Computed tomography-guided neurolytic celiac plexus block with alcohol complicated by superior mesenteric venous thrombosis.

Neurolytic celiac plexus block (CPB) under radiological guidance is often performed to manage pain associated with pancreatic cancer. Serious complications related to the block are rare. Computed Tomography (CT)-guided neurolytic CPB is advocated to improve the efficacy of the block and to reduce the incidence of associated complications. We describe a case of superior mesenteric vein thrombosis associated with neurolytic CPB performed under CT guidance.

Improved method for in vivo magnetic resonance contrast media research.

This paper describes an approach for contrast media research with which high resolution MR images of rats can be studied before, during, and after intravenous contrast media administration. Using a probe designed to hold up to eight rats, the contrast-enhancing properties in normal rat brains of Gd-DTPA, a low molecular weight compound, and polylysine-(Gd-DTPA), a high molecular weight compound, were compared simultaneously in two groups of four rats each. Signal intensity-time graphs, as measured over various anatomical structures of the normal rat head, demonstrated the feasibility of directly comparing enhancement patterns of two pharmacologically different contrast agents and obtaining relevant data in a single experiment.

Hepatic contrast-enhancing properties of manganese-mesoporphyrin and manganese-TPPS4. A comparative magnetic resonance imaging study in rats.

OBJECTIVES: Manganese (III) mesoporphyrin (Mn-mesoporphyrin), a synthetic and stable complex, was investigated for its hepatic magnetic resonance imaging (MRI) properties and compared with manganese tetrakis-(4 sulfonatophenyl) porphyrin (Mn-TPPS4). METHODS: Liver abscesses (n = 10) and tumors (n = 14) were induced in rats. These rats then underwent MRI at 2.0 T. Animals received one of the two contrast agents, and measurement of lesion enhancement was performed. RESULTS: At an intravenous dose of 0.035 mmol/kg, Mn-mesoporphyrin caused significant enhancement of normal liver parenchyma and increased the lesion-to-liver contrast in both the models of heptic liver abscess and metastatic liver disease. Mn-TTPS4 at an intravenous dose of 0.04 mmol/kg typically enhanced both lesion and normal liver parenchyma and therefore did not improve the lesion-to-liver contrast. CONCLUSIONS: The hepatotrophic properties of Mn-mesoporphyrin indicate its potential as an intravenous contrast agent for liver imaging.

Imaging of exocrine pancreatic function. Investigation of the bioavailability of weak organic acids as potential pancreatic contrast agents for computed tomography.

RATIONALE AND OBJECTIVES: The feasibility of targeting iodinated contrast agents to the exocrine pancreas was investigated. Iodinated weak organic acids including succinic acid-mono-3-amino-2,4,6-triiodo- N-ethylanilide (compound I), the ethanolamine salt of N-ethylsuccinic acid-(2,4,6-triiodo-3-methylamino anilide) (compound II), and the sodium salt of 2,4,6-triiodo-3-N-ethylacetylamino-phenylpropionic acid (compound III) were studied as potential contrast agents for computed tomography (CT) of the pancreas. METHODS: An ex vivo perfusion system was used to compare pancreatic uptake of the three compounds. In vivo CT studies were conducted using domestic pigs to study potential enhancement of the pancreas after intravenous injection of the compound. RESULTS: Ex vivo perfusion studies with isolated rat pancreas demonstrated nearly identical extraction ratios of approximately 0.6 for all three compounds tested. Average iodine concentrations measured in pancreas at the end of the perfusion studies was 0.27 mg/g +/- 0.20 for compound I, 0.18 mg/g +/- 0.06 for compound II, and 0.16 mg/g +/- 0.09 for compound III. Differences in iodine concentrations retained were not statistically significant. Computed tomography studies in domestic pigs demonstrated up to 30% enhancement of the pancreas after intravenous injection of 75 and 150 mg/kg of compound II at 45 minutes. Whereas ex vivo perfusion studies indicated increasing extraction of the three compounds with increasing doses/concentrations in the perfusate, no improved contrast enhancement was observed at the higher dose level compared with the lower dose in CT. CONCLUSION: Both ex vivo perfusion studies and dose-independent enhancement levels achieved seem to indicate a transport maximum in the pancreas for the iodinated weak organic acids studied.

Association with oleic acid vesicles enhances manganese III mesoporphyrin absorption and biliary elimination in rats.

OBJECTIVE: To determine whether the association of manganese III mesoporphyrin (MnMeso), an oral MR contrast agent, to oleic acid (OA) vesicles will improve absorption and delivery of MnMeso to the liver. METHODS: MnMeso or MnMeso-OA vesicle suspension was intraduodenally administered to rats and the time course of MnMeso concentration in plasma, bile, and intestinal solution was determined. Tissue concentrations of MnMeso in the liver were also determined. RESULTS: Association of MnMeso to OA reduced the time it took to reach one-half absorption maximum, TC50, and enhanced the rate and the extent of biliary elimination of this contrast agent. In addition, the results obtained from dose-titration studies indicate that MnMeso-OA vesicle complex may enhance MnMeso accumulation in the liver, observed as a lower dose required to reach equivalent tissue concentration. Taken together, complexion to OA vesicles may provide rapid absorption, enhanced liver accumulation, and efficient elimination of MnMeso. CONCLUSIONS: Association with OA vesicles may enhance the rate of MnMeso absorption and biliary excretion while promoting the extent of liver accumulation of MnMeso in rats. This strategy may provide a means to provide safe and effective use of MnMeso as an MR contrast medium.

Albumin labeled with Gd-DTPA. An intravascular contrast-enhancing agent for magnetic resonance blood pool imaging: preparation and characterization.

A paramagnetic-labeled macromolecule, albumin-(Gd-DTPA), was prepared for use as an intravascular contrast agent for magnetic resonance imaging. An average of 19 Gd-DTPA chelates were covalently conjugated to human serum albumin through the bifunctional anhydride of DTPA. The albumin-(Gd-DTPA) was characterized with use of high-performance liquid chromatography, sodium dodecyl sulfate gel electrophoresis, atomic absorption, biuret and Bradford protein tests, and by its effect on proton relaxation (relaxivity). The average molecular weight was 92,000 daltons, indicating the albumin conjugate was predominantly monomeric. The T1 relaxivity of albumin-(Gd-DTPA) was 273 mM-1 sec-1 relative to carrier concentration, which corresponds to a relaxivity of 14.9 mM-1 sec-1 relative to gadolinium concentration. The average conditional stability constant for albumin-bound Gd-DTPA chelate was log K = 20.0. Spin-echo images of rats demonstrated persistent enhancement of vascular tissues and slowly flowing blood. Application of albumin-(Gd-DTPA) may augment the MR assessments of blood volume, tissue perfusion, and flow characteristics.

Magnetic resonance imaging of experimental renal hemorrhage.

Experimental renal hemorrhage was induced by injecting autologous blood into the left kidney of 13 rats. To investigate the magnetic resonance (MR) characteristics of acute renal hemorrhage and subsequent stages of resolution, repetitive MR images were obtained using a 0.35 Tesla imager during a period of 21 days postinduction. A dual spin-echo imaging (TR 500 and 2,000 msec, TE 28 and 56 msec) was used to calculate the relaxation times and record the intensities in the renal medulla and cortex. Histologic examination (n = 9) indicated that blood was dispersed intrarenally, and no encapsulated hematoma developed. The signal intensity on the T1- and T2-weighted images, as well as the relaxation times in the hemorrhagic renal parenchyma were unchanged during 21 days when compared with intact kidney values. Subcapsular fresh blood had a high signal intensity on T2-weighted images. A marked overlap of the relaxation parameters between intact kidney parenchyma and diffuse intrarenal hemorrhage was observed. Detection of dispersed intrarenal blood using spin echo MR imaging may be difficult.

Magnetic resonance imaging of myocardial infarction using albumin-(Gd-DTPA), a macromolecular blood-volume contrast agent in a rat model.

Magnetic resonance (MR) contrast enhancement of acute myocardial infarction was studied in rats using albumin-(Gd-DTPA), a paramagnetic macromolecule with prolonged intravascular retention after intravenous injection. Histologic examination and distribution measurements of radiolabeled microspheres confirmed induction of regional myocardial infarction after ligation of the left coronary artery. ECG-gated spin-echo images at 2.0 Tesla, employing short, T1-weighted pulse sequence settings, demonstrated time-persistent and significant (P less than .05) enhancement of normal myocardium (66%) and an even greater enhancement of the infarcted area (100%), for as long as 60 minutes after injection of 160 mg/kg albumin-(Gd-DTPA). The contrast difference between normal and infarcted myocardium was increased significantly (P less than .05) after administration of albumin-(Gd-DTPA). The prolonged enhancing effects of albumin-(Gd-DTPA) on MR images are useful for evaluating regional differences in blood volume and capillary integrity between normal and infarcted myocardium.

Pharmaceutical properties, biodistribution, and imaging characteristics of manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic resonance imaging.

OBJECTIVES: Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for its pharmaceutical properties and magnetic resonance imaging characteristics as a potential hepatobiliary contrast agent. METHODS: Solubility, partition coefficient, plasma binding, proton relaxation enhancement, biodistribution, biliary excretion, liver extraction ratio, and liver enhancement were measured in various in-vitro and in-vivo systems. RESULTS: Mn-mesoporphyrin was soluble and stable at moderate alkaline pH in phosphate buffer. The octanol/water coefficient was 25.98, and the compound was highly protein bound. R1 for water and plasma were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calculated to be 15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed hepatotrophic properties and biliary excretion was 65% over 24 hours. First pass liver uptake was 15%. Magnetic resonance imaging studies showed persistent liver enhancement at 0.05 mmol/kg. CONCLUSION: Mn-mesoporphyrin is a lipophilic compound that shows potential as a hepatobiliary magnetic resonance contrast agent.

Dyke Award Paper. Kinetics of pathologic blood-brain-barrier permeability in an astrocytic glioma using contrast-enhanced MR.

PURPOSE: The feasibility of measuring blood-brain barrier permeability was studied in a 36B-10 brain glioma model in rats. MATERIALS AND METHODS: In stage I of our study, sequential MR images of glioma-implanted rats were obtained following intravenous administration of three contrast agents of different molecular sizes--Gd-DTPA, polylysine-(Gd-DTPA), and albumin-(Gd-DTPA). In a second set of experiments, sequential MR imaging with Gd-DTPA, quantitative measurements of plasma Gd-DTPA concentration, and postmortem tumor Gd-DTPA measurements were used to estimate the blood-to-tissue transport coefficient (Ki) in the rat glioma model at 11 and 15 days postimplantation. RESULTS: In stage I, Gd-DTPA caused rapid and greatest tumor enhancement with a significant washout from the tumor during the 120-min experiment. Tumor enhancement using polylysine-(Gd-DTPA) occurred later and was significantly less compared to Gd-DTPA. Tumor signal intensity increased only slowly over time and the peak level of enhancement was least using albumin-(Gd-DTPA). In stage II, the mean (+/- 1 SD) Ki values were 1.1 +/- .24 at 11 days, and 9.3 +/- .8 at 15 days postimplantation. These results correspond well with published data obtained by autoradiography. CONCLUSION: We believe that the differential enhancement pattern using contrast agents of different molecular sizes reflects a differential permeability of the pathologic blood-brain barrier, and that our studies demonstrate the feasibility of using frequent sequential images and a graphical approach to Ki calculation to determine the blood-to-tissue transport coefficient using contrast-enhanced MR.

Lesion enhancement in radio-frequency spoiled gradient-echo imaging: theory, experimental evaluation, and clinical implications.

PURPOSE: To investigate the lesser lesion conspicuity after gadolinium contrast infusion with radio-frequency spoiled gradient-echo (SPGR) sequences relative to conventional T1-weighted spin-echo techniques. METHODS: The influences of repetition time, echo time, and flip angle on spin-echo and SPGR signal were studied with mathematical modeling of the image signal amplitude for concentrations of gadopentetate dimeglumine solute from 0 to 10 mM. Predictions of signal strength were verified in vitro by imaging of a doped water phantom. The effects of standard (0.1 mmol/kg) and high-dose (0.3 mmol/kg) gadoteridol on spin-echo and SPGR images were also investigated in three patients. RESULTS: The measured amplitude of undoped water and the rate of increase of doped water signal with increasing gadopentetate concentration (slope) for spin-echo 600/11/1/90 degrees (repetition time/echo time/excitations/flip angle) and SPGR (600/11/190 degrees) were similar and exceeded those of SPGR (35/5/145 degrees). Greater increases in SPGR doped water signal and its slope were produced by increasing TR than by varying echo-time or flip angle. The subjective lesion conspicuity and measured lesion contrast at 0.3 mmol/kg were greater with spin-echo (600/11/1/90 degrees) than with SPGR (35/5/145 degrees) in all three patients; the measured lesion enhancement was similar for both techniques in two patients and decreased for SPGR in the third patient. CONCLUSIONS: The phantom studies suggest that the short repetition time of 35 msec, typically used in clinical SPGR imaging, is largely responsible for a reduced signal amplitude and a diminished rate of increase of signal with increasing gadopentetate concentration, relative to spin-echo. Phantom and clinical studies suggest that the dose of paramagnetic agent required to achieve SPGR lesion conspicuity with short repetition time comparable with spin-echo would have to be higher than the dose in current clinical use.

MR assessment of radiation-induced blood-brain barrier permeability changes in rat glioma model.

PURPOSE: To assess the potential of a T1-weighted, gadolinium-enhanced MR technique for quantifying radiation-induced changes of blood-brain barrier permeability in a model of stereotactically implanted intracerebral gliomas in rats. METHODS: We calculated the gadolinium blood-to-tissue transport coefficient for gadopentetate dimeglumine from signal intensities in sequential MR images in nine control animals that were not irradiated and in five and three animals that had received 2500 cGy and 1500 cGy whole-brain irradiation, respectively, at 2 days before imaging. RESULTS: The average blood-to-tissue transport coefficient values were 9.76 mL.kg-1.min-1 in the control group, 23.41 mL.kg-1.min-1 in the 2500 cGy group, and 25.63 mL.kg-1.min-1 in the 1500-cGy group. Blood-to-tissue transport coefficients were significantly higher after irradiation, indicating increased radiation-induced blood-brain barrier permeability. Similar increased blood-brain barrier leakiness in brain tumors after high-dose irradiation has been shown by previous nuclear medicine studies using quantitative autoradiography. CONCLUSION: Contrast-enhanced dynamic MR of brain gliomas is a sensitive method to document radiation-induced blood-brain barrier breakdown. Quantitative gadolinium-enhanced MR may become a useful tool for the management of patients with brain tumors undergoing radiation therapy.

Detection and characterization of atherosclerotic fibrous caps with T2-weighted MR.

PURPOSE: We assessed the performance of T2-weighted MR imaging in detecting atherosclerotic fibrous caps and in depicting their integrity. METHODS: Twenty atherosclerotic lesions removed by carotid endarterectomy were imaged on a 1.5-T system using T2-weighted spin-echo sequences. The MR images were reviewed independently by four blinded interpreters for fibrous caps and ruptures. The results obtained from the observers were then graded against histologic findings by using receiver-operating characteristic (ROC) curve analysis. RESULTS: The area under the ROC curve for fibrous cap detection was 0.80, indicating that T2-weighted MR imaging was a good but not definitively diagnostic test for detecting ex vivo fibrous caps. The ROC curve for fibrous cap characterization yielded an area of 0.75, indicating that T2-weighted MR imaging was a fair but not highly diagnostic test for depicting fibrous cap integrity. A definite reading for detection of fibrous caps or rupture was fairly specific (90% and 98%, respectively) but not very sensitive (37% and 12%, respectively). CONCLUSIONS: T2-weighted MR imaging of ex vivo atherosclerotic plaques aided in the detection and evaluation of fibrous caps. In both cases, MR imaging proved more useful for ruling out disease than for confirming its presence.

MR imaging of liver abscesses; application of Gd-DTPA.

The potential utility of Gd-DTPA contrast enhancement of MR images in the evaluation of liver abscesses was assessed in rodents. Twelve rats with surgically implanted sterile liver abscesses were imaged at various stages of focal hepatic inflammation, 48 hours, 4 days, 7 days, 14 days and 21 days after lesion induction. Spin echo images, acquired before and repeatedly after intravenous injection of 0.2 mmol/kg Gd-DTPA, demonstrated improvement of the lesion-to-background contrast ranging from 2% to 40% depending on the stage of the disease. The enhancement pattern also varied with abscess evolution. Two, four and seven-day-old abscesses typically showed a ring enhancement, whereas two- and three-week-old abscesses presented largely homogeneously enhancing lesions. In the earlier lesions, contrast enhanced rim surrounding the low intensity center corresponded histologically to the formation of a capsule consisting of fibrous tissue and inflammatory cells. The center was necrotic. Data show that abscesses can be detected on images acquired with long repetition and echo times without injection of Gd-DTPA. The administration of Gd-DTPA, however, improved the lesion-to-background contrast and helped to define the abscess capsule evolution.

Liver hemostasis using high-intensity focused ultrasound.

Liver hemorrhage, the major cause of death in hepatic trauma, is notoriously difficult to control. We report on the use of high-intensity focused ultrasound (HIFU) to arrest the bleeding from incisions made in rabbit livers. A HIFU transducer, with a spherically curved aperture of 6.34 cm2 area, a focal length of 4 cm and a frequency of 3.3 MHz was used. In approximately 94% of the incisions, the hemorrhage was reduced to a slow oozing of blood in less than 2 min. The maximum temperature of liver tissue around the incision area, during HIFU application, was measured to be 86 degrees C. The mechanism of hemostasis, confirmed by histological examination, appears to be coagulative necrosis of a volume of liver tissue around the incision. We believe that acoustic hemostasis, with the unique characteristic of "volume cauterization," offers a novel method for the management of liver hemorrhage and, thus, has major clinical implications.

Two prototype blood-pool agents for contrast-enhanced magnetic resonance angiography of the portal vein in pigs.

RATIONALE AND OBJECTIVES: Macromolecular "blood-pool" agents such as polylysine-gadopentetate dimeglumine or albumin-gadopentetate dimeglumine, which provide prolonged intravascular enhancement, were tested as magnetic resonance (MR) angiography contrast agents for the portal vein in pigs. METHODS: Phase-contrast MR angiography of the portal veins was performed on six pigs before and after intravenous administration of polylysine-gadopentetate dimeglumine (n = 3) or albumin-gadopentetate dimeglumine (n = 3). RESULTS: The contrast-to-noise ratio of the portal veins was improved by 74% and 52%, respectively, using polylysine-gadopentetate dimeglumine or albumin-gadopentetate dimeglumine. More branches of the intrahepatic portal veins were visualized on postcontrast images. CONCLUSION: Blood-pool paramagnetic contrast agents improved the visualization of hepatic vasculature using phase-contrast MR angiography in our experimental model.

CT blood pool enhancement in primates with lopromide-carrying liposomes containing soy phosphatidyl glycerol.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the feasibility of using iodinated liposomes as blood pool agents for computed tomography (CT) in nonhuman primates. MATERIALS AND METHODS: Five normal adult baboons (15-21 kg) were anesthetized and intravenously injected with iopromide containing soy phosphatidyl glycerol liposomes with a diameter of 195 nm. Each animal received a dose of 300 mg total iodine per kilogram (46% encapsulation). RESULTS: The animals tolerated the injections well, experiencing no measurable electrocardiographic changes, and recovered uneventfully from anesthesia. Sequential helical CT scans of the baboons from the base of the skull to the symphysis pubis acquired up to 40 minutes after injection showed persistent blood pool enhancement. Maximum mean enhancement of major vascular structures was 106 HU at 1 minute after contrast medium injection. Mean blood pool enhancement was 76, 72, and 67 HU at 10, 20, and 40 minutes after injection, respectively. Liver and spleen were enhanced by 40 and 41 HU, respectively, 40 minutes after injection. No significant enhancement was measured in the brain and pancreas. CONCLUSION: Soy phosphatidyl glycerol with iopromide liposomes produces prolonged vascular enhancement and has potential as a blood pool CT contrast agent in primates.

Intestinal absorption of Mn-mesoporphyrin in a small bowel sac system: effect of oleic acid.

RATIONALE AND OBJECTIVES: The authors investigated the effect of oleic acid (cis-9-octadecenoic acid) (OA), a lipidic carrier, on the intestinal absorption rate and T1 relaxation time of manganese (III) mesoporphyrin (Mn-mesoporphyrin), a prototype hepatobiliary contrast agent for magnetic resonance imaging. METHODS: Mn-mesoporphyrin was formulated with OA at various concentrations. Small bowel sacs were created in 36 rats and filled with complexed and free Mn-mesoporphyrin. Intestinal absorption of Mn-mesoporphyrin was measured with spectrophotometry at 364 nm. T1 relaxation times were measured in samples of Mn-mesoporphyrin solutions, bowel wall, liver, and bile. RESULTS: Absorption rates ranged from 4.2%/cm2/h to 13%/cm2/h. Absorption was greatest (13%/cm2/h) when a combination of 1 mmol/L Mn-mesoporphyrin and 26.5 mmol/L OA was used. The T1 of bile decreased from 2,480 to 248 msec (maximum decrease) in rats that received Mn-mesoporphyrin. CONCLUSION: Mn-mesoporphyrin is absorbed from the small bowel in both the lipid-associated and free form, resulting in substantial shortening of the T1 in bile.

Intravenous manganese-mesoporphyrin as a magnetic resonance imaging contrast agent: an experimental model using VX-2 carcinoma in rabbits.

RATIONALE AND OBJECTIVES: We investigated the potential of manganese (III) mesoporphyrin (Mn-mesoporphyrin) as a hepatobiliary contrast agent for magnetic resonance (MR) imaging in rabbits given VX-2 carcinoma liver implants. METHODS: Rabbits given VX-2 carcinoma liver implants (n = 8) were imaged before and after the intravenous (i.v.) administration of 0.04 mmol/kg Mn-mesoporphyrin. MR images were correlated with gross-specimen cross-sections. The distribution of Mn in various tissues following i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin was determined using atomic absorption analysis. A standard panel of serum chemistries was followed over 7 days in six rabbits following this same dose of Mn-mesoporphyrin and compared with chemistries from two control rabbits. RESULTS: I.v. administration of 0.04 mmol/kg (25 mg/kg) Mn-mesoporphyrin resulted in improvement of tumor-to-liver contrast, with enhancement of normal liver (99.7 +/- 14.7%) and the gallbladder (442 +/- 116%), but not VX-2 tumor tissue (14.8 +/- 13.9%), (n = 8, p = .05). Analysis of tissue Mn levels 100 min after i.v. Mn-mesoporphyrin injection demonstrated preferential distribution of Mn to normal liver tissue (57.8 +/- 15.3 micrograms Mn/g) compared with VX-2 tumor (4.28 +/- 1.48 micrograms Mn/g). No significant change was found in the serum chemistries of six normal rabbits over a 7-day period after the i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin. CONCLUSION: I.v. Mn-mesoporphyrin improved lesion-to-liver contrast because of preferential distribution of Mn-mesoporphyrin to normal liver parenchyma and bile.

Liver contrast enhancement in primates using iopromide liposomes.

RATIONALE AND OBJECTIVES: We studied the feasibility of using iodinated liposomes as computed tomography (CT) liver contrast agents in nonhuman primates. METHODS: Iopromide-containing liposomes were investigated as reticuloendothelial (RES) contrast agents for CT scanning of the liver in normal adult baboons. For intravenous (i.v.) injection, liposomes were resuspended in mannitol solution, filtered under sterile conditions, and injected i.v. at doses of 200 and 400 mg l/kg to each of five anesthetized adult baboons. RESULTS: Animals tolerated the injections without measurable electrocardiographic changes and recovered uneventfully from anesthesia. Sequential CT scans of the baboons' upper abdomen acquired up to 60 min postinjection showed persistent enhancement of the liver 10-60 min after injection. Maximum enhancement levels were 36 and 61 delta Hounsfield units (delta H) after the 200- and 400-mg/kg doses, respectively. The mean time to plateau enhancement was 20 min with the 200-mg/kg dose and 10 min with the 400-mg/kg dose. The greatest splenic enhancements were 181 and 301 delta H after the 200- and 400-mg/kg doses, respectively. CONCLUSION: Iopromide liposomes are effective as RES contrast agents in primates.