In vivo magnetic resonance imaging of single cells in mouse brain with optical validation

Heyn, Chris; Ronald, John A.; MacKenzie, Lisa T.; Macdonald, Ian; Chambers, Ann F.; Rutt, Brian K.; Foster, Paula J.

doi:10.1002/mrm.20747

Cited by 264 publications

(220 citation statements)

References 25 publications

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“…In the in-vivo experiments the detection of single co-labeled MSC could be demonstrated by MRI. For a systemic delivery and peripheral single cell distribution bypassing the lung barrier [44], the MSC were injected into the left ventricular cavity of the heart as described for magnetically labeled macrophages by Heyn et al [12]. However, instead of a surgical method with an open-chest incision, a minimally invasive ultrasound-guided approach was used.…”

Section: Discussionmentioning

confidence: 99%

“…The large amount of intracellular iron oxide particles and the use of high-resolution T2*-weighted gradient echo sequences permits cellular MRI techniques to be very sensitive. Thus, MRI of single magnetically labeled cells could be demonstrated in-vitro [11] and promising results have been shown also in-vivo, e. g. the detection of single macrophages in the brain after intracardial injection [12] and migration of hepatocytes to the liver after injection into the spleen [13]. Multipotent mesenchymal stromal cells (MSC), also known as mesenchymal stem cells [14], are bone marrow-derived precursor cells with the potential to differentiate into different mesenchymal lineages, such as adipocytes, chondroblasts and osteoblasts [15].…”

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confidence: 99%

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Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Salamon

Wicklein

Didié

et al. 2014

Fortschr Röntgenstr

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Ziel: Etablierung einer Doppelmarkierung mesenchymaler Stromazellen (MSZ) zur in-vivo Detektion einzelner MSZ mittels MRT und zur histologischen Validierung. Material und Methoden: Murine MSZ wurden mit fluoreszierenden Eisenmikropartikeln und Carboxyfluorescein Succinimidyl Ester (CFSE) markiert. Der zelluläre Eisengehalt wurde mittels Atomabsorptionsspektrometrie bestimmt. Zellprolieferation und Expression charakteristischer Oberflächenmarker wurden mittels Durchflusszytometrie bestimmt. Die chondrogene Differenzierungskapazität wurde überprüft. Verschiedene Zellanzahlen (n1 = 5000, n2 = 15 000, n3 = 50 000) wurden bei 12 Mäusen in den linken Herzventrikel injiziert. Es erfolgte die sequenzielle MRT der Tiere an einem klinischen 3.0 T MRT. Zur histologischen Validierung wurden Kryostatschnitte fluoreszensmikroskopisch untersucht. Ergebnisse: Die magnetische und fluoreszierende Doppelmarkierung von MSZ wurde etabliert (mittlerer zellulärer Eisengehalt 23,6 ± 4,3 pg). Durchflusszytometrisch zeigten sich ähn-liche Zellprolieferationsraten und Rezeptorexpressionsprofile von markierten und unmarkierten MSZ. Die chondrogene Differenzierung der doppelt markierten MSZ wurde verifiziert. Nach Zellinjektion zeigten sich im MRT multiple Signalauslöschungen im Hirn und geringer in der Niere. Im Hirn fanden sich durchschnittlich 4,6 ± 1,2 (n1), 9,0 ± 3,6 (n2) und 25,0 ± 1,0 (n3) Signalauslöschungen pro Schicht. Durchschnittlich fanden sich 8,7 ± 3,1 (n1), 22,0 ± 6,1 (n2) und 89,8 ± 6,5 (n3) Zellen pro korrespondierendem Kryostatschnitt. Die statistische Korrelation der mittels MRT detektierten Signalauslöschungen und der histologisch nachgewiesenen Zellen ergab einen Korrelationskoeffizienten von r = 0,91. Schlussfolgerung: Die Studie zeigt die erfolgreiche magnetische und fluoreszierende DoppelmarkieAbstract ! Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Salamon

Wicklein

Didié

et al. 2014

Fortschr Röntgenstr

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“…Moreover, the migration of macrophages in apoptotic tissue replacement [167], tumors [168], or vascular aneurysms [169] was able to be visualized in vivo. With respect to in vivo sensitivity, it is possible under ideal conditions to detect single SPIO-labeled cells [170].…”

Section: Cell Labeling and Cell Imaging In Mrimentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Ittrich¹,

Peldschus²,

Raabe³

et al. 2013

Fortschr Röntgenstr

125

101

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Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image physiological processes and anatomical, cellular and molecular changes in diseases. The clinical applications range from the imaging of tumors and metastases in the liver, spleen and bone marrow, the imaging of lymph nodes and the CNS, MRA and perfusion imaging to atherosclerotic plaque and thrombosis imaging. New experimental approaches in molecular imaging describe undirected SPIO trapping (passive targeting) in inflammation, tumors and associated macrophages as well as the directed accumulation of SPIO ligands (active targeting) in tumor endothelia and tumor cells, areas of apoptosis, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerotic plaques or thrombi. The labeling of stem or immune cells allows the visualization of cell therapies or transplant rejections. The coupling of SPIO to ligands, radio- and/or chemotherapeutics, embedding in carrier systems or activatable smart sensor probes and their externally controlled focusing (physical targeting) enable molecular tumor therapies or the imaging of metabolic and enzymatic processes. Monodisperse SPIO with defined physicochemical and pharmacodynamic properties may improve SPIO-based MRI in the future and as targeted probes in diagnostic magnetic resonance (DMR) using chip-based ?NMR may significantly expand the spectrum of in vitro analysis methods for biomarker, pathogens and tumor cells. Magnetic particle imaging (MPI) as a new imaging modality offers new applications for SPIO in cardiovascular, oncological, cellular and molecular diagnostics and therapy. Key Points: Citation Format:

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“…These studies were facilitated by the development of novel magnetic resonance imaging (MRI) techniques and hardware ('Single Cell MRI') that allow detection of single cancer cells that remain dormant in vivo, detectable due to their retention of iron microparticles loaded into cells prior to their in vivo injection (e.g. [21][22][23][24], reviewed in [25]). Examples of iron-loaded cells in vitro and in vivo, along with in vivo mouse brain MRI images, are shown in figure 1.…”

confidence: 99%

“…The journal Convergent Science Physical Oncology is providing a valuable new forum for facilitating these interactions. [21][22][23][24] and as reviewed in [25]. Scale bars in A and B, 100 µm.…”

confidence: 99%

Tumor metastasis, physical sciences and the value of multidisciplinary collaborations

Chambers¹

2016

Converg. Sci. Phys. Oncol.

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In vivo magnetic resonance imaging of single cells in mouse brain with optical validation

Cited by 264 publications

References 25 publications

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Tumor metastasis, physical sciences and the value of multidisciplinary collaborations

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