The paper deals with subject concerning MRI and definition of its capacities in estimation of brain and pituitary condition in athletes. It was performed MRI of 70 persons (43 males and 27 females, aged 18-35) which were divided into 2 groups: the 1st group consisted of 44 athletes and the 2nd – of 26 healthy volunteers. All examined persons in both groups had normal blood indexes results, electrocardiogram, arterial pressure but during the physical stress some of the athletes had transitory arterial hypertension. MRI identified different changes in brain and pituitary (a small hydrocephalus, arachnoidal and unilocular cysts, microadenomas, «Empty cellar syndrome», etc.), more in athletes. It’s shown that MRI gives important information about the condition of brain and pituitary in athletes at the preclinical stage, which may play an important role in addressing issues as training mode, conditions of training, as well as opportunities of selected sports and preventive measures.
Alterations in regional brain iron are a feature of many neurodegenerative disorders, and provide a degree of natural contrast in magnetic resonance imaging (MRI). However, the nature of the iron species causing this is generally not known, but this will likely have a significant effect on relaxation times. We are using high field high resolution imaging to investigate the contribution of iron to magnetic relaxation in autopsy tissues for Alzheimer's and matched control cases to assess the potential for a non-invasive MRI-based early detection and monitoring technique. The relaxation parameters T1, T2 and T2* are measured for a variety of iron standards, including iron solutions and ferritin, using Bruker 750MHz and 600MHz instruments (17.6 and 14 Tesla respectively). A protocol to image unfixed fresh-frozen tissue is developed in order to quantify the same relaxation parameters in autopsy tissue, where standard fixation significantly affects iron states. Imaging parameters were optimized using iron standards to permit accurate determination of T1, T2 and T2* in unfixed human autopsy brain tissue. Tissue from both Alzheimer's cases and controls was selected from the hippocampus, superior temporal gyrus and inferior parietal cortex, and imaged at high resolution allowing quantitative comparisons between cases and regions. Synchrotron X-ray imaging is subsequently used to determine the extent to which iron accumulations contribute to T2 shortening and T2* contrast in these tissues. In figure 1, an example of hippocampal tissue imaged using a gradient echo sequence in a 14 Tesla field is shown. The field of view is 8 × 8 mm, slice thickness is 80 microns, and in-plane resolution is 60 × 60 microns. The experimental technique presented here allows high resolution quantitative MRI of unfixed autopsy tissues. Combined with subsequent synchrotron X-ray analysis, these techniques will enable identification and validation of specific iron compounds responsible for altered relaxation parameters – an approach which has potential application to a broad range of neurodegenerative disorders.
There is a well-established link between iron overload in the brain and pathology associated with neurodegeneration in a variety of disorders such as Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases [1]. This association was first di
Abnormal accumulations of metals, protein aggregation, and oxidative stress are uniting features in neurodegenerative conditions, such as Alzheimer's (AD), Huntington's (HD) and Parkinson's (PD) diseases. At present, little is understood about the mechanisms behind these abnormalities and the role of metals in HD pathogenesis remains a mystery. Here we describe a novel method for the detection and identification of anomalous iron compounds and related metals in mammalian brain tissue using x–ray fluorescence (XRF) methods. The potential for high–resolution iron mapping using microfocused x–ray beams has direct application to investigations of the location and structural form of metal compounds associated with human neurodegenerative disorders – a problem which has vexed researchers for 50 years. (i) To develop techniques for investigating iron in brain tissue using synchrotron x–ray fluorescence methods; (ii) to characterize iron compounds in situ allowing for direct correlation with the disease pathology at cellular resolution; (iii) to use immunohistochemistry to evaluate regional changes in tissue. Synchrotron x–ray analysis, light and transmission electron microscopy were employed to examine brain tissue of transgenic model of HD and control animals. The synchrotron findings were supported by a SQUID magnetometry study. Using the XRF we have shown the iron oxide deposits in the basal ganglia of the HD transgenic mice. A variety of iron oxides were found to be present, including normal ferritin iron, and some deposits of magnetite which contain both Fe3+ and Fe2+, a finding that has not been reported previously in the literature. The presence of magnetite was supported by the SQUID magnetometry data. An increasing microglial reaction which paralleled the iron accumulation in R6/2 brain tissue was found in some samples, though neither neuronal death nor atrophy was observed. Together, these observations provide a preliminary indication that alterations in iron deposition occur prior to pronounced neuronal cell death in the model of HD. In view of the neuronal damage caused by iron–catalyzed free radical formation, these alterations are likely to contribute to the vulnerability of striatal neurons. Therefore, early–onset iron deposition may be relevant to the pathogenesis of the disease.
Abstract Quantitative phase imaging (QPI) through holographic time-lapse microscopy allows for non-invasive measurements of cell dry mass and the ability to track cells for long periods of time with minimal damage, making it most beneficial for research on cancer treatment. Research with this enhanced method of observation can help decipher various morphologies present in specific cell lines and show how each cell can respond differently to provided signals. In this assay, we studied N2a murine neuroblast differentiation in response to Retinoic acid, as well as the anticancerous activity of Saffron and UV in MDA-MB-468 breast carcinoma and HCT116 colon carcinoma cell lines. Cells were observed using Telight’s Q-Phase, a multimodal microscope that utilizes QPI holographic time-lapse technology with label-free monitoring. The cells were able to survive in optimum conditions for up to 96 hours without any appreciative loss of viability. With the emergence of phytochemicals being used as alternative cancer treatments, specific pigments in saffron have shown therapeutic effects against cancer tissues such as apoptosis and decreased carcinogen presence. A microanalysis of the effects of saffron on reducing the invasion potential, viability, and tumorigenicity of breast cancer cell lines was performed. QPI microscopy was performed on MDA-MB-468 human breast adenocarcinoma and HCT116 colon carcinoma cell lines treated with varying doses of saffron and ultraviolet radiation. Cell lines were observed under the microscope for 58-hour periods for changes in mass, movement, and replication. The quantitative data showed a reduction of projections from saffron treatment but did not show any significant reduction in cell movement over the 58-hours. These results were later confirmed through scratch wound and Boyden chamber assays. Similarly, when examining the process of N2a neuroblast differentiation, it was observed that cells do not move towards differentiation in a linear manner, but rather changed their direction and path several times before committing to their final phenotype. These types of observations are critical in understanding the biological processes behind differentiation and drug response and could not have been done without using the various quantitative and analysis tools provided by the QPI technology. Citation Format: Rida Khan, Meaghan McDonald, Albina Mikhaylova, Fatima K. Rehman. Quantitative phase imaging provides new insights into diverse morphologies in cell lines and their behavior in response to alternative cancer treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2384.
Abnormal accumulations of iron have been known to be associated with Alzheimer's disease (AD) for over 50 years. In the intervening time, however, very little progress has been made in understanding the origin, nature and role of iron compounds in neurodegeneration. We have recently developed novel techniques which, when combined, allow us to not only locate and map the distribution of anomalous iron compounds in situ in AD tissue but also to identify and quantify the specific compounds present. (i) To modify and develop physics–based methods for imaging, locating and characterizing anomalous iron compounds in Alzheimer's Disease. (ii) To use information obtained from these studies to inform the development of MRI–based early diagnosis techniques and to understand the possible role of iron and other metals in AD pathology. Synchrotron ×–ray analysis, Superconducting Quantum Interference Device magnetometry and transmission electron microscopy/electron tomography were employed to map and characterize iron compounds in AD and control tissue samples. Using these novel techniques, we have identified specific, anomalous iron compounds associated with Alzheimer's tissue in general and plaque cores in particular. High concentrations of magnetite (a mix–valence iron oxide) appear to be dominant in the plaque core with levels also raised in bulk tissue samples from AD females. A second, ferrous iron oxide is also present in some anomalies. Both of these compounds may promote oxidative damage by providing a source of ferrous iron and via triplet state stabilization due to the magnetic fields they generate. In addition, electron microscopy analysis indicates a potential malfunction of ferritin within AD plaque cores. The results of these studies will shed light on the potential role of iron in AD pathogenesis and help to inform the development of early detection techniques and new investigations of chelation therapies. Electron tomographic reconstruction of an AD plaque core.
This work describes a novel method for the detection, identification and mapping of anomalous iron compounds in mammalian brain tissue using X-ray absorption spectroscopy. We have located and identified individual iron anomalies in an avian tissue model associated with ferritin, biogenic magnetite and haemoglobin with a pixel resolution of less than 5 μm. This technique represents a breakthrough in the study of both intra- and extra-cellular iron compounds in brain tissue. The potential for high-resolution iron mapping using microfocused X-ray beams has direct application to investigations of the location and structural form of iron compounds associated with human neurodegenerative disorders—a problem which has vexed researchers for 50 years.
Microbeam capabilities have been recently added to the Biophysics Collaborative Access Team (BioCAT) beamline 18-ID at the Advanced Photon Source to allow x-ray elemental mapping, micro x-ray absorption fine structure and microdiffraction studies on biological samples. The microprobe setup comprises a pair of platinum coated silicon KB mirrors; a sample holder mounted in a high precision positioner (100 nm accuracy); fluorescence detectors including a Si drift detector, Fe and Zn Bent Laue analyzers and a Ge detector; and a CCD detector for micro-diffraction experiments. The energy range of the microprobe is from 3.5 keV up to 17 keV. The fast scanning capabilities of the Bio-CAT beamline facilitate rapid acquisition of x-ray elemental images and micro-XAFS spectra. This paper reports the results of commissioning the KB mirror system and its performance in initial x-ray fluorescence mapping and micro-diffraction studies.
The form and distribution of brain iron in neurodegeneration is significant for pathogenesis, chelation therapy, and as a potential biomarker. Iron easily changes valence state in–vivo, ensuring that it is present in a variety of forms. Disrupted iron metabolism is a common feature in neurodegeneration, and redox–active Fe(II) is understood to drive excess free radical generation via the Fenton reaction and thereby contribute to oxidative stress damage. Storage typically involves Fe(II) being taken up and stored in ferritin as Fe(III)–based ferrihydrite–like core. However, recent work has demonstrated unusual iron oxide accumulations associated with Alzheimer's disease pathology. We are utilizing a powerful mapping/characterization approach with synchrotron X–rays to study autopsy tissue. This enables micron–resolution location and identification of iron deposits in situ, and their correlation with disease pathology. This is contributing to our understanding of the role of unusual iron accumulations in disease pathogenesis, and should inform developments in metal chelation therapy and optimize the potential of iron as a biomarker for early detection and diagnosis. Iron fluorescence was mapped in Alzheimer's tissue from the superior frontal gyrus. Anomalous iron concentrations were identified and characterized using X–ray absorption spectroscopy. Standards (including ferritin, hemoglobin, and a variety of iron oxide standards) were fitted to the individual traces using linear combination fitting routines, allowing the relative proportions to be determined in micron–scale regions exhibiting a variety of iron compounds. Concentrations of both ferritin and magnetite, a mixed–valence magnetic iron oxide potentially indicating disrupted brain–iron metabolism, were evident. Most significantly, deposits including a predominantly Fe(II)–based oxide were identified in–situ at several sites within the tissue. This is evidence that redox–active iron is concentrated and stabilized in Alzheimer's tissue, which is particularly important in the context of oxidative stress damage. The presence of Fe(II) may indicate a failure to fully oxidise iron during uptake and storage, or may be a consequence of reduction by amyloid as has been recently shown in vitro. Overall, these results demonstrate a practical means of correlating iron compounds and disease pathology in–situ and have clear implications for disease pathogenesis and potential therapies.
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