Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke.

Neonatal stroke occurs in one in 4,000 live births and leads to significant morbidity and mortality. Approximately two thirds of the survivors have long-term sequelae including seizures and neurological deficits. However, the pathophysiological mechanisms of recovery after neonatal stroke are not clearly understood, and preventive measures and treatments are nonexistent in the clinical setting. In this study, we investigated the effect of vascular endothelial growth factor (VEGF) treatment on histological recovery and angiogenic response to the developing brain after an ischemic insult. Ten-day-old Sprague-Dawley rats underwent right middle cerebral arterial occlusion (MCAO) for 1.5 h. Diffusion-weighted MRI during occlusion confirmed focal ischemia that was then followed by reperfusion. On group of animals received 5-bromo-2-deoxyuridine and sacrificed at postnatal day (P)18 or P25. A second group of animals was treated with VEGF (1.5 µg/kg, icv) or phosphate-buffered saline (PBS) at P18 and perfusion fixed at P25. Based on Nissl and iron staining, a single VEGF injection reduced the injury score, compared to the animals that underwent MCAO and PBS injection. Furthermore, neurodegeneration represented by neuronal nuclei staining was markedly diminished. In addition, animals treated with VEGF revealed a positive trend in endothelial proliferation and a significant increase in total vessel volume in the peri-infarct region of the caudate. The number of Iba1-positive microglial cells was significantly reduced after a single VEGF injection, and myelin basic protein expression was enhanced in the caudate after ischemia without an effect of VEGF treatment. In conclusion, delayed treatment with VEGF ameliorates injury, promotes endothelial cell proliferation, and increases total vascular volume following neonatal stroke. These results suggest that VEGF has a neuroprotective effect, in part by enhancing endogenous angiogenesis. These data contribute to a better understanding of neonatal stroke.

Assessment of nicorandil therapy in ischemic myocardial injury by using contrast-enhanced and functional MR imaging.

PURPOSE: To determine the potential of mesoporphyrin- and gadopentetate dimeglumine-enhanced and functional magnetic resonance (MR) imaging in the assessment of the acute effect of nicorandil on ischemic injury of the myocardium. MATERIALS AND METHODS: Spin-echo MR imaging was used to monitor changes in myocardial contrast and function in reperfused myocardial injury. Inversion-recovery echo-planar MR imaging was used to depict the injured region. Myocardial injury in rats was produced by using 30 minutes of coronary occlusion followed by 24 hours reperfusion. Nicorandil (n = 9) was infused during occlusion and early reperfusion. Control animals (n = 11) received no therapy. At 24 hours, after administration of mesoporphyrin and gadopentetate dimeglumine and histochemical staining, the function and size of the injured region of the left ventricle (LV) were determined. A t test was used to compare data between groups of animals, whereas regression and Bland-Altman analyses were used to determine correlation and agreement between MR imaging and histomorphometry, respectively. RESULTS: Treated animals showed reduced infarction size as compared with the control group from 25.6% +/- 7.9 (SD) to 7.9% +/- 6.8 of LV myocardial area (P < .001), as defined with mesoporphyrin-enhanced MR imaging; while the size of the rim increased from 10.8% +/- 10.0 to 16.1% +/- 14.4 (P < .05). The diastolic-midventricular cavity area was smaller in treated animals (15.2 mm(2) +/- 4.3) compared with the control group (28.5 mm(2) +/- 7.9; P < .001). At functional MR imaging, nicorandil improved systolic reduction in LV cavity area (57.5% +/- 17.3) compared with the control group (38.0% +/- 16.0; P < .05) and preserved regional LV wall thickening at the site of injury (12.2% +/- 11.1 in treated group vs 0.3% +/- 8.6 in the control group; P < .05). CONCLUSION: Contrast material-enhanced MR imaging has the potential to demonstrate reduction in size of ischemically injured myocardium, whereas functional MR imaging demonstrated the recovery of LV function 24 hours after nicorandil therapy.

MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology.

A new contrast medium, MS-325, was compared to albumin-(Gd-DTPA)(30) in 18 chemically induced rat breast tumors based on quantitative estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) using a two-compartment bidirectional model. No significant correlation was found between MS-325-enhanced microvascular assays with either tumor grade or with microvascular counts (MVCs). In comparison, the correlation coefficient between K(PS) and histologic tumor grade using albumin-(Gd-DTPA)(30) (r =.58) was statistically significant (P <.01). Also, using albumin-(Gd-DTPA)(30), a significant correlation (r =.55, P <.05) was observed between the K(PS) and MVC, a biomarker of angiogenesis. Correlations between fPV and MVC were not statistically significant for either contrast medium. In conclusion, using MS-325, no significant correlations between the MR-estimated permeability values or plasma volumes were observed in experimental breast tumors with either the histologic tumor grade or MVC. This analysis confirms our previous determination that capillary permeability estimates, using a prototype large molecular contrast medium, albumin-(Gd-DTPA)(30), correlate significantly with both histologic tumor grade and MVC.

Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow in a phantom simulating cardiac motion.

The purpose of this study was to investigate the accuracy of conventional, segmented, and echo-shared MR velocity mapping sequences to measure pulsatile flow in small moving vessels using a phantom with simulated cardiac motion. The phantom moved either cyclically in-plane, through-plane, in- and through-plane, or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD) for all sequences under all conditions, with or without background correction, as long as the region of interest (ROI) size was equal to the vessel cross-sectional size. Overestimation of flow as a result of an oversized ROI was less than 20%, and independent of field of view (FOV) and matrix, as long as the offset in angle between the imaging plane and flow direction was less than 10 degrees. Segmented velocity mapping sequences are surprisingly accurate in measuring average flow and render flow profiles in small moving vessels despite the blurring in the images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.

Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media.

BACKGROUND: Because ischemically injured myocardium is frequently composed of viable and nonviable portions, a method to discriminate the two is useful for clinical management. METHODS AND RESULTS: Ischemically injured myocardium was characterized with extracellular nonspecific (Gd-DTPA) and necrosis-specific (mesoporphyrin) MR contrast media in rats. Relaxation rates (R1) were measured on day 1 and day 2 by inversion-recovery echoplanar imaging. Spin-echo imaging was used to define contrast-enhanced regions and regional wall thickening. Gadolinium concentration, area at risk, and infarct size were measured at postmortem examination. DeltaR1 ratio (DeltaR1(myocardium)/DeltaR1(blood)) after administration of Gd-DTPA was greater in ischemically injured myocardium (1.20+/-0.15) than in normal myocardium (0.47+/-0.05, P<0.05), which was attributed to differences in gadolinium concentration and water content. The Gd-DTPA-enhanced region on day 2 was larger (32.8+/-0.9%) than true infarction as demonstrated by triphenyltetrazolium chloride (TTC) (24.6+/-1.4%, P<0.001, r=0.21). Bland-Altman analysis revealed that the Gd-DTPA-enhanced region overestimated true infarct size by 7.8+/-5.9%. On the other hand, the mesoporphyrin-enhanced region (26.9+/-1.8%, P=NS, r=0.87) and true infarct size were identical. The difference in the areas demarcated by the 2 agents is the peri-infarction. Systolic and diastolic MR images revealed no wall thickening in the mesoporphyrin-enhanced region (0.3+/-3.3%) but reduced thickening in the Gd-DTPA-enhanced rim (8.5+/-5.5%, P<0.05). CONCLUSIONS: The Gd-DTPA-enhanced region encompasses both viable and nonviable portions of the ischemically injured myocardium. The Gd-DTPA-enhanced area overestimated infarct size, but the mesoporphyrin-enhanced area matched true infarct size. The salvageable peri-infarction zone can be characterized with double-contrast-enhanced and functional MR imaging; the mismatched area of enhancement between the 2 agents shows residual wall thickening.

MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation.

PURPOSE: To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature. MATERIALS AND METHODS: NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)(30) were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) for each contrast medium. RESULTS: Strongly positive and significant correlations were observed between MR imaging-derived K(PS )estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)(30) (r = 0.88; P <.001) or larger particulate USPIO (r = 0.82; P <.001). A significant correlation (P <.05) was observed with each contrast medium between K(PS) and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging-derived mean permeability values generated with the two contrast media. CONCLUSION: USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K(PS) correlated strongly with histopathologic tumor grade, MVD, and K(PS) values derived by using albumin-(Gd-DTPA)(30) in the same tumors.

Myocardial viability: magnetic resonance assessment of functional reserve and tissue characterization.

The determination of myocardial viability is crucial in patients with left ventricular dysfunction resulting from acute myocardial ischemia or chronic coronary artery disease. Viable myocardium will most likely benefit from revascularization procedures. However, the revascularization of scar tissue will not lead to improvement of ventricularfunction andfurthermore bears unnecessary riskfor the patient. Currently, echocardiographic and radionuclide techniques are the most established methods for the assessment of presence and extent of viable myocardium. Magnetic resonance imaging (MRI) also provides multiple approaches for determining viability of acute ischemically injured and hibernating myocardium. MRI can assess contractile reserve in a manner similar to echocardiography. Additionally, contrast-enhanced MRI can characterize myocardial ischemic injury, including the ability to discriminate viable from nonviable zones. Several new contrast media have been introduced for this purpose. This review addresses the progress toward the goal of defining myocardial viability based on MR techniques and focuses on the current and future role of MR in the assessment of viable myocardium.

Quantitative gadopentetate-enhanced MRI of breast tumors: testing of different analytic methods.

This study assessed several proposed imaging strategies and analytic methods based on gadopentetate-enhanced MRI to differentiate benign from malignant breast tumors in a blinded experimental animal study. Steady-state dynamic MRI and first-pass imaging, performed with either T(1)- or T*(2)- weighted sequences, were compared. Semiquantitative and quantitative analysis methods, based on empirical measures of the data or physiological models, were subsequently applied to the imaging datasets. Comparative measures provided pathologic distinction of benign from malignant tumors, tumor grading, and histologic determination of microvascular density. Of the eight tested methods, only one, an estimate of first-pass perfusion using T *(2)-weighted imaging, showed an almost significant (P = 0.05) difference between benign and malignant tumors and correlated almost significantly (r =.3, P = 0.06) with the tumor grade. All other tests, performed either with steady-state imaging or with T(1)-weighted first-pass imaging, failed to differentiate benign from malignant tumors. In addition, they yielded poor correlations with tumor grade and microvascular density.

Blood pool MR contrast agents for cardiovascular imaging.

Currently available magnetic resonance (MR) contrast agents are not confined to the intravascular space because of their small molecular size. These agents produce peak vascular enhancement for only a short period. Conversely, blood pool agents have longer intravascular residence time and higher relaxivity. Therefore these agents provide MR angiography with flexibility, versatility, and accuracy. With blood pool agents, the timing of contrast injection becomes less significant because the optimal imaging window is in tens of minutes rather than seconds. In addition, larger anatomic regions can be imaged optimally. Preliminary evidence appears to support the notion that blood pool agents may play a diagnostic role in coronary, peripheral, and pulmonary angiography. Besides their ability to increase vascular contrast, blood pool agents provide physiologic information, including rate of entry, rate of accumulation, and rate of elimination. MR imaging with blood pool agents also have proven to be of significant value in the assessments of myocardial perfusion and microvascular permeability. In anticipation of broad clinical use, blood pool agents are currently being evaluated in human trails. Examples include gadolinium-chelate that binds in vivo to albumin to form blood pool agents and ultrasmall superparamagnetic iron oxide particles. This review discusses the applications of MR blood pool agents in the cardiovascular system. J. Magn. Reson. Imaging 2000;12:890-898.

Coronary sinus flow measurement by means of velocity-encoded cine MR imaging: validation by using flow probes in dogs.

PURPOSE: To validate coronary sinus flow measurements for quantification of global left ventricular (LV) perfusion by means of velocity-encoded cine (VEC) magnetic resonance (MR) imaging and flow probes. MATERIALS AND METHODS: Measurements of coronary sinus flow were performed in seven dogs by using VEC MR imaging at baseline, single coronary arterial stenosis, dipyridamole stress, and reactive hyperemia. These measurements were compared with flow probe measurements of coronary blood flow (CBF) in the left anterior descending coronary (LAD) and circumflex (CFX) arteries (CBF(LAD+CFX)) and coronary sinus. LV blood perfusion was calculated in milliliters per minute per gram from coronary sinus flow, and LV mass was obtained by using VEC and cine MR imaging. LV mass was validated at autopsy. RESULTS: CBF(LAD+CFX) and coronary sinus flow at VEC MR imaging showed close correlation (r = 0.98, P: <.001). The difference between CBF(LAD+CFX) and MR coronary sinus flow was 3.1 mL/min +/- 8.5 (SD). LV mass at cine MR imaging was not significantly different from that at autopsy (73.2 g +/- 12.8 vs 69. 4 g +/- 12.8). At baseline, myocardial perfusion was 0.40 mL/min/g +/- 0.09 at VEC MR imaging, and CBF(LAD+CFX) was 0.44 mL/min/g +/- 0. 08 (not significant). Reactive hyperemia resulted in 2.7- and 2. 3-fold increases in coronary sinus flow at VEC MR imaging and flow probe CBF(LAD+CFX), respectively. CONCLUSION: VEC MR imaging has the potential to measure coronary sinus flow during different physiologic conditions and can serve as a noninvasive modality to quantify global LV perfusion in patients.

Magnetic resonance imaging in an experimental model of human ovarian cancer demonstrating altered microvascular permeability after inhibition of vascular endothelial growth factor.

OBJECTIVE: Magnetic resonance imaging enhanced with macromolecular contrast medium was used to monitor effects of angiogenesis inhibition on tumor microvascular permeability and ascites volume in an athymic rat model of human ovarian cancer. STUDY DESIGN: Groups of 6 athymic rats implanted intraperitoneally with SKOV-3, a human ovarian cancer cell line, were treated through a 14-day course with antibody to vascular endothelial growth factor or with saline solution for control animals. Dynamic magnetic resonance imaging was performed with a 92,000-d contrast agent, albumin-(gadolinium-diethylenetriaminepentaacetic acid)(30). Vascular permeability was estimated from dynamic enhancement data that were analyzed with a unidirectional 2-compartment kinetic model. RESULTS: Animals treated with vascular endothelial growth factor antibody accumulated significantly smaller volumes of peritoneal ascites (P <.05) and showed significantly lower magnetic resonance imaging-assayed tumor microvascular permeabilities (P <.05) than did control animals. CONCLUSION: Magnetic resonance imaging enhanced with a macromolecular contrast agent in an athymic rat model of human ovarian cancer treated with anti-vascular endothelial growth factor antibody can be used to measure a reduction in tumor microvascular permeability, corresponding to a reduction in ascites production.

MR contrast media for myocardial viability, microvascular integrity and perfusion.

Cardiovascular imaging requires an appreciation of rapidly evolving MR imaging sequences as well as careful utilization of intravascular, extracellular and intracellular MR contrast media. At the present time, clinical studies are restricted to the use of extracellular MR contrast media. MR imaging has the potential to noninvasively measure multiple parameters of the cardiovascular system in a single imaging session. Recent advances in fast and ultrafast MR imaging have considerably enhanced the capability of this technique, beyond the assessment of left ventricular wall motion and morphology into visualization of the coronary arteries and measurement of blood flow. During the course of the last several years, multiple strategies for imaging viable myocardium have been developed and validated using MR contrast media. Contrast enhanced dynamic MR imaging provides information regarding microvascular integrity and perfusion. Because these information can be provided noninvasively by MR imaging, repeated measurements can be performed in longitudinal studies to monitor the progression or regression of myocardial injury. Similar studies are needed to examine the effects of newly developed cardioprotective therapeutics. Development of suitable intravascular MR contrast medium may be essential for visualization of the coronary arteries and interventional therapies. MR imaging may emerge as one-stop-shop for evaluating the heart and coronary system. This capability will make MR imaging cost-effective in the first decade of this millennium.

Normal and infarcted myocardium: differentiation with cellular uptake of manganese at MR imaging in a rat model.

PURPOSE: To assess whether normal myocardium can be distinguished from infarction at magnetic resonance (MR) imaging with low doses of manganese dipyridoxyl diphosphate (Mn-DPDP). MATERIALS AND METHODS: After 1-hour coronary arterial occlusion and 2-hour reperfusion, three groups of eight rats each were injected with 25, 50, or 100 micromol of Mn-DPDP per kilogram of body weight. The longitudinal relaxation rate (R1) in normal myocardium, reperfused infarction, and blood was repeatedly measured at inversion-recovery echo-planar imaging before and for 1 hour after the administration of contrast material. Afterward, several animals from each group were examined at high-spatial-resolution inversion-recovery spin-echo (SE) MR imaging. RESULTS: Manganese accumulated in normal myocardium but was cleared from reperfused infarction and blood. One hour after the administration of Mn-DPDP, R1 in normal myocardium (1.53 sec(-1) +/- 0.03, 1.73 sec(-1) +/- 0.03, and 1.94 sec(-1) +/- 0.02, respectively, for 25, 50, and 100 micromol/kg) was significantly (P <.05) faster than that of reperfused infarction (0.99 sec(-1) +/- 0.03, 1.11 sec(-1) +/- 0.03, and 1.48 sec(-1) +/- 0.06). Normal myocardium appeared hyperintense on T1-weighted inversion-recovery SE MR images and was clearly distinguishable from reperfused infarction. CONCLUSION: Mn-DPDP-enhanced inversion-recovery echo-planar and SE MR images demonstrated retention of manganese in normal myocardium and clearance of manganese from infarction. Mn-DPDP has characteristics similar to those of widely used thallium and may be useful in the assessment of myocardial viability at MR imaging.

Three-dimensional MR imaging of pulmonary vessels and parenchyma with NC100150 injection (Clariscan).

The influence of increasing doses of NC100150 Injection (Clariscantrade mark) and echo times on visualization of pulmonary vessels and parenchyma was evaluated. The effects of 0.5, 1, 2, 4, and 8 mg Fe/kg NC100150 Injection and echo times (TE) of 1.1, 1.8, 2. 2, and 4.3 msec were determined in six dogs using breath-hold three-dimensional (3D) spoiled gradient-echo magnetic resonance (MR) sequence. At 2 mg Fe/kg and TE of 1.1 msec, the signal-to-noise ratio of the central pulmonary arteries and parenchyma was significantly increased (5.3 +/- 2.2 to 50.3 +/- 2.4) and (2.2 +/- 0. 9 to 6.4 +/- 1.1), respectively. Using the TE of 1.1 msec, signal intensity in the main arteries continued to increase with increasing dose. Moreover, the enhancement of pulmonary parenchyma and microvasculature had a positive dose response. 3D MR imaging with ultrashort echo time and 2 mg Fe/kg NC100150 Injection produces angiograms with strong vascular contrast and allows qualitative assessment of pulmonary parenchyma and microvasculature.

Reperfused rat myocardium subjected to various durations of ischemia: estimation of the distribution volume of contrast material with echo-planar MR imaging.

PURPOSE: To estimate and compare the fractional distribution volume (fDV) of gadodiamide injection and technetium 99m-diethylenetriaminepentaacetic acid (DTPA) in the reperfused myocardium of rat hearts subjected to various durations of ischemia. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and autoradiography were performed in rats subjected to 20, 30, 40, or 60 minutes of regional ischemia followed by 1 hour of reperfusion. The fDVs of gadodiamide injection and (99m)Tc-DTPA were measured and compared by using inversion-recovery echo-planar imaging and autoradiographic phosphor imaging, respectively. RESULTS: The mean fDV of both tracers (gadodiamide and (99m)Tc-DTPA) in normal myocardium was 18% +/- 1, whereas that in the entire area at risk increased significantly (P <.05) with 20, 30, 40, and 60 minutes of ischemia to 32% +/- 1, 57% +/- 4, 66% +/- 2, and 68% +/- 2, respectively. The fDV was significantly (P <.05) greater in the core of infarction-78% +/- 4, 89% +/- 5, and 88% +/- 5 with 30, 40, and 60 minutes of ischemia, respectively-than in the normal myocardium or in the area at risk. CONCLUSION: The fDV of MR contrast material in the periinfarcted rim was significantly (P <. 05) greater than that in the normal myocardium, but significantly less than that in the core of infarcted myocardium.

T1-relaxation kinetics of extracellular, intracellular and intravascular MR contrast agents in normal and acutely reperfused infarcted myocardium using echo-planar MR imaging.

The objective of this study was to determine and compare if MR contrast agents distributed into various compartments can provide estimation of fractional distribution volume (FDV) in normal and infarcted myocardium using inversion recovery echo-planar MR imaging (IR EPI). Three different types of MR agents were investigated: (a) an extracellular agent, GdDTPA-BMA (0.1 mmol/kg); (b) an intravascular agent, GdDTPA-albumin (0.025 mmol/kg); and (c) an intracellular agent, manganese chloride (0.025 mmol/kg). The null point was determined from a series of IR EPI images in which TI was varied. Temporal changes in DeltaR1 (DeltaR1 = 1/T1(post)-1/T1(pre)) were measured during the initial 29-59 min after administration. Rats (n = 24) were subjected to 1-h coronary artery occlusion/reperfusion. Histochemical staining confirmed the presence and location of infarction. GdDTPA-BMA caused increase in DeltaR1 of infarction < blood < < normal myocardium. DeltaR1 ratios were 1.55 +/- 0.08 for infarction and 0.33 +/- 0.03 for normal myocardium, consistent with FDV of 0.82 +/- 0.04 and 0.18 +/- 0.01. The fractional distribution of this agent in normal myocardium approximated the extracellular space of myocardium. GdDTPA-albumin caused increase in DeltaR1 of blood < < infarction < < normal myocardium. DeltaR1 ratio in normal, but not infarcted, myocardium was constant at 0.10 +/- 0.02 and approximated fractional blood volume. MnCl(2) caused equivalent increase in DeltaR1 of normal and infarcted myocardium. DeltaR1 of normal myocardium did not change overtime, whereas DeltaR1 of blood rapidly decreased, leading to overestimation of FDV in normal and infarcted myocardium. In conclusion, extracellular, intravascular and intracellular MR contrast agents exhibited different T1-relaxation kinetics in both normal and infarcted myocardium. Constant DeltaR1 ratio (myocardium/blood) after administration of MR contrast agent is a prerequisite for estimation of FDV of MR contrast agent in myocardium.

Contrast-enhanced MRI for quantification of myocardial viability.

During the past 10 years substantial advances have taken place in magnetic resonance imaging (MRI) capabilities and in contrast media development. Furthermore, knowledge of in vivo contrast media interactions with surrounding water and distribution into tissue has increased, permitting regional quantification of concentration-time profiles in the myocardium. The combination of these advances has substantially improved the capability of contrast-enhanced MRI characterization of myocardial ischemic injury, including its ability to discriminate viable from nonviable zones. Discrimination of viable from nonviable myocardial subregions is important for patient management and for research applications. This review addresses recent progress toward the goal of defining viable and nonviable myocardium based on MRI detection of contrast media effects. J. Magn. Reson. Imaging 1999;10:694-702.

Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats.

PURPOSE: To measure the difference in size of reperfused myocardial infarction with necrosis-specific (bis-gadolinium-mesoporphyrin [hereafter, mesoporphyrin]) and standard extracellular (gadopentetate dimeglumine) magnetic resonance (MR) contrast media. MATERIALS AND METHODS: Echo-planar (for T1 measurement) and spin-echo (for infarction size) MR imaging were conducted in 32 rats subjected to reperfused reversible (n = 16) and irreversible (n = 16) myocardial injuries. All animals received gadopentetate dimeglumine 1 hour after reperfusion and underwent imaging. Sixteen rats received mesoporphyrin at 2 hours, the other 16 rats received gadopentetate dimeglumine at 24 hours, and all animals underwent imaging at 24 hours. RESULTS: Mesoporphyrin produced prolonged (22 hours) reduction in T1 in irreversibly, but not in reversibly, injured myocardium. The size of the mesoporphyrin-enhanced region (37% +/- 4 [SEM] of left ventricular surface area) closely correlated with the true infarction size as measured by means of histomorphometry (36% +/- 3, r = 0.90). The size of the gadolinium-enhanced region overestimated (48% +/- 2 and 43% +/- 1 at 1 and 24 hours of reperfusion, respectively) the size of true infarction (36% +/- 3, P < .05, r = 0.02), but it was close to the size of the area at risk (r = 0.93). CONCLUSION: The sizes of hyperenhanced regions displayed by using mesoporphyrin and gadopentetate dimeglumine differed from each other. The difference in size of the hyperenhanced region demarcated by mesoporphyrin and gadopentetate dimeglumine may provide an estimation of potentially salvageable myocardium.

Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular and small-molecular contrast media--preliminary experience.

PURPOSE: To differentiate prostate cancers of different histopathologic grades with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Results with a conventional small-molecular contrast medium (CM) were compared to those with a prototypic macromolecular CM. MATERIALS AND METHODS: High- and low-grade tumors, sublines of the Dunning R3327 rat prostate cancer line, were subcutaneously implanted into the flanks of 12 male Copenhagen rats. Dynamic contrast material-enhanced MR imaging was performed with small-molecular CM and macromolecular CM at an interval of 1 day. Microvascular permeability, as estimated with the endothelial transfer coefficient, and fractional plasma volume were calculated for each tumor and each CM by means of a two-compartmental, bidirectional kinetic model. RESULTS: Mean endothelial transfer coefficient values for both macromolecular CM and small-molecular CM were significantly different between the two tumor sublines (P = .0004 and P = .01, respectively). For the high- and low-grade tumors, no overlap of values was seen with macromolecular CM, but a broad overlap was seen with small-molecular CM despite a significant difference in mean values. CONCLUSION: Dynamic contrast-enhanced MR imaging permits differentiation of histopathologic prostatic tumor types. Quantitative microvascular permeability characteristics estimated from macromolecular CM-enhanced data were significantly superior to those derived from small-molecular CM-enhanced data.