Purpose A combined diffusion‐relaxometry MR acquisition and analysis pipeline for in vivo human placenta, which allows for exploration of coupling between and apparent diffusion coefficient (ADC) measurements in a sub 10‐minute scan time. Methods We present a novel acquisition combining a diffusion prepared spin echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint ‐ADC spectra using an inverse Laplace transform. Results ‐ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas. Conclusions Combined ‐diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The ‐ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs.

The emergence of multiparametric diffusion models combining diffusion and relaxometry measurements provides powerful new ways to explore tissue microstructure, with the potential to provide new insights into tissue structure and function. However, their ability to provide rich analyses and the potential for clinical translation critically depends on the availability of efficient, integrated, multi-dimensional acquisitions. We propose a fully integrated sequence simultaneously sampling the acquisition parameter spaces required for T1 and T2* relaxometry and diffusion MRI. Slice-level interleaved diffusion encoding, multiple spin/gradient echoes and slice-shuffling are combined for higher efficiency, sampling flexibility and enhanced internal consistency. In-vivo data was successfully acquired on healthy adult brains. Obtained parametric maps as well as clustering results demonstrate the potential of the technique to provide eloquent data with an acceleration of roughly 20 compared to conventionally used approaches. The proposed integrated acquisition, which we call ZEBRA, offers significant acceleration and flexibility compared to existing diffusion-relaxometry studies, and thus facilitates wider use of these techniques both for research-driven and clinical applications.

Purpose To investigate, visualize and quantify the physiology of the human placenta in several dimensions ‐ functional, temporal over gestation, and spatial over the whole organ. Methods Bespoke MRI techniques, combining a rich diffusion protocol, anatomical data and T2* mapping together with a multi‐modal pipeline including motion correction and extracted quantitative features were developed and employed on pregnant women between 22 and 38 weeks gestational age including two pregnancies diagnosed with pre‐eclampsia. Results A multi‐faceted assessment was demonstrated showing trends of increasing lacunarity, and decreasing T2* and diffusivity over gestation. Conclusions The obtained multi‐modal acquisition and quantification shows promising opportunities for studying evolution, adaptation and compensation processes.

PurposeTo assess which microstructural models best explain the diffusion‐weighted MRI signal in the human placenta.MethodsThe placentas of nine healthy pregnant subjects were scanned with a multishell, multidirectional diffusion protocol at 3T. A range of multicompartment biophysical models were fit to the data, and ranked using the Bayesian information criterion.ResultsAnisotropic extensions to the intravoxel incoherent motion model, which consider the effect of coherent orientation in both microvascular structure and tissue microstructure, consistently had the lowest Bayesian information criterion values. Model parameter maps and model selection results were consistent with the physiology of the placenta and surrounding tissue.ConclusionAnisotropic intravoxel incoherent motion models explain the placental diffusion signal better than apparent diffusion coefficient, intravoxel incoherent motion, and diffusion tensor models, in information theoretic terms, when using this protocol. Future work will aim to determine if model‐derived parameters are sensitive to placental pathologies associated with disorders, such as fetal growth restriction and early‐onset pre‐eclampsia. Magn Reson Med 80:756–766, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

We develop a Bayesian analysis framework to detect heterogeneity in the diffusive behaviour of single particle trajectories on cells, implementing model selection to classify trajectories as either consistent with Brownian motion or with a two-state (diffusion coefficient) switching model. The incorporation of localisation accuracy is essential, as otherwise false detection of switching within a trajectory was observed and diffusion coefficient estimates were inflated. Since our analysis is on a single trajectory basis, we are able to examine heterogeneity between trajectories in a quantitative manner. Applying our method to the lymphocyte function-associated antigen 1 (LFA-1) receptor tagged with latex beads (4 s trajectories at 1000 frames s−1), both intra- and inter-trajectory heterogeneity were detected; 12–26% of trajectories display clear switching between diffusive states dependent on condition, whilst the inter-trajectory variability is highly structured with the diffusion coefficients being related by D 1 = 0.68D 0 − 1.5 × 104 nm2 s−1, suggestive that on these time scales we are detecting switching due to a single process. Further, the inter-trajectory variability of the diffusion coefficient estimates (1.6 × 102 − 2.6 × 105 nm2 s−1) is very much larger than the measurement uncertainty within trajectories, suggesting that LFA-1 aggregation and cytoskeletal interactions are significantly affecting mobility, whilst the timescales of these processes are distinctly different giving rise to inter- and intra-trajectory variability. There is also an ‘immobile’ state (defined as D < 3.0 × 103 nm2 s−1) that is rarely involved in switching, immobility occurring with the highest frequency (47%) under T cell activation (phorbol-12-myristate-13-acetate (PMA) treatment) with enhanced cytoskeletal attachment (calpain inhibition). Such ‘immobile’ states frequently display slow linear drift, potentially reflecting binding to a dynamic actin cortex. Our methods allow significantly more information to be extracted from individual trajectories (ultimately limited by time resolution and time-series length), and allow statistical comparisons between trajectories thereby quantifying inter-trajectory heterogeneity. Such methods will be highly informative for the construction and fitting of molecule mobility models within membranes incorporating aggregation, binding to the cytoskeleton, or traversing membrane microdomains.