{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T23:11:44Z","timestamp":1773789104820,"version":"3.50.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Recently, new MRI systems working at magnetic field below 10 mT (Very and Ultra Low Field regime) have been developed, showing improved T<jats:sub>1<\/jats:sub>-contrast in projected 2D maps (i.e. images without slice selection). Moving from projected 2D to 3D maps is not trivial due to the low SNR of such devices. This work aimed to demonstrate the ability and the sensitivity of a VLF-MRI scanner operating at 8.9 mT in quantitatively obtaining 3D longitudinal relaxation rate (R<jats:sub>1<\/jats:sub>) maps and distinguishing between voxels intensities. We used phantoms consisting of vessels doped with different Gadolinium (Gd)-based Contrast Agent (CA) concentrations, providing a set of various R<jats:sub>1<\/jats:sub> values. As CA, we used a commercial compound (MultiHance\u00ae, gadobenate dimeglumine) routinely used in clinical MRI.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>3D R<jats:sub>1<\/jats:sub> maps and T<jats:sub>1<\/jats:sub>-weighted MR images were analysed to identify each vessel. R<jats:sub>1<\/jats:sub> maps were further processed by an automatic clustering analysis to evaluate the sensitivity at the single-voxel level. Results obtained at 8.9 mT were compared with commercial scanners operating at 0.2 T, 1.5 T, and 3 T.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>VLF R<jats:sub>1<\/jats:sub> maps offered a higher sensitivity in distinguishing the different CA concentrations and an improved contrast compared to higher fields. Moreover, the high sensitivity of 3D quantitative VLF-MRI allowed an effective clustering of the 3D map values, assessing their reliability at the single voxel level. Conversely, in all fields, T<jats:sub>1<\/jats:sub>-weighted images were less reliable, even at higher CA concentrations.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In summary, with few excitations and an isotropic voxel size of 3 mm, VLF-MRI 3D quantitative mapping showed a sensitivity better than 2.7 s<jats:sup>-1<\/jats:sup> corresponding to a concentration difference of 0.17 mM of MultiHance in copper sulfate doped water, and improved contrast compared to higher fields. Based on these results, future studies should characterize R<jats:sub>1<\/jats:sub> contrast at VLF, also with other CA, in the living tissues.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0285391","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T17:33:28Z","timestamp":1683308008000},"page":"e0285391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analyzing the sensitivity of quantitative 3D MRI of longitudinal relaxation at very low field in Gd-doped phantoms"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-2464","authenticated-orcid":true,"given":"Danilo","family":"de Iure","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allegra","family":"Conti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Galante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Spadone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Hilschenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Caulo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Sensi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosimo","family":"Del Gratta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Della Penna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"pone.0285391.ref001","article-title":"A low-cost and shielding-free ultra-low-field brain MRI scanner","author":"Y Liu","year":"2021","journal-title":"Nature Communications"},{"key":"pone.0285391.ref002","article-title":"Low-Field MRI: How Low Can We Go? A Fresh View on an Old Debate.","volume":"v","author":"M Sarracanie","year":"2020","journal-title":"Frontiers in Physics"},{"issue":"3 PART 1","key":"pone.0285391.ref003","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1109\/TASC.2010.2088353","article-title":"Co-registration of interleaved MEG and ULF MRI using a 7 channel low-T c SQUID system","volume":"21","author":"PE Magnelind","year":"2011","journal-title":"IEEE Transactions on Applied Superconductivity"},{"issue":"6","key":"pone.0285391.ref004","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1002\/mrm.24413","article-title":"Hybrid ultra-low-field MRI and magnetoencephalography system based on a commercial whole-head neuromagnetometer","volume":"69","author":"PT Vesanen","year":"2013","journal-title":"Magnetic Resonance in Medicine"},{"key":"pone.0285391.ref005","doi-asserted-by":"crossref","DOI":"10.2528\/PIER13070404","article-title":"NMR detection at 8.9 mT with a GMR based sensor coupled to a superconducting Nb flux tranformer","volume":"142","author":"R Sinibaldi","year":"2013","journal-title":"Progress In Electromagnetics Research"},{"key":"pone.0285391.ref006","doi-asserted-by":"crossref","first-page":"e0142701","DOI":"10.1371\/journal.pone.0142701","article-title":"Fast room temperature very low field-magnetic resonance imaging system compatible with magnetoencephalography environment.","volume":"10","author":"A Galante","year":"2015","journal-title":"PLoS One."},{"key":"pone.0285391.ref007","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jmr.2013.10.011","article-title":"An advanced phantom study assessing the feasibility of neuronal current imaging by ultra-low-field NMR","author":"R K\u00f6rber","year":"2013","journal-title":"Journal of Magnetic Resonance"},{"key":"pone.0285391.ref008","doi-asserted-by":"crossref","DOI":"10.3389\/fphy.2021.647376","article-title":"Computational and Phantom-Based Feasibility Study of 3D dcNCI With Ultra-Low-Field MRI.","volume":"9","author":"N H\u00f6fner","year":"2021","journal-title":"Frontiers in Physics"},{"key":"pone.0285391.ref009","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.mri.2014.01.012","article-title":"Current-density imaging using ultra-low-field MRI with zero-field encoding.","author":"PT Vesanen","year":"2014","journal-title":"Magnetic Resonance Imaging."},{"key":"pone.0285391.ref010","first-page":"1","article-title":"Ultra-sensitive SQUID systems for applications in biomagnetism and ultra-low field MRI.","author":"R K\u00f6rber","year":"2019","journal-title":"2019 IEEE International Superconductive Electronics Conference (ISEC);"},{"key":"pone.0285391.ref011","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780199796434.001.0001","volume-title":"Ultra-low field nuclear magnetic resonance: a new MRI regime","author":"RH Kraus","year":"2014"},{"key":"pone.0285391.ref012","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jmr.2005.11.005","article-title":"SQUID-detected microtesla MRI in the presence of metal","author":"M M\u00f6\u00dfle","year":"2006","journal-title":"Journal of Magnetic Resonance"},{"key":"pone.0285391.ref013","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.pbiomolbio.2004.08.010","article-title":"A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus","author":"JPD Wilde","year":"2005","journal-title":"Progress in Biophysics and Molecular Biology"},{"key":"pone.0285391.ref014","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejrad.2019.07.005","article-title":"Safety and efficiency of low-field magnetic resonance imaging in patients with cardiac rhythm management devices","author":"C Schukro","year":"2019","journal-title":"European Journal of Radiology"},{"key":"pone.0285391.ref015","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.1038\/s41598-022-09760-2","article-title":"Development of a mobile low-field MRI scanner","author":"S Deoni","year":"2022","journal-title":"Scientific Reports"},{"key":"pone.0285391.ref016","doi-asserted-by":"crossref","first-page":"19194","DOI":"10.1073\/pnas.1319334110","article-title":"MRI of the human brain at 130 microtesla","author":"B Inglis","year":"2013","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0285391.ref017","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/mrm.24177","article-title":"Measurements of T1-relaxation in ex vivo prostate tissue at 132 \u03bcT","author":"S Busch","year":"2012","journal-title":"Magnetic Resonance in Medicine"},{"key":"pone.0285391.ref018","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature11971","article-title":"Magnetic resonance fingerprinting","author":"D Ma","year":"2013","journal-title":"Nature"},{"key":"pone.0285391.ref019","doi-asserted-by":"crossref","first-page":"xxxvii","DOI":"10.1016\/B978-0-12-817057-1.00001-9","article-title":"Quantitative MRI: Rationale and Challenges","author":"V Gulani","year":"2020","journal-title":"In Advances in Magnetic Resonance Technology and Applications"},{"issue":"11394","key":"pone.0285391.ref020","article-title":"Deep learning for fast low-field MRI acquisitions.","volume":"12","author":"R Ayde","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0285391.ref021","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1039\/b510982p","article-title":"Strategies for increasing the sensitivity of gadolinium based MRI contrast agents","volume":"35","author":"P. Caravan","year":"2006","journal-title":"Chemical Society Reviews"},{"key":"pone.0285391.ref022","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/cmmi.100","article-title":"Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents.","author":"S Laurent","year":"2006","journal-title":"Contrast media & molecular imaging."},{"key":"pone.0285391.ref023","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1007\/s003300050781","article-title":"Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents.","volume":"9","author":"PA Rinck","year":"1999","journal-title":"European radiology."},{"key":"pone.0285391.ref024","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1097\/01.rli.0000184756.66360.d3","article-title":"Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths.","volume":"40","author":"M Rohrer","year":"2005","journal-title":"Investigative radiology."},{"key":"pone.0285391.ref025","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/cmmi.267","article-title":"Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents.","volume":"4","author":"P Caravan","year":"2009","journal-title":"Contrast Media & Molecular Imaging."},{"issue":"1","key":"pone.0285391.ref026","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/mrm.20316","article-title":"SQUID-detected MRI at 132 \u03bcT with T1-weighted contrast established at 10 \u03bcT-300 mT","volume":"53","author":"SK Lee","year":"2005","journal-title":"Magnetic Resonance in Medicine"},{"key":"pone.0285391.ref027","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/mrm.1910300211","article-title":"Novel approaches to low-cost MRI","volume":"30","author":"A Macovski","year":"1993","journal-title":"Magnetic resonance in medicine"},{"key":"pone.0285391.ref028","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/mrm.1910150305","article-title":"NMR imaging in the earth\u2019s magnetic field","author":"J Stepi\u0161nik","year":"1990","journal-title":"Magnetic resonance in medicine"},{"key":"pone.0285391.ref029","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1088\/0957-0233\/8\/2\/015","article-title":"A 4.2 K receiver coil and SQUID amplifier used to improve the SNR of low-field magnetic resonance images of the human arm","volume":"8","author":"HC Seton","year":"1997","journal-title":"Measurement Science and Technology"},{"key":"pone.0285391.ref030","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1081\/JCMR-120026928","article-title":"Erratum: How We Perform Delayed Enhancement Imaging (Journal of Cardiovascular Magnetic Resonance (2003) 5: 3 (505\u2013514)).","volume":"5","author":"RJ Kim","year":"2003","journal-title":"Journal of Cardiovascular Magnetic Resonance."},{"key":"pone.0285391.ref031","doi-asserted-by":"crossref","first-page":"e26366","DOI":"10.1371\/journal.pone.0026366","article-title":"Assessing antiangiogenic therapy response by DCE-MRI: development of a physiology driven multi-compartment model using population pharmacometrics.","volume":"6","author":"A Steingoetter","year":"2011","journal-title":"PloS one"},{"key":"pone.0285391.ref032","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1103\/PhysRev.80.580","article-title":"Spin echoes.","author":"EL Hahn","year":"1950","journal-title":"Physical review"},{"key":"pone.0285391.ref033","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1088\/0031-9155\/29\/12\/004","article-title":"Derivation of quantitative information in NMR imaging: a phantom study","volume":"29","author":"CJG Bakker","year":"1984","journal-title":"Physics in Medicine and Biology"},{"key":"pone.0285391.ref034","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/mrm.1910030505","article-title":"Improved formulae for signal amplitudes in repeated NMR sequences: Applications in NMR imaging","author":"GO Sperber","year":"1986","journal-title":"Magnetic Resonance in Medicine"},{"issue":"5","key":"pone.0285391.ref035","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1148\/rg.295095034","article-title":"Principles, Techniques, and Applications of T2*-based MR Imaging and its Special Applications.","volume":"29","author":"GB Chavhan","year":"2009","journal-title":"Radiographics.September"},{"key":"pone.0285391.ref036","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1109\/LCOMM.2018.2797057","article-title":"Impact of LoRa Imperfect Orthogonality: Analysis of Link-Level Performance","volume":"22","author":"D Croce","year":"2018","journal-title":"IEEE Communications Letters"},{"key":"pone.0285391.ref037","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.neuroimage.2012.05.051","article-title":"A K-means multivariate approach for clustering independent components from magnetoencephalographic data","volume":"62","author":"S Spadone","year":"2012","journal-title":"NeuroImage"},{"key":"pone.0285391.ref038","doi-asserted-by":"crossref","first-page":"118005","DOI":"10.1016\/j.neuroimage.2021.118005","article-title":"Temporal modes of hub synchronization at rest.","volume":"235","author":"F de Pasquale","year":"2021","journal-title":"NeuroImage"},{"key":"pone.0285391.ref039","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/term.2494","article-title":"Multimodal-3D imaging based on \u03bcMRI and \u03bcCT techniques bridges the gap with histology in visualization of the bone regeneration process","volume":"12","author":"R Sinibaldi","year":"2018","journal-title":"Journal of Tissue Engineering and Regenerative Medicine"},{"key":"pone.0285391.ref040","doi-asserted-by":"crossref","first-page":"e0149260","DOI":"10.1371\/journal.pone.0149260","article-title":"In vitro longitudinal relaxivity profile of Gd (ABE-DTTA), an investigational magnetic resonance imaging contrast agent.","volume":"11","author":"A Varga-Szemes","year":"2016","journal-title":"PLoS One"},{"key":"pone.0285391.ref041","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.bioeng.9.060906.152010","article-title":"SQUID-Detected Magnetic Resonance Imaging in Microtesla Fields","author":"J Clarke","year":"2007","journal-title":"Annual review of biomedical engineering"},{"issue":"6","key":"pone.0285391.ref042","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1002\/mrm.25060","article-title":"Prototype phantoms for characterization of ultralow field magnetic resonance imaging","volume":"72","author":"MA Boss","year":"2014","journal-title":"Magnetic resonance in 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