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Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies
Acknowledgements We thank Craig Lambert for his help in processing the MRS data. The study was funded by the Sir Jules Thorn Charitable Trust (grant ref: 05/JTA) and was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre and Biomedical Research Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge.Peer reviewedPublisher PD
Advances in proton MR spectroscopy for quantifying pain associated metabolic changes in the human brain
In this work non-invasive in vivo detection of excitatory neurotransmitter
glutamate andother cortical metabolites and their changes in the presence
of acute and chronic pain wasperformed in the human brain with proton
magnetic resonance spectroscopy (1H-MRS).This information can be used to
better understand biochemical processes of cerebral painprocessing.
Following introductory material, the first part of this thesis describes
theimplemented method for post-processing of MR spectroscopic data to
estimate absoluteconcentrations of the brain metabolites by considering the
heterogeneous tissue compositionin the spectroscopic voxel. Phantom and in
vivo brain studies demonstrated theadvantage of this method by reduced
inter-individual variation of calculated metabolicconcentrations as well as
enhanced quantitation accuracy. The second part of this workpresents the
implemented method for the stimulus triggered data sampling permittingthe
acquisition of in vivo 1H-MR spectra with a time resolution of few seconds.
It wasshown that this method enables detection of changes of the
neurotransmitter glutamateinduced by short acute pain stimuli. Considering
these data, it was possible to characterisechanges of the glutamatergig
neurotransmission associated with the sensation ofthe acute pain. The third
part describes in vivo measurements on chronic pain patientsand healthy
controls aiming to evaluate the changes of several brain metabolites in
thedifferent cerebral pain processing regions associated with chronic pain.
Patients revealeddecreased concentrations of the metabolic cell density
markers and neurotransmitters indicatingthe degenerative processes as well
as neurotransmitter dysfunctions, respectively.Results of this thesis
indicate that pain induced metabolic changes in the human brainare
traceable with the 1H-MRS by using experimental environment as it is used
in clinicalroutine. This offers a broad spectrum of further applications
aiming to explore thecerebral pain processing as well as to improve the
specificity of the diagnostic assessmentof the chronic pain disease.Die vorliegende Arbeit beschreibt die Anwendung der Protonenmagnetresonanzspektroskopie(1H-MRS) zum nicht invasiven Nachweis von schmerzinduzierten Änderungen des erregenden Neurotransmitters Glutamat sowie anderer Metaboliten im menschlichen Gehirn. Diese Informationen könnten zu einem tieferen Verständnis der biochemischen Prozesse während der zerebralen Schmerzverarbeitung beitragen. Nach einer kurzen Einführung in die Problematik der Schmerzforschung sowie in die Grundlagen der MRSTechnikwird eine im Rahmen dieser Arbeit implementierte Methode zur Berechnung absoluter Metabolitenkonzentrationen unter Berücksichtigung der heterogenen Gewebezusammensetzung im spektroskopischen Volumen beschrieben. Der Vorteil dieses Verfahrens in Bezug auf die Verbesserung der Quantifizierungsgenauigkeit wird anhand von Ergebnissen spektroskopischer Messungen in einem Phantom sowie in Gehirnen gesunder Probanden belegt. Der zweite Teil befasst sich mit der Implementierung einer Technik zur reizgetriggerten Akquisition von MR Spektren, welche eine Abtastung verschiedener Stimulationszustände mit einer zeitlichen Auflösung von wenigen Sekunden zulässt und somit die Detektion dynamischer Änderungen von Metaboliten im Gehirn ermöglicht. Durch die Anwendung dieser Methode bei Messungen an gesunden Probanden konnten Änderungen im Glutamatstoffwechsel infolge einer Stimulation mit kurzen akuten Schmerzreizen nachgewiesen werden. Im dritten Teil der Arbeit wird schließlich eine an gesunden Probanden und Patienten mit chronischen Schmerzen durchgeführte Studievorgestellt, innerhalb derer die Auswirkungen der Schmerzchronifizierung auf den Metabolismus in schmerzverarbeitenden kortikalen Regionen untersucht wurden. Die Ergebnisse dieser Studie belegen die Hypothese, dass chronischer Schmerz mit Veränderungen imNeurotransmitterstoffwechsel sowie mit degenerativen Prozessen auf zellulärer Ebene einhergeht. Zusammenfassend lässt sich sagen, dass es mit der 1H-MRS möglich ist, schmerzinduzierte Änderungen der Metaboliten im menschlichen Gehirn unter Verwendung von klinischen Standartverfahren zu quantifizieren. Dies wiederum eröffnet ein breites Feld für weitere Untersuchungen, welche zur Erforschung der zerebralen Schmerzverarbeitung sowie zur Verbesserung der Spezifität diagnostischer Verfahren bei chronischen Schmerzen beitragen könnten
Quantitative proton spectroscopic imaging of the neurochemical profile in rat brain with microliter resolution at ultra-short echo times.
Proton spectroscopy allows the simultaneous quantification of a high number of metabolite concentrations termed the neurochemical profile. The spin echo full intensity acquired localization (SPECIAL) scheme with an echo time of 2.7 ms was used at 9.4T for excitation of a slab parallel to a home-built quadrature surface coil in conjunction with phase encoding in the two remaining spatial dimensions to yield an effective spatial resolution of 1.7 microL. The absolute concentrations of at least 10 metabolites were calculated from the spectra of individual voxels using LCModel analysis. The calculated concentrations were used for constructing quantitative metabolic maps of the neurochemical profile in normal and pathological rat brain. Summation of individual spectra was used to assess the neurochemical profile of unique brain regions, such as corpus callosum, in rat for the first time. Following focal ischemia in rat pups, imaging the neurochemical profile indicated increased choline groups in the ischemic core and increased glutamine in the penumbra, which is proposed to reflect glutamate excitotoxicity. We conclude that it is feasible to achieve a sensitivity that is sufficient for quantitative mapping of the neurochemical profile at microliter spatial resolution
Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.
BackgroundAlthough the contrast-enhancing (CE) lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden.MethodsFifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy.ResultsThe Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data.ConclusionsThe similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM
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