Application of CT in the investigation of angiogenesis in oncology.
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Contrast Media↗
Biomedical subjects
F T Lee
Publications and source records attributed to F T Lee.
Combined hepatocyte-selective and blood-pool contrast agents for the CT detection of experimental liver tumors in rabbits.
PURPOSE: To determine the imaging characteristics of a new computed tomographic (CT) contrast material with both hepatocyte-selective and blood-pool components (iodinated triglyceride (ITG)-dual) versus standard iohexol. MATERIALS AND METHODS: VX2 carcinoma was inoculated in seven rabbits. Animals underwent nonenhanced, iohexol-enhanced (600 mg of iodine per kilogram of body weight), and ITG-dual-enhanced (blood-pool moiety, 100 mg of iodine per kilogram; hepatocyte-selective moiety, 100 or 200 mg of iodine per kilogram, injected 90 minutes apart) helical CT. Livers were removed, preserved in formalin, suspended in agar, and sectioned transversely at 3-mm intervals. Attenuation values for normal liver and tumors were obtained, and blinded readers evaluated images for lesions by using a modified free-response receiver operating characteristic (ROC) method. RESULTS: A total of 47 separate tumor sites were detected at pathologic examination. ITG-dual-enhanced scans obtained with 300 mg of iodine per kilogram demonstrated similar liver opacification to iohexol-enhanced scans obtained with 600 mg of iodine per kilogram, but with less lesion enhancement, which resulted in better liver-to-lesion contrast. Blinded readers had a higher sensitivity, accuracy, and area under the ROC curve for ITG-dual-enhanced scans as compared with iohexol-enhanced scans (P: <.01). CONCLUSION: ITG-dual-enhanced CT quantitatively and qualitatively improved liver lesion detection versus iohexol-enhanced CT. Future clinical trials with various human tumor types after potential approval for human use are needed to determine the ultimate role of this or other dual-mechanism contrast materials.
Animals↗
CT versus sonography for monitoring radiofrequency ablation in a porcine liver.
OBJECTIVE: The objective of this study was to compare CT and sonography for monitoring radiofrequency (RF) lesions in porcine livers. SUBJECTS AND METHODS: RF lesions (n = 12) were created in three pig livers by applying 13 min of current to a multielectrode RF probe with a target temperature of 95 degrees C. Helical unenhanced CT and corresponding axial sonography were performed before ablation, at 2 min, 8 min, and immediately after ablation. Contrast-enhanced CT was performed after ablation. CT scans and sonograms were evaluated by blinded observers for conspicuity of the RF lesion, edge detection (visibility of liver-lesion interface), and artifacts. Hounsfield units were recorded at every time interval, and radiologic-pathologic correlation for lesion size and configuration was performed. RESULTS: Mean size of RF lesions was 3. 03 +/- 0.9 cm. On CT, RF lesions had consistently lower attenuation values than surrounding liver (22.2 H lower than liver at 8 min, p < 0.0001). Echogenicity was variable with sonography (hypoechoic = 59%, hyperechoic = 25%, isoechoic = 16%). Unenhanced CT significantly improved conspicuity, edge detection of RF lesions, and decreased artifacts compared with sonography (p < 0.05). Contrast-enhanced CT improved RF lesion detection, border discrimination, and artifacts compared with sonography (p < 0.05). Unenhanced CT had the best correlation to pathologic size (r = 0.74), followed by contrast-enhanced CT (r = 0.72) and sonography (r = 0.56). Contrast-enhanced CT best correlated with lesion shape, but slightly overestimated size because of areas of ischemia peripheral to the RF lesion. CONCLUSION: In this animal model, unenhanced CT was an effective way to monitor RF ablation compared with sonography because of increased lesion discrimination, reproducible decreased attenuation during ablation, and improved correlation to pathologic size.
Animals↗
Therapeutic efficacy of anti-Lewis(y) humanized 3S193 radioimmunotherapy in a breast cancer model: enhanced activity when combined with taxol chemotherapy.
Monoclonal antibody therapy may provide new treatment options in the management of metastatic breast cancer by selectively targeting tumors and producing a therapeutic effect, by delivering radiation or other toxins directly to tumor cells, or by producing an intrinsic immune inflammatory response. The effect of 131I-labeled humanized anti-Lewis(y) monoclonal antibody 3S193 (hu3S193) was compared with that of placebo and radiolabeled huA33 control antibody in a series of radioimmunotherapy experiments in a MCF-7 xenografted BALB/c nude mouse breast cancer model. The maximum tolerated dose of 131I-labeled antibody occurred at 200 microCi/mouse, at which dose level three of six mice that received 131I-hu3S193 showed significant tumor growth inhibition in contrast to no responses in the comparable 131I-huA33 control treatment arm. Breast cancer is an ideal model to test the efficacy of combined modalities given its known sensitivity to both radiotherapy and chemotherapy. The synergy between radioimmunotherapy and chemotherapy was therefore also explored using a combination of 131I-labeled hu3S193 antibody and Taxol using subtherapeutic doses of each agent. The combination of Taxol and 100 microCi of 131I-hu3S193 produced significant tumor inhibition in 80% of mice, whereas no responses were seen with either treatment modality alone or the combination of Taxol and 131I-huA33. These results support a potential therapeutic role of radiolabeled hu3S193 in the treatment of breast cancer, including combination therapy with Taxol, and warrants further investigation of this promising new agent.
Adenocarcinoma↗
Intraoperative sonographic assessment of graft patency during extracranial-intracranial bypass.
Extracranial-intracranial (EC-IC) bypass may be necessary to facilitate treatment of unclippable posterior circulation fusiform aneurysms. Although intraoperative digital subtraction angiography (DSA) allows assessment of graft patency, this technique, because of difficulties inherent in performing selective catheterization and angiography in the operating room, has limitations. Duplex sonography, in contrast, is easily performed, and provides information regarding graft patency and blood flow direction during EC-IC bypass procedures. This latter information proved useful in determining the time of parent artery occlusion after two EC-IC bypass procedures performed for treatment of a fusiform midbasilar artery aneurysm.
Adult↗
Hepatic cryosurgery via minilaparotomy in a porcine model: an alternative to open cryosurgery.
BACKGROUND: Cryosurgery of liver lesions is becoming increasingly accepted for the ablation of liver tumors. Attempts at laparoscopic cryosurgery have been very limited and often need to be converted to open laparotomy due to the complexity of the procedure. METHODS: Seven domestic pigs were anesthetized, and 17 small (0.7 cm mean diameter) tumor mimicking agar "lesions" were percutaneously placed in the liver. Two small subcostal incisions ( approximately 2.0 cm) were placed, and an endocavitary ultrasound transducer (with a 2. 4-mm cryoprobe mounted on it) was placed on the liver surface. Lesions were localized and directly punctured with one or two cryoprobes under ultrasound guidance, and a single 15-min freeze was undertaken. The animals were then killed, and their livers were removed and serially sectioned. RESULTS: Total time for probe placement was approximately 10 min after incisions had been made. Animals tolerated the procedure well and all survived until they were killed. No intraabdominal complications were detected at exploration. Mean cryolesion dimensions were 3.0 cm (single probe) and 3.3 cm (dual probe) (p > 0.05). Positive margins were detected in one lesion treated with a single probe, and in none of the lesions treated with dual probes. Mean margins were 0.9 cm: 1.2 cm for the single probe and dual probe techniques, respectively. Liver surrounding control agar lesions demonstrated a thin rim of necrosis, approximately 0.5 mm wide. CONCLUSIONS: We conclude that minilaparotomy is an effective, safe, and simple method for performing hepatic cryosurgery in this animal model. This minimally invasive technique may benefit a subset of patients with lesions in accessible locations. Lesions in posterior locations may not be as amenable to this technique due to deterioration of ultrasound image quality in the far field.
Animals↗
Benefits and safety of hepatic resection for colorectal metastases.
BACKGROUND: Metastatic colorectal carcinoma to the liver is a potentially curable disease. The purpose of this study was to determine the safety and efficacy of hepatic resection for metastatic colorectal carcinoma. METHODS: One hundred twenty-one consecutive hepatic resections in 110 patients with metastatic colorectal cancer between January 1978 and September 1998 performed by a single surgeon were reviewed. RESULTS: The actuarial 5-year survival for all patients in the series was 46%. Of the patients operated on before 1993, the actual 5-year survival was 43% and actual disease-free 5-year survival was 28%. The actual 10-year survival was 27%, and of all patients operated on in the last 20 years, 48% are alive today. When comparing initial regional lymph node status, the 5-year survival was 54% for the patients with negative lymph nodes and 40% for patients with positive nodes. Only 18% of patients required a perioperative blood transfusion, and the median length of stay was 7 days. There were complications in 34% of cases, and the operative mortality was 4%. CONCLUSIONS: Hepatic resection for metastatic colon cancer is safe, and significant longevity and cure can be obtained after resection.
Adult↗
Ultrasound backscatter and attenuation in human liver with diffuse disease.
Ultrasound backscatter and attenuation in the liver were measured in patients with diffuse liver disease and in 35 volunteers who had no history of liver ailments. Measurements were done using radiofrequency (RF) echo signals derived from a clinical scanner; a reference phantom was scanned to account for effects of gain, transmit-receive frequency response and transducer beam patterns on echo data. The mean backscatter coefficient at 3 MHz in livers of 7 patients with fatty infiltration was 6.8 x 10(-3) cm(-1)sr(-1) compared to a mean of 0.5 x 10(-3) cm(-1)sr(-1) in healthy patients. Mean attenuation at 3 MHz was 2.54 dB/cm in fatty livers compared to 1.66 dB/cm in healthy patients. A total of 7 patients with end-stage liver disease (cirrhosis) had attenuation values similar to those in the healthy group, and their mean liver backscatter was somewhat greater than the mean backscatter for healthy livers. Quantitating both backscatter and attenuation should be considered for detecting fatty infiltration; additional processing methods are needed to differentiate cirrhotic changes on the basis of acoustic signals.
Adolescent↗
Evaluation of an experimental low-attenuation gastrointestinal contrast agent for CT imaging of intestinal ischemia in an animal model.
RATIONALE AND OBJECTIVES: The authors evaluated the use of MRX-320, a low-attenuation, expansile oral contrast agent, for the demonstration of intestinal ischemia in an animal model. MATERIALS AND METHODS: Nine dogs were given either MRX-320, water, or diatrizoate as an oral contrast agent through a jejunostomy tube. Two dogs received no oral contrast agent. Helical computed tomography (CT) was performed before the intravenous injection of 2.5 mL/kg iohexol at 4 mL/sec, during the arterial phase, and during the portal venous phase. Mesenteric ischemia was surgically induced, and the imaging protocol was repeated. Three readers rated the randomly assigned images for quality and demonstration of ischemia. Attenuation values for the intestinal lumen and wall were recorded. RESULTS: Examinations performed with MRX-320 provided the best discrimination between ischemic and nonischemic conditions (P < .05), followed by examinations with no oral contrast medium, examinations with water, and examinations with diatrizoate. Images obtained with MRX-320 also scored significantly higher on measures of image quality than those obtained with water or no oral contrast medium (P < .05). On images obtained with MRX-320, the bowel lumen measured -836.5 HU (P < .05 compared with other techniques). Water provided the least uniformity of distention, and diatrizoate provided the least mucosal detail. CONCLUSION: The use of MRX-320 as an oral contrast agent with an intravenous bolus of iohexol at CT increased reader confidence for the diagnosis of intestinal ischemia and improved subjective measures of image quality.
Administration, Oral↗
Radiofrequency ablation of hepatic malignancies: is heat better than cold?
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Cryosurgery↗
Computed tomographic angiography in the preoperative evaluation of potential renal transplant donors.
The preoperative screening of potential renal transplant donors has undergone a major evolution with the introduction of computed tomographic angiography. With computed tomographic angiography, the radiologist is able to provide the surgeon with precise and valuable preoperative details of renal arterial and venous anatomy. In addition, computed tomographic angiography provides valuable information regarding the renal parenchyma and adjacent organs. This helps reduce the risks and complications associated with transplant surgery and improves the chances of a successful outcome. Helical computed tomographic angiography is rapidly replacing intravenous urography and conventional angiography as the imaging modality of choice for evaluating renal donors.
Angiography↗
CT-monitored percutaneous cryoablation in a pig liver model: pilot study.
PURPOSE: To determine the safety and feasibility of percutaneous cryoablation with computed tomographic (CT) guidance in a pig liver model. MATERIALS AND METHODS: Nine angiographic balloons (mean diameter, 9 mm) were placed in the livers of seven domestic pigs (mean weight, 30.0 kg +/- 14.0 [SD]) as tumor-mimicking lesions. By using ultrasonographic and CT guidance, two 2.4- or 3.0-mm cryoprobes were placed flanking the balloon, and a 15-20-minute freezing process was performed. Hemostasis was achieved by placing absorbable cellulose fabric down the probe tract. After 24-96 hours, animals were sacrificed, and their livers were removed and were sectioned axially at 5-mm intervals for comparison with CT images. RESULTS: All animals survived the procedure without complication. No serious hemorrhage was found in any case. Ice balls were readily visualized at CT because they appeared as areas of decreased attenuation (1.0 HU +/- 20.7) when compared with areas of normal liver (48.2 HU +/- 6.3, P < .05). The mean ablative margin was 1.7 cm, and only one of nine cases, the one with probe failure, had a positive margin. Beam-hardening artifact from the metal probes was present but did not interfere with the procedure. Ice-ball size and shape corresponded closely to the area of necrosis determined at histopathologic analysis. CONCLUSION: CT-monitored percutaneous cryoablation is feasible and safe in this pig liver model.
Animals↗
Mucinous vacuolar change of porcine urothelium induced by regional embolism or cryoablation.
Porcine urinary tract epithelium responds to systemic infections with an increase in mucin secretion that has been called "mucinous degeneration." Here we describe similar changes in calyceal, pelvic, and ureteric urothelium in pig renal tracts 14 days after local embolism and cryoablation (four kidneys) or cryoablation alone (six kidneys). Large mucin-filled vacuoles surrounded by smaller cytoplasmic vesicles were present in the affected urothelium but were rare in calyceal urothelium of normal kidneys. These mucinous vacuolar changes were proportional to the extent of renal necrosis and could be important in the pathologic responses of xenotransplanted pig kidneys.
Animals↗
Monitoring renal cryosurgery: predictors of tissue necrosis in swine.
PURPOSE: To examine parameters for monitoring renal cryosurgery and correlate with histopathologic necrosis in a porcine model. Parameters include: 1) tissue temperature, 2) distance of tissue from the cryosurgical probe insertion site, and 3) inclusion of tissue by the visible iceball. MATERIALS AND METHODS: Following midline incision, 6 healthy kidneys from 3 domestic pigs were treated using a nitrogen-based cryosurgical system with 3.4 mm outer diameter cryoprobe. Temperatures were monitored at 6 sites in each kidney using prototype thermocouples. Gross and histologic analysis was performed on tissue harvested from each thermosensor site 24 hours postoperatively. RESULTS: All animals survived to complete the full protocol. Post-procedure bleeding was managed surgically. Histopathology revealed that complete ablation was uniformly produced at temperatures of -19.4C or lower in 13/13 tissue samples. Within 16 mm. of the probe insertion site, cells were uniformly ablated in 17/17 samples while degree of tissue death varied widely beyond this margin. Cell death was more likely found at points encompassed by the visible iceball (16/18, 89%) than those beyond it (2/18, 11%) [p <0.0001, Chi-square] while 2/18 (11%) of samples harvested from within the iceball margin were partially viable. CONCLUSIONS: Temperature monitoring using thermocouples during porcine renal cryosurgery demonstrated complete homogeneous necrosis of tissues reaching -19.4C or lower. Distance beyond 16 mm. from the cryoprobe and direct visualization of the iceball proved to be less reliable predictors of tissue necrosis. Management of bleeding post-thaw was necessary in every case.
Animals↗
Laparoscopic cryosurgery of the kidney in the porcine model: an acute histological study.
OBJECTIVES: To verify histologically whether cryosurgery of the kidney can be accomplished reproducibly without injuring adjacent structures, using a combination of ultrasound and laparoscopic guidance. MATERIALS AND METHODS: Six kidneys from three domestic female farm pigs were utilized in the study. Under general anesthesia and after obtaining pneumoperitoneum, the lower pole of the kidney was mobilized laparoscopically and the ureter and adjacent bowel were protected with saline-soaked gauze. Two 3.8 mm-cryoprobes were placed percutaneously into the lower pole and cryoablation was carried out under laparoscopic and ultrasound guidance using a double-freeze technique (10-minute freeze and 5-minute thaw cycles to a probe temperature of -185 degrees C to -196 degrees C) in five kidneys (one control). The kidneys, adjacent ureter and bowel were harvested acutely, and macroscopic, histologic, and electron microscopic evaluation of all specimens was performed. RESULTS: Macroscopically, clear margins of cryodestruction corresponded with the ultrasound images of the iceball. In all five treated kidneys, reproducible cell death corresponding to visible margins of cryodestruction were verified histologically. Cell death was further corroborated by electron microscopy. Adjacent structures (ureter and bowel) were sectioned and no significant damage was noted. Blood pressure remained constant throughout the procedure. A crack in the renal parenchyma of one kidney was noted during the thaw phase; at harvest that animal was found to have an intraperitoneal hemorrhage. CONCLUSION: Combined laparoscopic and ultrasound-guided cryoablation of the lower pole of the kidney can be accomplished reproducibly in the porcine model without injury to adjacent structures.
Animals↗
Lipid-based blood-pool CT imaging of the liver.
RATIONALE AND OBJECTIVES: We have recently developed an iodinated lipid-based contrast agent capable of residing in the blood pool for extended periods of time relative to conventional water-soluble contrast agents. The purpose of this study was to examine the effects of combining this new blood-pool agent (ITG-PEG) with a hepatocyte-selective agent (ITG-LE; Molecular Biosystems) for accurate CT detection of small (< 10 mm) VX2 tumors in rabbit liver. MATERIALS AND METHODS: Preliminary pharmacokinetic analyses were conducted in SD rats (12) by injection of either I-125-labeled ITG-PEG or I-125-labeled ITG-LE followed by subsequent blood collection and quantification of radioactivity. Preliminary CT studies were conducted in both normal (3) and tumor-bearing NZW rabbits (2). Tumor-bearing rabbits were laparotomized and VX2 cells injected directly into the hepatic parenchyma to produce a total of eight focal lesions (2-10 mm diameter). Animals underwent CT scanning 10 days later with multiple techniques including noncontrast and helical i.v. enhanced (600 mg I/kg iohexol), and then 24 hours later using both ITG-PEG and ITG-LE (200 mg I/kg). Tissue density measurements (HU) of liver, tumor, and blood (descending aorta) were acquired in each case for comparison. Tumor morphology was verified by gross pathologic inspection. RESULTS: Pharmacokinetic analysis in rats as well as CT studies in normal rabbits revealed that ITG-PEG remains in the blood-pool phase for more than 2 hours following i.v. administration. In fact, blood density in normal rabbit obtained with ITG-PEG was 95.1 HU +/- 5.8 at 120 minutes compared to 90.7 HU +/- 6.1 immediately after injection. Although liver enhancement was greater with iohexol (67 HU within 1 minute of injection), than for ITG-PEG/ITG-LE (32 HU, 60 minutes postinjection), liver to lesion ratios favored ITG-PEG/ITG-LE due to significant enhancement of tumor itself with iohexol (+40 HU). Tumor enhancement was minimal with ITG-PEG/ITG-LE. Lesions were subjectively much better defined with ITG-PEG/ITG-LE with sharper edge definition. CONCLUSION: In these animal models, a new iodinated lipid-based contrast agent composed of both blood pool and hepatocyte-selective components afforded favorable CT imaging results compared to a conventional urographic agent, albeit at one-third the total iodine dose.
Animals↗
Laparoscopic renal cryotherapy in swine: comparison of puncture cryotherapy preceded by arterial embolization and contact cryotherapy.
Variable results of open, percutaneous, and laparoscopic cryosurgery of the kidney have been reported. Minimally invasive approaches to lower-pole renal ablation were prospectively compared in swine: laparoscopic puncture cryoablation preceded by arterial embolization, laparoscopic contact cryosurgery, and arterial embolization alone. Eighteen kidneys in nine domestic pigs were randomized to one of three treatment groups of six organs each: (1) puncture cryotherapy preceded by selective lower-pole arterial embolization; (2) contact cryotherapy alone; and (3) arterial embolization alone. Under general anesthesia, appropriate animals underwent selective arterial embolization of the lower pole via femoral cutdown using Gelfoam pledgets. Animals randomized to cryotherapy underwent dissection of the lower pole of the kidney using a single 12-mm umbilical and two midclavicular-line ports in the lateral position. Under external ultrasound guidance, two 3-mm cryoprobes (Cryomedical Sciences, Rockville, MD) were positioned in the lower pole of the kidney, and double-freeze technique to -190 degrees C was performed using puncture or contact application. Ultrasonography was used to guide probe insertion during puncture cryotherapy only. Kidneys were harvested 11 to 14 days after the procedure. Both puncture and contact kidneys demonstrated cell death and subsequent necrosis by light microscopy and electron micrography. On average, puncture lesions were heavier than contact lesions, 19.3 g v 10.1 g (P = 0.02; unpaired t-test), whereas the kidneys were equivalent in weight: 74.1 g v 74.1 g. Puncture lesions represented 26.4% of total kidney weight v 13.5% in the contact group (P = 0.002; unpaired t-test). Only focal infarcts were identified in the embolization group. No evidence of adjacent visceral injury was identified in any of the groups, and no animal required conversion to open laparotomy. One kidney bled after contact cryotherapy, and hemostasis was achieved laparoscopically. Laparoscopic cryotherapy is reproducible and effective using either the puncture technique preceded by arterial embolization or the contact technique, without evidence of damage to adjacent structures. Contact lesions were less voluminous and more peripheral than puncture lesions. Embolization alone produces focal infarcts and focal zones of cell death.
Animals↗
Direct immobilization of gangliosides onto gold-carboxymethyldextran sensor surfaces by hydrophobic interaction: applications to antibody characterization.
We describe a novel immobilization technique to investigate interactions between immobilized gangliosides (GD3, GM1, and GM2) and their respective antibodies, antibody fragments, or binding partners using an optical biosensor. Immobilization was performed by direct injection onto a carboxymethyldextran sensor chip and did not require derivatization of the sensor surface or the ganglioside. The ganglioside appeared to bind to the sensor surface by hydrophobic interaction, leaving the carbohydrate epitope available for antibody or, in the case of GM1, cholera toxin binding. The carboxyl group of the dextran chains on the sensor surface did not appear to be involved in the immobilization as evidenced by equivalent levels of immobilization following conversion of the carboxyl groups into acyl amino esters, but rather the dextran layer provided a hydrophilic coverage of the sensor chip which was essential to prevent nonspecific binding. This technique gave better reactivity and specificity for anti-ganglioside monoclonal antibodies (anti-GD3: KM871, KM641, R24; and anti-GM2: KM966) than immobilization by hydrophobic interaction onto a gold sensor surface or photoactivated cross-linking onto carboxymethydextran. This rapid immobilization procedure has facilitated detailed kinetic analysis of ganglioside/antibody interactions, with the surface remaining viable for a large number of cycles (>125). Kinetic constants were determined from the biosensor data using linear regression, nonlinear least squares and equilibrium analysis. The values of kd, ka, and KAobtained by nonlinear analysis (KAKM871 = 1.05, KM641 = 1.66, R24 = 0.14, and KM966 = 0.65 x 10(7) M-1) were essentially independent of concentration and showed good agreement with data obtained by other analytical methods.
Antibodies, Monoclonal↗