Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.

Altered cerebral connectivity is one of the core pathophysiological mechanism underlying the development and progression of information-processing deficits in schizophrenia. To date, most diffusion tensor imaging (DTI) studies used fractional anisotropy (FA) to investigate disrupted white matter connections. However, a quantitative interpretation of FA changes is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of white matter alterations could be achieved by measuring fiber density (FD) - a novel non-tensor-derived diffusion marker. This study investigates, for the first time, FD alterations in schizophrenia patients. FD and FA maps were derived from diffusion data of 25 healthy controls (HC) and 21 patients with schizophrenia (SZ). Using tract-based spatial statistics (TBSS), group differences in FD and FA were investigated across the entire white matter. Furthermore, we performed a region of interest (ROI) analysis of frontal fasciculi to detect potential correlations between FD and positive symptoms. As a result, whole brain TBSS analysis revealed reduced FD in SZ patients compared to HC in several white matter tracts including the left and right thalamic radiation (TR), superior longitudinal fasciculus (SLF), corpus callosum (CC), and corticospinal tract (CST). In contrast, there were no significant FA differences between groups. Further, FD values in the TR were negatively correlated with the severity of positive symptoms and medication dose in SZ patients. In summary, a novel diffusion-weighted data analysis approach enabled us to identify widespread FD changes in SZ patients with most prominent white matter alterations in the frontal and subcortical regions. Our findings suggest that the new FD measure may be more sensitive to subtle changes in the white matter microstructure compared to FA, particularly in the given population. Therefore, investigating FD may be a promising approach to detect subtle changes in the white matter microstructure of altered connectivity in schizophrenia.

Objectives To compare ultra-low-dose CT (ULD-CT) of the osseous pelvis with tin filtration to standard clinical CT (CT), and to assess the quality of computed virtual pelvic radiographs (VRs). Methods CT protocols were optimized in a phantom and three pelvic cadavers. Thirty prospectively included patients received both standard CT (automated tube voltage selection and current modulation) and tin-filtered ULD-CT of the pelvis (Sn140kV/50mAs). VRs of ULD-CT data were computed using an adapted cone beam–based projection algorithm and were compared to digital radiographs (DRs) of the pelvis. CT and DR dose parameters and quantitative and qualitative measures (1 = worst, 4 = best) were compared. CT and ULD-CT were assessed for osseous pathologies. Results Dose reduction of ULD-CT was 84% compared to CT, with a median effective dose of 0.38 mSv (quartile 1–3: 0.37–0.4 mSv) versus 2.31 mSv (1.82–3.58 mSv; p < .001), respectively. Mean dose of DR was 0.37 mSv (± 0.14 mSv). The median signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of bone were significantly higher for CT (64.3 and 21.5, respectively) compared to ULD-CT (50.4 and 18.8; p ≤ .01), while ULD-CT was significantly more dose efficient (figure of merit (FOM) 927.6) than CT (FOM 167.6; p < .001). Both CT and ULD-CT were of good image quality with excellent depiction of anatomy, with a median score of 4 (4–4) for both methods (p = .1). Agreement was perfect between both methods regarding the prevalence of assessed osseous pathologies (p > .99). VRs were successfully calculated and were equivalent to DRs. Conclusion Tin-filtered ULD-CT of the pelvis at a dose equivalent to standard radiographs is adequate for assessing bone anatomy and osseous pathologies and had a markedly superior dose efficiency than standard CT. Key Points • Ultra-low-dose pelvic CT with tin filtration (0.38 mSv) can be performed at a dose of digital radiographs (0.37 mSv), with a dose reduction of 84% compared to standard CT (2.31 mSv). • Tin-filtered ultra-low-dose CT had lower SNR and CNR and higher image noise than standard CT, but showed clear depiction of anatomy and accurate detection of osseous pathologies. • Virtual pelvic radiographs were successfully calculated from ultra-low-dose CT data and were equivalent to digital radiographs.