SUMMARY: MR spectroscopy allows insight into the chemical composition of human tissue noninvasively. Thereby it can help to better characterize pathologic processes affecting the spinal cord and may provide important clinical markers for differential diagnosis. However, due to technical challenges, it has been rarely applied to the spinal cord. The aim of this review was to summarize the technical development and clinical studies using MR spectroscopy in the spinal cord. Main challenges of applying MR spectroscopy in the spinal cord are discussed, and a description of a state-of-the-art scan protocol is given. In conclusion, MR spectroscopy is a promising tool for research and diagnosis of the spinal cord because it can provide additional information complementary to other noninvasive imaging methods. However, the application of MR spectroscopy in the spinal cord is not straightforward, and great care is required to attain optimal spectral quality.

Detection of GABA, Aspartate and Glutathione in the Human Spinal Cord Andreas Hock, Bertram Wilm, Giorgia Zandomeneghi, Garyfalia Ampanozi, Sabine Franckenberg, Nicola De Zanche, Jurek Nordmeyer-Maßner, Spyros S. Kollias, Thomas Kraemer, Michael Thali, Matthias Ernst, and Anke Henning Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, Department of Psychiatry, Psychotherapy and Psychosomatics Hospital of Psychiatry, University of Zurich, Zurich, Zurich, Switzerland, Physical Chemistry, ETH Zurich, Zurich, Zurich, Switzerland, Institute of Forensic Medicine, University of Zurich, Zurich, Zurich, Switzerland, Department of Medical Physics, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada, Institute of Neuroradiology, University Hospital of Zurich, Zurich, Zurich, Switzerland, Institute for Biological Cybernetics, Max Planck Institute, Tuebingen, Baden Württemberg, Germany

Background: Interactive, multimodal sensory stimuli and training using virtual reality (VR) allow the investigation of unique neuroscientific questions and clinical applications.

Andreas Hock, Bertram Wilm, Erin L. MacMillan, Roland Kreis, Spyros S Kollias, Peter Boesiger, and Anke Henning Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, Dept. of Clinical Research and Institute of Diagnostic, Interventional and Pediatric Radiology, University of Bern, Bern, Switzerland, Institute of Neuroradiology, University Hospital of Zurich, Zurich, Switzerland, Max Planck Institute for Biological Cybernetics, Tübingen, Germany

before inner-volume saturation (IVS), up-/downfield inversion for the metabolite cycling, and PRESS localization. They consist of a two dimensional selective excitation pulse exciting a pencil beam (r=30mm, l=120mm). Figure 1: Sagittal and axial T2 weighted turbo spinecho images of the cervical spinal cord showing the MRS voxel (red), the navigator (white), the innervolume saturation bands (blue) and the shim box (green).

Introduction: Scyllo-Inositol (sI) is one of the stereoisomers of inositol consisting of six equivalent CH protons yielding a singlet resonance at the chemical shift of 3.35 ppm in MR spectroscopy (H MRS). The function of sI remains uncertain but changes compared to healthy subjects were observed in brain tumors (1), mitochondrial enzyme deficiency (2), chronic alcoholism (3), Alzheimer’s disease (4) and HIV (5) indicating that sI is an important marker in many neurological disorders. This work represents the first report of sI detection in the human spinal cord, which was enabled by non-water suppressed H MRS via metabolite cycling (MC) [6] at 3T. Methods: After approval from the local ethics committee, spinal cord H MRS measurements were performed in 14 subjects (mean age ~28) using nonwater-suppressed H MRS via the inner-volume saturated PRESS localized MC technique (6) at 3T (Achieva, Philips Healthcare, Best, TE/TR = 30/2000 ms, voxel size = 1.2 ml) at the cervical level C3-4 (Fig 1). The MC method enables frequency alignment of each single FID even with the very low SNR available in the spinal cord, which improves the spectral quality (increased SNR and reduced FWHM of the metabolite peaks) and reproducibility of H MRS measurements in the human spinal cord. Second order ECG-triggered FASTERMAP shimming as well as ECG triggering during F0 determination and spectral acquisition was used. One female subject also participated in another study (7) where four healthy volunteers were scanned with a Philips 7T Achieva MR system (Philips Healthcare, Cleveland). In that study, the MRS voxel was placed in the occipital cortex, and SPECIAL (8) localization and VAPOR water suppression was used (TE/TR = 11.8/7000 ms, voxel size = 6.9 ml). This female subject showed a strongly increased sI peak in the spinal cord as well as in the brain. All MRS data were quantified using LCModel (9) and a set of basis spectra simulated including 20 metabolites using GAMMA (10). Results and Discussion: Fig. 1 shows exemplary spectra of a control volunteer (a, c)) and the female volunteer with the increased sI peak (b, d) measured in the spinal cord (3 T) (a, b) and in the occipital cortex (7 T) (c, d). Although, sI is even hardly visible healthy control in Fig 1 c at 7 T, it was possible to identify sI in all 14 healthy subjects in the spinal cord at 3T (Cramer–Rao lower bounds (CRLB) < 25%). In addition, the increased sI resonance in spinal cord (b) and brain spectra (d) from the same female subject supports the assignment of the resonance line detected at 3.35 ppm in the 3 T spinal cord MRS measurements in all volunteers to sI, while a systematic artifact introduced by the MC technique was excluded. Table 1 shows metabolite ratios, standard deviations (SD) and the CRLB of NAA, choline (Cho), myo-Inositol (mI) and sI over Creatine (Cr) of the controls and the volunteer with the increased sI peak in the spinal cord. In addition, the fraction of mI and sI is shown in the last column. Brain sI concentrations measured in controls as published by Griffith et al. (posterior cingulate, grey matter, mean age ~67 Y, 3 T, TE = 32 ms) (4) and Michaelis et al. (cerebellum, white matter, age 18 – 28 Y, 2 T, TE = 20 ms) (2,11) are also displayed in table 1 for comparison. Concentration ratios of mI/Cr and sI/Cr in the spinal cord are higher compared to the brain (2,4,11), although NAA/Cr concentrations are quite similar, which is indicative for a slightly altered metabolism and tissue composition in the spinal cord. In addition, Michaelis et al. (2) noticed a proportionality of mI and sI concentrations of about 12-13 in healthy tissue. Our results in the spinal cord and the data of Griffith et al. (4) support this finding; however, measurements in the volunteer with increased sI shows reduced mI/Cr and increased sI/Cr resulting in a reduced mI/sI ratio of about 4. This may be an indicator of a mutated inositol epimerase. Seaquist and Gruetter (12) also reported an elevation of sI in proton MRS measurements in a healthy man and in this case they reported a reduction of mI/sI ratio to 5. Conclusion: SI was investigated for the first time in spinal cord MRS in vivo. The results show an increased mI/Cr and sI/Cr ratio compared to the brain which might be an indicator of a different metabolism in the spinal cord. This finding may help in better understanding the special tissue characteristics in the spinal cord.

A. Hock, A. Henning, M. Schär, A. Fuchs, S. Kollias, and P. Boesiger University and ETH Zurich, Institute for Biomedical Engineering, Zurich, Switzerland, University Hospital of Zurich, Institute for Biomedical Engineering, Zurich, Switzerland, The Johns Hopkins University School of Medicine, 1Russel H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, United States, Philips Healthcare, Cleveland, OH, United States, University Hospital of Zurich, Institute of Neuroradiology, Zurich, Switzerland

Background Rest tremor is a hallmark of Parkinson’s disease (PD), but its pathogenesis remains incompletely understood. Nigro-striatal dopamine deficiency correlates best with bradykinesia, but not with tremor. Oscillating neurons in one or multiple localizations within the basal gangliathalamo-cortical loop may cause rest tremor, and an active contribution of the cerebellum and the cerebello-thalamo-cortical projections has been postulated. Objective To compare the pattern of grey matter volume in PD patients with and without tremor to identify structural correlates of rest tremor. Methods Voxel-based morphometry (VBM) of a high-resolution 3 Tesla, T1-weighted MR images, pre-processed according to an optimized protocol using SPM2, was performed in 24 patients with mild to moderate PD comparing local grey matter volume in patients with (n = 14) and without rest tremor (n = 10). Results Grey matter volume is decreased in the right quadrangular lobe and declive of the cerebellum in PD with tremor compared to those without (PFDR < 0.05). Conclusions These results demonstrate for the first time morphological changes in the cerebellum in PD patients with rest tremor and highlight the involvement of the cerebellum and cerebello- thalamo-cortical circuit in the pathogenesis of parkinsonian rest tremor.

In spite of their diagnostic potential, the poor quality of available diffusion-weighted spinal cord images often restricts clinical application to cervical regions, and improved spatial resolution is highly desirable. To address these needs, a novel technique based on the combination of two recently presented reduced field-of-view approaches is proposed, enabling high-resolution acquisition over the entire spinal cord. Field-of-view reduction is achieved by the application of non-coplanar excitation and refocusing pulses combined with outer volume suppression for removal of unwanted transition zones. The non-coplanar excitation is performed such that a gap-less volume is acquired in a dedicated interleaved slice order within two repetition times. The resulting inner volume selectivity was evaluated in vitro. In vivo diffusion tensor imaging data on the cervical, thoracic and lumbar spinal cord were acquired in transverse orientation in each of four healthy subjects. An in-plane resolution of 0.7 X 0.7 mm(2) was achieved without notable aliasing, motion or susceptibility artifacts. The measured mean +/- SD fractional anisotropy was 0.69 +/- 0.11 in the thoracic spinal cord and 0.75 +/- 0.07 and 0.63 +/- 0.08 in cervical and lumbar white matter, respectively. Copyright (C) 2009 John Wiley & Sons, Ltd.

BACKGROUND AND PURPOSE: The inherent low anisotropy of gray matter and the lack of adequate imaging sensitivity and resolution has, so far, impeded depiction of axonal fibers to their intracortical origin or termination. We tested the hypothesis that an experimental approach with high-resolution diffusion tensor imaging (DTI) provides anisotropic data for fiber tractography with sufficient sensitivity to visualize in vivo the fine distribution of white matter bundles at the intracortical level. MATERIALS AND METHODS: We conducted phantom measurements of signal-to-noise ratio (SNR) and obtained diffusion tensor maps of the occipital lobe in 6 healthy volunteers using a dedicated miniature phased array detector at 3T. We reconstructed virtual fibers using a standard tracking algorithm. RESULTS: The coil array provided a SNR of 8.0 times higher at the head surface compared with a standard quadrature whole head coil. Diffusion tensor maps could be obtained with an in-plane resolution of 0.58 × 0.58 mm2. The axonal trajectories reconstructed from the diffusion data penetrate into the cortical ribbon perpendicular to the pial surface. This is the expected pattern for the terminations of thalamocortical afferent fibers to the middle layers of the occipital cortex and is consistent with the known microstructural organization of the mammalian cerebral cortex. CONCLUSION: High-resolution DTI reveals intracortical anisotropy with a distinct parallel geometrical order, perpendicular to the pial surface, consistent with structures that may be identified as the terminal afferents in cortical gray matter.

Ziele: Die klinische Symptomatik des M.Parkinson lässt sich in eine primär akinetisch-rigide sowie eine primär tremor-dominate Form differenzieren.

Brain activation during motor imagery has been the subject of a large number of studies in healthy subjects, leading to divergent interpretations with respect to the role of descending pathways and kinesthetic feedback on the mental rehearsal of movements. We investigated patients with complete spinal cord injury (SCI) to find out how the complete disruption of motor efferents and sensory afferents influences brain activation during motor imagery of the disconnected feet. Eight SCI patients underwent behavioral assessment and functional magnetic resonance imaging. When compared to a healthy population, stronger activity was detected in primary and all non-primary motor cortical areas and subcortical regions. In paraplegic patients the primary motor cortex was consistently activated, even to the same degree as during movement execution in the controls. Motor imagery in SCI patients activated in parallel both the motor execution and motor imagery networks of healthy subjects. In paraplegics the extent of activation in the primary motor cortex and in mesial non-primary motor areas was significantly correlated with the vividness of movement imagery, as assessed by an interview. The present findings provide new insights on the neuroanatomy of motor imagery and the possible role of kinesthetic feedback in the suppression of cortical motor output required during covert movements.

A distinction should be made between anatomical variations and congenital malformations. Variants are not considered to be anomalies because of their frequent occurrence and their lack of associated functional deficits. Congenital malformations, on the other hand, are less frequent deviations of normal anatomical development and are frequently associated with functional disorders (GULYA and SCHUKNECHT 1993). Both anatomical variants and congenital malformations, however, are clinically significant for their otological surgeon; the former should be identified for avoiding complications during surgical interventions in the temporal bone and the latter should be precisely diagnosed for patient counseling and for deciding on the appropriate therapeutic procedure. In this respect, imaging probably plays the most essential role, and the accuracy of the information it provides to the surgeon is of utmost importance.