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     

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.     

Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model

The aim of this study was to validate an experimental model designed to distinguish four categories of contrast agents, non specific agents (NDA, Gd-DOTA) characterized by rapid and total extravasation; low diffusion agents (LDA, P760) characterized by delayed extravasation; and rapid (P792) and slow clearance (P717) blood pool agents (BPA) characterized by limited extravasation. Plasma and peritoneal gadolinium concentrations were simultaneously measured after intravenous injection of various contrast agents in mice. Products of each category were compared in this model. The plasma pharmacokinetic profiles were similar for Gd-DOTA and P760 (t1/2 = 13.3 and 13.8 min. respectively), whereas the half-lives were 22 and 1212 min for P792 and P717, respectively. The plasma clearance was inversely related to the size of the contrast agent. The intraperitoneal diffusion patterns of the various products were related to the molecular volume; C_max per dose decreased progressively (78.7, 51.2, 44.2, 33.5 1/1) and t_max increased (7, 15, 40, and 120 min) for Gd-DOTA, P760, P792 and P717, respectively. Nevertheless, the same quantities of Gd-DOTA and P760 (AUC ratio of 78.4 and 76.8, respectively) diffused into the peritoneum, whereas only 44.5% of P792 and 21.5% of P717 extravasated. The data obtained in this peritoneal permeability model with the various categories of contrast agents provide an estimation of the quantities of contrast agents diffusing into a permeable interstitium and may be used to predict the corresponding signal intensity, which can be measured locally.     

Simultaneous dynamic T1 and T2* measurement for AIF assessment combined with DCE MRI in a mouse tumor model

A double-delay SR-MGE-SNAP sequence allowing simultaneous T1 and T2* measurement was developed for integrating arterial input function (AIF) measurement into DCE MRI. Implemented on a 4.7-T animal MR system, this technique was applied to mice with colorectal tumor xenografts. AIF, measured in the mouse heart, was modeled by a bi-exponential function, whereas tumor K(trans) and v(e) parameter maps were obtained from analysis with a two- compartment model using an individually measured AIF. AIF analysis of T2*-corrected data yielded A1 = 9.2 +/- 4.3 kg/l, A(2) = 4.2 +/- 0.8 kg/l, m1 = 2.3 +/- 1.1 min(-1), and m2 = 0.05 +/- 0.02 min(-1). The mean initial plasma concentration C ( p )(t = 0) = 8.0 +/- 2.7 mM was compatible with estimated 8.6 mM. Without T2*-correction distribution phase parameters A1, m1, and C(p)(t = 0) were underestimated. In tumors, neglect of T2* effects yielded mean K(trans) values which were reduced by 14% (P < 0.05), whereas v(e) showed only a slight non-significant reduction. Simultaneous measurement of DeltaR1 and DeltaR2* studied in highly and poorly vascularized and (pre-)necrotic tumor regions revealed complementary behavior of both parameters with respect to vascular properties. In conclusion, the presented measurement technique is a promising tool for dynamic MRI applications studied in animal models at high field strengths and/or with CA of high relaxivities, as it combines classical DCE MRI integrating AIF assessment with dynamic T2* measurement.     

Technical note—Approach to myocardial perfusion with echo planar imaging

Purpose: To evaluate the feasibility of MRI-based myocardial first-pass contrast perfusion imaging with a multi-shot echo planar imaging (EPI) technique. Subjects and methods: A non-sequential (ECG-triggered) gradient echo two-shot EPI acquisition strategy capable of covering the entire heart in contiguous 10-mm sections every two cardiac cycles with an in-plane resolution of 1.56 × 1.56 mm was implemented on a 1.5-T Signa Advantage Scanner equipped with prototype hardware for non-resonant EPI in the transverse plane. The heart of a single volunteer was studied prior to and following the intravenous bolus application of a paramagnetic contrast agent (Gd-DOTA, 0.2 mmol/kg). Results: Twelve contiguous transaxial 10-mm EPI images were obtained every two RR intervals for a total of 40 s. The myocardial contrast perfusion study was technically adequate. Contrast caused a signal loss of 87% in the right and 67% in the left ventricle and 59% in the myocardium. Conclusion: First-pass myocardial perfusion imaging with a gradient echo, two-shot echo planar imaging strategy is feasible.This work has been supported in part by SNF grant 32-2549.88 and KWF grant 2194.1.     

P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results

An original MRI contrast agent, called P792, is described. P792 is a gadolinium macrocyclic compound based on a Gd-DOTA structure substituted by hydrophilic arms. The chemical structure of P792 has been optimized in order to provide (1) a high r₁ relaxivity in the clinical field for MRI: 29 mM⁻¹ x s⁻¹ at 60 MHz. (2) a high biocompatibility profile and (3) a high molecular volume: the apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA. As a result of this high molecular volume, P792 presents an unusual pharmacokinetic profile, as it is a Rapid Clearance Blood Pool Agent (RCBPA) characterized by limited diffusion across the normal endothelium. The original pharmacokinetic properties of this RCBPA are expected to be well suited to MR coronary angiography, angiography, perfusion imaging (stress and rest), and permeability imaging (detection of ischemia and tumor grading). Further experimental imaging studies are ongoing to define the clinical value of this compound.     

Water proton T 1 measurements in brain tissue at 7, 3, and 1.5T using IR-EPI, IR-TSE, and MPRAGE: results and optimization

Method This paper presents methods of measuring the longitudinal relaxation time using inversion recovery turbo spin echo (IR-TSE) and magnetization-prepared rapid gradient echo (MPRAGE) sequences, comparing and optimizing these sequences, reporting T ₁ values for water protons measured from brain tissue at 1.5, 3, and 7T. T ₁ was measured in cortical grey matter and white matter using the IR-TSE, MPRAGE, and inversion recovery echo planar imaging (IR-EPI) pulse sequences. Results In four subjects the T ₁ of white and grey matter were found to be 646±32 and 1,197±134ms at 1.5T, 838±50 and 1,607±112ms at 3T, and 1,126±97, and 1,939±149ms at 7T with the MPRAGE sequence. The T ₁ of the putamen was found to be 1,084±63ms at 1.5T, 1,332±68ms at 3T, and 1,644±167ms at 7T. The T ₁ of the caudate head was found to be 1,109± 66ms at 1.5T, 1,395±49ms at 3T, and 1,684±76ms at 7T. Discussion There was a trend for the IR-TSE sequence to underestimate T ₁ in vivo. The sequence parameters for the IR-TSE and MPRAGE sequences were also optimized in terms of the signal-to-noise ratio (SNR) in the fitted T ₁. The optimal sequence for IR-TSE in terms of SNR in the fitted T ₁ was found to have five readouts at TIs of 120, 260, 563, 1,221, 2,647, 5,736ms and TR of 7 s. The optimal pulse sequence for MPRAGE with readout flip angle = 8° was found to have five readouts at TIs of 160, 398, 988, 2,455, and 6,102ms and a TR of 9 s. Further optimization including the readout flip angle suggests that the flip angle should be increased, beyond levels that are acceptable in terms of power deposition and point-spread function.     

On the correlation between T<Subscript>2</Subscript> and tissue diffusion coefficients in exercised muscle: quantitative measurements at 3T within the tibialis anterior

PURPOSE: To assess the transverse relaxation time T(2) and diffusion coefficient D before and following exercise in the tibialis anterior muscle and determine whether T(2) and D values were correlated. METHODS: Measurements of T(2) and D were performed at 3 T within axial slices through the calf muscles of six healthy volunteers at 95 s intervals before and for 10-12 min after a dorsiflexion exercise to exhaustion. RESULTS: The mean +/- standard deviation (SD) of T(2) and D before exercise were 32 +/- 1.55 ms and 1.52 +/- 0.15 mum(2)/ms, and after exercise were 43 +/- 2.5 ms and 1.72 +/- 0.13 mum(2)/ms, respectively. The mean +/- SD inter-individual recovery times of the % change in T(2) and D after exercise were 7.9 +/- 4.2 and 10.9 +/- 7.0 min, respectively. The T(2) and D values showed a significant correlation throughout the experiments (r (2) = 0.45). CONCLUSIONS: The increase in T(2) of skeletal muscle after exercise is correlated with the increase of the diffusion coefficient D and the recovery times appear similar, indicating that any model used to explain T(2) increases with exercise must also account for increased diffusion coefficients.     

Standardized MR protocol for the evaluation of MRA sequences and/or contrast agents effects in high-degree arterial stenosis analysis

Purpose To investigate the relative role of high resolution (spatial or temporal) magnetic resonance angiography (MRA) sequence and of contrast agent properties in the evaluation of high-degree arterial stenosis. Methods We qualitatively and quantitatively studied both 50 and 95% (300 μm diameter) stenosis of a 6 mm arterial phantom with two contrast agents (CA), Gd-DOTA (r₁ =2.9 mM⁻¹ s⁻¹) versus P760 (r₁ =25 mM⁻¹ s⁻¹) at several CA concentrations, including arterial peak concentration after injection of either a single or double dose of CA, using either a high temporal (booster) or high spatial (HR) resolution 3D MRA sequences. Experimental data were then compared to theoretical data. Results With the 3D HR sequence, both visual and quantitative analysis were significantly better compared to the 3D booster sequence, at each phantom diameter. Quantitative analysis was significantly improved by injection of a double versus a single dose of each CA (Gd-DOTA or P760), primarily in high degree stenosis. Conclusion Combined MRA spatial resolution and high CA efficiency are mandatory to correctly evaluate high degree stenosis.     

Signal losses in diffusion preparation: Comparison between spin-echo, stimulated echo and SEASON

Diffusion-weighted magnetic resonance imaging and spectroscopy commonly apply a spin-echo or stimulated echo preparation including sensitizing field gradients. The article reports on a systematic numerical approach to an optimum diffusion preparation considering undesired signal losses caused by relaxation. A large range of possible applications on whole-body units and animal scanners is covered. Instructions for an optimized type and timing of the diffusion preparation are provided for the readership, based on the desired diffusion weighting (b-value), the available maximum field gradient amplitudes, the RF pulse durations and gradient ramp times, and the relaxation characteristics of the specimen (or tissue) of interest. In addition, a new type of diffusion preparation named SEASON (simultaneous Spin-Echo And Stimulated echO preparatioN) is introduced and compared with spin-echo and stimulated echo diffusion preparation. It is demonstrated that spin-echo preparation is superior to stimulated echo preparation in all cases with T₂ ≈ T₁ and in all cases with relatively low diffusion weighting resulting in short duration of diffusion sensitizing gradients δ « T₂. For tissues with T₂ « T₁ (as musculature or red bone marrow) stimulated echo preparation becomes superior to spin-echo preparation for high ratios b/A² (b-value indicates diffusion weighting,A is the maximum gradient amplitude). The new SEASON technique allows a higher yield in signal intensity compared to spin-echo or stimulated echo preparations in clinically relevant cases. © 1998 Elsevier Science B.V. All rights reserved.     

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.     

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.     

Absolute cerebral blood flow measured by dynamic susceptibility contrast MRI: a direct comparison with Xe-133 SPECT

Absolute regional cerebral blood flow (CBF) was measured in ten healthy volunteers, using both dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI) and Xe-133 SPECT within 4 h. After i.v. injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.), the bolus was monitored with a Simultaneous Dual FLASH pulse sequence (1.5 s/image), providing one slice through brain tissue and a second slice through the carotid artery. Concentration C(t) is proportional to -(1/TE) ln[S(t)/S(0)] was related to CBF as C(t) = CBF [AIF(t) x R(t)], where AIF is the arterial input function and R(t) is the residue function. A singular-value-decomposition-based deconvolution technique was used for retrieval of R(t). Absolute CBF was given by Zierler's area-to-height relation and the central volume principle. For elimination of large vessels (ELV), all MRI-based CBF values exceeding 2.5 times the mean CBF value of the slice were excluded. A correction for partial-volume effects (CPVE) in the artery used for AIF monitoring was based on registration of signal in a phantom with tubes of various diameters (1.5-6.5 mm), providing an individual concentration correction factor applied to AIF data registered in vivo. In the Xe-133 SPECT investigation, 3,000-4,000 MBq of Xe-133 was administered intravenously, and CBF was calculated using the Kanno Lassen algorithm. When ELV and CPVE were applied, DSC-MRI showed average CBF values from the entire slice of 43 +/- 10 ml/(min 100 g) (small-artery AIF) and 48 +/- 17 ml/(min 100 g) (carotid-artery AIF) (mean +/- S.D., n = 10). The corresponding Xe-133-SPECT-based CBF was 33 +/- 6 ml/(min 100 g) (n = 10). The relationships of CBF(MRI) versus CBF(SPECT) showed good linear correlation (r = 0.74-0.83).     

T2 relaxation time study of iron overload in b-thalassemia

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18–44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml^-1). Results were compared with nine controls, with a mean age of 25 (18–43) years. Heart T2 relaxation time in controls (44.3 ± 3.5 ms) was higher than in group A (29.9 ± 5.7 ms,P< 0.001) and group B (33.4 ± 6.8 ms,P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 ± 0.27) was lower than in group B (0.82 ± 0.33,P < 0.001) and the controls (1.15 ± 0.20,P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels(r = - 0.52, P<0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time. © 1998 Elsevier Science B.V. All rights reserved.     

Creatine loading and resting skeletal muscle phosphocreatine flux: a saturation-transfer NMR study

³¹P saturation-transfer nuclear magnetic resonance spectroscopy was used to study skeletal muscle phosphocreatine (PCr) flux in healthy male volunteers. Data analysis included consideration of effects from incomplete saturation and radiofrequency spillover. Spectra were recorded from the resting gastrocnemius muscle before and after 6 days of creatine monohydrate (Cr·H₂O) intake (20 g/day). Parallel to an improved muscle performance during maximal intermittent exercise following Cr·H₂O supplementation, the concentration of PCr increased(P = 0.01) by 23% (34.9 ± 2.8 mmol/ 1 vs. 28.6 + 2.7 mmol/1), whereas other metabolites were unaffected (inorganic phosphate: 4.3± 1.4 mmol/1, free intracellular Mg²⁺: 1.1 ±0.7 mmol 1, cytosolic pH: 7.04 ± 0.02). Forward and reverse fluxes through the creatine kinase (CK) reaction did not change significantly from their baseline levels (v_for: 11.8 ± 5.4 mmol/1 per second vs. 15.3 ± 6.8 mmol 1 per second. (v_rev: 9.5 ± 3.4 mmol/1 per second vs. 10.9 ± 3.7 mmol/ 1 per second). The rate of PCr resynthesis in resting muscle is not limited by the CK reaction, which is near equilibrium. Consequently, the post-load increase in total creatine has no effect on the unidirectional CK reaction rates.     

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.     

Use of spin-traps during warm ischemia-reperfusion in rat liver: comparative effect on energetic metabolism studied using31P nuclear magnetic resonance

Detection of free radicals by electron spin resonance (ESR) proves the involvement of reactive oxygen species (ROS) in reperfused organ injuries. Spin-traps are known to ameliorate hemodynamic parameters in an isolated postischemic heart. The effects of 5 mmol/L DMPO (5,5-dimethyl-1-pyrroline-N-oxide) or DEPMPO (5-(diethylphosphoryl)-5-methyl-1-pyrrolineN-oxide) on intracellular pH (pH_in) and ATP level were evaluated by³¹P nuclear magnetic resonance on isolated rat liver submitted to 1 hour of warm ischemia and reperfusion. At the end of the reperfusion period, during which pH_in recovered to its initial value (7.16±0.03) in all groups, the ATP recovery level (expressed in percentage of initial value) was similar in controls and DEPMPO (60%±5%,n=6 and 54%±4%,n=6, respectively), but only 37%±1% in DMPO-treated livers (n=6) (p<0.05 versus controls andp<0.05 versus DEPMPO). Oxidative phosphorylation was not affected by an addition of nitrones on isolated mitochondria extracted from livers not submitted to ischemia-reperfusion. In contrast, mitochondria extracted at the end of the ischemia-reperfusion showed an impairment in the phosphorylation parameters, particularly in the presence of DMPO. Mass spectrum of ischemic liver perchloric acid extracts evidenced probable catabolites in treated groups. The differences in the effect of the two nitrones on energetic metabolism may be explained by the production of deleterious catabolites by DMPO as compared to DEPMPO. Even though a specific radical scavenging effect could be operative in the liver, our results indicate that catabolic effects were predominant. The absence of deleterious effects of DEPMPO in contrast to DMPO on the liver energetic metabolism was evidenced, allowing the use of DEPMPO for ESR detection.     

Effect of Concentration of SH U 555A Labeled Human Melanoma Cells on MR Spin Echo and Gradient Echo Signal Decay at 0.2, 1.5, and 3T

In the current study the effect of increasing concentrations of superparamagnetic iron oxide labeled cells on the MRI signal decay at magnetic field strengths of 0.2, 1.5, and 3 T was evaluated. The spin echo and gradient echo cellular transverse relaxivity was systematically studied for various concentrations (N = 1, 5, 10, 20, 40, and 80 cells/μl_gel) of homogeneously suspended SH U 555A labeled SK-Mel28 human melanoma cells. For all field strengths investigated a linear relationship between cellular transverse relaxation enhancement and cell concentration was found. In the spin echo case, the cellular relaxivities [i.e., d(ΔR ₂)/dN] were determined to 0.12 s⁻¹ (cell/μl)⁻¹ at 0.2 T, 0.16 s⁻¹ (cell/μl)⁻¹ at 1.5 T, and 0.17 s⁻¹ (cell/μl) at 3 T. In the gradient echo case, the calculated cellular relaxivities (i.e., d(ΔR ₂ ^* )/dN) were 0.51 s⁻¹ (cell/μl)⁻¹ at 0.2 T, 0.69 s⁻¹ (cell/μl)⁻¹ at 1.5 T, and 0.71 s⁻¹ (cell/μl)⁻¹ at 3 T. The proposed preparation technique has proven to be a simple and reliable approach to quantify effects of magnetically labeled cells in vitro. On the basis of this quantification well suited tissue specific models can be derived.     

Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Object: Demonstrating the feasibility of magnetic resonance imaging (MRI) at 1.5 T of ultrasmall particle iron oxide (USPIO)-antibody bound to tumor cells in vitro and in a murine xenotransplant model. Methods: Human D430B cells or Raji Burkitt lymphoma cells were incubated in vitro with different amounts of commercially available USPIO-anti-CD20 antibodies and cell pellets were stratified in a test tube. For in vivo studies, D430B cells and Raji lymphoma cells were inoculated subcutaneously in immunodeficient mice. MRI at 1.5 T was performed with T1-weighted three-dimensional fast field echo sequences (17/4.6/13°) and T2-weighted three-dimensional fast-field echo sequences (50/12/7°). For in vivo studies MRI was performed before and 24 h after USPIO-anti-CD20 administration. Results: USPIO-anti-CD20-treated D430B cells, showed a dose-dependent decrease in signal intensity (SI) on T2*-weighted images and SI enhancement on T1-weighted images in vitro. Raji cells showed lower SI changes, in accordance to the fivefold lower expression of CD20 on Raji with respect to D430B cells. In vivo 24 h after USPIO-anti-CD20 administration, both tumors showed an inhomogeneous decrease of SI on T2*-weighted images and SI enhancement on T1-weighted images. Conclusions: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.     

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.