Phase III, randomized, double-blind, cross-over comparison of gadoteridol and gadopentetate dimeglumine in magnetic resonance imaging of patients with intracranial lesions.

This study compares the efficacy and safety of gadoteridol with that of gadopentetate dimeglumine for enhanced MRI in subjects with intracranial lesions. A total of 92 subjects at three European centres underwent one MRI study enhanced with 0.1 mmol/kg gadoteridol and another with 0.1 mmol/kg gadopentetate dimeglumine. Contrast agents were assigned in random order, separated by 3-7 days. Eighty subjects were evaluated for efficacy. The presence of pathology, degree of enhancement, location and number of lesions, as well as additional information gained, were compared for each subject's unenhanced and enhanced scans for both the gadoteridol and gadopentetate dimeglumine examination. Safety was evaluated in all treated subjects by means of pre- and post-dose vital signs, laboratory tests and by monitoring for adverse events. There was no significant difference in the number of lesions visualized pre- and post-contrast for the two contrast agents. A high degree of correlation was noted between the two blinded readers. When post-contrast image sets were compared between contrast agents, there was no significant difference in superiority of one agent over the other for any of the evaluators (P > 0.05). No significant differences for any safety parameter were noted between the two agents. Gadoteridol and gadopentetate dimeglumine are effective and well tolerated for use in contrast-enhanced MRI of the CNS at a dose of 0.1 mmol/kg.

Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging--a multicenter phase III clinical study.

PURPOSE: To evaluate gadobenate dimeglumine (Gd-BOPTA) for dynamic and delayed magnetic resonance (MR) imaging of focal liver lesions. MATERIALS AND METHODS: In 126 of 214 patients, MR imaging was performed before Gd-BOPTA administration, immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA, and 60-120 minutes after an additional intravenously infused 0.05-mmol/kg dose. In 88 patients, imaging was performed before and 60-120 minutes after a single, intravenously infused 0.1-mmol/kg dose. T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired. On-site and blinded off-site reviewers prospectively evaluated all images. Intraoperative ultrasonography, computed tomography (CT) during arterial portography, and/or CT with iodized oil served as the reference methods in 110 patients. RESULTS: Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone (P <. 01). All reviewers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images. All on-site reviewers and two off-site reviewers reported increased overall diagnostic confidence (P <.01). Additional lesion characterization information was provided on up to 109 (59%) of 184 delayed images and for up to 50 (42%) of 118 patients in whom dynamic images were assessed. Gd-BOPTA would have helped change the diagnosis in 99 (47%) of 209 cases and affected patient treatment in 408 (23%) of 209 cases. CONCLUSION: Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions.

Use of the magnetic resonance contrast agent gadodiamide in the central nervous system. Results of a multicenter trial.

To investigate the safety and efficacy of the low-osmolar, nonionic contrast agent, gadodiamide injection (Omniscan, Sanofi Winthrop Pharmaceuticals, New York, NY), for magnetic resonance imaging (MRI) of the head and spine, a multicenter study involving 439 patients was done at 15 centers as part of a Phase II/III clinical trial. Unenhanced MRI scans were obtained after which the patients were injected with 0.1 mmol/kg gadodiamide, and the MRI was repeated. The patients' vital signs were monitored, and laboratory studies were conducted. Neurologic status was examined before and after the study. The images were evaluated for contrast enhancement. No patient had any significant adverse event or serious change in clinical status. Abnormalities were found in 80% (351) of all patients studied, and it was found that, in 75% (266) of these, the postgadodiamide injection images were improved or facilitated visualization of lesions compared with preinjection images. The investigators believe that, based on the results of this study, gadodiamide injection is safe and effective for imaging the head and spine. They suggest that future studies further assess and compare the safety parameters of gadodiamide injection with those of other nonionic and ionic gadolinium ligands.

Early MR follow-up of partial hepatectomy.

Twenty-seven patients were studied with MRI between 3 and 40 days following partial liver resection. Twenty-four patients had undergone major hepatectomy (three to six segments) and three had undergone minor hepatectomy (tumorectomy, one; bisegmentectomy, two). Indications for surgery were as follows: metastases (n = 16), hepatocellular carcinoma (n = 5), hemangioma (n = 3), focal nodular hyperplasia (n = 2), and cholangiocarcinoma (n = 1). A total of 36 MR examinations were performed using a 1.5 T superconducting unit. Three patients were studied three times and three patients were studied twice. The MR images were evaluated to detect and to characterize liver parenchymal abnormalities and intraabdominal fluid or blood collections as well as to assess vascular and/or graft patency. The MR images showed hepatic ischemia in two cases and allowed differentiation between intraabdominal hemorrhagic (n = 30 and nonhemorrhagic (n = 4) fluid collections. Gradient echo images allowed assessment of polytetrafluoroethylene graft patency as well as demonstration of iliac vein (one case) and portal vein (one case) thrombosis. The presence of surgical clips at the resection margins did not affect image quality.

Multicenter study of gadodiamide injection as a contrast agent in MR imaging of the brain and spine.

To evaluate the safety and efficacy of gadodiamide injection, a nonionic gadolinium chelate complex, in magnetic resonance (MR) imaging of the head and spine, a phase II-III trial was conducted in 439 patients with known or suspected lesions in the central nervous system. All patients received gadodiamide injection in a dosage of 0.1 mmol/kg and were monitored; MR images were evaluated for contrast material enhancement. No serious adverse events or clinically important trends in vital signs, laboratory values, or neurologic status were observed. Gadodiamide injection enhanced or facilitated the visualization of lesions in 266 or 353 patients (75.4%) in whom lesions were shown on unenhanced images, enhanced images, or both; in these 266 patients, the diagnosis was changed in 76 patients (28.6%) and facilitated in 190 patients (71.4%). It is concluded that gadodiamide injection is safe and effective for MR imaging of the head and spine in patients with suspected abnormalities of the central nervous system.

Spin-echo and STIR MR imaging of sports-related muscle injuries at 1.5 T.

Seventy patients with clinically diagnosed athletic muscle injuries of varying severity were studied with MR imaging at 1.5 T. Twenty underwent follow-up MR studies. In all cases, SE T1-weighted and double-echo T2-weighted pulse sequences were used. These were supplemented by short T1 inversion recovery (STIR) sequence in 36 cases. Muscle injuries were more readily seen with STIR images than with SE T2-weighted images. In both initial assessment and follow-up of tears, the use of the STIR technique allowed the greatest lesion/muscle contrast. Short TR, short TE SE images provided anatomic detail and were an adjunct to T2-dependent SE images in the evaluation of organized hematomas (11 cases). Follow-up MR studies in 20 patients at variable time intervals allowed demonstration of regression of the tear in 11 cases, fibrous scar formation in 5 cases, and recurrence of the tear in 4 cases. Evolution of hematomas into scar and into cyst was demonstrated in three and two cases, respectively. Owing to the additive effect of T1 and T2 mechanisms, the STIR sequence is well suited for initial evaluation and can replace T2-weighted images in the follow-up of muscle trauma.

Gadodiamide injection: nonionic gadolinium chelate for MR imaging of the brain and spine--phase II-III clinical trial.

Seventy-three patients with clinically suspected central nervous system abnormalities (44 intracranial, 29 medullospinal) were studied with magnetic resonance (MR) imaging before and after administration of nonionic gadodiamide injection. MR imaging showed intracranial lesions in 37 patients. Eight patients had spinal tumors, and 21 had disk disease. Structural abnormalities were shown in 37 of 44 head studies and in all 29 spine studies. Lesions enhancement was seen in 31 head studies and 28 spine studies, and distinction of lesion(s) from associated edema was possible in 10 head studies and in one study of intrinsic cord tumor. Administration of gadodiamide injection provided improved definition of lesion borders in 19 of 44 head studies and 26 of 29 spine studies. The use of the contrast agent changed the diagnosis that was based on the unenhanced images in nine head studies and 13 spine studies. Early postcontrast, T1-weighted spin-echo images of postoperative spines were adequate in distinguishing epidural scar (enhancing) from herniated disk (nonenhancing). The contrast agent was well tolerated, and no drug-related adverse events occurred.

Characterization of high-energy phosphate compounds during reperfusion of the irreversibly injured myocardium using 31P MRS.

Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to monitor regional changes in high-energy phosphorus compounds and intracellular pH during 60 min of acute regional ischemia (acute occlusion of left anterior descending artery) and reperfusion in open-chest cats using a 1.2-cm two-turn coil sutured to the myocardium. During the 60-min ischemic phase, phosphocreatine (PCr) intensity was reduced to 47 +/- 4.9% (mean +/- SE) of control (p less than 0.01) by 15 min postocclusion while adenosine triphosphate (ATP) intensity decreased more slowly with the decrease (66 +/- 5.6%) achieving significance (p less than 0.05) only at 60 min postocclusion. Inorganic phosphate (Pi) increased to a maximum of 397 +/- 42% of control (p less than 0.01) while the pH decreased progressively from 7.36 +/- 0.02 to 6.02 +/- 0.14 (p less than 0.01). After release of occlusion PCr intensity recovered to 86 +/- 12% of the initial control value at 15 min postreperfusion but showed a subsequent downward trend to 79 +/- 8.8%. The ATP did not recover but tended to decline further during reperfusion. The Pi intensity decreased to 260 +/- 38% of control while the pH increased to 7.01 +/- 0.23 by 15 min postreperfusion. Thus, the reperfused irreversibly injured myocardium is characterized by persistent depletion of PCr and ATP and elevation of Pi. Phosphorus-31 MRS provides a nondestructive method for characterizing the reperfused irreversibly damaged myocardium.

Measurement of regional myocardial blood flow in dogs by ultrafast CT.

We measured blood flow within each of eight segments of the left ventricular myocardium in dogs by an Ultrafast CT scanner. The results were compared with flow determined by radiolabeled microspheres. Computed tomography (CT) flow was measured by an intravenous injection of nonionic contrast agent done simultaneously with the left atrial injection of microspheres. We calculated flow from the CT data by obtaining CT number versus time curves for regions of interest in the myocardium and by using a formula that related flow to both the time and value of the peak enhancement. Measurements were obtained in five dogs at rest and during hyperperfusion induced by chromonar. Based on 169 regional measurements, the Ultrafast CT and microsphere-determined flows correlated moderately (r = 0.68) over a range of 0.4 to 8 mL/min/g. However, when the data were divided into resting and hyperperfusion (ie, 20 to 30 minutes after the injection of the chromonar) states, a significant (P less than .001) increase in regional flow was determined from the CT measurements. The conclusion was that Ultrafast CT can distinguish between low and high myocardial flow states in dogs and has considerable potential for evaluating coronary flow reserve.

Hepatobiliary magnetic resonance contrast agents assessed by gadolinium-153 scintigraphy.

A simple method to test new gadolinium complexes potentially useful as enhancement agents for magnetic resonance imaging was developed. Healthy rats underwent scintigraphy with two potential hepatobiliary agents, diethyl IDA and diisopropyl IDA complexed with gadolinium-153. Control products included 153Gd DTPA, 153GdCl3 and technetium-99m diethyl IDA. As shown scintigraphically, 153Gd IDA complexes were partially excreted by urinary and hepatobiliary excretion early after administration. These findings paralleled significant reduction in 1H T1 values of excised livers. However, these agents exhibited prolonged 153Gd whole-body retention. The prolonged tissue distribution of 153Gd activity in animals given 153Gd diethyl IDA did not differ significantly from that observed in animals given GdCl3, and could be attributed to chemical instability or reticuloendothelial uptake. The scintigraphic method permits screening of gadolinium complexes in animals by showing mass balance, kinetics, distribution, and effective stability. Biologic effects of tracer or pharmacologic levels can be compared with those of carrier-free and carrier-added pharmaceuticals.

Acute myocardial infarction: MR evaluation in 29 patients.

This study evaluated the ability of MR to identify and characterize the region of myocardial infarction in humans. Twenty-nine patients, all with ECG and enzyme rises consistent with an acute myocardial infarction, were studied by MR 3-17 days from the onset of acute chest pain. Four patients were excluded because of inability to acquire adequate MR studies. For comparison, 20 normal subjects were studied who also had gated MR examinations. The site of infarction was visualized in 23 patients as an area of high signal intensity in relation to the normal myocardium, a contrast that increased on the second-echo image. The regions of abnormal signal intensity corresponded to the anatomic site of infarction as defined by the ECG changes. The mean T2 relaxation time of the infarcted myocardium (79 +/- 22 msec) was significantly prolonged in comparison with the mean T2 (43.9 +/- 9 msec) of normal myocardium (p less than .01). The mean percentage of contrast (intensity difference) between normal and infarcted myocardium was much greater on the second-echo images (65.6 +/- 34.0%) than the first-echo images (27.5 +/- 18.7%). In the normal subjects there was no difference in T2 between the anterolateral (40.3 +/- 5.7 msec) and septal (39.5 +/- 7.4 msec) regions, and percentages of contrast between these two regions of myocardium on the first-echo (9.1 +/- 7.4%) and second-echo (15.0 +/- 13.3%) images were similar. Thus, MR can be used to directly visualize acute infarcts. However, it has several pitfalls, including the necessity to differentiate signal from slowly flowing blood in the ventricle, from increased signal from a region of infarction and artifactual variation of signal intensity in the myocardium due to respiratory motion or residual cardiac motion.

MR imaging of the thyroid.

The thyroid gland was evaluated with MR imaging in six normal subjects and 32 patients with thyroid disease. The purpose was to evaluate signal characteristics of normal and diseased thyroid tissue; determine the contrast between normal and diseased tissue on T1- and T2-weighted images; compare relaxation times of normal thyroid, adenomas, and carcinoma; and assess the capability of MR for showing the extent of large thyroid masses. Adenomas and carcinomas were frequently isointense with normal thyroid tissue on T1-weighted images but had markedly higher intensity on T2-weighted images. The mean T1 (1202 +/- 717 msec) and T2 (118 +/- 48 msec) relaxation times of adenomas were markedly longer than the T1 (721 +/- 97 msec) and T2 (59 +/- 10 msec) times of normal thyroid tissue. Likewise, the T1 and T2 values of carcinomas were markedly prolonged compared with normal thyroid but the values overlapped with those of the adenomas. Sagittal and coronal images effectively depicted the extent of large goiters, adenomas, and carcinomas and indicated extension below the cervicothoracic junction. The marked prolongation of relaxation times associated with thyroid disease causes excellent contrast of lesions with normal thyroid and surrounding structures. The large field of view possible with coronal and sagittal images is useful for assessing extensive thyroid masses. These attributes indicate the potential clinical utility of MR for evaluating thyroid disease.

Occlusive and reperfused myocardial infarcts: effect of Gd-DTPA on ECG-gated MR imaging.

In vivo magnetic resonance (MR) imaging was performed to determine the effect of gadolinium-DTPA on MR intensity and relaxation times of occlusive and reperfused acute myocardial infarcts. In 18 dogs the left anterior descending (LAD) coronary artery was ligated. Five hours after LAD artery occlusion, six dogs in group 1 received intravenous Gd-DTPA, 0.5 mmol/kg, and 6 dogs in group 2 received 0.1 mmol/kg. The myocardia of the remaining six dogs (group 3) were reperfused after 1 hour of coronary artery occlusion; these dogs received 0.1 mmol/kg Gd-DTPA intravenously 5 hours later. MR imaging was performed before (control) and 5 minutes after Gd-DTPA administration. Intravenous administration of 0.1 mmol/kg Gd-DTPA significantly improved contrast between infarcted and normal myocardium on T1-weighted spin echo images in group 3. In all groups, T2-weighted precontrast images provided contrast between infarcted and normal myocardium equivalent or better than that provided by T1-weighted postcontrast images. Thus, Gd-DTPA did not improve contrast between ischemically injured and normal myocardium in the early hours after coronary artery occlusion.

Early-phase myocardial infarction: evaluation by MR imaging.

In vivo gated magnetic resonance (MR) imaging was performed in 12 dogs immediately after occlusion of the left anterior descending coronary artery and serially up to 5 hours and again between 4 and 14 days. This was done to evaluate the appearance of acute myocardial infarcts and to determine how soon after coronary artery occlusion MR imaging can demonstrate the site of acute myocardial ischemia. In nine dogs with postmortem evidence of myocardial infarction, regional increase of signal intensity of the myocardium was present by 3 hours after coronary artery occlusion and conformed to the site of myocardial infarct found at autopsy. The signal intensity on T2-weighted images of the infarcted myocardium was significantly greater than that of normal myocardium at 3, 4, and 5 hours after occlusion. The T2 (spin-spin) relaxation time was significantly prolonged in the region of myocardial infarct at 3, 4, and 5 hours postocclusion compared with normal myocardium. Myocardial wall thinning and increased intracavitary flow signal were found in six dogs with comparable pre- and postocclusion images in late systole.

Influence of physiologic motion on the appearance of tissue in MR images.

Studies were performed to determine the possible influence of physiologic motion on the parenchymal intensity of organs in magnetic resonance (MR) images. It is known that periodic motion associated with respiration and cardiac function causes characteristic artifacts in spin-warp images. The present study shows that bulk motion can also cause striking intensity changes at velocities equivalent to the craniocaudal respiratory excursion of organs in the upper abdomen. The magnitude of the effect depends on the velocity and direction of motion with respect to the three orthogonal axes of the imager and on the technical details of the imager and pulse sequence. Large systematic errors in calculated tissue relaxation times are possible due to this phenomenon. The findings have important implications for clinical imaging because motion can cause artifactual changes in the gray-scale relationships among tissues. Some pulse sequences are much less sensitive to these effects. These results provide guidance for selecting MR techniques that reduce the detrimental effect of respiratory and other physiologic motion on examinations of the upper abdomen and thorax.

Acute experimental cerebral ischemia: MR enhancement using Gd-DTPA.

The effects of a paramagnetic contrast agent, gadolinium-DTPA (Gd-DTPA), on magnetic resonance (MR) imaging of acute cerebral ischemia was investigated in a feline model of middle cerebral artery occlusion. Imaging was performed both before and after administration of an intravenous dose of 0.2 mmol/kg of Gd-DTPA. The animals were then sacrificed for pathologic correlation. No changes in intensity or relaxation times were noted before or after Gd-DTPA administration in two animals with 2 hours of occlusion. Infarcts were noted before and after contrast enhancement in all six cats with ischemia of greater than 16-hours duration. Gd-DTPA caused significant increase in intensity of infarct but not in that of normal cerebral tissue. Rapid enhancement was visible in infarcts of 16-24 hours, but such enhancement was slower in infarcts of 72-168 hours, presumably owing to slowed inflow caused by increased vasogenic edema in the latter group. Contrast enhancement of acute cerebral ischemic lesions with Gd-DTPA offers no improvement in sensitivity of MR imaging, although the conspicuity of the lesion may be improved. Additionally, contrast media may provide potential temporal and pathophysiological data for better characterization of cerebral ischemia.

Differentiation of reversible and irreversible myocardial injury by MR imaging with and without gadolinium-DTPA.

The current study evaluated the capability of magnetic resonance (MR) imaging to distinguish myocardium subjected to reversible and irreversible ischemic injury. Nine dogs underwent left anterior descending coronary arterial occlusion for 15 minutes (reversible injury) and nine for 1 hour (irreversible injury), followed by reperfusion for 24 hours in both groups. Six dogs from each group received 0.5 mmol/kg of gadolinium-DTPA intravenously; the remaining dogs received no contrast media. In the dogs with irreversible injury but no contrast media, there were prolonged T1 and T2 of the infarcted myocardium and adequate visualization of the infarct. The percentage of contrast between normal and infarcted myocardium was greatest on T2-weighted images. In the group with irreversible injury and contrast media, Gd-DTPA produced significant T1 shortening of injured myocardium, with resultant high signal intensity of the infarct, and significantly enhanced contrast compared with the group that did not receive Gd-DTPA. In the dogs with reversible injury, there were no regional differences in intensity or relaxation times. MR has the capability to distinguish myocardium with irreversible injury from that with reversible injury. The difference of T1 between normal and reperfused infarcted myocardium is increased by Gd-DTPA; thus, contrast between these two is enhanced on MR images.

Magnetic resonance imaging of chronic myocardial infarcts in man.

To evaluate the magnetic resonance imaging (MRI) features of chronic myocardial infarction (MI), 22 patients and several normal volunteers were studied with a 0.35-T cryogenic imaging system. The MIs were 9 months to 16 years old. The patients also had either left ventriculography (17 patients) or two-dimensional echocardiography (17 patients). At least one abnormality indicative of prior infarction was demonstrated on MRI in 20 of the 22 patients. Wall thinning was seen in 20 patients; in six of these, the thinning resulted in aneurysm formation. The other 14 patients had sufficient residual wall thickness to permit measurement of T2 relaxation times and MR signal intensity in the infarcted region. Ten of these 14 patients demonstrated low intensity and shortened T2 of the thinned segments (mean T2 = 28.7 msec) compared to adjacent normal myocardium (mean T2 = 45.4 msec) and to the myocardium of volunteers (mean T2 = 41.3 msec). The percentage of difference in intensity between thinned and normal myocardium was greater on 56-msec-TE images (98.2%) than on 28-msec-TE images (46.1%). In the other four patients, no difference in intensity of the myocardium was perceptible in the thinned region of the myocardial wall. Thus MRI shows regional wall thinning at the site of prior MI. In some patients, the chronic infarct is characterized as decreased spin-echo signal intensity and shortened T2 consistent with replacement of myocardium by fibrous scar.