Depiction Fidelity and Specificity in Direct MRI of Collagen: Addressing Signal Decay at the Microsecond Timescale

Purpose Gap‐filled zero echo time (ZTE) acquisitions combined with dedicated short‐ T 2 hardware enable direct collagen imaging on the timescale of macromolecular (MM) signals, with T 2 s ˜ 10 μs. However, present methods offer limited depiction fidelity, and their specificity towards MM content is poorly understood. This work presents methodology to improve depiction fidelity of MM signals and investigates how imaging parameters influence MM specificity. Methods 1D simulations of gap‐filled ZTE sequences acquiring MM signals are used to evaluate depiction fidelity and specificity via the modulation transfer function (MTF) and point spread function (PSF). Insights are used to address signal decay at the microsecond timescale by (i) modifying the k‐space sampling pattern through gap filling with MTF smoothing, (ii) selecting acquisition parameters that optimize MM specificity and (iii) designing a post‐processing filter to improve resolution. The approaches are demonstrated with 3D imaging simulations and experiments. Results Gap‐filled ZTE with specialized hardware targets MM signals but enters a unique imaging regime where depiction fidelity is limited: the PSF exhibits a broad main lobe from T 2 blurring and far‐reaching side lobes caused by a kink in the k‐space sampling pattern. The latter is addressed through MTF smoothing. MM specificity is then maximized by subtracting two images acquired at different times but maintaining imaging bandwidth. Finally, post‐processing filters narrow MM PSF main lobe, reducing T 2 blurring and improving depiction fidelity. Conclusion The investigation and developed methods improve collagen MM imaging, with potential applications for in vivo imaging or assessing materials that exhibit decay on MM timescales.