Research article1H-MRS of the macaque monkey primary visual cortex at 7 T: strategies and pitfalls of shimming at the brain surface
Introduction
The primary visual cortex is one of the most extensively investigated areas in the primate brain. A great deal is known about its cyto-architectonics and myeloarchitectonics, its functional architecture, its physiologic properties, its connectivity and its role in visual information processing [1], [2]. The functional units of V1 (and those of other cortical areas) are subcolumnar functional aggregates termed canonical microcircuits whose operation shapes the local and modular properties of the area. The pronounced characteristics of these microcircuits are their weak feedforward input (e.g., thalamic input), strong excitation recurrence and electrically inseparable excitation–inhibition events [3], [4]. An integrative approach that investigates both the electrical and neurochemical processes is required to understand how functional properties, such as orientation, direction and color selectivity, arise in this area.
In vivo magnetic resonance spectroscopy (MRS) has been demonstrated to be a powerful technique for achieving localized neurochemical information from the brain noninvasively [5], [6]. MRS studies aiming at the elucidation of brain function, typically focus on the detection and quantization of neurotransmitters and metabolites of the brain's energy metabolism. Based on 1H-MRS measurements, changes in metabolite concentrations related to sensory stimulation have been reported for several substances, including lactate [7], [8], [9], [10], [11], [12], [13], [14], glucose [8], [13], [14], glutamate (Glu) [13], [14], [15] and the conversion of phosphocreatine (PCr) to creatine (Cr) [16]. Such studies unambiguously provided important information on the brain's neurochemistry and metabolism; they failed, however, to address questions regarding the organization of cortical microcircuitry, the principles of regional information processing and the role of sensory (e.i., driver) versus modulatory (i.g., the effects of ascending diffuse systems such as the noradrenergic and cholinergic systems that determine synaptic efficacy and response sensitivity in the cortex) inputs. Animal-preparations are appropriate for such investigations as they can combine MRS studies with other, invasive neuroscientific techniques, that can examine electrical and chemical processes at the same time. The non-human primate model is ideally suited for the latter approach as the sensory systems of monkeys are almost identical in organization to those of humans. In addition, monkey sensory areas (e.g., in this study, the monkey visual system) offer considerable practical advantages for achieving the best possible resolution in MRS experiments.
In general, MRS is limited by its inherently low sensitivity when based on Boltzmann spin polarization, and concentrations of MR-detectable brain metabolites are at best in the millimolar range. Therefore, MRS studies focusing on the visual cortex in humans commonly use sample volumes larger than 10 cm3, which include not only V1 but also white matter tissue, cerebrospinal fluid (CSF) and, in some cases, higher cortical areas [7], [8], [9], [10], [11], [12], [13]. Furthermore, the reported results of functional MRS studies during sensory stimulation have not always been consistent. For instance, for lactate, time courses and quantitative ranges of the observed concentration changes differed considerably. Potential explanations range from differences in experimental conditions or stimulation paradigms to varying compositions of gray matter, white matter and CSF within the MRS volume. The latter component is critical because cells, synapses, astrocytes and other elements involved in the neurometabolic link are not uniformly distributed in the brain and most are known to be confined within the gray matter. In addition, the spatial stimulation profile (i.e., the retinotopic representation of the visual stimulus within the MRS voxel) was poorly defined in all human studies. The functional specificity of MRS can be improved if samples are obtained exclusively from a special functional subunit of the brain (e.g., from the representation of a limited visual field area in V1). Most of the representation of the central visual field in the human brain is located inside the calcarine sulcus on the medial surface of the occipital part of the brain. Due to the curvature of inflated cortex and the cortical thickness in the human of 1.7–2.2 mm [17], [18], minimal voxel sizes in MRS studies were orders of magnitude bigger than what would be required by the anatomical constraints for an exclusive study on V1 regions. To the best of our knowledge, no MRS study to date has been sufficiently spatially selective to provide information on the metabolism of the striate cortex only.
In contrast to human neuroanatomy, the representation of the central visual field in the striate cortex is located in the operculum in monkeys, namely on the posterior–lateral surface of the occipital lobe rather than within the banks of the calcarine sulcus (Fig. 1). In addition, the location of the vertical meridian that commonly runs parallel to the lunate and inferior–occipital sulcus is well defined, and can be used as a landmark for the mapping of the visual field on the cortical surface. With a thickness of 1.7–2.0 mm [18], the macaque V1 is only slightly thinner than the human striate cortex. On the other hand, the monkey V1 follows the curvature of the adjacent cranial bone and is void of sulci (i.e., it is largely flat). Furthermore, the small distance to the skull surface enables the use of radiofrequency (RF) surface coils for increased sensitivity of MR investigations. In other words, the topology and position of the macaque striate cortex permit good positioning of an MRS voxel, albeit the volume of the latter component (in the range of 30–70 μl) remains to be a challenging problem.
To exploit the advantages of monkey-MRS and optimize data acquisition, we used a dedicated high-field setup and the well-established anesthetized monkey preparation in our laboratory that permit the accomplishment of the currently highest possible sensitivity under physiological and experimentally well-controlled conditions. Our optimization strategies included the quantitative mapping of local field disturbances due to the cortical vasculature, and shimming strategies to minimize inhomogeneities of the magnetic field within the sensitive voxel volume in the direct vicinity of the cranial bone. The MRS voxel was selected according to the anatomical dimensions of V1 in the macaque. Spectra were exclusively acquired from V1 to provide for the first time metabolite MRS from that cortical area without partial volume effects. The preliminary results of this work have been published in abstract form [19], [20].
Section snippets
MR system and experimental setup
Measurements were performed on a vertical 7 T/60 cm Bruker BioSpec system (Bruker BioSpin, Ettlingen, Germany) dedicated to MR imaging and MRS in the monkey [21]. The system was initially equipped with a BGA38 gradient and shim insert (80 mT/m, 200 μs; Bruker BioSpin), which was temporarily substituted by an AC44 gradient and shim insert (40 mT/m, 200 μs; Siemens Medical Solutions, Erlangen, Germany). Because the AC44 system was designed for a 3 T human head scanner, the second-order shim
Results
This article presents both the evaluation of our optimization procedures and the first data acquired following all developmental work. This section is therefore organized such that the outcome of methodological development is presented together with a description of the actual spectral data.
Discussion
This article reports on the first spatially localized V1-specific spectra from the primate brain. A number of methodological advances was necessary to obtain the spectra quality displayed in Fig. 5.
First, imperfections of the RF pulse profile lead to signal contributions that originate from erroneous physical locations. For MRS voxels inside the brain, such artifacts could go unnoticed. In this study, however, the direct vicinity of the MRS voxel to the cranial bone marrow required a
Acknowledgments
This work was supported by the Max-Planck Society.
We thank Dr. Rhodri Cusack (MRC Cognition and Brain Science Unit, Cambridge, England) for providing the three-dimensional phase unwrapping algorithm, available at http://www.mrc-cbu.cam.ac.uk/~rhodri/, and Dr. Hellmut Merkle for constructing the RF saddle coil as well as helping with scanner optimization.
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