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Biomedical subjects

A Bifone

Publications and source records attributed to A Bifone.

15 recordsLinked to original sources

Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration.

The mechanisms underlying the signal changes observed with pharmacological magnetic resonance imaging (phMRI) remain to be fully elucidated. In this study, we obtained microdialysis samples in situ at 5-min intervals during phMRI experiments using a blood pool contrast agent to correlate relative cerebral blood volume (rCBV) changes with changes in dopamine and cocaine concentrations following acute cocaine challenge (0.5 mg/kg iv) in the rat over a duration of 30 min. Three brain areas were investigated: the dorsal striatum (n = 8), the medial prefrontal cortex (mPFC; n = 5), and the primary motor cortex (n = 8). In the striatum and mPFC groups, cocaine and dopamine temporal profiles were tightly correlated, peaking during the first 5-min period postinjection, then rapidly decreasing. However, the local rCBV changes were uncorrelated and exhibited broader temporal profiles than those of cocaine and dopamine, attaining maximal response 5-10 min later. This demonstrates that direct vasoactivity of dopamine is not the dominant component of the hemodynamic response in these regions. In the motor cortex group, microdialysis revealed no local change in dopamine in any of the animals, despite large local cocaine increase and strong rCBV response, indicating that the central hemodynamic response following acute iv cocaine challenge is not driven directly by local dopamine changes in the motor cortex. The combination of phMRI and in situ microdialysis promises to be of great value in elucidating the relationship between the phMRI response to psychoactive drugs and underlying neurochemical changes.

Animals↗

Multiple spin echoes for the evaluation of trabecular bone quality.

We report a simple and efficient MR method for the evaluation of trabecular bone quality. This technique is based on detection and imaging of Multiple Spin-Echoes (MSE), a manifestation of the dipolar field generated by residual intermolecular dipolar couplings in liquids. In the particular implementation we have used, originally proposed by Bowtell [J. Magn. Reson. 100 (1992) 1; J. Magn. Reson. 88 (1990) 643; Phys. Rev. Lett. 76 (1996) 4971], multiple spin echoes (MSE) are refocused in a two-pulse experiment in the presence of a correlation linear magnetic field gradient G(c). This gradient generates a magnetisation helix and results in the spatial modulation of the sample magnetisation. In heterogeneous systems, the amplitude of the MSE signal depends on sample heterogeneity over a distance d=pi/(gammaG(c)tau) which is half a cycle of the magnetisation helix, thus providing a novel contrast mechanism that can be tuned to a specific length scale. We have exploited this mechanism to study young bovine trabecular bone samples ex-vivo. We show that MSE images present a different contrast from conventional MR images, and that, by varying the experimental parameters, the image contrast can be related to specific trabecular pore sizes. The potential of this technique for the early diagnosis of osteoporotic diseases is discussed.

Animals↗

In vivo hyperpolarized 129Xe NMR spectroscopy in tumors.

The first in vivo hyperpolarized 129Xe NMR study in experimental tumors is presented. Hyperpolarized 129Xe was dissolved in solutions, and was injected intratumorally in GH-3 prolactinomas in rats and RIF-1 fibrosarcomas in mice. The 129Xe NMR spectra and apparent spin-lattice relaxation times in the two tumor types present characteristic differences. These differences are discussed in terms of xenon exchange between the carrier medium and the tissue compartments.

Animals↗

Characterization of trabecular bone by dipolar demagnetizing field MRI.

A multiple spin-echo (MSE) sequence has been applied for the first time to study trabecular bone ex vivo. The second echo generated by the demagnetizing field presents discrete drops in signal intensity for certain values of the pitch of the magnetization helix created by the correlation gradient. These dips may reflect characteristic pore sizes in the trabecular bone specimens. This hypothesis is supported by similar experiments performed on a phantom with uniform pore size distribution. Trabecular bone images weighted in the MSE contrast mechanism are reported.

Animals↗

Hyperpolarized 129Xe NMR as a probe for blood oxygenation.

Optically enhanced NMR with (129)Xe and (3)He is emerging as a novel and promising technique for medical imaging of lungs and other tissues. Here it is shown that hyperpolarized (129)Xe NMR provides a powerful means of measuring blood oxygenation quantitatively and noninvasively. The interaction of xenon with hemoglobin is responsible for an oxygen-dependent NMR shift of (129)Xe in red blood cells, in sharp contrast to the current model of xenon-hemoglobin binding. This effect could be exploited in brain functional studies, and in the assessment of conditions and diseases affected by blood oxygenation.

Humans↗

On the oxygenation-dependent (129)Xe T (1) in blood.

The spin-lattice relaxation time, T(1), of hyperpolarized (129)Xe in blood is sensitive to blood oxygenation. In particular, it has been shown that (129)Xe T(1) is shorter in venous blood than in arterial blood. We have studied the T(1) of hyperpolarized (129)Xe dissolved in human blood as a function of blood oxygenation level, sO(2), in the physiological oxygenation range. We show that the (129)Xe relaxation rate, T(1)(-1), varies in a nonlinear fashion as a function of sO(2). This finding suggests that direct interaction of xenon with the paramagnetic heme group of deoxyhemoglobin is not the dominant oxygenation-dependent relaxation mechanism for (129)Xe in blood. These results corroborate the idea that the oxygenation-dependence of (129)Xe T(1) is determined by conformational changes of hemoglobin induced by oxygen binding.

Carbon Dioxide↗

Intravenous delivery of hyperpolarized (129)Xe: a compartmental model.

There is an increasing interest in the use of hyperpolarized 129-xenon (HpXe) NMR for the measurement of tissue perfusion. In this paper we present a theoretical study designed to assess the merit of intravenous HpXe delivery compared with the existing respiration techniques. A compartmental model was created to describe the behavior of the injected bolus in the circulatory system and in the lungs. The dependence of the tissue concentration on the T(1) and solubility of the Xe in the various compartments, and on injection rate, were evaluated. By this process the critical loss mechanisms are identified. It is shown that the predicted tissue concentrations of HpXe in gray and white matter are comparable using respiration or injection techniques.

Humans↗

Spin-lattice relaxation of laser-polarized xenon in human blood.

The nuclear spin polarization of 129Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other in vivo applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (T1) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured in vitro as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of 129Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of 129Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the 129Xe T1s at 37 degrees C and a magnetic field of 1.5 T were 6.4 s +/- 0.5 s and 4.0 s +/- 0.4 s, respectively. The 129Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of T1 in oxygenated blood to that in deoxygenated blood is the same at 37 degrees C and 25 degrees C. A competing ligand has been used to show that xenon binding to albumin contributes to the 129Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules.

Arteries↗

Perfluorocarbon emulsions as intravenous delivery media for hyperpolarized xenon.

The use of perfluorooctyl bromide (PFOB) emulsions as delivery media for hyperpolarized xenon has been investigated. Emulsion droplet size was controlled by varying the content of egg yolk phospholipid (EYP), which served as an emulsifier. Hyperpolarized 129Xe nuclear magnetic resonance (NMR) spectra of the dissolved gas were obtained. The NMR spectra were found to be correlated strongly with the emulsion droplet size distribution. The NMR line width is determined by xenon exchange between the PFOB droplets and the aqueous environment. Our findings show that, in a 1.5-Tesla field, relatively narrow 129Xe NMR spectra are obtained for droplet sizes larger than 5 microm. Preliminary results on animal models show that PFOB emulsions have potential as hyperpolarized 129Xe carriers for in vivo magnetic resonance applications.

Animals↗

In vivo multiple spin echoes.

The demagnetizing field produced by the nuclear polarization can induce refocusing of multiple spin echoes. We show that multiple spin echoes can be observed in vivo with a clinical MR system at 1.5 T. Strategies for the spatial localization of the multiple spin echo signals are considered. Multiple spin echo studies in brain white matter and skeletal muscle in healthy volunteers are reported. The dependence of the signal amplitudes on the experimental parameters is compared with the theory. The sources of contrast for MRI and the perspectives for medical applications are discussed.

Brain↗

NMR of laser-polarized xenon in human blood.

By means of optical pumping with laser light it is possible to enhance the nuclear spin polarization of gaseous xenon by four to five orders of magnitude. The enhanced polarization has allowed advances in nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI), including polarization transfer to molecules and imaging of lungs and other void spaces. A critical issue for such applications is the delivery of xenon to the sample while maintaining the polarization. Described herein is an efficient method for the introduction of laser-polarized xenon into systems of biological and medical interest for the purpose of obtaining highly enhanced NMR/MRI signals. Using this method, we have made the first observation of the time-resolved process of xenon penetrating the red blood cells in fresh human blood-the xenon residence time constant in the red blood cells was measured to be 20.4 +/- 2 ms. The potential of certain biologically compatible solvents for delivery of laser-polarized xenon to tissues for NMR/MRI is discussed in light of their respective relaxation and partitioning properties.

Erythrocytes↗