A

Figure 4 Pathologically proved benign lymph node in a patient with prostate cancer. Axial MR images, obtained with a 3 mm section thickness before (A) and after (B) administration of ferumoxtran-10 show a node (circle) with peripheral uptake of contrast material and a prominent central fatty hilum. Thin sections allow robust nodal characterization. Source: From Ref. 12.

Figure 4 Pathologically proved benign lymph node in a patient with prostate cancer. Axial MR images, obtained with a 3 mm section thickness before (A) and after (B) administration of ferumoxtran-10 show a node (circle) with peripheral uptake of contrast material and a prominent central fatty hilum. Thin sections allow robust nodal characterization. Source: From Ref. 12.

limiting the influence of T1 effects (12). These include a lengthening repetition time (TR) or reducing flip angle to control T1 weighting and therefore heighten T2* effects. In addition, selecting a sufficiently long time-to-echo (TE) results in satisfactory signal intensity drop within benign nodes. A short TE can result in an inadequate signal intensity reduction leading to misinterpretation of a benign lymph node as being malignant (12).

In our practice, pre- and post-contrast scanning are done using the following sequences (appendix): two-dimensional (2D) axial T1-weighted gradient-echo, 2D axial T2-weighted fast spin echo and 2D axial T2*-weighted gradient-echo sequences (Fig. 5). In addition, post-contrast three-dimensional (3D) T1-weighted gradientecho sequence can be performed for the surgical mapping of lymph nodes.

Figure 5 Sequences for MR imaging with ferumoxtran-10. (A) Axial T1-weighted gradientecho, (B) T2*-weighted fast spin echo, and (C) T2*-weighted gradient-echo MR images, all obtained after administration of ferumoxtran-10, show a benign left inguinal lymph node (arrow). The node demonstrates homogeneous uptake of ferumoxtran-10 on the T2*-weighted gradient-echo image. Note the presence of artifacts from surgical clips that are greatest in Figure 5C due to greater susceptibility weighting. Source: From Ref. 12.

Figure 5 Sequences for MR imaging with ferumoxtran-10. (A) Axial T1-weighted gradientecho, (B) T2*-weighted fast spin echo, and (C) T2*-weighted gradient-echo MR images, all obtained after administration of ferumoxtran-10, show a benign left inguinal lymph node (arrow). The node demonstrates homogeneous uptake of ferumoxtran-10 on the T2*-weighted gradient-echo image. Note the presence of artifacts from surgical clips that are greatest in Figure 5C due to greater susceptibility weighting. Source: From Ref. 12.

Figure 6 Fatty hilum of a lymph node at ferumoxtran-10 imaging of the pelvis. (A) Axial T2*-weighted gradient-echo MR image, obtained 24 hours after administration of ferumoxtran-10, shows a right inguinal node with peripheral decreased signal intensity (black arrow) and central high signal intensity (white arrow), an appearance that may be misinterpreted as representing a metastatic deposit. (B) Axial T1-weighted gradient-echo MR image shows that the central area of the node has high signal intensity (top white arrow), which indicates that this area represents the normal fatty hilum of the node. Note the enhancement of the femoral vessels (bottom white arrow) adjacent to the node, an appearance caused by the residual effect of circulating ferumox-tran-10. Peripheral decreased signal intensity (black arrow) in the node is seen but this effect is less reliable than on T2* sequence as shown in Figure 6A. Source: From Ref. 12.

Figure 6 Fatty hilum of a lymph node at ferumoxtran-10 imaging of the pelvis. (A) Axial T2*-weighted gradient-echo MR image, obtained 24 hours after administration of ferumoxtran-10, shows a right inguinal node with peripheral decreased signal intensity (black arrow) and central high signal intensity (white arrow), an appearance that may be misinterpreted as representing a metastatic deposit. (B) Axial T1-weighted gradient-echo MR image shows that the central area of the node has high signal intensity (top white arrow), which indicates that this area represents the normal fatty hilum of the node. Note the enhancement of the femoral vessels (bottom white arrow) adjacent to the node, an appearance caused by the residual effect of circulating ferumox-tran-10. Peripheral decreased signal intensity (black arrow) in the node is seen but this effect is less reliable than on T2* sequence as shown in Figure 6A. Source: From Ref. 12.

Of the acquired sequences, T1- and T2-weighted sequences are used for nodal detection and anatomic localization. Additionally, the T1-weighted sequence helps to reduce false-positive interpretation by distinguishing fatty hilum from a metastatic node (Fig. 6). Postcontrast 3D T1-weighted gradient-echo sequence with a short TE can exploit the T1 enhancement properties of circulating Ferumoxtran-10 to delineate the vascular anatomy; mapping of the lymph nodes in relation to enhanced vessels on 3D rendering can be very useful to the operating surgeon (Fig. 7). The most crucial sequence for lymph node characterization is the T2*-weighted gradient-echo sequence (12). Normal nodes show drop in signal intensity owing to the susceptibility effects of iron oxide reducing T2*, while malignant lymph nodes will appear hyperintense.

Optimal TE for T2* Sequence

As imaging of normal lymph nodes with ferumoxtran-10 relies on signal intensity reductions due to susceptibility effects, choosing an appropriate TE value is important for making optimal diagnosis. Imaging with a very short TE may result in an

Figure 7 Mapping of lymph nodes in a patient with prostate cancer. Surface-shaded 3D-MR image showing the iliac vessels, distal aorta, and inferior vena cava, which are enhanced due to the effect of circulating ferumoxtran-10 on a T1-weighted 3D-GRE sequence. Malignant nodes are coded in red (arrows), thus showing their relationships to the major vessels; such renderings are useful for surgical planning. (See color insert.) Source: From Ref. 12.

Figure 7 Mapping of lymph nodes in a patient with prostate cancer. Surface-shaded 3D-MR image showing the iliac vessels, distal aorta, and inferior vena cava, which are enhanced due to the effect of circulating ferumoxtran-10 on a T1-weighted 3D-GRE sequence. Malignant nodes are coded in red (arrows), thus showing their relationships to the major vessels; such renderings are useful for surgical planning. (See color insert.) Source: From Ref. 12.

Figure 8 Optimal TE for imaging with ferumoxtran-10. Axial T2*-weighted MR imaging of the pelvis was performed in a patient with prostate cancer after administration of ferumox-tran-10. (A) Image obtained with a TE of 14 msec shows a left external iliac node with central heterogeneity (arrow), a finding that may be interpreted as representing metastatic infiltration. (B) Image obtained with a TE of 24 msec at the same time as Figure 8A above shows a more homogeneous drop in signal intensity (arrow). This finding indicates benignity, which was proven pathologically. Source: From Ref. 12.

Figure 8 Optimal TE for imaging with ferumoxtran-10. Axial T2*-weighted MR imaging of the pelvis was performed in a patient with prostate cancer after administration of ferumox-tran-10. (A) Image obtained with a TE of 14 msec shows a left external iliac node with central heterogeneity (arrow), a finding that may be interpreted as representing metastatic infiltration. (B) Image obtained with a TE of 24 msec at the same time as Figure 8A above shows a more homogeneous drop in signal intensity (arrow). This finding indicates benignity, which was proven pathologically. Source: From Ref. 12.

inadequate signal drop resulting in erroneous interpretation. Figure 8 shows the differences in susceptibility with two different TE's in a benign lymph node.

Postferumoxtran-10 Imaging Only

A question often posed is whether it is necessary to image before and after ferumox-tran-10 administration. For "beginners," the best results will be obtained by comparing preferumoxtran-10 images with postferumoxtran-10 images. For more experienced users, the precontrast MRI can be replaced by postferumoxtran-10 sequences that are less sensitive to the susceptibility effects of iron oxide particles. For this purpose, a Tl-weighted turbo spin-echo sequence can be used (Fig. 3B). If the same resolution and slice parameters are used, an insensitive image to iron can be compared with its corresponding sensitive T2* GRE image (Fig. 3C).

Quantitative Estimation of T2*

In the clinic, lymph node characterization following ferumoxtran-10 administration is based on qualitative assessment of signal intensity changes within the nodes. The accuracy of this technique can be further improved by using quantitative methods to detect minimal malignant infiltration of small nodes. By performing a dual-echo T2*-weighted gradient-echo sequence, it is possible to quantify ferumoxtran-10 uptake by calculating the T2* relaxation rate of the lymph node (12). However, an optimal T2* value that clearly differentiates between benign and malignant lymph nodes is yet to be determined.

CONCLUSIONS

Accurate nodal staging is important for deciding the choice of therapy and for predicting patient prognosis. MR lymphangiography using the intravenously administered contrast agent ferumoxtran-10, has emerged as a powerful new tool for the evaluation of nodal involvement. Accurate image interpretation of ferumox-tran-10-enhanced MR lymphangiography demands that careful attention be paid to the contrast administration and MR scanning technique.

APPENDIX

Typical Pulse Sequence Parameters

Pulse sequence parameters for the 1.5-T Horizon imager (GE Medical Systems,

Milwaukee, Wisconsin, U.S.A.) are as follows:

1. T2-weighted fast spin-echo sequence: repetition time (TR) = 4500 to 5500 msec, time-to-echo (TE) = 80 to 100 msec, flip angle = 90°, three signals acquired, section thickness = 3 mm, gap = 0 mm, 256 x 256 matrix, and field of view = 22 to 30 cm.

2. T2*-weighted gradient-echo sequence: TR = 300 to 400 msec, TE = 24 msec, flip angle = 20°, two signals acquired, section thickness = 3 mm, gap = 0 mm, 160 x 256 matrix, and field of view = 22 to 30 cm.

3. 2D T1-weighted gradient-echo sequence: TR = 175msec, TE = 1.8msec, flip angle = 80°, two signals acquired, section thickness = 4 mm, gap =

0 mm, 128 x 256 matrix, and field of view = 22 to 30 cm.

4. 3D T1-weighted gradient-echo sequence: TR = 4.5 to 5.5msec, TE = 1.4 msec, flip angle = 15°, two signals acquired, section thickness = 5 mm, gap = 0 mm, 256 x 256 matrix, and field of view = 24 to 32 cm.

Pulse sequence parameters for the 1.5-T Magnetom Symphony imager (Siemens

Medical Solutions, Erlangen, Germany) are as follows:

1. High spatial resolution 3D T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) sequence: TR = 1540msec, TE = 3.93 msec, TI = 800 msec, flip angle = 8°, one signal acquired, section thickness =

1 mm, gap = 0mm, 256 x 256matrix, extrapolated to 512 x 512, and field of view = 300 mm.

2. T1-weighted turbo spin-echo sequence: TR = 1800 to 2000msec, TE = 15 msec, ETL 3, flip angle = 180°, two signals acquired, section thickness = 3 mm, gap = 0 mm, 512 x 384 matrix, and field of view = 285 mm. Images are obtained in the axial and oblique plane parallel to the iliac vessels.

3. 2D T2*-weighted fast low-angle shot (FLASH) or T2*-weighted multiecho data image combination (MEDIC) sequences: TR = 800 to 1500 msec, TEeff = 18 msec, flip angle = 30°, two signals acquired, section thickness = 3 mm, matrix 512 x 512, and field of view 285 mm. Images are obtained in the same planes as the T1-weighted turbo spin-echo sequences.

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