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AJNR Awards, New Junior Editors, and more. Read the latest AJNR updates

Research ArticleBRAIN

An Exploratory Study of Ferumoxtran-10 Nanoparticles as a Blood-Brain Barrier Imaging Agent Targeting Phagocytic Cells in CNS Inflammatory Lesions

Sándor P. Manninger, Leslie L. Muldoon, Gary Nesbit, Tulio Murillo, Paula M. Jacobs and Edward A. Neuwelt
American Journal of Neuroradiology October 2005, 26 (9) 2290-2300;
Sándor P. Manninger
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Leslie L. Muldoon
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Gary Nesbit
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Tulio Murillo
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Paula M. Jacobs
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Edward A. Neuwelt
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    Fig 1.

    Patient 6, with MS. Axial T1-weighted images without (A) and with (B) gadolinium show intense enhancing lesions in the left frontoparietal region. One day later, the lesions showed minimal enhancement with ferumoxtran-10 on axial T1-weighted image (C). The lesions show no significant change on T2 (D) and GRE T2*-weighted (E) images. Notice the low-intensity changes in blood vessels caused by the blood pool agent ferumoxtran-10.

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    Fig 2.

    Patient 1, with ADEM. Axial T1-weighted images without (A) and with (B) gadolinium (inset coronal) show faint, subtle enhancement in multiple brain stem lesions. Six days later (C) significant, more prominent, larger ferumoxtran-10 enhancement can be seen on the same site (inset, coronal). Three months later (D) the lesions no longer enhance on T1-weighted images with gadolinium.

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    Fig 3.

    Patient 2, with biopsy-confirmed ADEM. Axial T1-weighted images without (A) and with (B) gadolinium show multiple, confluent, strongly enhancing lesions around both lateral ventricles. Six days later (C), smaller, less-intense areas were visible with ferumoxtran-10 at the same sites. The lesions show no significant change on T2- and GRE T2*-weighted images (D and E).

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    Fig 4.

    Patient 4, with biopsy-confirmed MS. Axial T1-weighted images without (A and B) and with (C and D) gadolinium show multiple, bilateral temporoparietal, enhancing lesions. Six days later (E and F), smaller, less-intense areas were visible with ferumoxtran-10 at the same site on T1 MR.

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    Fig 5.

    Patient 11, with stroke. Three days after ictus, axial T1-weighted images without (A) and with (B) gadolinium show no significant enhancement in left insular cortex, basal ganglia, and frontoparietal lobe. The corresponding DWI, T2, and fluid-attenuated inversion recovery images showed high intensity (not shown) consistent with acute middle cerebral artery infarction. T1 images obtained 10 days later with ferumoxtran-10 (C) show significant enhancement in the same region. Ninety days later (D), axial T1-weighted image after gadolinium shows no enhancement. It is clear that ferumoxtran-10 enhancement was intense, but because the BBB opening in stroke generally occurs 4–7 days after the ictus, gadolinium may have also enhanced the lesion if the gadolinium scan had been done a few days later.

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    Fig 6.

    Patient 13, with cavernous venous vascular malformation. Sagittal T1-weighted images without (A) and coronal T1-weighted images with (B) gadolinium show no significant enhancement in the left pons lesion. Four days later, prominent ferumoxtran-10 enhancement can be seen in the same lesion on T1 MR (C).

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    Fig 7.

    Patient 18, with PCNSL. Axial T1-weighted images without (A) and with (B) gadolinium show intense ring-enhancing lesions in the head of both caudate nuclei. In the T1-weighted image with ferumoxtran-10 produced 15 days later (C), the lesions in the caudate head are larger and show more intense enhancement. Another lesion is visible in the splenium of the corpus callosum that also shows larger and more intense enhancement than seen on the baseline gadolinium image (not shown). Low-intensity changes in both lesions are visible on T2-weighted images after ferumoxtran-10 administration (D and E).

Tables

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  • Demographics and MR imaging results with iron particles in patients having different intracranial lesions

    Patient No./Age (y)/SexDiagnosisLesion LocationDays Between ScansGadolinium EnhancementIron Enhancement Compared to GadoliniumSteroid Treatment
    NoFaintGoodNo−=+++
    Demyelinatinglesions
        1/25/MAcute disseminated encephalomyelitisBrainstem6xxNo
        2/24/FAcute disseminated encephalomyelitis *Multifocal6xxNo
        3/18/FAcute disseminated encephalomyelitisMultiple12xxxxNo
        4/47/FMultiple sclerosis *Multifocal4xxNo
        5/51/MMultiple sclerosisDiffuse24xxNo
        6/45/FMultiple sclerosisLeft frontoparietal1xxxxYes
        7/51/MMultiple sclerosisDiffuse29xx?
        8/44/FMultiple sclerosisMultiple2xx?
        9/39/FMultiple sclerosisDiffuse3xx?
        10/53/FMultiple sclerosisDiffusexx?
    MeningiomaParasellar6xx
    Vascular lesionRight frontalxx
    Vascular lesions
        11/72/FStroke†Left basal ganglia10xxYes
        12/77/MStroke†Right parietal2xxNo
        13/28/FCavernous vascular malformationBrainstem4xxNo
        14/26/MCavernous vascular malformationSplenium corpus callosum5xxNo
        15/39/MCavernous vascular malformationLeft frontal22xxNo
        16/59/MVasculitis*Diffuse dural23xxYes
        17/34/MVasculitis*Multiple5xxNo
    Hematopoietic neoplasms
        18/72/MPCNSL* with ocular involvementMultiple15xxYes
        19/40/MPCNSL* with ocular involvementDiffuse7xxNo
        20/75/MLymphoma*Tentorium, skull base3xxYes
        21/59/MPCNSL*Multiple14xxxYes‡
        22/58/FPCNSL*Multiple8xxxYes
        23/54/FInflammatory myofibroblastic tumor*Multifocal23xx?
    • Note.—PCNSL indicates primary central nervous system lymphoma; −, less enhancement; =, same enhancement; +, increased enhancement, ++, either larger volume of enhancement or additional enhancing lesion; ?, no definitive data.

    • * Biopsy proven.

    • † Previous history of PCNSL.

    • ‡ Steroid stopped between the 2 scans.

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American Journal of Neuroradiology: 26 (9)
American Journal of Neuroradiology
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Cite this article
Sándor P. Manninger, Leslie L. Muldoon, Gary Nesbit, Tulio Murillo, Paula M. Jacobs, Edward A. Neuwelt
An Exploratory Study of Ferumoxtran-10 Nanoparticles as a Blood-Brain Barrier Imaging Agent Targeting Phagocytic Cells in CNS Inflammatory Lesions
American Journal of Neuroradiology Oct 2005, 26 (9) 2290-2300;

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An Exploratory Study of Ferumoxtran-10 Nanoparticles as a Blood-Brain Barrier Imaging Agent Targeting Phagocytic Cells in CNS Inflammatory Lesions
Sándor P. Manninger, Leslie L. Muldoon, Gary Nesbit, Tulio Murillo, Paula M. Jacobs, Edward A. Neuwelt
American Journal of Neuroradiology Oct 2005, 26 (9) 2290-2300;
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