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PubMed2000

Gastric lymphography and detection of sentinel nodes.

The lymphatic drainage system of the stomach was studied using lymphography with various dyes, and several major routes have been shown. Gastric lymph channels are multidirectional and form complex networks. We conducted a retrospective study to know the first site of metastasis from small gastric cancers by examining 89 cases with only one lymph node metastasis. The perigastric nodal area close to the primary tumor was the first site of metastasis in only 62% of the cases. N2 metastasis without N1 involvement was seen in 13%. In order to identify sentinel nodes for local resection of gastric cancer, a novel method needs to be developed.

Carbon↗
PubMed1999

Subcutaneous and intravenous delivery of diagnostic agents to the lymphatic system: applications in lymphoscintigraphy and indirect lymphography.

Lymph node status is important in the staging of many malignancies. Although tissue characterization by histologic analysis of biopsy samples may improve staging, noninvasive staging is more acceptable to both patients and clinicians. Several imaging techniques may serve this goal. Modern noninvasive techniques such as computed tomography and magnetic resonance detect lymph node abnormality by nodal enlargement, but that does not always imply malignant involvement. On the other hand, many nodes are infiltrated or replaced by tumour without change in size. This becomes a serious diagnostic defect by these modalities. Consequently, attention has been focused to develop contrast agents and radiolabelled complexes for better cancer detection as well as characterization of individual tumours in lymph nodes. For delivery of such materials to regional lymph nodes one can take advantage from the distinct physiological function of the lymphatic capillaries. The thin-walled and fenestrated lymphatic microvessel is easily penetrated by particulate and macromolecular agents after injection into the extracellular space. Once inside the vessel, materials that are transported with the lymph either specifically target certain nodal elements (e.g. neoplastic cells) or become cleared by macrophages located in the lymph nodes. Indeed, interstitial delivery of diagnostic agents have been of benefit in determining regional spread of cancer and assessing lymphatic function either by lymphoscintigraphy or indirect lymphography. On the other hand, development of contrast materials that can reach lymph nodes after a single intravenous injection is highly desirable because of the large number of lymph nodes in the body and access being difficult to most of them. Today, a number of contrast agents exist that can reach a vast array of lymph nodes in the body, particularly those that are not readily accessible for histologic evaluation, after a single intravascular injection to help distinguish between normal and tumour-bearing nodes or reactive and metastatic nodes with magnetic resonance. In this article we critically examine advantages and limitations of both subcutaneous and intravenous routes of injection for the delivery of diagnostic agents to the lymphatic system.

Journal Article↗
PubMed1996

Magnetic resonance lymphography in rats: effects of muscular activity and hyperthermia on the lymph node uptake of intravenously injected superparamagnetic iron oxide particles.

RATIONALE AND OBJECTIVES: We investigated the influence of muscular activity and regional body temperature changes on the accumulation of intravenously (i.v.) administered, dextran-coated superparamagnetic iron oxide (SPIO) particles in the lymph nodes of rats. METHODS: Four groups of rats (N = 21) were used. Five rats were allowed to move freely after i.v. contrast administration (group 1). In another five rats, muscular inactivity (group 2) was induced during i.v. injection of SPIO particles and for up to 2 hr thereafter by anesthesia. In seven rats (likewise anesthetized), the contrast agent was administered while the extremities of one side of the body were warmed in a water bath for 2 hr (group 3). The rats in groups 1-3 received 100 mumol Fe/kg of the contrast agent. Four rats not given SPIO particles served as the control group (group 4). The lymph nodes of all animals were removed 24 hr after SPIO administration and were embedded in an agar matrix for magnetic resonance imaging at 1.5 T using a proton-density-weighted spin-echo (PD-SE) sequence and a T2*-weighted gradient-recalled echo (T2* GRE) sequence. RESULTS: Signal loss varied widely among the different lymph nodes in group 1. A pronounced signal reduction was observed in the mesenteric (PD-SE = 20 +/- 6%, T2* GRE = 55 +/- 19%), iliac (PD-SE = 13 +/- 13%, T2* GRE = 44 +/- 24%), and popliteal (PD-SE = 24 +/- 7%, T2* GRE = 70 +/- 11%) lymph nodes and only a moderate reduction in the mandibular (PD-SE = 4 +/- 7%, T2* GRE = 42 +/- 15%), axillary (PD-SE = 0 +/- 4%, T2* GRE = 8 +/- 7%), and inguinal (PD-SE = 5 +/- 5%, T2* GRE = 34 +/- 18%) lymph nodes. The least pronounced signal loss occurred in the peripheral lymph nodes of group 2, ranging from 0 +/- 3% for PD-SE sequences and 10 +/- 11% for T2* GRE sequences to 13 +/- 15% for PD-SE sequences and 41 +/- 19% for T2* GRE sequences. In group 3, the uptake of contrast material in the peripheral lymph nodes of the hyperthermal side was significantly more pronounced than on the contralateral side (p < .01), and the contrast agent was distributed more evenly to the different lymph node groups than in group 1. CONCLUSION: Muscular activity and regional hyperthermia markedly influence the accumulation of SPIO particles in different lymph node groups in rats. These findings must be considered in preclinical studies and in the clinical administration of MR lymphography.

Anesthesia↗
PubMed2005

Breast sentinel lymph node navigation with three-dimensional interstitial multidetector-row computed tomographic lymphography.

OBJECTIVE: Three-dimensional multidetector-row computed tomographic lymphography (3D MDCT-LG) with interstitial injection of a widely available nonionic monometric contrast medium iopamidol was used for navigation of breast sentinel lymph node (SLN) biopsy. METHODS: 3D MDCT-LG was obtained after massage of the interstitially injection sites of a total of 4-5 mL undiluted iopamidol at periareolar and peritumoral areas in 68 consecutive patients with early-stage breast cancer, using a 4 detector-row CT scanner. Drainage lymphatic patterns and SLN anatomy were assessed on 3D MDCT-LG images. 3D MDCT-LG-navigated SLN biopsy with combined use of blue dye was followed by backup axillary lymph node dissection to evaluate accuracy of SLN biopsy. RESULTS: The 3D MDCT-LG images clearly localized primary SLNs by visualizing the direct connection between these nodes and their afferent lymphatic vessels on detailed anatomy of the surrounding structures in all patients. Drainage lymphatic pathways on these images were classified into 4 patterns: single route/single SLN (39 cases, 57%), multiple routes/multiple SLNs (10 cases, 15%), single route/multiple SLNs (9 cases, 13%), and multiple routes/single SLN (10 cases, 15%). Under 3D MDCT-LG navigation, SLNs was found at the accurate location in all patients. With backup axillary lymph node dissection, metastasis was found in 14 (20%) patients, and 8 of these patients had metastasis only in the preoperatively identified SLNs. In other 5 positive patients, metastasis was found both in the SLN and non-SLNs. However, micrometastasis eventually was found only in non-SLN in an elderly patient. Overall, the sensitivity, false-negative rate, and accuracy of 3D CT-L-navigated SLN biopsy were 92% (13/14 patients), 7% (1/14 patients), and 98% (67/68 patients), respectively. CONCLUSIONS: Topographic 3D interstitial MDCT-LG can be a widely available and reliable navigator for breast SLN biopsy.

Adult↗
PubMed1994

AMI-227-enhanced MR lymphography: usefulness for differentiating reactive from tumor-bearing lymph nodes.

PURPOSE: To determine the value of magnetic resonance (MR) lymphography enhanced with AMI-227, a superparamagnetic reticuloendothelial-system-specific contrast agent, to distinguish normal and reactive from tumor-bearing lymph nodes. MATERIALS AND METHODS: Mature male Copenhagen rats were inoculated with cell suspensions of R3327-MATLyLu rat prostate carcinoma (n = 16) or Complete Freund Adjuvant (n = 15) to generate ipsilateral popliteal lymph node metastases or lymphadenitis. At 12-14 days after inoculation, T1- and T2-weighted MR images of bilateral popliteal areas were obtained before and 24 hours after administration of AMI-227 (dose, 30 mumol Fe/kg). The contralateral popliteal nodes served as controls. Contrast-to-noise ratios (C/Ns) between the nodes and adjacent muscle were calculated in pre- and postcontrast images. Subsequently, bilateral popliteal nodes were excised. RESULTS: AMI-227 resulted in decreased C/N in reactive nodes (T1-weighted, -186% +/- 90% [standard deviation]; T2-weighted, -205% +/- 96%) and normal nodes (n = 7) (T1-weighted, -306% +/- 82; T2-weighted, -350% +/- 96). C/N remained unchanged or increased (T1-weighted, 88% +/- 92; T2-weighted, 306% +/- 256) (P < .05). CONCLUSION: Differences in AMI-227 uptake at MR imaging may help differentiate tumor-bearing from nontumor-bearing nodes.

Animals↗
PubMed1999

Thoracic duct: visualization at nonenhanced MR lymphography--initial experience.

In six healthy volunteers, the thoracic duct was examined at magnetic resonance (MR) lymphography without contrast agent. With a 1.5-T clinical imager, a short echo spacing, three-dimensional, half-Fourier fast spin-echo sequence with electrocardiographic gating was employed to depict the thoracic duct along the thoracic aorta. The images clearly depicted the main duct in the region of the thoracic aorta in all six volunteers, drainage into the left subclavian region in four, and the cisterna chyli in one.

Adult↗
PubMed2001

Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits.

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.

Animals↗
PubMed1994

MR lymphography with superparamagnetic iron nanoparticles in rats: pathologic basis for contrast enhancement.

OBJECTIVE: The purpose of this study in rodents was to determine the pathologic basis for enhancement patterns of hyperplastic and tumours lymph nodes shown by MR lymphography after IV injection of superparamagnetic iron oxide nanoparticles (AMI-227). MATERIALS AND METHODS: Hyperplastic and tumorous lymph nodes were imaged in vivo at 1.5 T 1 day after IV administration of AMI-227 (40-200 mumol Fe/kg) to rats. Inguinal and axillary lymph nodes were surgically resected, and in vitro imaging was done by using the same magnet with a prototype coil that allowed a pixel size of 70 x 230 microns. Imaging findings were correlated with histologic findings and iron staining of the nodes. RESULTS: With all sequences, at doses of 80 mumol Fe/kg or higher, the signal intensity of hyperplastic nodes was lower than on unenhanced images. The same pattern was seen in the remaining normal tissue of tumourous lymph nodes. This T2* effect was a result of clustered particles inside macrophages in the lymphatic sinuses. At doses of 200 mumol/kg, the tumor itself consistently showed an increase in signal intensity on T1-weighted images. This T1 effect probably resulted from particles leaking into the interstitial spaces of the tumor. CONCLUSION: After IV injection of superparamagnetic nanoparticles, a decrease in signal intensity indicates active uptake of particles into macrophages, whereas an increase in signal intensity indicates altered capillary permeability in tumor. These findings in rats may prove to be clinically useful in the future for differentiating benign from malignant enlarged lymph nodes.

Animals↗
PubMed2002

Interstitial MR lymphography with MS-325: characterization of normal and tumor-invaded lymph nodes in a rabbit model.

OBJECTIVE: The aim of our study was to evaluate the performance of a new blood-pool contrast agent, MS-325, in depicting regional lymph nodes when injected interstitially and in allowing the subsequent classification of the lymph nodes as normal or tumor-bearing (VX2 tumor). MATERIALS AND METHODS: Six New Zealand white rabbits underwent adapted fast three-dimensional (3D) MR imaging before implantation of VX2 tumor cells in the flank and again 3 weeks after the implantation. For each imaging session, 0.5 mL of undiluted MS-325 was injected subcutaneously into both dorsal foot pads. For more than 120 min, the rabbits underwent repeated 3D MR imaging. The size of the individual lymph nodes and the amount of contrast agent uptake in the nodes were measured 5, 10, 15, 30, 60, and 120 min after the injection. After the rabbits had been sacrificed, their lymph nodes were removed and histopathologically analyzed. RESULTS. In normal as well as tumor-bearing hindlegs, the subcutaneous administration of MS-325 resulted in rapid delineation of popliteal, inguinal, iliac, and paraaortal lymph nodes. Tumor invasion into lymph nodes presented as circumscribed signal voids in the areas infiltrated by tumor, whereas the surrounding residual lymphatic tissue showed enhancement identical to that of normal nodes. CONCLUSION: In addition to providing a safe means of displaying the normal lymphatic system, MS-325-enhanced 3D MR lymphography depicts direct tumor invasion in lymph nodes.

Animals↗
PubMed2004

Model to quantify lymph node enhancement on indirect sonographic lymphography.

OBJECTIVE: Our goal was to develop a reliable technique that has minimal operator dependence for quantifying lymph node enhancement to test and optimize new sonography contrast formulations. MATERIALS AND METHODS: Twenty healthy rabbits were studied using five agents, labeled A-G. Agents D and E were the same agent and agents F and G were Imagent, studied blindly to test reproducibility. One milliliter of contrast agent was injected into each hind footpad. A 13-MHz transducer was fixed over the popliteal node, which was imaged at a 4.8-MHz central transmit frequency using phase-inversion technology at 100% power and one frame per second. Immediately after each injection, the footpad was massaged 12 times for 30 sec each time and then imaged after each massage to assess the number of times the node could be refilled from each injection. Lymph node video intensity was measured, and the degree of enhancement was evaluated using analysis of variance with the massage number and the agent used as independent variables. RESULTS: Lymph node enhancement was observed after the first massage with all agents. Degree of enhancement was least with agents A and B, intermediate with agents D and F, and greatest with agent C. Agent A was effective after the first two massages, agent B after the first four, agent C after all 12, agent D after the first eight, and agent F after the first nine. Performance of agents D and F was similar to that of their duplicates, E and G. CONCLUSION: We established a reproducible technique to quantify lymph node enhancement that can distinguish between different agents. The differences in performance suggest that it is possible to optimize agent formulation for indirect sonographic lymphography.

Analysis of Variance↗
PubMed2003

Visualization of normal and interrupted lymphatic drainage in dog legs with interstitial MR lymphography using an extracellular MR contrast agent, gadopentetate dimeglumine.

PURPOSE: The capability of the interstitial magnetic resonance lymphography (MR-LG) using a widely available extracellular contrast agent, gadopentetate dimeglumine, for the visualization of normal and interrupted lymphatic drainage was tested in dog legs. MATERIALS AND METHODS: With a 7-day interval, 1 mL and 2 mL undiluted gadopentetate dimeglumine were injected intradermally into the dorsal foot of both hind legs of 12 dogs. T1-weighted 3-dimensional (3D) spoiled gradient-echo (repetition time/echo time = 6.7/1.6 ms) and maximum intensity projection (MIP) images covering the legs and pelvic region were acquired at 1.5 T for 10 minutes after 30 seconds gentle massage at the injection sites. These dogs also underwent the MR-LG with 2 mL of this contrast agent 7 days after surgical ligation of the popliteal lymphatic vessels. RESULTS: In the normal dogs, the interstitial MR-LG quickly and consistently visualized the direct connection of the lymphatic vessels and lymph nodes draining from the injection sites up to the inguinal region, without any late adverse effects. The enhancement effect was significantly greater with a 2-mL dose than with a 1-mL dose. After lymphatic obstruction, the MR-LG clearly revealed the anatomic compromises of the lymphatics, such as poor enhancement of the affected lymphatic vessels and lymph nodes, collateral lymphatic vessels, abnormal soft-tissue enhancement, and delayed lymphatic migration of the contrast agent. The topographic 3D images provided a comprehensive anatomy of these normal and compromised lymphatic drainage. CONCLUSION: Although gadopentetate dimeglumine is not lymphotropic, the interstitial MR-LG using this T1-contrast agent appears to have potential for quick and sufficient mapping of the lymphatic drainage from the injection sites and for the characterization of interrupted lymph flow.

Animals↗
PubMed1990

[A preliminary study on MR lymphography with iron chondroitin sulfate colloid].

We investigated MR lymphography with iron chondroitin sulfate colloid, which was an intravenous agent for iron deficiency anemia. MR images (SE350/30) of the medial iliac lymph nodes were obtained before and after subcutaneous++ injection of this agent (2 mg Fe) on dorsal hindfeet bilaterally in five rabbits (3.0 kg weight). Signal intensities of the nodes were increased 5-15 minutes after the injection and the nodes were clearly identified in three of them. In the other two, increase in the signal intensity was not shown and any nodes could not be detected macroscopically at the investigated region on dissection. These results indicated the possibility of positive contrast enhancement of lymph nodes on MR imaging using iron colloid.

Animals↗
PubMed1989

[Cytopuncture of lymph nodes opacified by lymphography in the pretreatment evaluation of prostatic cancer].

Fine needle aspiration of iliac lymph nodes after lymphography was performed in nineteen patients with prostatic carcinoma, ranging from stage A to C. In four patients (21%), fine needle aspiration showed lymph node dissemination. 3 patients were classified as stage B, and 1 as stage C before aspiration. In this study, fine needle aspiration biopsy proved to be useful in the staging of prostatic carcinoma.

Aged↗
PubMed1987

[Indirect radionuclide lymphography in the evaluation of the completeness of iliac lymphadenectomy and the diagnosis of postoperative lymphatic cysts in uterine cancer].

Indirect radionuclide lymphography was performed in 152 women in the next 1-2 weeks after operation on the iliac lymph nodes. In 136 of them a radiopharmaceutical (198Au-colloid, 113mIn-coind, 113mIn-coinol) was accumulated in the inguinofemoral lymph nodes only, being in favor of radical iliac lymphadenectomy. X-ray lymphographic control confirmed in all cases that the iliac lymph nodes had been completely removed. Lymphatic cysts were detected in 16 out of 152 patients and verified in all the cases. Thus radiolymphography is indicated in early terms after lymphadenectomy for the assessment of its efficacy and diagnosis of lymphatic cysts.

Colloids↗
PubMed1987

[Lymphography with lymph node puncture biopsy. A reliable procedure for assessing the lymphatic spread of bladder tumors].

119 patients with bladder tumors of category Ta, Tis, T4, considered for radical treatment because of local conditions were studied by pedal lymphography (LAG) and percutaneous fine needle aspiration biopsy (FNA). 41% had a positive LAG. Adequate material was obtained for FNA in 94% of the patients. Of 70 patients with normal LAG none had a positive FNA; only 36% of those with a positive LAG had a positive FN. The high rate of positive LAG with negative FNA is attributed to inflammatory changes due to previous transurethral resection. Radical lymphadenectomy (LND) was done in 64 patients of whom 54 had a negative FNA. In this group, 8 (17%) had a positive LND. There was no mortality and morbidity was mild. LAG with FNA has a role in the pre-operative staging of bladder carcinoma.

Aged↗
PubMed1980

[Lymphoedema of the upper limb following surgery or radiotherapy. Investigation by indirect radioactive lymphography (author's transl)].

Indirect radioactive isotope lymphography using intravenous 99 m Tc-labelled colloidal antimony sulfide was performed on 76 patients with lymphoedema of the upper limb consecutive to surgery or radiotherapy. The time required to reach 50% of maximum radioactivity was taken as index of the lymphatic flow rate, and the patients were divided into 3 groups depending upon the index (< 20 min; 20-60 min; > 60 min). It appears that in huge lymphoedemas the lymphatic flow rate index may remain subnormal, owing to associated veno-occlusive oedema. This non-invasive method provides data on the site and, frequently, on the nature and importance of lymph blockade. It might also help to predict the efficacy of a new drug currently under study.

Arm↗
PubMedDate not supplied

[Radioisotope lymphography. Methods].

Radio-isotopic lymphography is based on lymphatic transport and reticulo-endothelial colloidopexy. Colloid is injected subcutaneously in a dose of 125 microcuries, at the level of the first interdigital space of both feet. The gamma emission sent out by this tracer is detected by seintillation probes, amplified, collected by a system of discrimination and fed to an integrator or a scaler. A functional specification is thus obtained of the accumulation of particles in the inguinal glands, expressed as a percentage of the initial activity in the foot, and set out graphically as a function of time, while at the same time a morphological examination of the groups of glands visualised by scintigraphy can be carried out.

Gold Colloid, Radioactive↗