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Detection of Neurotransmitters in the Human Brain Using Magnetic Resonance SpectroscopyTapper, Sofie January 2013 (has links)
There is an increasing interest in studying the concentration of the inhibitory neurotransmitter γ-Amino Butyric Acid (GABA), both in the healthy and diseased brain by using Magnetic Resonance Spectroscopy (MRS). Recent studies have shown correlations between an abnormal GABA concentration in certain regions of the brain and disorders as e.g. Parkinson’s disease and depressive disorders. There are presently many technical difficulties with the absolute quantification of GABA and the method MEGA-PRESS is currently the standard technique used in data acquisitions and processing of spectra. In this thesis, different techniques of GABA quantification have been evaluated and the most important aspect was to explore the precision of the method for further usage as a clinical tool. This project involved the exploration of data acquisitions by using a MEGA-PRESS sequence on a 3 T MR-system, processing of the resulting datasets using different methodologies, GABA quantification by using linear combination of model spectra (LCModel), and interpretation of the results by performing statistical analyses. The thesis resulted in a low resolution GABA-atlas of the brain which did not indicate any significant differences in the GABA concentration within the healthy subject group. However, a significant regional difference was observed in the brain. The main uncertainties arose mainly due to the relatively small subject groups and the large measurement error. Future measurements will require improvements both in the data acquisition and in analyzing these with an improved method of processing. The final conclusion was that the GABA quantification sequence MEGA-PRESS is useful both in diagnosis and as a research tool, although further improvements are required.
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以MEGA-PRESS頻譜編輯技術偵測大腦乳酸 及探討平均頻譜次數與擬合參數之影響 / The detection of lactate in human brain using MEGA-PRESS spectral editing technique and the affect between times of average spectrum and fitting parameters粘政緯, Nien, Cheng Wei Unknown Date (has links)
乳酸(Lactate)是一種人體內常見的代謝物,也是無氧代謝後的最終產物。人體在運動過後血液中的乳酸濃度會上升,但在一般情況下大腦中的乳酸含量非常低,正常人腦乳酸濃度約低於0.5毫莫耳(mM),由於腦乳酸的低濃度,以及在磁共振頻譜中的乳酸訊號與大分子(macromolecular)部分訊號重疊,導致在正常大腦中不易得到乳酸的頻譜訊號。近年來,有文獻指出在3T的磁場下利用MEGA-PRESS技術可以量測到乳酸在大腦經由低氧與高氧交替過程中的改變,而Mescher-Garwood(MAGA) point-resolved spectroscopy sequence(PRESS)頻譜編輯技術是由原本的PRESS脈衝序列再增加兩個選擇性的脈衝,透過頻譜相減消除不具有J-耦合特性的代謝物,來針對具有J-耦合特性的代謝物訊號做測量。本研究的目的為在3T的磁場下,利用MEGA-PRESS技術量到乳酸的頻譜訊號之外,再藉由不同的擬合(fitting)方式以及處理頻譜平均次數來得到不同條件下乳酸頻譜的標準差及變異係數值,以衡量利用在視覺刺激下是否能得到大腦視覺區中乳酸的改變差異,並提供一份乳酸對擬合參數的改變及平均次數多寡的參考依據。
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Edited magnetic resonance spectroscopy detects an age-related decline in monkey brain GABA levelsHe, Xuanzi 12 March 2016 (has links)
Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA) the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on posterior cingulate cortex, which is the 'core hub' of the Default mode network. In this study, 14 monkeys between 4 and 21 years were recruited and MEGA-PRESS to measure GABA level in order to explorea potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r= -0.523, p=0.081). There was also a near-significant trend between grey matter/ white matter ratio and GABA+/Creatine ratio (r = -0.518, p=0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r= -0.028, p = 0.93). Therefore, age and grey matter/ white matter ratio accounts for different part of R-squared as independent variables for predicting GABA levels. These finding suggest that there the internal neurochemical variation of GABA levels in the nonhuman primate is associated with normal aging and brain structural decline.
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Magnetic resonance spectroscopy as part of a comprehensive neuroimaging assessment toolSanaei Nezhad, Faezeh January 2018 (has links)
Magnetic resonance spectroscopy (MRS) allows the non-invasive measurement of selected biological compounds in vivo. Despite MRS proven potential it is not yet a routine clinical tool operated by clinicians. This is mainly due to the complex procedure of MRS acquisition, lack of standardisation in both acquisition and analysis protocols along with lack of a standard quality control. This thesis intended to address these issues with the focus on four metabolites glutathione, glutamate, glutamine and GABA using MEGA-PRESS pulse sequence. Recommendations on acquisition and spectra analysis is made for the MRS protocol MEGA-PRESS aiming to detect glutathione in vivo. This is based on an investigation of glutathione acquisition in vivo and in vitro and was aimed to answer the question: can glutathione be measured reliably using conventional pulse sequence PRESS or does it require editing? The results showed strong evidence of using editing in order to have a reliable glutathione concentration measurement. An analysis along with a quality control method is also presented to enable the extraction of glutamate and glutamine from a GABA-optimised MEGA-PRESS pulse sequence. This enables simultaneous measurements of GABA, glutamate and glutamine in a single acquisition. A criterion of NAA linewidth < 8 Hz and Glx CRLB < 16% were defined as optimum features in the GABA-edited spectrum for a reliable glutamate and glutamine quantification. Finally, due to the increasing interest in functional MRS of GABA using MEGAPRESS an investigation on the feasibility of measuring GABA in a functional-MRS setting was performed with recommendations on study designs and subject size. Power calculations suggest that detecting a 40% change in GABA using a 4'30" acquisition requires 9-93 subjects per group in a between-group study design and 13- 68 participants in a within-session design, depending on the region of interest. This thesis is set out in the Journal format thesis. Three introductory chapters, with each experimental study presented as a chapter and a final chapter that summarizes and discusses the work. Results in this thesis provide a basis for a standard and reliable MRS pipeline to reliably measure glutathione, glutamate, glutamine and GABA using MEGA-PRESS pulse sequence at 3 Tesla.
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Utilização da fMRS para o estudo da variação de N-acetil-aspartato e N-acetil-aspartil-glutamato durante a ativação cerebral / Use of fMRS for the study of N-acetyl-aspartate and N-acetyl-aspartyl-glutamate variation during brain activationLandim, Ricardo Cesar Giorgetti, 1986- 19 May 2006 (has links)
Orientador: Gabriela Castellano / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-21T20:54:35Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013 / Resumo: As variações metabólicas que ocorrem no cérebro subjacentes á ativação neuronal ainda estão longe de ser bem compreendidas e, portanto, constituem objeto de estudo de grande interesse por parte da comunidade cientifica da área. Uma forma de estudar estas variações é por meio da técnica de espectroscopia funcional por ressonância magnética (functional Magnetic Resonance Spectroscopy - fMRS), na qual espectros de uma dada região cerebral são coletados de forma dinâmica, enquanto o indivíduo é sujeito a algum estimulo sensorial ou tarefa cognitiva. Em particular, o N-acetil-aspartato (NAA) _e o metabólito que gera o principal pico encontrado em espectros cerebrais de espectroscopia por ressonância magnética utilizando o núcleo do hidrogênio. Na verdade, este pico provém do próprio NAA (90%) e também de um derivado deste, o N-acetil-aspartil-glutamato (NAAG). Em experimentos de fMRS realizados por nosso grupo, foi encontrada variação de NAA e NAAG no córtex visual de indivíduos normais, quando estes são sujeitos á apresentação de um estimulo visual. Porem, as variações do sinal de MRS do NAA em experimentos de fMRS são um assunto controverso na literatura da área, pois há trabalhos que apontam para sua variação com o estímulo e outros que dizem que não há variações. Além disso, os trabalhos existentes na literatura mediram a variação conjunta de NAA e NAAG. Dessa forma, para elucidar o que acontece com estes metabólitos durante a ativação cerebral seria interessante medí-los separadamente. O objetivo principal deste trabalho foi, portanto, realizar experimentos de fMRS nos quais estes metabólitos pudessem ser medidos de forma independente, através da implementação da sequência de pulsos MEGA-PRESS, que separa as contribuições do NAA e NAAG já no momento da medida. Os experimentos foram realizados em sujeitos saudáveis durante estimulação visual. Foram realizados vários testes para se padronizar o pré -processamento e duas metodologias foram utilizadas. Diversas quantificações foram feitas e como resultado foram encontradas variações de NAA (diminuição) e NAAG (aumento) durante o estímulo. Os resultados concordam com os apresentados em dois dos três trabalhos similares encontrados na literatura, e também com os resultados anteriores de nosso grupo. A diminuição de NAA pode ser explicada através da hipótese de que ele funcione como uma bomba de _agua molecular, enquanto que a produção de NAAG concorda com o fato de que este metabólito _e um neuropeptídeo que é liberado nas sinapses e atua como modulador para a liberação de certos neurotransmissores, e também concorda com modelos para o metabolismo energético que apontam para este metabólito como relacionado á resposta hiperêmica vascular que origina o sinal BOLD / Abstract: Metabolic changes that occur in the brain underlying neuronal activation are still far form being understood and, therefore, are a subject matter of great interest for the scientific community of this research field. One way to study these variations is through the technique of functional Magnetic Resonance Spectroscopy (fMRS), in which spectra from a given brain region are collected dynamically, while the volunteer is subject to some sensory stimulus or cognitive task. In particular, N-acetyl-aspartate (NAA) is the metabolite that generates the main peak found the MR spectra of the brain using the hydrogen nucleus. Indeed, this peak originates from NAA itself (90 %) and also from a derivative thereof, N-acetylaspartyl-glutamate (NAAG). In fMRS experiments performed by our group, NAA and NAAG changes were found in the visual cortex of normal individuals when they are subject to a visual stimulus. However, the MRS signal variations of NAA in fMRS experiments are a controversial subject in the literature, since there are studies that point to its variation with the stimulus and others that show that there is no variation. In addition, the existing works measured the joint NAA and NAAG variation. Thus, to elucidate what happens to these metabolites during brain activation it would be interesting to measure them separately. The main objective of this study was, therefore, to perform fMRS experiments in which these metabolites could be measured independently by implementing the MEGA-PRESS pulse sequence, which separates the NAA and NAAG contributions at the time of measurement. The experiments were performed in healthy subjects during visual stimulation. Several tests were performed to standardize the preprocessing and two methods were used. Several quantifications were made and as result NAA and NAAG variations (decrease and increase, respectively) were found during the stimulus. The results agree with those presented in two out of three similar studies found in the literature, and also with the previous results from our group. The NAA decrease may be explained through the hypothesis that it works as a molecular water pump, whereas the NAAG production agrees with the fact that this metabolite is a neuropeptide that is released at the synapses and acts as a modulator for the release of certain neurotransmitters, and also agrees with models for energy metabolism that point to this metabolite as related to the vascular hyperemic response that originates the BOLD signal / Mestrado / Física / Mestre em Física
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Molecular markers of gliomas : implications for diagnosis and new target therapies / Les marqueurs moléculaires de gliomes : implications pour diagnostics et nouvelles thérapies ciblesDi Stefano, Anna Luisa 21 February 2017 (has links)
Le travail de thèse est dédié à la caractérisation de fusions spécifiques oncogéniques entre les gènes FGFR et TACC dans les gliomes. Nous avons analysé 907 gliomes pour la présence du gène de fusion FGFR3-TACC3. Nous avons montré que les fusions FGFR3-TACC3 ne touchent que les gliomes IDH wild-type (3%), sont mutuellement exclusives avec l'amplification de EGFR et avec la forme tronquée EGFRvIII et inversement, sont associées à l'amplification de CDK4 et de MDM2 et à la délétion du 10q. Les fusions FGFR3-TACC3 sont associées à une expression intense et diffuse de FGFR3 en immunohistochimie (IHC) et l'IHC pour FGFR3 est un marqueur prédictif très sensible de la présence des fusions FGFR3-TACC3. Les patients porteurs d'une fusion FGFR3-TACC3 ont une survie globale significativement plus longue comparés aux patients avec gliome IDH wild-type. Nous avons traité deux patients porteurs d'un gène de fusion FGFR3-TACC3 avec un inhibiteur tyrosine-kinase (TK) spécifique pour FGFR et nous avons observé une stabilisation de maladie et une réponse mineur chez un patient. Dans la deuxième section nous avons optimisé une nouvelle séquence de spectroscopie différentielle-MEGA-PRESS-pour la détection de l'oncometabolite 2-hydroxyglutarate (2 HG) qui s'accumule de manière spécifique dans les gliomes IDH mutés. Nous avons analysé de façon prospective une cohorte de 25 patients avant chirurgie pour probable gliome de grade II et grade III. Nous avons trouvé que la MEGA-PRESS est hautement spécifique (100%) et sensible (80%) dans la prédiction de la présence de la mutation IDH. Son taux est corrélé aux concentrations de 2 HG mesurés sur tissu congelé par spectrométrie de masse (GC-MS/MS). / This work is devoted to the characterization of a specific oncogenic fusion between FGFR and TACC genes in gliomas. Overall, we screened 907 gliomas for FGFR3-TACC3 fusions. We found that FGFR3-TACC3 fusions exclusively affect IDH wild-type gliomas (3%), and are mutually exclusive with the EGFR amplification and the EGFR vIII variant, whereas it co-occurs with CDK4 amplification, MDM2 amplification and 10q loss. FGFR3–TACC3 fusions were associated with strong and homogeneous FGFR3 immunostaining. We show that FGFR3 immunostaining is a sensitive predictor of the presence of FGFR3-TACC3 fusions. FGFR3-TACC3 glioma patients had a longer overall survival than those patients with IDH wild-type glioma. We treated two patients with FGFR3–TACC3 rearrangements with a specific FGFR-TK inhibitor and we observed a clinical improvement in both and a minor response in one patient. In the second section, we developed a non-invasive diagnostic tool by 1H-magnetic resonance spectroscopy in IDH mutant gliomas. We optimized a uniquely different spectroscopy sequence called MEGA-PRESS for the detection of the oncometabolite 2-hydroxyglutarate (2 HG) that specifically accumulates in IDH mutant gliomas. We analysed a prospective cohort of 25 patients before surgery for suspected grade II and grade III gliomas and we assessed specificity and sensitivity, correlation with 2 HG concentrations in the tumor and associations with grade and genomic background. We found that MEGA-PRESS is highly specific (100%) and sensitive (80%) for the prediction of IDH mutation and correlated with 2 HG levels measured by gas chromatography-tandem mass spectrometry (GC-MS/MS) in frozen tissue.
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Att utvärdera samband mellan subjektivt skattad smärta och transmittorsubstanser med magnetresonansspektroskopi : - En pilotstudieLundmark, Hanna, Yamamoto, Helya January 2022 (has links)
Att utvärdera samband mellan subjektivt skattad smärta och transmittorsubstanser med magnetresonansspektroskopi Bakgrund: Smärta är en komplex upplevelse, som involverar olika delar av hjärnan. Regionen anterior cingulate cortex (ACC) är kopplad till upplevelsen av smärta och delas in i ett flertal mindre regioner, till exempel den pregenuala regionen (pgACC) och dorsala regionen (dACC). För att studera olika metaboliter och transmittorsubstanser kan magnetresonansspektroskopi (MRS) användas. MRS och sekvensen MEGA-PRESS kan mäta specifika transmittorsubstanser såsom Gamma-AminoButyric Acid (GABA) och glutamin-glutamat (Glx). Motiv: Det finns kunskapsluckor kring hur individens subjektiva smärtupplevelse i relation till transmittorsubstanser objektivt kan mätas och utvärderas. Syfte: Att med MRS och MEGA-PRESS undersöka GABA+ och Glx-nivåer i hjärnområdena pgACC och dACC samt undersöka samband mellan smärtkänslighet och GABA+ och Glx i pgACC och dACC. Metod: En kvantitativ, experimentell pilotstudie genomfördes med tio friska deltagare. Initialt skannades deltagarna i MRT och smärtstimulerades, sedan skattade de den upplevda smärtan med hjälp av Numeric Rating Scale. MRS och tekniken MEGA-PRESS användes för att mäta transmittorsubstansnivåerna. Resultat: Studien visade att det fanns en statistiskt signifikant negativ korrelation mellan skattad smärtintensitet och uppmätta nivåer av GABA+ i pgACC (Spearman´s rho = -0,67; p = 0,04). Det fanns även ett statistiskt signifikant positivt samband mellan skattad smärtintensitet och uppmätta nivåer av Glx i dACC (Spearman´s rho =0,73; p=0,02). Vidare fanns signifikant skillnad i Glx mellan pgACC och dACC och en icke signifikant skillnad i GABA+. Konklusion: Sammanfattningsvis visar resultatet att MRS och MEGA-PRESS kan kvantifiera transmittorsubstanser vid utvärdering av smärtkänslighet och att det finns en positiv korrelation mellan Glx och skattad smärtintensitet, samt en negativ korrelation mellan GABA+ och skattad smärtintensitet. Detta kan ge fördjupad insikt i individens smärtupplevelse och kan främja den individuella behandlingen. Genom att ta hänsyn till sambandet mellan smärta och transmittorsubstanser kan det bidra till ökad förståelse kring individens smärtupplevelse. / To evaluate the relation between subjectively estimated pain and neurotransmitters using magnetic resonance spectroscopy Background: Pain is a complex experience that involves different parts of the brain. The region anterior cingulate cortex (ACC) is connected to the experience of pain and can be divided into several smaller areas, such as the pregenual region (pgACC) and the dorsal region (dACC). To study different metabolites and neurotransmitters, magnetic resonance spectroscopy (MRS) can be used. MRS and the sequence (MEGA-PRESS) can measure specific neurotransmitters such as Gamma-AminoButyric Acid (GABA) and glutamin-glutamate (Glx). Motive: There are knowledge gaps about how the individual's subjective pain experience in relation to neurotransmitters can be objectively measured and evaluated. Aim: Using MRS and MEGA-PRESS to examine levels of GABA+ and Glx in the brain regions pgACC and dACC and to examine the relationship between pain sensitivity and GABA+ and Glx in pgACC and dACC. Methods: A quantitative, experimental pilot study was conducted which included ten healthy participants. The participants were initially scanned in the MRI and subjected to pain-stimulation, thereafter the participants rated the perceived pain using Numeric Rating Scale. MRS and the sequence MEGA-PRESS were used to quantify the neurotransmitters of interest. Result: There was a significant, negative correlation between rated pain intensity and measured GABA+ levels in pgACC (Spearman´s rho = -0,67; p = 0,04). There was also a significant, positive correlation between rated pain intensity and measured levels of Glx in dACC (Spearman´s rho =0,73; p=0,02). Furthermore, there was a significant difference in Glx between pgACC and dACC as well as a non-significant difference in GABA+ between regions. Conclusion: In summary, the result shows that MRS and MEGA-PRESS can quantify neurotransmitters when evaluating pain sensitivity and that there is a positive correlation between Glx and estimated pain intensity, and also a negative correlation between GABA+ and estimated pain intensity. This can provide a deeper insight into the individual’s pain experience and promote individual treatment. Further research regarding the meaning of the different brain regions when measuring neurotransmitters is recommended.
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