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Characteristics of Ultrasmall Superparamagnetic Iron Oxides in Patients with Brain Tumors

¹ Department of Neuroradiology, University Hospital Basel, Basel 4031, Switzerland.
² Department of Neuropathology, University Hospital Basel, Basel 4031, Switzerland.
³ Guerbet, Zürich, Switzerland.
⁴ Department of Neurosurgery, University Hospital Basel, Basel 4031, Switzerland.

View larger version (78K): [in a new window]   Fig. 1 —Comparison of tumor enhancement with ultrasmall superparamagnetic iron oxides (USPIO) versus gadolinium (Gd) chelate in 67-year-old woman with recurrent gliosarcoma (World Health Organization grade IV). Lesion in right frontoparietal lobe shows homogeneous, circular enhancement of gadolinium. On T1-weighted sequences (top row), enhancement of USPIO is less distinct. Gadolinium-enhancing area of radiation necrosis (arrowhead) along course of catheter for interstitial radiation therapy (black arrows on unenhanced images) does not enhance with USPIO (arrowhead). Posteromedially to lesion, area of neovascularization (white arrow) is depicted. On T2*-weighted images (bottom row), corresponding area enhances strongly with USPIO (white arrow).

View larger version (83K): [in a new window]   Fig. 2 —40-year-old man with glioblastoma multiforme (World Health Organization grade IV). Pattern of enhancement with gadolinium (Gd) and ultrasmall superparamagnetic iron oxides (USPIO) is comparable on T1-weighted sequences (top row). On T2*-weighted (bottom row) USPIO series, tumor margins are hypointense, clearly demarcating enhancing portions of tumor from surrounding edema (arrows).

View larger version (81K): [in a new window]   Fig. 3A —52-year-old man with recurrent anaplastic ependymoma (World Health Organization grade III). On unenhanced T1-weighted images (top row), intratumoral hemorrhage is present in frontal white matter (white arrow). Lesion appears larger with gadolinium (Gd)-enhanced than with ultrasmall superparamagnetic iron oxides (USPIO)-enhanced (white arrowheads) images. On T2*-weighted images (bottom row), enhancement is focused in central parts of lesion. Sulcal veins and anterior cerebral artery are particularly well delineated on T2*-weighted USPIO image (bottom right).

View larger version (149K): [in a new window]   Fig. 3B —52-year-old man with recurrent anaplastic ependymoma (World Health Organization grade III). Diaminobenzidine (DAB)-enhanced Perls stain reveals presence of intracellular iron deposits in macrophages at brain-tumor interface (black arrowheads). Note presence of perivascular hemorrhage (white arrowheads). (x200)

View larger version (156K): [in a new window]   Fig. 3C —52-year-old man with recurrent anaplastic ependymoma (World Health Organization grade III). Many CD68 reactive monocytic cells (arrows) are found in tumor specimen. (Intratumoral CD68 immunohistochemistry, x200)

View larger version (87K): [in a new window]   Fig. 4 —69-year-old woman with cerebral B-cell lymphoma. On T1-weighted images (top row), gadolinium (Gd) series shows enhancing tumor in fornix and in ependyma at level of left foramen of Monroe. On T1-weighted ultrasmall superparamagnetic iron oxides (USPIO) image, reduced enhancement is present (arrowhead). No enhancement appears on T2*-weighted USPIO images (bottom row). Note improved delineation of sulcal veins, choroid plexus in occipital horns of lateral ventricles, and internal cerebral vein in third ventricle on USPIO-enhanced T2*-weighted images (bottom right).

View larger version (19K): [in a new window]   Fig. 5 —Bar-and-whisker chart shows change of normalized signal intensity in enhancing tumor rind and in enhancing solid tumor parts on T1-weighted images with gadolinium (Gd), T1-weighted images with ultrasmall superparamagnetic iron oxides (USPIO), and T2*-weighted images with USPIO. On T1-weighted Gd series, normalized changes of signal intensity were most prominent, with a mean decrease in enhancing tumor rind (dark gray bars) of 52.3% ± 23.4% (SD) and in enhancing solid tumor parts (light gray bars) of 53.7% ± 22.1%. On T1-weighted USPIO series, changes of normalized signal intensity were slightly less distinct measured in corresponding enhancing parts of tumor. Changes measured in tumor rind were 40.1% ± 26.7% and in solid tumor parts were 47.2% ± 31.9%. Decrease of signal intensity in enhancing areas of tumor was less pronounced on T2*-weighted USPIO images; it measured 33.1% ± 18.4% in enhancing tumor rind and 28.4% ± 16.4% in enhancing solid tumor parts. Changes of signal intensity on T1- and T2*-weighted USPIO images were statistically significant in relation to T1-weighted Gd images (p < 0.015). Error bars indicate confidence interval.

View larger version (11K): [in a new window]   Fig. 6 —Scatterplot of volumes of enhancing tumors determined on T1-weighted gadolinium versus T1-weighted ultrasmall superparamagnetic iron oxides (USPIO) images (icon triangle) and T1-weighted gadolinium versus T2*-weighted USPIO images (icon diamond) with line of isovolume shown. In three cases, tumor volumes determined on basis of T1-weighted gadolinium, T1-weighted USPIO, and T2*-weighted USPIO images were comparable. In one case, tumor volume was largest on T2*-weighted USPIO, second largest on T1-weighted gadolinium, and smallest on T1-weighted USPIO. In one case, tumor volumes were comparable on T1-weighted gadolinium and T1-weighted USPIO, whereas tumor volume appeared to be much larger on T2*-weighted USPIO. In two cases, tumor volumes were comparable in USPIO series, whereas they differed in size on T1-weighted gadolinium images. These differences were not statistically significant (p > 0.2).

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