Avdo Celik

Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T.

Multi-modal MR-PET-EEG data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. The three modalities complement each other well; structural-functional imaging being the domain of MRI, molecular imaging with specific tracers is the strength of PET, and EEG provides a temporal dimension where the other two modalities are weak. The utility of hybrid MR-PET at 3 T in a clinical setting is presented and critically discussed. The potential problems and the putative gains to be accrued from hybrid imaging at 9.4 T, with examples from the human brain, are outlined. Steps on the road to 9.4 T multi-modal MR-PET-EEG are also illustrated. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented, setting the stage for hybrid imaging at ultra-high field. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are presented. Examples of tumour imaging on a 3 T MR-PET system are presented and discussed. Finally, the perspectives for multi-modal imaging are discussed based on two on-going studies, the first comparing MR and PET methods for the measurement of perfusion and the second which looks at tumour delineation based on MRI contrasts but the knowledge of tumour extent is based on simultaneously acquired PET data.

Novel multisection design of anisotropic diffusion phantoms

Diffusion-weighted magnetic resonance imaging provides access to fiber pathways and structural integrity in fibrous tissues such as white matter in the brain. In order to enable better access to the sensitivity of the diffusion indices to the underlying microstructure, it is important to develop artificial model systems that exhibit a well-known structure, on the one hand, but benefit from a reduced complexity on the other hand. In this work, we developed a novel multisection diffusion phantom made of polyethylene fibers tightly wound on an acrylic support. The phantom exhibits three regions with different geometrical configuration of fibers: a region with fibers crossing at right angles, a region with parallel fibers and homogeneous density, and, finally, a region with parallel fibers but with a gradient of fiber density along the axis of symmetry. This gives rise to a gradual change of the degree of anisotropy within the same phantom. In this way, the need to construct several phantoms with different fiber densities is avoided, and one can access different fractional anisotropies in the same experiment under the same physical conditions. The properties of the developed phantom are demonstrated by means of diffusion tensor imaging and diffusion kurtosis imaging. The measurements were performed using a diffusion-weighted spin-echo and a diffusion-weighted stimulated-echo pulse sequence programmed in-house. The influence of the fiber density packing on the diffusion parameters was analyzed. We also demonstrate how the novel phantom can be used for the validation of high angular resolution diffusion imaging data analysis.

EEG acquisition in ultra-high static magnetic fields up to 9.4 T

The simultaneous acquisition of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data has gained momentum in recent years due to the synergistic effects of the two modalities with regard to temporal and spatial resolution. Currently, only EEG-data recorded in fields of up to 7 T have been reported. We investigated the feasibility of recording EEG inside a 9.4 T static magnetic field, specifically to determine whether meaningful EEG information could be recovered from the data after removal of the cardiac-related artefact. EEG-data were recorded reliably and reproducibly at 9.4 T and the cardiac-related artefact increased in amplitude with increasing B0, as expected. Furthermore, we were able to correct for the cardiac-related artefact and identify auditory event related responses at 9.4 T in 75% of subjects using independent component analysis (ICA). Also by means of ICA we detected event related spectral perturbations (ERSP) in subjects at 9.4 T in response to opening/closing the eyes comparable with the response at 0 T. Overall our results suggest that it is possible to record meaningful EEG data at ultra-high magnetic fields. The simultaneous EEG-fMRI approach at ultra-high-fields opens up the horizon for investigating brain dynamics at a superb spatial resolution and a temporal resolution in the millisecond domain.

Mapping tissue sodium concentration in the human brain: A comparison of MR sequences at 9.4 Tesla

Sodium is the second most abundant MR-active nucleus in the human body and is of fundamental importance for the function of cells. Previous studies have shown that many pathophysiological conditions induce an increase of the average tissue sodium concentration. To date, several MR sequences have been used to measure sodium. The aim of this study was to evaluate the performance and suitability of five different MR sequences for quantitative sodium imaging on a whole-body 9.4Tesla MR scanner. Numerical simulations, phantom experiments and in vivo imaging on healthy subjects were carried out. The results demonstrate that, of these five sequences, the Twisted Projection Imaging sequence is optimal for quantitative sodium imaging, as it combines a number of features which are particularly relevant in order to obtain high quality quantitative images of sodium. These include: ultra-short echo times, efficient k-space sampling, and robustness against off-resonance effects. Mapping of sodium in the human brain is a technique not yet fully explored in neuroscience. Ultra-high field sodium MRI may provide new insights into the pathogenesis of neurological disorders, and may help to develop new and disease-specific biomarkers for the early diagnosis and therapeutic intervention before irreversible brain damage has taken place.

Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas Using Ex vivo Diffusion MRI and Its Validation

Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.

B0 insensitive multiple-quantum resolved sodium imaging using a phase-rotation scheme.

Triple-quantum filtering has been suggested as a mechanism to differentiate signals from different physiological compartments. However, the filtering method is sensitive to static field inhomogeneities because different coherence pathways may interfere destructively. Previously suggested methods employed additional phase-cycles to separately acquire pathways. Whilst this removes the signal dropouts, it reduces the signal-to-noise per unit time. In this work we suggest the use of a phase-rotation scheme to simultaneously acquire all coherence pathways and then separate them via Fourier transform. Hence the method yields single-, double- and triple-quantum filtered images. The phase-rotation requires a minimum of 36 instead of six cycling steps. However, destructive interference is circumvented whilst maintaining full signal-to-noise efficiency for all coherences.

[18F]Altanserin and small animal PET: Impact of multidrug efflux transporters on ligand brain uptake and subsequent quantification of 5-HT2A receptor densities in the rat brain☆

INTRODUCTION The selective 5-hydroxytryptamine type 2a receptor (5-HT(2A)R) radiotracer [(18)F]altanserin is a promising ligand for in vivo brain imaging in rodents. However, [(18)F]altanserin is a substrate of P-glycoprotein (P-gp) in rats. Its applicability might therefore be constrained by both a differential expression of P-gp under pathological conditions, e.g. epilepsy, and its relatively low cerebral uptake. The aim of the present study was therefore twofold: (i) to investigate whether inhibition of multidrug transporters (MDT) is suitable to enhance the cerebral uptake of [(18)F]altanserin in vivo and (ii) to test different pharmacokinetic, particularly reference tissue-based models for exact quantification of 5-HT(2A)R densities in the rat brain. METHODS Eighteen Sprague-Dawley rats, either treated with the MDT inhibitor cyclosporine A (CsA, 50 mg/kg, n=8) or vehicle (n=10) underwent 180-min PET scans with arterial blood sampling. Kinetic analyses of tissue time-activity curves (TACs) were performed to validate invasive and non-invasive pharmacokinetic models. RESULTS CsA application lead to a two- to threefold increase of [(18)F]altanserin uptake in different brain regions and showed a trend toward higher binding potentials (BP(ND)) of the radioligand. CONCLUSIONS MDT inhibition led to an increased cerebral uptake of [(18)F]altanserin but did not improve the reliability of BP(ND) as a non-invasive estimate of 5-HT(2A)R. This finding is most probable caused by the heterogeneous distribution of P-gp in the rat brain and its incomplete blockade in the reference region (cerebellum). Differential MDT expressions in experimental animal models or pathological conditions are therefore likely to influence the applicability of imaging protocols and have to be carefully evaluated.

9.4 T small animal MRI using clinical components for direct translational studies

BackgroundMagnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software.MethodsA small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength.ResultsThe constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained.ConclusionCoupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.