Tierärztliche Hochschule Hannover
Tierärztliche Hochschule Hannover Tierärztliche Hochschule Hannover
Manuskript I The cause for unreliable measurements may be enhanced noise. In Tab. 2 unreliable measurements indicated by interrogation marks were quantified in the brain and spinal cord. Using small voxel an increased percentage of unreliable results occurred in comparison to measurements in large voxel. Tab. 2: Percentage of unreliable values Total: Brain: Spinal cord: p- value: Small voxel: 71.76 57.75 88.33 0.0003 Large voxel: 21.05 32.00 0.00 0.0665 p- value: < 0.0001 0.0268 < 0.0001 Tab. 2: Shows the percentage distribution of unreliable values (distinct by interrogation marks) of all metabolite measurements (169 measured values) of the brain and spinal cord comparing small and large voxel sizes, calculated by the chisquare-test. An error probability of p < 0.05 was the significance level. The spectral resolution is improved using large voxel. 4.5 Discussion MRS could be a valuable tool to better evaluate pathological changes in vivo in the spinal cord of dogs with SCI and other pathological changes in the CNS. Therefore, the hypothesis should be proven that MRS examinations of the canine spinal cord are feasible in dogs. This hypothesis was corroborated only in part by the current study, since some restrictions have to be considered. To the best of our knowledge up to now studies about the use of spectroscopy to measure metabolites in the canine spinal cord are not yet published. Therefore, some prerequisites needed to be assessed as the first steps to introduce this technique into clinical settings. Measurements were performed in unaffected canine CNS which was measured by conventional MRI. Concentrations of the major metabolites such as NAA, Cho, mI, Glx, Lac, and Cr were analyzed. The effect of different voxel sizes was evaluated to improve the quality of measurements and the number of reliable results. For the definition of pathological changes in the spinal cord, the following metabolites were considered to be good candidates. NAA is known to produce the highest peak 34
Manuskript I in normal CNS tissue and is found in axons and neurons as a special marker for neuronal efficiency and axonal integrity. NAA is decreased in neurological disorders with axonal or neuronal loss. 7, 24 Lactate (Lac) is the end product of glycolysis and normally emerges only under pathological conditions with low oxygen content (local ischemia, neuronal mitochondrial dysfunction or inflammation) or in voxel with cerebrospinal fluid (CSF) contamination. 5, 7, 25 Under normal conditions, a Lac peak should not be detectable in the spectrum. 5 Creatine, composed of creatine and phosphocreatine, indicates the energy metabolism of neurons and glia cells and is assumed to be a representative marker of inflammation and active gliosis. 26 However, under several pathological conditions creatine displayed nearly constant values and was frequently used as an internal reference peak. 4, 7 Choline, consisting of choline, glycerophosphocholine and phosphocholine, is a metabolite involved in membrane turnover (synthesis and degradation) and increases in demyelinating, remyelinating and inflammatory diseases. 7 Based on the location in glial cells myoinositol, a polyol, 27 is assumed to be a glia marker, which increases in gliosis, inflammation, 26 demyelinating disorders and is involved in the osmotic regulation of brain tissue volume. 4, 5, 7 Glx, consisting of glutamate and glutamine is a combination of amino acids and bioamides. In the CNS glutamate is the major excitatory neurotransmitter released with excitation, but rapidly metabolized and converted into 5, 21, 23 glutamine. The range of concentration estimates of all measured metabolites in the current study was larger in the spinal cord than in the brain (Fig. 2 and Tab. 1). In addition, we could confirm that the concentrations of the metabolites NAA, Cho, Cr, mI, Lac, and Glx measured in dogs are higher in the spinal cord than in the brain which is in 19, 24 line with findings in other species. A possible explanation might be that the distribution of white and gray matter and the content of CSF considerably changes along the longitudinal axis of the spinal cord. 13 Therefore, the evaluated concentrations are dynamic and may vary in different regions of the spinal cord. Additionally, these facts explain the increased lactate peak in the spinal cord as a result of its high CSF content. Due to our experimental design with the use of clinical patients, dogs with idiopathic epilepsy were included in the study. No structural 35
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Manuskript I<br />
The cause for unreliable measurements may be enhanced noise. In Tab. 2 unreliable<br />
measurements indicated by interrogation marks were quantified in the brain and<br />
spinal cord. Using small voxel an increased percentage of unreliable results occurred<br />
in comparison to measurements in large voxel.<br />
Tab. 2: Percentage of unreliable values<br />
Total: Brain: Spinal cord: p- value:<br />
Small voxel: 71.76 57.75 88.33 0.0003<br />
Large voxel: 21.05 32.00 0.00 0.0665<br />
p- value: < 0.0001 0.0268 < 0.0001<br />
Tab. 2: Shows the percentage distribution of unreliable values (distinct by<br />
interrogation marks) of all metabolite measurements (169 measured values) of the<br />
brain and spinal cord comparing small and large voxel sizes, calculated by the chisquare-test.<br />
An error probability of p < 0.05 was the significance level. The spectral<br />
resolution is improved using large voxel.<br />
4.5 Discussion<br />
MRS could be a valuable tool to better evaluate pathological changes in vivo in the<br />
spinal cord of dogs with SCI and other pathological changes in the CNS. Therefore,<br />
the hypothesis should be proven that MRS examinations of the canine spinal cord<br />
are feasible in dogs. This hypothesis was corroborated only in part by the current<br />
study, since some restrictions have to be considered. To the best of our knowledge<br />
up to now studies about the use of spectroscopy to measure metabolites in the<br />
canine spinal cord are not yet published. Therefore, some prerequisites needed to be<br />
assessed as the first steps to introduce this technique into clinical settings.<br />
Measurements were performed in unaffected canine CNS which was measured by<br />
conventional MRI. Concentrations of the major metabolites such as NAA, Cho, mI,<br />
Glx, Lac, and Cr were analyzed. The effect of different voxel sizes was evaluated to<br />
improve the quality of measurements and the number of reliable results.<br />
For the definition of pathological changes in the spinal cord, the following metabolites<br />
were considered to be good candidates. NAA is known to produce the highest peak<br />
34
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