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G L Wolf

Publications and source records attributed to G L Wolf.

At least 37 records · Page 2Linked to original sources
PubMed1996

A model of focal cancer in rabbit lymph nodes.

RATIONALE AND OBJECTIVES: We sought to develop a model of focal cancer in the rabbit lymph node. METHODS: Under computed tomography (CT) guidance, 4-5 million VX2 cells were directly injected into the popliteal nodes of 14 anesthetized New Zealand White rabbits. Fifteen to 18 days later, percutaneous lymphography was performed with CT scanning using radiopaque nanoparticulates and massage. Histologic correlation also was obtained. RESULTS: In 12 of the 14 animals, focal lesions were successfully created within (n = 6) and adjacent (n = 6) to the node, and all animals appeared to be healthy when euthanized. Within 15 min after massage, CT lymphography showed homogeneous enhancement of normal node regions and no enhancement of cancer. There was good agreement between histology and lymphography. CONCLUSION: This method is suitable as a model to test for diagnostic and therapeutic interventions.

Animals↗
PubMed1996

Functional CT with an experimental intravascular contrast agent in the assessment of liver vascular physiology.

RATIONALE AND OBJECTIVES: We evaluated liver vascular physiology with a functional spiral computed tomography (CT) technique and an intravascular contrast agent. METHODS: Eleven rabbits were studied by means of continuous 40-second single-section data acquisition after bolus injection of an experimental contrast agent. Sequential images were reconstructed at 200-msec intervals. Aortic, portal and hepatic venous, and liver time-HU curves were obtained. From these, hepatic blood volume and flow, tissue transit times, and arterial and portal contributions to total liver blood supply were assessed. RESULTS: The following measures were obtained: hepatic blood volume fraction, 0.33 +/- 0.03 (mean +/- standard error); total flow, 241.1 mL/min +/- 33.6 per 100 g of tissue (arterial component, 11.3 mL/min +/- 3.0 per 100 g of tissue; portal component, 226.4 mL/min +/- 30.7 per 100 g of tissue); arterial transit time, 8.7 seconds +/- 1.6; portal transit time, 8.7 seconds +/- 1.3; arterial to portal perfusion ratio, 0.06 +/- 0.01; and calculated arterial and portal perfusion indexes, 0.05 +/- 0.01 and 0.95 +/- 0.01, respectively. CONCLUSION: Functional CT is a promising, high-resolution tomographic imaging technique for evaluating liver perfusion.

Animals↗
PubMed1996

Stable polymeric micelles: lymphangiographic contrast media for gamma scintigraphy and magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Amphiphilic biocompatible polyoxyethylene (PEO)-based polymers form particles (micelles) that are 10-50 nm in diameter. In the current research, we successfully incorporated amphiphilic indium-111 (111In) and gadolinium chelates into these particles and used them as particulate contrast media in percutaneous lymphography. METHODS: Micelles of amphiphilic PEO-lipid conjugates were loaded with 111In and gadolinium diethylenetriamine pentaacetic acid-phosphatidylethanolamine (Gd-DTPA-PE) and were injected subcutaneously into the rabbit's paw. Corresponding images of local lymphatics were acquired using a gamma camera and a magnetic resonance (MR) imager. RESULTS: The entire lymphatic chain from the paw to the thoracic duct could be visualized using 111In micelles after injection site massage. T1-weighted MR images of the primary lymph node and collecting vessels were obtained within 4 min after administration of gadolinium micelles and massage. CONCLUSION: Polymeric PEO-containing micelles can be loaded with diagnostic metals and, on subcutaneous injection, can visualize elements of lymphatic system. The major fraction of injected micelles stays within the lymph fluid, thus serving as lymphangiographic agents for indirect MR or gamma lymphography.

Animals↗
PubMed1996

Hemodynamic alterations in focal cerebral ischemia: temporal correlation analysis for functional imaging.

We describe a novel approach for analysing the hemodynamic alterations that result after focal cerebral ischemia. This approach utilizes a temporal correlation analysis of first pass transit data obtained with functional imaging. First pass transits of injected contrast agents are measured with dynamic CT scanning. Normal transit profiles are obtained from contralateral cortical regions to serve as reference profiles. Normalized correlations are then calculated to compare transit profiles from each individual pixel within the brain to the normal reference profile. The normalized correlation coefficient is used as a measure of temporal similarity to quantitatively assess deviations from normal hemodynamics. The method is based on the premise that perturbed hemodynamics are manifested as changes in the shape of the cerebral transit profiles. Correlation maps are produced that display regional alterations in cerebral hemodynamics. Results from rabbit (n=4) and rat (n=4) models of focal ischemia are presented. In the normal contralateral hemisphere, correlation values range from 0.83-0.93 with coefficients of variation of less than 3-4% . The ischemic core is comprised of regions without significant bolus transit. The peripheral zones that lie between normal brain and the ischemic core are composed of intermediate correlation values. By setting statistical thresholds (mean minus 2SD, p < 0.05), we quantitatively define these intermediate zones as the hemodynamic penumbra, i.e. regions where the shape of the first pass transit profile has been altered. The resulting correlation maps clearly image gradients of altered cerebral hemodynamics. Perfusion indices calculated based on transit profile peaks revealed that the penumbral zones possess reduced perfusion on the order of about 40 percent of contralateral values. In summary, we believe that temporal correlation analysis of first pass transit profiles can be used to image the hemodynamic penumbra in focal cerebral ischemia.

Animals↗
PubMed1996

Evaluation of selected two-dimensional segmentation techniques for computed tomography quantitation of lymph nodes.

RATIONALE AND OBJECTIVES: As contrast agents that selectively target normal lymph nodes are undergoing development and evaluation, it has become important to accurately and reproducibly determine nodal boundaries to study the agents and determine such values as lymph node area or mean nodal contrast concentration. This study was performed to evaluate the accuracy of different two-dimensional computer segmentation methods, tested on acrylic phantoms constructed to imitate the appearance of lymph nodes surrounded by fat. METHODS: Five segmentation techniques (manual tracing, semiautomatic local criteria threshold selection, Sobel/watershed technique, interactive deformable contour algorithm and thresholding) were evaluated using phantoms. Subsequently, the first three methods were applied to the images of enhanced lymph nodes in rabbits. RESULTS: Minimum errors in phantom area measurement (< 5%) and interoperator variation (< 5%) were seen with the Sobel/watershed technique and the interactive deformable contour algorithm. These two techniques were significantly better than thresholding and semiautomated thresholding based on local properties. CONCLUSION: Methods based on Sobel edge detection offer more objective tools than thresholding methods for segmenting objects similar to lymph nodes in computed tomography images. Both methods, Sobel/watershed and interactive deformable contour algorithm, are fast and have simple user interfaces.

Algorithms↗
PubMed1996

Temporal correlation analysis of penumbral dynamics in focal cerebral ischemia.

A novel temporal correlation technique was used to map the first-pass transit of iodinated contrast agents through the brain. Transit profiles after bolus injections were measured with dynamic computed tomography (CT) scanning (1 image/s over 50 s). A rabbit model of focal cerebral ischemia (n = 6) was used, and dynamic CT scans were performed at 30, 60, 90, and 120 min postocclusion. Within the ischemic core, no bolus transit was detectable, demonstrating that complete ischemia was present after arterial occlusion. In the periphery of the ischemic distribution, transit dynamics showed smaller peaks, broadened profiles, and overall delay in bolus transit. A cross-correlation method was used to generate maps of delays in ischemic transit profiles compared with normal transit profiles from the contralateral hemisphere. These maps showed that penumbral regions surrounding the ischemic core had significantly delayed bolus transit profiles. Enlargement of the ischemic core over time (from 30 to 120 min postocclusion) was primarily accomplished by the progressive deterioration of the penumbral regions. These results suggest that (a) temporal correlation methods can define regions of abnormal perfusion in focal cerebral ischemia, (b) peripheral regions of focal cerebral ischemia are characterized by delays in bolus transit profiles, and (c) these regions of bolus transit delay deteriorate over time and thus represent a hemodynamic penumbra.

Animals↗
PubMed1996

Temporal correlation mapping analysis of the hemodynamic penumbra in mutant mice deficient in endothelial nitric oxide synthase gene expression.

BACKGROUND AND PURPOSE: Mice containing deletions in the genes encoding nitric oxide (NO) synthase have been useful to dissect the role of NO in cerebral ischemia. We recently reported that mice lacking expression of the endothelial isoform of NO synthase (eNOS) develop larger infarcts after middle cerebral artery occlusion. Because NO or a related product of NO synthase activity is important for relaxation of cerebral blood vessels, we examined for possible hemodynamic differences in the peri-ischemic zone of eNOS-deficient and wild-type mice after middle cerebral artery occlusion using functional CT scanning techniques. METHODS: Wild-type SV129 mice (n = 10) and mice deficient in eNOS gene expression (n = 10) were subjected to middle cerebral artery occlusion under halothane anesthesia. Thirty minutes after ischemia, functional CT scanning was performed with dynamic scanning protocols to measure the cerebral transit profiles of injected contrast agents. A temporal correlation mapping technique was used to analyze the pattern of hemodynamic perturbations based on alterations in the shape of the cerebral transit profiles. Statistical thresholds defined the hemodynamic core and penumbra. RESULTS: Hemodynamic deficits were more severe in the mutant than wild-type mouse. When expressed as a percentage of the total insult, core areas were significantly increased in mutant mice (39.8 +/- 3.7%) compared with wild types (28.8 +/- 3.4%). Conversely, areas of the hemodynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2 +/- 3.7%) than in wild-type mice (71.2 +/- 3.4%). Furthermore, the calculated relative perfusion index within the hemodynamic penumbra was significantly lower in the group with eNOS gene deletion (35.6 +/- 1.5% in mutants versus 43.0 +/- 2.4% in wild types). CONCLUSIONS: These data indicate that mice lacking eNOS expression show a greater degree of hemodynamic compromise after middle cerebral artery occlusion and suggest that a product of eNOS activity (eg. NO) may protect brain after focal cerebral ischemia, possibly by improving blood flow within the penumbral zone.

Animals↗
PubMed1996

Basic principles of MR contrast agents.

Although familiar for CNS enhancement, contrast agents for body MR applications are both similar and different. This short summary emphasizes the basics of tissue relaxation and the added influences of paramagnetic or superparamagnetic pharmaceuticals. An overview of safety and cost considerations is included.

Contrast Media↗
PubMed1996

Quantitative high-resolution measurement of cerebrovascular physiology with slip-ring CT.

PURPOSE: To implement and validate spiral slip-ring CT for use in cerebrovascular studies. METHODS: Continuous data were acquired from an experimental, first-pass, iodine contrast, bolus study by unidirectional X-ray tube rotation, and images were reconstructed at 100-millisecond intervals. Functional maps of cerebral blood volume (CBV) and cerebral blood flow (CBF) were constructed with voxel-by-voxel gamma variate fitting. Reproducibility studies, different injection volumes and sites, and CO2 challenge were applied to verify the technique. RESULTS: Average absolute cortical gray and white matter and basal ganglia results were reproducible within +/- 0.8 ml/100 g for CBV and +/- 20 ml/100 g per minute for CBF, CBV response to changing arterial CO2 tension was significant only in cortical gray matter and basal ganglia; CBF response was significant in gray and white matter, as well as in the basal ganglia. CONCLUSION: Functional CT and constructed functional maps provide an optimal, high-resolution tool with which to visualize cerebrovascular parameters and their changes.

Animals↗
PubMed1995

Controlled delivery of Gd-containing liposomes to lymph nodes: surface modification may enhance MRI contrast properties.

Surface modification of liposomes containing Gd-diethylenetriaminepentaacetyl-phosphatidylethanolamine (Gd-DTPA-PE) as an amphiphilic paramagnetic label influences their contrast properties as MRI agents. Liposomes with the mean diameter ca. 220 nm and 10% mol content of Gd-DTPA-PE were modified with dextran (molecular weight 6 kDa) or polyethyleneglycol (PEG, molecular weight 5 kDa). The preparations obtained were used for MR visualization of axillary and subscapular lymph nodes after SC injection into rabbit's paw. Dextran-modified liposomes were found to have limited or no effect on lymph node/muscle MR signal intensity ratio during the first 2 h after the administration when compared to nonmodified plain liposomes, whereas the liposomes modified with PEG demonstrated a 3-3.5-fold enhancement of lymph node signal. However, the partial biodistribution studies with the 111In-labeled liposomes revealed that PEG-modified vesicles accumulated in the axillary lymph node at half the amount comparing with nonmodified and dextran-modified liposomes. The phenomenon found might be explained by noticeably increased relaxivity of PEG-modified Gd-liposomes.

Animals↗
PubMed1995

Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits.

RATIONALE AND OBJECTIVES: We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. METHODS: Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. RESULTS: EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. CONCLUSION: EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.

Animals↗
PubMed1995

Use of nitroxides as NMR contrast enhancing agents for joints.

NMR imaging is a well-established technology for obtaining cross-sectional anatomic pictures of organs and tissues. In addition, NMR can provide valuable information about the physiologic state of organs and tissues, especially, as a consequence of cellular injury. With this in mind, NMR in combination with gadolinium-based contrast enhancing agents has been used to assist in the detection of abnormalities to joints as well as to evaluate the status of damage resulting from an injury to this site. We describe the synthesis of a new nitroxide, which is bioresistant to the one-electron reduction mediated by superoxide in the presence of cysteine. This model mimics the reduction of nitroxides by extracellular secretion of superoxide by PMA-stimulated neutrophils. With this nitroxide, we found, in the range from 15 to 17.5 mumoles, enhancement of an NMR image in the knee joint of rabbits. Of interest is the finding that the contrast image remained for at least 90 minutes. These results demonstrate the utility of nitroxides as contrast enhancing agents for NMR imaging of joints.

Animals↗
PubMed1994

Spatial heterogeneity in tumor perfusion measured with functional computed tomography at 0.05 microliter resolution.

High speed (200 ms temporal resolution) functional computed tomography was used to demonstrate tumor vascular heterogeneity with 0.05 microliter spatial resolution. Vascular topologies were investigated in 2 human small cell lung cancer lines implanted either s.c. or as a tissue isolated preparation in immunocompromised mice. Peripheral versus central vascular topology was identified in the s.c. and tissue-isolated preparations, respectively. Pharmacokinetic analysis demonstrated that tumor physiology was influenced by cell line (P = 0.016) and not by location (P > 0.6). This new technique has the potential to characterize individual tumors in patients with minimal invasiveness, permitting more detailed prognosis and management.

Animals↗
PubMed1994

Percutaneous computed tomography lymphography in the rabbit by subcutaneously injected nanoparticulates.

RATIONALE AND OBJECTIVES: Surgical lymphangiography is infrequently used in staging cancer because of its inherent limitations. Radiopaque nanoparticulates target lymph nodes draining interstitial tissues and could make percutaneous lymphography feasible. METHODS: Experimental nanoparticulate contrast agent formulations were injected subcutaneously in the forepaw or hindpaw of normal rabbits or rabbits with induced reactive nodal hyperplasia. Axillary and popliteal nodes were imaged with thin-section computed tomography (CT) using quantitative methods to measure node enhancement. Dose-response (0.1-2.0 ml) and time course (4 hr to 10 weeks) of enhancement were assessed. RESULTS: Nodal enhancement above 100 Hounsfield units was consistently obtained. Enhancement was significantly related to dose and peaked at 10 hr with slow washout over the observation period. Nodes with reactive hyperplasia were larger and had heterogeneous enhancement patterns distinctly different from normal nodes. CONCLUSION: Percutaneous CT lymphography effectively depicts the macroscopic intranodal architecture in rabbits.

Animals↗
PubMed1994

Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo.

RATIONALE AND OBJECTIVES: Immobility and massage produce different local limb lymph flow rates. We studied their influence on accumulation of radiopaque nanoparticulates in regional lymph nodes of normal rabbits. METHODS: Quantitative lymphography at 10-min intervals was used to follow the transport of subcutaneous (s.c.) nanoparticulates produced from insoluble esters of diatrizoic acid. In one design, both hindpaws received 0.5 ml of nanoparticulate s.c., and one hindpaw was massaged. In a second design, one hindpaw was injected and massaged while imaging the popliteal, presacral, and paraaortic nodes every 10 min. RESULTS: Gentle massage rapidly increased popliteal node accumulation in comparison with the immobile limb. On the massaged side, mean Hounsfield (HU) units, maximum Hounsfield units, and calculated iodine were significantly greater at 10 min and all subsequent times. In the node transfer experiments, it took 12, 30, and 45 min, respectively, to obtain 100-HU mean attenuation; 200-HU maximum attenuation thresholds were achieved at 20, 47, and 69 min, respectively. CONCLUSION: Quantitative computed tomography lymphography reflects local lymph physiology. Gentle massage of the s.c. injection site is a powerful lymphotropic stimulus.

Analysis of Variance↗
PubMed1994

Nanoparticulate computed tomography contrast agents for blood pool and liver-spleen imaging.

RATIONALE AND OBJECTIVES: We investigated the properties of a group of iodine-containing, insoluble compounds formulated as nanoparticles for use as potential blood pool and liver-spleen contrast agents. METHODS: High-resolution, quantitative computed tomography (CT) was performed prior to and at intervals following the intravenous administration of the contrast agents to rabbits. Time-density characteristics for three organs were evaluated. RESULTS: Excellent enhancement of blood (< or = 232 Hounsfield units [HU]), liver (< or = 263 HU), and spleen (< or = 350 HU) was achieved at the administered dose of 3.0 ml/kg. The composition of the agents influenced the biodistribution, as well as the residence time in blood, and time to peak enhancement in liver. CONCLUSION: Iodinated nanoparticulate compounds are promising CT contrast agents. Development of agents with desirable pharmacokinetic and biodistribution profiles may permit application-specific contrast enhancement.

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