Indirect Computed Tomography Lymphography Research Articles

Dendrimer-Entrapped Gold Nanoparticles as Potential CT Contrast Agents for Localizing Sentinel Lymph Node via Indirect CT Lymphography on Rabbit Model.

Objective To investigate the potential use of indirect computed tomography lymphography (CT-LG) with dendrimer-entrapped gold nanoparticles (Au DENPs) in the localization and enhanced imaging of cervical sentinel lymph node (SLN) on rabbit model. Methods Twelve rabbits were randomly divided into two groups: the positive control group and the experimental group. In the control group, indirect CT-LG was performed with the injection of 0.5 ml activated carbon nanoparticles (ACNP) and Omnipaque mixture suspension in the right tongue submucosa. CT images were acquired before the injection and 1, 5, 10, and 15 min after the injection, respectively. In the experimental group, indirect CT-LG injection with 0.5 ml Au DENPs suspension was performed in the right tongue submucosa. CT images were obtained before the injection and 1, 5, 10, and 15 min and 1, 2, 6, 24, 48, and 72 h after the injection, respectively. Then, SLN identification and enhancement characteristics were evaluated. Results Indirect CT-LG revealed the enhancement of one right deep cervical lymph nodes in all animals, which was SLN. SLN location was marked with black color (ACNP dye) or purple-black color (Au DENPs dye). At each detection time point, the enhanced SLN attenuation values of control rabbits were statistically significantly higher than that of the plain scan, respectively (P < 0.05). Also the values of experimental rabbits were statistically significantly higher than that of the control at the same time point after injection (P < 0.05). The detection rate of SLN was 100%. Conclusions Indirect CT-LG with injection of Au DENPs as CT contrast agents can locate the SLN for a long period of time and enrich the SLN black dye. It is helpful for SLNs identification during the operation.

Enhanced CT imaging of human laryngeal squamous carcinoma and indirect CT lymphography imaging using PEGylated PAMAM G5·NH2-entrapped gold nanoparticles as contrast agent

Abstract We report the utilization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for enhanced computed tomography (CT) imaging of human laryngeal squamous carcinoma and indirect CT lymphography imaging in New Zealand rabbits. In this work, PEG-modified amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH2) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The formed PEGylated Au DENPs was used for both enhanced CT imaging of human laryngeal squamous carcinoma cells (Hep-2 cells) and the xenograft tumor mode, and indirect CT lymphography imaging in New Zealand rabbits. In vitro cytotoxicity assay, flow cytometry analysis, and cell morphology observation revealed that the formed PEGylated Au DENPs were non-cytotoxic at a Au concentration up to 400 μM for 24 h and indicated their good biocompatibility. Transmission electron microscopy data confirmed that the PEGylated Au DENPs was uptaken dominantly by the lysosomes of the cells. The PEGylated Au DENPs enabled not only enhance CT imaging of a xenograft tumor model in nude mice after intravenous injection of the particles, but also effective indirect CT lymphography imaging in rabbits. These findings suggest that the designed PEGylated Au DENPs can be used as a potentially effective contrast agent for CT imaging of various biological systems and different kinds of carcinoma, especially lymphatic mapping and human laryngeal squamous carcinoma.

Indirect computed tomography lymphography identifies lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.

Indirect computed tomography lymphography (CT-LG) could be used to determine the regional spread of cancer and assess lymphatic function by the interstitial delivery of diagnostic agents. Few studies have been reported on its use in pyriform sinus carcinoma. The aim of the present study was to establish the rabbit VX2 tumor as a model for pyriform sinus carcinoma and to observe its neck lymph node metastasis by indirect CT-LG. VX2 tumor tissue suspension was transplanted into the pyriform sinus submucosa of 15 rabbits under direct laryngoscope. Rabbits were randomly placed into one of three groups, each comprised of five rabbits. Observation of the tumor growth and neck lymph node metastases were taken on days 14 (group 1), 21 (group 2) and 28 (group 3) following transplantation using the method of indirect CT-LG. VX2 tumors were transplanted successfully in all rabbits. Deep cervical lymph nodes were enhanced clearly in indirect CT-LG. The contrast agent filling defected appeared on the metastasis nodes while the lymph node without metastasis was smooth. The metastasis rates of deep cervical lymph nodes were 100% in all three groups on CT-LG. The CT attenuation value of CT-LG reached peak values of 400 and 600 Hu at 1 and 3 min after the injection, which then decreased gradually. In this study, CT-LG could demonstrate the internal architecture of lymph nodes and their lymphatic vessels, and therefore may have the advantages of radiological methods such as B ultrasound, CT, magnetic resonance imaging and positron emission tomography.

Assessment of cervical lymph node metastases using indirect computed tomography lymphography with iopamidol in a tongue VX2 carcinoma model

To investigate the performance of indirect computed tomography lymphography with iopamidol for detecting cervical lymph node metastases in a tongue VX2 carcinoma model. A metastatic cervical lymph node model was created by implanting VX2 carcinoma suspension into the tongue submucosa of 21 rabbits. Computed tomography images were obtained 1, 3, 5, 10, 15 and 20 minutes after iopamidol injection, on days 11, 14, 21 (six rabbits each) and 28 (three rabbits) after carcinoma transplantation. Computed tomography lymphography was performed, and lymph node filling defects and enhancement characteristics evaluated. Indirect computed tomography lymphography revealed bilateral enhancement of cervical lymph nodes in all animals, except for one animal imaged on day 28. There was significantly slower evacuation of contrast in metastatic than non-metastatic nodes. A total of 41 enhanced lymph nodes displayed an oval or round shape, or local filling defects. One lymph node with an oval shape was metastatic (one of 11, 9.1 per cent), while 21 nodes with filling defects were metastatic (21/30, 70 per cent). The sensitivity, specificity, accuracy, and positive and negative predictive values when using a filling defect diameter of 1.5 mm as a diagnostic criterion were 86.4, 78.9, 82.9, 82.6 and 83.3 per cent, respectively. When using indirect computed tomography lymphography to detect metastatic lymph nodes, filling defects and slow evacuation of contrast agent are important diagnostic features.

Correlative study of indirect computed tomography lymphography using iopamidol and histopathology in a cervical lymph node metastasis model

To investigate the potential usefulness of indirect computed tomography lymphography (CT-LG) with iopamidol in the detection of cervical lymph node metastases in a VX2 rabbit tongue cancer model. Randomized controlled trial. Thirty-seven rabbits were randomly divided into control (n = 7) and tongue tumor-bearing (n = 30) groups. In the control group, indirect CT-LG was performed with 0.5- and 0.25-mL injections of iopamidol in the right and left tongue submucosa, respectively. In the tumor-bearing group, indirect CT-LG with 0.5 mL of iopamidol was performed on day 11 (n = 8), 14 (n = 8), 21 (n = 8), or 28 (n = 6) after carcinoma transplant. The correlation between indirect CT-LG and histopathology was investigated. In normal rabbits, oval or round enhanced cervical lymph nodes in each side of the neck were visualized by indirect CT-LG. In tumor-bearing rabbits, one enhanced lymph node on each side of the neck was visualized with or without filling defects in all rabbits except two on day 28 in which lymph nodes were not enhanced. The sensitivity, specificity, accuracy, and positive and negative predictive values for using filling defects on CT-LG as a diagnostic criterion were 77.4%, 77.8%, 77.6%, 80%, and 75%, respectively. Indirect CT-LG detected 84.6% of 2- to 6-mm intranodal tumor deposits. Indirect CT-LG may be useful for differentiating metastatic from nonmetastatic lymph nodes.

Localization of the sentinel lymph node in tongue VX2 carcinoma via indirect CT lymphography combined with methylene blue dye injection

Conclusions: Indirect computed tomography lymphography (CT-LG) combined with blue dye injection can locate the sentinel lymph node (SLN) in tongue carcinoma. Objective: To localize the SLN in tongue VX2 carcinoma using indirect CT-LG combined with methylene blue injection. Methods: Eighteen rabbits were placed into three groups: metastasis, hyperplasia, and control. Indirect CT-LG was performed with an iohexol injection into the tongue submucosa. CT images were acquired at 1, 5, and 15 min after injection. Methylene blue was injected into the same area 24 h after indirect CT-LG, followed by SLN identification and histopathological examination. Results: SLNs were visualized with an identification rate of 100%. SLN location identified using CT lymphography was confirmed by methylene blue dye. Control and hyperplastic enhanced SLNs were round or oval without any filling defects. Control rabbits had enhanced SLN attenuation values of 689.2 ± 55.4 HU, 278.4 ± 33.5 HU, and 71.7 ± 9.2 HU at 1, 5, and 15 min after injection, respectively. Hyperplastic rabbits had values of 877.4 ± 69.4 HU, 352.5 ± 43.3 HU, and 80.2 ± 11.5 HU. Filling defects were only observed in the ipsilateral metastatic SLNs of the metastasis group. CT attenuation values of the metastatic SLNs were 687.4 ± 55.6 HU, 535.1 ± 86.6 HU, and 282.3 ± 19.4 HU at 1, 5, and 15 min, respectively, after iohexol injection. Metastatic lymph node attenuation values were significantly greater than those of the control or hyperplastic nodes at 5 (p < 0.001) and 15 min (p < 0.001) after injection.

Visualization of breast lymphatic pathways with an indirect computed tomography lymphography using a nonionic monometric contrast medium iopamidol: preliminary results.

The capability of an indirect computed tomographic lymphography (CT-LG) using a nonionic monometric contrast medium iopamidol for visualizing breast lymphatic pathways was preliminarily tested. In 10 female dogs, a total of 0.5 and 1 mL of undiluted iopamidol was injected subcutaneously into the skin areas overlying the both caudal mammary glands. Contiguous 2-mm-thick multidetector raw helical CT images were obtained through the upper thorax and axilla before and during 60 minutes after gentle massage at the injection sites, with reconstruction into three-dimensional (3D) postcontrast CT images. The first lymph node (1st LN) directly draining from the injection sites was marked under CT guidance, followed by pre- and postmortem examinations. This CT-LG with 2-mL iopamidol was also attempted in five human female volunteers. Even with 0.5-mL iopamidol, the CT-LG clearly visualized the direct connection of the 1st LN and lymphatic vessels draining from the injection sites throughout the examination time in all the animals, with the maximum CT attenuation of 269 Hounsfield units (HU) +/- 137 in the 1st LN on the first postcontrast images. The topographic 3D images provided comprehensive anatomic outlines of these lymphatic pathways. Of the total of 20 opacified 1st LN and 110 distant nodes, all the 1st LN (100%) and 92 (83.6%) distant nodes could be resected at pre- or postmortem, with a good correlation with the CT images. The CT-LG also effectively localized the 1st LN with the maximum attenuation of 223 HU +/- 63 in the human volunteers, without any significant late adverse effects. Indirect CT-LG with iopamidol may have excellent potential for visualizing breast lymphatic drainage and for preoperative localization of breast sentinel lymph nodes.

Indirect computed tomography lymphography using iodinated nanoparticles to detect cancerous lymph nodes in a cutaneous melanoma model.

To evaluate differences in contrast uptake in normal and cancerous lymph nodes on indirect computed tomography (CT) in swine, we conducted lymphographic examinations after subcutaneous injection of a lymphotropic iodinated nanoparticle suspension. Perilesional subcutaneous contrast injections (2 ml per lesion) of a 15% wt/vol iodinated nanoparticle suspension were made in immature Sinclair miniature swine (n = 5) with cutaneous melanomas. Average attenuation, iodine concentration, node volume, and total iodine uptake were estimated on the CT scans for each opacified lymph node 24 hr after injection. Nodes were classified as normal or cancerous microscopically, and the percentage of tumor replacement was estimated in cancerous nodes. Average attenuation and iodine concentration were higher in normal nodes, and total iodine uptake was higher in cancerous nodes with greater than 25% replacement (p < .05). Architectural alterations in opacified cancerous nodes included medullary filling defects, expansile cortical lesions, and disruption of corticomedullary junctions. Quantitative and qualitative differences in iodinated nanoparticle enhancement characteristics are useful in distinguishing between normal and cancerous lymph nodes on indirect CT lymphography examinations.

Indirect computed tomography lymphography using iodinated nanoparticles: Time and dose response in normal canine lymph nodes

We evaluated the effect of time and dose on lymph node iodine uptake after subcutaneous or submucosal administration of iodinated nanoparticles used for computed tomography lymphography. We injected 0.1-6 ml of a 15% wt/vol iodinated nanoparticle suspension into the distal extremities subcutaneously (n = 5) or into the buccal submucosa (n = 7) of normal dogs. Precontrast and 4, 12, 24, and 48 hr after contrast administration, CT scans of opacified lymph nodes were obtained. Iodine concentration, node volume, and total iodine uptake were estimated for each node. All estimated parameters increased between 4 and 12 hr postcontrast (p < .05), with no significant increase thereafter. At 24 hr postcontrast, iodine concentration ranged from 0.01 to 16.1 mg/ml (47-568 Hounsfield units). The average iodine concentration and total iodine uptake increased with contrast dose (p < .05) for all lymph node groups evaluated. Node opacification also revealed internal architectural detail. Subcutaneous and submucosal injections of iodinated nanoparticles result in a dose-dependent iodine uptake in targeted lymph nodes. In addition, architectural detail within opacified nodes can be visualized.

Indirect computed tomography lymphography of subdiaphragmatic lymph nodes using iodinated nanoparticles in normal dogs

We evaluated the imaging characteristics of an iodinated particulate contrast agent for indirect computed tomography (CT) lymphography of normal subdiaphragmatic lymph nodes in dogs. Four milliliters of a 15% (wt/vol) iodinated nanoparticle suspension was injected into the gastric, colonic, rectal, or cervical submucosa, loose paraprostatic fascia, or metatarsal subcutaneous tissues in 10 healthy beagles. Endoscopic, CT, or ultrasound guidance was used when necessary to facilitate contrast agent delivery. CT and radiographic images were obtained prior to contrast administration and at 4 hr, 24 hr, and 7 days postcontrast injection. Postmortem examinations were then conducted. CT images showed enhancement of regional lymph nodes draining the various injection sites. The mean attenuation of opacified nodes was 678 +/- 463 Hounsfield units 24 hr after injection and remained elevated 7 days later. Lymph node opacification on CT images correlated well with the node location observed on postmortem examinations. Subdiaphragmatic lymph nodes can be effectively opacified using an iodinated nanoparticle contrast agent for indirect CT lymphography.

Iodinated Nanoparticles for Indirect Computed Tomography Lymphography of the Craniocervical and Thoracic Lymph Nodes in Normal Dogs

We evaluated the imaging characteristics of an interstitially or intraperitoneally delivered iodinated particulate contrast agent for computed tomography (CT) lymphography of the craniocervical and thoracic lymph nodes. We injected 2-4 ml of 15% wt/vol iodinated nanoparticle suspension subcutaneously, submucosally, or intraperitoneally in eight normal dogs. CT and plain radiographic images were obtained prior to contrast administration and 4 hr, 24 hr, and 7 days after injection. Correlation was made to detailed postmortem assessment. CT images showed enhancement of regional nodes draining injection sites. Mean attenuation of opacified nodes was 313 +/- 297 (mean +/- standard deviation), 536 +/- 453, and 492 +/- 372 Hounsfield units at 4 hr, 24 hr, and 7 days postinjection, respectively. Lymph node opacification on CT images correlated well with node location found at postmortem. Craniocervical and thoracic lymph nodes can be effectively opacified from interstitial or intraperitoneal delivery of this iodinated nanoparticulate contrast agent.