Multi-modal functional MRI to explore placental function over gestation

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

InSpect: INtegrated SPECTral Component Estimation and Mapping for Multi-Contrast Microstructural MRI

We introduce a novel algorithm for deriving meaningful maps from multi-contrast MRI experiments. Such experiments enable the estimation of multidimensional correlation spectra, in domains such as T1- diffusivity, T2-diffusivity, or T1-T2. These spectra combine information from complementary MR properties, and therefore have the potential for improved quantification of distinct tissue types compared to singlecontrast analyses. However, spectral estimation is an ill-conditioned problem which is highly sensitive to noise and requires significant regularisation. We propose an Expectation-Maximisation based method - which we term InSpect - for unified analysis of multi-contrast MR images. The algorithm simultaneously estimates canonical spectra associated with distinct tissue types within an image, and produces maps quantifying the spatial distribution of these spectra. We test the algorithm’s capabilities on simulated data, then apply to placental diffusion-relaxometry data. On placental data we identified significant within-organ and acrosssubject variation in T2*-ADC spectra - showing the potential of InSpect for detailed separation and quantification of distinct microstructural environments

Genetic Modification of Alternative Respiration Has Differential Effects on Antimycin A-Induced versus Salicylic Acid-Induced Resistance to Tobacco mosaic virus

Salicylic acid (SA), a natural defensive signal chemical, and antimycin A, a cytochrome pathway inhibitor, induce resistance to Tobacco mosaic virus (TMV). Pharmacological evidence suggested signaling during resistance induction by both chemicals involved alternative oxidase (AOX), sole component of the alternative respiratory pathway (AP). Roles of the AP include regulation of intramitochondrial reactive oxygen species and maintenance of metabolic homeostasis. Transgenic tobacco (Nicotiana tabacum) with modified AP capacities (2- to 3-fold increased or decreased) showed no alteration in phenotype with respect to basal susceptibility to TMV or the ability to display SA-induced resistance to systemic viral disease. However, in directly inoculated tissue, antimycin A-induced TMV resistance was inhibited in plants with increased AP capacities, whereas SA and antimycin A-induced resistance was transiently enhanced in plant lines with decreased AP capacities. We conclude that SA-induced TMV resistance results from activation of multiple mechanisms, a subset of which are inducible by antimycin A and influenced by AOX. Other antiviral factors, potentially including the SA-inducible RNA-dependent RNA polymerase, are regulated by AOX-independent mechanisms

Integrated and efficient diffusion-relaxometry using ZEBRA

Abstract 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

Placental magnetic resonance imaging in chronic hypertension: A case-control study

INTRODUCTION: We aimed to explore the use of magnetic resonance imaging (MRI) in vivo as a tool to elucidate the placental phenotype in women with chronic hypertension. METHODS: In case-control study, women with chronic hypertension and those with uncomplicated pregnancies were imaged using either a 3T Achieva or 1.5T Ingenia scanner. T2-weighted images, diffusion weighted and T1/T2* relaxometry data was acquired. Placental T2*, T1 and apparent diffusion coefficient (ADC) maps were calculated. RESULTS: 129 women (43 with chronic hypertension and 86 uncomplicated pregnancies) were imaged at a median of 27.7 weeks’ gestation (interquartile range (IQR) 23.9-32.1) and 28.9 (IQR 26.1-32.9) respectively. Visual analysis of T2-weighted imaging demonstrated placentae to be either appropriate for gestation or to have advanced lobulation in women with chronic hypertension, resulting in a greater range of placental mean T2* values for a given gestation, compared to gestation-matched controls. Both skew and kurtosis (derived from histograms of T2* values across the whole placenta) increased with advancing gestational age at imaging in healthy pregnancies; women with chronic hypertension had values overlapping those in the control group range. Upon visual assessment, the mean ADC declined in the third trimester, with a corresponding decline in placental mean T2* values and showed an overlap of values between women with chronic hypertension and the control group. DISCUSSION: A combined placental MR examination including T2 weighted imaging, T2*, T1 mapping and diffusion imaging demonstrates varying placental phenotypes in a cohort of women with chronic hypertension, showing overlap with the control group

Multi‐modal functional MRI to explore placental function over gestation

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