Quantitative methods in high field MRI

The increased signal-to-noise ratio available at high magnetic field makes possible the acquisition of clinically useful MR images either at higher resolution or for quantitative methods. The work in this thesis is focused on the development of quantitative imaging methods used to overcome difficulties due to high field MRI systems (> 3T). The protocols developed and presented here have been tested on various studies aiming at discriminating tissues based on their NMR properties. The quantities of interest in this thesis are the longitudinal relaxation time T1, as well as the magnetization transfer process, particularly the chemical exchange phenomenon involving amide protons which is highlighted particularly well at 7T under specific conditions. Both quantities (T1 and amide proton transfer) are related to the underlying structure of the tissues in-vivo, especially inside the white matter of the brain. While a standard weighted image at high resolution can provide indices of the extent of the pathology, a robust measure of the NMR properties of brain tissues can detect earlier abnormalities. A method based on a 3D Turbo FLASH readout and measuring reliably the T1 in-vivo for clinical studies at 7T is first presented. The other major part of this thesis presents magnetization transfer and chemical exchange phenomena. First a quantitative method is investigated at 7T, leading to a new model for exchange as well as contrast optimization possibility for imaging. Results using those methods are presented and applied in clinical setting, the main focus being to image reliably the brain of both healthy subjects and Multiple Sclerosis patients to look at myelin structures

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

Earthworms mitigate pesticide effects on soil microbial activities

Earthworms act synergistically with microorganisms in soils. They are ecosystem engineers involved in soil organic matter degradation and nutrient cycling, leading to the modulation of resource availability for all soil organisms. Using a soil microcosm approach, we aimed to assess the influence of the earthworm Aporrectodea caliginosa on the response of soil microbial activities against two fungicides, i.e. Cuprafor micro® (copper oxychloride, a metal) and Swing® Gold (epoxiconazole and dimoxystrobin, synthetic organic compounds). The potential nitrification activity (PNA) and soil enzyme activities (glucosidase, phosphatase, arylamidase, and urease) involved in biogeochemical cycling were measured at the end of the incubation period, together with earthworm biomass. Two common indices of the soil biochemistry were used to aggregate the response of the soil microbial functioning: the geometric mean (Gmean) and the Soil Quality Index (SQI). At the end of the experiment, the earthworm biomass was not impacted by the fungicide treatments. Overall, in the earthworm-free soil microcosms, the two fungicides significantly increased several soil enzyme and nitrification activities, leading to a higher GMean Index as compared to the non-treated control soils. The microbial activity responses depended on the type of activity (nitrification was the most sensitive one), on the fungicide (Swing® Gold or Cuprafor micro®), and on the doses. The SQI indices revealed higher effects of both fungicides on the soil microbial activity in the absence of earthworms. The presence of earthworms enhanced all soil microbial activities in both the control and fungicide-contaminated soils. Moreover, the magnitude of the fungicide impact, integrated through the SQI index, was mitigated by the presence of earthworms, conferring a higher stability of microbial functional diversity. Our results highlight the importance of biotic interactions in the response of indicators of soil functioning (i.e., microbial activity) to pesticides

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, -1.7ppm 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 -3.5ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra

Mapping data elements to terminological resources for integrating biomedical data sources

BACKGROUND: Data integration is a crucial task in the biomedical domain and integrating data sources is one approach to integrating data. Data elements (DEs) in particular play an important role in data integration. We combine schema- and instance-based approaches to mapping DEs to terminological resources in order to facilitate data sources integration. METHODS: We extracted DEs from eleven disparate biomedical sources. We compared these DEs to concepts and/or terms in biomedical controlled vocabularies and to reference DEs. We also exploited DE values to disambiguate underspecified DEs and to identify additional mappings. RESULTS: 82.5% of the 474 DEs studied are mapped to entries of a terminological resource and 74.7% of the whole set can be associated with reference DEs. Only 6.6% of the DEs had values that could be semantically typed. CONCLUSION: Our study suggests that the integration of biomedical sources can be achieved automatically with limited precision and largely facilitated by mapping DEs to terminological resources

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

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

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 7T 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 7T 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