Eddy Solomon

Major mouse placental compartments revealed by diffusion-weighted MRI, contrast-enhanced MRI, and fluorescence imaging.

Significance Fluid motion measurements can provide valuable insight regarding the structure and function of developing placentas. This study presents to our knowledge the first MRI characterization of multicompartmental diffusion and incoherent flow in pregnant mice at different gestation stages, made possible by methods herein introduced for the single-scan acquisition of diffusion-encoded images in the challenging environment associated with in vivo embryonic studies. These methods were combined with a customized contrast agent to reveal a freely diffusive maternal blood pool, a strongly perfused fetal blood flow, and an intermediate behavior for the trophoblastic labyrinth cell layer. Structural features associated with these dynamics were corroborated with ex vivo fluorescence microscopy and are discussed within the context of the anatomical structure of developing mouse placentas. Mammalian models, and mouse studies in particular, play a central role in our understanding of placental development. Magnetic resonance imaging (MRI) could be a valuable tool to further these studies, providing both structural and functional information. As fluid dynamics throughout the placenta are driven by a variety of flow and diffusion processes, diffusion-weighted MRI could enhance our understanding of the exchange properties of maternal and fetal blood pools—and thereby of placental function. These studies, however, have so far been hindered by the small sizes, the unavoidable motions, and the challenging air/water/fat heterogeneities, associated with mouse placental environments. The present study demonstrates that emerging methods based on the spatiotemporal encoding (SPEN) of the MRI information can robustly overcome these obstacles. Using SPEN MRI in combination with albumin-based contrast agents, we analyzed the diffusion behavior of developing placentas in a cohort of mice. These studies successfully discriminated the maternal from the fetal blood flows; the two orders of magnitude differences measured in these fluids’ apparent diffusion coefficients suggest a nearly free diffusion behavior for the former and a strong flow-based component for the latter. An intermediate behavior was observed by these methods for a third compartment that, based on maternal albumin endocytosis, was associated with trophoblastic cells in the interphase labyrinth. Structural features associated with these dynamic measurements were consistent with independent intravital and ex vivo fluorescence microscopy studies and are discussed within the context of the anatomy of developing mouse placentas.

Diffusion weighted MRI by spatiotemporal encoding: Analytical description and in vivo validations

Diffusion-weighted (DW) MRI is a powerful modality for studying microstructure in normal and pathological tissues. The accuracy derived from DW MRI depends on the acquisition of quality images, and on a precise assessment of the b-values involved. Conventional DW MRI tends to be of limited use in regions suffering from large magnetic field or chemical shift heterogeneities, which severely distort the MR images. In this study we propose novel sequences based on SPatio-temporal ENcoding (SPEN), which overcome such shortcomings owing to SPENs inherent robustness to offsets. SPEN, however, relies on the simultaneous application of gradients and radiofrequency-swept pulses, which may impart different diffusion weightings along the spatial axes. These will be further complicated in DW measurements by the diffusion-sensitizing gradients, and will in general lead to complex, spatially-dependent b-values. This study presents a formalism for analyzing these diffusion-weighted SPEN (dSPEN) data, which takes into account the concomitant effects of adiabatic pulses, of the imaging as well as diffusion gradients, and of the cross-terms between them. These analytical b-values derivations are subject to experimental validations in phantom systems and ex vivo spinal cords. Excellent agreement is found between the theoretical predictions and these dSPEN experiments. The ensuing methodology is then demonstrated by in vivo mapping of diffusion in human breast - organs where conventional k-space DW acquisition methods are challenged by both field and chemical shift heterogeneities. These studies demonstrate the increased robustness of dSPEN vis-à-vis comparable DW echo planar imaging, and demonstrate the value of this new methodology for medium- or high-field diffusion measurements in heterogeneous systems.

Referenceless reconstruction of spatiotemporally encoded imaging data: Principles and applications to real-time MRI

Ultrafast sequences based on “Hybrid” spatiotemporal encoding (SPEN) replace echo‐planar imagings phase encoding “blips,” while retaining a k‐space readout acquisition. Hardware imperfections during acquisition may lead to ghosts and striped artifacts along the SPEN dimension; akin to echo‐planar imagings Nyquist ghosts, but weaker. A referenceless method to eliminate these artifacts in Hybrid SPEN is demonstrated.

Overcoming limitations in diffusion‐weighted MRI of breast by spatio‐temporal encoding

Evaluating the usefulness of diffusion‐weighted spatio‐temporal encoding (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)‐based characterizations of healthy and malignant human breast tissues, in comparison with results obtained using techniques based on spin‐echo echo planar imaging (SE‐EPI).

Ultrafast in vivo diffusion imaging of stroke at 21.1 T by spatiotemporal encoding.

This study quantifies in vivo ischemic stroke brain injuries in rats using ultrahigh‐field single‐scan MRI methods to assess variations in apparent diffusion coefficients (ADCs).

fMRI contrast at high and ultrahigh magnetic fields: insight from complementary methods.

This manuscript examines the origins and nature of the function-derived activation detected by magnetic resonance imaging at ultrahigh fields using different encoding methods. A series of preclinical high field (7 T) and ultra-high field (17.2 T) fMRI experiments were performed using gradient echo EPI, spin echo EPI and spatio-temporally encoded (SPEN) strategies. The dependencies of the fMRI signal change on the strength of the magnetic field and on different acquisition and sequence parameters were investigated. Artifact-free rat brain images with good resolution in all areas, as well as significant localized activation maps upon forepaw stimulation, were obtained in a single scan using fully refocused SPEN sequences devoid of T2* effects. Our results showed that, besides the normal T2-weighted BOLD contribution that arises in spin-echo sequences, fMRI SPEN signals contain a strong component caused by apparent T1-related effects, demonstrating the potential of such technique for exploring functional activation in rodents and on humans at ultrahigh fields.

Removing silicone artifacts in diffusion-weighted breast MRI by means of shift-resolved spatiotemporally encoding.

Evaluate the usefulness of diffusion‐weighted spatiotemporally encoded (SPEN) methods to obtain apparent diffusion coefficient (ADC) maps of fibroglandular human breast tissue, in the presence of silicone implants.

Robust diffusion tensor imaging by spatiotemporal encoding: Principles and in vivo demonstrations.

Evaluate the usefulness of single‐shot and of interleaved spatiotemporally encoded (SPEN) methods to perform diffusion tensor imaging (DTI) under various preclinical and clinical settings.

Diffusion MRI measurements in challenging head and brain regions via cross-term spatiotemporally encoding

Cross-term spatiotemporal encoding (xSPEN) is a recently introduced imaging approach delivering single-scan 2D NMR images with unprecedented resilience to field inhomogeneities. The method relies on performing a pre-acquisition encoding and a subsequent image read out while using the disturbing frequency inhomogeneities as part of the image formation processes, rather than as artifacts to be overwhelmed by the application of external gradients. This study introduces the use of this new single-shot MRI technique as a diffusion-monitoring tool, for accessing regions that have hitherto been unapproachable by diffusion-weighted imaging (DWI) methods. In order to achieve this, xSPEN MRI’s intrinsic diffusion weighting effects are formulated using a customized, spatially-localized b-matrix analysis; with this, we devise a novel diffusion-weighting scheme that both exploits and overcomes xSPEN’s strong intrinsic weighting effects. The ability to provide reliable and robust diffusion maps in challenging head and brain regions, including the eyes and the optic nerves, is thus demonstrated in humans at 3T. New avenues for imaging other body regions are also briefly discussed.

Multiple-coil k-space interpolation enhances resolution in single-shot spatiotemporal MRI

Spatio‐temporal encoding (SPEN) experiments can deliver single‐scan MR images without folding complications and with robustness to chemical shift and susceptibility artifacts. Further resolution improvements are shown to arise by relying on multiple receivers, to interpolate the sampled data along the low‐bandwidth dimension. The ensuing multiple‐sensor interpolation is akin to recently introduced SPEN interleaving procedures, albeit without requiring multiple shots.