An Exploratory Study of Ferumoxtran-10 Nanoparticles as a Blood-Brain Barrier Imaging Agent Targeting Phagocytic Cells in CNS Inflammatory Lesions
Sándor P. Manningerc,
Leslie L. Muldoona,
Gary Nesbita,b,c,
Tulio Murillob,
Paula M. Jacobsd and
Edward A. Neuwelta,b
a Department of Neurology, Oregon Health & Science University, Portland, OR
b Department of Neurosurgery, Oregon Health & Science University, Portland, OR
c Department of Radiology, Oregon Health & Science University, Portland, OR
d Advanced Magnetics, Cambridge, MA
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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).
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