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1.
ACS Appl Mater Interfaces ; 11(27): 24412-24422, 2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31199615

ABSTRACT

Sensing of a few unpaired electron spins, such as in metal ions and radicals, is a useful but difficult task in nanoscale physics, biology, and chemistry. Single negatively charged nitrogen-vacancy (NV-) centers in diamond offer high sensitivity and spatial resolution in the optical detection of weak magnetic fields produced by a spin bath but often require long acquisition times on the order of seconds. Here, we present an approach based on coupled spin and charge dynamics in dense NV ensembles in strongly fluorescent nanodiamonds (NDs) to sense external magnetic dipoles. We apply this approach to various paramagnetic species, including gadolinium complexes, magnetite nanoparticles, and hemoglobin in whole blood. Taking advantage of the high NV density, we demonstrate a dramatic reduction in acquisition time (down to tens of milliseconds) while maintaining high sensitivity to paramagnetic centers. Strong luminescence, high sensitivity, and short acquisition time make dense NV- ensembles in NDs a potentially promising tool for biosensing and bioimaging applications.

2.
Addict Biol ; 24(5): 981-993, 2019 09.
Article in English | MEDLINE | ID: mdl-30328656

ABSTRACT

Alcoholism is often associated with other forms of drug abuse, suggesting that innate predisposing factors may confer vulnerability to addiction to diverse substances. However, the neurobiological bases of these factors remain unknown. Here, we have used a combination of imaging, neurochemistry and behavioral techniques to investigate responses to the psychostimulant amphetamine in Marchigian Sardinian (msP) alcohol-preferring rats, a model of vulnerability to alcoholism. Specifically, we employed pharmacological magnetic resonance imaging to investigate the neural circuits engaged by amphetamine challenge, and to relate functional reactivity to neurochemical and behavioral responses. Moreover, we studied self-administration of cocaine in the msP rats. We found stronger functional responses in the extended amygdala, alongside with increased release of dopamine in the nucleus accumbens shell and augmented vertical locomotor activity compared with controls. Wistar and msP rats did not differ in operant cocaine self-administration under short access (2 hours) conditions, but msP rats exhibited a higher propensity to escalate drug intake following long access (6 hours). Our findings suggest that neurobiological and genetic mechanisms that convey vulnerability to excessive alcohol drinking also facilitate the transition from psychostimulants use to abuse.


Subject(s)
Alcoholism/diagnostic imaging , Amphetamine/pharmacology , Brain/drug effects , Central Nervous System Stimulants/pharmacology , Cocaine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Alcoholism/metabolism , Amygdala/diagnostic imaging , Amygdala/drug effects , Amygdala/metabolism , Animals , Brain/diagnostic imaging , Brain/metabolism , Conditioning, Operant , Disease Models, Animal , Dopamine/metabolism , Functional Neuroimaging , Glutamic Acid/drug effects , Glutamic Acid/metabolism , Locomotion , Magnetic Resonance Imaging , Microdialysis , Nucleus Accumbens/diagnostic imaging , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Self Administration , gamma-Aminobutyric Acid/drug effects , gamma-Aminobutyric Acid/metabolism
3.
Nanoscale ; 10(12): 5738-5744, 2018 Mar 28.
Article in English | MEDLINE | ID: mdl-29537021

ABSTRACT

Nanodiamonds (NDs) containing negatively charged Nitrogen-Vacancy (NV) centers are promising materials for applications in photonics, quantum computing, and sensing of environmental parameters like temperature, strain and magnetic fields. However, the production of fluorescent NDs remains a technological challenge, requiring a complex multi-step process involving controlled introduction of substitutional nitrogen into the diamond lattice, annealing and fragmentation from macrocrystals to nanocrystals. Here, we report on a single-step, all-optical process for the production of nanometric-sized fluorescent diamonds based on laser ablation of a carbon substrate at low temperature (100 °C) under a nitrogen atmosphere. We demonstrate that this synthesis route yields fluorescent NDs with a concentration of native NV centers controlled by adjusting the experimental ablation conditions. Spin-polarization dependent optical-transitions are observed by optically detected magnetic resonance spectroscopy, thus providing strong evidence of the presence of negatively charged NV centers in the as-grown NDs. Finally, we propose a thermodynamic model able to describe the nucleation of NDs and the formation of NV centers in the present single-step optical process.

4.
Sci Rep ; 6: 35244, 2016 10 12.
Article in English | MEDLINE | ID: mdl-27731385

ABSTRACT

Nanodiamonds are the subject of active research for their potential applications in nano-magnetometry, quantum optics, bioimaging and water cleaning processes. Here, we present a novel thermodynamic model that describes a graphite-liquid-diamond route for the synthesis of nanodiamonds. Its robustness is proved via the production of nanodiamonds powders at room-temperature and standard atmospheric pressure by pulsed laser ablation of pyrolytic graphite in water. The aqueous environment provides a confinement mechanism that promotes diamond nucleation and growth, and a biologically compatible medium for suspension of nanodiamonds. Moreover, we introduce a facile physico-chemical method that does not require harsh chemical or temperature conditions to remove the graphitic byproducts of the laser ablation process. A full characterization of the nanodiamonds by electron and Raman spectroscopies is reported. Our model is also corroborated by comparison with experimental data from the literature.

5.
Mater Sci Eng C Mater Biol Appl ; 59: 488-499, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26652400

ABSTRACT

This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs.


Subject(s)
Drug Carriers , Lactic Acid , Materials Testing , Nanoparticles/chemistry , Polyglycolic Acid , Rhodamines , Adsorption , Animals , Blood Proteins/chemistry , Cell Line, Transformed , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Lactic Acid/chemistry , Lactic Acid/pharmacokinetics , Lactic Acid/pharmacology , Mice , Polyglycolic Acid/chemistry , Polyglycolic Acid/pharmacokinetics , Polyglycolic Acid/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer , Rhodamines/chemistry , Rhodamines/pharmacokinetics , Rhodamines/pharmacology
6.
Transl Psychiatry ; 4: e427, 2014 Aug 19.
Article in English | MEDLINE | ID: mdl-25136890

ABSTRACT

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T(+) Itpr3(tf)/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations.


Subject(s)
Child Development Disorders, Pervasive/physiopathology , Disease Models, Animal , Dopamine/physiology , Synaptic Transmission/physiology , Animals , Arousal/physiology , Behavior, Animal/physiology , Child Development Disorders, Pervasive/diagnosis , Child Development Disorders, Pervasive/psychology , Limbic System/physiopathology , Magnetic Resonance Imaging , Mesencephalon/physiopathology , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Nerve Net/physiopathology , Receptors, Dopamine D2/physiology , Reference Values , Social Behavior , Stereotyped Behavior
7.
Neuroimage ; 23(1): 296-304, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15325377

ABSTRACT

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.


Subject(s)
Brain/blood supply , Cocaine/pharmacokinetics , Dopamine/metabolism , Hemodynamics/drug effects , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Microdialysis , Animals , Blood Volume/drug effects , Cocaine/pharmacology , Corpus Striatum/blood supply , Corpus Striatum/drug effects , Dose-Response Relationship, Drug , Half-Life , Infusions, Intravenous , Mass Spectrometry , Motor Cortex/blood supply , Motor Cortex/drug effects , Prefrontal Cortex/blood supply , Prefrontal Cortex/drug effects , Rats , Reference Values , Regional Blood Flow/drug effects
8.
MAGMA ; 14(1): 3-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11796247

ABSTRACT

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.


Subject(s)
Bone Marrow/pathology , Bone and Bones/pathology , Magnetic Resonance Imaging/methods , Animals , Cattle , Femur/pathology , Humans , Magnetics , Models, Theoretical , Osteoporosis/diagnosis , Time Factors
9.
Magn Reson Med ; 46(4): 683-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11590644

ABSTRACT

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.


Subject(s)
Bone and Bones/anatomy & histology , Magnetic Resonance Imaging , Animals , Cattle , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Magnetics , Phantoms, Imaging
10.
Magn Reson Med ; 46(3): 586-91, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11550253

ABSTRACT

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.


Subject(s)
Contrast Media/pharmacokinetics , Fibrosarcoma/diagnosis , Image Enhancement , Image Processing, Computer-Assisted , Magnetic Resonance Spectroscopy , Prolactinoma/diagnosis , Xenon Isotopes/pharmacokinetics , Animals , Female , Fibrosarcoma/pathology , Humans , Mice , Mice, Inbred C3H , Neoplasm Transplantation , Prolactinoma/pathology , Rats , Rats, Inbred WF , Tumor Cells, Cultured/pathology
11.
NMR Biomed ; 13(4): 234-7, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10867702

ABSTRACT

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.


Subject(s)
Oxygen/blood , Xenon/blood , Carbon Dioxide/blood , Humans , Hydrogen-Ion Concentration , Nuclear Magnetic Resonance, Biomolecular , Oxyhemoglobins/chemistry , Oxyhemoglobins/metabolism , Partial Pressure , Protein Conformation , Xenon Isotopes
12.
NMR Biomed ; 13(4): 238-44, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10867703

ABSTRACT

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.


Subject(s)
Xenon/pharmacokinetics , Humans , Injections, Intravenous , Kinetics , Models, Biological , Tissue Distribution , Xenon/administration & dosage , Xenon/blood , Xenon Isotopes
13.
Magn Reson Med ; 43(4): 491-6, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10748422

ABSTRACT

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.


Subject(s)
Magnetic Resonance Spectroscopy/methods , Oxygen/blood , Xenon Radioisotopes , Humans , Image Enhancement/methods , Magnetic Resonance Spectroscopy/instrumentation , Optics and Photonics , Oxygen Consumption , Sensitivity and Specificity
14.
Magn Reson Med ; 41(3): 442-9, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10204864

ABSTRACT

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.


Subject(s)
Fluorocarbons/administration & dosage , Magnetic Resonance Spectroscopy/methods , Xenon Radioisotopes , Animals , Contrast Media/administration & dosage , Drug Interactions , Image Enhancement/methods , Injections, Intravenous , Male , Models, Theoretical , Particle Size , Rats , Rats, Inbred Strains , Sensitivity and Specificity
15.
Proc Natl Acad Sci U S A ; 96(7): 3664-9, 1999 Mar 30.
Article in English | MEDLINE | ID: mdl-10097094

ABSTRACT

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.


Subject(s)
Xenon/blood , Arteries , Carbon Dioxide/blood , Humans , Lung , Magnetic Resonance Spectroscopy/instrumentation , Magnetic Resonance Spectroscopy/methods , Oxygen/blood , Partial Pressure , Sensitivity and Specificity , Veins
16.
J Magn Reson ; 135(1): 30-6, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9799671

ABSTRACT

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.


Subject(s)
Brain/anatomy & histology , Magnetic Resonance Imaging , Muscle, Skeletal/anatomy & histology , Brain/metabolism , Humans , Magnetic Resonance Spectroscopy , Magnetics , Models, Theoretical , Muscle, Skeletal/metabolism , Sensitivity and Specificity
17.
Proc Natl Acad Sci U S A ; 93(23): 12932-6, 1996 Nov 12.
Article in English | MEDLINE | ID: mdl-8917521

ABSTRACT

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.


Subject(s)
Xenon Isotopes , Xenon/blood , Erythrocytes/metabolism , Humans , Kinetics , Lasers , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy/methods
18.
Phys Rev Lett ; 77(21): 4474-4477, 1996 Nov 18.
Article in English | MEDLINE | ID: mdl-10062547
19.
Phys Rev B Condens Matter ; 53(8): 4428-4433, 1996 Feb 15.
Article in English | MEDLINE | ID: mdl-9983996
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