Bone marrow: ultrasmall superparamagnetic iron oxide for MR imaging.

Senéterre, E; Weissleder, Ralph; Jaramillo, Diego; Reimer, Peter; Lee, A S; Brady, T J; Wittenberg, J

doi:10.1148/radiology.179.2.2014305

Cited by 99 publications

(60 citation statements)

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“…Khurana et al as the liver (31,32), the spleen (31), lymph nodes (32,33), and bone marrow (34)(35)(36). 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).…”

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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“…The immature bone marrow of the New Zealand white rabbit is a model well suited for the current study since hematopoietic marrow is found within the central skeleton and its MR appearance has been well described before. 32,33 In addition, good anatomical resolution can be achieved for rabbits using a clinical MR scanner, which would not have been possible for smaller rodents. Our findings still have to be confirmed in humans.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Assessing permeability alterations of the blood–bone marrow barrier due to total body irradiation: in vivo quantification with contrast enhanced magnetic resonance imaging

Daldrup-Link

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Rummeny

et al. 2000

Bone Marrow Transplant

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Summary:Our aim was to quantify irradiation-induced permeability alterations of the blood-bone marrow barrier (BMB) with dynamic contrast enhanced magnetic resonance imaging (MRI). The standard small molecular contrast agent, gadoterate meglumine, and a new macromolecular contrast agent, carboxymethyldextran-Gd-DOTA (CMD-Gd-DOTA), were compared. Twenty New Zealand white rabbits underwent MRI of the bone marrow before and 1-2 days after total body irradiation (TBI). Dynamic, repetitive T1-weighted MRI was performed before and after injection of either 0.05 mmol/kg BW CMD-Gd-DOTA (n = 10) or 0.5 mmol/kg BW gadoterate (n = 10). Bone marrow contrast enhancement was quantified as delta signal intensity: ⌬SI = ͉(SI post − SI pre ) / SI pre ͉ * 100%. All MRI data were compared with the histopathologic BMB ultrastructure. Dynamic bone marrow ⌬SI data steadily increased after CMD-Gd-DOTA injection, while blood ⌬SI data slightly decreased. This bone marrow contrast enhancement, indicative of contrast agent extravasation, was significantly higher and prolonged in the irradiated group as compared to non-irradiated controls (P Ͻ 0.05) and corresponded to irradiation-induced alterations of the BMB ultrastructure seen on electron microscopy. By contrast, ⌬SI data of non-irradiated and irradiated marrow were not significantly different following gadoterate injection (P Ͼ 0.05). We conclude that irradiation-induced alterations in BMB permeability could be reliably assessed with dynamic MRI, using the new macromolecular contrast agent CMD-Gd-DOTA. Bone Marrow Transplantation (2000) 25, 71-78.

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“…It was di‹cult to detect normal hematopoietic cells, including macrophages, in the histologicalˆndings of the rabbit model of bone tumor, whereas pseudoeosinocytes acting as macrophages were seen in in‰ammatory models. 9 Although tumor cells occupied the bone marrow in bone metastasis, and thus, SPIO was not taken up by neoplastic bone marrow in clinical cases, 7,16 in general, macrophages are generated in bone marrow with in‰ammation. 17 As a result, the signal intensity of bone marrow decreased in the osteomyelitis.…”

Section: Discussionmentioning

confidence: 99%

“…6 Several studies using animal models report that SPIO particles were taken up in the bone marrow and signiˆcantly decreased relaxation time of tissue to improve diagnostic ability for focal lesions occurring within 1 to 24 hours or 2 hours. 7,8 We recently reported the potential of SPIO in diŠerentiating between metastasis and osteomyelitis at 24 hours post administration in a rabbit model; we used ferucarbotran, an SPIO particle used clinically as a liver-speciˆc contrast agent. The values show mean±SD (n＝5).…”

Section: Introductionmentioning

confidence: 99%

Superparamagnetic Iron Oxide (SPIO) MRI Contrast Agent for Bone Marrow Imaging: Differentiating Bone Metastasis and Osteomyelitis

Fukuda

Ando

Ishikura

et al. 2006

MRMS

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Purpose: We explored appropriate scan timing for bone marrow imaging enhanced using superparamagnetic iron oxide (SPIO) and evaluated the usefulness of SPIO in diŠerentiat-ing metastasis and osteomyelitis in patients.Methods: To determine the adequate scan timing after administration of SPIO, 5 healthy subjects were examined using a 1.5T magnetic resonance (MR) imaging scanner. Sagittal images of their lumbar spines were obtained using short-TI inversion recovery (STIR) sequence before and 3, 6, 9, 24, and 48 hours after intravenous injection of 8 mmol Fe W kg SPIO (ferucarbotran). MR signal intensities (SIs) were evaluated. Based on the results, 12 patients,ˆve with bone metastasis and seven with vertebral osteomyelitis, were examined using the same procedure before and 3 hours after intravenous injection of ferucarbotran at the same dose. SIs of the bone metastases, osteomyelitis, and surrounding normal bone marrow were measured, and relative enhancement (RE) was calculated for each lesion.Results: In the healthy volunteers, maximum reduction in signal was observed 3 to 24 hours ( Pº0.05) after administration of SPIO; thereafter and up to 48 hours, the SI gradually recovered. In the patients, the RE of the bone metastases was -12.2z, which was signiˆcantly higher than that in the osteomyelitis (-35.0z, Pº.001) and normal bone marrow Pº.0005).Conclusion: Maximum suppression of signal intensity in bone marrow was seen 3 hours after injection of ferucarbotran, the point at which ferucarbotran allows diŠerentiation of bone metastasis from ostoemyelitis.

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Bone marrow: ultrasmall superparamagnetic iron oxide for MR imaging.

Cited by 99 publications

References 0 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

Assessing permeability alterations of the blood–bone marrow barrier due to total body irradiation: in vivo quantification with contrast enhanced magnetic resonance imaging

Superparamagnetic Iron Oxide (SPIO) MRI Contrast Agent for Bone Marrow Imaging: Differentiating Bone Metastasis and Osteomyelitis

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