lesion-Specific Metabolic Alterations in Relapsing-Remitting Multiple Sclerosis Via 7 T Magnetic Resonance Spectroscopic Imaging.

BACKGROUND: Magnetic resonance spectroscopic imaging (MRSI) of the brain enables in vivo assessment of metabolic alterations in multiple sclerosis (MS). This provides complementary insights into lesion pathology that cannot be obtained via T1- and T2-weighted conventional magnetic resonance imaging (cMRI). PURPOSE: The aims of this study were to assess focal metabolic alterations inside and at the periphery of lesions that are visible or invisible on cMRI, and to correlate their metabolic changes with T1 hypointensity and the distance of lesions to cortical gray matter (GM). METHODS: A 7 T MRSI was performed on 51 patients with relapsing-remitting MS (30 female/21 male; mean age, 35.4 ± 9.9 years). Mean metabolic ratios were calculated for segmented regions of interest (ROIs) of normal-appearing white matter, white matter lesions, and focal regions of increased mIns/tNAA invisible on cMRI. A subgroup analysis was performed after subdividing based on T1 relaxation and distance to cortical GM. Metabolite ratios were correlated with T1 and compared between different layers around cMRI-visible lesions. RESULTS: Focal regions of, on average, 2.8-fold higher mIns/tNAA than surrounding normal-appearing white matter and with an appearance similar to that of MS lesions were found, which were not visible on cMRI (ie, ~4% of metabolic hotspots). T1 relaxation was positively correlated with mIns/tNAA ( P ≤ 0.01), and negatively with tNAA/tCr ( P ≤ 0.01) and tCho/tCr ( P ≤ 0.01). mIns/tCr was increased outside lesions, whereas tNAA/tCr distributions resembled macroscopic tissue damage inside the lesions. mIns/tCr was -21% lower for lesions closer to cortical GM ( P ≤ 0.05). CONCLUSIONS: 7 T MRSI allows in vivo visualization of focal MS pathology not visible on cMRI and the assessment of metabolite levels in the lesion center, in the active lesion periphery and in cortical lesions. This demonstrated the potential of MRSI to image mIns as an early biomarker in lesion development.

7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors.

(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.

High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques.

Objective: Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments. Methods: Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics). Results: High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies. Conclusion: Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.