Validating the sensitivity of inhomogeneous magnetization transfer (ihMT) MRI to myelin with fluorescence microscopy.

Inhomogeneous Magnetization Transfer (ihMT) is a development from the MT MRI technique. IhMT can be considered as a dipolar order relaxation time (T1D) weighted imaging modality whose signal has shown an enhanced selectivity for myelin-rich structures. However, a formal validation of the ihMT sensitivity relative to a gold standard myelin density measurement has not yet been reported. To address this need, we compared ihMT MRI with green fluorescence protein (GFP) microscopy, in a study performed on genetically-modified plp-GFP mice, considered as a reference technique for myelin-content assessment. Various ihMT protocols consisting of variable T1D-filtering and radiofrequency power temporal distributions, were used for comparison with fluorescence microscopy. Strong and significant linear relationships (r2 (0.87-0.96), p < 0.0001) were found between GFP and ihMT ratio signals across brain regions for all tested protocol variants. Conventional MT ratios showed weaker correlations (r2 (0.24-0.78), p ≤ 0.02) and a much larger signal fraction unrelated to myelin, hence corresponding to a much lower specificity for myelin. T1D-filtering reduced the ihMT signal fraction not attributed to myelin by almost twofold relative to zero filtering suggesting that at least half of the unrelated signal has a substantially shorter T1D than myelin. Overall, these results strongly support the sensitivity of ihMT to myelin content.

Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T1D ) filtering.

A pulsed inhomogeneous magnetization transfer (ihMT)-prepared fast imaging sequence was implemented at 11.75 T for preclinical studies on mouse central nervous system. A strategy based on filtering the ihMT signal originating from short dipolar relaxation time (T1D ) components is proposed. It involves increasing the repetition time of consecutive radiofrequency (RF) pulses of the dual saturation and allows improved signal specificity for long T1D myelinated structures. Furthermore, frequency offset, power and timing saturation parameters were adjusted to optimize the ihMT sensitivity. The optimization of the ihMT sensitivity, whilst preserving the strong specificity for the long T1D component of myelinated tissues, allowed measurements of ihMT ratios on the order of 4-5% in white matter (WM), 2.5% in gray matter (GM) and 1-1.3% in muscle. This led to high relative ihMT contrasts between myelinated tissues and others (~3-4 between WM and muscle, and ≥2 between GM and muscle). Conversely, higher ihMT ratios (~6-7% in WM) could be obtained using minimal T1D filtering achieved with short saturation pulse repetition time or cosine-modulated pulses for the dual-frequency saturation. This study represents a first stage in the process of validating ihMT as a myelin biomarker by providing optimized ihMT preclinical sequences, directly transposable and applicable to other preclinical magnetic fields and scanners. Finally, ihMT ratios measured in various central nervous system areas are provided for future reference.

Disinfection of human musculoskeletal allografts in tissue banking: a systematic review.

Musculoskeletal allografts are typically disinfected using antibiotics, irradiation or chemical methods but protocols vary significantly between tissue banks. It is likely that different disinfection protocols will not have the same level of microorganism kill; they may also have varying effects on the structural integrity of the tissue, which could lead to significant differences in terms of clinical outcome in recipients. Ideally, a disinfection protocol should achieve the greatest bioburden reduction with the lowest possible impact on tissue integrity. A systematic review of three databases found 68 laboratory and clinical studies that analyzed the microbial bioburden or contamination rates of musculoskeletal allografts. The use of peracetic acid-ethanol or ionizing radiation was found to be most effective for disinfection of tissues. The use of irradiation is the most frequently published method for the terminal sterilization of musculoskeletal allografts; it is widely used and its efficacy is well documented in the literature. However, effective disinfection results were still observed using the BioCleanse™ Tissue Sterilization process, pulsatile lavage with antibiotics, ethylene oxide, and chlorhexidine. The variety of effective methods to reduce contamination rate or bioburden, in conjunction with limited high quality evidence provides little support for the recommendation of a single bioburden reduction method.

Tissue recovery practices and bioburden: a systematic review.

For successful transplantation, allografts should be free of microorganisms that may cause harm to the allograft recipient. Before or during recovery and subsequent processing, tissues can become contaminated. Effective tissue recovery methods, such as minimizing recovery times (<24 h after death) and the number of experienced personnel performing recovery, are examples of factors that can affect the rate of tissue contamination at recovery. Additional factors, such as minimizing the time after asystole to recovery and the total time it takes to perform recovery, the type of recovery site, the efficacy of the skin prep performed immediately prior to recovery of tissue, and certain technical recovery procedures may also result in control of the rate of contamination. Due to the heterogeneity of reported recovery practices and experiences, it cannot be concluded if the use of other barriers and/or hygienic precautions to avoid contamination have had an effect on bioburden detected after tissue recovery. Qualified studies are lacking which indicates a need exists for evidence-based data to support methods that reduce or control bioburden.

Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype.

Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity.

Cox-2 inhibition enhances the activity of sunitinib in human renal cell carcinoma xenografts.

BACKGROUND: Sunitinib (Su), a tyrosine kinase inhibitor of VEGFR, is effective at producing tumour response in clear cell renal cell carcinoma (cRCC), but resistance to therapy is inevitable. As COX-2 is a known mediator of tumour growth, we explored the potential benefit of COX-2 inhibition in combination with VEGFR inhibition in attempts at delaying tumour progression on Su. METHODS: COX-2 expression was compared with areas of hypoxia in tumours that progressed on Su vs untreated tumours. Mice bearing human cRCC xenografts were treated with Su and the COX-2 inhibitor, celecoxib, and the effects on tumour growth were assessed. Sequential vs concurrent regimens were compared. RESULTS: COX-2 expression was increased in cRCC xenografts in areas of tumour hypoxia. The combination of Su and celecoxib achieved longer times to tumour progression compared to treatment with either agent alone or to untreated control animals in four models. This effect was seen with concurrent but not with sequential therapy. CONCLUSION: COX-2 inhibition can extend the effectiveness of VEGFR inhibition. This effect is dependent on the timing of therapy. Clinical trials combining Su and COX-2 inhibitors should be considered as a means delaying time to progression on sunitinib in patients with metastatic cRCC.

Coupling between resting cerebral perfusion and EEG.

While several studies have investigated interactions between the electroencephalography (EEG) and functional magnetic resonance imaging BOLD signal fluctuations, less is known about the associations between EEG oscillations and baseline brain haemodynamics, and few studies have examined the link between EEG power outside the alpha band and baseline perfusion. Here we compare whole-brain arterial spin labelling perfusion MRI and EEG in a group of healthy adults (n = 16, ten females, median age: 27 years, range 21-48) during an eyes closed rest condition. Correlations emerged between perfusion and global average EEG power in low (delta: 2-4 Hz and theta: 4-7 Hz), middle (alpha: 8-13 Hz), and high (beta: 13-30 Hz and gamma: 30-45 Hz) frequency bands in both cortical and sub-cortical regions. The correlations were predominately positive in middle and high-frequency bands, and negative in delta. In addition, central alpha frequency positively correlated with perfusion in a network of brain regions associated with the modulation of attention and preparedness for external input, and central theta frequency correlated negatively with a widespread network of cortical regions. These results indicate that the coupling between average EEG power/frequency and local cerebral blood flow varies in a frequency specific manner. Our results are consistent with longstanding concepts that decreasing EEG frequencies which in general map onto decreasing levels of activation.

Low duty-cycle pulsed irradiation reduces magnetization transfer and increases the inhomogeneous magnetization transfer effect.

Intense off-resonant RF irradiation can lead to saturation of the macromolecular pool magnetization and enhance bound pool dipolar order responsible for the inhomogeneous magnetization transfer (ihMT) effect, but the intensity of RF power in human imaging studies is limited by safety constraints on RF heating. High RF intensities can still be achieved if applied in short pulses with low duty-cycle. Here we investigate the benefits of low duty-cycle irradiation for MT and ihMT studies with both theoretical and experimental methods. Solutions for pulsed irradiation of a two-pool model including dipolar order effects were implemented. Experiments were conducted at 3 T in the brain and through the calf of healthy human subjects. 2D echo planar images were acquired following a preparation of RF irradiation with a 2 s train of 5 ms pulses repeated from between 10 to 100 ms for duty-cycles (DCs) of 50% to 5%, and at varying offset frequencies, and time averaged RF powers. MT and ihMT data were measured in regions of interest within gray matter, white matter and muscle, and fit to the model. RF irradiation effects on signal intensity were reduced at 5% relative to 50% DCs. This reduced RF effect was much larger for single than dual frequency irradiation. 5% DC irradiation reduced single and dual frequency MT ratios but increased ihMT ratios up to 3 fold in brain tissues. Muscle ihMT increased by an even larger factor, depending on the frequency and applied power. The model predicted these changes with duty-cycle. The model fit the data well and constrained model parameters. Low duty-cycle pulsed irradiation reduces MT effects and markedly increases dipolar order effects. This approach is an attractive method to enhance ihMT signal-to-noise ratio and demonstrates a measurable ihMT effect in muscle tissue at 3 T under acceptable specific absorption rates. The effects of duty-cycle changes demonstrated in a separate MT/ihMT preparation provide a route for new applications in magnetization-prepared MRI sequences.

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis.

BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous MR imaging contrast mechanism that has demonstrated high specificity for myelin. Here, we tested the hypothesis that inhomogeneous magnetization transfer is sensitive to pathology in a population of patients with relapsing-remitting MS in a way that both differs from and complements conventional magnetization transfer. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20 healthy volunteers were enrolled in a prospective MR imaging research study, whose protocol included anatomic imaging, standard magnetization transfer, and inhomogeneous magnetization transfer imaging. Magnetization transfer and inhomogeneous magnetization transfer ratios measured in normal-appearing brain tissue and in MS lesions of patients were compared with values measured in control subjects. The potential association of inhomogeneous magnetization transfer ratio variations with the clinical scores (Expanded Disability Status Scale) of patients was further evaluated. RESULTS: The magnetization transfer ratio and inhomogeneous magnetization transfer ratio measured in the thalami and frontal, occipital, and temporal WM of patients with MS were lower compared with those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio measured in lesions was lower than that in normal-appearing WM (P < .05). Significant (P < .05) negative correlations were found between the clinical scores and inhomogeneous magnetization transfer ratio measured in normal-appearing WM structures. Weaker nonsignificant correlation trends were found for the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the inhomogeneous magnetization transfer technique for MS was highlighted by the reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in normal-appearing WM of patients compared with controls. Stronger correlations with the Expanded Disability Status Scale score were obtained with the inhomogeneous magnetization transfer ratio compared with the standard magnetization transfer ratio, which may be explained by the higher specificity of inhomogeneous magnetization transfer for myelin.

Sleep-dependent motor memory plasticity in the human brain.

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules.

Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f≠1. From such fits, estimated T1Ds of mice in the white matter, (34±14) ms, were much longer than in muscle, T1D=(1±1) ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.

Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow.

Herein, we present a theoretical framework and experimental methods to more accurately account for transit effects in quantitative human perfusion imaging using endogenous magnetic resonance imaging (MRI) contrast. The theoretical transit time sensitivities of both continuous and pulsed inversion spin tagging experiments are demonstrated. We propose introducing a delay following continuous labeling, and demonstrate theoretically that introduction of a delay dramatically reduces the transit time sensitivity of perfusion imaging. The effects of magnetization transfer saturation on this modified continuous labeling experiment are also derived, and the assumption that the perfusion signal resides entirely within tissue rather than the arterial microvasculature is examined. We present results demonstrating the implementation of the continuous tagging experiment with delay on an echoplanar scanner for measuring cerebral blood flow (CBF) in normal volunteers. By varying the delay, we estimate transit times in the arterial system, values that are necessary for assessing the accuracy of our quantification. The effect of uncertainties in the transit time from the tagging plane to the arterial microvasculature and the transit time to the tissue itself on the accuracy of perfusion quantification is discussed and found to be small in gray matter but still potentially significant in white matter. A novel method for measuring T1, which is fast, insensitive to contamination by cerebrospinal fluid, and compatible with the application of magnetization transfer saturation, is also presented. The methods are combined to produce quantitative maps of resting and hypercarbic CBF.

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Noninvasive MRI evaluation of cerebral blood flow in cerebrovascular disease.

Previous studies have demonstrated that cerebral blood flow (CBF) can be assessed noninvasively by MRI using magnetic labeling of arterial water as a diffusible flow tracer. The purpose of this study was to assess the quality of CBF images obtained from patients with cerebrovascular disease using this method, and to begin to evaluate the potential clinical role for this technique. We recruited 14 patients who presented with stroke, TIA, or severe carotid stenosis and were likely to have altered CBF based on clinical assessment. In many of these patients, CBF imaging disclosed both focal and hemispheric hypoperfusion, either in vascular territories or in watershed regions. In 11 patients with significant proximal arterial stenosis, hemispheric CBF abnormalities localized to the side of most significant stenosis for the anterior circulation distribution. In several patients watershed hypoperfusion was even more pronounced. Our results suggest that good-quality MR CBF images can be obtained reliably from patients with cerebrovascular disease. CBF imaging can be combined with standard structural imaging within a single MRI examination, and provides clinically meaningful information. The capability of measuring CBF easily provides a potentially useful tool for clinical assessment and further investigation of stroke pathophysiology.

A functional MRI study of mental image generation.

The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left.

Detection of acute pathologic changes following experimental traumatic brain injury using diffusion-weighted magnetic resonance imaging.

Standard magnetic resonance imaging (MRI) has been shown to be remarkably insensitive to acute changes following traumatic brain injury. Because diffusion-weighted MRI has recently demonstrated excellent sensitivity to acute ischemic injury and other CNS abnormalities, we evaluated the use of diffusion MRI for the detection of pathologic changes in the rat brain during the first hours following parasagittal fluid percussion brain injury. Diffusion MRI was able to demonstrate a significant diffusion decrease in the primary cortical contusion injury and a comparable decrease in the ipsilateral thalamus. Tissue damage in the thalamus region is much weaker than in the cortex, but the thalamus is a primary site of axonal and dendritic injury in this model. T2 imaging in the same subjects showed slight enhancement in the neighborhood of the injured cortex but was unable to demonstrate injury elsewhere. Diffusion imaging was superior to T2 at demonstrating injury and the prominent diffusion decrease in the thalamus suggests that diffusion MRI is preferentially sensitive to axonal or dendritic injury.

New magnetic resonance imaging techniques for the evaluation of traumatic brain injury.

Although current computerized tomography (CT) and magnetic resonance imaging (MRI) techniques have shown great utility in diagnosing various aspects traumatic brain injury, damage resulting from mild diffuse brain injury often goes undetected with these procedures. Newly developed MRI techniques, including magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI), have been proposed to have enhanced sensitivities for identifying damage induced by both diffuse and focal brain injury. Results from recent initial studies with experimental models of brain injury suggest that MTI may be useful for evaluating diffuse white matter damage, while DWI may demonstrate regions of focal contusion more acutely and with greater accuracy than conventional MRI procedures.

The interactive effects of feeding and exercise on oxygen consumption, swimming performance and protein usage in juvenile rainbow trout (Oncorhynchus mykiss)

The impacts of feeding on the rate of O2 consumption (O2), aerobic swimming performance, nitrogenous waste excretion (ammonia-N and urea-N) and protein utilization as an aerobic fuel were investigated in juvenile rainbow trout. Feeding trout to satiation (in groups of 120) resulted in rapid growth and elevated routine O2 by 68% relative to fasted fish and by 30% relative to trout fed a maintenance ration of 1% of body mass daily. This in-tank O2 of satiation-fed trout was approximately 70% of the O2max observed at the critical swimming speed (UCrit) when trials were performed on individual trout in swimming respirometers. Feeding increased O2 at all swimming speeds; the absolute elevation (specific dynamic action or SDA effect) was dependent on ration but independent of swimming velocity. There was no difference in O2max at UCrit amongst different ration treatments, but UCrit was significantly reduced by 15% in satiation-fed fish relative to fasted fish. These results suggest that the irreducible SDA load reduces swimming performance and that O2max is limited by the capacity to take up O2 at the gills and/or to deliver O2 through the circulatory system rather than by the capacity to consume O2 at the tissues. Ammonia-N and urea-N excretion increased with protein intake, resulting in a 6.5-fold elevation in absolute protein use and a fourfold elevation in percentage use of protein as an aerobic fuel for routine metabolism in satiation-fed trout (50-70%) relative to fasted fish (15%). Urea-N excretion increased greatly with swimming speed in all treatments, but remained a minor component of overall nitrogen excretion. However, even in satiation-fed fish, ammonia-N excretion remained constant as swimming speed increased, and protein did not become more important as a fuel source during exercise. These results suggest that the reliance on protein as a fuel is greatly dependent on feeding quantity (protein intake) and that protein is not a primary fuel for exercise as suggested by some previous studies.

A respirometric analysis of fuel use during aerobic swimming at different temperatures in rainbow trout (Oncorhynchus mykiss)

Instantaneous fuel usage at 5 degreesC or 15 degreesC was assessed by measurement of rates of O2 consumption (O2), CO2 excretion (CO2) and nitrogenous waste excretion (nitrogen =ammonia-N + urea-N) in juvenile rainbow trout (Oncorhynchus mykiss) at rest and during swimming at 45 % and 75 % of aerobic capacity (Ucrit). After 2 weeks of training at approximately 1 body length s-1 (BL s-1), critical swimming speeds (approximately 3.0 BL s-1) and whole-body energy stores (total protein, lipids and carbohydrates) were identical in fish acclimated to 5 degreesC or 15 degreesC. O2 and CO2 increased with swimming speed at both temperatures and were higher at 15 degreesC than at 5 degreesC at all speeds, but the overall Q10 values (1.23-1.48) were low in these long-term (6 weeks) acclimated fish. The respiratory quotient (CO2/O2, approximately 0.85) was independent of both temperature and swimming speed. In contrast to O2 and CO2, the rate of ammonia excretion was independent of swimming speed, but more strongly influenced by temperature (Q10 1. 4-2.8). Urea excretion accounted for 15-20 % of nitrogen, was unaffected by swimming speed and showed a tendency (P<0.07) to be positively influenced by temperature at one speed only (45 % Ucrit). Nitrogen quotients (NQ nitrogen/O2) were generally higher in warm-acclimated fish, remaining independent of swimming speed at 15 degreesC (0.08), but decreased from about 0.08 at rest to 0.04 during swimming at 5 degreesC. Instantaneous aerobic fuel use calculations based on standard respirometric theory showed that both acclimation temperature and swimming speed markedly influenced the relative and absolute use of carbohydrates, lipids and proteins by trout. At rest, cold-acclimated trout used similar proportions of carbohydrates and lipids and only 27 % protein. During swimming, protein use decreased to 15 % at both speeds while the relative contributions of both lipid and carbohydrate increased (to more than 40 %). On an absolute basis, carbohydrate was the most important fuel for fish swimming at 5 degreesC. In contrast, resting fish acclimated to 15 degreesC utilized 55 % lipid, 30 % protein and only 15 % carbohydrate. However, as swimming speed increased, the relative contribution of carbohydrate increased to 25 %, while the protein contribution remained unchanged at approximately 30 %, and lipid use decreased slightly (to 45 %). On an absolute basis, lipid remained the most important fuel in fish swimming at 15 degreesC. These results support the concept that lipids are a major fuel of aerobic exercise in fish, but demonstrate that the contribution of protein oxidation is much smaller than commonly believed, while that of carbohydrate oxidation is much larger, especially at higher swimming speeds and colder temperature.

Mapping of secondary somatosensory cortex activation induced by vibrational stimulation: an fMRI study.

Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a vibratory stimulus applied to the pad of the first finger of the left hand. The data was normalized to a standard atlas, and individual and group statistical parametric maps were computed. Robust bilateral activation was demonstrated in the secondary somatosensory cortex (SII), indicating a bilateral representation of SII in humans. Greater maxima and activation volumes were achieved in contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay for probing the nature and function of SII in vivo.