(Radiology. 2001;218:664-669.)
© RSNA, 2001
Interstitial MR Lymphography with a Conventional Extracellular Gadolinium-based Agent: Assessment in Rabbits1
Stefan G. Ruehm, MD,
Claire Corot, PhD and
Jörg F. Debatin, MD
1 From the Department of Diagnostic Radiology, University Hospital Zurich, Switzerland (S.G.R., J.F.D.); and Laboratoire Guerbet, Aulnay-sous-Bois, France (C.C.). Received April 27, 2000; revision requested June 12; revision received July 11; accepted August 7. Address correspondence to S.G.R., Department of Diagnostic Radiology, University Hospital Essen, Hufelandstrasse 55, D-45122 Essen, Germany (e-mail: stefan.ruehm@uni-essen.de).
 |
ABSTRACT
|
|---|
PURPOSE: To evaluate gadoterate meglumine as a contrast agent for interstitial magnetic resonance (MR) lymphography in combination with an adapted fast three-dimensional (3D) MR sequence.
MATERIALS AND METHODS: In 12 New Zealand White rabbits, 0.5 mL of undiluted gadoterate meglumine was injected subcutaneously into the dorsal foot pad (n = 9) or the foreleg (n = 3) bilaterally. Immediately after administration, a slight massage was performed at the injection site. Imaging was performed with a 3D spoiled gradient-recalled echo sequence (6.7/1.6 [repetition time msec/echo time msec]; field of view, 28.0 x 19.6; two signals acquired) similar to that used for 3D MR angiography. Thus, 3D maximum intensity projection images could be obtained. Images were obtained before injection and 5, 15, 30, 60, and 120 minutes after injection.
RESULTS: In the hind legs, as many as four successive lymph node groups were depicted with maximum enhancement after 5–15 minutes for the popliteal lymph node group, 15–30 minutes for the inguinal lymph group, and 30–60 minutes for the iliac-paraaortal lymph node group; the iliac-paraaortal lymph node group was not consistently enhanced. In the forelegs, four successive lymph node groups, including axillary and mediastinal lymph node groups, showed marked gadolinium uptake, with maximum enhancement 5–15 minutes after injection.
CONCLUSION: As a widely tested positive-enhancing T1 contrast agent with favorable safety features, gadoterate meglumine allows the depiction of three to four successive lymph node groups early after subcutaneous injection. With the sequence used, 3D MR lymphangiograms can be obtained.
Index terms: Animals, 99.129412, 99.12942, 99.12943, 99.91 • Gadolinium, 99.12943, 99.91 • Lymphatic system, MR, 99.129412, 99.12942, 99.12943, 99.91 • Magnetic resonance (MR), contrast enhancement, 99.12943 • Magnetic resonance (MR), contrast media, 99.12943
|
INTRODUCTION
|
|---|
Involvement of the lymphatic system by a malignancy harbors grave implications regarding prognosis and choice of therapy. Knowledge of the status of lymphatic vessels and nodes must thus be considered critical. Reflecting the small size and indistinct tissue properties of the lymphatic system, display of the lymphatic system requires contrast agents that can be delivered by using different routes.
Direct lymphography, usually performed with fluoroscopic guidance with iodinated contrast agents, permits enhancement of only those lymph nodes contained within the draining route of the cannulated vessel. Although it provides the highest accumulation of contrast agent in lymph nodes, the technique has been abandoned owing to its invasiveness, technical difficulties, and potential for side effects, including pulmonary embolism and local wound infection (1). Selected display of lymph nodes is also possible after intravenous administration of contrast agent. Authors of several studies (2–4) have described the use of superparamagnetic iron oxide particles and ultrasmall superparamagnetic iron oxide particles for systemic lymph node display in conjunction with magnetic resonance (MR) imaging. Results have been mixed, as accumulation of contrast agent in lymph nodes appears unreliable, and images depict many artifacts (2,4–7).
The contrast agent can be administered into the subcutaneous interstitium. Several MR imaging agents have been evaluated for this purpose, including superparamagnetic iron oxide particles (8,9); polymeric gadolinium compounds (gadopentetate dimeglumine–labeled polyglucose associated macrocomplex) (5); and perfluorinated lipophilic compounds, which form aggregates or micelles (10). All three compounds remain in the preclinical phase of development. In contrast to intravenously used paramagnetic gadolinium-based agents, their safety profile remains largely unknown.
The purpose of this study was to evaluate the performance of a conventional extracellular paramagnetic contrast agent, gadoterate meglumine (Dotarem; Laboratoire Guerbet, Aulnay-sous-Bois, France) as an interstitial agent for the depiction of regional lymph nodes with an adapted fast three-dimensional (3D) MR sequence.
|
MATERIALS AND METHODS
|
|---|
Contrast Agent
Gadoterate meglumine is a commercially available, extracellular, water-soluble paramagnetic contrast agent that is generally administered intravenously in a dose of as much as 0.3 mmol per kilogram of body weight for a host of different indications. The chelate structure of the macrocyclic gadolinium complex has been shown to be extremely stable (11). Gadoterate meglumine is not subject to being metabolized. These water-soluble agents are characterized by a favorable safety profile: anaphylactoid reactions are rare, and they are not nephrotoxic (12). The agent is inert even when extravasated: no substantial inflammatory reaction could be demonstrated when the agent was injected into the subcutaneous tissues of rats (13). The agent, therefore, offers a favorable safety potential with good tolerance for nonintravenous routes of administration, such as subcutaneous injections.
Experimental Design
Twelve mature female New Zealand White rabbits (weight, 3–4 kg; Central Biological Laboratory, Zurich, Switzerland) served as the animal model. The experiments were performed in accordance with all state regulations governing the performance of animal studies with use of full anesthesia with ketamine hydrochloride (0.6 mL/kg Ketasol-100; Gräub, Bern, Switzerland) and xylazine hydrochloride (0.2 mL/kg Rompun 2%; Bayer, Leverkusen, Germany).
A volume of 0.5 mL undiluted gadoterate meglumine (0.06–0.08 mmol/kg) was injected subcutaneously into the interdigital skin fold of either the dorsal aspect of both hind legs (n = 18) or of both forelegs (n = 6). The contrast agent injection depot was placed at the level of the metatarsal or metacarpal bones, respectively. Immediately after administration of the contrast agent, the injection site was gently massaged for about 30 seconds in all three of the animals with foreleg injections and six of those with hind-leg injections. The remaining three rabbits with hind-leg injections did not receive any massaging.
MR Imaging
All MR imaging was performed with a 1.5-T whole-body MR system (Signa EchoSpeed; GE Medical Systems, Milwaukee, Wis). To maximize signal-to-noise ratio, the rabbits were placed in a standard transmit-receive quadrature head coil for imaging.
To determine the anteroposterior extension of the 3D acquisition volume, 21 transverse 10-mm-thick two-dimensional gradient-recalled echo images were collected at 5-mm intervals through either the thorax and upper extremities or pelvis and lower extremities. On the basis of these images, a 3D acquisition volume with a section thickness of 1.4 mm was prescribed. The number of sections was individually adapted to ensure coverage of the entire territory of interest and ranged between 48 and 58. For the T1-weighted 3D spoiled gradient-recalled echo sequence, we used the following parameters: 6.7/1.5 (repetition time msec/echo time msec); inversion time, 28 msec; flip angle, 30°. Two signals were acquired. A 28.0 x 19.6-cm field of view combined with a 256 x 256 matrix rendered an in-plane spatial resolution of 1.1 x 0.8 mm. Zero interpolation improved the latter to 0.55 x 0.40 mm. Acquisition time for the 3D data set was 90–150 seconds. The 3D acquisition was obtained once prior to administration of the contrast agent, as well as successively 5, 15, 30, 60, and 120 minutes thereafter. Between acquisitions the examined rabbit remained in an unchanged position.
Data Analysis
To assess time dependency of accumulation of contrast agent in the different lymph node locations, the signal-to-noise ratio (SNR) was calculated: SNR = SIvessel/noise, where SI is signal intensity. Noise was defined as the SD of the signal intensity in a region of interest placed outside the rabbit. Regions of interest were placed on source images within the individual lymph nodes. To assess the degree of vascular enhancement, region-of-interest measurements were also performed in the inferior vena cava for hind-leg injections or the superior vena cava for foreleg injections. The region-of-interest size was adapted to encompass as much of the node or vessel depicted on an individual source image as possible. Regions of interest were placed by one author (S.G.R.). In regions with several individual lymph nodes, such as the inguinal and iliac regions, signal-to-noise ratio measurements were performed in those lymph nodes that showed most signal intensity enhancement in the successive 3D acquisitions (maximum intensity projection images). The source images obtained after injection of contrast agent facilitated identification of the nonenhanced lymph nodes or vessels on the images obtained before administration of contrast agent. Within the same animal, measurements were performed at identical locations.
Enhancement profiles of the different lymph node locations were compared. The effect of manual massage was determined on the basis of comparing enhancement profiles of the popliteal node group in animals with hind-leg injections with massage (n = 6) and animals with hind-leg injections without massage (n = 3). Enhancement profiles of massaged rabbits with hind-leg (n = 6) and foreleg injections (n = 3) were compared. Statistical analysis was based on a nonpaired Student t test by using a P value of .05 to denote statistical significance. In addition, enhancement of the bladder was visually inspected.
|
RESULTS
|
|---|
Administration of contrast agent resulted in depiction of as many as four successive lymph node groups. Although enhancement in the popliteal lymph node group was seen in all nine rabbits with hind-leg injections, the inguinal, iliac, and paraaortal lymph node groups were identified in only those six rabbits in which the injection site had been massaged (Fig 1). The administration of gadoterate meglumine into the forelegs revealed comparable findings: four successive lymph node groups, including anterior and posterior axillary, anterior thoracic, parasternal, and mediastinal, were depicted in all three examined rabbits (Fig 2).
View larger version (127K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1a. Anteroposterior 3D maximum intensity projection images (frontal view, rabbit placed in supine position) of the pelvis and hind legs of a rabbit were obtained (a) before, (b) 5 minutes after, and (c) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally, followed by a slight massage of the injection site. Images show enhancement of the distal (arrows in b) and proximal (arrowheads in b) popliteal lymph node groups, as well as the inguinal lymph node group (arrows in c) bilaterally. (d) Coronal reformatted image obtained 30 minutes after administration of contrast agent demonstrates homogeneous enhancement of the right iliac lymph node (arrow), which was obscured by contrast agent-filled bladder on 3D maximum intensity projection images (not shown).
|
|
View larger version (129K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1b. Anteroposterior 3D maximum intensity projection images (frontal view, rabbit placed in supine position) of the pelvis and hind legs of a rabbit were obtained (a) before, (b) 5 minutes after, and (c) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally, followed by a slight massage of the injection site. Images show enhancement of the distal (arrows in b) and proximal (arrowheads in b) popliteal lymph node groups, as well as the inguinal lymph node group (arrows in c) bilaterally. (d) Coronal reformatted image obtained 30 minutes after administration of contrast agent demonstrates homogeneous enhancement of the right iliac lymph node (arrow), which was obscured by contrast agent-filled bladder on 3D maximum intensity projection images (not shown).
|
|
View larger version (122K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1c. Anteroposterior 3D maximum intensity projection images (frontal view, rabbit placed in supine position) of the pelvis and hind legs of a rabbit were obtained (a) before, (b) 5 minutes after, and (c) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally, followed by a slight massage of the injection site. Images show enhancement of the distal (arrows in b) and proximal (arrowheads in b) popliteal lymph node groups, as well as the inguinal lymph node group (arrows in c) bilaterally. (d) Coronal reformatted image obtained 30 minutes after administration of contrast agent demonstrates homogeneous enhancement of the right iliac lymph node (arrow), which was obscured by contrast agent-filled bladder on 3D maximum intensity projection images (not shown).
|
|
View larger version (158K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1d. Anteroposterior 3D maximum intensity projection images (frontal view, rabbit placed in supine position) of the pelvis and hind legs of a rabbit were obtained (a) before, (b) 5 minutes after, and (c) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally, followed by a slight massage of the injection site. Images show enhancement of the distal (arrows in b) and proximal (arrowheads in b) popliteal lymph node groups, as well as the inguinal lymph node group (arrows in c) bilaterally. (d) Coronal reformatted image obtained 30 minutes after administration of contrast agent demonstrates homogeneous enhancement of the right iliac lymph node (arrow), which was obscured by contrast agent-filled bladder on 3D maximum intensity projection images (not shown).
|
|
View larger version (107K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2a. Anteroposterior 3D data acquisition images (frontal view, rabbit placed in prone position) centered on the forelegs and upper thorax of a rabbit (a) before and (b) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally in the dorsal aspect of the forepaw, followed by a slight massage of the injection site. The following lymph node groups are depicted in b: anterior (open arrows) and posterior (short solid arrows) axillary, anterior thoracic (arrowheads), parasternal (curved arrow), and mediastinal (long solid arrow). (c, d) Coronal reformatted images allow individual display of homogeneously enhanced anterior axillary lymph nodes (arrows in c) and bilateral anterior thoracic lymph nodes (arrowheads in d), with enhanced lymphatic vessels on the left side.
|
|
View larger version (113K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2b. Anteroposterior 3D data acquisition images (frontal view, rabbit placed in prone position) centered on the forelegs and upper thorax of a rabbit (a) before and (b) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally in the dorsal aspect of the forepaw, followed by a slight massage of the injection site. The following lymph node groups are depicted in b: anterior (open arrows) and posterior (short solid arrows) axillary, anterior thoracic (arrowheads), parasternal (curved arrow), and mediastinal (long solid arrow). (c, d) Coronal reformatted images allow individual display of homogeneously enhanced anterior axillary lymph nodes (arrows in c) and bilateral anterior thoracic lymph nodes (arrowheads in d), with enhanced lymphatic vessels on the left side.
|
|
View larger version (150K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2c. Anteroposterior 3D data acquisition images (frontal view, rabbit placed in prone position) centered on the forelegs and upper thorax of a rabbit (a) before and (b) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally in the dorsal aspect of the forepaw, followed by a slight massage of the injection site. The following lymph node groups are depicted in b: anterior (open arrows) and posterior (short solid arrows) axillary, anterior thoracic (arrowheads), parasternal (curved arrow), and mediastinal (long solid arrow). (c, d) Coronal reformatted images allow individual display of homogeneously enhanced anterior axillary lymph nodes (arrows in c) and bilateral anterior thoracic lymph nodes (arrowheads in d), with enhanced lymphatic vessels on the left side.
|
|
View larger version (158K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2d. Anteroposterior 3D data acquisition images (frontal view, rabbit placed in prone position) centered on the forelegs and upper thorax of a rabbit (a) before and (b) 15 minutes after subcutaneous administration of 0.5 mL of gadoterate meglumine bilaterally in the dorsal aspect of the forepaw, followed by a slight massage of the injection site. The following lymph node groups are depicted in b: anterior (open arrows) and posterior (short solid arrows) axillary, anterior thoracic (arrowheads), parasternal (curved arrow), and mediastinal (long solid arrow). (c, d) Coronal reformatted images allow individual display of homogeneously enhanced anterior axillary lymph nodes (arrows in c) and bilateral anterior thoracic lymph nodes (arrowheads in d), with enhanced lymphatic vessels on the left side.
|
|
Gadoterate meglumine was absorbed quickly into the lymphatic system. Figure 3 summarizes the time course of signal intensities measured in different lymph nodes representing drainage locations of the hind-leg injection site. Signal intensity measurements in the popliteal lymph node group reached a maximum as early as 5–15 minutes after subcutaneous injection, whereas signal intensities in the inguinal lymph node group reached a maximum after 15–30 minutes. The iliac-paraaortal lymph node group contained the most contrast agent 30 minutes after the interstitial injection (Fig 3).
View larger version (41K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3. Bar graph shows signal-to-noise ratio (SNR) for different lymph node groups in rabbits (n = 6) after subcutaneous injection of gadoterate meglumine into the hind legs bilaterally. The distal (dist.) popliteal lymph node group shows a signal intensity maximum as early as 5-15 minutes after injection, while signal intensities in the inguinal lymph node group reach a maximum after 15-30 minutes. The iliac-paraaortic lymph node group contained the most contrast agent 30 minutes after the interstitial injection. Error bars represent standard errors of the mean. Although it was intended to keep the experimental conditions as standardized as possible, the larger standard errors in the 5- and 15-minute data most likely reflect an inevitable variability with regard to injection of contrast agent, its distribution at the injection site, and differences in massaging intensity, which appear to be more pronounced in the early period after injection.
|
|
Comparison of the enhancement profiles in the proximal lymph node location in rabbits after hind-leg injections (Fig 4) with (n = 6) and without (n = 3) massaging of the injection site 5 and 15 minutes after injection of contrast agent revealed significantly more enhancement in the lymph nodes of massaged animals (P < .05). Comparison of the enhancement profiles of massaged animals receiving hind-leg (n = 6) and foreleg (n = 3) injections failed to demonstrate any statistically significant difference (P > .05).
View larger version (49K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4. Bar graph shows comparison of the enhancement profiles in the popliteal (popl.) lymph node location in rabbits after subcutaneous hind-leg injections with (n = 6) and without (n = 3) massage of the injection site. There is significantly more enhancement in the lymph nodes of massaged animals (P < .05). Error bars represent standard errors of the mean. SNR = signal-to-noise ratio.
|
|
Within 5 minutes after the injection, enhancement of the bladder was evident on the T1-weighted 3D images, which suggests a considerable degree of capillary absorption of the agent at the injection site or rapid drainage of the contrast agent via the lymphatic vessels into the venous system (Fig 1). The enhancement profile as determined with signal-to-noise ratio measurements in the vena cava over time reached an early peak at 5 minutes and showed a gradual decline over time (Fig 5). Nodal enhancement exceeded venous enhancement in the 15–30-minute time window.
View larger version (25K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5. Graph of enhancement profile over time as determined with signal-to-noise ratio (SNR) measurements in the vena cava shows an early peak at 5 minutes and a gradual decline over time. Error bars represent standard errors of the mean.
|
|
|
DISCUSSION
|
|---|
Assessment of the regional lymphatic system yields clinically important information for treatment planning and determination of prognosis in patients with various pathologic conditions, especially cancer (14). The results of this study indicate that gadoterate meglumine, a commercially available extracellular paramagnetic agent, drains to regional lymph nodes after subcutaneous administration. Gadoterate meglumine may thus be used as a positive enhancing contrast agent for interstitial MR lymphography.
As many as four successive lymph node groups in the hind legs and in the forelegs of rabbits showed marked contrast enhancement after the interstitial administration of 0.5 mL of contrast agent. In view of weight differences, the volume would need to be increased by a factor of 10–20 for human use. The resultant volume would still be acceptable for subcutaneous injection. The inertness of the agent, which has been shown to not cause any inflammatory reaction if extravasated into subcutaneous tissues in considerably larger volumes (13), underscores the safety of this concept. The addition of small amounts of a local anesthetic such as lidocaine would quell any associated pain sensation.
Use of a more concentrated gadolinium formulation (1 mol/L instead of 0.5 mol/L) such as gadobutrol (Gadovist; Schering, Erlangen, Germany) (15) would further facilitate the examination by decreasing the required volume of contrast agent by half. However, the sequence we used might require further reduction of repetition and echo times to avoid T2 shortening effects induced by the more highly concentrated contrast agent. In addition, further studies would need to be performed to verify if differences concerning viscosity, osmolality, and lipophilicity would possibly result in a different efficacy with regard to lymphatic uptake.
After the subcutaneous administration of paramagnetic contrast agent, the agent is absorbed by the lymphatic system. Lymph node enhancement reaches a peak around 5–15 minutes after administration of contrast agent; washout of the extracellular contrast agent is also quick, with signal intensities reaching almost baseline values within 2 hours after the injection. In the early phase, the enhancement of the proximal lymph nodes is rather homogeneous (Fig 6), whereas in the later phases (30–120 minutes) a heterogeneous pattern of nodal enhancement is present: washout is more evident in the periphery of the node, with the central portion revealing more enhancement.
View larger version (119K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6a. Coronal reformatted images of a right popliteal lymph node (arrows) (a) before, (b) 5 minutes after, and (c) 60 minutes after subcutaneous injection of gadoterate meglumine into the dorsal foot. Whereas the lymph node appears homogeneously enhanced in b, its appearance changes over time, with a more enhanced central portion in c.
|
|
View larger version (134K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6b. Coronal reformatted images of a right popliteal lymph node (arrows) (a) before, (b) 5 minutes after, and (c) 60 minutes after subcutaneous injection of gadoterate meglumine into the dorsal foot. Whereas the lymph node appears homogeneously enhanced in b, its appearance changes over time, with a more enhanced central portion in c.
|
|
View larger version (117K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6c. Coronal reformatted images of a right popliteal lymph node (arrows) (a) before, (b) 5 minutes after, and (c) 60 minutes after subcutaneous injection of gadoterate meglumine into the dorsal foot. Whereas the lymph node appears homogeneously enhanced in b, its appearance changes over time, with a more enhanced central portion in c.
|
|
Although no differences regarding the time course of lymphatic enhancement were evident between foreleg and hind-leg injections, massaging of the injection site proved critical for optimal enhancement of the lymphatic system. Signal intensity measurements in the popliteal lymph node group in three animals in which the injection site had not been massaged revealed significantly less enhancement (P < .05). Similar observations have been made with other subcutaneously administered agents (16,17). To our knowledge, the exact means of gadoterate meglumine uptake into the lymphatic system have not been examined. It is likely, however, that a combination of pressure, osmosis, and phagocytosis are responsible (18).
The quick appearance of contrast agent in the urinary bladder after 5 minutes (Fig 1) confirms a considerable degree of absorption of contrast agent through the capillary system at the injection site. At 60 minutes, enhancement of the popliteal node group was in the range of the enhancement of the vascular system at the same time (Figs 3, 5). Considerably less enhancement of the vascular system compared with that of lymph nodes at 15–30 minutes suggests a more continuous venous enhancement pattern (Fig 5).
The lymphatic system of the forelegs and of the hind legs was well depicted on the heavily T1-weighted 3D gradient-echo images. Characterized by a short repetition time, the sequence renders all tissues dark, except those containing a considerable amount of T1-shortening contrast agent. Beyond good background suppression, the short repetition and echo times inherent to the sequence used result in less sensitivity to susceptibility effects caused by the presence of highly concentrated contrast agent. The accumulated lymphatic gadolinium concentration was sufficient for select depiction of the lymph node groups (Figs 1, 2). Although gadoterate meglumine was administered in an undiluted fashion, there were no signal distortions due to T2-shortening effects, except at the administration site (Fig 1). Although the nodes were evident to best advantage on the individual source or reformatted images, maximum intensity projection images provided a comprehensive overview of the entire lymphatic system and depicted not merely nodal structures but also afferent and efferent lymphatic vessels.
Interstitial MR lymphography has been performed with other T1-enhancing contrast agents. Several of these agents have provided more favorable results with regard to duration, maximal signal intensity, and number of successive enhancing lymph node groups within the lymphatic system (5,10,19). Larger, protein-bound gadolinium compounds have fared particularly well. These agents, many of which are being developed for the prolonged enhancement of the vascular system (blood pool agents), have lymphotropic properties and are preferentially phagocytized (20). They do not penetrate the capillary membranes and are thus not absorbed by the vascular system. None of the agents, however, is commercially available.
Similar to other studies in which investigative iron-based (2,8,9) and T1-enhancing gadolinium-based lymphotropic contrast agent compounds (19) were used, this study did not attempt to differentiate metastatic from nonmetastatic lymph nodes. Reflecting the microstructural anatomy of the lymph node itself, which contains nonenhancing follicles largely devoid of macrophages and enhancing follicles with medullary sinuses (21), the detection of small metastases in lymph nodes can be challenging. The three-dimensionality inherent to the underlying gradient-echo data sets aids in the morphologic analysis of individual nodes. Beyond tumor imaging, interstitial MR lymphography may prove helpful in the assessment of a variety of other pathologic conditions, including peripheral lymphedema (22), regeneration of lymphatic vessels after transplantation of extremities, or characterization of postoperative fluid collections as lymphoceles.
Practical application: We conclude from the results of this study that gadoterate meglumine, a commercially available paramagnetic agent, may be used for display of proximal lymph nodes after interstitial injection of small volumes. With the outlined imaging strategy, 3D image sets can be obtained to demonstrate the regional lymphatic drainage. Further investigation is required to optimize dosage, assess the performance in the detection of lymph node metastases, and determine its efficacy in humans.
|
FOOTNOTES
|
|---|
Abbreviation: 3D = three-dimensional
Author contributions: Guarantors of integrity of entire study, S.G.R., J.F.D.; study concepts and design, S.G.R., C.C., J.F.D.; definition of intellectual content, S.G.R., J.F.D.; literature research, S.G.R., C.C.; experimental studies, S.G.R.; data acquisition, S.G.R.; data analysis, S.G.R., J.F.D.; statistical analysis, S.G.R.; manuscript preparation, S.G.R.; manuscript editing, S.G.R; manuscript review and final version approval, J.F.D.
|
REFERENCES
|
|---|
-
Witte CL, Williams WH, Witte MH. Lymphatic imaging (editorial). Lymphology 1993; 26:109-111.[Medline]
-
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]
-
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. Radiology 1990; 175:494-498.[Abstract/Free Full Text]
-
Wagner S, Pfefferer D, Ebert W, et al. Intravenous MR lymphography with superparamagnetic iron oxide particles: experimental studies in rats and rabbits. Eur Radiol 1995; 5:640-646.
-
Harika L, Weissleder R, Poss K, Zimmer C, Papisov MI, Brady TJ. MR lymphography with a lymphotropic T1-type MR contrast agent: Gd-DTPA-PGM. Magn Reson Med 1995; 33:88-92.[Medline]
-
Bengele HH, Palmacci S, Rogers J, Jung CW, Crenshaw J, Josephson L. Biodistribution of an ultrasmall superparamagnetic iron oxide colloid, BMS 180549, by different routes of administration. Magn Reson Imaging 1994; 12:433-442.[Medline]
-
Muhler A, Zhang X, Wang H, Lawaczeck R, Weinmann HJ. Investigation of mechanisms influencing the accumulation of ultrasmall superparamagnetic iron oxide particles in lymph nodes. Invest Radiol 1995; 30:98-103.[Medline]
-
Vassallo P, Matei C, Heston WD, McLachlan SJ, Koutcher JA, Castellino RA. Characterization of reactive versus tumor-bearing lymph nodes with interstitial magnetic resonance lymphography in an animal model. Invest Radiol 1995; 30:706-711.[Medline]
-
Taupitz M, Wagner S, Hamm B, Binder A, Pfefferer D. Interstitial MR lymphography with iron oxide particles: results in tumor-free and VX2 tumor-bearing rabbits. AJR Am J Roentgenol 1993; 161:193-200.[Abstract/Free Full Text]
-
Misselwitz B, Platzek J, Raduchel B, Oellinger JJ, Weinmann HJ. Gadofluorine 8: initial experience with a new contrast medium for interstitial MR lymphography. MAGMA 1999; 8:190-195.
-
Bousquet JC, Saini S, Stark DD, et al. Gd-DOTA: characterization of a new paramagnetic complex. Radiology 1988; 166:693-698.[Abstract/Free Full Text]
-
Bellin MF, Deray G, Assogba U, et al. Gd-DOTA: evaluation of its renal tolerance in patients with chronic renal failure. Magn Reson Imaging 1992; 10:115-118.[Medline]
-
Cohan RH, Leder RA, Herzberg AJ, et al. Extravascular toxicity of two magnetic resonance contrast agents: preliminary experience in the rat. Invest Radiol 1991; 26:224-226.[Medline]
-
Berek JS, Hacker NF, Fu YS, Sokale JR, Leuchter RC, Lagasse LD. Adenocarci-noma of the uterine cervix: histologic variables associated with lymph node metastasis and survival. Obstet Gynecol 1985; 65:46-52.[Abstract/Free Full Text]
-
Staks T, Schuhmann-Giampieri G, Frenzel T, Weinmann HJ, Lange L, Platzek J. Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers. Invest Radiol 1994; 29:709-715.[Medline]
-
Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev 1990; 70:987-1028.[Abstract/Free Full Text]
-
Wolf GL, Na GC, Gazelle GS, et al. Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo. Acad Radiol 1994; 1:358-363.[Medline]
-
Ikomi F, Hanna GK, Schmid-Schonbein GW. Mechanism of colloidal particle uptake into the lymphatic system: basic study with percutaneous lymphography. Radiology 1995; 196:107-113.[Abstract/Free Full Text]
-
Misselwitz B, Sachse A. Interstitial MR lymphography using Gd-carrying liposomes. Acta Radiol Suppl 1997; 412:51-55.[Medline]
-
Mohr U, Weissleder R. Lymph node diagnosis with imaging methods: an overview with special reference to recent developments in the area of MR contrast media. Z Lymphol 1996; 20:15-20[German].[Medline]
-
Lee AS, Weissleder R, Brady TJ, Wittenberg J. Lymph nodes: microstructural anatomy at MR imaging. Radiology 1991; 178:519-522.[Abstract/Free Full Text]
-
Gmeinwieser J, Lehner K, Golder W. Indirect lymphography: indications, technic, clinical results. ROFO Fortschr Geb Rontgenstr Nuklearmed 1988; 149:642-647.
This article has been cited by other articles:
|
|
|
|
 
S. K. Verma, D. G. Mitchell, D. Bergin, R. Mehta, S. Chopra, and D. Choi
The Cisterna Chyli: Enhancement on Delayed Phase MR Images after Intravenous Administration of Gadolinium Chelate
Radiology,
September 1, 2007;
244(3):
791 - 796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Lohrmann, E Foeldi, J-P Bartholomae, and M Langer
Gadoteridol for MR imaging of lymphatic vessels in lymphoedematous patients: initial experience after intracutaneous injection
Br. J. Radiol.,
July 1, 2007;
80(955):
569 - 573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lohrmann, E. Foeldi, O. Speck, and M. Langer
High-resolution MR lymphangiography in patients with primary and secondary lymphedema.
Am. J. Roentgenol.,
August 1, 2006;
187(2):
556 - 561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Misselwitz, J. Platzek, and H.-J. Weinmann
Early MR Lymphography with Gadofluorine M in Rabbits
Radiology,
June 1, 2004;
231(3):
682 - 688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Suga, Y. Yuan, M. Okada, N. Matsunaga, A. Tangoku, S. Yamamoto, and M. Oka
Breast Sentinel Lymph Node Mapping at CT Lymphography with Iopamidol: Preliminary Experience
Radiology,
February 1, 2004;
230(2):
543 - 552.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. U. Herborn, T. C. Lauenstein, F. M. Vogt, R. B. Lauffer, J. F. Debatin, and S. G. Ruehm
Interstitial MR Lymphography with MS-325: Characterization of Normal and Tumor-Invaded Lymph Nodes in a Rabbit Model
Am. J. Roentgenol.,
December 1, 2002;
179(6):
1567 - 1572.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Ruehm, T. Schroeder, and J. F. Debatin
Interstitial MR Lymphography with Gadoterate Meglumine: Initial Experience in Humans
Radiology,
September 1, 2001;
220(3):
816 - 821.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION
