Reduced Creatine Kinase B Activity in Multiple Sclerosis Normal Appearing White Matter

Background: Two studies using 31 P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained. Methodology/Principal Findings: We performed 31 P-MRS and 1 H-MRS in the NAWM in 36 subjects, including 17 with progressive MS, 9 with benign MS, and 10 healthy controls. Compared to controls, PCr/b-ATP and PCr/total 31 P ratios were significantly increased in subjects with progressive MS, but not with benign MS. There was no correlation between PCr ratios and the N-acetylaspartate/creatine ratio, suggesting that elevated PCr levels in NAWM were not secondary to axonal loss. In the central nervous system, PCr is degraded by creatine kinase B (CK-B), which in the white matter is confined to astrocytes. In homogenates of NAWM from 10 subjects with progressive MS and 10 controls without central nervous system disease, we measured CK-B levels with an ELISA, and measured its activity with an enzymatic assay kit. Compared to controls, both CK-B levels and activity were decreased in subjects with MS (22.41 versus 46.28 mg/ml; p = 0.0007, and 2.89 versus 7.76 U/l; p,0.0001). Conclusions/Significance: Our results suggest that PCr metabolism in the NAWM in MS is impaired due to decreased CK-B levels. Our findings raise the possibility that a defective PCr metabolism in astrocytes might contribute to the degeneratio

Characterization of Tryptophanase from Vibrio cholerae O1

AbstractTryptophanase (Trpase) encoded by the tnaA gene catalyzes the conversion of tryptophan to indole, which is an extracellular signaling molecule detected in various bacteria including Vibrio cholerae. Indole has been demonstrated to regulate biofilm formation, drug resistance, plasmid maintenance and spore formation of bacteria. In the present study, the tnaA gene from V. cholerae O1 (VcTrpase) was cloned and expressed in E. coli BL21(DE3) tn5:tnaA (a Trpase-deficient competent). VcTrpase was purified by Ni2+-NTA chromatography. The obtained VcTrpase had a molecular mass of approximately 49 kDa, a specific activity of 3 U/mg protein, and absorption peaks at 330 and 435nm. Using a site-directed mutagenesis technique, replacement of Arg419 by Val resulted in a VcTrpase completely devoid of activity. Thus, this site can be a target for drug design for controlling V. cholerae

7 T renal MRI: challenges and promises

The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging

Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI

To develop technical recommendations on the acquisition and post-processing of renal longitudinal (T1) and transverse (T2) relaxation time mapping. A multidisciplinary panel consisting of 18 experts in the field of renal T1 and T2 mapping participated in a consensus project, which was initiated by the European Cooperation in Science and Technology Action PARENCHIMA CA16103. Consensus recommendations were formulated using a two-step modified Delphi method. The first survey consisted of 56 items on T1 mapping, of which 4 reached the pre-defined consensus threshold of 75% or higher. The second survey was expanded to include both T1 and T2 mapping, and consisted of 54 items of which 32 reached consensus. Recommendations based were formulated on hardware, patient preparation, acquisition, analysis and reporting. Consensus-based technical recommendations for renal T1 and T2 mapping were formulated. However, there was considerable lack of consensus for renal T1 and particularly renal T2 mapping, to some extent surprising considering the long history of relaxometry in MRI, highlighting key knowledge gaps that require further work. This paper should be regarded as a first step in a long-term evidence-based iterative process towards ever increasing harmonization of scan protocols across sites, to ultimately facilitate clinical implementation

Occipital Proton Magnetic Resonance Spectroscopy ((1)H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

BACKGROUND: Progressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative processes, are reduced in the occipital brain region. METHODOLOGY/PRINCIPAL FINDINGS: Participants known with glaucoma, age-related macular degeneration (the two leading causes of visual impairment in the developed world), and controls were examined by proton MR spectroscopic ((1)H-MRS) imaging. Absolute NAA, Creatine and Choline concentrations were derived from a single-voxel in the occipital region of each brain hemisphere. No significant differences in metabolites concentrations were found between the three groups. CONCLUSIONS/SIGNIFICANCE: We conclude that progressive retinal visual field defects do not affect metabolite concentration in visual brain areas suggesting that there is no ongoing occipital degeneration. We discuss the possibility that metabolite change is too slow to be detectable

Shaping and timing gradient pulses to reduce MRI acoustic noise

A method to reduce the acoustic noise generated by gradient systems in MRI has been recently proposed; such a method is based on the linear response theory. Since the physical cause of MRI acoustic noise is the time derivative of the gradient current, a common trapezoid current shape produces an acoustic gradient coil response mainly during the rising and falling edge. In the falling edge, the coil acoustic response presents a 180 degrees phase difference compared to the rising edge. Therefore, by varying the width of the trapezoid and keeping the ramps constant, it is possible to suppress one selected frequency and its higher harmonics. This value is matched to one of the prominent resonance frequencies of the gradient coil system. The idea of cancelling a single frequency is extended to a second frequency, using two successive trapezoid-shaped pulses presented at a selected interval. Overall sound pressure level reduction of 6 and 10 dB is found for the two trapezoid shapes and a single pulse shape, respectively. The acoustically optimized pulse shape proposed is additionally tested in a simulated echo planar imaging readout train, obtaining a sound pressure level reduction of 12 dB for the best case. Magn Reson Med 64:546-553, 2010. (C) 2010 Wiley-Liss, Inc

Acoustic fMRI noise:Linear time-invariant system model

Functional magnetic resonance imaging (fMRI) enables sites of brain activation to be localized in human subjects. For auditory system studies, however, the acoustic noise generated by the scanner tends to interfere with the assessments of this activation. Understanding and modeling fMRI acoustic noise is a useful step to its reduction. To study acoustic noise, the MR scanner is modeled as a linear electroacoustical system generating sound pressure signals proportional to the time derivative of the input gradient currents. The transfer function of one MR scanner is determined for two different input specifications: 1) by using the gradient waveform calculated by the scanner software and 2) by using a recording of the gradient current. Up to 4 kHz, the first method is shown as reliable as the second one, and its use is encouraged when direct measurements of gradient currents are not possible. Additionally, the linear order and average damping properties of the gradient coil system are determined by impulse response analysis. Since fMRI is often based on echo planar imaging (EPI) sequences, a useful validation of the transfer function prediction ability can be obtained by calculating the acoustic output for the EPI sequence. We found a predicted sound pressure level (SPL) for the EPI sequence of 104 dB SPL compared to a measured value of 102 dB SPL. As yet, the predicted EPI pressure waveform shows similarity as well as some differences with the directly measured EPI pressure waveform

Semantic ambiguity processing in sentence context: Evidence from event-related fMRI

Lexical semantic ambiguity is the phenomenon when a word has multiple meanings (e.g. 'bank'). The aim of this event-related functional MRI study was to identify those brain areas, which are involved in contextually driven ambiguity resolution. Ambiguous words were selected which have a most frequent, dominant, and less frequent, subordinate meaning. These words were presented in two types of sentences: (1) a sentence congruent with the dominant interpretation and (2) a sentence congruent with the subordinate interpretation. Sentences without ambiguous words served as a control condition. The ambiguous words always occurred early in the sentences and were biased towards one particular meaning by the final word(s) of the sentence; the event at the end of the sentences was modeled. The results indicate that a bilaterally distributed network supports semantic ambiguity comprehension: left (BA 45/44) and right (BA 47) inferior frontal gyri and left (BA 20/37) and right inferior/ middle temporal gyri (BA 20). The pattern of activation is most consistent with a scenario in which initially a frequency-based probabilistic choice is made between the alternative meanings, and the meaning is updated when this interpretation does not fit into the final disambiguating context. The neural pattern is consistent with the results of other neuroimaging experiments which manipulated various aspects of integrative and context processing task demands. The presence of a bilateral network is also in line with the lesion and divided visual field literature, but contrary to earlier claims, the two hemispheres appear to play similar roles during semantic ambiguity resolution. (c) 2006 Elsevier Inc. All rights reserved

Simultaneous EMG-functional MRI recordings can directly relate hyperkinetic movements to brain activity

OBJECTIVE:: To apply and validate the use of electromyogram (EMG) recorded during functional magnetic resonance imaging (fMRI) in patients with movement disorders, to directly relate involuntary movements to brain activity. METHODS:: Eight "familial cortical myoclonic tremor with epilepsy" (FCMTE) patients, with tremor-like cortical myoclonus and cerebellar Purkinje cell degeneration, and nine healthy controls performed hand posture and movement in an on/off fashion (block design). Superfluous movements were quantified as deviations in EMG power, positive and negative, with respect to the average EMG per session. This measure, "residual EMG" (r-EMG), was derived by Gram-Schmidt orthogonalization. Activation maps resulting from conventional block regressors and novel r-EMG regressors were compared. RESULTS:: In healthy participants, the block posture regressor identified mainly cerebellar activity and some activity in other areas belonging to motor circuitry. In FCMTE patients, no cerebellar activity was seen with the block posture regressor, compatible with cerebellar Purkinje cell changes in FCMTE. EMG power showed little variation during posture in healthy controls. Therefore, the r-EMG regressor was almost constant and revealed no brain activity as expected. In contrast, in FCMTE patients the r-EMG posture regressor was highly variable due to continuous myoclonic jerks. It identified sensorimotor cortical areas, compatible with cortical hyperexcitability in FCMTE patients. CONCLUSION:: Conventional block regressors can be used to identify neuronal circuitry associated with a specific motor task, whereas r-EMG regressors can help identify brain activation directly related to involuntary movements. Simultaneous EMG-fMRI is complementary to conventional fMRI and will facilitate studies of hyperkinetic movement disorders. Hum Brain Mapp 2007. (c) 2007 Wiley-Liss, In