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DOI:10.2214/AJR.05.0873
AJR 2006; 187:W582-W588
© American Roentgen Ray Society


Original Research

Comparison of Lymphotropic Nanoparticle-Enhanced MRI Sequences in Patients with Various Primary Cancers

Mansi Saksena1, Mukesh Harisinghani1, Peter Hahn1, John Kim1, Anuradha Saokar1, Benjamin King1 and Ralph Weissleder1

1 All authors: Division of Abdominal Imaging, Massachusetts General Hospital and Harvard Medical School, White 270, 55 Fruit Street, Boston, MA 02114.

Received May 23, 2005; accepted after revision November 17, 2005.

 
Address correspondence to M. Harisinghani (mharisinghani{at}partners.org).

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Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
OBJECTIVE. This study was performed to empirically evaluate T2-weighted fast spin-echo, moderately T2*-weighted gradient-refocused echo (GRE), and heavily T2*-weighted GRE sequences to determine which sequence is the most effective for nodal characterization on lymphotropic nanoparticle-enhanced MRI (LNMRI).

MATERIALS AND METHODS. The study included 65 patients who had proven primary cancer and were scheduled for either surgical lymph node dissection or imaging-guided lymph node biopsy. All patients underwent LNMRI using T2-weighted fast spin-echo, moderately T2*-weighted GRE, and heavily T2*-weighted GRE sequences. Unequivocal correlation of histopathology and MRI could be made in 140 nodes and only these were included in the analysis. Two blinded reviewers performed qualitative analysis of the nodes. Alternative free-response receiver operating characteristic (ROC) curves with a continuous rating scale were plotted for each sequence for both reviewers and the diagnostic accuracy of fast spin-echo T2-weighted and GRE T2*-weighted images were compared by calculating the area under the curve (Az). A two-tailed Student's t test was performed to test the significance (p < 0.05) of the differences between the ROC curves derived from the three sequences.

RESULTS. Irrespective of reviewer experience, T2*-weighted sequences showed better nodal characterization when compared with T2-weighted sequences. For both reviewers, there was a statistically significant difference between the Az for T2- and the two T2*-weighted sequences (p < 0.05). Neither reviewer showed a statistically significant difference between the two T2*-weighted sequences.

CONCLUSION. GRE T2*-weighted sequences are superior for nodal characterization on LNMRI to fast spin-echo T2-weighted sequences. Imaging protocols for LNMRI should include fast spin-echo T2-weighted imaging for anatomic localization, but characterization of nodes should be based on their appearance on contrast-enhanced T2*-weighted images. The T2*-weighted images acquired with dual TE values, one of which is intermediate and the other longer, improve nodal characterization.

Keywords: cancer • lymph nodes • MR contrast agents • MRI


Introduction
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
Accurate pretreatment staging of an oncologic patient helps in both selecting appropriate therapy and assessing prognosis. Cross-sectional imaging is routinely used, not only to evaluate the primary tumor (T stage) and detect regional or distant metastatic disease (M stage), but also for nodal evaluation (N stage). Over the past decade, CT and MRI have been the mainstays of nodal staging. However, the size criteria used to detect nodal metastatic disease with these techniques are both nonspecific and insensitive [1-4]. The inaccuracy of size criteria for nodal characterization has led to the development of newer techniques that evaluate nodal function.

Lymphotrophic nanoparticle-enhanced MRI (LNMRI) using ferumoxtran-10 (Combidex, Advanced Magnetics; Sinerem, Guerbet) is a particularly promising technique for nodal evaluation in the setting of malignancy.

This technique is highly accurate for nodal staging in patients with various primary cancers [5-15]. It evaluates nodal macrophage function and does not rely on nodal size to detect metastatic disease. It is postulated that macrophages present in normal benign nodes take up the contrast agent causing a drop in nodal signal intensity on contrast-enhanced imaging. Benign nodes show homogeneous ferumoxtran-10 uptake and signal intensity drop on contrast-enhanced T2-weighted fast spin-echo and T2*-weighted gradient-refocused echo (GRE T2*) images, whereas a node replaced by malignant cells shows no change in signal intensity after ferumoxtran-10 administration [16]. Therefore, imaging with ferumoxtran-10 typically involves 2D axial T1-weighted gradient-echo, 2D axial T2-weighted fast spin-echo, and 2D axial T2*-weighted gradient-refocused echo sequences, the ideal imaging parameters for which have been described [17].

To accurately characterize nodes, the optimal sequence for LNMRI should have a good contrast-to-noise ratio (CNR). T2-weighted images have a good signal-to-noise ratio (SNR) but are not very sensitive to the change in intranodal susceptibility caused by ferumoxtran-10. The T2* sequence is a heavily T2-weighted gradient-echo sequence with additional sensitivity for the susceptibility changes induced by the intranodal ferumoxtran-10 in normal nodes [18]. T2*-weighted images have good CNR ratio but lower SNR. With increasing TE, T2* weighting becomes progressively stronger, with better CNR but lower SNR. The T1-weighted images are used for anatomic localization of nodes and for the detection of a fatty hilum, whereas nodal characterization depends on its signal intensity on the contrast-enhanced T2- and T2*-weighted images.

Multiple clinical studies have evaluated the technique using the above mentioned sequences [5-15]. Harisinghani et al. [9] evaluated 80 patients with prostate cancer and reported a sensitivity of 100% with a specificity of 95.7% in characterizing pelvic lymph nodes [9]. Anzai et al. [7], reporting on the overall phase III multicenter trial in evaluating various primary cancers, reported a sensitivity, specificity, and accuracy of 83%, 77%, and 80%, respectively, with paired unenhanced and contrast-enhanced MRI. Tabatabaei et al. [15] reported a sensitivity of 100% and a specificity of 97% on seven patients with squamous cell carcinoma of the pelvis. All studies, however, evaluated primary efficacy parameters of sensitivity, specificity, and accuracy for nodal characterization on LNMRI without attention being paid to the accuracy of T2 and T2* sequences individually. This study empirically evaluates T2-weighted fast spin-echo, moderately T2*-weighted GRE, and heavily T2*-weighted GRE sequences to determine which is the most effective sequence for nodal characterization on LNMRI.


Materials and Methods
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
Patients
The study included 65 patients (51 men, 14 women; mean age, 60.5 years; range, 28-80 years) with proven primary cancer (bladder, 15; breast, 10; renal, 1; penile, 4; prostate, 27; rectal, 1; testicular, 5; ureteral, 2) who were scheduled for either surgical lymph node dissection or imaging-guided lymph node biopsy. Patient inclusion criteria were age older than 18 years, a confirmed primary cancer, and suspected nodal metastases on staging CT scans. The study was approved by the institutional review board. Patients provided written informed consent for the examinations performed.

Ferumoxtran-10 Administration
Ferumoxtran-10 was provided as a lyophilized powder consisting of ultrasmall superparamagnetic iron oxide nanoparticles covered with low-molecular-weight dextran. The contrast material was reconstituted using 10 mL of normal saline after which a weight-adjusted dose (2.6 mg of iron per kg of body weight) was withdrawn and diluted with 50 mL of saline and infused through a 5-µm filter at a rate of 4 mL/min. For a 70-kg patient the injected volume of reconstituted ferumoxtran-10 was 9.1 mL (0.13 mL per kg of body weight). Total volume of diluted contrast material injected was 59.1 mL. None of the patients suffered any severe adverse reactions to the agent, although seven patients reported back pain during the administration of contrast material. This resolved when administration was temporarily withheld with no recurrence on resuming administration.

MRI
MRI was performed at 1.5 T (System 9X, GE Healthcare) with region-specific phased-array coils. Identical sequences were performed before and 24-36 hours after ferumoxtran-10 administration. The pulse sequences performed included T2-weighted fast spin-echo (TR/TE, 4,000-4,500/80; flip angle, 90°; field of view, 24-28 cm; slice thickness, 3 mm; matrix, 256 x 256; number of excitations, 3; echo-train length, 8-12; number of slices, 25-32; average acquisition time, 4.2 minutes), a dual TE T2*-weighted gradient-echo (2,100/12.2, 21; flip angle, 70°; field of view, 26-28 cm; slice thickness, 3 mm; matrix, 128 x 256; number of excitations, 2; average acquisition time, 9 minutes), and a T1-weighted gradient-echo sequence obtained in axial and coronal planes (175/1.8; flip angle, 80°; field of view, 22-30 cm; slice thickness, 4 mm; matrix, 128 x 256; number of excitations, 1; average acquisition time, 22 seconds). Care was taken to ensure that all relevant locoregional nodal drainage areas were included in the imaging. All sequences were performed in the standard axial plane, because this allowed a consistent inclusion of all local and regional lymph nodes; for T1-weighted gradient-echo sequences, additional coronal and oblique images were also obtained to localize the nodes in relationship to vascular anatomic landmarks. The above listed imaging sequences and parameters were optimized to reduce motion artifacts; maximize SNR; and provide diagnostically useful images of the pelvis, abdomen, and chest within clinically acceptable time limits. In particular, when scanning the abdomen and lower chest, respiratory triggering was used for the T2-weighted fast spin-echo sequences, respiratory gating was used for the T2*-weighted gradient-echo sequences, and breath-holding was used for the T1-weighted gradient-echo sequences. To further reduce respiratory artifacts from anterior abdominal wall motion, anterior saturation bands were placed on the subcutaneous fat.

Pathologic Correlation
Histopathologic correlation was obtained by using surgical resection in 20 (31%) patients, imaging-guided biopsy in 41 (63%) patients, and sentinel node biopsy in four (6%) patients.

The average time interval between imaging and pathologic analysis was 8.3 days (range, 0-34 days). Surgically resected nodes were placed on a grid identifying their location and orientation and sent for histopathologic analysis. All nodal tissue was routinely processed and embedded in paraffin. Surgically resected nodes were sliced into multiple parallel slices of 2-3 mm and stained with H and E. The slides were reviewed by a pathologist who had no knowledge of the MRI findings. The histopathologic results for each lymph node were catalogued for subsequent comparison with MRI findings. The nodes that underwent imaging-guided biopsy were correlated at biopsy by two radiologists. Unequivocal correlation of histopathology and MRI could be made in 140 nodes and only these were included in the analysis.

Interpretation of MR Images
Two radiologists who were blinded to the histopathologic diagnosis and not involved in patient enrollment or the primary patient evaluation performed qualitative analysis of the nodes. Reviewer 1 had recently completed a fellowship in abdominal imaging that included occasional discussion of ferumoxtran-10-enhanced MRI. Reviewer 2 had 6 years of experience interpreting ferumoxtran-10-enhanced MR images of lymph nodes. All images were viewed and analyzed on an Advantage Windows workstation (version 4.0, GE Healthcare). Nodes that had undergone pathologic evaluation were marked with arrows and provided to the reviewers. The reviewers did not evaluate the entire study. The images were reviewed in three sessions, with an 8-week interval between each session. To eliminate learning bias, the cases were presented randomly in each session.

In the first session, the reviewers evaluated combined unenhanced and contrast-enhanced fast spin-echo T2-weighted images followed 8 weeks later by the unenhanced and contrast-enhanced GRE T2*-weighted images obtained with a TE of 12.2 msec. In the third session, 8 weeks after the second session, the reviewers evaluated the combined unenhanced and contrast-enhanced GRE T2*-weighted images obtained with a higher TE of 21 msec. The reviewers used established diagnostic guidelines for subjective nodal characterization [7] (Fig. 1). At each session, the reviewers assigned a confidence rating to each node based on a 6-point scale as follows: 1, definitely benign; 2, most likely benign; 3, probably benign; 4, probably malignant; 5, most likely malignant; and 6, definitely malignant.


Figure 1
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Fig. 1 Diagnostic guidelines used for nodal characterization on lymphotropic nanoparticle-enhanced MRI. Adapted from [21].

 

Statistical Analysis
Statistical analysis was performed using Med-Calc for Windows, version 7.4.1.0 (MedCalc Software). Alternative free-response receiver operating characteristic (ROC) curves with a continuous rating scale were plotted for each sequence for both reviewers on a per-nodal basis. The diagnostic accuracy of fast spin-echo T2 and GRE T2* images was compared by calculating the area under the curve (Az). A two-tailed Student's t test was performed to test the significance of the differences among the ROC curves derived from the three sequences (p < 0.05).

Because the reviewers used a 6-point scale for nodal characterization, primary efficacy parameters of sensitivity, specificity, and accuracy were also calculated on a node-to-node basis for T2- and T2*-weighted sequences (scale points 1-3 were designated as benign and 4-6 were designated as malignant). Interobserver agreement was assessed using a weighted kappa statistic, with a kappa value equal to or less than 0.2 indicating slight agreement; 0.21-0.40 indicating fair agreement; 0.41-0.60 indicating moderate agreement; 0.61-0.80 indicating substantial agreement; and 0.81-1.00 indicating almost perfect agreement.


Results
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
On imaging, 140 nodes were seen that were unequivocally correlated with histopathology. The various primary tumors were bladder (38 nodes), breast (19 nodes), renal (1 node), penile (10 nodes), prostate (58 nodes), rectal (2 nodes), testicular (8 nodes) and ureteral (4 nodes). Twenty-five patients contributed one node, 16 patients contributed two nodes and 24 patients contributed three or more nodes. Of the 140 nodes, 89 (63.5%) were evaluated by surgical dissection, 47 (33.5%) by imaging-guided biopsy, and four (2.8%) by sentinel node biopsy. Of the evaluated lymph nodes (mean size, 10.5 mm), 46 (32.8%) were benign and 94 (67.2%) were malignant on histopathologic analysis; seven nodes showed fibrotic changes on pathologic analysis.

ROC analysis evaluating the performances of the two reviewers was performed. Table 1 shows the Az values for each reviewer. The Az value for reviewer 1 was highest for T2*-weighted sequences obtained with a higher TE of 21 (95% confidence interval [CI], 0.85 [0.78-0.90]). The Az value for reviewer 2 was highest for T2*-weighted sequences obtained with a lower TE of 12.6 (95% CI, 0.94 [0.89-0.97]). For both reviewers there was a statistically significant difference between the Az for T2- and the two T2*-weighted sequences (p < 0.05). Neither reviewer showed a statistically significant difference between the two T2*-weighted sequences. These results indicate that irrespective of reviewer experience, T2*-weighted sequences show better nodal characterization than do T2-weighted sequences (Figs. 2A, 2B, 2C, 2D, 2E, 2F, 3A, 3B, 3C, 3D, 3E, and 3F).


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TABLE 1: Area Under the Curve for Receiver Operating Characteristic Curves Obtained for Each Sequence for the Two Reviewers

 

Figure 2
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Fig. 2A 85-year-old woman with bladder cancer. Unenhanced T2-weighted MRI image shows enlarged left external iliac lymph node (arrow) with minimal drop in signal intensity.

 

Figure 3
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Fig. 2B 85-year-old woman with bladder cancer. Unenhanced T2*-weighted MRI image shows enlarged left external iliac lymph node (arrow) with more prominent loss in signal intensity than on T2-weighted images. This is characteristic of benign lymph node and diagnosis was confirmed by CT-guided biopsy.

 

Figure 4
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Fig. 2C 85-year-old woman with bladder cancer. Unenhanced heavily T2*-weighted MRI image shows enlarged left external iliac lymph node (arrow) with more prominent loss in signal intensity than on T2-weighted images. This is characteristic of benign lymph node and diagnosis was confirmed by CT-guided biopsy.

 

Figure 5
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Fig. 2D 85-year-old woman with bladder cancer. Contrast-enhanced T2-weighted MRI image shows enlarged left external iliac lymph node (arrow) with minimal drop in signal intensity.

 

Figure 6
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Fig. 2E 85-year-old woman with bladder cancer. Contrast-enhanced T2*-weighted MRI image shows enlarged left external iliac lymph node (arrow) with more prominent loss in signal intensity than on T2-weighted images. This is characteristic of benign lymph node and diagnosis was confirmed by CT-guided biopsy.

 

Figure 7
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Fig. 2F 85-year-old woman with bladder cancer. Contrast-enhanced heavily T2*-weighted MRI image shows enlarged left external iliac lymph node (arrow) with more prominent loss in signal intensity than on T2-weighted images. This is characteristic of benign lymph node and diagnosis was confirmed by CT-guided biopsy.

 

Figure 8
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Fig. 3A 61-year-old man with prostate cancer. Unenhanced T2-weighted image shows hyperintense 7-mm left external iliac lymph node (arrow). Node is benign by size criteria.

 

Figure 9
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Fig. 3B 61-year-old man with prostate cancer. Unenhanced T2*-weighted image shows hyperintense 7-mm left external iliac lymph node (arrow). Node is benign by size criteria.

 

Figure 10
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Fig. 3C 61-year-old man with prostate cancer. Unenhanced heavily T2*-weighted image shows hyperintense 7-mm left external iliac lymph node (arrow). Node is benign by size criteria. This node was sampled at surgery and found to be completely replaced by metastatic prostate cancer.

 

Figure 11
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Fig. 3D 61-year-old man with prostate cancer. Contrast-enhanced T2-weighted image of 7-mm left external iliac lymph node (arrow) shows no drop in signal intensity. Such an appearance on contrast-enhanced lymphotropic nanoparticle-enhanced MRI is diagnostic of metastatic node.

 

Figure 12
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Fig. 3E 61-year-old man with prostate cancer. Contrast-enhanced T2*-weighted image of 7-mm left external iliac lymph node (arrow) shows no drop in signal intensity. Such an appearance on contrast-enhanced lymphotropic nanoparticle-enhanced MRI is diagnostic of metastatic node.

 

Figure 13
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Fig. 3F 61-year-old man with prostate cancer. Contrast-enhanced heavily T2*-weighted image of 7-mm left external iliac lymph node (arrow) shows no drop in signal intensity. Such an appearance on contrast-enhanced lymphotropic nanoparticle-enhanced MRI is diagnostic of metastatic node. This node was sampled at surgery and found to be completely replaced by metastatic prostate cancer.

 

Table 2 summarizes the sensitivity and specificity values. The images with a TE of 21 msec showed higher specificity but low sensitivity, whereas the images with a TE of 12.2 msec showed higher sensitivity but decreased specificity.


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TABLE 2: Primary Efficacy Parameters of Both Reviewers

 

The weighted kappa value was 0.754. This is interpreted as good agreement within the reviewers (weighted kappa value = 0.61-0.80; strength of agreement between reviewers, good.)


Discussion
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 
Ferumoxtran-10 is an ultrasmall superparamagnetic iron oxide nanoparticle characterized by a large magnetic moment and a high dipolar relaxivity when compared with conventional paramagnetic agents, which gives it a strong T2* effect [19]. Consequently, the GRE T2*-weighted sequence, which is a heavily T2-weighted sequence, is very sensitive to the susceptibility changes induced by the intranodal ferumoxtran-10 and allows for detection of small quantities of intranodal ferumoxtran-10. When administered IV, these nanoparticles are internalized by nodal macrophages, resulting in a decrease in signal intensity of healthy lymph nodes on contrast-enhanced T2*-weighted images [9] (Figs. 3A, 3B, 3C, 3D, 3E, and 3F). Therefore, intuitively, one would expect better nodal characterization on T2*-weighted images.

Although an overview of optimized imaging parameters for LNMRI was recently published [17], no published studies compare the performance of various sequences for nodal characterization. This article compares T2 fast spin-echo and GRE T2* sequences to determine which sequence provides better lymph node characterization on LNMRI. In addition, a comparison of GRE T2* sequences obtained with two different TE values evaluates the optimal TE for nodal characterization.

Our results show that T2*-weighted images have a higher accuracy in contrast-enhanced nodal characterization than do T2-weighted images (Table 1). Independent of reviewer experience, there is a statistically significant difference in nodal characterization of the two sequences with T2*-weighted sequences, demonstrating improved detection of metastatic nodal disease. This may be attributable to the fact that the T2*-weighted images are more sensitive to the susceptibility changes caused by intranodal ferumoxtran-10, allowing for the detection of small amounts of ferumoxtran-10 taken up by the healthy regions of partially infiltrated nodes. This makes smaller metastatic deposits easier to identify. However, T2* images did have a number of false-positives, particularly on the sequence with the shorter TE. The T2* sequence with the longer TE had fewer false-positives and, hence, a higher specificity. All of the nodes that were seen as false-positive on T2*-weighted images showed intranodal fibrosis on histopathologic examination (Figs. 4A and 4B). We postulate that fibrosis replaces healthy nodal cells, including intranodal macrophages, preventing ferumoxtran-10 uptake and mimicking nodal infiltration by metastatic tumor.


Figure 14
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Fig. 4A 59-year-old man with penile cancer. Unenhanced heavily T2*-weighted (A) and contrast-enhanced heavily T2*-weighted (B) images obtained with TE of 21 msec show two left inguinal lymph nodes (arrows, A). Contrast-enhanced image (B) shows a drop in signal intensity (arrows, B) compared with unenhanced image (A). This was interpreted as malignant nodal infiltration. Patient underwent inguinal lymphadenectomy, which revealed nodal fibrosis without any evidence of malignancy.

 

Figure 15
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Fig. 4B 59-year-old man with penile cancer. Unenhanced heavily T2*-weighted (A) and contrast-enhanced heavily T2*-weighted (B) images obtained with TE of 21 msec show two left inguinal lymph nodes (arrows, A). Contrast-enhanced image (B) shows a drop in signal intensity (arrows, B) compared with unenhanced image (A). This was interpreted as malignant nodal infiltration. Patient underwent inguinal lymphadenectomy, which revealed nodal fibrosis without any evidence of malignancy.

 


Figure 16
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Fig. 5A 58-year-old man patient with prostate cancer. Reprinted with permission from [17]. Contrast-enhanced T2* image obtained with shorter TE shows 4-mm left external iliac node with central heterogeneity (arrow), a finding that can be interpreted as representing malignant infiltration.

 


Figure 17
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Fig. 5B 58-year-old man patient with prostate cancer. Reprinted with permission from [17]. Contrast-enhanced heavily T2*-weighted image obtained at same time as A but with longer TE shows more homogeneous drop in signal intensity (arrow), which is consistent with benign node. This node was benign on pathologic analysis.

 
Although T2*-weighted sequences are sensitive to the susceptibility effects of ferumoxtran-10, the parameters used to acquire images influence the signal drop induced by intranodal accumulation of ferumoxtran-10 [17]. The TE must be long enough to adequately decrease the signal in a benign lymph node after it takes up the contrast. Our purpose in comparing the two TE values of 12.2 and 21 msec was to identify the optimal TE for ferumoxtran-10-enhanced T2* imaging. In our study, the experienced reviewer had a higher Az value on the more heavily T2*-weighted sequence, whereas the other reviewer had a higher Az value on T2*-weighted sequences obtained with a lower TE. Neither reviewer, however, had a statistically significant difference between the Az values for the two sequences. On comparing primary efficacy parameters, we saw that the shorter TE was more sensitive, whereas the longer TE was more specific. This may be because the longer TE detected even small concentrations of ferumoxtran-10 within nodes, hence identifying more true-negative nodes, but also had more false-negatives because metastases were missed in small nodes. This could be a result of blooming artifact caused by ferumoxtran-10 in the healthy nodal regions obscuring small metastases. However, the images with a TE of 12.2 msec had higher false-positives, indicating that in some benign nodes, the intranodal ferumoxtran-10 was not seen (Figs. 5A and 5B). Consequently, we recommend using dual-echo T2* sequences with nodal evaluation being based on assessment of images obtained with both TE values. This has the added advantage of allowing numeric estimation of the T2* value, which has the potential for semiautomated nodal cancer staging by imaging [20]. However, because of the drop in SNR on the higher TE value, it may not be possible to make anatomic distinctions, regardless of contrast. This may be the limiting factor to how much the TE can be increased.

The main limitation of our study was that the reviewers did not undertake nodal detection. Nodes that were unequivocally correlated with histology were marked out and shown to the reviewers. As mentioned before, T2* sequences have poor SNR. This may pose a problem in nodal detection, especially in anatomic locations where there may be significant artifact, such as close to bowel. Therefore, although GRE T2* sequences have the highest accuracy in characterizing nodes on LNMRI, fast spin-echo T2-weighted images may have an added value in detection and anatomic localization of nodes, which this study did not assess. Additionally, although learning bias was minimized by a time interval of 8 weeks between interpretation of various sequences, reviewers were presented with all images of one sequence first, followed by images from the other sequence, which may have introduced some bias at interpretation.

In conclusion, our results show that the GRE T2*-weighted sequences are superior for nodal characterization on LNMRI to fast spin-echo T2-weighted sequences. Imaging protocols for LNMRI should include fast spin-echo T2-weighted imaging for anatomic localization, but characterization of nodes should be based on their appearance on contrast-enhanced T2*-weighted images. The T2*-weighted images acquired with dual TE values, one of which is intermediate and the other longer, improve nodal characterization.


References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
 

  1. Jager GJ, Barentsz JO, Oosterhof GO, Witjes JA, Ruijs SJ. Pelvic adenopathy in prostatic and urinary bladder carcinoma: MR imaging with a three-dimensional TI-weighted magnetization-prepared-rapid gradient-echo sequence. AJR 1996;167 : 1503-1507[Abstract/Free Full Text]
  2. Bipat S, Glas AS, van der Velden J, Zwinderman AH, Bossuyt PM, Stoker J. Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol 2003; 91:59 -66[CrossRef][Medline]
  3. Tiguert R, Gheiler EL, Tefilli MV, et al. Lymph node size does not correlate with the presence of prostate cancer metastasis. Urology 1999; 53:367 -371[CrossRef][Medline]
  4. Borley N, Fabrin K, Sriprasad S, et al. Laparoscopic pelvic lymph node dissection allows significantly more accurate staging in "high-risk" prostate cancer compared to MRI or CT. Scand J Urol Nephrol 2003;37 : 382-386[CrossRef][Medline]
  5. Anzai Y, Blackwell KE, Hirschowitz SL, et al. Initial clinical experience with dextran-coated superparamagnetic iron oxide for detection of lymph node metastases in patients with head and neck cancer. Radiology 1994;192 : 709-715[Abstract/Free Full Text]
  6. Anzai Y, McLachlan S, Morris M, Saxton R, Lufkin RB. Dextran-coated superparamagnetic iron oxide, an MR contrast agent for assessing lymph nodes in the head and neck. Am J Neuroradiol1994; 15:87 -94[Abstract]
  7. Anzai Y, Piccoli CW, Outwater EK, et al. Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study. Radiology2003; 228:777 -788[Abstract/Free Full Text]
  8. Bellin MF, Roy C, Kinkel K, et al. Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide par ticles—initial clinical experience. Radiology 1998;207 : 799-808[Abstract/Free Full Text]
  9. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003; 348:2491 -2499[Abstract/Free Full Text]
  10. Harisinghani MG, Barentsz JO, Hahn PF, et al. MR lymphangiography for detection of minimal nodal disease in patients with prostate cancer. Acad Radiol 2002;9 [suppl 2]:S312 -S313
  11. Mack MG, Balzer JO, Straub R, Eichler K, Vogl TJ. Superparamagnetic iron oxide-enhanced MR imaging of head and neck lymph nodes. Radiology 2002;222 : 239-244[Abstract/Free Full Text]
  12. Michel SC, Keller TM, Frohlich JM, et al. Preoperative breast cancer staging: MR imaging of the axilla with ultrasmall superparamagnetic iron oxide enhancement. Radiology 2002;225 : 527-536[Abstract/Free Full Text]
  13. Nguyen BC, Stanford W, Thompson BH, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999; 10:468 -473[CrossRef][Medline]
  14. Rockall AG, Sohaib SA, Harisinghani MG, et al. Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer. J Clin Oncol 2005;23 : 2813-2821[Abstract/Free Full Text]
  15. Tabatabaei S, Harisinghani M, McDougal WS. Regional lymph node staging using lymphotropic nanoparticle enhanced magnetic resonance imaging with ferumoxtran-10 in patients with penile cancer. J Urol 2005; 174:923 -927; discussion 927[CrossRef][Medline]
  16. Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ. Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology1990; 175:494 -498[Abstract/Free Full Text]
  17. Harisinghani MG, Dixon WT, Saksena MA, et al. MR lymphangiography: imaging strategies to optimize the imaging of lymph nodes with ferumoxtran-10. RadioGraphics 2004;24 : 867-878[Abstract/Free Full Text]
  18. Stets C, Brandt S, Wallis F, Buchmann J, Gilbert FJ, Heywang-Kobrunner SH. Axillary lymph node metastases: a statistical analysis of various parameters in MRI with USPIO. J Magn Reson Imaging 2002; 16:60 -68[CrossRef][Medline]
  19. Koenig SH, Kellar KE. Theory of 1/T1 and 1/T2 NMRD profiles of solutions of magnetic nanoparticles. Magn Reson Med1995; 34:227 -233[Medline]
  20. Harisinghani MG, Weissleder R. Sensitive, noninvasive detection of lymph node metastases. PLoS Med 2004;1 : e66[CrossRef][Medline]
  21. Harisinghani MG, Saksena MA, Hahn PF, King B, Kim J, Torabi MT, Weissleder R. Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization? AJR 2006;186 : 144-148[Abstract/Free Full Text]

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