Contrast-enhanced first pass myocardial perfusion imaging: Correlation between myocardial blood flow in dogs at rest and during hyperemia

The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180° inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T₁-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.     

Magnetic resonance imaging of myocardial perfusion and viability using a blood pool contrast agent

RATIONALE AND OBJECTIVES: A comprehensive cardiac magnetic resonance (MR) examination should comprise imaging of myocardial perfusion, viability, and the coronary arteries. Blood pool contrast agents (BPCAs) improve coronary MR angiography, whereas their potential for imaging of perfusion and viability is unknown. The abilities to noninvasively image myocardial perfusion and viability using the BPCA P792 (Guerbet, France) were tested in a closed-chest model of nonreperfused myocardial infarction in 5 pigs. MATERIALS AND METHODS: Two to 3 days after instrumentation, myocardial perfusion imaging with a saturation-recovery steady-state free precession technique and viability imaging with an inversion-recovery fast low-angle shot sequence were conducted on a 1.5-T MR scanner using the extracellular contrast agents (ECCA) Gd-DOTA (0.1 mmol Gd/kg) and blood pool contrast agent (BPCA) P792 (0.013 mmol Gd/kg). RESULTS: Perfusion defects were visualized in all pigs with good correlation between the ECCA and the BPCA (1.77 +/- 1.16 cm2 vs. 1.80 +/- 1.19 cm2, r = 0.959, P < 0.01). Reduced myocardial perfusion was detected using the ECCA up to 80 seconds after injection. In contrast, BPCA administration enabled visualization of perfusion defects on equilibrium perfusion imaging in all cases for 10 minutes. The size of myocardial infarction detected with viability MR imaging correlated well between the standard method (ECCA) and delayed-enhancement imaging with the BPCA (5.40 +/- 3.16 versus 5.52 +/- 3.13 cm3, r = 0.994, P < 0.002). CONCLUSIONS: The BPCA investigated in this study allows both reliable detection of perfusion defects on first pass and equilibrium perfusion imaging and characterization of viability after myocardial infarction. Thus, this contrast agent is suitable for a comprehensive cardiac MR examination.     

Evaluation of myocardial perfusion abnormalities with gadolinium-enhanced snapshot MR imaging in humans. Work in progress.

To determine whether myocardial perfusion abnormalities could be detected in patients with coronary artery disease by means of contrast material-enhanced magnetic resonance (MR) images, a snapshot imaging technique was used in six patients with coronary artery disease and four healthy subjects in conjunction with pharmacologic stress (dipyridamole infusion) and bolus injection of gadopentetate dimeglumine. MR images from all patients and healthy subjects were quantitatively analyzed to define spatial changes in signal intensity after administration of dipyridamole and gadopentetate dimeglumine. The resultant findings were compared with findings on thallium-201 scintigrams obtained after administration of dipyridamole and on coronary arteriograms in all patients. Nine myocardial regions supplied by stenosed arteries showed diminished levels of signal intensity after infusion of the contrast agent compared with those of normally perfused regions. These findings were in agreement with those obtained with T1-201 scintigraphy (in eight of nine regions) and arteriography. Thus, contrast-enhanced high-speed MR imaging with use of dipyridamole enabled detection of regional perfusion abnormalities in humans.     

Dynamic contrast-enhanced myocardial perfusion imaging using saturation-prepared TrueFISP

PURPOSE: To develop and test a saturation-recovery TrueFISP (SR-TrueFISP) pulse sequence for first-pass myocardial perfusion imaging. MATERIALS AND METHODS: First-pass magnetic resonance imaging (MRI) of Gd-DTPA (2 mL) kinetics in the heart was performed using an SR-TrueFISP pulse sequence (TR/TE/alpha = 2.6 msec/1.4 msec/55 degrees ) with saturation preparation TD = 30 msec before the TrueFISP readout. Measurements were also performed with a conventional saturation-recovery TurboFLASH (SRTF) pulse sequence for comparison. RESULTS: SR-TrueFISP images were of excellent quality and demonstrated contrast agent wash-in more clearly than SRTF images. The signal increase in myocardium was higher in SR-TrueFISP than in SRTF data. Precontrast SNR and peak CNR were not significantly different between both sequences despite 57% improved spatial resolution for SR-TrueFISP. CONCLUSION: SR-TrueFISP first-pass MRI of myocardial perfusion leads to a substantial improvement of image quality and spatial resolution. It is well suited for first-pass myocardial perfusion studies at cardiovascular MR systems with improved gradient hardware.     

Respiratory reordered UNFOLD perfusion imaging

PURPOSE: To propose a respiratory reordered UNFOLD (RR-UNFOLD) imaging sequence to significantly reduce the amount of k-space data required for first-pass MR myocardial perfusion imaging. MATERIALS AND METHODS: Rapid acquisition of high-resolution imaging data is essential to detailed quantitative analysis of first-pass myocardial perfusion. Existing MR sequences have explored the full capacity of the imaging hardware to reduce the acquisition window within each cardiac cycle while maintaining the desired spatial resolution. Further improvement in perfusion imaging will require a more efficient use of the information content of the k-space data. The method uses prospective diaphragmatic navigator echoes to ensure that temporal filtering of UNFOLD is carried out on a series of images that are spatially registered. An adaptive real-time rebinning algorithm is developed for the creation of static image subseries related to different levels of respiratory motion. Issues concerning the temporal smoothing of tracer kinetic signals are discussed, and a solution based on oversampling of the central k-space is provided. The method is assessed in 10 normal subjects without the administration of contrast agent, and further validated by administration of Gd-DTPA in 10 patients at rest. RESULTS: The results of this study show that RR-UNFOLD significantly extends the applicability of UNFOLD to perfusion imaging, which yields a 40% reduction in image artifact when the same amount of k-space information is used. CONCLUSION: The scan efficiency achieved can be used in combination with MR hardware improvements for extending the three-dimensional spatial coverage and shortening the data acquisition window to provide detailed information on regional myocardial perfusion abnormalities.     

Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction: Intraindividual Comparison of ECIII-60 and Gd-DTPA in a Swine Model

Purpose To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). Methods Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio and relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. Results A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80× smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. Conclusion Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.     

Cardiac CT: coronary arteries and beyond

Multi-detector-row computed tomography (MDCT) has emerged as a rapidly developing method for non-invasive imaging of the heart. An understanding of ECG synchronization, contrast material administration, patient preparation and image post-processing is needed to optimize image quality. The basic technical principles and essentials of these technical basics are described here. Correctly applied cardiac MDCT allows imaging of the coronary arteries including coronary anatomy and stenosis detection. The same is true for evaluation of coronary artery bypass grafts and, to some extent, coronary artery stents. While quantification of total calcified plaque burden has been long established, coronary MDCT allows assessing plaque morphology and constitution. Recent approaches go beyond the coronaries and include evaluation of left ventricular function at rest and myocardial viability. In combination with experimental approaches for assessing aortic valve function and myocardial perfusion imaging, cardiac MDCT offers the potential for a comprehensive examination of the heart using a single breath-hold examination.     

Comparison of ultrafast dipyridamole magnetic resonance imaging with dipyridamole sestamibi SPECT for detection of perfusion abnormalities in patients with one-vessel coronary artery disease: Assessment by quantitative model fitting

The value of ultrafast MRI for detection of myocardial perfusion abnormalities in patients with coronary artery disease (CAD) was assessed in 10 patients with stable angina pectoris and angiographically proven one-vessel CAD using double-level short-axis ultrafast MRI with bolus injection of gadolinium-DTPA and tomographic technetium-99m SestaMIBI imaging (SPECT) during dipyridamole-induced coronary hy-peremia. Abnormally perfused regions were assessed with SPECT and MRI in all (100%) patients. Agreement in localization between arteriography and SPECT was 80%; between arteriography and MR, 70%; and between SPECT and MR, 90%. The signal intensity increase after the bolus injection of gadolinium-DTPA using a linear fit, and the slope of gado-linium-DTPA wash-in using double exponential model fitting were significantly different between abnormally and normally perfused regions. These preliminary results demonstrate the potential of dipyridamole ultrafast MR to monitor stress-induced flow maldistribution in patients with single vessel CAD.     

Contrast-enhanced magnetic resonance imaging of hypoperfused myocardium.

Contrast-enhanced magnetic resonance (MR) imaging can define myocardial perfusion defects due to acute coronary occlusion. However, since most clinically important diagnostic examinations involve coronary arteries with subtotal stenoses, we investigated the ability of MR imaging with a manganese contrast agent to detect perfusion abnormalities in a canine model of partial coronary artery stenosis. The contrast agent was administered after the creation of a partial coronary artery stenosis with the addition of the coronary vasodilator dipyridamole in six of 12 animals. The hearts were imaged ex situ using gradient reversal and spin-echo sequences, and images were analyzed to determine differences in signal intensity between hypoperfused and normally perfused myocardium. Comparison of MR images with regional blood flow and thallium-201 measurements showed good concordance of hypoperfused segments in those animals given dipyridamole, with 75% of the abnormal segments correctly identified. In those animals not given dipyridamole, 48% of segments were correctly identified. Thus, ex vivo MR imaging with a paramagnetic contrast enhancement can be used to detect acute regional myocardial perfusion abnormalities due to severe partial coronary artery stenoses.     

Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease.

In order to clarify the relationship between coronary artery disease (including myocardial infarction) and image contrast in gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI it was decided to model the myocardial tissue distribution and clearance of Gd-DTPA using the modified Kety equation. Using a canine model, myocardial tissue Gd-DTPA concentrations ([Gd-DTPA]m) were measured 1 or 5 min after a bolus injection of Gd-DTPA or immediately after the end of a constant infusion of Gd-DTPA in a total of 35 dogs. It was found that within 5 min of a bolus injection [Gd-DTPA]m is determined primarily by myocardial blood flow (MBF) and after about 10 min primarily by myocardial extracellular volumes (MECV). This study suggests that repeat, rapid (every 2-4 s) measurements of myocardial T1 relaxation rates following the bolus injection of Gd-DTPA are required to calculate MBF (i.e., myocardial tissue perfusion) and MECV.     

Long-circulating liposomal contrast agents for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a dynamic technique for imaging vasculature. However, the currently used gadolinium (Gd) chelates, such as Gd-DTPA, restrict the time window for image acquisition due to their rapid elimination from blood and their rapid diffusion into the extravascular space, which prevents their use in steady-state imaging, particularly for MR angiography (MRA). The goal of this study was to prepare long-circulating polyethylene glycol-bearing ((PEG)ylated) liposomes encapsulating Gd chelate, and characterize and demonstrate their utility for MRA. The liposomes were prepared by hydrating a mixture of lipids with gadodiamide (Omniscan). The liposomes were sized down to around 100 nm by extruder and exhaustively dialysed to remove the unencapsulated gadodiamide. The Gd liposomes exhibited a significant sustained (>4 hr) contrast enhancement of the vasculature with improved spatial details in a rat model with little leakage relative to Gd-DTPA controls as shown by MRI. We suggest that such long-circulating liposomal formulations allow for high spatial resolution imaging without the confounding effects of clearance and extravascular diffusion of the agent complicating the data and image analysis.     

Infarcted myocardium in pigs: MR imaging enhanced with slow-interstitial-diffusion gadolinium compound P760.

PURPOSE: To assess the value of P760, a gadolinium chelate with slow interstitial diffusion and high relaxivity, for magnetic resonance (MR) imaging of acute myocardial infarction in pigs. MATERIALS AND METHODS: First-pass gradient-echo MR imaging and spin-echo MR imaging were performed with P760 and then with gadoterate meglumine in eight pigs with occlusive acute myocardial infarction. P760 signal intensity enhancement and clearance were compared with those of gadoterate meglumine. RESULTS: The first-pass enhancement ratio of P760 in normal myocardium was higher than that in infarcted myocardium (1.37 +/- 0.06 [SEM] vs 1.05 +/- 0.03, P = .03). The myocardial first pass showed a blood pool-like curve for P760. The blood pool enhancement ratio 40 seconds after injection was higher for P760 than for gadoterate meglumine (left ventricular cavity, 1.75 +/- 0.06 vs 1.45 +/- 0.06, P = .009). Spin-echo MR imaging showed improved contrast between normal and infarcted myocardium after P760 administration: The ratio before contrast material administration was 0.21 +/- 0.03, that at 15 minutes was 0.48 +/- 0.05 (P = .002), and that at 25 minutes was 0.47 +/- 0.07 (P = .003). CONCLUSION: P760 is an MR imaging contrast agent characterized by low diffusion, a blood pool effect soon after low-dose administration, and fast elimination. This agent is useful for improved myocardial perfusion MR imaging of acute myocardial infarction.     

Dynamic multi-section CT imaging in acute myocardial infarction: preliminary animal experience

To evaluate the feasibility of myocardial first-pass perfusion imaging with multidetector CT (MDCT). In five pigs, myocardial infaction was induced by permanent balloon occlusion of the left anterior descending coronary artery. Dynamic contrast-enhanced MDCT (12×1.5 mm, 120 kV, 30 mAs, 64 acquisitions, 40 ml iopromide 370@4ml/s) and contrast-enhanced first-pass perfusion magnetic resonance (MR) imaging (TR 7.7 ms/TE 2.6 ms, 64 acquisitions, 0.05 mmol/kg Gd-DTPA) were performed. Finally, the animals were sacrificed, and the heart was excised and stained with triphenyltetrazolin-chloride (TTC). Maximum signal intensity (SI_max), contrast material arrival time (CAT), wash-in time (T_max) and slope were calculated from time-density/signal-intensity curves. The area of myocardial hypoperfusion was measured as the percentage of the left-ventricular area (%LV). Parameters were compared using Bland-Altman plots and Student's t-tests. The hypoperfused area on MDCT was 19.3±4.5%LV (MR imaging 17.2±4.0%LV). The mean size of infarction was 18.7±5.7%LV with TTC. Semiquantitative analysis of MR imaging and MDCT for SI_max, T_max and slope showed significant differences between normal and infarcted myocardium (P<0.05). No significant differences were found for CAT. MDCT and MR imaging both allowed for the differentiation of hypoperfused and normal myocardium. Results given in absolute values differed significantly between both imaging modalities (P<0.05). MDCT has the potential for visual and semiquantitative assessment of first-pass myocardial perfusion.     

Preliminary evaluation of EVP 1001-1: a new cardiac-specific magnetic resonance contrast agent with kinetics suitable for steady-state imaging of the ischemic heart

RATIONALE AND OBJECTIVES: To investigate the potential of a novel manganese-based magnetic resonance (MR) contrast agent, EVP 1001-1 for the evaluation of myocardial ischemia. METHODS: MR imaging with EVP 1001-1 was performed on 6 Yorkshire pigs, and T1 relaxation times were calculated. One animal served as a control, 2 were subjected to an acute coronary artery occlusion and 3 provided a model of chronic ischemia. RESULTS: Administration of the agent in the control and acute coronary occlusion model demonstrated a short plasma half-life (approximately 1.5 minutes) and rapid myocardial uptake in nonoccluded regions, with long retention times in the myocardium (>1 hour) and no evidence of redistribution. In the chronic ischemia model, differential enhancement was observed between normal and ischemic tissue, particularly under dobutamine-induced stress. CONCLUSIONS: These properties suggest the use of EVP 1001-1 for steady-state imaging of myocardial perfusion. Contrast administration could be performed under stress conditions outside the scanner, with high-resolution MR images reflecting the stress condition acquired after the stress has subsided.     

Gd-BOPTA transport into rat hepatocytes: pharmacokinetic analysis of dynamic magnetic resonance images using a hollow-fiber bioreactor

RATIONALE AND OBJECTIVES: To investigate the transport of the hepatobiliary magnetic resonance (MR) imaging contrast agent Gd-BOPTA into rat hepatocytes. MATERIALS AND METHODS: In a MR-compatible hollow-fiber bioreactor containing hepatocytes, MR signal intensity was measured over time during the perfusion of Gd-BOPTA. For comparison, the perfusion of an extracellular contrast agent (Gd-DTPA) was also studied. A compartmental pharmacokinetic model was developed to describe dynamic signal intensity-time curves. RESULTS: The dynamic signal intensity-time curves of the hepatocyte hollow-fiber bioreactor during Gd-BOPTA perfusion were adequately fitted by 2 compartmental models. Modeling permitted to discriminate between the behaviors of the extracellular contrast agent (Gd-DTPA) and the hepatobiliary contrast agent (Gd-BOPTA). It allowed the successfully quantification of the parameters involved in such differences. Gd-BOPTA uptake was saturable at high substrate concentrations. CONCLUSIONS: The transport of Gd-BOPTA into rat hepatocytes was successfully described by compartmental analysis of the signal intensity recorded over time and supported the hypothesis of a transporter-mediated uptake.     

Myocardial paramagnetic contrast agents for MR imaging

Several different paramagnetic contrast agents have been investigated for use in myocardial MR imaging. Gd-DTPA, the most extensively studied agent, has been shown to improve the conspicuity of acute myocardial infarcts on MR images in experimental animals and humans. However, this agent is limited as a marker of perfusion because of its rapid elimination by renal excretion and equilibration within the extracellular fluid space. Future investigation of Gd-DTPA as a myocardial perfusion agent may involve rapid-scanning techniques to define time-dependent accumulation of the contrast agent in normal and ischemic myocardium during the first pass after IV injection. Nondiffusable paramagnetic agents and agents with prolonged retention in myocardium are being studied actively, but further tests of toxicity and metabolism are needed before clinical trials. Additional macromolecular-bound metal chelates will be tested in the future. It is hoped that these agents will allow detection of the jeopardized region of myocardium in the setting of acute ischemia, before the onset of myocardial edema.     

Dynamic coronary MR angiography and first-pass perfusion with intracoronary administration of contrast agent

PURPOSE: To evaluate whether dynamic imaging of the coronary arteries can be performed with intracoronary infusion of low-dose gadolinium (Gd)-based contrast agent and assess the effect of long duration and multiple infusions on the image signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). MATERIALS AND METHODS: Dynamic coronary magnetic resonance (MR) imaging (130 msec/image) and contrast agent first pass myocardial perfusion studies were performed with intracoronary infusions of low-dose Gd-based MR contrast agent on dogs (N = 4) using a fast multislice gradient recalled echo (GRE) sequence. RESULTS: Contrast-enhanced coronary arteries were clearly imaged during infusion periods as long as 2.3 minutes. The SNR and CNR of the contrast-enhanced coronary arteries remained essentially unchanged over multiple consecutive angiographic sessions. In addition, we demonstrated that first pass studies performed with intracoronary injection of MR contrast agent can be used as a means of assessing regional myocardial perfusion. CONCLUSION: These studies demonstrated that, using intracoronary infusion of Gd, coronary magnetic resonance angiography (MRA) can be performed with high temporal resolution, and multiple low-dose slow infusions of Gd-based MR contrast agent can be performed without compromise of the vessel SNR and CNR.     

Functional dynamic MRI,pharmacokinetics and safety of Gd-DTPA in patients with impaired renal function

Renal elimination of the paramagnetic contrast agent Gadolinium-DTPA (Gd-DTPA) was analyzed in 24 patients with impaired renal function and 3 normal controls. Dynamic magnetic resonance studies were performed using fast gradient-echo sequences with single images during suspended respiration and a temporal resolution of 10s per image. The time between appearance of the contrast agent in the renal cortex and signal intensity drop mL/min the medulla, due to a high concentration of Gd-DTPA and predominant T2-shortening, was an indicator of glomerular filtration rate and correlated well with creatinine clearance values (r=0.81). Fractionate urine collections and serum analysis up to 120h following administration showed a prolonged but complete elimination of Gd-DTPA mL/min patients with creatinine clearance above 20 mL/min. Renal functional parameters did not change after administration of Gd-DTPA and no nephrotoxic effects were observed.     

MR imaging at rest early after myocardial infarction: detection of preserved function in regions with evidence for ischemic injury and non-transmural myocardial infarction

Patients with subacute myocardial infarction were studied to detect regions of ischemic injury but with preserved myocardial function combining different MRI techniques. On a 1.5-T imaging system 27 patients were examined 7–14 days after acute myocardial infarction. The imaging protocol included T2-weighted fast spin-echo imaging, a cine fast low-angle shot (FLASH) 2D technique to determine regional function at rest, and a first pass as well as late contrast enhancement perfusion study injecting 0.1 mmol/kg Gd-DTPA. Preserved function was compared with the transmural extent of first-pass perfusion phenomena, increased T2 signal intensity (SI), and late contrast enhancement. Semi-quantitative first-pass perfusion parameters were correlated with quantitative myocardial wall thickening (MWT) and degree of coronary artery stenosis. Indicating ischemic injury increased T2 SI and late enhancement was present in 29 and 26% of segments. Preserved function was found predominantly in segments with non-transmural late enhancement (112 of 338 segments with late enhancement) and transmural increase of T2 SI (129 of 386 segments with increased T2 SI). A high-grade perfusion deficit was detected in 4% of all segments and regularly associated with markedly decreased systolic function. Correlation of first-pass perfusion parameters was observed with MWT (r=0.50–0.90, p<0.001) but not with the degree of coronary artery stenosis. Our data suggest that preserved function was detected in non-transmural myocardial infarction demonstrated by non-transmural late enhancement and increase of T2 SI. Electronic Publication     

MRI of acute myocardial ischemia: comparing a new contrast agent, Gd-DTPA-24-cascade-polymer, with Gd-DTPA

A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent delineation of acute myocardial ischemia. Acute myocardial ischemia was produced in 12 rats by occluding the anterior branch of the left coronary artery for 20-40 minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30 minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal intensity (deltaSI) in normal and ischemic myocardium were observed. In normal myocardium, both contrast agents caused a sharp increase in deltaSI, followed by a decline to baseline values over the 30-minute period. Enhancement in the ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic myocardium than the cascade polymer, which gave rise to virtually no enhancement. Significant differences (P<0.05) in signal enhancement between normal and ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal window of dynamic contrast-enhanced MRI for the differentiation of ischemic and normal myocardium. Identification of the ischemic zone is easier with the cascade polymer, which demonstrates virtually no signal enhancement in this territory.