Prognostic factor from MR spectroscopy in rat with astrocytic tumour during radiation therapy

Objective: To investigate the relationship between the tumour volume and metabolic rates of astrocytic tumours using MR spectroscopy (MRS) during radiation therapy (RT). Methods: 12 healthy male Sprague-Dawley® rats (Sprague–Dawley Animal Company, Madison, WI) were used, and a tumour model was created through injecting C6 tumour cells into the right caudate nuclei of the rats. Tumours grew for 18 days after the injection and before the imaging study and radiation treatment. MRS was performed with two-dimensional multivoxel point-resolved spectroscopy sequence using a GE Signa VH/i 3.0-T MR scanner (GE Healthcare, Milwaukee, WI) equipped with rat-special coil. RT was given on the 19th day with a dose of 4 Gy in one single fraction. The image examinations were performed before RT, and on the 4th, 10th, 14th and 20th days after treatment, respectively. GE FuncTool software package (GE Healthcare) was used for post-processing of spectrum. Results: Metabolic ratios of serial MRS decrease progressively with time after RT. Choline-containing components (Cho)/creatine and creatine phosphate (Cr) ratios immediately prior to RT differed significantly from those on the 10th, 14th and 20th days after RT; both Cho/N-acetyl aspartate (NAA) ratios and NAA/Cr ratios immediately prior to RT differed significantly from those on the 14th and 20th days after RT. A positive correlation between changes of tumour volume and changes of Cho/Cr, lipid and lactate/Cr and glutamate plus glutamine/Cr ratio was observed on the 4th day after RT. Conclusion: MRS provides potential in monitoring tumour response during RT, and the imaging biomarkers predict the response of astrocytic tumours to treatment. Advances in knowledge: MRS is combined with both tumour size and Ki-67 labelling index to access tumour response to radiation.ECU Open Access Publishing Support Fun

Dynamic metabolic patterns tracking neurodegeneration and gliosis following 26S proteasome dysfunction in mouse forebrain neurons

Metabolite profling is an important tool that may better capture the multiple features of neurodegeneration. With the considerable parallels between mouse and human metabolism, the use of metabolomics in mouse models with neurodegenerative pathology provides mechanistic insight and ready translation into aspects of human disease. Using 400MHz nuclear magnetic resonance spectroscopy we have carried out a temporal region-specifc investigation of the metabolome of neuron-specifc 26S proteasome knockout mice characterised by progressive neurodegeneration and Lewy-like inclusion formation in the forebrain. An early signifcant decrease in N-acetyl aspartate revealed evidence of neuronal dysfunction before cell death that may be associated with changes in brain neuroenergetics, underpinning the use of this metabolite to track neuronal health. Importantly, we show early and extensive activation of astrocytes and microglia in response to targeted neuronal dysfunction in this context, but only late changes in myo-inositol; the best established glial cell marker in magnetic resonance spectroscopy studies, supporting recent evidence that additional early neuroinfammatory markers are needed. Our results extend the limited understanding of metabolite changes associated with gliosis and provide evidence that changes in glutamate homeostasis and lactate may correlate with astrocyte activation and have biomarker potential for tracking neuroinfammation

Metabolic changes in concussed American football players during the acute and chronic post-injury phases

<p>Abstract</p> <p>Background</p> <p>Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations.</p> <p>Methods</p> <p>The present study investigated the effects of sports concussion on brain metabolism using ¹H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years) and education (mean: 16 years) within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI.</p> <p>Results</p> <p>Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase.</p> <p>Conclusions</p> <p>These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.</p