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QTI metrics were computed for idealized as well as realistic oscillating and pulsed gradient waveforms using analytical diffusion spectra with 1D and 2D short\u2010range disorder along and perpendicular to axons. For in vivo validation, the waveforms were integrated into a multiband spiral spin\u2010echo sequence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The simulations demonstrate frequency\u2010dependent QTI metrics. The combination of tuning and spectral isotropy led to metrics close to the simulated ground\u2010truth at the centroid frequency of the encoding spectrum. Realistic waveforms with broader bandwidth compared to idealized waveforms introduce little additional error in QTI metrics due to truncation of the cumulant expansion. In agreement with literature, omitting tuning and spectral isotropy reduces isotropic variance and increases microscopic fractional anisotropy when LTE contains lower frequencies, and vice versa for PTE. This observation is confirmed qualitatively by the in vivo measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The accuracy of the centroid frequency approximation depends on the combination of encoding spectra and investigated tissue. Using similar encoding spectra for tuning and spectral isotropy leads to metrics, characteristic to the centroid frequency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mrm.70529","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T03:53:27Z","timestamp":1786679607000},"page":"2642-2659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human In Vivo Validation of Frequency\u2010Dependent\n                    <scp>QTI<\/scp>"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3094-1333","authenticated-orcid":false,"given":"Svenja","family":"Niesen","sequence":"first","affiliation":[{"name":"MR Physics, German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Faculty of Mathematics and Natural Sciences University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2444-9649","authenticated-orcid":false,"given":"Marten","family":"Veldmann","sequence":"additional","affiliation":[{"name":"MR Physics, German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2251-0361","authenticated-orcid":false,"given":"Ali","family":"Ajouz","sequence":"additional","affiliation":[{"name":"Department of Radiology and Neuroradiology UKSH, CAU Kiel  Kiel Germany"},{"name":"Section Biomedical Imaging, Department of Radiology and Neuroradiology University Hospital Schleswig\u2010Holstein, Christian\u2010Albrechts\u2010Universit\u00e4t zu Kiel  Kiel Germany"},{"name":"Siemens Healthineers AG  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-9141","authenticated-orcid":false,"given":"Tony","family":"St\u00f6cker","sequence":"additional","affiliation":[{"name":"MR Physics, German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Department of Physics &amp; 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