Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood-brain barrier (BBB)-permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T 1 -mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1-oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9±0.35 and 3.0±0.50 mmol/L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.

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A double-tuned NMR microprobe with dual RF microcoil assemblies was fabricated and tested. The coils for the proton and X (low frequency) nuclei were a variant of a loop gap resonator and Helmholtz pair, respectively. 1-D 31P spectra of phosphoric acid and 13C-labeled spectra of methanol were recorded from 1.4-μL samples. Signal was easily observable in one scan. A COSY spectrum of 13C-labeled acetic acid was acquired in ∼1 h, demonstrating sufficient sensitivity to perform 2-D 13C direct detect experiments. Thus, the ability to obtain direct detection spectra of low-γ nuclei is demonstrated.

There are few in vivo noninvasive methods to study neuroplasticity in animal brains. Functional MRI (fMRI) has been developed for animal brain mapping, but few fMRI studies have analyzed functional alteration due to plasticity in animal models. One major limitation is that fMRI maps are characterized by statistical parametric mapping making the apparent boundary dependent on the statistical threshold used. Here, we developed a method to characterize the location of center-of-mass in fMRI maps that is shown not to be sensitive to statistical threshold. Utilizing centers-of-mass as anchor points to fit the spatial distribution of the BOLD response enabled quantitative group analysis of altered boundaries of functional somatosensory maps. This approach was used to study cortical reorganization in the rat primary somatosensory cortex (S1) after sensory deprivation to the barrel cortex by follicle ablation (F.A.). FMRI demonstrated an enlarged nose S1 representation in the 3D somatotopic functional maps. This result clearly demonstrates that fMRI enables the spatial mapping of functional changes that can characterize multiple regions of S1 cortex and still be sensitive to changes due to plasticity.