Comparison of Two Superparamagnetic Viral-Sized Iron Oxide Particles Ferumoxides and Ferumoxtran-10 with a Gadolinium Chelate in Imaging Intracranial Tumors
Peter Varallyaya,b,
Gary Nesbitb,
Leslie L. Muldoona,d,
Randal R. Nixone,
Johnny Delashawc,
James I. Cohenf,
Annie Petrilloa,
Doris Rinka and
Edward A. Neuwelta,c
a Department of Neurology, Oregon Health and Science University, Portland, Oregon
b Department of Radiology, Oregon Health and Science University, Portland, Oregon
c Department of Neurosurgery, Oregon Health and Science University, Portland, Oregon
d Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon
e Department of Pathology, Oregon Health and Science University, Portland, Oregon
f Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon

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FIG 1. Patient 2 with anaplastic oligodendroglioma.
A, Gadolinium-enhanced SE T1-weighted image shows an intensely enhancing tumor nodule in the posterior right temporal lobe.
B and C, Four hours after ferumoxides infusion, SE T1-weighted image (B) shows only a tiny area of increased signal intensity (arrow), whereas the GRE T2*-weighted image (C) demonstrates no decreased signal intensity (arrow). The rounded hypointense lateral region in C is from a craniotomy plate.
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FIG 2. Patient 5 with anaplastic oligodendroglioma.
A and B, SE T1-weighted images obtained 6 hours (A) and 24 hours (B) after ferumoxtran infusion show progressive peripheral and patchy central enhancement in the left temporal tumor.
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FIG 3. Patient 9 with anaplastic oligodendroglioma.
A and B, Nonenhanced (A) and gadolinium-enhanced (B) SE T1-weighted images of the right temporal tumor. The gadolinium-enhanced image shows evidence of strong, lobulated peripheral enhancement with a central nonenhancing zone.
C, At 24 hours after ferumoxtran infusion, SE T1-weighted image demonstrates marked high signal intensity in a similar distribution but with less peripheral lobulation compared with the gadolinium-enhanced image. Also note that the nongadolinium-enhancing central zone became isointense to white matter, suggesting some ferumoxtran accumulation.
DF, Fast SE T2-weighted image obtained before ferumoxtran infusion (D) and fast SE T2-weighted (E) and GRE T2*-weighted (F) images obtained 24 hours after ferumoxtran infusion show a heterogeneous tumor mass with peripheral decreased signal intensity that is more prominent on the GRE T2*-weighted image. The distribution of the low-signal-intensity areas is similar to that of the high-signal-intensity areas on the SE T1-weighted image in C.
G and H, Photomicrographs from histologic staining for iron (DAB-enhanced Perls stain). In G (original magnification x7.5; bar indicates 1 mm), tumor (T) and reactive brain interface (RB) show the intense staining for iron at the periphery of the tumor. In H (original magnification x100; bar indicates 0.1 mm), cellular iron staining at the tumorreactive brain interface shows iron uptake by the parenchymal cells with fibrillar processes (arrows) rather than by the round tumor cells (T).
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FIG 4. Patient 12 with meningioma, after radiation therapy.
A and B, Nonenhanced (A) and gadolinium-enhanced (B) SE T1-weighted images. The image in B shows evidence of strong enhancement, except in the central region.
C, At 24 hours after ferumoxtran infusion, SE T1-weighted image shows strong ferumoxtran enhancement in the less gadolinium-enhancing central region and only minimal ferumoxtran enhancement in the surrounding intensely gadolinium-enhancing portion.
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FIG 5. Patient 6 with oligodendroglioma.
A, Gadolinium-enhanced SE T1-weighted image shows a large left frontotemporal mass (arrow) with only small areas of enhancement in its anterior aspect.
B and C, At 24 hours after ferumoxtran infusion, SE T1-weighted (B) and GRE T2*-weighted (C) images demonstrate no signal intensity changes (arrow), indicating no accumulation of iron.
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FIG 6. Quantitation of SE T1-weighted MR images. Normalized mean SE T1 signal intensity values with standard mean error in areas of absent, minimal, and maximal ferumoxtran enhancement in the tumor as well as in brain around tumor (BAT) (n = 15 patients). a indicates P < .05 for gadolinium (Gd) enhancement compared with precontrast images; b, P < .05 for gadolinium enhancement compared with ferumoxtran (Combidex) enhancement; c, P < .001 compared with precontrast image; d, P < .005 compared with precontrast images.
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FIG 7. Quantitation of fast SE T2-weighted and GRE T2*-weighted MR images. Normalized mean T2 signal intensity values with standard mean error in areas of absent, minimal, and maximal ferumoxtran enhancement in the tumor as well as in brain around tumor (BAT) (n = 15 patients). a indicates P < .01 compared with the precontrast fast SE (FSE) T2-weighted images; b, P < .005 comparing ferumoxtran (Combidex)-enhanced GRE T2*-weighted images with ferumoxtran-enhanced fast SE T2-weighted images; c, P < .001 compared with precontrast fast SE T2-weighted images; d, P < .05 comparing ferumoxtran-enhanced GRE T2*-weighted images with ferumoxtran-enhanced fast SE T2-weighted images.
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