1,720,956 research outputs found
SPIRAL MRI for in vivo lithium-7 imaging: a feasibility study in mice after oral lithium treatment
No full textAbstract
Lithium has been the frontline treatment for bipolar disorder for over 60 years. However, its mode of action and distribution in the brain is still incompletely understood. The primary isotope of lithium, lithium-7 (
7
Li), is a magnetic resonance (MR) active, spin-3/2 nucleus. However, its low MR sensitivity and the small brain size of mice make
7
Li MR imaging (MRI) difficult in preclinical research. We tested four MRI sequences (FLASH, RARE, bSSFP, and SPIRAL) on lithium-containing phantoms, and bSSFP and SPIRAL on orally lithium-treated adult C57BL/6 mice.
7
Li MR spectroscopy was acquired weekly at 9.4T to monitor the lithium uptake. The in vivo T1 relaxation time of
7
Li was estimated in four mice. 4-h SPIRAL
7
Li MRI was acquired in ten mice at a resolution of 2 × 2 × 3 mm
3
. SPIRAL MRI provided the highest signal-to-noise ratio (SNR) per unit acquisition time and the best image quality. We observed a non-homogeneous distribution of lithium in the mouse brain, with the highest concentrations in the cortex, ventricles, and basal brain regions. Almost no lithium signal was detected in the olfactory bulb and the cerebellum. We showed that in vivo
7
Li MRI in mice is feasible, although with limited spatial resolution and SNR
Deep learning-based automated segmentation of cardiac real-time MRI in non-human primates
No full textA Custom-Built, Cost-Efficient Lithium-7 Tx/Rx Coil for In Vivo 7Li Magnetic Resonance Imaging and Spectroscopy
No full textX-nuclei magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are powerful tools for the in vivo investigation of metabolism. Most nuclei require a dedicated radio frequency (RF) coil for signal detection; however, RF coils are often expensive. Coupled with the need for experts to create RF coils, X-nuclei MR measurements are often inaccessible to the general user. In this paper, we present cost-efficient and easy to assemble 7Li RF coils that achieved comparable signal-to-noise ratios (SNRs) to their commercial counterpart. Our 7Li RF coils were built as single resonance, transmit-receive (Tx/Rx) coils with sufficient design flexibility to allow for future implementations for other nuclei. We found that for a mouse surface coil the optimal number of segmentation capacitors was two. In vitro 7Li MRS yielded a 75% SNR increase and in vivo 7Li MRS yielded a 42% SNR increase compared with a commercial dual-tuned surface coil. Finally, we demonstrated that in vivo 7Li MRI of lithium-fed mice is possible with a custom-built, 2-segment surface coil
Multi-nuclear magnetic resonance imaging and spectroscopy of lithium in the brain
Full text linkEquipped with only three protons, lithium stands as one of the most unexpected drug discoveries in history. Despite its initial FDA approval in 1970, lithium's precise mechanism for regulating mood remains largely elusive. Lithium is generally considered a modulator of neurotransmission, an inhibitor of enzymes in the signaling cascade of inositol (1,4,5)-triphosphate and diacylglycerol, and neuroprotective. Yet, the true challenge lies in understanding how lithium effectively treats patients with bipolar disorder. Bipolar disorder is a psychiatric illness that is characterized by recurrent periods of mania and depression, often accompanied by a high suicide rate (12-fold higher than the population average) and various comorbidities. While lithium is an effective drug for some bipolar patients (between 30-50%), it also carries an increased risk of renal disease. It is therefore essential to understand the early stages of lithium treatment and find a way to predict whether a treatment is successful. However, despite extensive research, biomarkers for lithium treatment response have largely eluded scientists.
In this thesis, I aim to tackle a part of this problem, focusing on the effect of lithium on the healthy brain. By isolating the drug from its pathological context, I have focused on characterizing lithium treatment in mice during the first four weeks of treatment. My investigation encompasses three key aspects: lithium distribution in the brain, brain metabolism, and changes in water diffusivity in the brain.
Employing magnetic resonance imaging and spectroscopy, I have looked for biomarkers with a translational perspective. The primary isotope of lithium, lithium-7, is a spin-3/2 nucleus with a nuclear receptivity of 0.29 compared to 1 of protons. Lithium-7 is therefore magnetically active making it possible to detect lithium directly in the brain. Previous studies in humans and animals have revealed an inhomogeneous distribution of lithium in the brain. However, no in vivo imaging of lithium in mice has previously been performed. Through optimizing the magnetic resonance sequence and hardware, I successfully performed the first in vivo lithium-7 magnetic resonance imaging of the mouse brain (Chapters 2-3). I found lower lithium concentrations in the olfactory bulb and cerebellum compared to the rest of the brain. Furthermore, I successfully estimated the lithium concentration in the brain of mice.
To investigate brain metabolism, I employed magnetic resonance spectroscopy – a technique that relies on the principle of chemical shift. The conventional approach to analyze spectroscopy data is to fit it with a linear combination of basis spectra (model functions of different metabolites). I performed this analysis using a software package called LCModel, which is currently considered the gold standard for in vivo spectroscopy. I could show that this software has non-ideal behavior when adding noise to spectra (Chapter 4). To better characterize the impact of adding noise on the quality of the fit, I incorporated data from five different species: mice, rats, marmosets, macaques, and humans. I also developed an open-source toolbox for simulating cortical spectra from these species at various noise levels.
To analyze 3D astrocyte cell cultures within an MRI scanner I developed a magnetic resonance-compatible bioreactor linked to a compact incubator, enabling precise control of gas mixing and exchange (Chapter 5). Using the bioreactor, I investigated the metabolic response of astrocytes to lithium-enriched media. I found that astrocytes exposed to therapeutic concentrations of lithium (0.78 mM) exhibited reduced levels of myo-inositol and glutamate plus glutamine, while these levels increased at higher lithium concentrations (4.38 mM).
Finally, I established a magnetic resonance-based characterization of the effects of lithium treatment in mice, incorporating structural analysis, metabolic assessments, and diffusion-related changes. I found that mice on a lithium-enriched diet showed elevated levels of myo-inositol, decreased N-acetylaspartate, and reduced diffusivity. At first glance these changes looked bleak – considering that these suggest increased glial content, decreased neuronal health, and inflammation. However, upon further investigation, I found that these were accompanied by a change in the glutamate-to-glutamine ratio and increased neurite density index – changes associated with a potential shift in cell population rather than neurotoxicity.
This thesis starts by developing methods enabling the study of lithium treatment in mice in vivo. The second half demonstrates the application of these methodologies and presents evidence for a shift in cell population following lithium treatment. While I obviously cannot claim to have solved the mechanism of lithium action, I have succeeded in delineating a magnetic resonance-based profile of lithium treatment in both astrocytes and mice.2024-03-0
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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