菲立磁增强磁共振成像在肝脏疾病诊断中的价值

目的　评价菲立磁增强MRI在肝脏疾病诊断中的应用价值。方法　对 31例经CT或MRI检查确定或怀疑有肝脏病变者进一步行菲立磁增强MRI检查 ,分别测量增强前后肝脏、病变及背景噪声的T2 WI信号强度 ,计算增强前后肝脏及病变的信噪比(SNR)、对比噪声比 (CNR)。分析平扫及增强后扫描检测的病灶数目。结果　菲立磁增强后肝脏的SNR明显降低 (Ρ <0 .0 1) ;恶性病灶的SNR变化不明显 (Ρ >0 .0 5 ) ;病灶 -肝脏CNR明显增高 (Ρ <0 .0 1)。增强后病变的检出数量增加 ( χ2 =8.5 7,Ρ <0 .0 1)。结论　菲立磁能显著提高肝脏恶性肿瘤的检出率 ,而且对肝脏小病灶的鉴别诊断提供有利的依据     

In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction.

The therapeutic potential of administering stem cells to promote angiogenesis and myocardial tissue regeneration after infarction has recently been demonstrated. Given the advantages of using embryonic stem cells and mouse models of myocardial infarction for furthering the development of this therapeutic approach, the purpose of this study was to determine if embryonic stem cells could be loaded with superparamagnetic iron oxide (SPIO) particles and imaged in a mouse model of myocardial infarction over time using MRI. Mouse embryonic stem cells were labeled with SPIO particles. When incubated with 11.2, 22.4, and 44.8 microg Fe/ml of SPIO particles, cells took up increasing amounts of iron oxide. Embryonic stem cells loaded with SPIO compared to unlabeled cells had similar viability and proliferation profiles for up to 14 days. Free SPIO injected into infarcted myocardium was not observable within 12 hr after injection. After injection of three 10-microl aliquots of 10(7) SPIO-loaded cells/ml into infarcted myocardium, MRI demonstrated that the mouse embryonic stem cells were observable and could be seen for at least 5 weeks after injection. These findings support the ability of MRI to test the long-term therapeutic potential of embryonic stem cells in small animals in the setting of myocardial infarction.     

Chondrocyte gene expression is affected by very small iron oxide particles-labeling in long-term in vitro MRI tracking

Purpose:

To investigate the effect and dose response of very small iron oxide particles (VSOP) labeling of human chondrocytes for long‐term in vitro MRI tracking.

Materials and Methods:

Chondrocytes were isolated from cartilage biopsies from four patients. The cells for the dose–response study were labeled with 25, 50, or 100 μg/mL VSOP. Quantitative gene expression and cellular proliferation were compared with unlabeled controls at day 1, 3, and 7. The cells suited for MRI tracking were labeled with 50 μg/mL VSOP and embedded in alginate beads, followed by MRI (using T2‐weighted sequences) at day 0, 1, 3, 7, 14, 21, 28, and histology was performed at each time‐point.

Results:

Histology revealed that VSOP particles were intracellularly confined at all time‐points, whereas no extracellular VSOPs were observed. A mean reduction in T2‐value of 25.1 ms (±SD 3.5 ms) was found on T2‐maps. The chondrocyte‐specific genes aggrecan, collagen type 2, and sox9 were all affected by labeling, the two latter in a dose‐dependent manner. VSOPs had no effect on proliferation.

Conclusion:

VSOP labeling of chondrocytes affected gene expression but not proliferation. The labeled chondrocytes could be recognized by MRI for 4 weeks without significant changes in the T2 relaxation time. J. Magn. Reson. Imaging 2011;33:724–730. © 2011 Wiley‐Liss, Inc.     

菲立磁增强MRI在肝脏局灶性病变诊断中的价值

目的 评价菲立磁增强MRI在肝脏实性占位性病变诊断中的应用价值。材料与方法 对21例怀疑有肝脏局灶性占位病变患者行MR平行及菲立磁增强MRI检查。扫描序列包括频率选择脂肪抑制及非脂肪抑制ASTE T2WI、True FISP T2WI、频率选择脂肪抑制FLASH T1WI。比较增强前后T2WI及T2WI病灶及肝脏的信噪比（SNR）及对比噪声比（CNR）;观察增强前后病灶数量及形态;结合MR平扫及增强MRI表现进行定性诊断。结果 菲立磁增强T2WI及T2WI肝脏信号强度较平扫明显下降,病灶与肝脏的CNR较平扫明显提高,差异具有统计学意义。结论 菲立磁增强T2WI及T2WI可明显提高肝脏实性占位性病灶的检出率。菲立磁增强T1WI在脏局灶性病变的定性诊断中具有潜在价值,有待于进一步开发与研究。     

USPIO-enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys.

To evaluate first-pass renal perfusion with ultrasmall superparamagnetic iron oxide (USPIO) particles by MRI, 40 normal rats (20 Dark Agouti (DA) rats and 20 Brown Norway (BN) rats) and 16 transplanted rats (12 allografts and four isografts) were studied on day 4 post-transplantation with different USPIO doses (3.0-18.1 mg Fe/kg/body weight). All animals underwent 128 consecutive snapshot fast low-angle shot (FLASH) coronal dynamic studies in 43 s. In the normal rats, a larger maximum signal decrease (MSD) in the cortex and the outer medulla is observed with an increasing dose of USPIO particles (P < 0.01). No significant differences were observed between the right and left kidneys at all doses studied. Higher MSD, time of occurrence of MSD (tMSD), and wash-in slope appear with higher doses of USPIO particles. The dynamic curves for DA rats show similar shapes when compared to those for BN rats. In the transplanted rats, allograft kidneys show lower MSD, longer tMSD, and lower wash-in slope compared to those in the normal kidneys. Isograft kidneys show perfusion patterns similar to those of normal kidneys in the cortex and the outer medulla. Histopathology indicates acute vascular rejection in all allografts and normal kidney architecture in all isografts. The results clearly show good agreement between the renal graft perfusion measurements and histopathological changes associated with rejection. This work also introduces a new signal analysis methodology for the automatic detection of transplanted organ rejection. This method compares the dynamics of the intrarenal signal intensities for native and transplanted kidneys. A quantitative measurement to detect significant differences between these signals was developed, and showed that this technique exhibits good performance in identifying renal rejection.     

Hab18-SPIO磁共振造影剂的制备及其实验研究

目的制备靶向人肝细胞肝癌表面抗原Hab18g的MR特异性抗体显影剂Hab18-SPIO,探讨其合成原理、制备要点及物理性状。方法利用化学交联方法,采用人肝细胞癌单抗Hab18标记SPIO,制作出靶向显影剂Hab18-SPIO。并用同样方法制备阴性抗体显影剂SED-SPIO(SED为葡萄球菌肠毒素D抗体)。使用电镜及高压液相色谱仪(HPLC)对Hab18-SPIO进行测试。结果经电镜观察和液相色谱分析证明Hab18与SPIO有效地结合在一起,通过蛋白质含量测定得到抗体与SPIO的交联率为97.5%。经电镜观察制备的靶向显影剂Hab18-SPIO粒径在50~70 nm之间,并且SPIO中颗粒较小的部分与抗体的交联较多。结论成功构建了靶向人肝细胞肝癌表面抗原Hab18g的探针,该探针具有良好的理化性质,为进一步研究早期肝癌特异性MR诊断提供了有价值的手段。     

Quantification of superparamagnetic iron oxide (SPIO)-labeled cells using MRI

PURPOSE: To show the feasibility of using magnetic resonance imaging (MRI) to quantify superparamagnetic iron oxide (SPIO)-labeled cells. MATERIALS AND METHODS: Lymphocytes and 9L rat gliosarcoma cells were labeled with ferumoxides-protamine sulfate complex (FE-PRO). The cells were labeled efficiently (more than 95%) and the iron concentration inside each cell was measured by spectrophotometry (4.77-30.21 pg). Phantom tubes containing different numbers of labeled or unlabeled cells, as well as different concentrations of FE-PRO, were made. In addition, labeled and unlabeled cells were injected into fresh and fixed rat brains. RESULTS: Cellular viability and proliferation of labeled and unlabeled cells were shown to be similar. T2-weighted images were acquired using 7T and 3T MRI systems, and R2 maps of the tubes containing cells, free FE-PRO, and brains were made. There was a strong linear correlation between R2 values and labeled cell numbers, but the regression lines were different for the lymphocytes and gliosarcoma cells. Similarly, there was strong correlation between R2 values and free iron. However, free iron had higher R2 values than the labeled cells for the same concentration of iron. CONCLUSION: Our data indicate that in vivo quantification of labeled cells can be done by careful consideration of different factors and specific control groups.     

In vivo cellular imaging of magnetically labeled hybridomas in the spleen with a 1.5-T clinical MRI system.

The feasibility of in vivo cellular imaging using a 1.5 T clinical magnet was studied in the mouse. Hybridoma cells were labeled with anionic gamma-Fe2O3 superparamagnetic iron oxide nanoparticles. These were internalized by the endocytose pathway. Both electron spin resonance and magnetophoresis as a measure of the labeled cells migration velocity under a magnetic field were used to quantify particle uptake. A fast (< 2 hr) and substantial (up to 5 pg of iron per cell) internalization of nanoparticles by hybridomas was found, with good agreement between the two methods used. Hybridomas labeled with 2.5 pg iron per cell were injected intraperitoneally to male Swiss nude mice. A decrease in the spleen signal, suggesting a "homing" of labeled hybridomas to this organ, was found 24 hr later by MRI performed at 1.5 T. Furthermore, in labeled cells recovered from the spleen by ex vivo magnetic sorting, a mean of 0.5 pg iron per cell was found, i.e., a value five times lower than that of the injected hybridomas. This finding is consistent with in vivo proliferation of these cells. In addition, the amount of labeled hybridomas present in the spleen was found to correlate with MRI signal intensity.     

Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation.

Anatomical and functional information (renography, perfusion) was obtained by MRI in a life-supporting transplantation model, in which Lewis rats received kidneys from Fisher 344 donors. Renography and perfusion analyses were carried out with Gd-DOTA and small particles of iron oxide (SPIO), respectively. Starting 12 weeks posttransplantation, images from grafts of untreated recipients exhibited distinctive signal attenuation in the cortex. Animals treated with cyclosporin (Sandimmune Neoral; Novartis Pharma, Basel, Switzerland) to prevent acute rejection showed a signal attenuation in the cortex at 33 weeks posttransplantation, while kidneys from rats treated additionally with everolimus (Certican; Novartis), a rapamycin derivative, had no changes in anatomical appearance. A significant negative correlation was found between the MRI cortical signal intensity and the histologically determined iron content in macrophages located in the cortex. Renography revealed a significantly reduced functionality of the kidneys of untreated controls 33 weeks after transplantation, while no significant changes in perfusion were observed in any group of rats. These results suggest the feasibility, by labeling macrophages with SPIO, of detecting signs of graft rejection significantly earlier than when changes in function occur. Monitoring early changes associated with chronic rejection can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies for transplantation.     

In vivo cellular imaging of lymphocyte trafficking by MRI: a tumor model approach to cell-based anticancer therapy.

The aim of this study was to demonstrate the feasibility of in vivo cell tracking to monitor anticancer cell therapy by means of a high-resolution noninvasive MRI method. Ovalbumin-specific splenocytes (OT-1) labeled with anionic gamma-Fe2O3 superparamagnetic iron oxide (SPIO) nanoparticles were adoptively transferred into C57BL/6 mice with growing ovalbumin-expressing tumors. OT-1 cells were tracked in vivo by 7 T MRI 24, 48, and 72 hr after they were injected. The results showed significant negative enhancement of the spleen at 24 hr, and of the tumor at 48 and 72 hr, after labeled cell injection. This suggests that the lymphocytes initially homed toward the spleen and were then recruited by the tumor. The presence of labeled cells was confirmed in ex vivo by 9.4 T microimaging of tumors and magnetic sorting of spleen cells. These results confirm that MR tracking of lymphocytes is feasible in vivo. This high-resolution imaging method could be used to improve the monitoring of immune cell therapy.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

口服超顺磁性氧化铁在MRCP中的应用

目的：研究超顺磁性氧化铁(SPIO)作为胃肠道阴性对比剂在改善磁共根胰胆管成像(MRCP)质量的应用。方法：30例受检者口服2mmol/Fe／1的SPIO液100m1后进行TSE MRCP检查，采用西门子1．5T MRI扫描机，服药前后常规行单层和多层扫描，原始图像经工作站处理后，采用最大信号强度投影技术重建获得新图像。结果：口服SPIO溶液可以完全抑制胃及十二指肠内液体信号，排除其干扰，使MRCP时胰胆管显影更加清晰。结论：口服SPIO，行MRCP检查，能抑制胃肠道内液体信号，使胰胆管显影更加清晰，特别是在TSEMRCP成像时效果更佳。     

Iron-oxide labeling of hematogenous macrophages in a model of experimental autoimmune encephalomyelitis and the contribution to signal loss in fast imaging employing steady state acquisition (FIESTA) images

PURPOSE: To determine the contribution of blood-derived macrophages to the signal loss observed in MR images of inflammatory lesions in experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: A relapsing-remitting form of EAE was induced in transgenic mice that express enhanced green fluorescent protein (EGFP) specifically in hematopoietic cells of the myelomonocytic lineage. Animals were injected with Feridex, a superparamagnetic iron oxide (SPIO) nanoparticle, 24 hours prior to in vivo MRI. MRI was performed using a 1.5T whole-body scanner; a high-performance, custom-built gradient coil insert; and a 3D steady-state free precession (SSFP) imaging pulse sequence. Comparisons were made between MR images and corresponding anti-GFP and Perl's Prussian blue (PPB)-stained brain sections. RESULTS: MR images revealed the presence of discrete regions of signal loss throughout the brains of EAE animals that were administered Feridex. Histological staining showed that regions of signal loss on MR images corresponded anatomically with regions of PPB- and GFP-positive cells. CONCLUSION: This experiment provides the first direct evidence that macrophages of hematogenous origin are labeled with SPIO after intravenous administration of Feridex, and contribute to the regions of signal loss detected in MR images of EAE brain.     

In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides.

In vivo MRI of stem cells (SCs) is an emerging application to evaluate the role of cell therapy in restoring the injured myocardium. The high spatial and temporal resolution combined with iron-oxide-based intracellular labeling techniques will provide a sensitive, noninvasive, dual imaging modality for both cells and myocardium. In order to facilitate this novel imaging approach, much effort has been directed towards developing efficient transfection methods. While techniques utilizing poly-L-lysine (PLL), protamine sulfate (PS), and electroporation (ELP) have been proposed, the fundamental biological effects of these methods on mouse embryonic SCs (mESC) have not been investigated systematically. In this study a longitudinal in vitro evaluation of cellular viability, apoptosis, proliferation, and cardiac differentiation of magnetically labeled mESC was conducted. No significant difference was seen in these biological parameters among the three transfection methods. However, cardiac differentiation was most attenuated by ELP, and iron uptake was most effective by PS.     

Longitudinal in vivo susceptibility contrast MRI measurements of LS174T colorectal liver metastasis in nude mice

Purpose

To characterize longitudinal tumor progression in a murine orthotopic model of liver metastasis using susceptibility contrast magnetic resonance imaging (MRI).

Materials and Methods

Nude mice were inoculated intrasplenically with LS174T colorectal carcinoma cells 24 hours postadministration of 2.5 mgFe/kg of the ultrasmall superparamagnetic iron oxide particle preparation feruglose. Contiguous T₂ and T₂*‐weighted multislice MR images were acquired 10, 15, 20, 25, 30, and 35 days postinoculation to longitudinally evaluate metastatic progression. Functional tumor vasculature and hypoxia were histologically evaluated at the final timepoint using Hoechst 33342 uptake, pimonidazole and hematoxylin and eosin staining. A parallel cohort of subcutaneous tumors was included for comparison.

Results

All intrasplenically inoculated mice developed liver metastases, evident in both T₂*‐ and T₂‐weighted images as high‐signal deposits, compared to feruglose‐nulled normal liver. Small lesions were detected as early as day 10 and all mice exhibited progressing lesions over 35 days. Liver metastases took longer to establish, but exhibited a similar volume doubling time to the subcutaneously propagated tumors of ≈2–3 days. Different functional tumor vascular architectures between the two growth sites were apparent.

Conclusion

Susceptibility‐contrast MRI using a single dose of feruglose can be used to easily detect and longitudinally monitor orthotopically propagated liver metastases in vivo. J. Magn. Reson. Imaging 2008;9999:1451–1458. © 2008 Wiley‐Liss, Inc.     

Superparamagnetic iron oxide‐enhanced liver MRI with SHU 555 A (RESOVIST®): New protocol infusion to improve arterial phase evaluation—A prospective study

Purpose

To compare the arterial enhancement of hypervascular hepatic lesions by T1‐weighted 3D‐GRE (gradient‐recalled echo) fat‐sat sequence after slow (0.5 mL/sec) and fast (2 mL/sec) RESOVIST® infusion.

Materials and Methods

We prospectively enrolled 71 patients with hypervascular hepatic lesions to undergo dynamic magnetic resonance imaging (MRI) examination with RESOVIST®. A total of 92 benign and malignant lesions, 44 of which histologically confirmed, were examined. Three blinded and independent readers visually assessed the arterial enhancement using a score from 0 (none) to 3 (maximum), the latter score comparable to that achievable by MultiHance administration.

Results

Out of the 92 hypervascular lesions, 41, 31, and 20 nodules were examined using the slow, fast, and both protocols, respectively. Relevant enhancement (scores 2–3) was found in 42% vs. 14.5% of cases for slow and fast protocols, respectively. Intraindividual comparison evaluation confirmed the better results obtained by slow than fast protocol (25% vs. 10%), with statistically relevant difference in distribution of scores (P = 0.0004). The slow protocol showed values between 0 and 3 with an arithmetic mean of 1.1; the fast one, on the other hand, showed values between 0 and 2 with an arithmetic mean of 0.66.

Conclusion

Slow infusion improves arterial enhancement after RESOVIST® administration. J. Magn. Reson. Imaging 2009;29:607–616. © 2009 Wiley‐Liss, Inc.     

Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles

Experimental data show accumulation of superparamagnetic iron oxide (SPIO) particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting an increased endothelial permeability and macrophage infiltrates as signs of inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and arterial wall segments in patients who had originally received the magnetic resonance (MR) contrast agent for staging lymph node metastases. Twenty patients (19 male, 1 female; mean age, 64; range, 41-78 years) with bladder or prostate cancer underwent MR imaging (MRI) using a T2*-weighted high-resolution gradient-echo sequence prior to and 24-36 hours after intravenous injection of 2.6 mg of Fe/kg of SPIO (Sinerem). The aorta, both common external and internal iliac, as well as both superficial femoral arteries, were retrospectively analyzed for atherosclerotic wall changes. One patient was excluded. A positive finding was defined as an area of pronounced signal loss on postcontrast images clearly confined to the arterial wall, which was absent in the precontrast examination or increased in size. Such a finding was observed in one to three arteries in 7 of the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic arteries seen in part of an elderly patient population after intravenous SPIO administration strongly suggests that this contrast agent accumulates in human atherosclerotic plaques.     

USPIO-enhanced magnetic resonance imaging of the knee in asymptomatic volunteers

The aim of this study was to compare signal characteristics of the synovium in knees of asymptomatic volunteers before and after intravenous administration of ultrasmall superparamagnetic iron oxide particles (USPIO). Ten knees of 10 asymptomatic volunteers were examined before and 36 h after intravenous administration of USPIO on a 1.5-T MR system using T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo (GRE), and short inversion time inversion-recovery sequences. In addition, synovial perfusion was measured using Gd-enhanced GRE imaging during the first imaging session. Images were analyzed qualitatively for any visual changes before and after USPIO administration. Signal-to-noise ratios (SNR) of the synovium were determined on unenhanced and USPIO-enhanced sequences. All MR images were reviewed for presence of any degenerative changes. Qualitative image analysis revealed no visually detectable changes of any knee joint before and after USPIO administration. The SNR values of the synovium on T1w, T2w, and T2*w images before and after USPIO administration showed no significant difference (T1, P = 0.86; T2, P = 0.95; T2*, P = 0.86). None of the volunteers showed any relevant degenerative changes of the knee and synovial perfusion was within normal limits. In knees of asymptomatic volunteers without any relevant degenerative changes and normal synovial perfusion neither visual changes nor changes of SNR values of the synovium can be depicted after USPIO administration. This means that USPIO-enhanced MRI may be used for assessment of knee disorders with increased macrophage activity.