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We propose two novel strategies for tuning b-tensors to enable accurate measurements without interference from TDD due to restricted diffusion. The first strategy involves identifying encoding tensor projections that yield equal mean diffusivities (MD), providing robust tuning across a wide range of diffusion spectra. The second strategy uses geometric averaging of signals, ensuring tuning regardless of the diffusion spectra. Importantly, the same encoding waveforms used for geometric averaging to probe microscopic anisotropy (\u00b5A) can also generate an independent contrast due to TDD. This is enabled by considering spectral anisotropy of encoding and defining the spectral principal axis system (SPAS), which unfolds TDD as an additional independent dimension in tensor-valued encoding. Projections of encoding waveforms along the SPAS axes allow for the simultaneous acquisition of independent contrasts due to both \u00b5A and TDD within a single multidimensional diffusion encoding protocol. Additionally, SPAS projections inherit useful properties from the reference tensor, such as optimized b-value, motion nulling, and minimal concomitant field effects. This framework is demonstrated through simulations of various restricted diffusion compartments. Experimental validation on perfusion-fixed and in vivo rat brains highlights the method\u2019s potential for enhanced microstructural specificity. In addition to mapping MD, fractional anisotropy, and unbiased microscopic fractional anisotropy, we propose a model-free approach to independently map \u00b5A and TDD. This approach uses a minimal yet highly specific protocol, enabling the identification of distinct \u00b5A-TDD contrasts across different brain regions, including details in cortical gray matter, choroid plexus, dentate gyrus of the hippocampus, and white matter.<\/jats:p>","DOI":"10.1162\/imag.a.35","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T18:47:52Z","timestamp":1747853272000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":4,"title":["Spectral principal axis system (SPAS) and tuning of tensor-valued encoding for microscopic anisotropy and time-dependent diffusion in the rat brain"],"prefix":"10.1162","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-7182","authenticated-orcid":false,"given":"Samo","family":"Lasi\u010d","sequence":"first","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine, Copenhagen University Hospital\u2014Amager and Hvidovre, Copenhagen, Denmark"},{"name":"Department of Diagnostic Radiology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-0669","authenticated-orcid":false,"given":"Nathalie","family":"Just","sequence":"additional","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine, Copenhagen University Hospital\u2014Amager and Hvidovre, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-8223","authenticated-orcid":false,"given":"Markus","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-587X","authenticated-orcid":false,"given":"Filip","family":"Szczepankiewicz","sequence":"additional","affiliation":[{"name":"Medical Radiation Physics, Clinical Sciences Lund, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4769-5797","authenticated-orcid":false,"given":"Matthew","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-442X","authenticated-orcid":false,"given":"Henrik","family":"Lundell","sequence":"additional","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine, Copenhagen University Hospital\u2014Amager and Hvidovre, Copenhagen, Denmark"},{"name":"Magnetic Resonance Section, DTU Health Tech, Technical University of Denmark, Kgs. 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