Opportunistic bacterial infections in breeding colonies of the NSG mouse strain.

Spontaneous morbidity primarily affecting female breeders in 3 independent breeding colonies of NSG (NOD.Cg-Prkdc(scid) I12rg(tm1Wjl) /SzJ) mice prompted an investigation to uncover the cause of disease. Necropsies were performed on 264 (157 female and 107 male) spontaneously sick, experimentally unmanipulated NSG mice. In sum, 42 mice (15.9%) had acute or chronic renal inflammatory lesions, of which 12 had concurrent histologic evidence of an ascending urinary tract infection. From 94 kidneys cultured for bacterial organisms, 23 (24.5%) grew Enterococcus sp and 19 (20.2%) grew Klebsiella oxytoca. Female mice were twice more likely than males to present with nephritis. These findings indicate that bacterial nephritis is a major contributor to morbidity in the NSG strain.

Cyclin D3 expression in normal fetal, normal adult and neoplastic feline tissue.

Cyclin D3 is a tightly regulated cell cycle protein and member of the cyclin D family-a group of proteins that facilitates the progression of a cell through G(1) and into the S phase of the cell cycle. All cells use at least one of the cyclin D proteins for cell cycle regulation. In this study, feline tissues (normal fetal and adult, and neoplastic) were examined immunohistochemically for expression and topographical distribution of cyclin D3. Its distribution was similar to that in human tissues in health and neoplasia, and suggested a dual role of cyclin D3 in cell proliferation and differentiation. Immature lymphoid tissue and proliferating epithelial cells in health and neoplasia were immunoreactive for cyclin D3, whereas expression of the protein in other immunoreactive tissues reflected differentiated cell types. Immunoreactivity for cyclin D3 was particularly striking in germinal centre cells of normal lymph nodes and B-cell lymphomas, and in normal suprabasal epithelial cells of the skin and mucous membranes of the oropharynx and in squamous cell carcinomas at these sites.

CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice.

Immunocompromised mice that can support a human immune system are an increasingly important model for the investigation of haemopoietic stem/progenitor cell (HSPC) development and human infectious disease. NOD-SCID IL-2Rγ(-/-) (NSG) mice engrafted with human fetal liver and thymus prior to HSPC engraftment, commonly known as NSG-bone marrow-liver-thymus (NSG-hu-BLT) mice, are one such model and have robust reconstitution of human leucocytes within the peripheral blood and tissues. Four NSG-hu-BLT mice were submitted for diagnostic necropsy examination following the development of alopecia, pruritus and lethargy after HSPC engraftment. Histopathology revealed multifocal to coalescing single keratinocyte cell death in the epidermis and follicles with dermatitis and mild dermal fibrosis. Single-cell hepatocyte cell death was present in three cases, with various degrees of portal fibrosis. In the skin and liver, cell death was associated with lymphocytes that reacted with anti-human CD45, CD3 and CD8 antibodies, consistent with a diagnosis of graft-versus-host disease (GvHD). This study expands on recently reported microscopical features of GvHD in NSG-hu-BLT mice and suggests a role for CD8(+) T lymphocytes in the progression of the disease. NSG-hu-BLT mice represent an excellent model of GvHD, but its prevalence may compromise their use in other fields of biomedical research.

Effects of leflunomide and cyclosporine on myocutaneous allograft survival in the rat.

The immunosuppressive effects of leflunomide and cyclosporine were evaluated in a rat neurovascularized myocutaneous allograft model. Inbred Brown-Norway and Lewis rats were served as donors and recipients, respectively. All recipients were observed for 60 days or until allograft rejection occurred. All isograft controls (Lewis to Lewis, n=6) survived uneventfully. All control allografts (n=6) were rejected within 6 days. Allograft recipients (n=6) administered leflunomide (10 mg/kg/24 hr) rejected their allografts in 28.50+/-6.12 days, and allograft recipients (n=6), administered cyclosporine (5 mg/kg/24 hr) rejected their allografts in 24.33+/-10.48 days. When allograft recipients were administered a combination of leflunomide and cyclosporine (10 mg/kg/24 hr and 5 mg/kg/24 hr, respectively), all allografts survived to 60 days with only partial rejection of the skin of one graft. The neuromuscular function of the allografts of the rats receiving combination therapy was comparable to that of the isografts. The combination of leflunomide and cyclosporine controlled myocutaneous allorejection despite a strong immunological challenge.

Fluvastatin in combination with rad significantly reduces graft vascular disease in rat cardiac allografts.

BACKGROUND: RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. METHODS: Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. RESULTS: Rats treated with fluvastatin, at either dose, had a significant (P< or =0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22% reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. CONCLUSIONS: Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.

Combination leflunomide and cyclosporine prevents rejection of functional whole limb allografts in the rat.

Whole rear limbs were transplanted from Brown Norway or Lewis rat donors to Lewis rat recipients (n=6 per group). One group of allograft recipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclosporine (5 mg/kg24 hr/orally) starting 2 days before to surgery. Treatment continued for 60 days or until graft rejection. Untreated allografts were rejected over 6-8 days. After isograft transplantation, weight bearing began by day 17-25 after surgery. Sensory function was restored by 50 days after surgery. All allografts in the drug-treated group survived the 60-day period; survival in this group was significantly longer (P=0.0001) than the untreated controls. Weight bearing began by day 30, but was incomplete in two rats at 60 days. Peroneal nerve function was present in half the rats at 60 days after surgery. Leflunomide combined with cyclosporine prevented whole limb allograft rejection across a major histocompatibility barrier.

Analysis of the equine tumor suppressor gene p53 in the normal horse and in eight cutaneous squamous cell carcinomas.

Wild type equine p53 was amplified between exons 2 and 9 by the polymerase chain reaction using primers designed from conserved regions in other species. An 828 base pair region, corresponding to codons 25-313 of human p53, was sequenced in both directions. Human and equine amino acid sequences were 87% homologous in this region and 96% homologous in conserved domains II-V. Of eight equine cutaneous or mucocutaneous squamous cell carcinomas directly sequenced from exons 5-8, two had p53 point mutations resulting in single amino acid substitutions.

K-ras mutations in 239PuO2 canine lung neoplasms.

Single-strand conformational polymorphism (SSCP) analysis and direct sequencing methods were used to examine lung tumors derived from a cohort of beagle dogs with inhalational exposures to 239PuO2. These exposures were done at Pacific Northwest Laboratories where 18-month-old beagle dogs were given 239PuO2 by single-dose inhalation and allowed to live out their life-spans. Formalin-fixed paraffin-embedded blocks of tissues from 25 dogs exposed to 239PuO2 by aerosol inhalation which later developed lung tumors were available for this study. Two of 25 tumors had mutations within exon 1 of K-ras detected by SSCP analysis. Both mutations were GGT to GAT transitions at codon 12 confirmed by direct sequencing experiments. One was an adenocarcinoma from the medium-high exposure group and the other was a broncheolo-alveolar carcinoma from the medium-low exposure group. The rate of K-ras mutations in plutonium-induced lung tumors described herein (8%) was greater than previously described in canine plutonium-induced lung tumors (0%), but was less than that which we have described in spontaneous canine lung cancer (16%), less than that reported for human spontaneous non-small cell lung cancer (13-36%) and less than that described in rats with spontaneous lung cancer (40%) or lung tumors following 239Pu inhalation exposure (46%).

Differential regulation of c-jun expression in liver and lung of mice after thermal injury.

In addition to skin injury, burns may also damage distant organs. Understanding the mechanisms of distant organ injury will substantially improve the survival of burn patients. Transcription factors are the major regulators of gene expression in response to most types of injury. C-Jun, which is a part of the activator protein-1 transcription factor complex, is one of the major immediate-early response genes, which is rapidly induced after injury. The expression of c-Jun in mouse liver and lung at different time points (3 h to 29 days) after thermal injury was examined by using Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot, and immunohistochemistry. Rapid induction of c-Jun mRNA and protein was observed in the liver 3 h after an 18% TBSA burn. C-Jun expression returned to basal levels within 3 days after injury. In contrast to the up-regulation observed in liver, lungs from the same mice expressed c-Jun constitutively throughout the same time points. The finding that thermal injury leads to up-regulation of c-Jun in liver but not lungs suggests that either the liver has a lower threshold for early response to injury or that different cellular events exist when each organ is stressed.

A new method for thermocholecystectomy. Initial experience and comparison with other techniques.

RATIONALE AND OBJECTIVES: The authors tested the feasibility of thermocholecystectomy for gallbladder ablation in an animal model. METHODS: Thermal treatment of the cystic duct followed by heating of the saline-filled gallbladder using a separately designed heater/expander was performed in 13 pigs (group I). In four animals, heating of the gallbladder alone was performed (group II). Two animals served as controls (group III). All animals were killed 12 weeks after treatment. RESULTS: There was cystic duct occlusion in 10 (77%) of 13 of group I animals. In 6 (60%) of 10 of these animals with cystic duct occlusion, there was complete ablation of the gallbladder mucosa and complete obliteration of the gallbladder lumen. In group II animals, all cystic ducts were intact with an unchanged gallbladder volume in all four animals (100%), and normal gallbladder mucosa were intact in three (75%) of four animals. The gallbladders and cystic ducts in group III animals were normal. CONCLUSIONS: This study demonstrates many technical difficulties with thermal cholecystectomy. However, under ideal conditions, permanent gallbladder ablation is feasible in our animal model using a specially designed heating system.

Long-term effect of irradiation on lymph node uptake of interstitially delivered nanoparticulate contrast media.

RATIONALE AND OBJECTIVES: To characterize the long-term effects of therapeutic doses of ionizing radiation on the uptake and distribution of percutaneously delivered particulate contrast media in normal lymph nodes. METHODS: Two milliliters of an iodinated nanoparticle suspension (76 mg I/mL) was injected subcutaneously or submucosally into nine normal adult beagles. Region of interest analysis was used to estimate the volume, attenuation, and iodine concentration of opacified targeted lymph nodes and nonopacifled contralateral nodes on 24-hour postinjection CT images. All lymph nodes were then irradiated with 50 Gy in 25 fractions of 2 Gy/d. Contrast-enhanced quantitative CT was repeated 12 months after irradiation. RESULTS: Contrast-enhanced nodes averaged 2.3+/-0.8 times the volume of nonenhanced contralateral nodes before irradiation. The mean attenuation of contrast-enhanced nodes increased to 305 to 380 Hounsfield units from a pre-enhancement value of approximately 25 Hounsfield units. Opacified node volumes after irradiation averaged 61% to 86% of preirradiation volumes but were generally not statistically different. Contrast uptake assessed by average attenuation and iodine concentration decreased significantly by an average of 17% to 22% after irradiation and was significantly less than preirradiation uptake. Qualitatively, irradiated nodes generally appeared smaller than nonirradiated nodes, but the distribution pattern of contrast media did not appear to be appreciably altered. CONCLUSIONS: Lymph node irradiation resulted in only minimal decreases in contrast media uptake and node volume at 12 months. These effects presumably would not appreciably alter the potential clinical value of indirect lymphography for evaluating patients undergoing radiation therapy.

Refinement of a technique for thermocholecystectomy in an animal model.

RATIONALE AND OBJECTIVES: A modification of a thermal ablation system was tested for improved cystic duct occlusion and gallbladder mucosa ablation in an animal model. METHODS: Fourteen domestic swine were included in group 1 with thermal treatment of the cystic duct to 75 degrees C for 15 minutes, followed by heating of the gallbladder lumen with a catheter/heating device to 54 degrees C for 30 minutes. One swine served as a control (group 2). A ligature was placed around the cystic duct without thermal treatment of the cystic duct and with the catheter/heating device placed into the gallbladder for 30 minutes without thermal treatment. All animals were killed after 3 weeks with histologic examination of the gallbladder, cystic duct, and surrounding organs. RESULTS: In group 1, technical failure due to catheter clogging occurred in the first three animals, which were killed immediately. Eleven animals were treated with a redesigned catheter system. Three weeks after treatment, 10 of the 11 animals had complete cystic duct occlusion and complete obliteration of the cystic duct mucosa. One of the 11 animals experienced partial cystic duct ablation. Nine of the 11 treated animals experienced complete mucosal ablation of the gallbladder. Five of the 11 animals had no residual lumen, whereas 6 of the 11 had a luminal volume that averaged 4 mL compared to 35 mL before treatment. In group 2, the control subject had a gallbladder volume of 50 mL and normal gallbladder and cystic duct mucosa. CONCLUSIONS: This study demonstrates improvement in both cystic duct occlusion and gallbladder mucosa ablation with standardization of the technique for thermocholecystectomy in an animal model. However, a better system is required to promote complete obliteration of the gallbladder lumen.

Radiofrequency ablation of breast cancer: first report of an emerging technology.

HYPOTHESIS: Radiofrequency (RF) energy applied to breast cancers will result in cancer cell death. DESIGN: Prospective nonrandomized interventional trial. SETTING: A university hospital tertiary care center. PATIENTS: Five women with locally advanced invasive breast cancer, aged 38 to 66 years, who were undergoing surgical resection of their tumor. One patient underwent preoperative chemotherapy and radiation therapy, 3 patients received preoperative chemotherapy, and 1 had no preoperative therapy. All patients completed the study. INTERVENTIONS: While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode was inserted into the tumor under sonographic guidance. Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. Only a portion of the tumor was treated to evaluate the zone of RF ablation and the margin between ablated and nonablated tissue. Immediately after RF ablation, the tumor was surgically resected (4 mastectomies, 1 lumpectomy). Pathologic analysis included hematoxylin-eosin staining and enzyme histochemical analysis of cell viability with nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) staining of snap-frozen tissue to assess immediate cell death. MAIN OUTCOME MEASURE: Cancer cell death as visualized on hematoxylin-eosin-stained paraffin section and NADH-diaphorase cell viability stains. RESULTS: There was evidence of cell death in all patients. Hematoxylin-eosin staining showed complete cell death in 2 patients. In 3 patients there was a heterogeneous pattern of necrotic and normal-appearing cells within the ablated tissue. The ablated zone extended around the RF electrode for a diameter of 0.8 to 1.8 cm. NADH-diaphorase cell viability stains of the ablated tissue showed complete cell death in 4 patients. The fifth patient had a single focus of viable cells (<1 mm) partially lining a cyst. There were no perioperative complications related to RF ablation. CONCLUSIONS: Intraoperative RF ablation results in invasive breast cancer cell death. Based on this initial report of the use of RF ablation in breast cancer, this technique merits further investigation as a percutaneous minimally invasive modality for the local treatment of breast cancer.

Percutaneous ultrasound-guided radiofrequency electrocautery ablation of prostate tissue in dogs.

RATIONALE AND OBJECTIVES: We investigated the feasibility of percutaneous radiofrequency (RF) electrocautery in ablation of prostate tissue in dogs. METHODS: We used six dogs in whom a specially designed needle was placed percutaneously into the prostate. RF electrocautery was applied to the needle and treatment was monitored with ultrasound. Animals were sacrificed and gross examination of the prostate and surrounding tissues was performed. Histopathologic examinations of the prostate were also performed. RESULTS: The treatment zone appeared as an elliptical echogenic focus on ultrasound that increased in size with the application of current. Gross and histopathologic correlation demonstrated that the treatment area included a central area of char with a surrounding area of coagulation. There were no deleterious effects to surrounding tissues. CONCLUSION: Our results demonstrate the feasibility of percutaneous ultrasound-guided RF electrocautery ablation of canine prostate tissue.

Lymph node uptake of interstitially delivered particulate contrast media before and after irradiation in dogs.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of ionizing radiation on the uptake and distribution of interstitially delivered particulate contrast medium in normal lymph nodes in dogs. MATERIALS AND METHODS: Two milliliters of an iodinated nanoparticle suspension (NC 67722 Sterile Suspension, 76 mg of iodine per milliliter) was injected subcutaneously or submucosally into nine normal adult beagle dogs. Targeted lymph node groups were evaluated with computed tomography (CT). Region-of-interest analysis was used to estimate volume, attenuation, and iodine concentration of the opacified nodes and nonopacified contralateral nodes on CT images obtained before and 24 hours after the injection. All right-sided and some left-sided lymph nodes were irradiated with 50 Gy in 25 fractions of 2 Gy per day, beginning 28-35 days after the CT examination. Contrast medium administration and quantitative CT imaging were performed again 3 months after irradiation. RESULTS: Contrast material uptake resulted in a twofold increase in node volume before irradiation (P < .0001). Mean attenuation of contrast-enhanced nodes increased to 230-330 HU from a precontrast enhancement value of 36.5 HU. After irradiation, opacified node volumes decreased to approximately 25%-50% of their preirradiation volumes (P < .02). Contrast material uptake decreased 10%-15% after irradiation but was not significantly less than preirradiation uptake. Qualitatively, no substantial difference in contrast material distribution existed between irradiated and nonirradiated nodes. CONCLUSION: An elective irradiation dose decreased lymph node size, but the imaging characteristics of opacification were not otherwise appreciably altered 3 months after irradiation.

Preclinical evaluation of manganese carbonate particles for magnetic resonance imaging of the liver.

RATIONALE AND OBJECTIVES: We characterized the physical, biological, and imaging properties of a manganese (Mn) carbonate particle suspension, a contrast agent for hepatic magnetic resonance (MR) imaging. METHODS: Mn carbonate suspensions were produced by controlled precipitation and characterized using light microscopy, transmission electron microscopy, and in vitro relaxivity studies. Efficacy of the agent was studied in normal and tumor-bearing rats using T1-weighted MR imaging. RESULTS: Following intravenous injection of Mn carbonate particles at doses ranging from 10 to 100 mumol Mn/kg, peak hepatic contrast enhancement of approximately 35% occurred from about 125 min until the termination of the MR imaging studies that varied from 125 to 305 min. Lesion conspicuity was increased because of relative intensity differences between normal liver and tumor. Data also showed that Mn carbonate particles dissolved on delivery to the liver, allowing Mn to interact with intrahepatic macromolecular complexes to provide positive contrast enhancement. CONCLUSION: Mn carbonate particles produce significant and sustained hepatic enhancement and should improve detection of small or isointense liver lesions.

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

RATIONALE AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 using iodinated nanoparticles to detect cancerous lymph nodes in a cutaneous melanoma model.

RATIONALE AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 of subdiaphragmatic lymph nodes using iodinated nanoparticles in normal dogs.

RATIONALE AND OBJECTIVES: We evaluated the imaging characteristics of an iodinated particulate contrast agent for indirect computed tomography (CT) lymphography of normal subdiaphragmatic lymph nodes in dogs. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

RATIONALE AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Craniocervical and thoracic lymph nodes can be effectively opacified from interstitial or intraperitoneal delivery of this iodinated nanoparticulate contrast agent.