The DOI matches its Crossref record.
Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years
Abstract
Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Due to their high liver uptake, iron oxide nanoparticles have been employed relatively extensively for visualizing primary lesions in the liver, e.g. in case of hepatocellular carcinoma (HCC) (Figure 3 A, B) as well as liver metastases (Figure 3 C, D) [144, 145].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [145]
Citations
Cited by
Sorted by citations
Items 201–279 of 279
Okada, M., Katsube, T., Kumano, S., et al. (2011) · Acta Radiologica · doi:10.1258/ar.2011.100360 · Cited by 8
Dutta, B., Barick, K. C., Hassan, P. A., & Tyagi, A. K. (2024) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2024.103320 · Cited by 8
Nickel Ferrite Nanoparticles for In Vivo Multimodal Magnetic Resonance and Magnetic Particle Imaging
Herynek, V., Rajsiglová, L., Babič, M., et al. (2025) · ACS Applied Nano Materials · doi:10.1021/acsanm.5c03013 · Cited by 7
Yamada, S., Yukawa, H., Yamada, K. H., et al. (2022) · Sensors · doi:10.3390/s22155705 · Cited by 7
Taruno, K., Kuwahata, A., Sekino, M., Nakagawa, T., Kurita, T., Enokido, K., Nakamura, S., Takei, H., & Kusakabe, M. (2022) · Cancers · doi:10.3390/cancers14061409 · Cited by 7
“Iron content in human samples has only been previously analyzed by histological and imaging approaches [17,24,25].”
BackgroundDoerfler, A., Forsting, M., Reith, W., Heiland, S., Weber, J., Hacke, W., & Sartor, K. J. (1997) · PubMed Central · Cited by 7
Microfluidic Synthesis of Iron Oxide and Oxyhydroxide Nanoparticles
Abou‐Hassan, A., Sandre, O., & Cabuil, V. (2010) · doi:10.1002/9780470622551.ch9 · Cited by 7
Singh, A. K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801406-6.00005-4 · Cited by 9
Dynamic T1-weighted ferumoxides enhanced MRI for imaging liver hemangiomas: preliminary observations
Sahani, D., Saini, S., Sharma, R., et al. (2001) · Abdominal Imaging · doi:10.1007/s002610000123 · Cited by 6
Shahrouki, P., Felker, E. R., Raman, S. S., et al. (2021) · Abdominal Radiology · doi:10.1007/s00261-021-03271-w · Cited by 5
“The unique imaging features of the liver seen with ferumoxytol were established for other superparamagnetic iron oxides (SPIOs) more than two decades ago [6, 7].”
BackgroundMagnetic Resonance Imaging (MRI) Contrast Agents
Tweedle, M. F., & Kumar, K. (1999) · Springer eBooks · doi:10.1007/978-3-642-60061-6_1 · Cited by 5
New RES-Specific Contrast Agents for CT
Rummeny, E. J., Berning, W., Fuest, M., et al. (2002) · Academic Radiology · doi:10.1016/s1076-6332(03)80433-6 · Cited by 5
SPIO-enhanced MR imaging of focal fatty liver lesions
Lwakatare, F., Yamashita, Y., Nakayama, M., et al. (2001) · Abdominal Imaging · doi:10.1007/s002610000128 · Cited by 5
Takahama, K., Amano, Y., Hayashi, H., et al. (2002) · Journal of Nippon Medical School · doi:10.1272/jnms.69.571 · Cited by 5
Hori, M., Murakami, T., Kim, T., Iannaccone, R., Abe, H., Onishi, H., Tomoda, K., Catalano, C., Passariello, R., & Nakamura, H. (2006) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20542 · Cited by 5
“Ferumoxides, the first SPIO contrast agent introduced in clinical practice, cannot be administered by bolus injection (8).”
BackgroundHue, J. J., Lee, H.-J., Nam, S.-Y., et al. (2015) · Korean Journal of Veterinary Research · doi:10.14405/kjvr.2015.55.1.57 · Cited by 4
Liver MRI Technique: Pulse Sequences and Contrast Agents
Trieu, J., & Wu, L. (2010) · Journal of medical imaging and radiation sciences · doi:10.1016/j.jmir.2010.01.003 · Cited by 4
“Reticuloendothelial system agents are selectively taken up by Kupffer cells in the liver, as well as the spleen and bone marrow [34].”
BackgroundZare, T., Lotfi, M., Heli, H., et al. (2015) · Applied Physics A · doi:10.1007/s00339-015-9302-1 · Cited by 3
Benign and Malignant Lesions of the Spleen
Vos, P. M., Barnard, S. A., & Cooperberg, P. L. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-2332-6.50112-3 · Cited by 3
Molecular Imaging for Early-Stage Disease Diagnosis
Zhang, K., Xu, H., & Li, K. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9902-3_3 · Cited by 3
Direct observation of NMR transverse relaxation in nanopatterned clusters of iron oxide particles
Bok, I., Rauch, B. J., Ashtiani, A. O., et al. (2023) · Magnetic Resonance in Medicine · doi:10.1002/mrm.29898 · Cited by 3
“5 These provide powerful diagnostic tools for detecting structural and tissue manifestations of pathologies such as cirrhosis, 10 liver cancer, 10,11 spleen cancer, 15 and brain disorders.”
BackgroundFu, X. J., Yu, L., Li, Y., et al. (2018) · Nanotechnology · doi:10.1088/1361-6528/aacbb5 · Cited by 3
Goodwill, P. W., Krishnan, K. M., & Conolly, S. (2012) · CRC Press eBooks · doi:10.1201/b11760-26 · Cited by 3
Carbohydrate-Modified Magnetic Nanoparticles for Radical Scavenging
Moskvin, M., & Horák, D. (2016) · Physiological Research · doi:10.33549/physiolres.933426 · Cited by 3
“MR diagnostics of liver and spleen is their main application field as the particles with size ˂50 nm are readily and almost completely internalized by the macrophages of these organs (Ferrucci and Stark 1990).”
BackgroundMagnetic Materials for Nuclear Magnetic Resonance and Magnetic Resonance Imaging
Motovilova, E. A., & Huang, S. (2017) · CRC Press eBooks · doi:10.4324/9781315371573-3 · Cited by 3
Magnetic Resonance Imaging of the Liver Technique
CHEZMAR, J. L. (1991) · Radiologic Clinics of North America · doi:10.1016/s0033-8389(22)02476-9 · Cited by 3
Splénose : intérêt de l’IRM avec injection de produit de contraste superparamagnétique
Roussel, A., Petit, É., Mallet, L., et al. (2008) · Journal de Radiologie · doi:10.1016/s0221-0363(08)74792-9 · Cited by 2
Dey, K. K. (2014) · Pan Stanford Publishing eBooks · doi:10.1201/b15633-2 · Cited by 2
Zhang, Y., Xiao, X.-P., Shu, T., et al. (2018) · Nanotechnology · doi:10.1088/1361-6528/aab5fe · Cited by 2
Li, X., Lv, W., Yang, W., et al. (2022) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2022.103993 · Cited by 2
Charvátová, H., Plichta, Z., Hromádková, J., et al. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071982 · Cited by 2
“Reports on ferucarbotran in clinical practice state that the half-life is much shorter (7–14 days) [85,86].”
BackgroundWalter, T., Knobloch, G., Kasner, M., Diederichs, G., Hamm, B., Ebersberger, U., & Makowski, M. R. (2014) · Current Radiology Reports · doi:10.1007/s40134-013-0040-x · Cited by 2
“As iron oxide particles mainly shorten T2 and T2* relaxation times, they are usually visualized with strongly weighted T2 or T2* sequences [18].”
BackgroundHemolymphangiomatosis of the Spleen
Santoro, L., Santini, V., Lollo, S. D., et al. (2005) · Journal of Computer Assisted Tomography · doi:10.1097/01.rct.0000178713.40170.73 · Cited by 2
Characterizing Liver Hemangiomas on Ferumoxides-Enhanced Dynamic Tl-Weighted Imaging
Sahani, D. V., Saini, S., Sharma, R., et al. (2002) · Academic Radiology · doi:10.1016/s1076-6332(03)80450-6 · Cited by 2
Alghamdi, S. A. (2017) · The University of Queensland · doi:10.14264/uql.2017.729 · Cited by 2
Magnetic Resonance Imaging Methods for Assessing Cirrhosis and Portal Hypertension
Palaniyappan, N., Guha, I. N., & Aithal, G. P. (2018) · Springer eBooks · doi:10.1007/978-3-319-72628-1_14 · Cited by 1
Nano Particles: Types and Their Biomedical Applications
Ahmed, A., Khoshnaw, A., Mohammed, S. S., & Hassan, A. M. (2025) · Journal of Physical Chemistry and Functional Materials · doi:10.54565/jphcfum.1623212 · Cited by 1
Iron Oxide Nanoparticles Imaging Tracking by MR Advanced Techniques: Dual-Contrast Approaches
Wu, S. Y. (2012) · InTech eBooks · doi:10.5772/33648 · Cited by 1
Molecular MRI of Atherosclerosis with USPIO
Sigovan, M., & Canet‐Soulas, E. (2012) · Current Cardiovascular Imaging Reports · doi:10.1007/s12410-012-9174-0 · Cited by 2
“Several different types of agents have been optimized for a wide range of applications, including imaging of the liver, spleen [16], bone marrow, lymph node, vascular inflammation and angiography.”
BackgroundIttrich, H., Peldschus, K., Raabe, N., Kaul, M. G., & Adam, G. (2013) · Cited by 1
Suyasova, M. V., Borisenkova, A. A., Shilin, V. A., et al. (2019) · Nanosystems Physics Chemistry Mathematics · doi:10.17586/2220-8054-2019-10-4-447-455 · Cited by 1
“Practical interest in biocompatible iron-containing fullerene-polymer complexes is caused by the possibility of their use for improving resolution in magnetic resonance imaging [5], as well as for molecular-targeted drug delivery in the human body, including for the cancer treatment [6].”
BackgroundPolymer-endofullerene Fe@C60 complexes for biomedical applications
Yevlampieva, N. P., Lebedev, V. T., Szhogina, A. A., et al. (2018) · Vestnik of Saint Petersburg University Physics and Chemistry · doi:10.21638/11701/spbu04.2018.202 · Cited by 1
Benign and Malignant Lesions of the Spleen
Vos, P. M., Barnard, S. A., & Cooperberg, P. L. (2015) · Elsevier eBooks · doi:10.1016/b978-1-4557-5117-4.00105-7 · Cited by 1
Fu, J., Lin, G., Fang, C., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.131730 · Cited by 1
RetractedFocal Liver Lesions: Magnetic Resonance Imaging-Pathological Correlation
Ros, P. R. (1995) · Springer eBooks · doi:10.1007/978-94-011-0477-7_8 · Cited by 1
Sentinel Lymph Node Biopsy: Actual Topics
Porto, L. G., Vasques, P. H. D., Maia, M., et al. (2011) · InTech eBooks · doi:10.5772/22507 · Cited by 1
Pech, M., Ricke, J., Seidensticker, M., et al. (2008) · International Journal of Radiation Biology · doi:10.1080/09553000802389660 · Cited by 1
Amirshaghaghi, A., Cheng, Z., Josephson, L., & Tsourkas, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816386-3.00033-8 · Cited by 2
Utility of magnetization prepared GRE MRI for the detection of focal liver lesions
Winter, T. C., Freeny, P. C., Nghiem, H. V., et al. (1994) · Magnetic Resonance Imaging · doi:10.1016/0730-725x(94)92198-9 · Cited by 1
Development of hydroxyapatite-based nanoparticles for medical imaging diagnosis
Moço, A. A. (2013) · Open Repository of the University of Porto (University of Porto) · doi:10.34626/dktd-0e60 · Cited by 1
Cardiovascular Magnetic Resonance Imaging of Atherothrombosis
Kim, W. Y., Kock, S. A., Manning, W. J., & Botnar, R. M. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-306-6_28 · Cited by 1
Specific MR Contrast Media for Liver Imaging
Terrier, F., Vallée, J., Pochon, S., et al. (1999) · Medical radiology · doi:10.1007/978-3-642-58641-5_29 · Cited by 1
Metal Complexes for Diagnosing Disease
Dabrowiak, J. C. (2009) · doi:10.1002/9780470684986.ch8
Magnetic nanoparticle tagging and application of magnetophoresis to cellular therapy and imaging.
Jing, Y. (2006) · OhioLink ETD Center (Ohio Library and Information Network)
MR Imaging of Hepatocellular Carcinoma
Lee, D. H., & Lee, J. M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8498-1_7
Optimum conditions for iron colloid enhanced fast spin echo imaging in hepatocellular carcinoma.
Sugihara, S., Suto, Y., & Yoshida, K. (1997) · British Journal of Radiology · doi:10.1259/bjr.70.836.9486042
Leander, P., & Golman, K. (1996) · Academic Radiology · doi:10.1016/s1076-6332(96)80604-0
Sugihara, S., Suto, Y., Kamba, M., & Yoshida, K. (1996) · Yonago acta medica
Detection of Malignant Liver Lesions Using Different Imaging Modalities
Hamm, B. (1993) · Springer eBooks · doi:10.1007/978-3-642-77834-6_8
A Small Scale Magnetic Particle Relaxometer
Ghamrawy, A. E. (2013) · OakTrust (Texas A&M University Libraries)
Bildgebende Verfahren außer Endosonographie
Pistolesi, G. F., Barbi, E., Caruso, M., et al. (1994) · Springer eBooks · doi:10.1007/978-3-642-78606-8_7
Nanoparticle Tagging of Live Cells to Monitor Cell Migration
Miller, C. A. (2014) · Microscopy Today · doi:10.1017/s1551929514000753
Sudo, Y., Nagayama, J., Sasada, H., et al. (2006) · Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) · doi:10.3919/jjsa.67.1111
Gassel, H. ‐., Gasser, M., Buhler, C., et al. (1997) · Springer eBooks · doi:10.1007/978-3-642-60881-0_83
Cardiovascular magnetic resonance imaging (MRI)
Botnar, R. M., & Makowski, M. R. (2014) · Elsevier eBooks · doi:10.1533/9780857097477.2.214
Radiological Imaging in Hepatobiliary and Pancreatic Malignancies
Kulkarni, S. S., Gala, K. B., Shetty, N., et al. (2017) · Springer eBooks · doi:10.1007/978-3-319-60507-4_4
Translational Clinical Applications of Micro-/Nanoimaging Probes: Challenges and Perspectives
Wu, S., Zhu, H. F., Huang, J., et al. (2018) · Engineering materials · doi:10.1007/978-981-10-4804-3_4
Abstracts-part VIII (Continue in Part IX)
(1995) · Proceedings of the Society of Magnetic Resonance in Medicine · doi:10.1002/mrmp.22419950110
Magnetic Materials for Nuclear Magnetic Resonance and Magnetic Resonance Imaging
Motovilova, E. A., & Huang, S. (2017) · Advances in materials science and engineering · doi:10.1201/9781315371573-4
A Review of Enabling Technologies for Magnetic Particle Imaging
Khandani, M. K., & Vosoughi, A. (2022) · IEEE International Midwest Symposium on Circuits and Systems (MWSCAS) · doi:10.1109/mwscas54063.2022.9859431
“Another benefit of MPI is that SPION contrast agents are refined in the liver instead of kidneys [53].”
BackgroundInorganic nanosystems for imaging diagnostics
Mushtaq, U., Hussain, N., Ayoub, I., Rubab, S., Sehgal, R., & Kumar, V. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-85784-0.00002-9
Multiparametrische MRT-Bildgebung beim hepatozellulären Karzinom, Teil 1
Jahn, M., & Layer, G. (2024) · Die Radiologie · doi:10.1007/s00117-024-01285-1
Shaikh, S. (2024) · Springer eBooks · doi:10.1007/978-981-97-7292-6_16
Molekulare Bildgebung zur Diagnose von Krankheiten im Frühstadium
Zhang, K., Xu, H., & Li, K. (2025) · Springer eBooks · doi:10.1007/978-981-97-9693-9_3
Monitoring Antigen-Specific Responses in Clinical Trials of Cancer Immunotherapy
Chapuis, A. G., & Yee, C. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4732-0_14
Additional file 1 of Magnetic core–shell nanowires as MRI contrast agents for cell tracking
Martínez-Banderas, A. I., Aires, A., Plaza‐García, S., Colás, L., Moreno, J. A., Ravasi, T., Merzaban, J. S., Ramos‐Cabrer, P., Cortajarena, A. L., & Kosel, J. (2020) · Figshare · doi:10.6084/m9.figshare.11979390
Wansapura (1999) · doi:10.1002/(sici)1522-2586(199904)9:4
Metadata
- Authors
- Ferrucci, J. T., & Stark, D. D.
- Affiliations
- Massachusetts General Hospital (US)
- ORCID
- Stark, D D
- Venue
- American Journal of Roentgenology
- Publisher
- American Roentgen Ray Society
- Published
- 1990-11
- Volume
- 155
- Issue
- 5
- Pages
- 943-950
- ISSN
- 0002-9580 (ISSN-L)
- 0361-803X
- 1546-3141
- OpenAlex
- W2068366961
- Cited by
- 279
- References
- 0
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 18 · 2014: 9 · 2013: 10 · 2012: 18
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Roentgenology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › MRI in cancer diagnosis
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- superparamagnetic iron oxide nanoparticles, MRI contrast agents, liver tumors, splenic neoplasms, Kupffer cells, T2 relaxation, tumor detection, reticuloendothelial system, dose escalation, contrast-to-noise ratio, gradient-echo imaging, iron metabolism
- MeSH terms
- Animals, Humans, Image Enhancement, Iron, Liver Diseases, Magnetic Resonance Imaging, Oxides, Splenic Neoplasms, Ferrosoferric Oxide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
