Emmanuelle Canet

Influence of Severity of Myocardial Injury on Distribution of Macromolecules: Extravascular Versus Intravascular Gadolinium-Based Magnetic Resonance Contrast Agents☆

OBJECTIVES This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

A combined 1H perfusion/3He ventilation NMR study in rat lungs

The assessment of both pulmonary perfusion and ventilation is of crucial importance for a proper diagnosis of some lung diseases such as pulmonary embolism. In this study, we demonstrate the feasibility of combined magnetic resonance imaging lung ventilation and perfusion performed serially in rat lungs. Lung ventilation function was assessed using hyperpolarized 3He, and lung perfusion proton imaging was demonstrated using contrast agent injection. Both imaging techniques have been implemented using projection‐reconstruction sequences with free induction decay signal acquisitions. The study focused on fast three‐dimensional (3D) data acquisition. The projection‐reconstruction sequences used in this study allowed 3D data set acquisition in several minutes without high‐performance gradients. 3D proton perfusion/helium ventilation imaging has been demonstrated on an experimental rat model of pulmonary embolism showing normal lung ventilation associated with lung perfusion defect. Assuming the possibility, still under investigation, of showing lung obstruction pathologies using 3He imaging, these combined perfusion/ventilation methods could play a significant clinical role in the future for diagnosis of several pulmonary diseases. Magn Reson Med 41:645–648, 1999.

Dynamic 3He imaging for quantification of regional lung ventilation parameters.

Dynamic ventilation imaging using laser‐polarized 3He has a promising potential for elucidating the physiology and physiopathology of the lungs. In this study, a methodological approach is proposed for the assessment and quantification of local ventilation parameters. High‐temporal‐resolution coronal ventilation image series were obtained with a projection‐reconstruction (PR) sequence combined with the sliding‐window technique. After image series were processed, parametric pixel‐by‐pixel maps of the gas arrival time, filling time constant, inflation rate, and gas volume were generated. The acquisition technique and the signal processing procedure, which are referred to collectively as sliding pulmonary imaging for respiratory overview (SPIRO), were tested in vivo in healthy rat lungs using a contrast media injector for controlled 3He flow and volume injection in the animal lungs. The same protocol was applied to broncho‐constriction animal models using intravenous injection of methacholine solution. Inflation rate values measured in the lungs were found to decrease with increasing doses of injected methacholine solution. This study demonstrates that it is possible to obtain quantitative regional gas dynamic information using the SPIRO technique in a single polarized gas inspiration. Magn Reson Med 50:777–783, 2003.

Assessment of myocardial function and perfusion in a canine model of non-occlusive coronary artery stenosis using fast magnetic resonance imaging.

Magnetic resonance (MR) functional and perfusion imaging were employed in a canine model of coronary artery stenosis (n = 6) for the quantification of functional and perfusion deficits before and after dipyridamole administration. Left anterior descending and circumflex (LCX) coronary blood flow were measured continuously after placing Doppler flowmeters. Inversion recovery gradient echo images during the transit of MR contrast medium gadolinium‐benzyloxypropionictetraacetate dimeglumine (Gd‐BOPTA/Dimeg) and fast breath‐hold cine MR images were acquired at baseline, during LCX stenosis in basal state, and during LCX stenosis with vasodilation (dipyridamole 0.5 mg/kg). The extent of the functional defect and perfusion defect was expressed as percent of left ventricle (LV) circumference. During stenosis (LCX flow: 62.6 ± 5.6% of baseline) the extent of the functional defect was slightly larger than the perfusion defect (11.0 ± 1.8% versus 6.3 ± 1.7% of LV circumference, respectively; P < 0.01). During vasodilation the extent of the functional defect was considerably smaller than the perfusion defect (25.3 ± 2.5% versus 35.3 ± 3.5%; P < 0.01). Thus, the sizes of ischemic regions displayed by MR perfusion defect and functional defect differ from each other. J. Magn. Reson. Imaging 1999; 9:101–110. J. Magn. Reson. Imaging 1999;9:101–110

CARBOXYMETHYL-DEXTRAN-GADOLINIUM-DTPA AS A BLOOD-POOL CONTRAST AGENT FOR MAGNETIC RESONANCE ANGIOGRAPHY : EXPERIMENTAL STUDY IN RABBITS

RATIONALE AND OBJECTIVES The authors evaluate the efficiency of various doses of a paramagnetic macromolecular contrast agent, a gadolinium (Gd)-DTPA-dextran conjugate, as a blood-pool contrast media, in a transverse three-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography sequence of the abdominal aorta in rabbits. METHODS Imaging experiments were performed on a 1.5-T magnet, using a transverse three-dimensional TOF tilted optimized nonsaturating excitation (TONE) sequence. The macromolecular contrast media used was a carboxymethyl-dextran-Gd-DTPA (CMD-Gd-DTPA). Different concentrations of CMD-Gd-DTPA (0.005, 0.01, 0.03, 0.05 mmol Gd/kg) were evaluated. A comparative study using Gd-DOTA (0.01 and 0.1 mmol/kg) was performed. A visual analysis based on the gain in the visualized length of small arteries (renal arteries), and a quantitative analysis based on the percent contrast enhancement of the aorta plotted against distance in the slab from the top edge of the acquisition volume were obtained. RESULTS A signal-to-noise ratio enhancement of the distal part of the aorta and an improvement in the visualized length of the renal arteries were noted for concentrations of CMD-Gd-DTPA ranging form 0.01 to 0.05 mmol Gd/kg. Venous enhancement was noted for concentrations greater than 0.01 mmol Gd/kg when using CMD-Gd-DTPA or Gd-DOTA. CONCLUSION Carboxymethyl-dextran-Gd-DTPA reduced, in part, the saturation effect in a three-dimensional transverse TOF TONE MR angiography in rabbits. To prevent venous enhancement, observed with the higher concentrations used in this study, a decrease in the polydispersity of the polymer should be a goal in the future. Rapid extravasation of the low-molecular weight fraction of the polymer could explain the venous enhancement.

MR perfusion imaging using encapsulated laser‐polarized 3He

In this work, the use of a new carrier agent for intravascular laser‐polarized 3He imaging is reported. Lipid‐based helium microbubbles were investigated. Their average diameter of 3 μm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T  *2 of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal‐to‐noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects. Magn Reson Med 46:535–540, 2001.

Kinetic characterization of CMD-A2-Gd-DOTA as an intravascular contrast agent for myocardial perfusion measurement with MRI

Recent developments in magnetic resonance imaging (MRI) using specific contrast media allow the assessment of myocardial perfusion. The purpose of this study was to characterize the intravascular properties of a new macromolecular contrast agent, CMD‐A2‐Gd‐DOTA, to evaluate myocardial perfusion. Two groups of isolated pig hearts perfused at various controlled flows were used. To demonstrate the intravascular properties of CMD‐A2‐Gd‐DOTA, the agent was simultaneously injected with 99mTc‐labeled red blood cells in five hearts (group 1). Tracer kinetics of both compounds were assessed by coronary sinus effluent sampling, radioactivity counting and concentration determination in samples for first‐pass time curves measurements. Five other hearts (group 2) were studied using a two‐slice turboFLASH sequence on a 1.5‐T whole‐body MRI in order to evaluate first‐pass CMD‐A2‐Gd‐DOTA signal intensity (SI) versus time curves. In group 1, for the studied flows ranging from 0.8 to 3.1 ml/min−1 • g−1, CMD‐A2‐Gd‐DOTA showed first‐pass concentration curves typical of an intravascular contrast agent. In group 2, MRI parameters, i.e., upslope and mean transit time of SI time curves correlated strongly with myocardial perfusion. Within the physiologic range of flows, CMD‐A2‐Gd‐DOTA was able to demonstrate tracer kinetics for in vivo assessment of myocardial perfusion using MRI. Magn Reson Med 43:403–409, 2000.

Magnetic resonance perfusion imaging in ischemic heart disease.

This review explores the present status of contrast media available for myocardial perfusion studies, the magnetic resonance (MR) sequences adapted to multi‐slice first‐pass acquisitions, and the issue of myocardial perfusion quantification. To date, only low molecular weight paramagnetic gadolinium chelates have been used in clinical protocols for myocardial perfusion. With the availability of fast MR acquisition techniques to follow the first‐pass distribution of the contrast agent in the myocardium, the bolus tracking technique represents the more widely used protocol in MR perfusion studies. On T1‐weighted imaging, the ischemic zone appears with a delayed and lower signal enhancement compared with normally perfused myocardium. Visual analysis of the image series can be greatly improved by image post‐processing to obtain relative myocardial perfusion maps. With an intravascular tracer, myocardial kinetics are in theory easier to analyze in terms of perfusion. In experimental studies, different intravascular or blood pool MR contrast agents have been tested to measure quantitative perfusion parameters. If a simple flow‐limited kinetic model is developed with MR contrast agents, one important clinical application will be the evaluation of the functional consequence of coronary stenoses, ie, non‐invasive evaluation of the coronary reserve. J. Magn. Reson. Imaging 1999;10:423–433.

Noninvasive assessment of no-reflow phenomenon in a canine model of reperfused infarction by contrast-enhanced magnetic resonance imaging

The aim of this study was to test whether contrast-enhanced magnetic resonance (MR) imaging may assess in vivo the severity of the no-reflow phenomenon in a dog model of infarction with 2-hour coronary occlusion followed by reperfusion (6 hours). Subsecond MR imaging combined with intravenous bolus administration of superparamagnetic iron oxide particles (SPIO) was performed at the fifth hour of reperfusion. An MR index was calculated using the difference of signal-intensity enhancement between ischemic and nonischemic zones during the SPIO first pass. Dogs were separated into two groups according to the severity of ischemia: collateral blood flow in the central ischemic zone at 120 minutes of occlusion (radioactive microsphere technique) < 22.5% of the flow in the nonischemic zone (group I) or > 22.5% (group II). Mean collateral blood flow during occlusion was lower in group I (11.3% +/- 2.9%, n = 7) than in group II (66.8% +/- 19.8%, n = 6, p < 0.05). Mean infarct size was significantly larger in group I (58.6% +/- 4.9% of the area-at-risk, n = 7) than in group II (16.5% +/- 6.5%, n = 6, p < 0.05). For the entire population (n = 13), the infarct size was inversely correlated to the collateral blood flow (r = -0.64, p = 0.02, standard error of estimate = 0.24). The relative rate of enhancement in ischemic myocardium (MR index) was significantly lower in group I (38.1% +/- 10.9%) than in group II (142.8% +/- 32%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular and perfusion imaging using encapsulated laser-polarized helium

In this work, the use of hyperpolarized (HP)3He for in vivo intravascular imaging on animal is reported. To overcome the problem of the low solubility of helium in blood, we propose an approach based on helium encapsulation in lipid-based carrier agents. The mean diameter of the3He microbubbles. measured equal to 3.0 ±0.2 µm, makes it possible to conduct in vivo studies. In vitro spectroscopy yielded a longitudinal relaxation time T1 equal to 90 s and an apparent transverse relaxation timeT2* of 4.5 ms. Angiographie imaging (venous and cardiac cavity visualization), as well as lung perfusion imaging, were demonstrated in rats using intravenous injections of microbubble suspensions. Suitable signal and spatial resolution were achieved. The potential of this technique for lung perfusion assessment was assessed using an experimental animal embolism model. Lung perfusion defects and recovery towards a normal perfusion state were visualized. This study was completed with the demonstration of a new ventilation-perfusion lung exploration method based entirely on HP3He.