IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology.

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Purpose A temporal diffusion MRI spectroscopy based approach has been developed to quantify cancer cell size and density in vivo. Methods A novel Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) method selects a specific limited diffusion spectral window for an accurate quantification of cell sizes ranging from 10 to 20 μm in common solid tumors. In practice, it is achieved by a combination of a single long diffusion time pulsed gradient spin echo (PGSE) and three low-frequency oscillating gradient spin echo (OGSE) acquisitions. To validate our approach, H&E staining and immunostaining of cell membranes, in concert with whole slide imaging, were used to visualize nuclei and cell boundaries, and hence enabled accurate estimates of cell size and cellularity. Results Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes were obtained in vivo for three types of human colon cancers. The IMPULSED-derived apparent cellularities showed a stronger correlation (r=−0.81, p<0.0001) with histology-derived cellularities than conventional ADCs (r=−0.69, p<0.03). Conclusion The IMPULSED approach samples a specific region of temporal diffusion spectra with enhanced sensitivity to length scales of 10–20 μm, and enables measurements of cell sizes and cellularities in solid tumors in vivo.

Mapping mean axon diameter and intra-axonal volume fraction may have significant clinical potential because nerve conduction velocity is directly dependent on axon diameter, and several neurodegenerative diseases affect axons of specific sizes and alter axon counts. Diffusion-weighted MRI methods based on the pulsed gradient spin echo (PGSE) sequence have been reported to be able to assess axon diameter and volume fraction non-invasively. However, due to the relatively long diffusion times used, e.g. > 20 ms, the sensitivity to small axons (diameter < 2 µm) is low, and the derived mean axon diameter has been reported to be overestimated. In the current study, oscillating gradient spin echo (OGSE) diffusion sequences with variable frequency gradients were used to assess rat spinal white matter tracts with relatively short effective diffusion times (1 – 5 ms). In contrast to previous PGSE-based methods, the extra-axonal diffusion cannot be modeled as hindered (Gaussian) diffusion when short diffusion times are used. Appropriate frequency-dependent rates are therefore incorporated into our analysis and validated by histology-based computer simulation of water diffusion. OGSE data were analyzed to derive mean axon diameters and intra-axonal volume fractions of rat spinal white matter tracts (mean axon diameter ~ 1.27 – 5.54 µm). The estimated values were in good agreement with histology, including the small axon diameters (< 2.5 µm). This study establishes a framework for quantification of nerve morphology using the OGSE method with high sensitivity to small axons.

Purpose A new approach has been developed to quantify cell sizes and intracellular volume fractions using temporal diffusion spectroscopy with diffusion-weighted acquisitions. Theory and Methods Temporal diffusion spectra may be used to characterize tissue microstructure by measuring the effects of restrictions over a range of diffusion times. Oscillating gradients have been used previously to probe variations on cellular and subcellular scales, but their ability to accurately measure cell sizes larger than 10 μm is limited. By combining measurements made using oscillating gradient spin echo (OGSE) and a conventional pulsed gradient spin echo (PGSE) acquisition with a single, relatively long diffusion time, we can accurately quantify cell sizes and intracellular volume fractions. Results Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes and intracellular volume fractions were obtained in vitro for (i) different cell types with sizes ranging from 10 to 20 μm, (ii) different cell densities, and (iii) before and after anti-cancer treatment. Conclusion Hybrid OGSE-PGSE acquisitions sample a larger region of temporal diffusion spectra and can accurately quantify cell sizes over a wide range. Moreover, the maximum gradient strength used was lower than 15 G/cm, suggesting that this approach is translatable to practical MR imaging.