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

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

Validation report which details the advanced models developed to describe a) static and continuous and b) dynamic force transfer standards taking into account sensitivity stability, temperature and other parasitic influences on the measurement uncertainty (target uncertainty is 1 % up to 100 Hz and 2 % between 100 - 1000 Hz)

Current document reports on the development and validation of advanced practical models for describing force measuring devices used for the measurement of static, continuous forces in part A as well as dynamic forces in part B of the report. In the force measurement applications, the sensitivity curve of the force measuring devices determined in the calibration gives the traceability to national standards. The measurement uncertainty in an application is mainly affected by the sensitivity stability, the influence of temperature and other parasitic components. To capture these effects an advanced model for static and continuous forces was developed in part A which describes these influences especially in respect of their contribution to the measurement uncertainty. In contrast to the static calibration procedure, the dynamic calibration of the sensor has been always challenging because of several reasons such as the sophisticated nature of dynamic measurement, insufficient structural equipment, and parasitic effects which yield higher measurement uncertainty in comparison to static measurements and therefore inappropriate characterization of the force transducers. To close this knowledge gap in the dynamic calibration, the advanced model for dynamic forces was developed in part B. To consider the dynamic properties of force measuring devices the frequency dependency of the sensitivity and the influence of parasitic influences from temperature of the force measuring devices was considered and described. The target uncertainty is 1 % for up to 100 Hz and the target uncertainty is 2 % for higher frequency range from 100 Hz up to 1000 Hz

The use of random forests to classify amyloid brain PET

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.Purpose: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification. Methods: The data set included 57 baseline 18F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for super- vised training of an RF classifier programmed in MATLAB. Results: A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence in- terval [CI], 42%–100%), specificity = 92% (CI, 64%–100%), and classification accuracy = 90% (CI, 68%–99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right an- terior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees). Conclusions: Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.CIHR MITNEC C6 || Linda C Campbell Foundation || Lilly-Avid Radiopharmaceuticals