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Functional-Morphologic MR Imaging with Ultrasmall Superparamagnetic Particles of Iron Oxide in Acute and Chronic Soft-Tissue Infection: Study in Rats¹

¹ From the Department of Diagnostic Radiology (A.H.K., T.W.) and Institute of Pathology (G.J.), University Hospital Basel, Switzerland; Novartis Pharma, Basel, Switzerland (T.O., P.R.A.); Guerbet, Zurich, Switzerland (J.F.); and the Department of Nuclear Medicine, University Hospital Zurich, Switzerland (G.K.v.S.). Received April 29, 2002; revision requested June 6; revision received July 27; accepted September 23. Supported by Fröhlich Pharma Consulting, Zurich; Novartis-Stiftung, Basel; and Freiwillige Akademische Gesellschaft, Basel. Address correspondence to A.H.K., Brachmattstrasse 6, CH-4144 Arlesheim, Switzerland (e-mail: akaim@uhbs.ch).

View larger version (108K): [in a new window]   Figure 1a. MR images and photomicrographs of corresponding histologic appearance of acute soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows slight hyperintensity within infected muscle. (b) Diffuse edema pattern (arrows) in infected muscle is delineated on transverse T2 map obtained before USPIO administration. (c) Enhancement pattern 24 hours after USPIO administration is diffuse, relatively faint, and inhomogeneous on transverse T2*-weighted GRE MR image (500/10, 30° flip angle). (d) Inflammatory cell infiltrate consists mainly of granulocytes (arrows). (Chloracetatesterase reaction; original magnification, x10.) (e) Only some interspersed USPIO-loaded macrophages (arrows) are present. (Prussian blue stain; original magnification, x40.)

View larger version (119K): [in a new window]   Figure 1b. MR images and photomicrographs of corresponding histologic appearance of acute soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows slight hyperintensity within infected muscle. (b) Diffuse edema pattern (arrows) in infected muscle is delineated on transverse T2 map obtained before USPIO administration. (c) Enhancement pattern 24 hours after USPIO administration is diffuse, relatively faint, and inhomogeneous on transverse T2*-weighted GRE MR image (500/10, 30° flip angle). (d) Inflammatory cell infiltrate consists mainly of granulocytes (arrows). (Chloracetatesterase reaction; original magnification, x10.) (e) Only some interspersed USPIO-loaded macrophages (arrows) are present. (Prussian blue stain; original magnification, x40.)

View larger version (101K): [in a new window]   Figure 1c. MR images and photomicrographs of corresponding histologic appearance of acute soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows slight hyperintensity within infected muscle. (b) Diffuse edema pattern (arrows) in infected muscle is delineated on transverse T2 map obtained before USPIO administration. (c) Enhancement pattern 24 hours after USPIO administration is diffuse, relatively faint, and inhomogeneous on transverse T2*-weighted GRE MR image (500/10, 30° flip angle). (d) Inflammatory cell infiltrate consists mainly of granulocytes (arrows). (Chloracetatesterase reaction; original magnification, x10.) (e) Only some interspersed USPIO-loaded macrophages (arrows) are present. (Prussian blue stain; original magnification, x40.)

View larger version (137K): [in a new window]   Figure 1d. MR images and photomicrographs of corresponding histologic appearance of acute soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows slight hyperintensity within infected muscle. (b) Diffuse edema pattern (arrows) in infected muscle is delineated on transverse T2 map obtained before USPIO administration. (c) Enhancement pattern 24 hours after USPIO administration is diffuse, relatively faint, and inhomogeneous on transverse T2*-weighted GRE MR image (500/10, 30° flip angle). (d) Inflammatory cell infiltrate consists mainly of granulocytes (arrows). (Chloracetatesterase reaction; original magnification, x10.) (e) Only some interspersed USPIO-loaded macrophages (arrows) are present. (Prussian blue stain; original magnification, x40.)

View larger version (46K): [in a new window]   Figure 1e. MR images and photomicrographs of corresponding histologic appearance of acute soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows slight hyperintensity within infected muscle. (b) Diffuse edema pattern (arrows) in infected muscle is delineated on transverse T2 map obtained before USPIO administration. (c) Enhancement pattern 24 hours after USPIO administration is diffuse, relatively faint, and inhomogeneous on transverse T2*-weighted GRE MR image (500/10, 30° flip angle). (d) Inflammatory cell infiltrate consists mainly of granulocytes (arrows). (Chloracetatesterase reaction; original magnification, x10.) (e) Only some interspersed USPIO-loaded macrophages (arrows) are present. (Prussian blue stain; original magnification, x40.)

View larger version (87K): [in a new window]   Figure 2a. MR images and photomicrograph of corresponding histologic appearance in early chronic soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows an inhomogeneous pattern with predominantly high SI within the area of infection. (b) High SI (arrows) on transverse T2 map obtained before USPIO administration delineates the edema pattern that defines the extent of infection. (c) Enhancement pattern seen on transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration is sharply circumscribed and shows a strong decrease in SI (*) due to susceptibility effects. An area of central necrosis with high SI is surrounded by the strongly enhancing abscess wall. (d) Cellular infiltrate is characterized by a dense infiltrate of iron-loaded macrophages (arrows). (Prussian blue stain; original magnification, x10.)

View larger version (96K): [in a new window]   Figure 2b. MR images and photomicrograph of corresponding histologic appearance in early chronic soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows an inhomogeneous pattern with predominantly high SI within the area of infection. (b) High SI (arrows) on transverse T2 map obtained before USPIO administration delineates the edema pattern that defines the extent of infection. (c) Enhancement pattern seen on transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration is sharply circumscribed and shows a strong decrease in SI (*) due to susceptibility effects. An area of central necrosis with high SI is surrounded by the strongly enhancing abscess wall. (d) Cellular infiltrate is characterized by a dense infiltrate of iron-loaded macrophages (arrows). (Prussian blue stain; original magnification, x10.)

View larger version (96K): [in a new window]   Figure 2c. MR images and photomicrograph of corresponding histologic appearance in early chronic soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows an inhomogeneous pattern with predominantly high SI within the area of infection. (b) High SI (arrows) on transverse T2 map obtained before USPIO administration delineates the edema pattern that defines the extent of infection. (c) Enhancement pattern seen on transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration is sharply circumscribed and shows a strong decrease in SI (*) due to susceptibility effects. An area of central necrosis with high SI is surrounded by the strongly enhancing abscess wall. (d) Cellular infiltrate is characterized by a dense infiltrate of iron-loaded macrophages (arrows). (Prussian blue stain; original magnification, x10.)

View larger version (143K): [in a new window]   Figure 2d. MR images and photomicrograph of corresponding histologic appearance in early chronic soft-tissue infection. (a) Transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration shows an inhomogeneous pattern with predominantly high SI within the area of infection. (b) High SI (arrows) on transverse T2 map obtained before USPIO administration delineates the edema pattern that defines the extent of infection. (c) Enhancement pattern seen on transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration is sharply circumscribed and shows a strong decrease in SI (*) due to susceptibility effects. An area of central necrosis with high SI is surrounded by the strongly enhancing abscess wall. (d) Cellular infiltrate is characterized by a dense infiltrate of iron-loaded macrophages (arrows). (Prussian blue stain; original magnification, x10.)

View larger version (83K): [in a new window]   Figure 3a. MR images and photomicrograph of corresponding histologic appearance of late chronic soft-tissue infection. (a) High SI is seen within infected muscle on a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration. (b) Areas of high SI (arrows) are delineated on a transverse T2 map obtained before USPIO administration. The rather nonspecific term "edema pattern" is used to describe the extent of pathomorphologic changes. (c) On a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration, enhancement appears circumscribed in the abscess wall around the area of central necrosis (*) and is surrounded by a less intense and relatively unsharp enhancement pattern. (d) Iron-loaded macrophages (arrows) are interspersed within fibroblast-enriched granulation tissue. (Prussian blue stain; original magnification, x20.)

View larger version (95K): [in a new window]   Figure 3b. MR images and photomicrograph of corresponding histologic appearance of late chronic soft-tissue infection. (a) High SI is seen within infected muscle on a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration. (b) Areas of high SI (arrows) are delineated on a transverse T2 map obtained before USPIO administration. The rather nonspecific term "edema pattern" is used to describe the extent of pathomorphologic changes. (c) On a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration, enhancement appears circumscribed in the abscess wall around the area of central necrosis (*) and is surrounded by a less intense and relatively unsharp enhancement pattern. (d) Iron-loaded macrophages (arrows) are interspersed within fibroblast-enriched granulation tissue. (Prussian blue stain; original magnification, x20.)

View larger version (93K): [in a new window]   Figure 3c. MR images and photomicrograph of corresponding histologic appearance of late chronic soft-tissue infection. (a) High SI is seen within infected muscle on a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration. (b) Areas of high SI (arrows) are delineated on a transverse T2 map obtained before USPIO administration. The rather nonspecific term "edema pattern" is used to describe the extent of pathomorphologic changes. (c) On a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration, enhancement appears circumscribed in the abscess wall around the area of central necrosis (*) and is surrounded by a less intense and relatively unsharp enhancement pattern. (d) Iron-loaded macrophages (arrows) are interspersed within fibroblast-enriched granulation tissue. (Prussian blue stain; original magnification, x20.)

View larger version (148K): [in a new window]   Figure 3d. MR images and photomicrograph of corresponding histologic appearance of late chronic soft-tissue infection. (a) High SI is seen within infected muscle on a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained before intravenous USPIO administration. (b) Areas of high SI (arrows) are delineated on a transverse T2 map obtained before USPIO administration. The rather nonspecific term "edema pattern" is used to describe the extent of pathomorphologic changes. (c) On a transverse T2*-weighted GRE MR image (500/10, 30° flip angle) obtained 24 hours after USPIO administration, enhancement appears circumscribed in the abscess wall around the area of central necrosis (*) and is surrounded by a less intense and relatively unsharp enhancement pattern. (d) Iron-loaded macrophages (arrows) are interspersed within fibroblast-enriched granulation tissue. (Prussian blue stain; original magnification, x20.)

View larger version (12K): [in a new window]   Figure 4. Graph shows that decrease in relative SI was most prominent in the early chronic stage of infection due to high density of USPIO-loaded macrophages. In acute and late chronic stages, the cellular infiltrate had only some interspersed and fewer USPIO-loaded macrophages, leading to a smaller decrease in relative SI on MR images obtained 24 hours after USPIO administration.

View larger version (12K): [in a new window]   Figure 5. Relative macrophage extent (ratio of area of macrophage cellular pattern to area of edema pattern) decreased to 0.8 in the late chronic stage, indicating that the distribution of USPIO-loaded macrophages was less extensive than the edema pattern. In the early chronic stage, however, the extension was very similar for both patterns.