Complete elimination of the hepatobiliary mr contrast agent Gd-EOB-DTPA in hepatic dysfunction: An experimental study using transport-deficient,mutant rats

Mutant Wistar rats (TR^– rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR^/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25µmol kg^–1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250µmolkg^–1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR^– rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25µmol kg^–1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.     

Volumetric assessment of myocardial viability in rats using 3D double contrast enhanced T1 and T2-weighted MRI

Objective: Volumetric evaluation of the myocardial viability post-infarction in rats using 3D in vivo MR imaging at 7 T using injection of an extracellular paramagnetic contrast agent and intravascular superparamagnetic iron oxide nanoparticles in the same imaging session. Materials and methods: Five hours after induction of permanent myocardial infarction in rats (n=6), 3D in vivo T1- and T2-weighted MR Imaging was performed prior to and after Gd-DOTA injection (0.2 mmol/kg) and prior to and after nanoparticle injection (5 mg Fe/kg) to assess infarct size and myocardial viability. Results: 3D MR Imaging using a successive contrast agent injection showed a difference of infarct size after Gd-DOTA injection on T1-weighted images compared to the one measured on T2-weighted images after Gd-DOTA and nanoparticle injection. Conclusion: The use of 3D T1- and T2-weighted MR Imaging using a double contrast agents protocol made possible the accurate characterization of myocardial infarction volume and allowed the detection of myocardial viability post-infarction in rats     

Liver and spleen enhancement after intravenous injection of carboxydextran magnetite: effect of dose,delay of imaging,and field strength in anex vivo model

It has been predicted that liver and spleen enhancement after administration of superparamagnetic contrast agents may be different, depending on the strength of the main magnetic field. With the use of anex vivo model, we investigated at 0.3, 0.5, and 1.5 T the effects on liver and spleen signal intensity of 5, 15, and 45 µmol/kg body weight of dextran magnetite (SHU 555A) in 54 rats. Nine rats served as controls. At different time delays since injection, the animals were killed, and after perfusion with saline, the liver, brain, and spleen were fixed in formalin. The specimens were embedded in an agar gel matrix and imaged with inversion recovery T1-weighted, proton density spin echo, and T2*-weighted gradient recalled echo (GRE) sequences. At each magnetic field strength, peak liver and spleen signal loss increased with increasing dose of the contrast medium. Signal loss was significantly more conspicuous after a dose of 15 than 5 µmol/kg body weight, but not after a dose of 45 compared with 15 µmol/kg. No signal change was observed in the brain. GRE images showed higher enhancement than proton density-weighted spin echo and inversion recovery images but were noisier. The enhancement showed a plateau between 30 min and 24 hours. Only the signal decrease of the liver after a low dose of contrast medium on GRE images was significantly higher (p<0.01) at 1.5 than at 0.5 and 0.3 T. Other differences in respect to the field strength were less significant (p<0.05) or nonsignificant. Differences in the spleen enhancement were nonsignificant. SHU 555A at a dose of 15 µmol/kg is an efficient intracellular contrast agent for liver and spleen at low, mid, and high field strength. Proton density spin echo images are probably the sequence of choice to exploit SHU 555A contrast effects and a wide time window for imaging after its intravenous injection does exist.     

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4±0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k_ep and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k_ep decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.     

Intravascular contrast agent <Emphasis Type="Italic">T1</Emphasis> shortening: fast <Emphasis Type="Italic">T1</Emphasis> relaxometry in a carotid volunteer study

OBJECTIVE: To measure the T1 times in blood after the administration of the intravascular contrast agent gadofosveset trisodium in humans. MATERIALS AND METHODS: In a pilot study for parameter optimization, the T1-shortening induced by the injection of a single dose (0.03 mmol/kg body weight) of the MR contrast agent Vasovist (Bayer Schering Pharma AG) was measured at B (0) = 1.5 T as a function of time. In four sessions, T1 measurements were performed in the carotid vein of 9 volunteers up to 30 min after injection. T1 times were measured using a segmented saturation recovery turboFLASH (SSRTFL) pulse sequence with 7 different saturation recovery delay times in a total acquisition time of 20 s. RESULTS: The SSRTFL measurements showed T1 times of about 100 ms immediately after injection, which gradually increased to 175 ms at 30 min. The time curve of the R1 = 1/T1 averaged over all volunteers could be described with an exponential decay with a time constant T = 330 +/- 65 s and an amplitude DeltaR1 = 4.1 +/- 0.3 s(-1), and a constant offset of R1(0) = 5.7 +/- 0.2 s(-1). Mean relaxation values are in excellent agreement with theoretical predictions. CONCLUSION: An analytical expression for the initial T1-shortening of Vasovist was derived which can now be used for optimization of the pulse sequence parameters in clinical studies.     

Characterization of late radiation effects in the rat thoracolumbar spinal cord by MR imaging using USPIO

The aim of this study was to detect late radiation effects in the rat spinal cord using MR imaging with ultra-small particles of iron oxide (USPIO) contrast agent to better understand the development of late radiation damage with emphasis on the period preceding neurological signs. Additionally, the role of an inflammatory reaction was assessed by measuring macrophages that internalized USPIO. T₂-weighted spin echo MR measurements were performed at 7T in six rats before paresis was expected (130–150 days post-irradiation, early group), and in six paretic rats (150–190 days post-irradiation, late group). Measurements were performed before, directly after and, only in the early group, 40 h after USPIO administration and compared with histology. In the early group, MR images showed focal regions in grey matter (GM) and white matter (WM) with signal intensity reduction after USPIO injection. Larger lesions with contrast enhancement were located in and around edematous GM of three animals of the early group and five of the late group. Forty hours after injection, additional lesions in WM, GM and nerve roots appeared in animals with GM edema. In the late paretic group, MR imaging showed WM necrosis adjacent to areas with large contrast enhancement. In conclusion, detection of early focal lesions was improved by contrast administration. In the animals with extended radiation damage, large hypo-intense regions appeared due to USPIO, which might be attributed to blood spinal cord barrier breakdown, but the involvement of blood-derived iron-loaded macrophages could not be excluded.     

P846, a new gadolinium based low diffusion magnetic resonance contrast agent,in characterizing occlusive infarcts,reperfused ischemic myocardium and reperfused infarcts in rats

OBJECT: This study has two objectives: (1) to compare the kinetics of low diffusion P846 with Gd-DOTA using inversion recovery echo planar (IR-EPI) magnetic resonance (MR) imaging and (2) to determine the potential of P846 in defining myocardial viability in hearts subjected to various injuries using T1-weighted spin echo (T1-SE). MATERIALS AND METHODS: Rats were subjected to (1) occlusive infarcts (n = 16), (2) reperfused ischemic injuries (n = 8) or (3) reperfused infarcts (n = 16). A dose of 0.05 mmol/kg P846 was compared to 0.1 mmol/kg Gd-DOTA. IR-EPI and T1-SE images were obtained during 60 min. T(1), DeltaR(1) and DeltaR(1) ratio were measured on IR-EPI. Infarct extents were evaluated on T1-SE and compared with histochemical staining. RESULTS: Blood DeltaR(1) was higher at 5 min after P846 (6.36 +/- 0.32 s(-1)) than after Gd-DOTA (1.30 +/- 0.14 s(-1); P < 0.001). With P846, occlusive infarcts appeared as a hypoenhanced region surrounded by a hyperenhanced rim that lasted for 60 min. The increase in the DeltaR(1) ratio value was slower after P846 than with Gd-DOTA in the reperfused infarcts, suggesting low diffusion/convection of P846. Gd-DOTA homogenously enhanced both occlusive and reperfused infarcts at 30 min. CONCLUSION: P846 provides better contrast and extended discrimination between occlusive and reperfused infarcts compared with Gd-DOTA. The gadolinium dose could be reduced with P846.     

Comparison of sequences for depicting bone marrow alterations in osteomyelitis applied in a low field strength magnetic resonance imaging system

Objective/Patients: to investigate the efficacy of standard sequences of a low field system for the detection of osteomyelitis, we tested TlwI pre and post i.v. contrast, T2w and fat suppressed IR sequences. Design: on the basis of clinical and laboratory evidence, pathology reports, and three phase granulocyte scintigraphy, osteomyelitis was diagnosed in 18 of 21 patients with Charcot's joints. A consecutive low and high field magnetic resonance (MR) scan confirmed osteomyelitic bone marrow changes in the same osseous regions. These 18 diabetic patients were then studied on a 0.2 Tesla dedicated MR system (Esaote ArtoScan) using TlwI (SE: relaxation time (TR) 520/echo time (TE) 24: axial and coronal) before and after i.v. application of 0.1 mmol/1 Gd-DTPA/kg BW, T2w imaging (TSE: TR 3500/TE 80 or TR 2000/TE 120: axial), and fat suppressed inversion recovery (IR) imaging (short tau inversion recovery (STIR): TR 3000/TE 30/TI 80 or inversion recovery gradient echo (IRGE)/fat suppressed IRGE (GEFS): TR 1000/TE 16m 80: coronal). Results: the SE Tlw sequence showed a significantly higher contrast-to-noise ratio (CNR) before administration of i.v. contrast. The TSE T2w pulse sequence demonstrated bone marrow changes superiorily utilizing a TE of 120 ms (CNR=16.5±2.7 compared to 5.5±2.5 with TE=80 ms). The IRGE showed a higher CNR than the standard STIR (CNR=19.2±2.5 compared to 12.4±2.9). Conclusion: fat suppressed IRGE imaging and longer TE in T2w TSE sequences result in a significantly better, CNR in osteomyelitis. This way, using optimized sequences, low field systems are apt to depict bone marrow changes in the course of osteomyelitis.     

Quantification of Choline-containing Compounds in Malignant Breast Tumors by 1H MR Spectroscopy Using Water as an Internal Reference at 1.5 T

The quantification of choline-containing compounds (Cho) in breast tumors by proton MR spectroscopy (¹H-MRS) has been of great interest because such compounds have been linked to malignancy. In this study, an internal reference method for the absolute quantification of Cho metabolite in malignant breast tumors was presented using a clinical 1.5 T scanner. We performed in vitro measurements to examine the accuracy of absolute quantification using four phantoms of known choline chloride concentrations. There was a high correlation between the calculated concentrations by MRS and the known concentrations (r ² > 0.98). We applied the technique to in vivo breast study conducted on 45 patients with biopsy-confirmed breast cancer. After T ₁ and T ₂ relaxation times were corrected, the Cho levels in this work had a range of 0.76 – 21.20 mmol/kg from 34 MR spectra of 32 patients with malignant breast lesions. This result was rather consistent with the previously published value (i.e., 1.38 – 10 mmol/kg, Bolan et al. in Magn Reson Med 50:1134–1143, 2003). Therefore, we conclude that the internal method using the fully relaxed water as a reference could be used for quantifying Cho metabolite accurately in breast cancer patients using a clinical 1.5 T scanner.     

Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla

To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE^–/– mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.     

Turbo spin-echo sequences in magnetic resonance imaging of the brain: Physics and applications

Fast SE imaging provides considerable measure time reduction, high signal-to-noise ratios as well as similar contrast behavior compared to conventional SE sequences. Besides TR and TE_eff, echo train length (ETL), interecho time , and-space trajectory determine image contrast and image quality in fast SE sequences. True proton density contrast (CSF hypointense) and not too strong T2 contrast are essential requirements in routine brain MRI. A Turbo SE sequence with very short echo train length (ETL=3), short TE_eff and short interecho time (17 ms), and TR=2000 ms was selected for proton density contrast; a Turbo SE sequence with ETL=7, TE_eff=90 ms, =22 ms, and TR=3250 ms was selected for T₂-weighted images. Using both single-echo Turbo SE sequences yielded 50% measure time reduction compared to the conventional SE technique. Conventional SE and optimized Turbo SE sequences were compared in 150 patients resulting in very similar signal and contrast behavior. Furthermore, reduced flow artifacts in proton density—and especially in T₂-weighted Turbo SE images—and better contrast of high-intensity lesions in proton density-weighted Turbo SE images were found. Slightly reduced edge sharpness—mainly in T₂-weighted Turbo SE images—did not reduce diagnostic reliability. Differences between conventional and Turbo SE images concerning image contrast and quality are explained regarding special features of fast SE technique.Address for correspondence: Institut für Röntgendiagnostik, Klinikum der Universität Regensburg, Franz-Josef-Strauß-Allee 11, 93042 Regensburg, Germany. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Venn Plaza, New York, NY 10119.     

Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent

Rationale and objectives: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium. Methods: The pharmacokinetics of Gadomer-17 were investigated in different species (rat, rabbit, dog, monkey) for up to 7 days after intravenous (i.v.) injection of 25–100 μmol/kg body weight. In addition, elimination and biodistribution were evaluated after single i.v. injection of Gadomer-17 in rats. Results: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space without significant diffusion into the interstitial space. The volume of distribution (Vc) in the initial or α-phase ranged from 0.04 1/kg (rats, rabbits) to 0.06 1 kg (monkeys) and 0.07 1/kg (dogs), which reflects mainly the plasma volume. The blood/plasma concentration profile was found to be biphasic. The volume of distribution at a steady state is clearly smaller than that of other contrast media, which distribute to the extracellular space. After single i.v. injection in rats, the dendritic contrast medium was rapidly and completely eliminated from the body, mainly via glomerular filtration. No long-term accumulation or retention of the nonmetabolized agent was detectable in organs or tissues. Conclusions: Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.     

Contrast-enhanced abdominal echo planar imaging: Dynamic signal-intensity changes following intravenous injection of gadolinium-DOTA

Objectives: After I.V. administration of gadolinium-DOTA, the early contrast enhancement pattern and related signal-intensity (SI) changes in normal abdominal organs (kidney, spleen, liver) are evaluated over the first 4 min by using ultrafast spin-echo echo planar imaging (SE-EPI). Methods: On a 1.5-T magnetic resonance unit ultrafast EPI of the upper abdomen was performed in 12 patients in order to show the contrast enhancement pattern and related measurable SI changes onT ₁ andT ₂-weighted (w) images over the first 4 min after I.V. bolus injection of 0.1 mmol kg^–1 gadolinium (Gd)-DOTA in the spleen, liver, renal cortex, and renal medulla. A TR/TE of 500/44 or 45 ms inT ₁w SE-EPI and a TR/TE of 2000/80 or 100 ms inT ₂-w SE-EPI were used. Results: Typical time-dependent SI changes were noticed onT ₁w images: Subsequent to a SI increase in the renal cortex (starting 7 s after the I.V. injection of Gd-DOTA) SI increased first in the outer renal medulla (6 s later) and then in the inner renal medulla (21 s later). A SI increase was observed in the spleen (starting after 15 s) and in the liver (starting 7 s later). OnT ₂-w images, a SI decrease in the renal cortex (starting after 14 s) was followed by migration of a dark band from the outer (after 46 s) to the inner medulla (after 70 s). Only minimal changes were noticed in the spleen and liver. Conclusions: Ultrafast SE-EPI following I.V. bolus injection of Gd-DOTA enables the observation of the very early contrast agent kinetics in various abdominal organs. The associated SI changes onT ₁- andT ₂- SE EPI are related to organ perfusion and contrast agent tissue concentration and biodistribution.Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Penn Plaza, New York, NY 10119.     

Gadofluorine 8: initial experience with a new contrast medium for interstitial MR lymphography

Rationale and objectives: Differential diagnosis of malignant and benign lymph nodes is still a problem in lymphographic imaging modalities. Plain magnetic resonance imaging (MRI) and computed tomography (CT) are inadequate for detecting metastases in normal-sized lymph nodes and for differentiating enlarged nodes. Therefore it is important to have a contrast agent that accumulates in healthy lymphatic tissue but does not accumulate in metastatic deposits.Methods: The lymphographic constrast agent Gadofluorine 8 (Schering AG, Berlin, Germany) is a lipophilic but water-soluble gadolinium complex. Lymphographic effects were investigated in guinea pigs, dogs, and tumor-bearing rabbits after interstitial (subcutaneous or intracutaneous) injection. MR imaging was performed using T₁-weighted gradient-echo sequences until 120 min after administration.Results: After interstitial injection Gadofluorine 8 accumulates in regional, lymph nodes, resulting in a pronounced increase in signal intensity in the lymph nodes. Differentiation between normal and metastatic lymph nodes was achieved.Conclusions: Gadofluorine 8 is an innovative contrast agent that can distinguish between normal and tumorous lymph nodes in interstitial MR lymphography.     

Cerebral blood flow response to a hypoxic-ischemic insult differs in neonatal and juvenile rats

To compare the cerebral blood flow (CBF) response to a transient episode of hypoxia–ischemia producing damage in neonatal and juvenile rats. One- and four-week-old rats were subjected to unilateral carotid artery occlusion plus hypoxia (8% oxygen). Perfusion MR images were acquired either in sham controls or in hypoxic–ischemic rats before, during, 1 h and 24 h after hypoxia–ischemia. At 24 h post hypoxia–ischemia, T₂ maps and histology were used to assess damage. In sham controls, CBF increased twofold between the age of one and four weeks. Reductions in CBF ipsilateral to the occlusion occurred during hypoxia–ischemia followed by a substantial recovery at 1 h post in both age groups. However, contralaterally, hyperemia occurred during hypoxia–ischemia in four-week but not one-week-old rats. Similarly, hyperemia occurred ipsilaterally at 24 h post hypoxia–ischemia in four-week but not one-week-olds, corresponding to the distribution of elevations in T_2. Despite CBF differences, extensive cell death occurred ipsilaterally in both age groups. The CBF responses to hypoxia–ischemia and reperfusion differ depending on postnatal age, with hyperemia occurring in juvenile but not neonatal rats. The results suggest a greater CBF responsiveness and differential relationship between post-ischemic vascular perfusion and tissue injury in older compared with immature animals.     

Dose and scanning delay using USPIO for central nervous system macrophage imaging

Rationale and objectives: In experimental allergic encephalomyelitis (EAE), central nervous system (CNS) macrophage imaging is achievable by MRI using AMI-227 an ultra-small particle iron oxide contrast agent at a dose of 300 μmol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 μmol/kg Fe.Methods: Two groups of EAE rats were tested with AMI-227 using 45 and 300 μmol/kg Fe respectively. Following i.v. injection of AMI-227, they were scanned after a delay of 4–6 and 20–24 h.Results: With a high dose of AMI-227, all animals showed low signal intensity related to iron-loaded macrophages in the CNS. At low dose no abnormalities were found in the CNS. Furthermore, a delay of 4–6 h failed to demonstrate abnormalities even at high dose.Conclusions: Dose, scanning delay after administration and blood half-life are major parameters for T2^* CNS macrophage imaging.     

Short-echo-time magnetic resonance phase-shift velocity mapping for assessment of heart valve and great vessel stenoses: three years' experience

Shortening the echo times of magnetic resonance (MR) sequences used for phase-shift velocity mapping to 3.6 ms has extended use of the technique to measurement of velocities in turbulent, poststenotic jet flows. We used a 0.5-T MR machine and field even-echo rephasing (FEER) sequences with 3.6 ms echo times for jet velocity mapping.In vitro trials used continuous flow through a phantom with a 6-mm stenosis. Fifteen patients with mitral and/or aortic valve stenosis and 20 patients with repaired aortic coarctation were studied prospectively, with Doppler ultrasonic measurement of peak jet velocity performed independently on the same day. The clinical contribution of MR jet velocity mapping, used during a 3-year period in 306 patients with congenital and acquired disease of heart valves, great vessels, and conduits, was assessed retrospectively. The 3.6-ms sequence allowed accurate measurement of jet velocities up to 6 m s^–1 in vitro (r=0.996). Prospective studies in patients showed good agreement between MR and Doppler measurements of peak velocity:n=38; range, 1.2–6.1 m s^–1; mean, 2.7 m s^–1; mean of differences (Doppler-MR), 0.22 ms^–1; standard deviation of differences, ±0.38 m s^–1 (±14%). MR jet velocity mapping proved particularly valuable for assessment and localization of stenoses at sites where ultrasonic access was limited. The technique represents a diagnostic advance which can obviate the need for catheterization in selected cases.     

Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA

This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution²⁰¹Thallium (²⁰¹Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between²⁰¹Tl uptake and MRI signal intensity, i.e. infarcted tissue (low²⁰¹Tl uptake) had increased MR signal intensity. Segments were separated into normal (²⁰¹Tl uptake >90%) and infarcted (<60%). Infarcted MRI segments had greater signal intensity than normal segments (179±50 vs. 102±14%;P<0.0001). WTI in normal segments increased by 18±8.5% (P<0.0001) from baseline to 10 μg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8±7.2% (P=0.17). Thus regions of myocardium that were infarcted as defined by reduced²⁰¹Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.     

Magnetic resonance imaging of coronary arteries and coronary stenosis

Coronary artery imaging is an important investigation for the management of coronary artery disease. Alternative noninvasive imaging would be useful, but the small caliber and tortuosity of the coronary vessels and cardiac and respiratory motion create formidable imaging problems. We first studied 21 normal subjects and 5 with coronary artery disease established by X-ray contrast angiography, of whom 2 had undergone bypass grafting. Of these, 22 were imaged successfully. Identification of the artery was possible for the left main stem, left anterior descending, right coronary, and left circumflex arteries respectively in 95%, 91%, 95%, and 76%. The arterial diameter at the origin could be measured in 77%, 77%, 81%, and 63%. The mean ±SD arterial diameter in each case (4.8±0.8, 3.7±0.5, 3.9±0.9, and 2.9±0.6 mm) was not significantly different from reference values (allp=ns). The mean length of artery visualized was 10.4±5.2,46.7±22.8,53.7±27.9, and 26.3±17.5 mm. In 12 normal males, the total coronary area was 30.9±9.2 mm² and the ratio compared with body surface area was 16.4±4.4 mm² m^–2 (bothp=ns compared with reference values). In seven patients, with X-ray contrast coronary angiography, the proximal arterial diameter measured by magnetic resonance was 3.9±1.1 mm, and by X-ray contrast angiography 3.7±1.0 mm (p=ns). We then studied 17 patients with angina. Imaging of just the relevant artery was performed and analysis was blinded to the X-ray angiography results. Stenosis was identified on the magnetic resonance (MR) images by localized reduction in vessel signal intensity. Stenosis location by MR was assessed by measurement of its distance from a reference vessel, with correlation to the X-ray findings. X-ray coronary angiography showed 23 stenoses of which 15 (65%) were correctly located by blind assessment of the MR images. Of the eight remaining stenoses, a further 5 (63%) were correctly located on the MR images after retrospective comparison (overall sensitivity 87%). There were three lesions thought to represent stenosis by MR, which on review of the X-ray angiogram proved to be a minor stenosis <50% (two cases) or a tortuous vessel (one case). Greater signal loss was seen in the more severe stenoses. The stenosis length by MRI was greater than by X-ray (8.4 versus 5.1 mm,p<0.001). The overestimation of stenosis length may be due to turbulence.     

Effect of new manganese contrast agent on tissue intensities in human volunteers: comparison of 0.23, 0.6 and 1.5 T MRI,a part of a phase I trial

To evaluate the effect of a new oral manganese contrast agent (CMC-001) on magnetic resonance imaging (MRI) intensities at different magnetic field strengths. Twelve healthy volunteers underwent abdominal MRI 1 week before and within 2.5–4.5 h after CMC-001 (MnCl₂ and absorption promoters dissolved in water) intake at three different MR scanners of 0.23, 0.6 and 1.5 T. Image contrast and intensity enhancement of liver and pancreas were analysed relatively to muscle and fat intensities. Manganese blood levels were followed for 24 h. Whole-blood manganese concentration levels stayed within the normal range. The liver intensities on T2w images decreased about 10% for the 1/2 contrast dose and about 20% for the full contrast dose independent of the field strength. The liver intensities on T1w images increased more than 30% for 1/2 contrast dose and over 40% for full contrast dose. The maximum T1 enhancement was achieved at the highest field. Pancreas intensities were not affected. Contrast between liver, muscle and fat intensities increased with magnetic field, as well as standard errors of the volunteer-averaged intensities. Oral intake of CMC-001 influences liver intensities and does not affect pancreas intensities at different magnetic field strengths.