{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:50:44Z","timestamp":1760237444580,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T00:00:00Z","timestamp":1589068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Algorithms"],"abstract":"<jats:p>Developing tools for precise quantification of brain metabolites using magnetic resonance spectroscopy (MRS) is an active area of research with broad application in non-invasive neurodegenerative disease studies. The tools are mainly developed based on black box (data-driven), or basis sets approaches. In this study, we offer a multi-stage framework that integrates data-driven and basis sets methods. We first use truncated Hankel singular value decomposition (HSVD) to decompose free induction decay (FID) signals into single tone FIDs, as the data-driven stage. Subsequently, single tone FIDs are clustered into basis sets while using initialized K-means with prior knowledge of the metabolites, as the basis set stage. The generated basis sets are fitted with the magnetic resonance (MR) spectra while using a linear constrained least square, and then the metabolite concentration is calculated. Prior to using our proposed multi-stage approach, a sequence of preprocessing blocks: water peak removal, phase correction, and baseline correction (developed in house) are used.<\/jats:p>","DOI":"10.3390\/a13050120","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T10:01:18Z","timestamp":1589191278000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Data-Driven Magnetic Resonance Spectroscopy Signal Analysis Framework to Quantify Metabolite Concentration"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-6425","authenticated-orcid":false,"given":"Omid","family":"Bazgir","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas Tech University, 2500 Broadway, Lubbock, TX 79409, USA"}]},{"given":"Eric","family":"Walden","sequence":"additional","affiliation":[{"name":"Texas Tech Neuroimaging Institute, Texas Tech University, 2500 Broadway, Lubbock, TX 79409, USA"}]},{"given":"Brian","family":"Nutter","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas Tech University, 2500 Broadway, Lubbock, TX 79409, USA"}]},{"given":"Sunanda","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas Tech University, 2500 Broadway, Lubbock, TX 79409, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1016\/j.ejrad.2011.03.076","article-title":"In vivo proton magnetic resonance spectroscopic signal processing for the absolute quantitation of brain metabolites","volume":"81","author":"Mandal","year":"2012","journal-title":"Eur. J. Radiol."},{"unstructured":"Lambert, J.B., Mazzola, E.P., and Ridge, C.D. (2019). Nuclear Magnetic Resonance Spectroscopy: An Introduction to Principles, Applications, and Experimental Methods, Wiley.","key":"ref_2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2016.061","article-title":"Characterization of proteins by in-cell NMR spectroscopy in cultured mammalian cells","volume":"11","author":"Barbieri","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1074\/jbc.R115.643247","article-title":"A unique tool for cellular structural biology: In-cell NMR","volume":"291","author":"Luchinat","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1073\/pnas.1915010117","article-title":"Conformational changes upon gating of KirBac1. 1 into an open-activated state revealed by solid-state NMR and functional assays","volume":"117","author":"Amani","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jsb.2007.04.001","article-title":"Looking into live cells with in-cell NMR spectroscopy","volume":"158","author":"Selenko","year":"2007","journal-title":"J. Struct. Biol."},{"doi-asserted-by":"crossref","unstructured":"Bazgir, O., Mitra, S., Nutter, B., and Walden, E. (2018, January 8\u201310). Fully automatic baseline correction in magnetic resonance spectroscopy. Proceedings of the 2018 IEEE Southwest Symposium on Image Analysis and Interpretation (SSIAI), Las Vegas, NV, USA.","key":"ref_7","DOI":"10.1109\/SSIAI.2018.8470319"},{"doi-asserted-by":"crossref","unstructured":"Staniszewski, M., Binczyk, F., Skorupa, A., Boguszewicz, L., Sokol, M., Polanska, J., and Polanski, A. (2015). Comparison of black box implementations of two algorithms of processing of NMR spectra, gaussian mixture model and singular value decomposition. BIOSIGNALS.","key":"ref_8","DOI":"10.5220\/0005210300570065"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nature25781","article-title":"High-resolution magnetic resonance spectroscopy using a solid-state spin sensor","volume":"555","author":"Glenn","year":"2018","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jmr.2008.09.005","article-title":"MRS signal quantitation: A review of time-and frequency-domain methods","volume":"195","author":"Poullet","year":"2008","journal-title":"J. Magn. Reson."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ijpsycho.2019.05.009","article-title":"Relationship of auditory electrophysiological responses to magnetic resonance spectroscopy metabolites in early phase psychosis","volume":"145","author":"Bartolomeo","year":"2019","journal-title":"Int. J. Psychophysiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jiec.2019.04.037","article-title":"Smartphone with optical, physical, and electrochemical nanobiosensors","volume":"77","author":"Seo","year":"2019","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/mrm.1910300604","article-title":"Estimation of metabolite concentrations from localized in vivo proton NMR spectra","volume":"30","author":"Provencher","year":"1993","journal-title":"Magn. Reson. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mrm.22579","article-title":"A constrained least-squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data","volume":"65","author":"Wilson","year":"2011","journal-title":"Magn. Reson. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/mrm.21081","article-title":"An algorithm for the automated quantitation of metabolites in in vitro NMR signals","volume":"56","author":"Reynolds","year":"2006","journal-title":"Magn. Reson. Med. J. Int. Soc. Magn. Reson. Med."},{"key":"ref_16","first-page":"1","article-title":"Time-domain semi-parametric estimation based on a metabolite basis set","volume":"18","author":"Ratiney","year":"2005","journal-title":"NMR Biomed. Int. J. Devoted Dev. Appl. Magn. Reson. Vivo"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev-anchem-061417-125852","article-title":"Recent advances in solid-state nuclear magnetic resonance spectroscopy","volume":"11","author":"Ashbrook","year":"2018","journal-title":"Annu. Rev. Anal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/mrm.21961","article-title":"MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T","volume":"61","author":"Mekle","year":"2009","journal-title":"Magn. Reson. Med. J. Int. Soc. Magn. Reson. Med."},{"doi-asserted-by":"crossref","unstructured":"Woods, A.J., Bikson, M., Chelette, K., Dmochowski, J., Dutta, A., Esmaeilpour, Z., Gebodh, N., Nitsche, M.A., and Stagg, C. (2019). Transcranial direct current stimulation integration with magnetic resonance imaging, magnetic resonance spectroscopy, near infrared spectroscopy imaging, and electroencephalography. Practical Guide to Transcranial Direct Current Stimulation, Springer.","key":"ref_19","DOI":"10.1007\/978-3-319-95948-1_11"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104502","DOI":"10.1063\/1.5119387","article-title":"Adaptive pre-whiten filtering for the free induction decay transversal signal in weak magnetic detection","volume":"90","author":"Liu","year":"2019","journal-title":"Rev. Sci. Instrum."},{"doi-asserted-by":"crossref","unstructured":"Zhu, H., and Barker, P.B. (2011). MR spectroscopy and spectroscopic imaging of the brain. Magnetic Resonance Neuroimaging, Springer.","key":"ref_21","DOI":"10.1007\/978-1-61737-992-5_9"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1021\/ac60214a047","article-title":"Smoothing and differentiation of data by simplified least squares procedures","volume":"36","author":"Savitzky","year":"1964","journal-title":"Anal. Chem."},{"unstructured":"De Graaf, R.A. (2013). In Vivo NMR Spectroscopy: Principles and Techniques, John Wiley & Sons.","key":"ref_23"},{"key":"ref_24","first-page":"493","article-title":"An automated quantitation of short echo time MRS spectra in an open source software environment: AQSES","volume":"20","author":"Poullet","year":"2007","journal-title":"Nmr Biomed. Int. J. Devoted Dev. Appl. Magn. Reson. Vivo"},{"unstructured":"Experts\u2019 Working Group on Advanced Single Voxel 1H, MRS, \u00d6z, G., Deelchand, D.K., Wijnen, J.P., Mlyn\u00e1rik, V., Xin, L., Mekle, R., Noeske, R., Scheenen, T.W.J., and Tk\u00e1\u010d, I. (2020). Advanced single voxel 1H magnetic resonance spectroscopy techniques in humans: Experts\u2019 consensus recommendations. NMR Biomed.","key":"ref_25"},{"doi-asserted-by":"crossref","unstructured":"Staniszewski, M., Skorupa, A., Boguszewicz, L., Sokol, M., and Polanski, A. (2016). Preprocessing methods in nuclear magnetic resonance spectroscopy. Information Technologies in Medicine, Springer.","key":"ref_26","DOI":"10.1007\/978-3-319-39796-2_28"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jmr.2013.06.012","article-title":"A robust automatic phase correction method for signal dense spectra","volume":"234","author":"Bao","year":"2013","journal-title":"J. Magn. Reson."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0169-7439(95)80075-K","article-title":"A singular value decomposition based algorithm for multicomponent exponential fitting of NMR relaxation signals","volume":"29","author":"Lupu","year":"1995","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/1099-1492(200005)13:3<129::AID-NBM619>3.0.CO;2-V","article-title":"Proton NMR chemical shifts and coupling constants for brain metabolites","volume":"13","author":"Govindaraju","year":"2000","journal-title":"NMR Biomed."},{"key":"ref_30","first-page":"154","article-title":"Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1H-MR spectroscopy","volume":"35","author":"Minati","year":"2010","journal-title":"J. Med Phys. Assoc. Med Phys. India"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/nbm.1940060114","article-title":"Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference","volume":"6","author":"Barker","year":"1993","journal-title":"NMR Biomed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/mrm.1910360302","article-title":"Quantitation of automated single-voxel proton MRS using cerebral water as an internal reference","volume":"36","author":"Soher","year":"1996","journal-title":"Magn. Reson. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/RMR.0b013e31821e568f","article-title":"Quantitative proton magnetic resonance spectroscopy and spectroscopic imaging of the brain: A didactic review","volume":"21","author":"Alger","year":"2010","journal-title":"Top. Magn. Reson. Imaging TMRI"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0730-725X(93)90418-D","article-title":"In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard","volume":"11","author":"Christiansen","year":"1993","journal-title":"Magn. Reson. Imaging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1118\/1.1501822","article-title":"Proton magnetic resonance spectroscopy in the brain: Report of AAPM MR Task Group# 9","volume":"29","author":"Drost","year":"2002","journal-title":"Med. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mri.2016.12.010","article-title":"Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study","volume":"38","author":"Fayed","year":"2017","journal-title":"Magn. Reson. Imaging"},{"doi-asserted-by":"crossref","unstructured":"Shiino, A. (2017). Proton magnetic resonance spectroscopy for dementia. Neuroimaging Diagnosis for Alzheimer\u2019s Disease and Other Dementias, Springer.","key":"ref_37","DOI":"10.1007\/978-4-431-55133-1_7"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/mrm.21450","article-title":"Measurement of glycine in human brain by triple refocusing 1H-MRS in vivo at 3.0 T","volume":"59","author":"Choi","year":"2008","journal-title":"Magn. Reson. Med. J. Int. Soc. Magn. Reson. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jmrb.1994.1048","article-title":"\u201cFor in vivo localized\u201d H NMR spectroscopy","volume":"104","author":"Ogg","year":"1994","journal-title":"J. Magn. Reson. Ser. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1006\/jmrb.1993.1056","article-title":"Absolute quantitation of water and metabolites in the human brain. II. Metabolite concentrations","volume":"102","author":"Kreis","year":"1993","journal-title":"J. Magn. Reson. Ser. B"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1148\/radiology.187.1.8451417","article-title":"Absolute concentrations of metabolites in the adult human brain in vivo: Quantification of localized proton MR spectra","volume":"187","author":"Michaelis","year":"1993","journal-title":"Radiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/mrm.27067","article-title":"In vivo estimation of transverse relaxation time constant (T2) of 17 human brain metabolites at 3T","volume":"80","author":"Wyss","year":"2018","journal-title":"Magn. Reson. Med."},{"key":"ref_43","first-page":"325","article-title":"Proton T1 and T2 relaxation times of human brain metabolites at 3 Tesla","volume":"14","author":"Gruber","year":"2001","journal-title":"NMR Biomed. Int. J. Devoted Dev. Appl. Magn. Reson. Vivo"}],"container-title":["Algorithms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4893\/13\/5\/120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:27:22Z","timestamp":1760174842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4893\/13\/5\/120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,10]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["a13050120"],"URL":"https:\/\/doi.org\/10.3390\/a13050120","relation":{},"ISSN":["1999-4893"],"issn-type":[{"type":"electronic","value":"1999-4893"}],"subject":[],"published":{"date-parts":[[2020,5,10]]}}}