Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

BACKGROUND: Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. METHODS: Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. RESULTS: Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. CONCLUSIONS: Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

Natalizumab Treatment for Relapsing Multiple Sclerosis Stabilises Normal-Appearing White Matter Microstructure: A One-Year Prospective Ultra-High-Field Quantitative Imaging Study.

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing-remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment.

Measuring chemical exchange saturation transfer exchange rates in the human brain using a particle swarm optimisation algorithm.

The z-spectrum contains many pools with different exchange rates and T2 values, which can make it difficult to interpret in vivo data and complicates the design of experiments aimed at providing sensitivity to one pool. This work aims to characterise the main pools observable with MRI at 7T in the human brain. To achieve this, we acquired z-spectra at multiple saturation powers in the human brain at 7T. We used simulations to optimise the use of particle swarm optimisation (PSO) to fit these data, validating this approach using further simulations and creatine phantoms. We then used the PSO to fit data from grey and white matter for the pool size, exchange rate, and T2 of five proton pools (magnetisation transfer, amides, amines, nuclear Overhauser enhancement NOE-3.5ppm and NOE-1.7ppm in addition to water). We then devised an approach for using PSO to fit z-spectra while limiting the computational burden, and we investigated the sensitivity of the fit to T2 and k for three overlapping pools. We used this to measure the exchange rate of creatine and to show that it varied with temperature, as expected. In the brain we measured a significantly larger pool size in white matter than in grey matter for the magnetisation transfer pool and the NOE-3.5ppm pool. For all other parameters we found no significant difference between grey and white matter. We showed that PSO can be used to fit z-spectra acquired at a range of B1 to provide information about peak position, amplitude, exchange rate, and T2 in vivo in the human brain. These data could provide more sensitivity to change in some clinical conditions and will also provide key information for further experimental design.

Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis.

BACKGROUND: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. OBJECTIVE: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. METHODS: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. RESULTS: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1-3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. CONCLUSION: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS.

Quantitative T1 mapping using multi-slice multi-shot inversion recovery EPI.

An efficient multi-slice inversion-recovery EPI (MS-IR-EPI) sequence for fast, high spatial resolution, quantitative T1 mapping is presented, using a segmented simultaneous multi-slice acquisition, combined with slice order shifting across multiple acquisitions. The segmented acquisition minimises the effective TE and readout duration compared to a single-shot EPI scheme, reducing geometric distortions to provide high quality T1 maps with a narrow point-spread function. The precision and repeatability of MS-IR-EPI T1 measurements are assessed using both T1-calibrated and T2-calibrated ISMRM/NIST phantom spheres at 3 and 7 T and compared with single slice IR and MP2RAGE methods. Magnetization transfer (MT) effects of the spectrally-selective fat-suppression (FS) pulses required for in vivo imaging are shown to shorten the measured in-vivo T1 values. We model the effect of these fat suppression pulses on T1 measurements and show that the model can remove their MT contribution from the measured T1, thus providing accurate T1 quantification. High spatial resolution T1 maps of the human brain generated with MS-IR-EPI at 7 T are compared with those generated with the widely implemented MP2RAGE sequence. Our MS-IR-EPI sequence provides high SNR per unit time and sharper T1 maps than MP2RAGE, demonstrating the potential for ultra-high resolution T1 mapping and the improved discrimination of functionally relevant cortical areas in the human brain.

Age-related differences in myeloarchitecture measured at 7 T.

We have used the magnetisation transfer (MT) MRI measure as a primary measure of myelination in both the gray matter (GM) of the 78 cortical automated anatomical labeling (AAL) regions of the brain, and the underlying white matter in each region, in a cohort of healthy adults (aged 19-62 year old). The results revealed a significant quadratic trend in myelination with age, with average global myelination peaking at 42.9 year old in gray matter, and at 41.7 year old in white matter. We also explored the possibility of using the Nuclear Overhauser Enhancement (NOE) effect, which is acquired in a similar method to MT, as an additional measure of myelination. We found that the MT and NOE signals were strongly correlated in the brain and that the NOE effects displayed similar (albeit weaker) parabolic trends with age. We also investigated differences in cortical thickness with age, and confirmed a previous result of a linear decline of 4.5 ± 1.2 µm/y.

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: Results from the UK7T study.

INTRODUCTION: We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's "Travelling Heads" study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5-3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. METHODS: Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. RESULTS AND DISCUSSION: Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001-0.005 ppm (χ) and 0.0005-0.001 ms-1 (R2*). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. CONCLUSION: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

Multi-site harmonization of 7 tesla MRI neuroimaging protocols.

Increasing numbers of 7 T (7 T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7 T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7 T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7 T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described.

Reduced Myelin Signal in Normal-appearing White Matter in Neuromyelitis Optica Measured by 7T Magnetic Resonance Imaging.

Whether the integrity of normal-appearing white matter (NAWM) is preserved in neuromyelitis optica spectrum disorders (NMOSD) is open to debate. To examine whether the tissue integrity of NAWM in NMOSD is compromised compared to that in healthy controls and patients with multiple sclerosis (MS), we prospectively enrolled 14 patients with NMOSD, 12 patients with MS, and 10 controls for clinical functional assessments and quantitative imaging, including T1 relaxation time (T1) and magnetization transfer ratio (MTR) at 7 Tesla. Cognitive performance on the Paced Auditory Serial Addition Test with a 3-second interstimulus interval (PASAT-3) was significantly lower in the NMOSD compared to the MS group (mean number of correct answers, 34.1 vs. 47.6; p = 0.006), but there were no differences in disease duration or disability. Histograms of T1 and MTR maps of NAWM demonstrated a decreased peak height in patients with NMOSD compared to the healthy controls, but not compared to patients with MS. Using 7T quantitative magnetic resonance imaging (MRI), this study showed that the NAWM in patients with NMOSD is abnormal, with reduced myelin signal; this was not previously observed using MRI at a lower field strength.

Phase enhanced PSIR T1 weighted imaging improves contrast resolution of the nucleus basalis of Meynert at 7 T: a preliminary study.

BACKGROUND: The nucleus basalis of Meynert (NBM) provides the majority of cortical cholinergic innervation which is required for memory formation, maintaining attention and promoting learning. Neuronal loss within this area is implicated in a number of neurodegenerative disorders. Imaging the NBM is however limited by its small size and suboptimal contrast resolution at the base of the brain. PURPOSE: To develop a novel method of processing T1 weighted MRI data for improving contrast resolution and delineation of the NBM. STUDY TYPE: Technical development, case series. SUBJECTS: Five healthy volunteers. FIELD STRENGTH, SEQUENCE, ANALYSIS: Volunteers were scanned on a Philips 7 T Achieva imaging system. T1-weighted images were constructed from a double inversion phase sensitive inversion recovery (PSIR) sequence. Inversion recovery data were combined with the filtered phase data from the long inversion time image to produce a novel susceptibility weighted-PSIR (SW-PSIR) map. This process is similar to that used to combine T2* weighted image and phase maps to create susceptibility weighted images (SWI), but with the processing parameters optimized in terms of contrast-to-noise ratio to the NBM in the final SW-PSIR maps. Average NBM thickness was reported as mean ±â€¯standard deviation (SD). Intra-observer and inter-observer reliability were tested using intra-class correlation coefficient (ICC). RESULTS: 0.7mm3 isotropic resolution images were acquired in a 5 min and 50 s scan. The mean thickness ±â€¯SD of the left (right) NBM was 3.5 ±â€¯0.4 mm and 3.8 ±â€¯0.5 mm (3.6 ±â€¯0.5 mm and 3.7 ±â€¯0.5 mm) by the first and second observers respectively with excellent intra-observer and inter-observer agreement (>0.90). CONCLUSION: In this pilot study the SW-PSIR imaging approach improves delineation of the NBM between the ventral pallidum and chiasmatic cistern allowing accurate thickness measurement. The role of this sequence, in enabling robust morphometry of the NBM in health and disease, can be tested further in larger studies.

Aberrant myelination of the cingulum and Schneiderian delusions in schizophrenia: a 7T magnetization transfer study.

BACKGROUND: The structural integrity of the anterior cingulum has been repeatedly observed to be abnormal in patients with schizophrenia. More recently, aberrant myelination of frontal fasciculi, especially, cingulum has been proposed to underlie delayed corollary discharges that can affect sense of agency and contribute to delusions of control (Schneiderian delusions). Using the magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated the putative myelin content of cingulum bundle in patients with schizophrenia. METHODS: Seventeen clinically stable patients with schizophrenia and 20 controls were recruited for this 7T MRI study. We used a region-of-interest method and extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum bundles and estimated patients v. controls differences. We also related the cingulum MTR values to the severity of Schneiderian delusions. RESULTS: Patients had a significant reduction in the MTR, indicating reduced myelin content, in the cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The reduced MTR of left cingulum was associated with higher severity of Schneiderian delusions (τ = -0.45, p = 0.026) but no such relationship was seen for the right cingulum MTR (τ = -0.136, p = 0.50) among patients. The association between the left cingulum MTR and Schneiderian delusions was not explained by the presence of other delusions, hallucinations, disorganization or negative symptoms. CONCLUSIONS: Dysmyelination of the cingulum bundle is seen in a subgroup of patients with schizophrenia and may be involved in the mechanism of Schneiderian delusions.

Is Human Auditory Cortex Organization Compatible With the Monkey Model? Contrary Evidence From Ultra-High-Field Functional and Structural MRI.

It is commonly assumed that the human auditory cortex is organized similarly to that of macaque monkeys, where the primary region, or "core," is elongated parallel to the tonotopic axis (main direction of tonotopic gradients), and subdivided across this axis into up to 3 distinct areas (A1, R, and RT), with separate, mirror-symmetric tonotopic gradients. This assumption, however, has not been tested until now. Here, we used high-resolution ultra-high-field (7 T) magnetic resonance imaging (MRI) to delineate the human core and map tonotopy in 24 individual hemispheres. In each hemisphere, we assessed tonotopic gradients using principled, quantitative analysis methods, and delineated the core using 2 independent (functional and structural) MRI criteria. Our results indicate that, contrary to macaques, the human core is elongated perpendicular rather than parallel to the main tonotopic axis, and that this axis contains no more than 2 mirror-reversed gradients within the core region. Previously suggested homologies between these gradients and areas A1 and R in macaques were not supported. Our findings suggest fundamental differences in auditory cortex organization between humans and macaques.

Parkinson's disease related signal change in the nigrosomes 1-5 and the substantia nigra using T2* weighted 7T MRI.

Improved markers for the progression of Parkinson's disease (PD) are required. Previous work has proven that iron dependent MRI scans can detect the largest Nigrosome (N1) within the substantia nigra (SN) pars compacta and changes in PD. Histopathological studies have shown that N1 is particularly affected in early PD whereas the other nigrosomes (N2-N5) and the surrounding iron-rich SN are affected later. In this study we aimed to determine whether MRI can detect the smaller nigrosomes (N2-N5) and whether graded signal alterations can be detected on T2*-weighted MRI at different disease stages consistent with histopathological changes. An observational prospective study was performed within the research imaging centre at the University of Nottingham, UK. Altogether 26 individuals with confirmed PD (median Hoehn&Yahr stage = 1, Unified PD Rating Scale [UPDRS] = 12.5) and 15 healthy controls participated. High resolution T2*weighted 7T MRI of the brain was performed and visibility of N1-N5 within the SN was qualitatively rated. Normalised T2*weighted signal intensities in manually segmented N1-N5 regions and iron-rich SN were calculated. We performed group comparisons and correlations with severity based on UPDRS. Qualitative measures were a nigrosome visibility score and a confidence score for identification. Quantitative measures were T2*weighted contrast of N1-5 and iron-rich SN relative to white matter. We found that visual assessment of the SN for N1-N5 revealed normal range visibility scores in 14 of 15 controls. N1 was identified with the highest confidence and visibility was in abnormal range in all 26 PD patients. The other nigrosomes were less well visible and less confidently identified. There was a larger PD induced signal reduction in all nigrosomes than in the iron-rich SN (median signal difference N1-5 PD compared to controls: 19.4% [IQR = 24%], iron-rich SN 11% [IQR = 24%, p = 0.017]). The largest PD induced signal reduction was in N1: 37.2% [IQR = 19%] which inversely correlated with UPDRS in PD (R2 = 0.19). All nigrosomes can be detected using 7T MRI, and PD induced T2*weighted signal reduction was greatest in the nigrosomes (especially N1). The graded T2*weighted signal alterations in the nigrosomes match previously described differential histopathological effects of PD. N1 was identified with the highest confidence and T2*weighted signal in N1 correlated with UPDRS confirming N1 as the most promising SN marker of PD pathology.

Seven-Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization-transfer-weighted (MTw ) images in the detection of white matter lesions compared with 3T-FLAIR. METHODS: Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3-dimensional (D) MTw and 3T-2D-FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated. RESULTS: Of 662 lesions identified on 3T-2D-FLAIR images, 652 were detected on 7T-3D-MTw images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T-3D-MTw images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T-2D-FLAIR images (ICC 96.1% and 96.7%). CONCLUSION: Seven-Tesla MTw sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T-MTw imaging is a robust alternative for detecting demyelinating lesions in addition to 3T-FLAIR. Future studies need to compare the roles of optimized 7T-FLAIR and of 7T-MTw imaging.

The z-spectrum from human blood at 7T.

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7 ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5 ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra.

Comparison of pulsed three-dimensional CEST acquisition schemes at 7 tesla: steady state versus pseudosteady state.

PURPOSE: To compare two pulsed, volumetric chemical exchange saturation transfer (CEST) acquisition schemes: steady state (SS) and pseudosteady state (PS) for the same brain coverage, spatial/spectral resolution and scan time. METHODS: Both schemes were optimized for maximum sensitivity to amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects through Bloch-McConnell simulations, and compared in terms of sensitivity to APT and NOE effects, and to transmit field inhomogeneity. Five consented healthy volunteers were scanned on a 7 Tesla Philips MR-system using the optimized protocols at three nominal B1 amplitudes: 1 µT, 2 µT, and 3 µT. RESULTS: Region of interest based analysis revealed that PS is more sensitive (P < 0.05) to APT and NOE effects compared with SS at low B1 amplitudes (0.7-1.0 µT). Also, both sequences have similar dependence on the transmit field inhomogeneity. For the optimum CEST presaturation parameters (1 µT and 2 µT for APT and NOE, respectively), NOE is less sensitive to the inhomogeneity effects (15% signal to noise ratio [SNR] change for a B1 dropout of 40%) compared with APT (35% SNR change for a B1 dropout of 40%). CONCLUSION: For the same brain coverage, spatial/spectral resolution and scan time, at low power levels PS is more sensitive to the slow chemical exchange-mediated processes compared with SS. Magn Reson Med 77:2280-2287, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Quantitative analysis of the z-spectrum using a numerically simulated look-up table: Application to the healthy human brain at 7T.

PURPOSE: To develop a method that fits a multipool model to z-spectra acquired from non-steady state sequences, taking into account the effects of variations in T1 or B1 amplitude and the results estimating the parameters for a four-pool model to describe the z-spectrum from the healthy brain. METHODS: We compared measured spectra with a look-up table (LUT) of possible spectra and investigated the potential advantages of simultaneously considering spectra acquired at different saturation powers (coupled spectra) to provide sensitivity to a range of different physicochemical phenomena. RESULTS: The LUT method provided reproducible results in healthy controls. The average values of the macromolecular pool sizes measured in white matter (WM) and gray matter (GM) of 10 healthy volunteers were 8.9% ± 0.3% (intersubject standard deviation) and 4.4% ± 0.4%, respectively, whereas the average nuclear Overhauser effect pool sizes in WM and GM were 5% ± 0.1% and 3% ± 0.1%, respectively, and average amide proton transfer pool sizes in WM and GM were 0.21% ± 0.03% and 0.20% ± 0.02%, respectively. CONCLUSIONS: The proposed method demonstrated increased robustness when compared with existing methods (such as Lorentzian fitting and asymmetry analysis) while yielding fully quantitative results. The method can be adjusted to measure other parameters relevant to the z-spectrum. Magn Reson Med 78:645-655, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Relationships between cortical myeloarchitecture and electrophysiological networks.

The human brain relies upon the dynamic formation and dissolution of a hierarchy of functional networks to support ongoing cognition. However, how functional connectivities underlying such networks are supported by cortical microstructure remains poorly understood. Recent animal work has demonstrated that electrical activity promotes myelination. Inspired by this, we test a hypothesis that gray-matter myelin is related to electrophysiological connectivity. Using ultra-high field MRI and the principle of structural covariance, we derive a structural network showing how myelin density differs across cortical regions and how separate regions can exhibit similar myeloarchitecture. Building upon recent evidence that neural oscillations mediate connectivity, we use magnetoencephalography to elucidate networks that represent the major electrophysiological pathways of communication in the brain. Finally, we show that a significant relationship exists between our functional and structural networks; this relationship differs as a function of neural oscillatory frequency and becomes stronger when integrating oscillations over frequency bands. Our study sheds light on the way in which cortical microstructure supports functional networks. Further, it paves the way for future investigations of the gray-matter structure/function relationship and its breakdown in pathology.

Imaging gray matter with concomitant null point imaging from the phase sensitive inversion recovery sequence.

PURPOSE: To present an improved three-dimensional (3D) interleaved phase sensitive inversion recovery (PSIR) sequence including a concomitantly acquired new contrast, null point imaging (NPI), to help detect and classify abnormalities in cortical gray matter. METHODS: The 3D gradient echo PSIR images were acquired at 0.6 mm isotropic resolution on 11 multiple sclerosis (MS) patients and 9 controls subjects using a 7 Tesla (T) MRI scanner, and 2 MS patients at 3T. Cortical abnormalities were delineated on the NPI/PSIR data and later classified according to position in the cortex. RESULTS: The NPI helped detect cortical lesions within the cortical ribbon with increased, positive contrast compared with the PSIR. It also provided improved intrinsic delineation of the ribbon, increasing confidence in classifying the lesions' locations. CONCLUSION: The proposed PSIR facilitates the classification of cortical lesions by providing two T1 -weighted 3D datasets with isotropic resolution, including the NPI showing cortical lesions with clear delineation of the gray/white matter boundary and minimal partial volume effects. Magn Reson Med 76:1512-1516, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.