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MR Imaging with Ultrasmall Superparamagnetic Iron Oxide Particles in Experimental Soft-Tissue Infections in Rats¹

¹ From the Department of Nuclear Medicine, University Hospital Zurich, Switzerland (A.H.K., G.K.v.S.); Departments of Diagnostic Radiology (A.H.K., T.W.) and Pathology (G.J.), University Hospital Basel, Switzerland; Novartis Pharma, Basel, Switzerland (T.O., P.R.A.); and Guerbet, Zurich, Switzerland (J.F.). Received September 5, 2001; revision requested November 7; final revision received April 10, 2002; accepted May 6. Supported in part by Novartis-Stiftung (Basel, Switzerland), EMDO-Stiftung (Zurich, Switzerland), Freie Akademische Gesellschaft (Basel, Switzerland), and Fröhlich Pharma Consulting (Zurich, Switzerland). Address correspondence to A.H.K., Brachmattstrasse 6, CH-4144 Arlesheim, Switzerland (e-mail: akaim@uhbs.ch).

View larger version (87K): [in a new window]   Figure 1a. Transverse MR images in a rat with a predominantly diffuse intra- and intermuscular infection (4-6 days after injection) of the left calf. (a) T2-weighted multisection multiecho spin-echo 2,000/14-74 image obtained prior to USPIO application shows extended edema pattern (arrows). (b) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the edema pattern can be delineated but appears less obvious. (c) T2*-weighted GRE 500/10 image with a 30° flip angle: Note strong enhancement (low SI, arrows) due to susceptibility effects 3 hours after intravenous USPIO administration in the infected area. (d) T2*-weighted GRE 500/10 image with a 30° flip angle shows that 24 hours after USPIO application, the distribution of low SI has changed in comparison to that in b. The susceptibility effects can be delineated along the intermuscular fascia (arrowheads) and in areas that previously appeared unenhanced (arrow), reflecting the macrophage distribution pattern. (e) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the distribution pattern at 48 hours remained similar but showed a decrease of susceptibility effects.

View larger version (81K): [in a new window]   Figure 1b. Transverse MR images in a rat with a predominantly diffuse intra- and intermuscular infection (4-6 days after injection) of the left calf. (a) T2-weighted multisection multiecho spin-echo 2,000/14-74 image obtained prior to USPIO application shows extended edema pattern (arrows). (b) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the edema pattern can be delineated but appears less obvious. (c) T2*-weighted GRE 500/10 image with a 30° flip angle: Note strong enhancement (low SI, arrows) due to susceptibility effects 3 hours after intravenous USPIO administration in the infected area. (d) T2*-weighted GRE 500/10 image with a 30° flip angle shows that 24 hours after USPIO application, the distribution of low SI has changed in comparison to that in b. The susceptibility effects can be delineated along the intermuscular fascia (arrowheads) and in areas that previously appeared unenhanced (arrow), reflecting the macrophage distribution pattern. (e) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the distribution pattern at 48 hours remained similar but showed a decrease of susceptibility effects.

View larger version (88K): [in a new window]   Figure 1c. Transverse MR images in a rat with a predominantly diffuse intra- and intermuscular infection (4-6 days after injection) of the left calf. (a) T2-weighted multisection multiecho spin-echo 2,000/14-74 image obtained prior to USPIO application shows extended edema pattern (arrows). (b) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the edema pattern can be delineated but appears less obvious. (c) T2*-weighted GRE 500/10 image with a 30° flip angle: Note strong enhancement (low SI, arrows) due to susceptibility effects 3 hours after intravenous USPIO administration in the infected area. (d) T2*-weighted GRE 500/10 image with a 30° flip angle shows that 24 hours after USPIO application, the distribution of low SI has changed in comparison to that in b. The susceptibility effects can be delineated along the intermuscular fascia (arrowheads) and in areas that previously appeared unenhanced (arrow), reflecting the macrophage distribution pattern. (e) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the distribution pattern at 48 hours remained similar but showed a decrease of susceptibility effects.

View larger version (76K): [in a new window]   Figure 1d. Transverse MR images in a rat with a predominantly diffuse intra- and intermuscular infection (4-6 days after injection) of the left calf. (a) T2-weighted multisection multiecho spin-echo 2,000/14-74 image obtained prior to USPIO application shows extended edema pattern (arrows). (b) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the edema pattern can be delineated but appears less obvious. (c) T2*-weighted GRE 500/10 image with a 30° flip angle: Note strong enhancement (low SI, arrows) due to susceptibility effects 3 hours after intravenous USPIO administration in the infected area. (d) T2*-weighted GRE 500/10 image with a 30° flip angle shows that 24 hours after USPIO application, the distribution of low SI has changed in comparison to that in b. The susceptibility effects can be delineated along the intermuscular fascia (arrowheads) and in areas that previously appeared unenhanced (arrow), reflecting the macrophage distribution pattern. (e) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the distribution pattern at 48 hours remained similar but showed a decrease of susceptibility effects.

View larger version (70K): [in a new window]   Figure 1e. Transverse MR images in a rat with a predominantly diffuse intra- and intermuscular infection (4-6 days after injection) of the left calf. (a) T2-weighted multisection multiecho spin-echo 2,000/14-74 image obtained prior to USPIO application shows extended edema pattern (arrows). (b) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the edema pattern can be delineated but appears less obvious. (c) T2*-weighted GRE 500/10 image with a 30° flip angle: Note strong enhancement (low SI, arrows) due to susceptibility effects 3 hours after intravenous USPIO administration in the infected area. (d) T2*-weighted GRE 500/10 image with a 30° flip angle shows that 24 hours after USPIO application, the distribution of low SI has changed in comparison to that in b. The susceptibility effects can be delineated along the intermuscular fascia (arrowheads) and in areas that previously appeared unenhanced (arrow), reflecting the macrophage distribution pattern. (e) T2*-weighted GRE 500/10 image with a 30° flip angle shows that the distribution pattern at 48 hours remained similar but showed a decrease of susceptibility effects.

View larger version (21K): [in a new window]   Figure 2. Graph shows relative SI over time. = relative SI (SI of infected muscle divided by SI of noninfected muscle) on T2*-weighted GRE images before and after USPIO application over time (median values with interquartile range). = control values (without USPIO application). The T2* effect was most prominent 3 hours after USPIO application because of the high level of intravascular USPIO and because a significant increase of T2* occurred 24 hours after USPIO application, reflecting the intracellular iron accumulation within macrophages. Only a slight increase of T2* could be delineated at 48 and 72 hours after USPIO application compared with that at 24 hours.

View larger version (22K): [in a new window]   Figure 3. Graph shows T2 (median values with interquartile ranges) of infected () and noninfected () muscle before and after USPIO application over time. = control values (with infected muscle but without USPIO application). The shortening of T2 values 3 hours after USPIO application is followed by a significant increase at 24 hours. Only a slight increase of T2 value occurs 48 and 69 hours after USPIO application compared with that at 24 hours.

View larger version (215K): [in a new window]   Figure 4a. (a) Histologic section shows intermuscular inflammatory cellular infiltrates, which consist of predominantly macrophages, lymphocytes, and granulocytes. Granulation tissue (arrows) with fibroblasts delineates the area of inflammation from the adjacent muscle along the intermuscular fascias. (Hematoxylin-eosin stain; original magnification, x10.) (b) Histologic section shows intracellular iron deposits within the cytoplasm of macrophages, explaining the strong susceptibility effects on T2*-weighted GRE images in the infected area. (Perls Prussian blue stain; original magnification, x20.) (c) Electron microscopic image shows increased electron-dense lysosomes (arrows) corresponding to intraphagolysosomal iron particles within activated macrophages (original magnification, x5,000.)

View larger version (202K): [in a new window]   Figure 4b. (a) Histologic section shows intermuscular inflammatory cellular infiltrates, which consist of predominantly macrophages, lymphocytes, and granulocytes. Granulation tissue (arrows) with fibroblasts delineates the area of inflammation from the adjacent muscle along the intermuscular fascias. (Hematoxylin-eosin stain; original magnification, x10.) (b) Histologic section shows intracellular iron deposits within the cytoplasm of macrophages, explaining the strong susceptibility effects on T2*-weighted GRE images in the infected area. (Perls Prussian blue stain; original magnification, x20.) (c) Electron microscopic image shows increased electron-dense lysosomes (arrows) corresponding to intraphagolysosomal iron particles within activated macrophages (original magnification, x5,000.)

View larger version (202K): [in a new window]   Figure 4c. (a) Histologic section shows intermuscular inflammatory cellular infiltrates, which consist of predominantly macrophages, lymphocytes, and granulocytes. Granulation tissue (arrows) with fibroblasts delineates the area of inflammation from the adjacent muscle along the intermuscular fascias. (Hematoxylin-eosin stain; original magnification, x10.) (b) Histologic section shows intracellular iron deposits within the cytoplasm of macrophages, explaining the strong susceptibility effects on T2*-weighted GRE images in the infected area. (Perls Prussian blue stain; original magnification, x20.) (c) Electron microscopic image shows increased electron-dense lysosomes (arrows) corresponding to intraphagolysosomal iron particles within activated macrophages (original magnification, x5,000.)