Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis
<p>Multiple sclerosis (MS) is a demyelinating, immune-mediated disease of the central nervous system characterised by both acute episodes of neurological dysfunction and long-term neurodegeneration.</p> <p>Diagnosis and monitoring rely heavily on imaging, with magnetic resonance i...
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| Định dạng: | Luận văn |
| Ngôn ngữ: | English |
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2022
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| _version_ | 1826307748194680832 |
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| author | Healicon, R |
| author2 | Tyler, D |
| author_facet | Tyler, D Healicon, R |
| author_sort | Healicon, R |
| collection | OXFORD |
| description | <p>Multiple sclerosis (MS) is a demyelinating, immune-mediated disease of the central nervous system characterised by both acute episodes of neurological dysfunction and long-term neurodegeneration.</p>
<p>Diagnosis and monitoring rely heavily on imaging, with magnetic resonance imaging (MRI) the present gold-standard modality. Current MRI techniques, however, have poor sensitivity for monitoring the development of pre-demyelinated lesions and in assessing treatment response.</p>
<p>In MS lesions, highly active immune cells and dysregulated neuronal metabolism cause a localised metabolic shift towards glycolytic lactate production. Hyperpolarised <sup>13</sup>C magnetic resonance spectroscopy (MRS) is able to detect this shift, and here, I have demonstrated the ability of hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MRS to detect MS-like lesions, and their response to fingolimod treatment, in the focal experimental autoimmune encephalomyelitis rat model of MS. This paves the way for future studies using hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MR in rodent models of MS, and eventually in patients with MS.</p>
<p>In hyperpolarised MR, high levels of signal are generated in <sup>13</sup>C-labelled tracer molecules using the process of dynamic nuclear polarisation. This requires the tracer molecule to be mixed with a free radical, which facilitates transfer of electron polarisation to the tracer molecule. To optimise an experimental protocol for this and future hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MR experiments, I compared build-up times and maximum signal generation using AH111501 and Finland radicals, and demonstrated that the AH111501 radical was superior to the Finland radical in both build-up time and maximum signal generated.</p>
<p>Finally, to optimise an anaesthetic protocol for future neuroimaging studies, I compared healthy rats at 100%, 90% and 60% inspired oxygen, and demonstrated reduced cerebral perfusion and dysregulated cerebral metabolism with hyperoxia.</p> |
| first_indexed | 2024-03-07T07:07:47Z |
| format | Thesis |
| id | oxford-uuid:72610ff6-b076-48b7-820f-e2fbd37ccb97 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:07:47Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:72610ff6-b076-48b7-820f-e2fbd37ccb972022-05-26T17:06:36ZHyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosisThesishttp://purl.org/coar/resource_type/c_bdccuuid:72610ff6-b076-48b7-820f-e2fbd37ccb97Multiple sclerosisMagnetic resonance imagingEnglishHyrax Deposit2022Healicon, RTyler, DGrist, J<p>Multiple sclerosis (MS) is a demyelinating, immune-mediated disease of the central nervous system characterised by both acute episodes of neurological dysfunction and long-term neurodegeneration.</p> <p>Diagnosis and monitoring rely heavily on imaging, with magnetic resonance imaging (MRI) the present gold-standard modality. Current MRI techniques, however, have poor sensitivity for monitoring the development of pre-demyelinated lesions and in assessing treatment response.</p> <p>In MS lesions, highly active immune cells and dysregulated neuronal metabolism cause a localised metabolic shift towards glycolytic lactate production. Hyperpolarised <sup>13</sup>C magnetic resonance spectroscopy (MRS) is able to detect this shift, and here, I have demonstrated the ability of hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MRS to detect MS-like lesions, and their response to fingolimod treatment, in the focal experimental autoimmune encephalomyelitis rat model of MS. This paves the way for future studies using hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MR in rodent models of MS, and eventually in patients with MS.</p> <p>In hyperpolarised MR, high levels of signal are generated in <sup>13</sup>C-labelled tracer molecules using the process of dynamic nuclear polarisation. This requires the tracer molecule to be mixed with a free radical, which facilitates transfer of electron polarisation to the tracer molecule. To optimise an experimental protocol for this and future hyperpolarised [1-<sup>13</sup>C]ethylpyruvate MR experiments, I compared build-up times and maximum signal generation using AH111501 and Finland radicals, and demonstrated that the AH111501 radical was superior to the Finland radical in both build-up time and maximum signal generated.</p> <p>Finally, to optimise an anaesthetic protocol for future neuroimaging studies, I compared healthy rats at 100%, 90% and 60% inspired oxygen, and demonstrated reduced cerebral perfusion and dysregulated cerebral metabolism with hyperoxia.</p> |
| spellingShingle | Multiple sclerosis Magnetic resonance imaging Healicon, R Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title | Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title_full | Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title_fullStr | Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title_full_unstemmed | Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title_short | Hyperpolarised carbon-13 magnetic resonance spectroscopy with [1-13C]ethylpyruvate as a preclinical modality for detecting MS-like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| title_sort | hyperpolarised carbon 13 magnetic resonance spectroscopy with 1 13c ethylpyruvate as a preclinical modality for detecting ms like lesions and their response to fingolimod treatment in the focal experimental autoimmune encephalomyelitis rat model of multiple sclerosis |
| topic | Multiple sclerosis Magnetic resonance imaging |
| work_keys_str_mv | AT healiconr hyperpolarisedcarbon13magneticresonancespectroscopywith113cethylpyruvateasapreclinicalmodalityfordetectingmslikelesionsandtheirresponsetofingolimodtreatmentinthefocalexperimentalautoimmuneencephalomyelitisratmodelofmultiplesclerosis |