Compartment Size and Shape by Double-Pulsed-Field-Gradient (d-PFG) spectroscopy and imaging: Theoretical studies predicted that d-PFG methodologies should have several inherent advantages over conventional s-PFG methods. It was claimed, inter-alia, that d-PFG should offer microstructural information even when the specimen is characterized by broad size distributions and even when locally anisotropic compartments are randomly oriented. Therefore, we are systematically studying the new information that the d-PFG methodology conveys beginning with controlled samples in which the ground-truth is know a-priori, and then progressing to more realistic settings such as isolated biological cells and tissues, emulsion and porous materials such as rocks. We have already obtained very interesting and promising results which indicate that the d-PFG sequence may indeed be used for novel applications.

 

Most notably, we were able to show that the novel angular d-PFG experiment could be used to accurately measure compartment sizes of biologically relevant sizes (5±1 μm) in water filled impermeable microcapillaries of well defined dimensions; importantly, this measurement was achieved using low-amplitude gradients, which are clinically feasible. Moreover, we have been able to show that such accurate quantification is possible even in a real biological specimen such as yeast cells. We have shown that angular double-PFG methodology provides a mean to obtain compartment size and shape in randomly oriented pores with size distribution. Recently it was shown that such results can be obtained even in sample characterized by magnetic field inhomogeneity. Our methodology is pertinent not only in biomedicine but also in other disciplines, and allows quantification of restricted diffusion and extraction of microstructural information thereof in systems such as porous media, emulsions, polymer cavities, and rocks. Our future plans are to extend this methodology to MRI, to study axon size and shape in isolated neuronal tissue and in-vivo both in normal brain tissue and in various neuropathologies.