Magnetic resonance measurements of cellular and sub-cellular membrane structures in live and fixed neural tissue.
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ABSTRACT:
SUBMITTER: Williamson NH
PROVIDER: S-EPMC6977971 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPostmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens.MethodsThe study subjects were 21 autopsy cases in our hospital between May 26, 2019 and February 16, 2020 whose hearts were removed and scanned by MRI. The male:female ratio was 14:7, and their ages at death ranged from 9 to 92 years (mean age 65.0 ± 19.7 years). Postmortem (PM)-MRI was conducted with a 0.3-Tesla (0.3-T) scanner containing a permanent magnet. A 4-channel QD head coil was used as the receiver coil. Scans were performed immediately after removal, post-formalin fixation, and after slicing; 7 cases were scanned at all three time points.ResultsThe T1- and T2-values were calculated from the MRI signals of each sample organ at each scanning stage. Specimens were sliced from removed organs after formalin fixation, and the changes in T1- and T2-values over time were graphed to obtain an approximate curve. The median T1-values at each measurement time point tended to decrease from immediately after removal. The T2-values showed the same tendency to decrease, but this tendency was more pronounced for the T1-values.ConclusionMRI signal changes in images of heart specimens were investigated. Formalin fixation shortened both T1- and T2-values over time, and approximation formulae were derived to show these decreases over time. The shortening of T1- and T2-values can be understood as commensurate with the reduction in the water content (water molecules) of the formalin-fixed heart.
| S-EPMC8459544 | biostudies-literature
Project description:The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.
| S-EPMC4039561 | biostudies-literature
Project description:BackgroundLeft ventricular segmental wall motion analysis is important for clinical decision making in cardiac diseases. Strain analysis with myocardial tissue tagging is the non-invasive gold standard for quantitative assessment, however, it is time-consuming. Cardiovascular magnetic resonance myocardial feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be employed with standard CMR cine-imaging. The aim is to validate segmental peak systolic circumferential strain (peak SCS) and time to peak systolic circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and determine its intra and inter-observer variability.MethodsPatients in whom both cine CMR and tissue tagging has been performed were selected. CMR-FT analysis was done using endocardial (CMR-FTendo) and mid-wall contours (CMR-FTmid). The Intra Class Correlation Coefficient (ICC) and Pearson correlation were calculated.Results10 healthy volunteers, 10 left bundle branch block (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all 480 segments were analyzable and with tissue tagging 464 segments.Significant differences in mean peak SCS values of the total study group were present between CMR-FTendo and tissue tagging (-23.8 ± 9.9% vs -13.4 ± 3.3%, p<0.001). Differences were smaller between CMR-FTmid and tissue tagging (-16.4 ± 6.1% vs -13.4 ± 3.3%, p=0.001). The ICC of the mean peak SCS of the total study group between CMR-FTendo and tissue tagging was low (0.19 (95%-CI-0.10-0.49), p=0.02). Comparable results were seen between CMR-FTmid and tissue tagging. In LBBB patients, mean T2P-SCS values measured with CMR-FTendo and CMR-FTmid were 418 ± 66 ms, 454 ± 60 ms, which were longer than with tissue tagging, 376 ± 55 ms, both p<0.05. ICC of the mean T2P-SCS between CMR-FTendo and tissue tagging was 0.64 (95%-CI-0.36-0.81), p<0.001, this was better in the healthy volunteers and LBBB group, whereas the ICC between CMR-FTmid and tissue tagging was lower.The intra and inter-observer agreement of segmental peak SCS with CMR-FTmid was lower compared with tissue tagging; similar results were seen for segmental T2P-SCS.ConclusionsThe intra and inter-observer agreement of segmental peak SCS and T2P-SCS is substantially lower with CMR-FTmid compared with tissue tagging. Therefore, current segmental CMR-FTmid techniques are not yet applicable for clinical and research purposes.
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Project description:MR might be well suited to obtain reproducible and accurate measures of fat tissues in infants. This study evaluates MR-measurements of adipose tissue in young infants in vitro and in vivo.MR images of ten phantoms simulating subcutaneous fat of an infant's torso were obtained using a 1.5T MR scanner with and without simulated breathing. Scans consisted of a cartesian water-suppression turbo spin echo (wsTSE) sequence, and a PROPELLER wsTSE sequence. Fat volume was quantified directly and by MR imaging using k-means clustering and threshold-based segmentation procedures to calculate accuracy in vitro. Whole body MR was obtained in sleeping young infants (average age 67±30 days). This study was approved by the local review board. All parents gave written informed consent. To obtain reproducibility in vivo, cartesian and PROPELLER wsTSE sequences were repeated in seven and four young infants, respectively. Overall, 21 repetitions were performed for the cartesian sequence and 13 repetitions for the PROPELLER sequence.In vitro accuracy errors depended on the chosen segmentation procedure, ranging from 5.4% to 76%, while the sequence showed no significant influence. Artificial breathing increased the minimal accuracy error to 9.1%. In vivo reproducibility errors for total fat volume of the sleeping infants ranged from 2.6% to 3.4%. Neither segmentation nor sequence significantly influenced reproducibility.With both cartesian and PROPELLER sequences an accurate and reproducible measure of body fat was achieved. Adequate segmentation was mandatory for high accuracy.
| S-EPMC4338239 | biostudies-literature
Project description:The objective of this study was to develop, validate, and compare nomograms for malignancy prediction in soft tissue tumors (STTs) using conventional and diffusion-weighted magnetic resonance imaging (MRI) measurements. Between May 2011 and December 2016, 239 MRI examinations from 236 patients with pathologically proven STTs were included retrospectively and assigned randomly to training (n = 100) and validation (n = 139) cohorts. MRI of each lesion was reviewed to assess conventional and diffusion-weighted imaging (DWI) measurements. Multivariate nomograms based on logistic regression analyses were built using conventional measurements with and without DWI measurements. Predictive accuracy was measured using the concordance index (C-index) and calibration plots. Statistical differences between the C-indexes of the two models were analyzed. Models were validated by leave-one-out cross-validation and by using a validation cohort. The mean lesion size, presence of infiltration, edema, and the absence of the split fat sign were significant and independent predictors of malignancy and included in the conventional model. In addition to these measurements, the mean and minimum apparent diffusion coefficient values were included in the DWI model. The DWI model exhibited significantly higher diagnostic performance only in the validation cohort (training cohort, 0.899 vs. 0.886, P = 0.284; validation cohort, 0.791 vs. 0.757, P = 0.020). Calibration plots showed fair agreements between the nomogram predictions and actual observations in both cohorts. In conclusion, nomograms using MRI features as variables can be utilized to predict the malignancy probability in patients with STTs. There was no definite gain in diagnostic accuracy when additional DWI features were used.
| S-EPMC6427044 | biostudies-literature
Project description:Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa?Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface.Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm.Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm.DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n = 20). ROC curve analysis of these region showed significant ability to distinguish between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid ROC AUC = 0.86-0.87.Only 3-4 semen samples were used to assess the efficacy of each sperm washing protocol that were examined. The estimated minimum sperm concentration required for MRS is specific to the hardware used in our study and may be different in other spectrometers. Spectrum binning is a low resolution analysis method that sums MRS peaks within a chemical shift range. This can obscure the identity of which metabolite(s) are responsible for differences between sperm populations. Further work is required to determine the relative contribution of somatic cells to the MRS spectrum from the '40%' and '80%' sperm.1H MRS can provide information about the molecules present in live human sperm and may therefore permit the study of the underlying functional biology or metabolomics of live sperm. Given the relatively low concentration of sperm required to obtain a suitable MRS signal (~3 × 106/ml), this could be carried out on sperm from men with oligo-, astheno- or teratozoospermia. This may lead to the development of new diagnostic tests or ultimately novel treatments for male factor infertility.This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.
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Project description:In diffusion-weighted MRI studies of neural tissue, the classical model assumes the statistical mechanics of Brownian motion and predicts a monoexponential signal decay. However, there have been numerous reports of signal decays that are not monoexponential, particularly in the white matter.We modeled diffusion in neural tissue from the perspective of the continuous time random walk. The characteristic diffusion decay is represented by the Mittag-Leffler function, which relaxes a priori assumptions about the governing statistics. We then used entropy as a measure of the anomalous features for the characteristic function.Diffusion-weighted MRI experiments were performed on a fixed rat brain using an imaging spectrometer at 17.6 T with b-values arrayed up to 25,000 s/mm(2). Additionally, we examined the impact of varying either the gradient strength, q, or mixing time, ?, on the observed diffusion dynamics.In white and gray matter regions, the Mittag-Leffler and entropy parameters demonstrated new information regarding subdiffusion and produced different image contrast from that of the classical diffusion coefficient. The choice of weighting on q and ? produced different image contrast within the regions of interest.We propose these parameters have the potential as biomarkers for morphology in neural tissue.
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Project description:Decrypting the structure, function, and molecular interactions of complex molecular machines in their cellular context and at atomic resolution is of prime importance for understanding fundamental physiological processes. Nuclear magnetic resonance is a well-established imaging method that can visualize cellular entities at the micrometer scale and can be used to obtain 3D atomic structures under in vitro conditions. Here, we introduce a solid-state NMR approach that provides atomic level insights into cell-associated molecular components. By combining dedicated protein production and labeling schemes with tailored solid-state NMR pulse methods, we obtained structural information of a recombinant integral membrane protein and the major endogenous molecular components in a bacterial environment. Our approach permits studying entire cellular compartments as well as cell-associated proteins at the same time and at atomic resolution.
| S-EPMC3323964 | biostudies-literature
Project description:The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH∼6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood. Here, we show the first study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on residue-specific conformation and membrane location describe pHLIP in various surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical membrane-adsorbed state is more complex than previously envisioned. At pH 6.4, for the major unstructured population, the peptide sinks deeper into the membrane in a state II' that is distinct from the adsorbed state II observed at pH 7.4, which may enable pHLIP to sense slight change in acidity even before insertion.
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Project description:Excess abdominal visceral adipose tissue (VAT) is associated with cardiometabolic risk factors in adolescents. VAT is mainly measured using Magnetic Resonance Imaging (MRI), yet dual-energy x-ray absorptiometry (DXA) is more affordable and available. The purpose was to compare adolescent VAT values obtained by MRI and DXA. A sample of 330 adolescents 10-16 years of age were recruited (52.3% female, 58.5% White). Abdominal VAT was measured using a General Electric (GE) Discovery MRI scanner with imaging software. A whole-body DXA (GE iDXA) scan was performed, and software calculated VAT within the android region. Wilcoxon signed-rank t-tests were used to determine differences between VAT values, within sex, race (White, African American, and Other race), and BMI categories (normal weight, overweight, and obese). VAT values from MRI and DXA were significantly correlated (r = 0.78, p < 0.001). Average VAT from MRI (0.54 ± 0.43 kg) was significantly higher than VAT from DXA (0.33 ± 0.39 kg) in the overall sample (p < 0.001) and within all subgroups (p < 0.001). All standardized values between the two measurements fell within ±1.96 standard deviations, and differences between the methods were not associated with level of VAT. In this sample, DXA values were correlated with MRI values, but DXA consistently underestimated VAT compared with MRI.
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