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We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T2* weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.

Rationale and Objectives: The authors assess the effect of weak protein binding on the efficacy of gadolinium chelates as contrast agents for magnetic resonance imaging (MRI)., Methods: Chelates with no (gadopentetate dimeglumine), weak (gadobenate dimeglumine), and strong (B-21326/7) protein binding were compared by in vitro MRI at 2T (spin echo [SE]: repetition time [TR]/echo time [TE] 350/8 mseconds) on solutions in 0.5 mM bovine serum albumin and in rat whole blood, and by in vivo MRI at 2T on rat models of brain tumors (SE TR/TE 350/10 mseconds) and of focal blood-brain barrier disruption (SE TR/TE 400/15 mseconds) after injection of MPP+. Relaxation rate enhancement in the blood of normal rabbits was measured in vivo after administration of contrast agents using IR-Snapshot FLASH., Results: Signal intensity enhancement measured in vitro for whole rat blood 0.1 mM in gadobenate was 142% relative to the same concentration of gadopentetate. Peak signal intensity enhancement in brain tumors was 87% +/- 8% and 64% +/- 5% after 0.1 mmol/kg intravenous administration of gadobenate and gadopentetate, respectively; in MPP+ lesions, the peak signal intensity enhancement was 22% +/- 9%, 32% +/- 7%, and 64% +/- 14% after 0.2 mmol/kg intravenous of gadopentetate, gadobenate, and B-21326/7, respectively. In rabbits, the relaxation enhancement of blood 5 minutes after B-21326/7 and gadobenate administration was 323% and 182%, respectively, relative to the same dose (0.1 mmol/kg intravenous) of gadopentetate., Conclusions: Weak protein binding can substantially increase the efficacy of gadolinium chelates as general purpose contrast agents for MRI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin.

This work was conducted to test the hypothesis that contrast-enhanced MRI with hepatocyte-specific contrast agents facilitates quantitation and mapping of diffuse liver diseases such as hepatitis and cirrhosis. Gadobenate dimeglumine (Gd-BOPTA/Dimeg, Bracco SpA, Millano, Italy) is a new paramagnetic hepatocyte-specific contrast agent currently undergoing clinical trials. We have assessed the usefulness of gadobenate dimeglumine for the diagnosis of diffuse liver diseases in a rat model of chemically induced hepatitis. The study was based on the measurements of in vivo liver relaxation times as well as on the acquisition of standard SE images. Acute hepatitis considerably reduced the degree of T1 shortening of liver parenchyma caused by intravenous injection of .25 mmol/kg of gadobenate dimeglumine. Analogously, the enhancement of the MRI signal intensity of the liver of rats with hepatitis observed in T1-weighted spin-echo (SE) images was inferior, in terms of both strength and duration, to that recorded in control rats at doses of .25 mmol/kg and .075 mmol/kg of gadobenate dimeglumine. Our results show that gadobenate dimeglumine-enhanced MR imaging has the potential for visualization of hepatitis and for assessment of liver function. Our conclusions differ from those previously published on this subject by other authors. The reasons that led to differing conclusions are discussed.

Rationale and Objectives: We monitored the differences in the first passage of gadobenate dimeglumine through normal and ischemic myocardium with left anterior descending (LAD) coronary artery occlusion in dogs., Methods: Dynamic multislice images of the heart were taken on a 1.5-T magnetic resonance (MR) imager. In six normal dogs, inversion recovery (IR)-prepared fast gradient-recalled echo (GRE) images were acquired at five doses of gadobenate dimeglumine (0.005-0.1 mmol/kg). First passage of the contrast medium through normal and acutely ischemic myocardium were monitored in seven dogs subjected to LAD coronary artery occlusion., Results: IR-prepared GRE images showed a dose-dependent increase in the signal intensity (SI) of the myocardium. In dogs with LAD coronary artery occlusion, there was a significant increase in the SI of normal myocardium (p < .01) than in ischemic myocardium after injection of 0.025 mmol/kg gadobenate dimeglumine., Conclusion: The first-pass dynamics of gadobenate dimeglumine through normal and ischemic myocardium can be monitored with a multislice acquisition using a clinical MR imager and differentiated between normal and ischemic myocardium in dogs.

Purpose: To monitor with fast gradient-echo magnetic resonance (MR) imaging the dynamics of gadolinium benzyloxypropionictetraacetate (gadobenate) dimeglumine on myocardial signal intensity in dogs with critical left circumflex coronary artery stenosis., Materials and Methods: Fast gradient-echo MR images were acquired in a short axis of the left ventricle. Two bolus injections of 0.05 mmol/kg gadobenate dimeglumine were administered in the basal state after stenosis and after infusion of 0.5 mg/kg dipyridamole., Results: In the basal state, there was an equivalent increase in signal intensity of normal and hypoperfused myocardium during the first pass. Dipyridamole increased left anterior descending flow (287% +/- 36; P < .05) and decreased left circumflex flow (65% +/- 14; P < .05). The magnitude of signal intensity increase during the second bolus in the hypoperfused region was less than that of normal myocardium (P < .05). Contrast-enhanced images showed the hypoperfused region as smaller than the postmortem measurement (43.8% +/- 3.3; P < .05)., Conclusion: Contrast-enhanced fast MR imaging in the vasodilated state allows detection of hypoperfused myocardium in the presence of critical coronary stenosis.

The efficacy for tumor detection of the hepatocyte-specific contrast agent gadobenate dimeglumine (gadolinium-BOPTA/Dimeg) was evaluated in four different experimental tumor models in rats. Histologic findings were correlated with quantitative data derived from ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Noninfiltrating tumors showed maximal enhancement of liver parenchyma 5-10 minutes after contrast agent administration, with a plateau over the next 30 minutes. In contrast, infiltrating tumors, which caused hepatocellular injury and inflammatory changes, delayed maximal enhancement of tumor-free parenchyma by 15-20 minutes. Nonspecific tumor enhancement depended on tumor vascularity and occurred in the early phase after contrast agent administration. Despite differences in specific enhancement of tumor-free parenchyma and nonspecific tumor enhancement, tumor-liver contrast-to-noise ratios increased 96%-248% in all tumor models 30 minutes after intravenous administration of 75 mmol/kg Gd-BOPTA/Dimeg. Gd-BOPTA/Dimeg enhanced tumor conspicuity independently of the histologic characteristics of the tumor.

Rationale and Objectives: The purposes of this study are to evaluate the first-pass profile of gadolinium-BOPTA/Dimeg (Gd-BOPTA/Dimeg) during its transit through hearts subjected to acute myocardial infarction, and to delineate these infarcted regions by the use of ultrafast magnetic resonance imaging (MRI)., Methods: Regional ischemia was induced in anesthetized rats by occluding the left coronary artery. Imaging parameters for single shot EPI included TE, 10 mseconds; AT, 33 mseconds; and 64 x 64-pixel matrix. Consecutive images were obtained every 1 to 2 seconds over a 30-second period. After approximately two images, Gd-BOPTA/Dimeg was injected intravenously (0.05 and 0.25 mmol/kg)., Results: Gd-BOPTA/Dimeg (0.05 mmol/kg), with inversion recovery EPI, produced a substantial increase in signal intensity of right and then left ventricular blood. Normally perfused myocardium also was enhanced, but not the acutely infarcted region. Clear delineation of the infarcted region as negatively enhanced "cold spots" persisted for at least 20 seconds. Gd-BOPTA/Dimeg (0.25 mmol/kg) with standard gradient-recalled EPI produced a different profile of signal intensity changes. Signal intensities of ventricular blood and normal myocardium were greatly reduced, leaving the infarcted zone as a positively enhanced "hot spot." Delineation of the infarcted region persisted for 6 to 8 seconds. The infarcted zone detected with MRI corresponded to that observed at autopsy., Conclusions: Regions of acute myocardial infarction can be detected as negatively enhanced "cold spots" or positively enhanced "hot spots" by studying the first-pass dynamics of Gd-BOPTA/Dimeg through hearts with regional ischemia by use of single shot EPI.

The novel tissue-specific contrast agent, Gd-BOPTA/Dimeg, was tested in MR imaging of experimental focal liver disease and of acute myocardial ischemia in rats. Directly implanted liver tumors and blood-borne metastases were used as models for focal liver disease and occlusion of the lower anterior descending coronary artery as model for acute ischemia. The studies with implanted tumors, at a dose level of 250 mumol/kg, showed a very high (370%) and persistent (greater than 2 h) increase in the tumor-liver contrast-to-noise ratio (CNR), owing to selective enhancement of normal liver parenchyma signal intensity. While all blood-borne metastases showed a similar late CNR enhancement, some of them experienced early contrast loss due to transient signal intensity enhancement. In myocardial imaging, Gd-BOPTA/Dimeg produced a signal intensity enhancement in normal myocardium and an injured area-normal area CNR enhancement which were both much stronger and more persistent than those produced by Gd-DTPA/Dimeg.