Characterization and detection of experimental rat gliomas using magnetic resonance imaging.

Two different experimental rat brain tumours (F98 glioma and 9L glioma) were characterized using T1 and T2, apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Even though both tumours appeared homogenous at the early stage of growth, significant differences were measured for all parametric images between tumours and normal brain tissue. Irrespective of the sequence used, tumour lesion/normal parenchyma contrast for the non-infiltrative 9L was twice that of the infiltrative F98 glioma. The use of spin preparation via an inversion pulse in a fast spin echo sequence increases contrast by a factor of 20-30.

Clinical experience with 99mTc-MIBI scintimammography in patients with breast microcalcifications.

The aim of this study was to evaluate whether 99mTc-MIBI scintimammography can improve the diagnostic value of mammography for the differentiation of benign and malignant breast microcalcifications. In 41 women presenting 45 clusters of microcalcifications, a 99mTc-MIBI scintimammography was performed before open biopsy. There were 24 malignant lesions (53%). The sensitivity (SE) and specificity (SP) of 99mTc-MIBI scintimammography were 58.3% and 81%, and the positive and negative predictive values (PPV, NPV) were 78% and 63%, respectively. SE and PPV increased for lesions over 10 mm and for the younger patients (under 50 years). No correlation was found between true positive uptake and breast cancer invasiveness: 69% (9/13) for invasive lesions and 45% (5/11) for noninvasive lesions (P = 0.48). 99mTc-MIBI scintimammography was more often positive in high grade than in low- or intermediate-grade ductal carcinoma in situ (P = 0.03). The results were analysed according to the morphologic aspect of the microcalcifications. 99mTc-MIBI scintimammography could not be used for routine evaluation of all the microcalcifications detected by mammography.

New thermoluminescent dosimeters (TLD): optimization and characterization of TLD threads sterilizable by autoclave.

To improve the performance of mono-extruded TLD threads as a dosimetric thermoluminescent tool (French Patent 9903729), a new process was developed by co-extrusion methodology leading to threads of 600 microm diameter with a 50 microm homogeneous polypropylene sheath. In this optimization work, study of parameters such as LiF:Mg,Cu,P powder granulometry, load rate and proportion of components led to an increased sensitivity of around 40%. Moreover, the co-extrusion technique allowed the threads to be sterilized by humid steam (134 degrees C/18 min) without significant variation of the linearity response between 0 and 30 Gy after gamma irradiation (60Co).

Therapeutic efficacy of 5-fluorouracil-loaded microspheres on rat glioma: a magnetic resonance imaging study.

The aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5-fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast-growing C6-glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13 +/- 2 microl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow-up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p < 0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection.

In vivo quantitative microimaging of rat spinal cord at 7T.

In vivo T(2), ADC, and MT properties of the GM and WM of the rat spinal cord were measured at 7T in the cervical region. The GM T(2), T(2GM) = 43.2 +/- 1.0 msec is significantly reduced compared to the WM T(2), T(2WM) = 57.0 +/- 1.6 msec. Diffusion is anisotropic for both GM and WM, with a larger ADC value along the cord axis (ADC(GM//) = 1.05 +/- 0.09 10(-9) m(2)sec(-1) and ADC(WM//) = 1.85 +/- 0.18 10(-9) m(2)sec(-1)) than perpendicular to this plane (ADC(GM)( perpendicular) approximately 0.50 * 10(-9) m(2)sec(-1) and ADC(WM)( perpendicular) approximately 0.18 * 10(-9) m(2)sec(-1)). The MT properties do not significantly differ between the WM and the GM, but allow one to distinguish the thin CSF layer from the WM. DWI with the sensitizing gradient perpendicular to the cord axis leads to the best contrast between GM and WM in the cervical region.

High-field quantitative transverse relaxation time, magnetization transfer and apparent water diffusion in experimental rat brain tumour.

The potential of quantitative parameter images of transverse relaxation time T(2), apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) to characterize experimental brain tumours was studied. Necrosis or haemorrhage can be detected using either MTR, ADC or T(2) (necrosis-MTR reduced by 35%, ADC and T(2) increased respectively by 170% and 100% compared with normal brain tissue; haemorrhage-MTR increased by 60%, ADC and T(2) decreased by 40% and 20%, respectively). Normal brain tissue can only be distinguished from tumour on T(2) and MTR parameter images. However, for small tumours (10 microl), the best contrast is observed with MTR, ca. 30%, whereas for T(2) the contrast is ca. 10%.

MRI study of transient cerebral ischemia in the gerbil: interest of T2 mapping.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the diagnostic use of MRI and, more precisely, the use of quantitative T2 imaging at 7 T for the early detection of neuronal cerebral alterations after transient ischemia in the gerbil. METHODS: One hundred forty-seven Mongolian gerbils were separated into four groups for which a bicarotid artery occlusion lasted for 4, 6, 8, or 10 minutes, respectively. The animals were scanned before carotid artery occlusion and at 3, 6, 10, 24, and 48 hours and 5 days after the ischemic incident. MR images were acquired on a Bruker Avance DRX300 mini-imaging system. RESULTS: Our results show that T2 mapping is able to localize brain damage induced by transient ischemia and to detect early perturbations in water content (as early as 6 hours after ischemia). CONCLUSIONS: T2 measurements in the striata are correlated with the severity of the ischemic incident, since the changes observed on the T2 images are directly proportional to the duration of occlusion.

Error assessment due to coronary stents in flow-encoded phase contrast MR angiography: a phantom study.

Phase contrast magnetic resonance imaging (PC MRI) is a promising method for assessing coronary flow. MR angiography images in the presence of coronary stents display artifacts because of the metal present in the stent. Using a flow phantom, the goal of this in vitro study was to assess quantitatively the effects of flow dephasing caused by magnetic susceptibility in velocity measurements in a region where the artifact is not visualized in a magnitude image. The results showed that for high velocities, significant errors in measurements exist around the stent, outside the susceptibility artifact visible on a magnitude image. J. Magn. Reson. Imaging 1999;10:899-902.

[MRI quantification of regional variations of left ventricular parietal stress in normal subjects]. / Quantification par imagerie par résonance magnétique des variations régionales de la contrainte pariétale du ventricule gauche chez le sujet normal.

The object of this study was to analyse regional variations in end systolic left ventricular wall stress in normal subjects using three-dimensional magnetic resonance imaging (MRI) with excellent spatial resolution. Eight to 12 contiguous short axis sections of the left ventricle were acquired from the apex to the base in apnoea with a rapid echo-gradient sequence in 15 healthy volunteers. The end systolic wall stress was calculated by three methods: Grossman's formula (CR) using the wall thickness and radius of curvature, Janz's formula (CS) using the surfaces, and a three-dimensional approach (C3D) providing a precise calculation of the radius of curvature. The values of wall stress obtained by CS and CR were lower (p < 0.001) at the apex (3.2 and 3.3 10(3) newton/m2 respectively) than at the base (6.9 and 7.1 10(3) newton/m2). There was no difference between the base and apex with the C3D method (8.0 and 9.0 10(3) newton/m2 respectively, NS). The same results were observed at the inferior, lateral, anterior and septal segments with an increase at the base using the CS and CR formulae, the C3D remaining homogeneous in the left ventricle except for the interventricular septum. The lateral wall stress was significantly lower with respect to the interventricular septum in all sections from the apex to the base, irrespective of the method of calculation used. The differences in regional wall stress from the base to the apex reported in healthy subjects seem to be related to an underestimation of left ventricular wall thickness and an underestimation of the radius of curvature rather than to a physiological phenomenon.

Introduction of the closed cranial window technique in gerbils and verification by observation of the effects of specific drugs.

The exact mechanisms of cerebral arterial hypoxia are not perfectly defined. Our purpose is to adapt and validate, with drugs well known in rats and rabbits, a closed cranial window technique in gerbils. The method was used with seventeen gerbils to measure diameter changes of the pial arterioles under normoxia (after the topical application of agonists and antagonists of ATP-sensitive and Ca2+-dependent potassium channels), as well as under hypoxia. In normoxia, aprikalim (10(-6) M), a direct activator of ATP-sensitive potassium channels, increases the diameter of pial arterioles by 10+/-2% (N = 17). This effect is inhibited by glibenclamide (10(-6) M), but not affected by iberiotoxin (10(-6) M), a specific inhibitor of Ca2+-dependent potassium channels. The adenosine-induced dilation by 19+/-5% (N = 17) is reduced by 59+/-16% with iberiotoxin, by 33+/-23% with glibenclamide and inhibited by theophylline (10(-5) M). In hypoxia (15% O2), pial arteriole diameters are increased by 24+/-5% (N = 17) and partially decreased by the application of glibenclamide and iberiotoxin to 59+/-11% and 54+/-5%, respectively. These data are similar to those obtained in other species and validate the closed cranial window technique on gerbils. They indicate that, as for rats and rabbits, both ATP-sensitive and Ca2+-dependent potassium channels are present in gerbil pial vessels and play a role in hypoxia.

Three-dimensional coronary artery MR imaging using prospective real-time respiratory navigator and linear phase shift processing: comparison with conventional coronary angiography.

Respiratory gating with navigator echo is a recent technique to detect diaphragm position in 3D magnetic resonance (MR) coronary angiography. The purpose of our study was to image proximal coronary arteries and to detect significant stenoses in patients with coronary artery diseases and to compare with contrast enhanced angiography results. Twenty patients with coronary artery diseases who were referred for conventional angiography underwent magnetic resonance angiography (MRA). Three-dimensional gradient echo volumes were acquired using cardiac and respiratory gating and fat suppression. Using reformatted oblique planes and maximum intensity projection technique, visualization coronary segments and detection of significant coronary stenoses were made. Eighty-three coronary segments were analyzed. The sensitivity and specificity were 65% and 93%, respectively. The corresponding positive and negative predictive values were 69% and 91%. This study shows the ability to image correctly coronary arteries and to identify proximal stenoses, but image quality need to be improved for an efficiency detection of coronary artery stenoses in clinical practice.

Regional assessment of wall curvature and wall stress in left ventricle with magnetic resonance imaging.

Left ventricular functional abnormalities are associated with regional increases of wall stress and modifications of wall curvature. This study describes the integration of the short-axis and long-axis wall curvatures for determining peak systolic wall stress. Quantification was realized with cine magnetic resonance imaging (MRI) from the location of the endocardial and epicardial borders of the left ventricle on pairs of consecutive short-axis sections. Fifteen normal volunteers were subjected to cine MRI, and different methods of calculating peak systolic wall stress were compared. A short-axis analysis showed a 55 +/- 13% increase of the circumferential mean of the peak systolic wall stress between apical and basal sections. Regarding the curvature, no significant increase of wall stress was observed except on the septal wall (31 +/- 18%). Short-axis studies proved to be insufficient for determining the regional variations of left ventricular wall stress and for providing normal reference values for the location of abnormal regions in patients.

Noninvasive assessment of the infarct-related coronary artery blood flow velocity using phase-contrast magnetic resonance imaging after coronary angioplasty.

This study assesses infarct-related coronary artery blood flow velocity using phase-contrast magnetic resonance imaging (MRI) in patients with reperfused acute myocardial infarction (AMI) and compares these results with flow measurements obtained nonsimultaneously by intracoronary Doppler ultrasound. MRI examination was performed in 17 patients with AMI within 1 to 4 days (mean 2.5 days) after direct or rescue coronary angioplasty using a 0.014-in Doppler guidewire. MRI was performed on a 1.5-T clinical imager. The fast gradient echo segmented k-space phase-contrast pulse sequence was employed during breath-hold. The MRI and Doppler parameters of average peak velocity and maximum peak velocity were measured. Mean phase contrast MRI average peak velocity was 13.3+/-10.7 cm/s, and mean phase-contrast MRI maximum peak velocity was 27+/-16.6 cm/s. Mean Doppler average peak velocity was 17.1+/-5.1 cm/s, and mean Doppler maximum peak velocity was 35.5+/-10.1 cm/s. At the same anatomic levels, phase-contrast MRI average peak velocity correlated significantly to Doppler average peak velocity (r = 0.52; p<0.006) and Doppler maximum peak velocity (r = 0.42; p<0.03). Phase-contrast MRI velocity measurements were correlated with the same heterogeneity of Thrombolysis In Myocardial Infarction 3 flow velocity observed during Doppler examination. Thus, by comparing phase-contrast MRI with invasive intracoronary Doppler flow measurements, the measured MRI values showed significant correlation with Doppler data. Phase-contrast MRI has the potential to noninvasively quantify coronary flow velocity and to evaluate quality of reperfusion in patients with AMI after reperfused therapy.

Improving the detection of low concentration metabolites in magnetic resonance spectroscopy by digital filtering.

In vivo detection and quantitation of metabolites is often limited by their low concentration. As far as magnetic resonance spectroscopy (MRS) is concerned, detection and quantitation can be significantly improved by reduction of the observed spectral width (SW). The reduction is limited to the spreading of resonances in the bandwidth unless high performance digital filters are used. Indeed, these filters avoid the folding of unwanted resonances such as water peak into the main frequency spectrum and therefore allow reduction of the spectral width to its optimal value. These filters are now available on most MRS systems but their use is not common even if, as we show in the particular case of proton MRS, a significant increase in signal-to-noise ratio (two-fold factor for SW reduction from 5000 Hz to 1351 Hz) can be achieved. This signal-to-noise improvement allows better quantitation accuracy.

Thallium-201 right lung/heart ratio during exercise in patients with coronary artery disease: relation to thallium-201 myocardial single-photon emission tomography, rest and exercise left ventricular function and coronary angiography.

The aim of this study was to correlate lung thallium-201 uptake on exercise with 201Tl single-photon emission tomography (SPET) myocardial perfusion imaging, rest and exercise equilibrium radionuclide angiographic and coronary angiographic findings in patients with coronary artery disease (CAD) using a simple, reproducible lung/heart (L/H) ratio that would be easy to use in clinical practice. L/H ratio was defined on the anterior planar image obtained during exercise 201Tl SPET acquisition as the mean counts per pixel in an entire right lung field region of interest divided by the mean counts per pixel in the hottest myocardial wall region of interest. We studied 103 patients. Fifty-nine patients (group I) with <5% likelihood of CAD were used as a reference group. In 44 CAD patients (group II), L/H ratio was compared with 201Tl SPET, radionuclide angiographic and coronary angiographic variables. The group I L/H ratio of 0.35+/-0.05 (mean +/-1 SD) was significantly lower (P<0.001) than the group II L/H ratio of 0. 45+/-0.10. An L/H ratio >0.45 (mean + 2 SD in group I) was considered abnormal. In group II, L/H ratio showed a significant correlation with stress and rest 201Tl perfusion defect size (r = 0. 39 and r = 0.42, P<0.01, respectively), but not with extent of ischaemic myocardium. The mean L/H ratio was 0.41+/-0.10 in patients with one-vessel disease (n = 15), 0.46+/-0.08 in those with two-vessel disease (n = 17) and 0.47+/-0.12 in those with three-vessel disease (n = 12), but no significant difference was found between the three subgroups. L/H ratio showed a significant inverse relation with rest and exercise left ventricular ejection fraction (r = -0.37 and r = -0.50, P<0.05 and P<0.001, respectively). Using stepwise multiple regression analysis, exercise left ventricular ejection fraction and previous history of hypertension were the sole two variables independently predictive of the L/H ratio. In conclusion, although lung thallium uptake is usually found to correlate with extent and severity of CAD, increased L/H ratio should primarily be considered as a marker of exercise-induced left ventricular systolic and perhaps diastolic dysfunction, probably independent of the underlying cardiac disease.

Early detection of liposome brain localization in rat experimental allergic encephalomyelitis.

Blood-brain barrier (BBB) permeability increases prior to the development of clinical signs in early-stage multiple sclerosis (MS). Detection of subtle changes would thus be helpful for diagnostic purposes and rapid therapeutic decisions before new episodes. Since multiple sclerosis and experimental allergic encephalomyelitis (EAE) have numerous common features, in particular BBB-permeability characteristics, and since we have previously shown that BBB localization is disturbed by tumors, embolism, and mannitol injection, we investigated BBB-liposome permeability in an EAE rat model. Twenty young male Lewis rats received a single intradermal inoculation of guinea-pig spinal cord. The effect of the Freund's adjuvant and spinal cord alone on brain permeability were also assessed. In order to compare solution permeability and liposome localization, radioactive liposomes and, 1 h later, 99mTc-DTPA were injected intravenously. Scintigraphic acquisitions were obtained to follow the biodistribution of radioactivity in the whole body. Each rat was subjected to a first examination before inoculation and then every two days until completion and may be considered as its own control. EAE induced a previously unreported increase in global-body permeability, probably due to inflammation. Liposome brain localization and brain/heart ratio were significantly different between normal animals and those with early-stage EAE (before appearance of clinical signs) and distinguished between different disease stages in clinically patent EAE. The index of disease progression was modified earlier than with 99mTc-DTPA injection. One explanation may be particle pick-up by circulating macrophages, which cross the BBB during this pathology. For clinical applications, experiments must be confirmed on models more reliable for human multiple sclerosis.

Synthesis of Iron Oxide Nanoparticles Used as MRI Contrast Agents: A Parametric Study.

Colloidal iron oxides play an important role as magnetic resonance imaging (MRI) contrast agents. The superparamagnetic particles actually used are constituted by solid cores (diameter of 5-15 nm), generally coated by a thick polysaccharidic layer (hydrodynamic radii of 30-100 nm), and formulated by direct coprecipitation of iron salts in the presence of polymeric material. To better control the synthesis, we attempted to formulate new stable uncoated superparamagnetic nanoparticles. Colloids were generated by coprecipitation of an aqueous solution of iron salts and tetramethylammonium hydroxide (TMAOH) solution. The influence of parameters such as media composition, iron media, injection fluxes, Fe and TMAOH concentrations, temperature, and oxygen on size, magnetic and magnetic resonance relaxometric properties, and colloidal stability of particles were evaluated. We have determined the relative importance of these parameters as well as the optimal conditions for obtaining uncoated stable particles with an average size of 5 nm and interesting relaxivities. The interpretation of the observed limits takes into account diffusibilities of reactants and product, feeding rates of reactants, and surface properties of nanoparticles. A model of synthesis, related to spontaneous emulsification of suspensions, is proposed. Copyright 1999 Academic Press.

Global left ventricular cardiac function: comparison between magnetic resonance imaging, radionuclide angiography, and contrast angiography.

RATIONALE AND OBJECTIVES: Cardiac magnetic resonance imaging (MRI) has been shown to be a robust and noninvasive method to assess left ventricular (LV) cardiac function. This study sought to assess volumes and mass calculated with MRI using fast techniques for acquisition and postprocessing, and to compare results in terms of cost-effectiveness with those of radionuclide angiography (RNA) or contrast angiography (CA). METHODS: Thirty-five patients and 15 healthy volunteers were studied. All patients underwent an MRI examination during the same period that they underwent ventriculography (26 patients) or radiography (25 patients). From 7 to 11 short-axis slices were acquired with a breath-hold fast-gradient echo-segmented sequence from apex to base. Contours were drawn with an automated border detection software. RESULTS: Ejection fraction (EF) correlated well between modalities (r = 0.77, P<0.001, for MRI and RNA; r = 0.72, P< 0.001, for MRI and CA). CONCLUSIONS: Cardiac MRI is a fast and accurate technique for estimation of LV volumes, EF, and mass.

Phosphorylcholine Coating of Iron Oxide Nanoparticles.

In order to develop thin-walled superparamagnetic nanoparticle suspensions as a contrast agent for magnetic resonance imaging, phosphorylcholine PC was used to coat iron oxide cores of 5 nm. Weak stable positively charged suspensions can be obtained at concentration greater than 3 mmol.l-1 (corresponding to about 3.2 molecules per nm2), while the addition of phosphorylglycerol PG decreases the electrophoretic mobility. Raising the pH over 6 leads to flocculation: the binding of PC on iron oxides as a function of pH appears to be reversible. By Langmuir analysis, two adsorption domains may be observed with a maximal density of 3.48 and 6.55 mol.nm-2, interpreted as a multilayer formation. Copyright 1999 Academic Press.