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Biomedical subjects

B Quesson

Publications and source records attributed to B Quesson.

17 recordsLinked to original sources

Magnetic resonance temperature imaging.

Continuous, real-time, 3D temperature mapping during a hyperthermic procedure may provide (i) enhanced safety by visualizing temperature maps in and around the treated region, (ii) improved efficiency by adapting local energy deposition with feedback coupling algorithms and (iii) therapy end-points based on the accumulated thermal dose. Non-invasive mapping of temperature changes can be achieved with MRI and may be based on temperature dependent MRI parameters. The excellent linearity of the temperature dependency of the proton resonance frequency (PRF) and its near-independence with respect to tissue type make the PRF-based methods the preferred choice for many applications, in particular at mid- to-high field strength (> or =0.5 T). The PRF methods employ RF-spoiled gradient echo imaging methods and incorporate fat suppression techniques for most organs. A standard deviation of less than 1 degrees C, for a temporal resolution below 1 s and a spatial resolution of approximately 2 mm is feasible for immobile tissues. Special attention is paid to methods for reducing artifacts in MR temperature mapping caused by intra-scan and inter-scan motion and motion and temperature-induced susceptibility effects in mobile tissues. Real-time image processing and visualization techniques, together with accelerated MRI acquisition techniques, are described because of their potential for therapy guidance.

Humans↗

Spatial and temporal control of transgene expression in vivo using a heat-sensitive promoter and MRI-guided focused ultrasound.

BACKGROUND: Among the techniques used to induce and control gene expression, a non-invasive, physical approach based on local heat in combination with a heat-sensitive promoter represents a promising alternative but requires accurate temperature control in vivo. MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control allows automatic execution of a predefined temperature-time trajectory. The purpose of this study was to demonstrate temporal and spatial control of transgene expression based on a well-defined local hyperthermia generated by MRI-FUS. METHODS: Expression of the green fluorescent protein (GFP) marker gene was used. Two cell lines were derived from C6 glioma cells. The GFP expression of the first one is under the control of the CMV promoter, whereas it is under the control of the HSP70 promoter in the second one and thus inducible by heat. Subcutaneous tumours were generated by injection in immuno-deficient mice and rats. Tumours were subjected to temperatures varying from 42 to 50 degrees C for 3 to 25 min controlled by MRI-FUS and analyzed 24 h after the heat-shock. Endogenous HSP70 expression and C6 cell distribution were also analyzed. RESULTS: The results demonstrate strong expression at 50 degrees C applied during a short time period (3 min) without affecting cell viability. Induced expression was also clearly shown for temperature in the range 44-48 degrees C but not at 42 degrees C. CONCLUSIONS: Heating with MRI-FUS allows a tight and non-invasive control of transgene expression in a tumour.

Animals↗

Image-guided control of transgene expression based on local hyperthermia.

Spatial and temporal control of transgene expression is one of the major prerequisites of efficient gene therapy. Recently, a noninvasive, physical approach has been presented based on local heat in combination with a heat-sensitive promoter. This strategy requires tight temperature control in vivo. Here, we use MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control on a whole-body clinical MRI system for a completely automatic execution of a predefined temperature-time trajectory in the focal point. Feasibility studies on expression control were carried out on subcutaneously implanted rat tumors. A stable modified C6 glioma cell line was used carrying a fused gene coding for thymidine kinase (TK) and green fluorescent protein (GFP) under control of the human heat-shock protein 70 (HSP70) promoter. In vitro studies showed strong induction of the TK-GFP gene expression upon heat shock under various conditions and localization of the protein product in the nucleus. In vivo tumors were subjected to a 3-min temperature elevation using MRI-FUS with a constant temperature, and were analysed 24 hr after the heat shock with respect to GFP fluorescence. Preliminary results showed strong local induction in regions heated above 40 degrees C, and a good correspondence between temperature maps at the end of the heating period and elevated expression of TK-GFP.

Animals↗

On-line correction and visualization of motion during MRI-controlled hyperthermia.

Displacement of tissue during MRI-controlled hyperthermia therapy can cause significant problems. Errors in calculated temperature may result from motion-related image artifacts and inter-image object displacement, leading to incorrect spatial temperature reference. Here, cyclic navigator echoes were incorporated in rapid gradient-echo MRI sequences, used for temperature mapping based on the proton resonance frequency. On-line evaluation of navigator information was used in three ways. First, motion artifacts were minimized in echo-shifted (TE > TR) gradient-echo images using the phase information of the navigator echo. Second, navigator profiles were matched for a quantitative evaluation of displacement. Together with a novel processing method, this information was employed to correct the reference temperature maps, thereby avoiding persistence of motion-related temperature errors throughout the hyperthermic period. Third, on-line visualization of displacement, together with temperature maps and thermal dose images, was developed, allowing physician intervention at all times. Examples are given of on-line corrections during hyperthermia procedures with focused ultrasound and radiofrequency heat sources. Magn Reson Med 45:128-137, 2001.

Animals↗

Thermal therapies in interventional MR imaging. Focused ultrasound.

MR image-guided focused ultrasound (FUS) provides an entirely noninvasive approach for local thermal therapies. MR imaging allows target definition and continuous temperature mapping. Therefore, the heating procedure can be controlled spatially and temporally based on automatic feedback to the FUS apparatus. Phased-array ultrasound technology will further help the development. MR imaging/FUS may be applied not only for tissue ablation, but also for local drug delivery, gene therapy, and drug activation.

Animals↗

In vivo evaluation of remyelination in rat brain by magnetization transfer imaging.

The aim of this work was to assess quantitatively and qualitatively the ability of magnetization transfer imaging to follow in vivo remyelination. Demyelination lesions were induced in rats by the injection of L-alpha-lysophosphatidylcholine stearoyl into the corpus callosum and imaging was performed in vivo on a 4.7-Tesla system at different time points. The percentage of magnetization transfer ratio (MTR) decrease was calculated for each animal. To evaluate the MTR findings for remyelination, myelin was quantitated by histological analysis of the lesion size and counting the number of remyelinating axons. An MTR decrease was observed when demyelination was present at 7 days after injection. During the remyelinating phase between day 30 and 40 after injection, contralateral values almost complete returned to normal, thus indicating remyelination. Histologically, at days 30 and 40 after injection, the lesion area was reduced in size and the axons were surrounded by a thin myelin sheath, indicating the remyelination process. Statistical analysis showed that the profile of MTR values was significantly correlated with the course of remyelination. All the MTR changes show a correlation with both myelin damage and repair. In conclusion, the study of the MTR profile in this myelin lesion model demonstrates in vivo the loss of myelin and the presence of spontaneous remyelination. This methodological approach which can also be applied to multiple sclerosis patients to show demyelination, should prove helpful to determine the degree of spontaneous and therapeutically induced remyelination in multiple sclerosis lesions, and thus to validate therapeutic treatments for myelin repair.

Animals↗

Magnetic resonance temperature imaging for guidance of thermotherapy.

Continuous thermometry during a hyperthermic procedure may help to correct for local differences in heat conduction and energy absorption, and thus allow optimization of the thermal therapy. Noninvasive, three-dimensional mapping of temperature changes is feasible with magnetic resonance (MR) and may be based on the relaxation time T(1), the diffusion coefficient (D), or proton resonance frequency (PRF) of tissue water. The use of temperature-sensitive contrast agents and proton spectroscopic imaging can provide absolute temperature measurements. The principles and performance of these methods are reviewed in this paper. The excellent linearity and near-independence with respect to tissue type, together with good temperature sensitivity, make PRF-based temperature MRI the preferred choice for many applications at mid to high field strength (>/= 1 T). The PRF methods employ radiofrequency spoiled gradient-echo imaging methods. A standard deviation of less than 1 degrees C, for a temporal resolution below 1 second and a spatial resolution of about 2 mm, is feasible for a single slice for immobile tissues. Corrections should be made for temperature-induced susceptibility effects in the PRF method. If spin-echo methods are preferred, for example when field homogeneity is poor due to small ferromagnetic parts in the needle, the D- and T(1)-based methods may give better results. The sensitivity of the D method is higher that that of the T(1) methods provided that motion artifacts are avoided and the trace of D is evaluated. Fat suppression is necessary for most tissues when T(1), D, or PRF methods are employed. The latter three methods require excellent registration to correct for displacements between scans.

Animals↗

Local hyperthermia with MR-guided focused ultrasound: spiral trajectory of the focal point optimized for temperature uniformity in the target region.

The objective of hyperthermia treatment is to deliver a similar therapeutic thermal dose throughout the target volume within a minimum amount of time. We describe a noninvasive approach to this goal based on magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) with a spherical transducer that can be moved along two directions inside the bed of a clinical MR imager and that has an adjustable focal length in the third dimension. Absorption of FUS gives rise to a highly localized thermal buildup, which then spreads by heat diffusion and blood perfusion. A uniform temperature within a large target volume can be obtained using a double spiral trajectory of the transducer focal point together with constant and maximum FUS power. Differences between the real and target temperatures during the first spiral are evaluated in real time with temperature MRI and corrected for during the second spiral trajectory employing FUS focal point velocity modulation. Once a uniform temperature distribution is reached within the entire volume, FUS heating is applied only at the region's boundaries to maintain the raised temperature levels. Heat conduction, together with the design and timing of the trajectories, therefore ensures a similar thermal dose for the entire target region. Good agreement is obtained between theory and experimental results in vitro on gel phantoms, ex vivo on meat samples, and in vivo on rabbit thigh muscle. Edema in muscle was visible 1 hour after hyperthermia as a spatially uniform rise of the signal intensity in T(2)-weighted images.

Animals↗

Single-coil surface imaging using a radiofrequency field gradient

A method for in-plane imaging of large objects as compared to the RF coil is proposed based on the use of a single specially designed surface coil, without using B(0) gradients. A constant B(1) gradient was generated along the main axis of a ladder-shaped coil, and RF-encoding along the direction of the gradient made it possible to obtain spin-density profiles. Successive acquisitions of profiles obtained by translation of the NMR coil resulted in distorted images-due to the presence of non-zero gradients perpendicular to the constant gradient-that were successfully processed using a mathematical treatment based on linear combinations of calculated altered images from single-pixel objects. Copyright 2000 Academic Press.

Journal Article↗

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.

Animals↗

In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance.

Cell-specific imaging has been proposed to increase the potential of magnetic resonance imaging (MRI) for tissue analysis. The hypothezis of the present work was that following intravenous injection of ultra-small particle iron oxide, a contrast agent that accumulates in mononuclear phagocyte cells, macrophages with iron burden would be detectable by MRI within the central nervous system at sites of inflammatory cellular activity. In experimental autoimmune encephalomyelitis in Lewis rats (in which intense macrophage activity results from both hematogenous macrophages and activated microglia), lesions have been seen by MRI as low signal intensities related to magnetic susceptibility effects induced by iron particles. Electron microscopy has revealed the presence of such particles within the cytoplasm of cells that had the morphological aspect of macrophages. Macrophage activity imaging might increase MRI capability with regard to the in vivo pathophysiological aspects of central nervous system (CNS) diseases and might help in therapeutic trials in the numerous CNS diseases in which macrophages are involved.

Animals↗

Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report.

OBJECTIVES: Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy (1H-MRS) after birth asphyxia. MATERIALS AND METHODS: Thirty newborn infants suspected of having perinatal asphyxia (Apgar score < 3) were studied. The mean gestational age was 37 weeks, mean age at the MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for imaging and spectroscopy. None of the babies had mechanically assisted ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were obtained. 1H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. RESULTS: Image quality was good in 25 of 30 babies. 1H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. CONCLUSIONS: This study suggests that 1H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites.

Aspartic Acid↗

[1-(13)C]glucose metabolism in the tumoral and nontumoral cerebral tissue of a glioma-bearing rat.

C6 cells were used to establish a glioma-bearing rat model by stereotaxic injection in the left caudate nucleus. The tumor status was evaluated by magnetic resonance imaging and conventional histology. The glioma-bearing rats were infused for 1 h with a [1-(13)C]glucose solution. Perchloric acid extracts of the tumor and the ipsilateral and contralateral hemispheres were analyzed by 13C-NMR spectroscopy. The 13C-labeling patterns in compounds, mainly amino acids, indicated no drastic modification of carbon metabolism in both ipsilateral and contralateral hemispheres, as compared with control rats, whereas profound metabolic differences between brain tissue and tumor were observed. Glutamine C4 enrichment was lower in the glioma than in the brain [mean +/- SD values, 5.4 +/- 2.3 (n = 5) and 15.0 +/- 0.8% (n = 10), respectively] and also lower than the glutamate C4 enrichment in the glioma (mean +/- SD value, 22.6 +/- 4.2%; n = 5), indicating that tumor glutamine was neither synthesized inside the glioma nor taken up from the surrounding brain. The glutamine C4 enrichment in the serum (6.7 +/- 0.5%; n = 10) suggested that the glioma imported glutamine from the blood, a process probably connected with angiogenesis.

Alanine↗

13C nuclear magnetic resonance study of glycogen resynthesis in muscle after glycogen-depleting exercise in healthy men receiving an infusion of lipid emulsion.

In healthy individuals, glycogen recovery after a strong depletion is known to be rapid and insulin independent during the initial phase, and subsequently, slow and insulin dependent. Free fatty acids (FFAs) as a putative source of insulin resistance (IR) could thus impair glycogen recovery during the second period. Using in vivo 13C nuclear magnetic resonance (NMR), we studied the effect of long-chain triglyceride emulsion on gastrocnemius glycogen resynthesis during a 3-h recovery period after 90 min of moderate exercise consisting of plantar flexion on overnight-fasted healthy men (n = 8). In separate experiments, each subject was infused with 10% Ivelip (0.015 ml x kg(-1) x min(-1)) or 10% glycerol (0.13 mg x kg(-1) x min(-1)). NMR spectra were acquired before and at the end of the exercise and during the recovery period. Whole-body glucose and lipid oxidation rates (indirect calorimetry), plasma insulin, C-peptide, glucose, lactate, beta-hydroxybutyrate, triglycerides, and FFAs were determined. Glycogen consumption was 47.6 +/- 4.5% (glycerol) and 49.7 +/- 4.8% (Ivelip) of the initial glycogen. An acquired IR in the Ivelip group was significant at the onset of the recovery period by homeostasis model assessment (P = 0.002). Glycogen resynthesis in the glycerol group appeared faster during the 1st h than during the subsequent 2nd h of the postexercise period. The glycogen resynthesis level was significantly lower in the Ivelip group than in the glycerol group during the recovery period (P = 0.04 during the 1st h and P = 0.001 during the next 2 h). During the recovery, plasma lactate and whole-body oxidation rates were similar in the two groups, whereas glycemia was significantly higher in the Ivelip group. A decreased cellular uptake of glucose as a substrate for glycogenosynthesis, rather than a competition between oxidation of carbohydrate and FFA, is discussed.

Adult↗

Magnetization transfer imaging of rat brain under non-steady-state conditions. Contrast prediction using a binary spin-bath model and a super-lorentzian lineshape.

Magnetization transfer contrast imaging using turbo spin echo and continuous wave off-resonance irradiation was carried out on rat brain in vivo at 4.7 T. By systematically varying the off-resonance irradiation power and the offset-frequency, the signal intensities obtained under steady-state for both transverse and longitudinal magnetization were successfully analyzed with a simple binary spin-bath model taking into account a free water compartment and a pool of protons with restricted motions bearing a super-Lorentzian lineshape. Due to important RF power deposition, such experimental conditions are not practical for routine imaging on humans. An extension of the model was derived to describe the system for shorter off-resonance pulse duration, i.e., when the longitudinal magnetization of the free protons has not reached a steady-state. Data sets obtained for three regions of interest, namely the corpus callosum, the basal ganglia, and the temporal lobe, were correctly interpreted for off-resonance pulse durations varying from 0.3 to 3 s. The parameter sets obtained from the calculations made it possible to predict the contrast between the different regions as a function of the pulse power, the offset frequency, and pulse duration. Such an approach could be extended to contrast prediction for human brain at 1.5 T.

Animals↗

Magnetization transfer imaging in vivo of the rat brain at 4.7 T: interpretation using a binary spin-bath model with a superLorentzian lineshape.

Proton magnetization transfer contrast (MTC) imaging, using continuous wave off-resonance irradiation, was performed on the rat brain in vivo at 4.7 Tesla. The observed MTC was studied in three different brain regions: the corpus callosum, the basal ganglia, and the temporal lobe. By systematically varying the offset frequency and the amplitude of the RF irradiation, the observed signal intensities for each region of interest were modeled using a system including free water and a pool of protons with restricted motions (R. M. Henkelman, X. Huang, Q. Xiang, G. J. Stanisz, SD Swanson, M. J. Bronskill, Magn. Res. Med. 29, 759 (1993)). Most of the relaxation parameters of both proton pools remained fairly constant for the three regions of interest, with a T2 value of about 9 micros for the immobilized protons, whereas the rate of exchange increased significantly from the temporal lobe to the corpus callosum. The optimal acquisition parameters for the improved MTC under steady-state saturation were found to be 2-10 kHz offset frequency and 500-800 Hz RF irradiation amplitude. Conversely, an irradiation amplitude of 3 kHz at an offset frequency of 12 kHz is required to minimize the direct effect of off-resonance irradiation. Such an approach could be extended to human brain imaging with the aim of characterizing tissue-specific disease.

Animals↗

Magnetization transfer fast imaging of implanted glioma in the rat brain at 4.7 T: interpretation using a binary spin-bath model.

C6 glioma cells were implanted in the left caudate nucleus of the rat brain. Histologic studies confirmed the presence of neoplastic tissue surrounded by a thin edematous region. Proton magnetization transfer contrast (MTC) fast imaging, using continuous wave off-resonance irradiation, was performed in vivo at 4.7 T with the rapid acquisition with relaxation enhancement (RARE) sequence. The observed MTC allowed very clear distinction of the tumoral region, in which magnetization transfer (MT) ratios were lower than in healthy tissues. Contrasts were analyzed as a function of the offset frequency and the amplitude of the radiofrequency (RF) irradiation. The contrast was higher between the contralateral basal ganglia and the tumor and lower between the tumor and the temporal lobe. Modeling of MT in the three brain regions was performed using a system including free water and a pool of protons with restricted motions. The rate of exchange between the two pools exhibited a decreasing hierarchy from the basal ganglia to the tumor. T2B values for the immobile protons ranged from 9.3 microsec in the basal ganglia to 7.5 microsec for the glioma. The acquisition conditions leading to the highest contrasts between the tumor and the healthy tissues correspond to 3,000 Hz offset frequency and 300 to 700 Hz RF irradiation amplitude.

Animals↗