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However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve <jats:sup>1<\/jats:sup>H\u2010MRS quality in the PAG using spectral registration for frequency and phase error correction; (2) investigate whether spectral registration is particularly useful in cases of greater head motion; and (3) examine metabolite quantification using literature\u2010based or individual\u2010based water relaxation times.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Spectra were acquired in 33 healthy volunteers (50.1\u2009years, SD\u2009=\u200917.19, 18 females) on a 3\u2009T Philipps MR system using a point\u2010resolved spectroscopy (PRESS) sequence optimized with very selective saturation pulses (OVERPRESS) and voxel\u2010based flip angle calibration (effective volume of interest size: 8.8\u2009\u00d7\u200910.2\u2009\u00d7\u200912.2\u2009mm<jats:sup>3<\/jats:sup>). Spectra were fitted using LCModel and SNR, NAA peak linewidths and Cram\u00e9r\u2010Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Spectral registration improved SNR by 5% (<jats:italic>p<\/jats:italic>\u2009=\u20090.026, median value post\u2010correction: 18.0) and spectral linewidth by 23% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, 4.3\u2009Hz), and reduced the metabolites' CRLBs by 1% to 15% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.026). Correlational analyses revealed smaller SNR improvements with greater head motion (<jats:italic>p<\/jats:italic>\u2009=\u20090.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual\u2010based compared to literature\u2010based water relaxation times (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates high\u2010quality <jats:sup>1<\/jats:sup>H\u2010MRS acquisition in the PAG using spectral registration. This shows promise for future <jats:sup>1<\/jats:sup>H\u2010MRS studies in the PAG and possibly other clinically relevant brain regions with similar methodological challenges.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrm.29832","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T17:47:53Z","timestamp":1696614473000},"page":"28-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Improving magnetic resonance spectroscopy in the brainstem periaqueductal gray using spectral registration"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-3546","authenticated-orcid":false,"given":"Laura","family":"Sirucek","sequence":"first","affiliation":[{"name":"Department of Chiropractic Medicine, Integrative Spinal Research Group Balgrist University Hospital, University of Zurich  Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklaus","family":"Zoelch","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Imaging, Institute of Forensic Medicine University of Zurich  Zurich Switzerland"},{"name":"Department of Psychiatry, Psychotherapy, and Psychosomatics Psychiatric University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Schweinhardt","sequence":"additional","affiliation":[{"name":"Department of Chiropractic Medicine, Integrative Spinal Research Group Balgrist University Hospital, University of Zurich  Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823fcdee"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq075"},{"key":"e_1_2_7_4_1","article-title":"The impact of Alzheimer's disease on the functional connectivity between brain regions underlying pain perception","volume":"15","author":"Cole LJ","year":"2011","journal-title":"Eur J Pain"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22537"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20298"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-318886"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0b013e3182408f04"},{"key":"e_1_2_7_9_1","first-page":"S129","article-title":"Abnormal resting state functional connectivity of the periaqueductal grey in patients with fibromyalgia","volume":"34","author":"Truini A","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2018.01.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1647-17.2017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2014.08.019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-012-0491-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01452-6"},{"key":"e_1_2_7_15_1","first-page":"263","article-title":"Alteration of the antinociceptive systems in chronic daily headaches","volume":"43","author":"Buonanotte F","year":"2006","journal-title":"Rev Neurol"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000722"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-3078-0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00623"},{"key":"e_1_2_7_19_1","volume-title":"Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging","author":"Adam A","year":"2020"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910030413"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25094"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28287"},{"key":"e_1_2_7_23_1","unstructured":"BottomleyPA.Google Patents assignee. 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