Diffusion in hierarchical systems: A simulation study in models of healthy and diseased muscle tissue

PURPOSE: To investigate the sensitivity of diffusion-MR signal to microstructural change in muscle tissue associated with pathology, and recommend optimal acquisition parameters. METHODS: We employ Monte-Carlo simulation of diffusing spins in hierarchical tissue to generate synthetic diffusion-weighted signal curves over a wide range of scan parameters. Curves are analyzed using entropy-a measure of curve complexity. Entropy change between a baseline and various microstructural scenarios is investigated. We find acquisitions that optimize entropy difference in each scenario. RESULTS: Permeability changes have a large effect on the diffusion-weighted signal curve. Muscle fiber atrophy is also important, although differentiating between mechanisms is challenging. Several acquisitions over a range of diffusion times is optimal for imaging microstructural change in muscle tissue. Sensitivity to permeability is optimized for high gradient strengths, but sensitivity to other scenarios is optimal at other values. CONCLUSIONS: The diffusion-attenuated signal is sensitive to the microstructural changes, but the changes are subtle. Taking full advantage of the changes to the overall curve requires a set of acquisitions over a range of diffusion times. Permeability causes the largest changes, but even the very subtle changes associated with fiber radius distribution change the curves more than noise alone

Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

Playing with nonuniform grids

Numerical experiments with discretization methods on nonuniform grids are presented for the convection-diffusion equation. These show that the accuracy of the discrete solution is not very well predicted by the local truncation error. The diagonal entries in the discrete coefficient matrix give a better clue: the convective term should not reduce the diagonal. Also, iterative solution of the discrete set of equations is discussed. The same criterion appears to be favourable.

How do women prepare for pregnancy in a low-income setting? Prevalence and associated factors

Background Despite growing evidence of pregnancy preparation benefits, there is little knowledge on how women in developing countries prepare for pregnancy and factors influencing their preparedness for pregnancy. Here, we determine how women in Malawi prepare for pregnancy and factors associated with pregnancy preparation. Methods We used data from a previous cohort study comprising 4,244 pregnant mothers, recruited between March and December 2013 in Mchinji district, Malawi. Associations of pregnancy preparation with socio-demographic and obstetric factors were tested for using mixed effects ordinal regression, with the likelihood ratio and Wald's tests used for variable selection and independently testing the associations. Results Most mothers (63.9%) did not take any action to prepare for their pregnancies. For those who did (36.1%), eating more healthily (71.9%) and saving money (42.8%) were the most common forms of preparation. Mothers who were married (adjusted odds-ratio (AOR 7.77 (95% CI [5.31, 11.25]) or with no or fewer living children were more likely to prepare for pregnancy (AOR 4.71, 95% CI [2.89,7.61]. Mothers with a period of two to three years (AOR 2.51, 95% CI [1.47, 4.22]) or at least three years (AOR 3.67, 95%CI [2.18, 6.23]) between pregnancies were more likely to prepare for pregnancy than women with first pregnancy or shorter intervals. On the other hand, teenage and older (≥ 35 years old) mothers were less likely to prepare for pregnancy (AOR 0.61, 95%CI [0.47, 0.80]) and AOR 0.49 95%CI [0.33, 0.73], respectively). Conclusion While preconception care may not be formally available in Malawi, our study has revealed that over a third of mothers took some action to prepare for pregnancy before conception. Although this leaves around two thirds of women who did not make any form of pregnancy preparation, our findings form a basis for future research and development of a preconception care package that suits the Malawian context

Clinically feasible diffusion MRI in muscle: Time dependence and initial findings in Duchenne muscular dystrophy

Purpose: To characterize the diffusion time-dependence in muscle in healthy adult volunteers, boys with Duchenne’s muscular dystrophy (DMD), and age-matched controls in a clinically feasible acquisition time for pediatric applications. / Methods: Diffusion data were acquired using a pulsed gradient stimulated echo diffusion preparation at 5 different diffusion times (70, 130, 190, 250, and 330 ms), at 4 different b-values (0, 200, 400, 600, and 800 s/mm2) and 6 directions (orthogonal x, y, and z and diagonal xy, xz, and yz) and processed to obtain standard diffusion indices (mean diffusivity [MD] and fractional anisotropy [FA]) at each diffusion time. / Results Time-dependent diffusion was seen in muscle in healthy adult volunteers, boys with DMD, and age-matched controls. Boys with DMD showed reduced MD and increased FA values in comparison to age matched controls across a range of diffusion times. A diffusion time of Δ = 190 ms had the largest effect size. / Conclusions: These results could be used to optimize diffusion imaging in this disease further and imply that these diffusion indices may become an important biomarker in monitoring progression in DMD in the future

Validation and noise robustness assessment of microscopic anisotropy estimation with clinically feasible double diffusion encoding MRI

Purpose: Double diffusion encoding (DDE) MRI enables the estimation of microscopic diffusion anisotropy, yielding valuable information on tissue microstructure. A recent study proposed that the acquisition of rotationally invariant DDE metrics, typically obtained using a spherical “5‐design,” could be greatly simplified by assuming Gaussian diffusion, facilitating reduced acquisition times that are more compatible with clinical settings. Here, we aim to validate the new minimal acquisition scheme against the standard DDE 5‐design, and to quantify the proposed method's noise robustness to facilitate future clinical use. / Theory and Methods: DDE MRI experiments were performed on both ex vivo and in vivo rat brains at 9.4 T using the 5‐design and the proposed minimal design and taking into account the difference in the number of acquisitions. The ensuing microscopic fractional anisotropy (μFA) maps were compared over a range of b‐values up to 5000 s/mm2. Noise robustness was studied using analytical calculations and numerical simulations. / Results: The minimal protocol quantified μFA at an accuracy comparable to the estimates obtained by means of the more theoretically robust DDE 5‐design. μFA's sensitivity to noise was found to strongly depend on compartment anisotropy and tensor magnitude in a nonlinear manner. When μFA < 0.75 or when mean diffusivity is particularly low, very high signal‐to‐noise ratio is required for precise quantification of µFA. / Conclusion: Our work supports using DDE for quantifying microscopic diffusion anisotropy in clinical settings but raises hitherto overlooked precision issues when measuring μFA with DDE and typical clinical signal‐to‐noise ratio

The endogenous subcellular localisations of the long chain fatty acid-activating enzymes ACSL3 and ACSL4 in sarcoma and breast cancer cells

Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype. This study focuses on ACSL3 and ACSL4, closely related structural homologues that preferentially activate palmitate and arachidonate fatty acids, respectively. In this study, immunohistochemical screening of multiple soft tissue tumour arrays revealed that ACSL3 and ACSL4 were highly, but differentially, expressed in a subset of leiomyosarcomas, fibrosarcomas and rhabdomyosarcomas, with consistent cytoplasmic and granular stainings of tumour cells. The intracellular localisations of endogenously expressed ACSL3 and ACSL4 were further investigated by detailed subcellular fractionation analyses of HT1080 fibrosarcoma and MCF-7 breast cancer cells. ACSL3 distribution closely overlapped with proteins involved in trafficking from the trans-Golgi network and endosomes. In contrast, the ACSL4 localisation pattern more closely followed that of calnexin which is an endoplasmic reticulum resident chaperone. Confocal immunofluorescence imaging of MCF-7 cells confirmed the intracellular localisations of both enzymes. These observations reveal new information regarding the compartmentation of fatty acid metabolism in cancer cells

Motor Unit Magnetic Resonance Imaging (MUMRI) In Skeletal Muscle

\ua9 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.Magnetic resonance imaging (MRI) is routinely used in the musculoskeletal system to measure skeletal muscle structure and pathology in health and disease. Recently, it has been shown that MRI also has promise for detecting the functional changes, which occur in muscles, commonly associated with a range of neuromuscular disorders. This review focuses on novel adaptations of MRI, which can detect the activity of the functional sub-units of skeletal muscle, the motor units, referred to as “motor unit MRI (MUMRI).” MUMRI utilizes pulsed gradient spin echo, pulsed gradient stimulated echo and phase contrast MRI sequences and has, so far, been used to investigate spontaneous motor unit activity (fasciculation) and used in combination with electrical nerve stimulation to study motor unit morphology and muscle twitch dynamics. Through detection of disease driven changes in motor unit activity, MUMRI shows promise as a tool to aid in both earlier diagnosis of neuromuscular disorders and to help in furthering our understanding of the underlying mechanisms, which proceed gross structural and anatomical changes within diseased muscle. Here, we summarize evidence for the use of MUMRI in neuromuscular disorders and discuss what future research is required to translate MUMRI toward clinical practice. Level of Evidence: 5. Technical Efficacy: Stage 3

Resolving the human remains crisis in British archaeology

Human remains are a fundamental part of the archaeological record, offering unique insights into the lives of individuals and populations in the past. Like many archaeological materials human remains require distinctive and specialised methods of recovery, analysis and interpretation, while technological innovations and the accumulation of expertise have enabled archaeologists to extract ever greater amounts of information from assemblages of skeletal material. Alongside analyses of new finds, these advances have consistently thrown new light on existing collections of human remains in museums, universities and other institutions. Given the powerful emotional, social and religious meanings attached to the dead body, it is perhaps unsurprising that human remains pose a distinctive set of ethical questions for archaeologists. With the rise of indigenous rights movements and the emergence of post-colonial nations the acquisition and ownership of human remains became a divisive and politically loaded issue. It became increasingly clear that many human remains in museum collections around the world represented the traces of colonial exploitation and discredited pseudo-scientific theories of race. In the light of these debates and changing attitudes, some human remains were returned or repatriated to their communities of origin, a process which continues to this day. Recently a new set of challenges to the study of human remains has emerged from a rather unexpected direction: the British government revised its interpretation of nineteenth-century burial legislation in a way that would drastically curtail the ability of archaeologists to study human remains of any age excavated in England and Wales. This paper examines these extraordinary events and the legal, political and ethical questions that they raise