T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning

Simon, Gerhard; Bauer, Jan; Saborovski, Olaf; Fu, Yanjun; Corot, Claire; Wendland, Michael F.; Daldrup-Link, Heike E.

doi:10.1007/s00330-005-0031-2

Cited by 159 publications

(156 citation statements)

References 33 publications

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“…The relatively large nanoparticles, which have a size on the order of plasma proteins, initially distribute in the blood pool, where they cause strong T1 and T2 relaxation time enhancement (37). The nanoparticles subsequently slowly extravasate across the sinusoids of microvessels in RES organs and accumulate in the interstitium, where they are slowly phagocytosed by macrophages.…”

Section: Molecular Imaging: Mr Imaging Monitoring Of Macrophage Migramentioning

confidence: 99%

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Khurana¹,

Nejadnik²,

Gawande³

et al. 2012

Radiology

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Purpose:To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints. Materials andMethods:With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixedeffects model. MR imaging data were correlated with histopathologic findings. Results:All ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P = .0013). This corresponded to differential migration of ironloaded macrophages into MASIs. Conclusion:Iron oxide loading of macrophages in the reticuloendothelial system by means of intravenous ferumoxytol injection can be utilized to monitor differential migration of bone marrow macrophages into viable and apoptotic MASIs in a rat model.

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Section: Molecular Imaging: Mr Imaging Monitoring Of Macrophage Migramentioning

confidence: 99%

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Khurana¹,

Nejadnik²,

Gawande³

et al. 2012

Radiology

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“…In this experimental setup, diffusion of ferumoxtran-10 within the solution is unrestricted. It has been shown that r 1 and r 2 relaxivities of ferumoxtran-10 freely dispersed in solution are stronger compared to when the contrast agent is compartmentalized in cells (26). This needs to be considered especially when applying the results of the current study to imaging of intracellularly compartmentalized USPIOs.…”

Section: Discussionmentioning

confidence: 89%

Optimization of high‐resolution USPIO magnetic resonance imaging at 4.7 T using novel phantom with minimal structural interference

Antell¹,

Numminen

Abo‐Ramadan

et al. 2010

Magnetic Resonance Imaging

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Purpose: To characterize the effect of ultrasmall superparamagnetic iron oxides (USPIOs) on magnetic resonance imaging (MRI) signal at 4.7 T, and to find the highest sensitivity pulse sequence for high-resolution USPIO MRI. Materials and Methods:A novel phantom was constructed for optimization of sequence parameters for neuroradiological MR applications, and a wide range of dilutions of the USPIO ferumoxtran-10 was imaged using T 2 / T 1 -, T 1 -, T 2 -, T* 2 -, and PD-weighted sequences. The effect of varying sequence parameters was investigated using phantom measurements and simulations.Results: The relaxivities r 1 , r 2 , and r* 2 of ferumoxtran-10 at 4.7 T (21 C) were 5.1, 82.2, and 148.4 mmol À1 L s À1, respectively. Gradient echo sequences produced superior susceptibility artifacts at high concentrations; susceptibility artifacts were seen down to a concentration of 137 nmol Fe/mL. A concentration of 17.5 mmol Fe/mL caused a signal void independently of sequence and parameters, and at concentrations 273 nmol Fe/mL no signal void was caused. Signal enhancement on T 1 -weighted imaging was seen only at concentrations 137-547 nmol Fe/mL. For the same effective echo time T 2 -weighted rapid acquisition with relaxation enhancement (RARE) yielded significantly higher contrast-tonoise ratio with RARE factor 16 than with RARE factor 8. Conclusion:At nanomolar concentrations of USPIO, steady-state free precession offers an alternative to T 2 -and T* 2 -weighted sequences. Optimum parameters depend highly on USPIO concentration.

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“…The T2* effect is affected by the magnetic field strength, and according to the report by Simon et al (21), the T2 relaxivity of USPIO has been demonstrated to be stronger at 3.0 T as compared to 1.5 T. Therefore, a different SI change of USPIO-enhanced MRI between 1.5 T and 3.0 T could be expected, which might result in a different diagnostic accuracy of lymph node metastasis detection. Even though there was no significant difference of the SI ratio for malignant lymph nodes, we found significance of the SI ratio for benign lymph nodes.…”

Section: Discussionmentioning

confidence: 97%

Comparison of lymph node metastases assessment With the use of USPIO‐enhanced MR imaging at 1.5 T versus 3.0 T in a rabbit model

Choi¹,

Kim²,

Moon³

et al. 2009

Magnetic Resonance Imaging

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Purpose: To prospectively compare the diagnostic performances of 1.5 T and 3.0 T ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for the detection of lymph node (LN) metastases in a rabbit model. Materials and Methods:Experiments were approved by the animal care committee. VX2 carcinomas were implanted into the thighs of 18 rabbits 3 or 4 weeks before MRI examinations. T2*-weighted 1.5 T and 3.0 T MRI was performed 24 hours after USPIO (2.6 mg/kg iron) administration. Two radiologists calculated signal intensity (SI) ratios (ie, the ratios of postcontrast to precontrast signal intensity) of each LN and also evaluated for the presence of a metastasis in the iliac and retroperitoneal LNs at 1.5 T and 3.0 T MRI. Student's t-test, receiver operating characteristic (ROC) curve analysis, and a Z test were used for the statistical analysis. THE MOST WIDELY EVALUATED intravenous contrast agent for lymphographic magnetic resonance imaging (MRI) is ultrasmall superparamagnetic iron oxide (USPIO) particles, which accumulate slowly in macrophages of the lymph nodes and show a maximum lymphographic effect 24 hours after administration (1-3), whereas nonphagocytic metastatic tissues remain unchanged on USPIO-enhanced MRI. Even though this technique is still not approved by regulatory agencies in North America and Europe, several studies have demonstrated enhanced sensitivity and specificity for malignant lymph node evaluation after the administration of ferumoxtran-10 (Combidex; AMAG Pharmaceuticals, Lexington, MA), a USPIO agent, for pelvic, breast, head and neck, and chest malignancies (4-7). Diagnostic guidelines for the interpretation of USPIO-enhanced MRI have been reported and the results for the evaluation of malignant lymph nodes with sensitivities and specificities of 79%-91%, and 77%-98%, respectively, have been reported. However, the detection of a metastasis 5 mm or less and differentiation of a reactive change of a lymph node is still problematic (8,9). Clinical 3.0 T whole-body MR systems are increasingly available. In addition, a recent study has reported that USPIO-enhanced MRI of pelvic nodes at 3.0 T showed a higher spatial resolution and improved image quality as compared with the image quality at 1.5 T in patients with prostate cancer (10). Therefore, more enhanced accuracy for metastatic

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T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning

Cited by 159 publications

References 33 publications

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants

Optimization of high‐resolution USPIO magnetic resonance imaging at 4.7 T using novel phantom with minimal structural interference

Comparison of lymph node metastases assessment With the use of USPIO‐enhanced MR imaging at 1.5 T versus 3.0 T in a rabbit model

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