Investigation of MR contrast media utility with the VX-2 tumor model.
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Adenocarcinoma↗
Biomedical subjects
V M Runge
Publications and source records attributed to V M Runge.
Dynamic contrast-enhanced magnetic resonance imaging in a model of splenic metastasis.
RATIONALE AND OBJECTIVES: The use of rapid dynamic magnetic resonance (MR) imaging after bolus intravenous contrast injection, to improve detection and delineation of parenchymal disease, was evaluated in an experimental model of splenic metastasis. METHODS: An experimental model for splenic metastasis was first developed in the New Zealand White rabbit. Magnetic resonance studies were then obtained at 1.5 tesla in six animals. A 25 ga needle was used to penetrate the spleen and inject 0.1 mL of minced, screened VX2 adenocarcinoma (obtained from a carrier rabbit). The injections were performed by two techniques, percutaneously using ultrasound guidance (n = 3) and at the time of abdominal laparotomy (n = 3). The animals were imaged at 1.5 tesla on day 10 after implantation. Breath-hold T2-weighted and T1-weighted scans were acquired prior to contrast injection. A dose of 0.3 mmol/kg gadoteridol (ProHance) was then administered intravenously using an MR-compatible power injector, with both dynamic and delayed postcontrast scans obtained. The lesion was confirmed in each animal by gross pathologic and microscopic exam. RESULTS: On region of interest analysis of T2-weighted scans, the lesions could not be differentiated by signal intensity (with any statistical significance) from normal surrounding splenic parenchyma. Lesion conspicuity, assessed by signal difference/noise ratio on dynamic turbo-FLASH scans, increased from 6+/-5 precontrast to a peak of 16+/-5 at 31 seconds postcontrast, with P < 0.003 (n = 6). Lesion conspicuity steadily diminished from this time to 5 minutes postinjection, although it was still improved at 5 minutes over precontrast scans. CONCLUSIONS: On early dynamic contrast enhanced breath-hold MR, marked improvement in the differentiation of splenic metastases from surrounding normal parenchyma is achieved. The capability of dynamic MR in this regard is analogous to that demonstrated for helical computed tomography.
Adenocarcinoma↗
Magnetic resonance imaging in a spinal abscess model. Preliminary report.
RATIONAL AND OBJECTIVES: Magnetic resonance (MR) scan technique and lesion detectability were evaluated using a newly developed spinal abscess model in the New Zealand White rabbit. METHODS: To create the lesion, an epidural needle was inserted under fluoroscopic guidance in the lumbar region and advanced to penetrate the ligamentum flavum. Next, polyethylene tubing was fed through the needle into the epidural space. A mixed suspension of Staphylococcus aureus (Cowan I) and blue polystyrene microspheres then was injected. Lesions were evaluated by MR imaging in four animals at multiple time points (3, 6, and 9 days). Imaging was performed at 1.5 tesla using a surface coil. Precontrast T2-and T1-weighted scans were first obtained. The T1-weighted scans were acquired both with and without fat saturation, and were repeated after intravenous contrast administration. The contrast agent used was gadoteridol (gadolinium HP-DO3A or ProHance) at a dose of 0.3 mmol/kg. RESULTS: On prospective film review, postcontrast scans proved superior for lesion detection. A spinal abscess could be identified postcontrast in all cases, irrespective of the use of fat saturation. The next best imaging technique for lesion detection was the T2-weighted scan, with 5 of 8 lesions noted thereon. Visualization of lesion margins proved to be a primary factor in prospective lesion identification. Region of interest image analysis demonstrated the postcontrast scans to be superior to all precontrast scan techniques for conspicuity of the interface between the abscess and the compressed spinal cord, with these results statistically significant. The lesions were characterized histologically by infiltrates of heterophils into the meninges and outer spinal cord with accompanying mild hemorrhage, fibrin exudation, and bacterial colonies. The lesions in three animals were confirmed to be in the epidural space, with the lesion in one animal in the subdural space. CONCLUSIONS: The current animal model was developed to study spine infection and, specifically, imaging characteristics and lesion detectability on MR. With the increased use of epidural catheters for pain management and the large number of acquired immunodeficiency syndrome cases, epidural infection is becoming an increasingly important clinical problem. Imaging technique, in particular the use of intravenous contrast, is critical for lesion detection and evaluation.
Abscess↗
Evaluation of standard and high-dose contrast-enhanced breath-hold liver magnetic resonance for visualization of metastatic disease in an animal model.
RATIONALE AND OBJECTIVES: The ability of dynamic contrast-enhanced magnetic resonance imaging to improve detection of liver metastases was evaluated in an experimental rabbit model. Scans using two different contrast doses, 0.1 and 0.3 mmol/kg, of a gadolinium chelate with extracellular distribution were compared to precontrast T2- and T1-weighted scans. METHODS: Seven New Zealand White rabbits with VX-2 adenocarcinoma metastases to the liver were imaged at 1.5 tesla. Each animal was studied twice, on different days, to evaluate both contrast doses. Precontrast T2- and T1-weighted scans were compared to dynamic postcontrast T1-weighted scans obtained at 1, 2, 3, 4, and 5 minutes after intravenous injection. All scans were acquired during suspended respiration. The contrast agent, Gd HP-DO3A (gadoteridol or ProHance), was administered as a bolus. Images were analyzed by region of interest measurements. RESULTS: Injection of 0.3 mmol/kg Gd HP-DO3A produced liver enhancement which was statistically superior to 0.1 mmol/kg at all time points postcontrast. Enhancement of the paraspinous musculature at the higher dose was also statistically superior at all time points, with one exception (5 minutes postcontrast). Lesion detectability, evaluated by the signal difference over noise ratio, peaked at one minute postcontrast and was substantially greater at the higher contrast dose (31.4 +/- 8.3 at 0.3 mmol/kg versus 16.8 +/- 4.2 at 0.1 mmol/kg, P = 0.02). CONCLUSIONS: Using a rabbit model and breath-hold imaging technique, metastatic lesions in the liver were best visualized on early (1 minute) dynamic high dose (0.3 mmol/kg) postcontrast scans. Contrast dose and timing of image acquisition are critical issues for optimal liver lesion detection on magnetic resonance imaging.
Animals↗
Splitting vial of MR contrast is not good patient care.
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Central Nervous System Diseases↗
Worldwide clinical safety assessment of gadoteridol injection: an update.
Gadoteridol injection is a low molecular weight chelate complex of gadolinium (III) which is useful as a contrast agent for magnetic resonance imaging. A total of 2481 adult and pediatric subjects were studied with gadoteridol at doses from 0.025 to 0.3 mmol/kg in phase I-IIIb clinical trials in Europe and the United States. The study population had a mean age of 49 years, and included 119 patients under 18 years of age and 747 patients over 60 years of age. After 2656 administered injections of gadoteridol a total of 233 adverse events were recorded in 176 exposures, an incidence rate of 6.6 % irrespective of relationship to drug administration. The most frequently reported adverse events were nausea (1.5 %), taste perversion (0.9 %), and headache (0.6 %). All other adverse events occurred with an incidence of 0.5 % or less. This report confirms the excellent safety profile of gadoteridol in healthy subjects and patients with a variety of known or suspected pathologies.
Adolescent↗
Evaluation of the temporal evolution of acute spinal cord injury.
RATIONALE AND OBJECTIVES: After receiving a controlled injury to the thoracic cord, five rats were examined on a 1.5-T magnetic resonance (MR) imaging system at regular intervals over 1 month to assess evolution of the injury. METHODS: After the rats received pentobarbital anesthesia, a T10 laminectomy was performed on them, which exposed the dura over the dorsal surface of the spinal cord. With the animal placed in a New York University weight-drop device, a 10-g rod with a flat brass tip was dropped (free-fall) from a height of 50 mm to impact the cord. After injury, the incision was closed with suture material. Each animal was imaged on the day of injury, and at 7, 14, and 28 days after injury. Before contrast injection was administered, sagittal sections were obtained with T2 fast-spin echo and T1-spin echo technique. Each rat then received 0.3-mmol/kg gadoteridol (Gd HP-DO3A or ProHance) intravenously, with the T1 scan repeated. At 28 days, the animals were killed, and the cord was fixed and embedded in paraffin for histologic evaluation. RESULTS: The intensity of cord enhancement in the region of injury, after intravenous (i.v.) contrast injection, was at a maximum on the day of injury, and it decreased in a steady fashion thereafter. The intensity was 11.7 +/- 0.6 on the day of injury, 9.7 +/- 2.6 on day 7, 6.3 +/- 5.3 on day 14, and 0.0 +/- 2.3 on day 28. The results on day 0 and 7 were statistically significant in terms of a difference from that on day 28, with a P value < 0.001. The length of cord injury, assessed postcontrast, also decreased in a steady fashion from the day of injury. The length of injury (in cm) was 1.1 +/- 0.1 on the day of injury, 0.5 +/- 0.2 on day 7, 0.3 +/- 0.1 on day 14, and 0.1 +/- 0.1 on day 28. The results on day 0 and 14 were statistically significant in terms of a difference from those at the next time point, with P values from < 0.01 to < 0.001. Visually, on T2 images, substantial edema was noted on day 0, with progression to focal cord atrophy and gliosis by day 28. CONCLUSIONS: Acute spinal cord injury in a rat model is well visualized on pre- and postcontrast MR scans at 1.5 T. Observation of T2 changes and disruption of the blood-spinal cord barrier provide markers for temporal assessment of spinal cord injury in the rat model.
Acute Disease↗
Renal metastasis. Detection and characterization on enhanced magnetic resonance imaging using an animal model.
RATIONALE AND OBJECTIVES: A new animal model was developed in rabbits (renal metastasis using the VX-2 tumor line), and magnetic resonance (MR) imaging performed before and after intravenous gadoteridol injection to assess lesion conspicuity and characterization. METHODS: Six New Zealand White rabbits with renal metastases were studied on a 1.5-tesla Siemens Vision MR unit. Iodinated contrast was given intravenously to the rabbits, before implantation, to visualize the kidneys under fluoroscopy. Using a 5/8-inch 25-gauge needle, 0.1 mL of minced, screened VX-2 tumor was injected percutaneously into each kidney at the corticomedullary junction. Animals were studied on day 7 after implantation. Baseline fast low-angle shot (FLASH) T1-weighted and fast spin echo T2-weighted breathhold scans were first obtained. Then, an additional precontrast turbo-FLASH T1-weighted scan was acquired. After these scans, 0.1 mmol/kg gadoteridol (gadolinium HP-D03A; ProHance) was injected intravenously at a rate of 1.5 mL/second. Dynamic breathhold turbo-FLASH T1 images were then obtained at 0, 6, 12, 19, 25, and 31 seconds after injection and at 1, 2, and 10 minutes after injection. The T1 multislice FLASH two-dimensional scan was repeated at 10 minutes after contrast. Imaging results were analyzed by region of interest measurement and correlated with tissue pathology. RESULTS: On dynamic T1-weighted turbo-FLASH scans, lesion conspicuity, specifically (SI(kidney)-SI(tumor)/noise), increased from 7 +/- 7 signal intensity precontrast to a maximum of 14 +/- 8 at 1 minute after contrast. This increase was statistically significant (P = 0.002). An initial rapid increase in tumor conspicuity occurred within the first 30 seconds after contrast, with the curve flattening thereafter. Lesion conspicuity on the precontrast T2-weighted scans was 9 +/- 10, not statistically different from results with either of the precontrast T1-weighted scan techniques. Using T1-weighted FLASH technique, lesion conspicuity increased from 10 +/- 5 precontrast to 31 +/- 12 postcontrast. As with turbo-FLASH, the improvement in tumor conspicuity after contrast on FLASH scans was statistically significant (P = 0.02). The difference between postcontrast FLASH scans and precontrast T2-weighted scans also was statistically significant, with postcontrast scans superior for lesion conspicuity (P = 0.01). Each tumor was confirmed on pathologic exam. CONCLUSIONS: This research establishes a model of metastasis to the kidney for use in imaging studies. The conspicuity of a small renal metastasis is shown to be improved on early dynamic imaging, as well as at 10 minutes after intravenous injection of 0.1 mmol/kg gadoteridol. Observation of dynamic signal intensity changes provides additional information regarding lesion characterization, supplementing that from precontrast scans.
Animals↗
Detectability of small liver metastases with gadolinium BOPTA.
RATIONALE AND OBJECTIVES: The ability to detect small liver metastases was evaluated with both gadolinium Gd BOPTA and Gd HP-DO3A on high-field (1.5 tesla [T]) magnetic resonance (MR) imaging using a rabbit tumor model. METHODS: Five New Zealand White rabbits with metastatic liver disease (VX-2 adenocarcinoma) were imaged on a 1.5 T Siemens Vision MR system. Magnetic resonance studies were obtained in each animal on days 8 and 9 after tumor implantation. Each animal was studied twice, once after injection of 0.3 mmol/kg Gd HP-DO3A (gadoteridol or ProHance) and once after injection of 0.1 mmol/kg Gd BOPTA (gadobenate dimeglumine or MultiHance). The order of injection for the two agents was randomized with the two studies in any one animal separated by 24 hours to allow for clearance. Magnetic resonance image acquisition was performed in all cases with suspended respiration. Baseline two-dimensional FLASH T1-weighted and turbo-spin echo T2-weighted scans were acquired first. The contrast was then administered as an intravenous bolus. T1-weighted scans were acquired at 1, 5, 15, 30, 45, and 60 minutes after administration of Gd BOPTA and 1, 5, and 15 minutes after administration of Gd HP-DO3A. Each rabbit was killed after completion of imaging, their liver removed and taken to the veterinarian at the University's animal disease diagnostic laboratory for lesion confirmation. RESULTS: Despite acquisition of precontrast T2-weighted scans, lesions could not be identified with certainty in four of five animals in the Gd HP-DO3A study. Normal liver signal intensity increased from 895 +/- 17 to a peak of 1384 +/- 50 at 1 minute after Gd HP-DO3A administration. After Gd BOPTA administration, normal liver signal intensity increased from 899 +/- 105 to a peak of 1433 +/- 76 at 15 minutes. Liver enhancement thereafter decreased gradually to 1297 +/- 84 at 60 minutes. The injection of 0.3 mmol/kg Gd HP-DO3A resulted in parenchymal enhancement, which was statistically superior (P < 0.01) to an injection of 0.1 mmol/kg Gd BOPTA at 1 minute, not statistically different at 5 minutes, and inferior (P < 0.02) at 15 minutes. From region of interest measurements, lesion detectability was statistically superior on scans at 15 to 60 minutes after Gd BOPTA administration compared with precontrast T1- and T2-weighted scans (P values: < 0.03- < 0.005). Lesion detectability was maximum at 30 minutes postcontrast (15.2 +/- 4.5), markedly superior to that precontrast on both T1- (5.7 +/- 5.0) and T2-weighted scans (7.2 +/- 1.5). On masked film review of the Gd BOPTA case set, no lesions were noted prospectively on T2-weighted scans. Lesions in all five animals were well visualized on scans 45 to 60 minutes after Gd BOPTA administration. The Gd HP-DO3A case set was not read masked, as lesions could be identified only in one of the five animals with all films available for inspection. An additional feature of scans with Gd BOPTA (used at a dose of 0.1 mmol/kg), in distinction to those with Gd HP-DO3A (used at a dose of 0.3 mmol/kg), was the diminished enhancement of hepatic vessels. CONCLUSIONS: Using a rabbit model, small metastatic lesions (diameter, 2-4 mm) were well visualized on delayed postcontrast Gd BOPTA scans. These lesions could not be diagnosed prospectively on T2-weighted images. In only one of five animals were lesions detected on early dynamic post-contrast high-dose Gd HP-DO3A scans.
Adenocarcinoma↗
Contrast-enhanced magnetic resonance imaging in a spinal epidural tumor model.
RATIONALE AND OBJECTIVES: A spinal epidural tumor model was developed, using the VX-2 adenocarcinoma in rabbits, to assess the strengths and weaknesses of magnetic resonance (MR) as a cross-sectional imaging modality for the evaluation of epidural neoplastic disease. High-resolution MR images were acquired both before and after intravenous gadolinium chelate injection, assessing lesion detectability and efficacy of imaging technique. METHODS: An adenocarcinoma tumor (VX-2) was produced in the epidural space of six New Zealand White rabbits and subsequently studied on a 1.5 tesla whole body MR scanner. VX-2 tumor tissue was removed from the thigh of a carrier rabbit, minced, and screened. Under fluoroscopic guidance, 0.2 mL of the tumor preparation was then injected into the epidural space of the experimental rabbits. The injection was performed at the L5-6 level using an epidural needle and polyethylene tubing sleeved within the needle. The rabbits were imaged using a circular small parts surface coil 5 to 15 days after the epidural injection. In all six animals, one complete MR exam was obtained within the time frame of days 9 to 11. T1- and T2-weighted axial scans were obtained before contrast injection, with the T1 scans acquired both with and without fat saturation. Postcontrast T1 scans also were obtained, using fat saturation, after the injection of 0.1 and 0.3 (cumulative dose) mmol/kg gadoteridol (Gd HP-DO3A; ProHance) in all animals. The film images were interpreted in a prospective fashion by a single neuroradiologist who was masked to imaging technique and contrast dosing. The digital data was analyzed by region of interest measurement. At the end of the imaging studies, the animals were sacrificed and the epidural lesion confirmed by gross and microscopic exam. RESULTS: On a prospective masked read of the MR films, epidural tumor was depicted best on postcontrast fat saturation T1-weighted scans using a cumulative contrast dose of 0.3 mmol/kg. Substantial contrast enhancement of the tumor was observed in all instances on postcontrast scans. The precontrast T1-weighted scan was least efficacious for lesion identification and differentiation from the compressed spinal cord. Depending on the pulse sequence used, one (T2-weighted) to three (T1-weighted without fat saturation) of the lesions could not be identified prospectively on precontrast scans. Lesion growth with time after implantation was chronicled by MR imaging, accompanied by progression of symptoms. On region of interest analysis, differentiation of epidural tumor from normal cord was greatest (11.6 +/- 6.1) on postcontrast scans using a cumulative contrast dose of 0.3 mmol/kg. The level of differentiation achieved was twice that of postcontrast scans using a contrast dose of 0.1 mmol/kg (5.9 +/- 3.6). These results were superior on statistical analysis to that with all other scan techniques (P = 0.002-0.0005). Cord and tumor could not be differentiated on the basis of signal intensity, with any statistical significance, using precontrast T1 and T2 scans. The lesions were confirmed in each animal by gross and microscopic exam. On inspection of the gross specimen, the tumors were noted to be located in the epidural space and to cause cord compression. On microscopic exam, the tumor was composed of epithelial cells that were moderately pleomorphic. CONCLUSIONS: In the New Zealand White rabbit, an epidural tumor could be created consistently using the described percutaneous approach. These lesions are suitable for MR imaging studies, examining lesion detectability and efficacy of imaging technique. The lesions created in the current study could not be diagnosed prospectively in all cases on precontrast T1 and T2 scans images. Postcontrast scans were most efficacious for diagnosis and lesion delineation, with high-dose (0.3 mmol/kg) scans superior to standard dose (0.1 mmol/kg).
Adenocarcinoma↗
Magnetic resonance imaging of experimental pyelonephritis in rabbits.
RATIONALE AND OBJECTIVES: An experimental model of acute focal pyelonephritis was developed in the New Zealand White rabbit, with initial imaging evaluation performed using high-field contrast-enhanced magnetic resonance (MR) in six animals. METHODS: The left kidney was visualized fluoroscopically after intravenous injection of iodinated contrast. A 0.1 mL mixture of agarose/Streptococcus faecalis was then injected percutaneously into the kidney at the corticomedullary junction with a 25-gauge needle. The animals were imaged at 1.5 tesla on day 5 after injection of bacteria. Breathhold T2-weighted and T1-weighted scans were acquired prior to contrast injection. Using an MR-compatible power injector, 0.3 mmol/kg gadoteridol was then administered, with both dynamic and delayed postcontrast scans obtained. The lesion was confirmed in each animal by gross and microscopic exam. RESULTS: The area of acute focal pyelonephritis was somewhat difficult to identify on precontrast scans. The lesion was mildly hyperintense on T2-weighted scans and slightly hypointense to isointense on T1-weighted scans relative to normal surrounding renal parenchyma. On early dynamic turbo-fast low-angle shot scans, the lesion could be identified due to differential tissue enhancement. Direct visualization of the lesion, with increased conspicuity relative to precontrast scans, was possible because of delayed positive enhancement at 60 seconds postcontrast. Lesion conspicuity, assessed by signal difference/noise ratio, increased from 0 +/- 5 precontrast to a peak of 12 +/- 6 at 60 seconds postcontrast (P = 0.003; n = 6). CONCLUSIONS: On dynamic contrast-enhanced MR, acute focal pyelonephritis can demonstrate transient positive contrast enhancement (using a contrast dose of 0.3 mmol/kg) relative to surrounding normal renal parenchyma. This appearance is due to hyperconcentration of the contrast agent in normal parenchyma and T2 effects. The pattern is opposite that seen in spiral computed tomography.
Acute Disease↗
Liver MRI with contrast enhancement.
Liver MR imaging has improved substantially in the last decade due to advances in equipment design and pharmaceutical development. Contrast agents for the liver have been examined within three major classes. Extracellular agents (Gd HP-DO3A, Gd DTPA, and Gd DTPA-BMA) are currently in widespread clinical use. Gadolinium chelates with hepatobiliary excretion are in clinical trials (Gd BOPTA and Gd EOB-DTPA). With respect to particulate agents, one (AMI-25) has received Food and Drug Administration (FDA) approval recently. Imaging technique is critical to proper use, with different strategies employed depending on the class of agent. With gadolinium chelates, T1-weighted images are used for visualization, with dynamic scans being important for extracellular agents, and both dynamic and delayed scans being important for agents with hepatobiliary excretion. With the particulate iron compounds, T2-weighted images are used for visualization, with emphasis on delayed imaging.
Clinical Trials as Topic↗
Comparison of hepatobiliary gadolinium chelates for magnetic resonance imaging.
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Animals↗
Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging.
RATIONALE AND OBJECTIVES: A new hepatobiliary gadolinium chelate, gadolinium (Gd) 2,5-BPA-DO3A, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved extracellular contrast agent, and Gd Cy2-DOTA, a second hepatobiliary chelate in preclinical development. The ligand in Gd 2,5-BPA-DO3A is macrocyclic in nature, as opposed to the linear structure of Gd DTPA. Gadolinium 2,5-BPA-DO3A was evaluated on magnetic resonance imaging at 1.5 T, examining specifically liver parenchymal enhancement and lesion delineation, the latter in metastatic disease. METHODS: Gadolinium 2,5-BPA-DO3A was evaluated in five normal rhesus monkeys and four New Zealand White rabbits with implanted VX-2 liver tumors. These studies were compared with magnetic resonance exams in the same animals using Gd HP-DO3A and Gd Cy2-DOTA. A contrast dose of 0.1 mmol/kg intravenous was employed in each instance, with the sequence of administration (for the three agents) randomized and at least 72 hours between injections. Spin echo breathhold T1-weighted scans were obtained before and at multiple times after contrast administration. Postcontrast scans were acquired from 1 to 60 minutes after injection in the monkeys and from 1 to 240 minutes in the rabbits. RESULTS: Enhancement of normal liver parenchyma was markedly superior with Gd 2,5-BPA-DO3A compared with Gd HP-DO3A and Gd Cy2-DOTA in both monkeys and rabbits. At 2 and 60 minutes after contrast administration, the liver signal intensity in the monkey was 452 +/- 56 and 440 +/- 69 with Gd 2,5-BPA-DO3A compared with 295 +/- 34 and 256 +/- 38 with Gd HP-DO3A. The difference between agents was statistically significant at all postcontrast time points in the rhesus monkey. Excretion of contrast into the gall bladder was consistently observed after Gd 2,5-BPA-DO3A injection in both animal species. Maximum lesion conspicuity occurred in the rabbit at 45 minutes after Gd 2,5-BPA-DO3A administration. At 45 minutes postinjection, liver-lesion contrast was 0.60 +/- 0.15 with Gd 2,5-BPA-DO3A, 0.35 +/- 0.11 with Gd Cy2-DOTA, and 0.12 +/- 0.04 with Gd HP-DO3A, with the differences between agents being statistically significant. CONCLUSIONS: Gadolinium 2,5-BPA-DO3A is superior to both Gd Cy2-DOTA and Gd HP-DO3A in the degree of enhancement of normal liver parenchyma achieved after intravenous injection. This leads to improved liver lesion delineation with Gd 2,5-BPA-DO3A on delayed postcontrast magnetic resonance scans.
Animals↗
The use of gadolinium-BOPTA on magnetic resonance imaging in brain infection.
RATIONALE AND OBJECTIVES: The use of gadolinium (Gd)-BOPTA as a magnetic resonance contrast agent for central nervous system disease was studied in a canine brain abscess model. METHODS: A Streptococcus faecalis brain abscess was evaluated in five dogs at 1.5T. Imaging was performed during the late cerebritis stage, at 5 to 7 days after surgery. Magnetic resonance scans were acquired before and at 1, 5, 15, 30, 45, and 60 minutes after contrast administration, using a dose of 0.1 mmol/kg. Scans also were acquired both before and after contrast injection with the implementation of magnetization transfer. RESULTS: Lesion enhancement, quantified by region-of-interest measurement, peaked at 5 minutes after contrast injection. Both the increase in lesion enhancement from 1 to 5 minutes after injection and the decrease from 5 to 15 minutes after injection, although small, were statistically significant (P < 0.004 and P < 0.03, respectively). The application of magnetization transfer improved lesion enhancement, as measured by signal difference/noise, by 39%. This result also was statistically significant (P < 0.001). CONCLUSIONS: In intraparenchymal brain infection, Gd-BOPTA provides effective lesion enhancement when used at a dose of 0.1 mmol/kg. Further research is needed to compare the magnitude of enhancement achieved with Gd-BOPTA, which has weak protein binding and both hepatobiliary and renal excretion, with that with Gd chelates, which have pure renal excretion.
Animals↗
Choice of metal ion and formulation concentration for first-pass brain perfusion studies with magnetic resonance imaging at 1.5 tesla.
RATIONALE AND OBJECTIVES: Gadolinium (Gd) and dysprosium (Dy) analogues, chelated with HP-DO3A, were compared at both 0.5- and 1.0-mol/L concentrations for efficacy in first-pass brain studies on magnetic resonance (MR) imaging at 1.5 tesla (T). METHODS: Ten healthy cats were examined with a dose of 0.3 mmol/kg, using two concentrations of each agent (0.5 mol/L and 1.0 mol/L, 20 examinations). Gadolinium-HP-DO3A (gadoteridol or ProHance) or Dy-HP-DO3A was injected at 9 mL/second, with acquisition of 64 sequential steady-state free precession (SSFP) images at a rate of one each 0.6 second. RESULTS: The change in white matter signal intensity, at the peak of the first pass of the contrast agent bolus in the brain, was -231 +/- 68 for the 0.5-mol/L formulation of Gd-HP-DO3A, compared with -267 +/- 57 for the 1.0-mol/L formulation. Using the 0.5-mol/L formulation of Dy-HP-DO3A, the change at peak was -318 +/- 42, a result statistically improved compared with both the 0.5-mol/L (P < 0.02) and 1.0-mol/L (P < 0.04) Gd-HP-DO3A formulations. A further improvement was observed with the 1.0-mol/L Dy-HP-DO3A formulation, with the change being -368 +/- 33. CONCLUSIONS: First-pass brain MR studies at 1.5 T are improved by use of higher concentration Gd chelate formulations (1.0 versus 0.5 mol/L) and by substitution of the Dy ion for the Gd ion in the chelate. Injection of higher-concentration formulations results in higher initial arterial metal ion concentration. Incomplete blood mixing on transit during first pass causes the higher initial concentration, which then results in a greater susceptibility effect on imaging. The superiority of the Dy formulation compared with the Gd formulation is anticipated because of the higher magnetic moment of Dy. The curves for tissue signal intensity versus time during first pass return artifactually to near baseline after Gd chelate injection (when SSFP imaging techniques are used), a differentiating feature from results with the Dy chelate. This difference can be explained by a substantial T1 effect of the Gd chelate, despite acquisition of images that are predominantly susceptibility weighted.
Animals↗
Early dynamic magnetic resonance imaging of liver metastases with 0.3 and 0.6 mmol/kg gadoteridol injection.
RATIONALE AND OBJECTIVES: The potential for improvement in liver-lesion conspicuity on early dynamic scans after bolus intravenous gadolinium (Gd) chelate administration was evaluated using gadoteridol (Gd-HP-DO3A; Prohance) at doses of 0.3 and 0.6 mmol/kg. METHODS: Five New Zealand white rabbits with focal VX-2 adenocarcinoma liver metastases were studied on a 1.5-tesla Siemens Vision scanner. Each rabbit was imaged twice (on two separate days), after injections of 0.3 mmol/kg and 0.6 mmol/ kg Gd-HP-DO3A. The contrast dose (0.3 or 0.6 mmol/kg) was given as a single intravenous injection. The order of injection for the two doses was randomized, with the two studies (in any one rabbit) separated by 24 hours to allow for clearance. Contrast was administered using an autoinjector at a rate of 1.5 mL/second. Turbo-fast low-angle shot scans were obtained before and at 6, 12, 19, 25, 31, 60, 120, 180, 240, 300, and 600 seconds after contrast injection. The lesions were confirmed, after killing the rabbit, by gross and microscopic examination. RESULTS: The enhancement of normal liver parenchyma, assessed by (SIt-SIo)/SIo.100, (SI = signal intensity) peaked at 32% +/- 4% 19 seconds after injection of 0.3 mmol/kg and at 38% +/- 5% 31 seconds after injection of 0.6 mmol/kg. The difference in maximum parenchymal enhancement achieved, comparing the 0.3 and 0.6 mmol/kg doses, was statistically significant (P < 0.03). Lesion conspicuity, specifically (SIliver-SIlesion/noise), increased from 4.5 +/- 2.3 precontrast to a maximum of 6.8 +/- 1.2 at 19 seconds postcontrast using a dose of 0.3 mmol/kg, with the difference statistically significant (P < 0.03). The increase with a dose of 0.6 mmol/kg was from 4.2 +/- 0.7 to 6.5 +/- 1.9 with this difference also statistically significant (P < 0.02). There was no statistically significant difference in lesion conspicuity between the doses of 0.3 and 0.6 mmol/kg. CONCLUSIONS: Conspicuity of liver metastases can be improved substantially with dynamic magnetic resonance imaging and rapid intravenous bolus contrast injection with a dose of 0.3 mmol/kg. No further improvement is noted at a dose of 0.6 mmol/kg, despite greater positive contrast enhancement of normal liver parenchyma.
Adenocarcinoma↗
Hepatic abscesses. Magnetic resonance imaging findings using gadolinium-BOPTA.
RATIONALE AND OBJECTIVES: Gadolinium (Gd)-BOPTA was evaluated in a rabbit liver abscess model and compared with Gd-HP-DO3A, examining lesion conspicuity and characterization. METHODS: Five New Zealand White rabbits with a liver abscess were studied on a 1.5-tesla Siemens Vision magnetic resonance unit. The disease model was created by surgically implanting a gel capsule filled with fusobacterium into the central or left lobe of the liver. For imaging, the animals were ventilated using a Harvard pump. Pancuronium bromide (0.12 mg/kg) was administered to allow acquisition of breath-hold scans. Magnetic resonance scans were obtained in each animal on days 2 and 3 after surgery. Every animal was studied twice, once after intravenous injection of 0.3 mmol/kg Gd-HP-DO3A (gadoteridol; ProHance) and once after intravenous injection of 0.1 mmol/kg Gd-BOPTA (gadobenate dimeglumine; MultiHance). The order of injection for the two agents was randomized with the two studies in each animal, separated by 24 hours to permit clearance. Image acquisition was performed in each instance with respiration suspended. Baseline two-dimensional spin-echo T1-weighted and fast spin-echo T2-weighted breath-hold scans were obtained first. The voxel dimensions were 5 x 0.8 x 0.8 mm3. Imaging times were 23 seconds for the T1-weighted scan and 26 seconds for the T2-weighted scan. Postcontrast scans, using spin-echo T1-weighted technique, were obtained at 1, 3, 5, and 15 minutes after contrast injection, whether Gd-HP-DO3A or Gd-BOPTA was used. Additional scans were obtained at 30, 45, and 60 minutes after Gd-BOPTA administration. At the completion of imaging on day 3, each animal was killed and the liver was removed and taken to a veterinary pathologist at the University's animal disease diagnostic lab for gross and histologic examination. RESULTS: The enhancement of normal liver parenchyma, assessed by region of interest measurement and specifically as (SI(t) - SI0)/SI0 x 100, peaked at 119 +/- 37% 1 minute after injection of 0.3 mmol/kg Gd-HP-DO3A and at 126 +/- 30% 30 minutes after injection of 0.1 mmol/kg Gd-BOPTA. The difference in enhancement achieved, comparing results at each time point, was statistically significant only at 1 and 3 minutes postcontrast (P = 0.003 and 0.03). Lesion conspicuity, specifically (SIliver - SIlesion/noise), increased from 272 +/- 29 precontrast to a maximum of 639 +/- 73 at 30 minutes postcontrast using a dose of 0.1 mmol/kg Gd-BOPTA, with the improvement statistically significant (P = 0.0003). Lesion conspicuity on the T2-weighted scan was 137 +/- , with the Gd-BOPTA scan markedly superior (P = 0.00004). On scans at 45 and 60 minutes after Gd-BOPTA administration, a progressive increase in signal intensity in the central necrotic portion of the lesion was observed. This was most consistent with gradual diffusion of the agent from the adjacent liver into the lesion. Using Gd-HP-DO3A at 0.3 mmol/kg (three times the dose for Gd-BOPTA), lesion conspicuity increase from 305 +/- 37 precontrast to a maximum of 701 +/- 92 at 1 minute postcontrast, with this difference also statistically significant (P = 0.0004). The abscess rim exhibited moderate contrast enhancement, greater than that of normal liver parenchyma, on early postcontrast images with Gd-HP-DO3A. CONCLUSIONS: The conspicuity of an early liver abscess is improved markedly on delayed imaging after administration of 0.1 mmol/kg Gd-BOPTA. Although a similar magnitude of parenchymal enhancement can be obtained after the administration of an extracellular agent, such as Gd-HP-DO3A, high-contrast dose (0.3 mmol/kg) and early dynamic imaging are required. The appearance of a liver abscess on late scans (45 to 60 minutes) after Gd-BOPTA injection is distinct from that of nonnecrotic metastases, with diffusion of the agent into the lesion noted.
Animals↗