Effects of whole and refined grains in a weight-loss diet on markers of metabolic syndrome in individuals with increased waist circumference: a randomized controlled-feeding trial.

BACKGROUND: Higher whole-grain (WG) intake is associated with a lower prevalence of metabolic syndrome (MetS); however, there is inconsistent clinical evidence with regard to the benefit of WGs compared with refined grains (RGs) on MetS. OBJECTIVE: We hypothesized that consuming WGs in the place of RGs would improve MetS criteria in individuals with or at risk of MetS. DESIGN: A randomized, controlled, open-label parallel study was conducted in 50 overweight and obese individuals with increased waist circumference and one or more other MetS criteria. Participants consumed a controlled weight-loss diet containing either WG or RG (control) products for 12 wk. Body composition, MetS criteria and related markers, and plasma alkylresorcinols (compliance marker of WG intake) were measured at baseline and at 6 and 12 wk. A subgroup (n = 28) underwent magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue (AT). RESULTS: Baseline variables were not significantly different between groups; however, the RG group tended to have higher triglycerides and lower high-density lipoprotein (HDL) cholesterol (P = 0.06). Alkylresorcinols increased with consumption of the WG diet and did not change with consumption of the RG diet (time × treatment, P < 0.0001), which showed dietary compliance. There were no differences in anthropometric changes between groups; however, weight, body mass index, and percentage of body AT decreased at both 6 and 12 wk (P < 0.05), and reductions in percentage of abdominal AT occurred by 6 wk and did not change between 6 and 12 wk (P = 0.09). Both glucose (P = 0.02) and HDL cholesterol (P = 0.04) were lower with the consumption of the WG compared with the RG diet. However, when noncompliant individuals (n = 3) were removed, the glucose effect was stronger (P = 0.01) and the HDL-cholesterol effect was no longer significant (P = 0.14). CONCLUSIONS: Replacing RGs with WGs within a weight-loss diet does not beneficially affect abdominal AT loss and has modest effects on markers of MetS. WGs appear to be effective at normalizing blood glucose concentrations, especially in those individuals with prediabetes.

Changes in lumbar disk morphology associated with prolonged sitting assessed by magnetic resonance imaging.

OBJECTIVE: To determine what if any changes occur to the lumbar disks in the spine after prolonged sitting with and without intermittent breaks during a 4-hour period. DESIGN: A prospective observational study. SETTING: An academic outpatient clinic. METHODS: The measurement of lumbar disk changes was performed with 12 subjects after an analysis of a mid sagittal lumbar magnetic resonance image, which measured lumbar disk height and disk diameter. Scanning and analysis were done over a 2-day period: day 1 at the start of the work day and 4 hours later after continuous sitting; at the start of work day 2 and after four hours after a change in position and stretching protocol every 15 minutes. RESULTS: For this study, we first evaluated each level of the lumbar spine for any changes after prolonged sitting for 4 hours over the 2 days. Multiple comparisons bias was eliminated by a Bonferroni correction to limit the overall experiment-wise error rate to .05. The comparison was conducted by using a paired t-test when the normality condition was satisfied and by using a Wilcoxon signed rank test when normality was not satisfied. To test for normality, a Shapiro-Wilk test was used. We found that, for disk height, L4-5 was significantly decreased at the end of the sitting for day 1 but not for day 2. There were no significant height changes for the other lumbar disks. In addition, for disk diameter, there were no significant differences present for any of the disks. CONCLUSIONS: Analysis of the data shows that the greatest change in disk height is at the L4-5 level after prolonged sitting without intermittent breaks. The other levels did not show a significant change in their height. The findings also showed that the L4-5 height changes were not significant with brief positional changes every 15 minutes. Fewer changes in disk height may correlate with an improvement in low back pain and disability.

Cholesterol increases ventricular volume in a rabbit model of Alzheimer's disease.

One of the hallmarks of Alzheimer's disease is a significant increase in ventricular volume. To date we and others have shown that a cholesterol-fed rabbit model of Alzheimer's disease displays as many as fourteen different pathological markers of Alzheimer's disease including amyloid-ß accumulation, thioflavin-S staining, blood brain barrier breach, microglia activation, cerebrovasculature changes, and alterations in learning and memory. Using structural magnetic resonance imaging at 3T, we now report that cholesterol-fed rabbits also show a significant increase in ventricular volume following 10 weeks on a diet of 2% cholesterol. The increase in volume is attributable in large part to increases in the size of the third ventricle. These changes are accompanied by significant increases in the number of amyloid-ß immuno-positive cells in the cortex and hippocampus. Increases in the number of amyloid-ß neurons in the cortex also occurred with the addition of 0.24 ppm copper to the drinking water. Together with a list of other pathological markers, the current results add further validity to the value of the cholesterol-fed rabbit as a non-transgenic animal model of Alzheimer's disease.

Neurovascular changes measured by time-of-flight MR angiography in cholesterol-fed rabbits with cortical amyloid beta-peptide accumulation.

PURPOSE: To test the hypothesis that narrowing of cranial blood vessels in cholesterol-fed rabbits is a function of the duration of the high cholesterol diet. Such neurovascular changes, caused by elevated serum cholesterol, are linked to stroke and Alzheimer's disease risk. MATERIALS AND METHODS: Four groups of New Zealand White rabbits were studied. Six were fed a normal diet, 19 were fed a 2% cholesterol diet with 0.12 ppm copper in the drinking water for 8 weeks, 10 weeks, or 12 weeks. Time-of-flight (TOF) MR angiography (MRA) at 3 Tesla was used to measure arterial diameters in 11 vessels. Previously published data for amyloid beta-peptide (Abeta) accumulation in the brains measured postmortem were correlated to vessel diameters. Ventricular volumes of rabbits were measured on group-averaged data. RESULTS: Several vessel diameters decreased with cholesterol diet duration. The posterior communicating arteries showed the largest significant effect. Abeta accumulation was inversely correlated with arterial diameter. Ventricular volumes between the normal diet and 12 weeks cholesterol-fed groups were not significantly different. CONCLUSION: Reduction in vessel diameter of medium-sized vessels but not large vessels was measured in these hypercholesterolemic rabbits. The vessel diameter narrowing and cortical Abeta deposition occurred before measurable ventricular enlargement.

Audiovisual non-verbal dynamic faces elicit converging fMRI and ERP responses.

In an everyday social interaction we automatically integrate another's facial movements and vocalizations, be they linguistic or otherwise. This requires audiovisual integration of a continual barrage of sensory input-a phenomenon previously well-studied with human audiovisual speech, but not with non-verbal vocalizations. Using both fMRI and ERPs, we assessed neural activity to viewing and listening to an animated female face producing non-verbal, human vocalizations (i.e. coughing, sneezing) under audio-only (AUD), visual-only (VIS) and audiovisual (AV) stimulus conditions, alternating with Rest (R). Underadditive effects occurred in regions dominant for sensory processing, which showed AV activation greater than the dominant modality alone. Right posterior temporal and parietal regions showed an AV maximum in which AV activation was greater than either modality alone, but not greater than the sum of the unisensory conditions. Other frontal and parietal regions showed Common-activation in which AV activation was the same as one or both unisensory conditions. ERP data showed an early superadditive effect (AV > AUD + VIS, no rest), mid-range underadditive effects for auditory N140 and face-sensitive N170, and late AV maximum and common-activation effects. Based on convergence between fMRI and ERP data, we propose a mechanism where a multisensory stimulus may be signaled or facilitated as early as 60 ms and facilitated in sensory-specific regions by increasing processing speed (at N170) and efficiency (decreasing amplitude in auditory and face-sensitive cortical activation and ERPs). Finally, higher-order processes are also altered, but in a more complex fashion.

Hippocampal volume change in the Alzheimer Disease Cholesterol-Lowering Treatment trial.

Numerous clinical studies suggest a link between elevated cholesterol and increased risk of Alzheimer disease (AD), and the preponderance of data suggests that statin therapy may reduce the risk of AD later in life. The first clinical investigation of statin therapy in patients with AD, the AD Cholesterol-Lowering Treatment (ADCLT) trial, found that atorvastatin 80 mg/day was associated with improvements relative to placebo on some, but not all, cognitive measures after 6 months and 1 year of therapy. We report here findings from a pilot ADCLT substudy showing a nonsignificant reduction in total hippocampal volume with 1 year of atorvastatin therapy compared with placebo, driven by a highly significant reduction in right hippocampal volume with atorvastatin therapy.

Improvement of vessel visibility in time-of-flight MR angiography of the brain.

PURPOSE: To improve vessel visibility in time-of-flight MR angiography (TOF-MRA) by careful consideration of coil choice, coil position, and frequency offset and profile of the nonspatially selective chemical shift selective (CHESS) presaturation pulse. MATERIALS AND METHODS: The effects of both the CHESS and the excitation radiofrequency (RF) pulses on flow signal and signals from stationary substances were evaluated by changing the spatial area where RF pulses were applied to upstream flow in a flow phantom and in human subjects. The difference between the eight-channel phased-array receive-only coil and the transmit-receive coil was evaluated. RESULTS: The CHESS pulse suppresses the flow signal over a wider frequency range than the signals from stationary substances, especially when using the body coil for transmission. Even without presaturation pulse, the excitation pulse slightly suppressed the flow signal. Adjusting the position of the transmit-receive coil relative to the head improved these TOF-MRA images. The results were better than those obtained with the eight-channel coil. CONCLUSION: The excitation and the nonspatially selective CHESS pulses degraded the flow signal. Our results suggest that reduced spatial extent of RF pulse application to upstream flow can improve image quality of TOF-MRA. This result can be implemented on conventional scanners.

Implementation and validation of localized constant-time correlated spectroscopy (LCT-COSY) on a clinical 3T MRI scanner for investigation of muscle metabolism.

PURPOSE: To implement and evaluate a novel single-volume two-dimensional localized constant-time-based correlated spectroscopy (2D LCT-COSY) sequence on a clinical 3T MR scanner. This sequence exhibits homonuclear decoupling along the F1 dimension, leading to improved spectral resolution compared to that of non-constant-time localized correlated spectroscopy (L-COSY). MATERIALS AND METHODS: A GE 3T MR scanner equipped with a quadrature transmit and receive extremity coil was used in this study. The 2D LCT-COSY sequence was programmed using General Electric's EPIC compiler. Simulations for a two-spin 1/2 system were performed using GAMMA libraries to evaluate the theoretical performance of the sequences, and were also compared with corresponding phantom experiments using trans-cinnamic acid. Finally, spectra were acquired from the soleus muscle of healthy volunteers in order to evaluate performance in vivo. RESULTS: Simulations and experimental results confirmed the improved spectral resolution of LCT-COSY over L-COSY, as well as its homonuclear decoupling performance. The behavior of resonance amplitudes as a function of evolution time in the experiment also was appropriately reflected by the simulation. Corresponding results were obtained for the in vivo muscle spectra, in which separation of overlapping olefinic and allylic methylene protons from the intra- and extramyocellular lipids (IMCL and EMCL, respectively) was achieved. CONCLUSION: Simulations and experimental results in vitro and in vivo demonstrate the strengths of LCT-COSY. This technique can be implemented on systems of any field strength, and has the potential to separate overlapping metabolites in tissue when employed on high-field clinical MRI scanners equipped for proton spectroscopy.

Detection of cerebral metabolites by single-voxel-based PRESS and COSY techniques at 3T.

PURPOSE: To compare point-resolved spectroscopy (PRESS) and localized two-dimensional (2D) correlated spectroscopy (L-COSY) in the detection of cerebral metabolites in humans on a clinical scanner at 3T and to estimate their respective inter- and intrasubject variances. MATERIALS AND METHODS: Measurements were made on nine healthy subjects to assess intersubject variance, and daily on a single subject over a period of seven days to assess intrasubject variance. All L-COSY measurements were performed with a voxel size of 27 mL (3 x 3 x 3 cm(3)) and a measurement time of approximately 34 minutes in the occipitoparietal lobe of the brain. Relative metabolite concentrations were estimated with respect to N-methyl creatine. RESULTS: While the sensitivity of PRESS is twice that of L-COSY, the greater spectral resolution offered by L-COSY resulted in greater consistency in estimates of the concentrations of several cerebral metabolites, as indicated by a superior intraclass correlation and a significantly lower standard deviation (SD) in a matched pair intrasubject analysis. CONCLUSION: Our pilot results demonstrate that L-COSY is an effective approach for resolving cerebral metabolites, and demonstrates a lower coefficient of variance (CV) than the conventional 1D localized spectroscopic approach using LC Model for quantification.

Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager.

Multi-modality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of approximately 14 cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2-m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12-cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with 17 brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.

Investigation of muscle lipid metabolism by localized one- and two-dimensional MRS techniques using a clinical 3T MRI/MRS scanner.

PURPOSE: To demonstrate the feasibility of estimating the relative intra- and extramyocellular lipid (IMCL and EMCL) pool magnitudes and calculating the degree of lipid unsaturation within soleus muscle using single-voxel localized one- and two-dimensional (1D and 2D) MR spectroscopy (MRS). MATERIALS AND METHODS: Localized 1D point resolved spectroscopy (PRESS) and 2D correlation spectroscopy (L-COSY) were performed in identical locations in the soleus muscle of 10 healthy subjects. A GE 3-T MRI/MRS scanner and a quadrature extremity transmit/receive coil was used. RESULTS: The 1D and 2D MR spectra were used to compute IMCL/creatine (Cr) and EMCL/Cr ratios. In addition to cross peaks between the methyl and methylene protons in the high-field region, the 2D spectra showed cross peaks due to J-coupling between allylic, diallylic methylene pro- tons, and olefinic protons. The cross-peak volume ratios also provided a measure of double bonds, suggesting that this ratio can be used to assess unsaturation within IMCL and EMCL lipid pools. CONCLUSION: We have demonstrated the feasibility of detecting 2D cross peaks between different groups of IMCL and EMCL, including the unsaturated protons within these two lipids pools. This protocol may be easily extended to study the lipids present in other tissues.

Simultaneous MRI and PET imaging of a rat brain.

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Anterior medial temporal lobe activation during encoding of words: FMRI methods to optimize sensitivity.

The existence of a rostrocaudal gradient of medial temporal lobe (MTL) activation during memory encoding has historically received support from positron emission tomography studies, but less so from functional MRI (FMRI) studies. More recently, FMRI studies have demonstrated that characteristics of the stimuli can affect the location of activation seen in the MTL when those stimuli are encoded. The current study tested the hypothesis that MTL activation during memory encoding is related to the modality of stimulus presentation. Subjects encoded auditorily or visually presented words in an FMRI novelty paradigm. Imaging and analysis parameters were optimized to minimize susceptibility artifact in the anterior MTL. Greater activation was observed in the anterior than posterior MTL for both modalities of stimulus presentation. The results indicate that anterior MTL activation occurred during encoding, independent of stimulus modality and provide support for the hypothesis that verbal-semantic memory processing occurs in anterior MTL. The authors suggest that technical factors are critical for observing the rostrocaudal gradient in MTL memory activation.

An fMRI investigation of covertly and overtly produced mono- and multisyllabic words.

Studies suggest that the left insula may play an important role in speech motor programming. We used functional magnetic resonance imaging to investigate the role of the left insula in the production of monosyllabic or multisyllabic words during overt and covert speech conditions. The left insula did not show a BOLD response for multisyllabic words (which should require more speech motor programming) that was different from that for monosyllabic words. Left parietal lobe regions showed a greater response for multisyllabic as compared to monosyllabic words. This is consistent with clinical studies showing that left parietal lobe lesions can produce a deficit in speech programming. Despite similarities, covert and overt speech did not demonstrate the same patterns of BOLD response. The BOLD response was greater during overt speech in areas that have been shown to play an important role in speech production including left premotor cortex/BA6, left primary motor cortex, left insula, and left superior temporal gyrus.

Retinotopic organization in children measured with fMRI.

Many measures of visual function reach adult levels by about age 5, but some visual abilities continue to develop throughout adolescence. Little is known about the underlying functional anatomy of visual cortex in human infants or children. We used fMRI to measure the retinotopic organization of visual cortex in 15 children aged 7-12 years. Overall, we obtained adult-like patterns for most children tested. We found that significant head motion accounted for poor quality maps in a few tested children who were excluded from further analysis. When the maps from 10 children were compared with those obtained from 10 adults, the magnitude of retinotopic signals in visual areas V1, V2, V3, V3A, VP, and V4v was essentially the same between children and adults. Furthermore, one measure of intra-area organization, the cortical magnification function, did not significantly differ between adults and children for V1 or V2. However, quantitative analysis of visual area size revealed some significant differences beyond V1. Adults had larger extrastriate areas (V2, V3, VP, and V4v), when measured absolutely or as a proportion of the entire cortical sheet. We found that the extent and laterality of retinotopic signals beyond these classically defined areas, in parietal and lateral occipital cortex, showed some differences between adults and children. These data serve as a useful reference for studies of higher cognitive function in pediatric populations and for studies of children with vision disorders, such as amblyopia.