Distribution of Hyperpolarized Xenon in the Brain Following Sensory Stimulation: Preliminary MRI Findings

In hyperpolarized xenon magnetic resonance imaging (HP 129Xe MRI), the inhaled spin-1/2 isotope of xenon gas is used to generate the MR signal. Because hyperpolarized xenon is an MR signal source with properties very different from those generated from water-protons, HP 129Xe MRI may yield structural and functional information not detectable by conventional proton-based MRI methods. Here we demonstrate the differential distribution of HP 129Xe in the cerebral cortex of the rat following a pain stimulus evoked in the animal's forepaw. Areas of higher HP 129Xe signal corresponded to those areas previously demonstrated by conventional functional MRI (fMRI) methods as being activated by a forepaw pain stimulus. The percent increase in HP 129Xe signal over baseline was 13–28%, and was detectable with a single set of pre and post stimulus images. Recent innovations in the production of highly polarized 129Xe should make feasible the emergence of HP 129Xe MRI as a viable adjunct method to conventional MRI for the study of brain function and disease

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE SPINAL CORD IN PAINFUL DIABETIC NEUROPATHY

ABSTRACT Diabetic neuropathy, a secondary complication of diabetes mellitus, is often first characterized by allodynia, hyperalgesia, or spontaneous pain. The mechanism by which diabetes alters pain transmission is not well understood, but recent evidence suggests spinal cord involvement. Behavioural studies have shown that streptozotocin (STZ) induced diabetic rats exhibit hyperalgesia. Functional magnetic resonance imaging (fMRI) was used to compare activity in the spinal cord upon noxious electrical stimulation (15 V, 0.3 ms, 0.3 Hz) of the hind paw in STZ-induced diabetic and control rats (7-8 mA). Experiments were conducted on rats one month following STZ injection (n=4) and healthy age-matched controls (n=4). Diabetic rats were smaller, hyperglycaemic, and had lower blood pH than control animals. FMRI activity at the lumbar enlargement of the spinal cord was observed in both control and diabetic animals in the dorsal horn ipsilateral to stimulus. Control animals exhibited greater fMRI activity in the contralateral dorsal horn, and ipsilateral and contralateral ventral horn, and had a higher percentage signal change compared to diabetic rats. The results of this study are consistent with reports that primary afferent input to the spinal cord is diminished by diabetes, and suggest fMRI may be useful in early detection of diabetic neuropathy. iii ACKNOWLEDGMENT

Correlation of functional activation in the rat spinal cord with neuronal activation detected by immunohistochemistry

NRC publication: Ye

Evaluation of spatial working memory function in children and adults with fetal alcohol spectrum disorders: A functional magnetic resonance imaging study

NRC publication: Ye

Mapping of neuronal function in the healthy and injured human spinal cord with spinal fMRI

Functional magnetic resonance imaging of the human spinal cord is carried out with a graded thermal stimulus in order to establish the relationship between signal changes and neural activity. Studies of the lumbar spinal cord in 15 healthy subjects with 10°C stimulation of the skin overlying the calf demonstrate a pattern of activity that matches the neuronal anatomy of the spinal cord. This pattern shows primarily dorsal horn activity, with expected components of motor reflex activity as well. Moreover, a later response shifting to noxious cold over time is also demonstrated with a shift to more dorsal horn activity. Signal intensity changes detected at different degrees of thermal stimulation have a biphasic nature, with much larger signal changes below 15°C as the stimulus becomes noxious, and agree well with electrophysiological results reported in the literature. These findings demonstrate a strong correspondence between Spinal fMRI results and neural activity in the human spinal cord. Spinal fMRI is also applied to studies of the injured spinal cord, below the site of injury. Results consistently demonstrate activity in the spinal cord even when the subjects cannot feel the stimulus being applied. Signal intensity changes demonstrate the same stimulus–response pattern as that in noninjured subjects, but the areas of activity in the spinal gray matter are notably altered. In subjects with complete injuries, activity is absent ipsilateral to the thermal stimulation, but appears to be enhanced on the contralateral side. These findings demonstrate the reliability of Spinal fMRI and its clinical potential. © 2002 Elsevier Science (USA

Functional MRI of the rat lumbar spinal cord involving painful stimulation and effect of peripheral joint mobilization

NRC publication: Ye

Functional MRI involving painful stimulation of the ankle and the effect of physiotherapy joint mobilization

NRC publication: Ye