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Biomedical subjects

E R Wisner

Publications and source records attributed to E R Wisner.

At least 19 recordsLinked to original sources

Ultrasonography of the thyroid and parathyroid glands.

High-resolution thyroid and parathyroid ultrasonography can play an integral part in the diagnosis and management of patients with clinically undifferentiated cervical masses, thyroid carcinomas or adenomas, and primary parathyroid hyperplasia or neoplasia. Because the study is inexpensive, noninvasive, and easily performed, ultrasonography can be performed as a screening test early in the evaluation of a patient, and ultrasound findings can corroborate the results of other diagnostic procedures, leading to a more accurate diagnosis.

Adenoma

A modular lymphographic magnetic resonance imaging contrast agent: contrast enhancement with DNA transfection potential.

A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRI) efficacy has been examined by indirect magnetic resonance lymphography. A lipidic N,N'-dimethylethylenediamine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was confirmed using MALDI spectrometry. An equimolar mixture of the Gd-chelate lipid and a commercially available diyne-PE was formulated as a liposome suspension and irradiated with UV light prior to imaging experiments. Subcutaneous injection of the liposomal gadolinium agent and subsequent MRI of rabbit axillary and popliteal lymph nodes revealed significant contrast enhancement up to 4 h postinjection. To explore the possibility of imaging a DNA transfection event, the gadolinium contrast mixture was formulated with the cationic transfection lipid DOTAP and complexed with the reporter gene encoding luciferase. DNA transfection studies on the NIH3T3 cell line confirmed the transfection activity of the dual-purpose contrast agent and exemplified the potential toward development of an imaging and DNA delivery vehicle.

3T3 Cells

Comparison of results of hormonal analysis of samples obtained from selected venous sites versus cervical ultrasonography for localizing parathyroid masses in dogs.

OBJECTIVE: To compare a technique in which samples obtained from selected venous sites are analyzed for parathyroid hormone (PTH) concentration versus usefulness of cervical ultrasonography for localizing primary hyperparathyroidism (PHP) in dogs. DESIGN: Prospective study. ANIMALS: 12 dogs with PHP. PROCEDURE: For each dog, blood samples were collected from the left and right jugular veins and 1 cephalic vein for determination of serum PTH concentration. Ultrasonography of the neck was performed in each dog. Each dog underwent exploratory surgery of the neck. Abnormal appearing parathyroid tissue was removed. Dogs were included in the study if serum calcium concentration decreased within 12 hours after surgery, hypercalcemia completely resolved within 96 hours after surgery, and serum calcium concentration was maintained within the reference range for at least 6 months after surgery. RESULTS: Serum PTH concentrations from the 3 veins were similar in 11 of 12 dogs with PHP. In 1 dog, the serum PTH concentration from the jugular vein ipsilateral to a parathyroid adenoma was greater than that from the contralateral jugular or cephalic vein. Ultrasonography correctly identified a parathyroid mass and its location in 10 of 11 dogs with a solitary abnormal parathyroid gland and in 1 dog in which both parathyroid glands were enlarged. CLINICAL IMPLICATIONS: Surgeons may benefit from knowing the location of abnormal parathyroid tissue in dogs with PHP before surgical exploration. Ultrasonography has potential value for identifying and localizing abnormal parathyroid tissue, whereas sample collection from selected sites for PTH analysis is not likely to be helpful.

Adenocarcinoma

Sentinel node imaging via a nonparticulate receptor-binding radiotracer.

UNLABELLED: Technetium-99m-labeled polydiethylenetriamine pentaacetic acid polymannosyl polylysine (DTPA-man-PL) was synthesized and tested for lymph node scintigraphy by subcutaneous administration. The agent was designed for receptor-mediated uptake by mannosebinding protein, which resides on the plasma membrane of reticuloendothelial cells. METHODS: Subcutaneous injections of a 99mTc-labeled agent having 18 DTPA and 82 mannosyl groups attached to a polylysine of 100 units ([99mTc]DTPA18-man82-PL100) were made at the level of the metacarpus and metatarsus of three healthy rabbits. Images were acquired at 1, 6, 12 and 24 hr. Popliteal and axillary nodes were then assayed for percent of injected dose (%ID). A negative control study was performed in three normal rabbits with [99mTc]DTPA18-PL100. RESULTS: Significant differences in mean 24-hr %ID between the receptor specific and nonspecific agents were observed for both the popliteal (p < 0.006) and axillary (p < 0.012) nodes. Popliteal percent injected dose at 24 hr was 3.00 +/- 0.72% for [99mTc]DTPA-man-PL and 0.13 +/- 0.08% for [99mTc] DTPA-polylysine. Axillary accumulation at 24 hr was 2.84 +/- 0.83% for [99mTc]DTPA-mannosyl-polylysine and 0.22 +/- 0.12% for [99mTc] DTPA-polylysine. Percent injected dose of the receptor-specific agent was highest (4%) during the 6-hr scan. Accumulation of the nonspecific agent by the popliteal and axillary nodes at 6-hr postinjection was approximately 0.5%. CONCLUSION: This study provides proof of principle for lymphoscintigraphy by receptor-mediated delivery of a nonparticulate imaging agent.

Animals

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.

Animals

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.

Analysis of Variance

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.

Abdomen

A molecular receptor-binding contrast agent for magnetic resonance imaging of the liver.

RATIONALE AND OBJECTIVES: A gadolinium complex of polydiethylenetriamine pentaacetic acid polyneogalactosyl polylysine (Gd-DTPA-gal-PL) was developed and tested as a paramagnetic contrast agent for magnetic resonance (MR) imaging of the liver. The agent was designed for receptor-mediated uptake by the asialoglycoprotein receptor (ASGP-R), which is unique to hepatocytes and exhibits high specificity for galactose-terminated glycoconjugates. METHODS: Polylysine was alkylated with a mixed anhydride of diethylenetriamine pentaacetic acid. This product was complexed with gadolinium and N-alkylated with 3-oxopropyl-1-thio-beta-D-galactopyranoside. With this reaction sequence, we prepared a gadolinium complex consisting of 2284 galactose groups and 858 chelators per polylysine having 2136 amino groups. Hepatic enhancement was tested by MR imaging of nine rats with liver-implanted mammary adenocarcinoma before and after injection of 20 x 10(-9) mol/kg Gd-DTPA858-gal2284-PL2136. The conjugate was labeled with technetium-99m and tested (1.5 x 10(-10) mol/kg) for hepatic specificity via nuclear imaging. RESULTS: Mean hepatic enhancement was 86% within 10 min and remained constant for 25 min. Hepatic relative intensity exceeded preinjection intensities by at least four times the standard deviation of the preinjection values (p < .01). The tumors, which are devoid of ASGP-R, did not exhibit significant enhancement (p > .1). The liver accumulated 90% of the technetium-99m-labeled conjugate. CONCLUSION: A molecular paramagnetic ligand to the asialoglycoprotein receptor has been developed for hepatocyte-specific MR contrast enhancement.

Adenocarcinoma

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.

Animals

Needle aspiration lung biopsy: reevaluation of the blood patch technique in an equine model.

PURPOSE: To reexamine the blood patch technique in a laboratory model of lung biopsy free of confounding clinical variables. MATERIALS AND METHODS: An equine model of lung biopsy was developed with an excised lobe connected to an insufflation bulb and pressure monitor. Patched and control unpatched punctures were made in the lung surface, and the pressure within the lung was raised to the maximum achievable. Whether air leakage from the puncture sites could be induced was determined and, if so, at what pressure it occurred. RESULTS: At statistical analysis with the Kaplan-Meier test and the Cox proportional hazards regression model, the difference between failure of the patched and unpatched punctures was statistically significant (P < .0001). CONCLUSION: The blood patch technique is effective in the laboratory setting and deserves reevaluation in a clinical series with updated biopsy techniques.

Animals

Morphologic and morphometric characterization of lung collagen content in clinically normal adult thoroughbreds in race training.

Interstitial and bronchointerstitial pulmonary patterns are commonly observed in thoracic radiographs of Thoroughbreds. Prominent interstitial and bronchointerstitial pulmonary patterns are observed in clinically normal horses, and in horses with respiratory tract disease. Until recently, the relevance of these pulmonary patterns was not known. Previous studies indicated that bronchiolitis, bronchiolar epithelial hyperplasia, epithelial metaplasia, and bronchial arteriolar recruitment correlated strongly with the prominence of the interstitial and bronchointerstitial pulmonary patterns observed radiographically. We examined the content and distribution of collagen in the lungs of 7 clinically normal Thoroughbreds in race training. After standardized fixation, lung tissue was treated with a compound that selectively stains collagen. Standard morphometric techniques were used to determine the volume density of parenchymal tissue and parenchymal airspace, mean linear intercept (estimate of alveolar size), alveolar surface area-to-volume ratio, percentage of parenchyma composed of collagen, percentage of airway wall composed of collagen, and airway wall thickness. These values were compared with radiographic and histopathologic scores obtained from the same horses. The volume density of parenchymal tissue and small airway wall thickness correlated strongly with the prominence of the bronchial and bronchointerstitial pulmonary patterns observed radiographically. Small airway thickness was also highly correlated with the perceived prominence of the interstitial pulmonary patterns observed radiographically, and morphometric estimates of parenchymal tissue and parenchymal collagen. There were also strong correlations between the volume density of parenchymal tissue, the percentage of parenchymal collagen, peribronchiolar mononuclear cell infiltrates, and bronchiolar mucosal plication estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

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.

Animals

Radiographic and microscopic correlation of diffuse interstitial and bronchointerstitial pulmonary patterns in the caudodorsal lung of adult thoroughbred horses in race training.

Complete thoracic radiographic examinations were performed on 7 horses ranging in age from 24 to 60 months, followed by in-situ lung fixation. Radiographs were examined by 3 radiologists for the presence, degree and distribution of generalised pulmonary patterns within a region of interest in the caudodorsal lung. Pulmonary tissue was obtained from 12 sites within a designated volume of interest in the caudodorsal lung, corresponding to the area of interest evaluated radiographically, and examined for the presence, character and severity of microscopic lesions. Radiographic findings within the volume of interest consisted of mild to moderate bronchial, bronchointerstitial, or interstitial pulmonary patterns. Interstitial and bronchointerstitial radiographic findings were related to severity of peribronchiolar mononuclear cell infiltrates, the degree of bronchiolar mucosal plication, and alveolar capillary and peribronchial blood vessel erythrocyte content. The severity of the interstitial radiographic pattern was inversely associated with the perceived diagnostic quality of the radiographic examinations. There was no evidence of spatial variation in the severity of the microscopic changes examined in this limited pulmonary region. Inter-rater reliability between radiologists was good in the assessment of diagnostic quality of the radiographic examinations but poor in assessing severity of the primary generalised pulmonary patterns within the radiographic region of interest.

Animals

Osteomyelitis of the axial border of the proximal sesamoid bones in seven horses.

Destructive lesions of the axial region of the proximal sesamoid bones were identified by radiography in eight fetlocks and seven lame adult horses. Lameness ranged from 2 to 5 (mean 4; scale 1 to 5) at the time of examination, with a duration of 10 days to two years (mean 5.6 months). Destructive lesions involved both proximal sesamoid bones when examined radiographically and were situated primarily at the level of the mid-body and apical region of the axial borders. Some lesions were cystic, whereas others eroded the axial border more diffusely. Scintigraphy revealed markedly increased activity within the proximal sesamoid bones of the clinically lame limb of four of the five horses examined. In four horses, post mortem computed tomography revealed axial border bone destruction and cavitary lesions within cancellous bone of affected proximal sesamoid bones. Lesions seen by computed tomography were larger than those identified on radiographic examination. Cavitary lesions not seen radiographically were identified in the proximal sesamoid bones of two clinically unaffected fetlocks examined for comparison in two of the seven horses. Evidence of acute, subacute or chronic/reparative osteomyelitis of the axial region of the proximal sesamoid bones was seen in the 10 fetlocks identified as abnormal from radiography or computed tomography. Also, three horses had septic synovitis of the flexor sheath of the clinically affected limb; of these, two had septic arthritis of the fetlock joint.

Animals

Arabinogalactan-coated superparamagnetic iron oxide: effect of particle size in liver MRI.

OBJECTIVE: We evaluated the effect of particle size on MR contrast-enhancing properties of arabinogalactan-coated superparamagnetic iron oxide (AG-SPIO) in tumor-bearing rats. MATERIALS AND METHODS: T2*-weighted gradient-recalled echo MR studies were performed on rats with surgically implanted liver tumors before and after AG-SPIO administration. Contrast-to-noise ratio (CNR) and percent contrast enhancement (PCE) were calculated for animals given small (15.7 +/- 9.5 nm: n = 6), medium (49.1 +/- 19.7 nm; n = 4), and large (86.9 +/- 27.5 nm; n = 4) particles intravenously (10 mumol Fe/kg). RESULTS: Postcontrast CNRs were 15.8 +/- 6.9, 8.9 +/- 4.1, and 10.0 +/- 1.8 for small, medium, and large particle groups, respectively. The PCE was -60.0 +/- 3.3, -75.5 +/- 7.9, and -80.5 +/- 1.2%. There was a significant difference in preversus postcontrast CNR for all particle sizes (p < 0.001) and in PCE for small particles as compared with the two larger sizes (p < 0.001). There was no between-group statistical difference in postcontrast CNR for any particle size. CONCLUSION: Larger AG-SPIO particles slightly improve liver contrast enhancement, but have no significant effect on hepatic lesion detection as assessed by CNR.

Animals