In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

The feasibility of in vitro mature mouse hepatocyte labeling with a novel iron oxide particle was assessed and the ability of 1.5-T magnetic resonance imaging (MRI) to track labeled mouse hepatocytes in syngenic recipient livers following intraportal cell transplantation was tested. Mouse hepatocytes were incubated with anionic iron oxide nanoparticles at various iron concentrations. Cell viability was assessed and iron oxide particle uptake quantified. Labeled hepatocytes were intraportally injected into 20 mice, while unlabeled hepatocytes were injected into two mice. Liver T2 values, spleen-to-muscle relative signal intensity (RI _{spleen/muscle} ), and liver-to-muscle relative signal intensity (RI _liver/muscle ) on gradient-echo T2-weighted imaging after injection of either labeled or unlabeled hepatocytes were compared with an ANOVA test followed by Fisher’s a posteriori PLSD test. Livers, spleens and lungs were collected for histological analysis. Iron oxide particle uptake was saturable with a maximum iron content of 20 pg per cell and without viability alteration after 3 days of culture. Following labeled-cell transplantation, recipient livers showed well-defined nodular foci of low signal intensity on MRI—consistent with clusters of labeled hepatocytes on pathological analysis—combined with a significant decrease in both liver T2 values and liver-to-muscle RI _liver/muscle (P = 0.01) with minimal T2 values demonstrated 8 days after transplantation. Conventional MRI can demonstrate the presence of transplanted iron-labeled mature hepatocytes in mouse liver.     

Monitoring bone marrow‐originated mesenchymal stem cell traffic to myocardial infarction sites using magnetic resonance imaging

How stem cells promote myocardial repair in myocardial infarction (MI) is not well understood. The purpose of this study was to noninvasively monitor and quantify mesenchymal stem cells (MSC) from bone marrow to MI sites using magnetic resonance imaging (MRI). MSC were dual‐labeled with an enhanced green fluorescent protein and micrometer‐sized iron oxide particles prior to intra‐bone marrow transplantation into the tibial medullary space of C57Bl/6 mice. Micrometer‐sized iron oxide particles labeling caused signal attenuation in T₂*‐weighted MRI and thus allowed noninvasive cell tracking. Longitudinal MRI demonstrated MSC infiltration into MI sites over time. Fluorescence from both micrometer‐sized iron oxide particles and enhanced green fluorescent protein in histology validated the presence of dual‐labeled cells at MI sites. This study demonstrated that MSC traffic to MI sites can be noninvasively monitored in MRI by labeling cells with micrometer‐sized iron oxide particles. The dual‐labeled MSC at MI sites maintained their capability of proliferation and differentiation. The dual‐labeling, intra‐bone marrow transplantation, and MRI cell tracking provided a unique approach for investigating stem cells' roles in the post‐MI healing process. This technique can potentially be applied to monitor possible effects on stem cell mobilization caused by given treatment strategies. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion

PURPOSE: Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution were recently developed, but hepatocyte transplantation systems must be optimized. The authors report their experience with In-111 oxyquinolone labeling of a test dose of hepatocytes (108 cells) for noninvasive assessment of the biodistribution of transplanted hepatocytes in a 5-year-old child with omithine transcarbamoylase deficiency. MATERIALS AND METHODS: Donor hepatocytes (approximately 108) were radiolabeled using a commercially available In-111 oxyquinolone solution (specific activity of 1 mCi/ml). RESULTS: The overall labeling efficiency was 36.4%. A final dose of approximately 290 ,uCi of the In-111-labeled hepatocytes in 10 ml serum-free phosphate-buffered saline was infused percutaneously into the portal vein approximately 2.5 hours after their preparation. The study was performed 3 hours before cell transplantation (109 cells). Quantitative analysis of the biodistribution of In-111-labeled hepatocytes indicated that cells were predominantly localized in the liver immediately after portal vein-infused transplantation. The predominant hepatic distribution was persistent for as long as 7 days after the procedure, with an average liver-to-spleen ratio of 9.5 to 1. No significant pulmonary radiotracer uptake was present. CONCLUSION: These results indicate that In-111 labeling of hepatocytes is useful for the short-term noninvasive analysis of the biodistribution of transplanted hepatocytes.     

MR and fluorescent imaging of low-density lipoprotein receptors

RATIONALE AND OBJECTIVES: Over-expression of low-density lipoprotein receptors (LDLRs) occurs in many types of malignancies and is related to the requirement for lipids for rapid proliferation of the tumors. On the other hand, LDLRs that are unable to bind LDL are found on hepatocytes of patients with familial hypercholesterolemia (FH), a genetic disease that leads to premature atherosclerosis and death. The highly selective binding of LDL to LDLR makes these particles ideal carriers of therapeutic and diagnostic contrast agents into the targeted cells. The objectives of this paper are to examine whether a prototype contrast agent (PTIR267) with dual detection properties is suitable for labeling of LDL particles for in vivo detection of LDLR by magnetic resonance imaging (MRI) and for in vitro monitoring of cellular localization by confocal fluorescence microscopy. MATERIALS AND METHODS: PTIR267 is a lipophilic GdDTPA derivative conjugated to a fluorescent dye. The conjugated dye molecule makes the probe sufficiently water soluble to allow labeling of LDL by a brief incubation of LDL with PTIR267 dissolved in PBS at 37 degrees C (mole ratio LDL: PTIR267 = 0.09:1). The molar relaxivity of PTIR267 in saline is 26 mM(-1)s(-1). Specific LDLR-mediated uptake of PTIR267-labeled LDL was demonstrated in vitro by confocal fluorescence imaging of B16 melanoma cells using confocal fluorescence imaging. In vivo uptake of PTIR267-labeled LDL by a subcutaneously implanted B16 melanoma in mice leads to 30% decrease in longitudinal relaxation time (T(1)) in the tumor. In vivo uptake of PTIR267-labeled LDL leads to 70% decrease in T(1) in a normal C57BL/6 mouse liver; however, in the liver of LDL receptor gene knockout (LDLr-/-) mice with C57BL/6 background, only 12% decrease in T(1) is observed. CONCLUSIONS: The dual fluorescence and MR imaging properties of PTIR267, combined with the ease of LDL labeling, suggest that it will be a useful tool for optimization of LDLR-targeted cancer diagnosis or therapy and for monitoring the efficacy of gene therapy of FH.     

心脏磁共振在体示踪移植细胞的可行性研究

目的：寻找一种能够对移植细胞进行在体示踪的标记方法,为移植细胞存留、迁移提供重要观察手段。方法：从中华小型猪髂骨处抽取骨髓,体外培养扩增骨髓间充质干细胞（MSCs）。将SPIO和MSCs共同孵育培养36h。普鲁士蓝染色评价细胞的标记效率;通过MTT比色实验评价SPIO对细胞生长能力的影响;台盼蓝染色检验标记后细胞的活性;使用Costar Transwell方法评价铁离子对细胞迁移能力的影响;用细胞分化诱导液培养标记后的细胞评价其向成脂肪细胞和成骨细胞的分化能力。在体内实验中将SPIO标记或未标记的自体MSCs注射到心肌内,通过心脏磁共振检查对移植细胞进行在体示踪观察,取材动物心脏行病理检查观察移植细胞的存活、存留。结果：MSCs经铁离子标记后普鲁士蓝染色阳性率在98%以上,可见蓝色颗粒位于细胞浆内,标记细胞电镜切片可见高密度铁颗粒位于细胞浆内。随着培养液中SPIO浓度的增加细胞增殖能力没有明显改变;标记后98%的细胞保持活性;SPIO标记后的细胞保持原有的形态,可继续培养、传代;SDF-1和VEGF诱导的迁移实验发现标记细胞迁移能力没有降低;铁离子标记后细胞仍可向成脂肪细胞和成骨细胞分化。注射到心肌内的SPIO标记的MSCs可通过心脏磁共振检查进行在体示踪,动态观察显示SPIO标记细胞在磁共振图像上表现为低信号,并且在移植后4周仍可成像。病理学检查可以看到移植细胞呈普鲁士蓝染色阳性,并和影像学有很好的一致性。结论：临床使用的SPIO磁共振对比剂可以安全、有效地标记MSCs,心脏磁共振检查可以实现SPIO标记的移植细胞的在体示踪。     

Gadofluorine m uptake in stem cells as a new magnetic resonance imaging tracking method: an in vitro and in vivo study

OBJECTIVES: Cell tracking using ultrasmall iron particles is well established in magnetic resonance imaging (MRI). However, in experimental models, intrinsic iron signals derived from erythrocytes mask the labeled cells. Therefore, we evaluated Gadofluorine M with other gadolinium chelates for a T1-weighted positive enhancement for cell tracking in vitro. In addition, Gadofluorine M was tested in vivo. MATERIAL AND METHODS: Gadofluorine M and other gadolinium chelates were used to label stem cells with and without uptake-mediating agents in vitro and in vivo using a 1.5 T MRI. In addition, histology and molecular modeling was investigated. RESULTS: Gadofluorine M revealed comparable properties to an uptake mediating agent in molecular modeling. Without an uptake-mediating agent Gadofluorine M-labeled cells were detected as a T1-weighted positive contrast in vitro and in vivo. Histology confirmed a 100% success rate for intracellular labeling. CONCLUSION: This study describes a novel contrast agent with the capability of intracellular accumulation without an uptake mediator providing a T1-positive MRI signal at 1.5 T and may be suitable for cell tracking in animal models with intraparenchymal hemorrhages such as stroke or malignant tumors.     

T-cell homing to the pancreas in autoimmune mouse models of diabetes: in vivo MR imaging

PURPOSE: To evaluate the efficiency of T-cell labeling with anionic magnetic nanoparticles (AMNPs) and in vivo magnetic resonance (MR) imaging monitoring of T-cell homing to the pancreas. MATERIALS AND METHODS: In vivo MR images of pancreas were obtained with a 7-T MR system in 12 NOD (nonobese diabetic) mice at 11 and 20 days after injection of AMNP-loaded or unloaded T cells. Homing of loaded T cells in pancreatic lymph nodes was detected by the presence of a focal dark spot with T2* effect in a caudal area of the pancreas. Detection of loaded T cells in pancreatic islets was evaluated by comparison of histograms of MR signal intensity generated in whole pancreas in mice injected with loaded and unloaded T cells. Homing of loaded T cells was confirmed at transmission electronic microscopy (TEM). Fifty-six mice underwent all experiments. RESULTS: Focal dark spots with T2* effect were observed at 11 days in all three mice injected with loaded T cells and in none of the three mice injected with unloaded T cells. At 20 days, a more diffuse negative enhancement of the whole pancreas was noticed in one mouse injected with loaded T cells than in three mice injected with unloaded T cells. Presence of loaded T cells was confirmed with TEM. In vitro and in vivo tests confirmed that survival and function were not altered by loading. CONCLUSION: The ability of MR imaging to depict cell homing in living organisms at least 20 days after cell labeling was demonstrated, opening the way of follow-up in autoimmune diseases and cell therapy.     

Sizing it up: cellular MRI using micron-sized iron oxide particles.

There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextran-coated iron oxide particles. The limitations of using nanometer-sized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 microm. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPIOs generally contained iron levels of approximately 100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as approximately 400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI.     

干细胞移植的磁性标记及磁共振成像活体示踪

干细胞移植的临床应用需要解决植入活体内干细胞在体内存活、迁移及分化的监测问题。通过对干细胞进行顺磁性标记,磁共振成像(MRI)能够在活体上显示标记的干细胞,并进行特异性地追踪及定位,是目前干细胞活体示踪极具前景的方法。干细胞进行磁性标记主要利用铁类或钆类对比剂,两者各有优缺点。利用铁类或钆类对比剂标记干细胞并进行MRI活体监测取得了成功。并在心脑缺血损伤的疾病模型中得到应用,但在干细胞磁性标记的载体选用及其标记率、标记的持久性、标记对细胞活力及遗传性状方面尚存在一定的问题。     

In vivo MR tracking of mesenchymal stem cells in rat liver after intrasplenic transplantation

PURPOSE: To prospectively track in vivo in rats intrasplenically transplanted stem cells labeled with superparamagnetic particles by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional Committee on Animal Research. Liver damage in 12 rats was induced with subcutaneous injection of carbon tetrachloride (CCl4). Intrasplenic transplantation of 6x10(6) rodent bone mesenchymal stem cells (BMSCs) with (n=6) and without (n=6) superparamagnetic particle Fe2O3-poly-L-lysine (PLL) labeling was performed via direct puncture. Cell labeling efficiency was assessed in vitro by using Prussian blue stain and an atomic absorption spectrometer. MR examinations were performed immediately before and 3 hours and 3, 7, and 14 days after transplantation. Liver-to-muscle contrast-to-noise ratios (CNRs) on T2*-weighted MR images obtained before and after injection were measured and correlated with histomorphologic studies. Statistical analyses were performed by using repeated-measures analysis of variance. RESULTS: Rat BMSCs could be effectively labeled with approximately 100% efficiency. Migration of transplanted labeled cells to the liver was successfully documented with in vivo MR imaging. CNRs on T2*-weighted images decreased significantly in the liver 3 hours after injection of BMSCs (P<.05) and returned gradually to the level achieved without labeled cell injection in 14 days. Histologic analyses confirmed the presence of BMSCs in the liver. The labeled cells primarily localized in the sinusoids of periportal areas and the foci of CCl4-induced liver damage. Quantitative analysis of Prussian blue-stained cells indicated gradual decrease of dye pigments from 3 hours to 3, 7, and 14 days after injection. No free iron particles were found in the interstitium or within hepatic microvessels. CONCLUSION: The rat BMSCs could be efficiently labeled with Fe2O3-PLL and the relocation of the labeled cells to rat livers after intrasplenic transplantation could be depicted at in vivo MR imaging.     

Magnetic resonance imaging detects differences in migration between primary and immortalized neural stem cells

RATIONALE AND OBJECTIVES: The study was performed to evaluate the effect of magnetic resonance imaging (MRI) contrast agent (super paramagnetic iron oxide [SPIO]) on differentiation and migration of primary murine neural stem cells (NSCs) in comparison to a neural stem cell line (C17.2). Because detection of labeled cells depends on the concentration of SPIO particles per imaging voxel, the study was performed at various concentrations of SPIO particles to determine the concentration that could be used for in vivo detection of small clusters of grafted cells. MATERIALS AND METHODS: Murine primary NSCs or C17.2 cells were labeled with different concentrations of SPIO particles (0, 25, 100, and 250 mug Fe/mL) and in vitro assays were performed to assess cell differentiation. In vivo MRI was performed 7 weeks after neonatal transplantation of labeled cells to evaluate the difference in migration capability of the two cell populations. RESULTS: Both the primary NSCs and the C17.2 cells differentiated to similar number of neurons (Map2ab-positive cells). Similar patterns of engraftment of C17.2 cells were seen in transplanted mice regardless of the SPIO concentration used. In vivo MRI detection of grafted primary and C17.2 cells was only possible when cells were incubated with 100 mug/mL or higher concentration of SPIO. Extensive migration of C17.2 cells throughout the brain was observed, whereas the migration of the primary NSCs was more restricted. CONCLUSIONS: Engraftment of primary NSCs can be detected noninvasively by in vivo MRI, and the presence of SPIO particles do not affect the viability, differentiation, or engraftment pattern of the donor cells.     

Cell labeling with the positive MR contrast agent Gadofluorine M

The purpose of this study was to label human monocytes with Gadofluorine M by simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages. Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities of the labeled cells and non-labeled controls were determined. Cellular contrast agent uptake was examined by fluorescence microscopy and quantified by ICP-AES. Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell without impairment of cell viability. Fluorescence microscopy confirmed internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T. Imaging studies showed stable labeling for at least 7 days. Human monocytes can be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell-tracking applications include targeting of inflammatory processes with Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the treatment of arthritis.     

Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: the case of the shiverer dysmyelinated mouse brain.

LacZ-transfected C17.2 neural stem cells (NSCs) were labeled with the superparamagnetic iron oxide formulation Feridex prior to ICV injection in shi/shi neonates. Feridex labeling did not alter cell differentiation in vitro and in vivo. Initially, MR images obtained at 11.7T correlated closely to NSC distribution as assessed with anti-dextran and anti-beta-galactosidase double-fluorescent immunostaining. However, at 6 days postgrafting there was already a pronounced mismatch between the hypointense MR signal and the histologically determined cell distribution, with a surprisingly sharp cutoff rather than a gradual decrease of signal. Positive in vivo BrdU labeling of NSCs showed that significant cell replication occurred post-transplantation, causing rapid dilution of Feridex particles between mother and daughter cells toward undetectable levels. Neural differentiation experiments demonstrated asymmetric cell division, explaining the observed sharp cutoff. At later time points (2 weeks), the mismatch further increased by the presence of non-cell-associated Feridex particles resulting from active excretion or cell death. These results are a first demonstration of the inability of MRI to track rapidly dividing and self-renewing, asymmetrically dividing SCs. Therefore, MR cell tracking should only be applied for nonproliferating cells or short-term monitoring of highly-proliferative cells, with mitotic symmetry or asymmetry being important for determining its applicability.     

异基因小鼠骨髓细胞程序移植后回巢的实验研究

目的探讨骨髓程序移植后移植次数与移植细胞数对回巢的影响.方法采用异基因小鼠骨髓移植模型及流式细胞术,观察不同次数异基因骨髓细胞程序移植后不同时间的回巢状况、不同细胞数异基因骨髓细胞程序移植与单次大剂量移植的回巢状况.结果不同次数移植后各组不同时间阳性回巢细胞数与回巢率均以第3次移植的检测值最高,在共同时间点第4天时均以2次移植组最高(P＜0.05),提示移植后每天都会有回巢发生,但不同移植次数可能在时间上有不同的回巢高峰阶段.不同细胞数异基因骨髓细胞程序移植后,移植细胞数低的移植组与单次大细胞数组比较,回巢细胞数无明显差异,回巢率却远远高于后者(P＜0.01).结果显示在一定剂量范围内多次小剂量移植的回巢效果可能等于或好于单次大剂量移植,且总剂量可能降低至105.结论单次大剂量移植会造成移植干细胞的浪费,在一定细胞量范围内改变移植次数有利于改善移植效果.     

Magnetosonoporation: Instant magnetic labeling of stem cells

The purpose of this study was to develop an instant MR cell labeling technique, called magnetosonoporation. First, a magnetosonoporation apparatus was successfully established for MR labeling of stem cells. Then, the safety of this new cell labeling approach was confirmed by evaluation of cell viability, proliferation, and differentiation of magnetosonoporation‐labeled and unlabeled C17.2 neural stem cells. Subsequently, the feasibility of using in vivo MRI to detect magnetosonoporation/Feridex‐labeled stem cells was validated in living animals and confirmed by histologic correlation. The magnetosonoporation technique is expected to be convenient, efficient, and safe for future clinical application of MRI‐guided cell therapies. Magn Reson Med 63:1437–1441, 2010. © 2010 Wiley‐Liss, Inc.     

Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model.

This article describes an in vivo imaging method for visualizing and quantifying a specific cell population. Cells are labeled ex vivo with a perfluoropolyether nanoparticle tracer agent and then detected in vivo using (19)F MRI following cell transfer. (19)F MRI selectively visualizes only the labeled cells with no background, and a conventional (1)H image taken in the same imaging session provides anatomical context. Using the nonobese diabetic mouse, an established model of type 1 diabetes, (19)F MRI data were acquired showing the early homing behavior of diabetogenic T cells to the pancreas. A computational algorithm provided T cell counts in the pancreas. Approximately 2% of the transferred cells homed to the pancreas after 48 hr. The technique allows for both unambiguous detection of labeled cells and quantification directly from the in vivo images. The in vivo quantification and cell trafficking patterns were verified using (19)F spectroscopy and fluorescence microscopy in excised pancreata. The labeling procedure did not affect T-cell migration in vivo. This imaging platform is applicable to many cell types and disease models and can potentially be used for monitoring the trafficking of cellular therapeutics.     

Stem Cell Monitoring with a Direct or Indirect Labeling Method

The molecular imaging techniques allow monitoring of the transplanted cells in the same individuals over time, from early localization to the survival, migration, and differentiation. Generally, there are two methods of stem cell labeling: direct and indirect labeling methods. The direct labeling method introduces a labeling agent into the cell, which is stably incorporated or attached to the cells prior to transplantation. Direct labeling of cells with radionuclides is a simple method with relatively fewer adverse events related to genetic responses. However, it can only allow short-term distribution of transplanted cells because of the decreasing imaging signal with radiodecay, according to the physical half-lives, or the signal becomes more diffuse with cell division and dispersion. The indirect labeling method is based on the expression of a reporter gene transduced into the cell before transplantation, which is then visualized upon the injection of an appropriate probe or substrate. In this review, various imaging strategies to monitor the survival and behavior change of transplanted stem cells are covered. Taking these new approaches together, the direct and indirect labeling methods may provide new insights on the roles of in vivo stem cell monitoring, from bench to bedside.     

MRI detection of macrophages labeled using micrometer-sized iron oxide particles

PURPOSE: To evaluate cellular labeling of immune cells using micron-sized iron oxide particles (MPIOs) and evaluate the MR relaxivity and MRI detection of the labeled cells. MATERIALS AND METHODS: Immune cells isolated from mice and rats were labeled with three different sizes of MPIO particles (0.35, 0.90, or 1.63 microm). These labeled cells were characterized using transmission electron microscopy (TEM), fluorescence microscopy, flow cytometry, MR relaxometry, and MRI. RESULTS: Macrophage uptake of MPIOs was found to be highest for the 1.63-microm size particles. MR relaxivity measurements indicated greater spin-spin relaxation for MPIO-labeled cells relative to cells labeled with nanometer-sized ultra-small superparamagnetic iron oxide (USPIO) particles with similar iron content. TEM and fluorescence microscopy indicated cellular uptake of multiple MPIO particles per cell. Macrophages labeled with 1.63-microm MPIOs had an average cellular iron uptake of 39.1 pg/cell, corresponding to approximately 35 particles per cell. CONCLUSION: Cells labeled with one or more MPIO particles could be readily detected ex vivo at 11.7 Tesla and after infusion of the MPIO-labeled macrophages into the kidney of a rat, hypointense regions of the outer cortex are observed, in vivo, by MRI at 4.7 Tesla.     

Temporal and noninvasive monitoring of inflammatory‐cell infiltration to myocardial infarction sites using micrometer‐sized iron oxide particles

Micrometer‐sized iron oxide particles (MPIO) are a more sensitive MRI contrast agent for tracking cell migration compared to ultrasmall iron oxide particles. This study investigated the temporal relationship between inflammation and tissue remodeling due to myocardial infarction (MI) using MPIO‐enhanced MRI. C57Bl/6 mice received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later (n = 7). For controls, two groups underwent either sham‐operated surgery without inducing an MI post‐MPIO injection (n = 7) or MI surgery without MPIO injection (n = 6). The MRIs performed post‐MI showed significant signal attenuation around the MI site for the mice that received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later, compared to the two control groups (P < 0.01). The findings suggested that the prelabeled inflammatory cells mobilized and infiltrated into the MI site. Furthermore, the linear regression of contrast‐to‐noise ratio at the MI site and left ventricular ejection function suggested a positive correlation between the labeled inflammatory cell infiltration and cardiac function attenuation during post‐MI remodeling (r² = 0.98). In conclusion, this study demonstrated an MRI technique for noninvasively and temporally monitoring inflammatory cell migration into the myocardium while potentially providing additional insight concerning the pathologic progression of a myocardial infarction. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

MR示踪技术在干细胞治疗心肌梗死中的研究进展

活体细胞MR示踪成像技术能有效在体内实时、准确评价干细胞治疗心肌梗死的效果，可分为MR对比剂标记细胞成像和MR报告基因成像。自体移植干细胞治疗心肌梗死的疗法中，能标记干细胞的MR对比剂主要有以钆剂为主的顺磁性对比剂、化学交换饱和转移成像（CEST）相关对比剂以及氧化铁类对比剂；MR 报告基因导入后能使细胞表达产生MR信号改变的蛋白质，以膜表面蛋白为主，包括铁蛋白受体、膜表面抗原、酶等。目前的MR细胞示踪技术对自体移植干细胞治疗的疗效评价、机制研究有一定的指导作用。