Comparison of 111In Leakage from Labeled Endocardial and Epicardial Cells: Impact on Modeling Viability of Cells to Be Transplanted into Myocardium

Introduction. Previously we proposed a cellular imaging technique to determine the surviving fraction of transplanted cells in vivo. Epicardial kinetics using Indium-111 determined the Debris Impulse Response Function (DIRF) and leakage coefficient parameters. Convolution-based modeling which corrected for these signal contributions indicated that 111In activity was quantitative of cell viability with half-lives within 20 hrs to 37 days. We determine if the 37-day upper limit remains valid for endocardial injections by comparing previous epicardial cell leakage parameter estimates to those for endocardial cells. Methods. Normal canine myocardium was injected (111In-tropolone) epicardially (9 injections) or endocardially (10 injections). Continuous whole body and SPECT scans for 5 hours were acquired with three weekly follow-up imaging sessions up to 20–26 days. Time-activity curves evaluated each injection type. Results. The epicardial and endocardial kinetics were not significantly different (Epi: 1286 ± 253; Endo: 1567 ± 470 hours P = .62). Conclusion. The original epicardial estimate of leakage kinetics has been validated for use in endocardial injections

Relating functional and structural signatures of Parkinson’s disease to changes in dopamine signalling: A PET/fMRI study

Cognitive impairments in early Parkinson\u27s disease are known to be linked to complex changes in the dopamine system within the brain. For example, dopamine-producing neurons in one key region of the brain are significantly degenerated, but those in another are spared. Dopamine-replacement therapy (DRT) has been pursued and it has produced significant improvements in certain cognitive functions - unfortunately it also produced significant impairments in others.https://ir.lib.uwo.ca/brainscanprojectsummaries/1019/thumbnail.jp

A noninvasive method for quantifying cerebral blood flow by hybrid PET/MRI

Although PET with 15O-water is the gold standard for imaging cerebral blood flow (CBF), quantification requires measuring the arterial input function (AIF), which is an invasive and noisy procedure. To circumvent this problem, we propose a noninvasive PET/MRI approach that eliminates the need to measure AIF by using global CBF determined by phase-contrast (PC) MRI as a reference region. This approach not only is noninvasive but also involves no additional imaging time, because PC MRI and 15O-water PET are acquired simultaneously. The purpose of this study was to test the accuracy of this hybrid method in an animal model in which AIF was measured directly and CBF was varied by changing the arterial CO2 tension. Methods: PET and MRI data were simultaneously acquired in juvenile pigs at hypocapnia (n 5 5), normocapnia (n 5 5), and hypercapnia (n 5 4). CBF was measured by the MRI reference method and by PET alone using an MRI-compatible blood sampling system to measure AIF. Results: Global CBF estimates from PC MRI and 15O-water PET agreed well, with a correlation coefficient of 0.9 and a slope of 0.88. Strong positive correlations (R2 . 0.96) were also found between regional CBF generated by the PET-only and the MRI-reference methods. Conclusion: These findings demonstrate the accuracy of this hybrid PET/MRI approach, which might prove useful in patients for whom obtaining accurate CBF measurements is challenging

Comparison of initial cell retention and clearance kinetics after subendocardial or subepicardial injections of endothelial progenitor cells in a canine myocardial infarction model

Neither intravenous nor intracoronary routes provide targeted stem cell delivery to recently infarcted myocardium in sufficient quantities. Direct routes appear preferable. However, most prior studies have used epicardial injections, which are not practical for routine clinical use. The objective of this study was to compare cell retention and clearance kinetics between a subepicardial and a subendocardial technique. Methods: We evaluated 7 dogs with each technique, using 111In-tropolone-labeled endothelial progenitor cells and serial SPECT/CT for 15 d after injection. Results: In vivo indium imaging demonstrated comparable degrees of retention: 57% ± 15% for the subepicardial injections and 54% ± 26% for the subendocardial injections. Clearance half-lives were also similar at 69 ± 26 and 60 ± 21 h, respectively. Conclusion: This study demonstrates that subendocardial injections, clinically more practical, show clearance kinetics comparable to those of subepicardial injections and will facilitate the ultimate clinical use of this treatment modality. Copyright © 2010 by the Society of Nuclear Medicine, Inc

Comparison of the myocardial clearance of endothelial progenitor cells injected early versus late into reperfused or sustained occlusion myocardial infarction

Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4-5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion. © 2012 The Author(s)

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method.

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored. METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with (18)F-flurodexoyglucose in several regions across the brain. RESULTS: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5-20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p \u3c 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps. CONCLUSION: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging

MagA expression attenuates iron export activity in undifferentiated multipotent P19 cells

© 2019 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Magnetic resonance imaging (MRI) is a non-invasive imaging modality used in longitudinal cell tracking. Previous studies suggest that MagA, a putative iron transport protein from magnetotactic bacteria, is a useful gene-based magnetic resonance contrast agent. Hem-agglutinin-tagged MagA was stably expressed in undifferentiated embryonic mouse teratocarcinoma, multipotent P19 cells to provide a suitable model for tracking these cells during differentiation. Western blot and immunocytochemistry confirmed the expression and membrane localization of MagA in P19 cells. Surprisingly, elemental iron analysis using inductively-coupled plasma mass spectrometry revealed significant iron uptake in both parental and MagA-expressing P19 cells, cultured in the presence of iron-supplemented medium. Withdrawal of this extracellular iron supplement revealed unexpected iron export activity in P19 cells, which MagA expression attenuated. The influence of iron supplementation on parental and MagA-expressing cells was not reflected by longitudinal relaxation rates. Measurement of transverse relaxation rates (R2* and R2) reflected changes in total cellular iron content but did not clearly distinguish MagA-expressing cells from the parental cell type, despite significant differences in the uptake and retention of total cellular iron. Unlike other cell types, the reversible component R20 (R2* – R2) provided only a moderately strong correlation to amount of cellular iron, normalized to amount of protein. This is the first report to characterize MagA expression in a previously unrecognized iron exporting cell type. The interplay between contrast gene expression and systemic iron metabolism substantiates the potential for diverting cellular iron toward the formation of a novel iron compartment, however rudimentary when using a single magnetotactic bacterial gene expression system like magA. Since relatively few mammalian cells export iron, the P19 cell line provides a tractable model of ferroportin activity, suitable for magnetic resonance analysis of key iron-handling activities and their influence on gene-based MRI contrast

Digital twin concept of a force measuring device based on the finite element method

In the framework of EMPIR project ComTraForce, the Digital Twin (DT) concept of force measurement device is developed. DT aims to shade static, continuous as well as dynamic calibration processes, preserving data quality and collecting calibration data for improved Decision-making. To illustrate the developed DT concept, a prototype realisation for static and continuous force calibration processes is developed, involving simulation with ANSYS engineering software. The focus of the current work is placed on the data connection between the physical device and the DT. The DT model is validated using traceable measurements