Perinatal and paediatric post-mortem magnetic resonance imaging (PMMR): sequences and technique

As post-mortem MRI (PMMR) becomes more widely used for investigation following perinatal and paediatric deaths, the best possible images should be acquired. In this article, we review the most widely used published PMMR sequences, together with outlining our acquisition protocol and sequence parameters for foetal, perinatal and paediatric PMMR. We give examples of both normal and abnormal appearances, so that the reader can understand the logic behind each acquisition step before interpretation, as a useful day-to-day reference guide to performing PMMR

Postmortem changes in brain cell structure: a review

Brain cell structure is a key determinant of neural function that is frequently altered in neurobiological disorders. Following the global loss of blood flow to the brain that initiates the postmortem interval (PMI), cells rapidly become depleted of energy and begin to decompose. To ensure that our methods for studying the brain using autopsy tissue are robust and reproducible, there is a critical need to delineate the expected changes in brain cell morphometry during the PMI. We searched multiple databases to identify studies measuring the effects of PMI on the morphometry (i.e. external dimensions) of brain cells. We screened 2119 abstracts, 361 full texts, and included 172 studies. Mechanistically, fluid shifts causing cell volume alterations and vacuolization are an early event in the PMI, while the loss of the ability to visualize cell membranes altogether is a later event. Decomposition rates are highly heterogenous and depend on the methods for visualization, the structural feature of interest, and modifying variables such as the storage temperature or the species. Geometrically, deformations of cell membranes are common early events that initiate within minutes. On the other hand, topological relationships between cellular features appear to remain intact for more extended periods. Taken together, there is an uncertain period of time, usually ranging from several hours to several days, over which cell membrane structure is progressively lost. This review may be helpful for investigators studying human postmortem brain tissue, wherein the PMI is an unavoidable aspect of the research

Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. This is the second review on the topic of g-ratio mapping using MRI. As such, it summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. Using simulations based on recently published data, this review demonstrates the relevance of the calibration step for three myelin-markers (macromolecular tissue volume, myelin water fraction, and bound pool fraction). It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest Editor

The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain

T(2)*-weighted gradient-echo MRI images at high field (≥ 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts

Target-specific contrast agents for magnetic resonance microscopy

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2007.Includes bibliographical references (p. 119-133).High-resolution ex vivo magnetic resonance microscopy (MRM) can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. The goal of this thesis is to employ target-specific MR contrast agents to regionally alter relaxation rates, resulting in increased contrast in ex vivo MRM of the human brain, with the aim of providing richer information about cyto- and/or myelo-architechtonics than is currently achievable. To accomplish this goal, a traditional optical myelin stain, luxol fast blue (LFB) MBSN with a paramagnetic copper core, has been introduced as a white-matter-selective MR contrast agent in ex vivo brain tissue. The solution relaxivity of LFB was measured at high (4.7 Tesla) and ultra-high (14 Tesla) field strengths. A methodology was developed for staining large tissue samples, enabling MR imaging. Longitudinal (R1) and transverse (R.2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Ri changes produced larger contrast-to-noise ratios (CNR), per unit time, on Ti-weighted images between the deeper, more myelinated cortical layers (IV-VI) and adjacent, superficial layers (I-III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229± 13 per cent at 4.7T and 269± 25 per cent at 14T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) became resolvable in 14TMR images after en bloc staining with LFB. After imaging was completed, the LFB-stained sample was prepared for light microscopy.(cont.) Both macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Next, the LFB-MR method was employed to investigate microstructure in X-linked adrenoleukodystrophy (ALD), a confluent demyelinating disorder characterized by accumulation of abnormal lipids. LFB-MR revealed an additional zone, unseen in formualin preparations and best visualized in T2*-weighted images, which produced four-fold increases in contrast-to-noise ratio. Immunohistological analysis identified a corresponding area of perivascular macrophages, and ultrastructural examination suggested LFB particulates bound to lipids within these macrophages. We thus conclude that LFB-MR is able to detect the actively demyelinating edge in cerebral ALD. The results presented in this thesis suggest target-specific contrast agents will 1) enable more detailed MR images, permitting the construction of better MR atlases and advancing the field of MR histopathology, and 2) guide the design of future in vivo contrast agents.by Megan Leticia Hepler Blackwell.Ph.D

MRI and histologic studies on early markers of Alzheimer's disease

This thesis adresses a variety of early markers of Alzheimer's disease, using MRI, histology and MRS. MRS is found to be promising for early diagnosis of AD. However this study is done on mice and should be replicated on AD patients over time. Besides the early markers the thesis descibes a potential difference between male and female in the development of AD in the brain. LUMC / Geneeskund

Assessment of the myelination of cerebral tissue using MRI

The aim of this study was to assess the myelination process of cerebral tissue in vivo using different Magnetic Resonance Imaging (MRI) techniques at high field strength and to suggest the optimum MRI technique for the correlation of myelination with the gestational age in the rat brain. Several different techniques have been implemented in order to assess brain maturation. The first approach has been to quantitatively measure the Nuclear Magnetic Resonance (NMR) Ti and T2 relaxation times of brain gray and white matter which is shown to provide a certain degree of tissue characterization (Davis et al 1981). The second approach has been to measure the Apparent Diffusion Coefficient (ADC) which has proven to be of value in cerebral white matter which has been shown to demonstrate anisotropy of water diffusion (Chevert et al 1990). Sprague Dawley (S/D) rats with different age groups ranging from 7 days to adult were used for this study. Studies were carried out in a 7T, 20 cm clear bore magnet (Bruker Biospec). Data were acquired using two different diameter inductively coupled saddle coils. Imaging pulse sequences used were the Spin Echo (SE) and the Stimulated Echo (STEAM). Images were obtained with sufficient resolution to permit clear delineation of selected regions of interest in both gray and white matter. T1 values did not show any significant difference with age in the selected regions of interest whereas T2 and ADC values showed a marked change in signal intensity as the animals age increase. The results obtained have demonstrated the feasibility of accurate high resolution quantitative MRI measurements in S/D rat brain. These techniques may be applied in the assessment of myelin related or white matter pathologies