A weighted and directed interareal connectivity matrix for macaque cerebral cortex.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks.

Intramyocellular lipid variations in active older men: relationship with aerobic fitness.

AIMS: Intramyocellular lipid (IMCL) variations in older men are poorly explored. In young adults, IMCL can be influenced by both diet and exercise interventions; this flexibility is related to aerobic fitness. We evaluated in active older adults the influence of maximal aerobic capacity on short-term diet and exercise-induced variations in IMCL stores. METHODS: Intramyocellular lipids were measured by (1) H magnetic resonance spectroscopy ((1) H-MRS) after a 3-day fat depletion-replenishment diet (IMCL(FDR) ) and immediately after a 2-h exercise at 50% VO(2) max (IMCL(FDR) (_) (EX) ). To further explore diet influence, the protocol was repeated after a high-fat diet (HF), with both pre- and post-exercise measurements (IMCL(HF) and IMCL(HF) (_) (EX) ). RESULTS: In active older men (69.8 ± 5.2 years), IMCL(FDR) was lowered by exercise (IMCL(FDR) = 3.45 ± 1.52 vs. IMCL(FDR) (_) (EX) = 2.74 ± 1.15 mmol kg(-1) wet weight, P < 0.05), and exercise-induced variations were correlated to the initial store (P < 0.05, r = -0.72). IMCL(FDR) was linked with aerobic fitness (P < 0.05, r = 0.76), when adjusted by fat mass. IMCL(HF) was lower than IMCL(FDR) (P < 0.05), decreased after exercise (P < 0.05) and varied also as a function of initial store (P < 0.05, r = -0.89), but without link with aerobic fitness. Finally, diet-induced IMCL store variations were positively linked to aerobic fitness (P < 0.05, r = 0.89). CONCLUSION: Variations of the IMCL stores in physically active older adults appear related to aerobic fitness, with similarly fast adaptation to short-term interventions combining diet and exercise as young active adults.

Reliability of longitudinal brain volume loss measurements between 2 sites in patients with multiple sclerosis: comparison of 7 quantification techniques.

BACKGROUND AND PURPOSE: Brain volume loss is currently a MR imaging marker of neurodegeneration in MS. Available quantification algorithms perform either direct (segmentation-based techniques) or indirect (registration-based techniques) measurements. Because there is no reference standard technique, the assessment of their accuracy and reliability remains a difficult goal. Therefore, the purpose of this work was to assess the robustness of 7 different postprocessing algorithms applied to images acquired from different MR imaging systems. MATERIALS AND METHODS: Nine patients with MS were followed longitudinally over 1 year (3 time points) on two 1.5T MR imaging systems. Brain volume change measures were assessed using 7 segmentation algorithms: a segmentation-classification algorithm, FreeSurfer, BBSI, KN-BSI, SIENA, SIENAX, and JI algorithm. RESULTS: Intersite variability showed that segmentation-based techniques and SIENAX provided large and heterogeneous values of brain volume changes. A Bland-Altman analysis showed a mean difference of 1.8%, 0.07%, and 0.79% between the 2 sites, and a wide length agreement interval of 11.66%, 7.92%, and 11.94% for the segmentation-classification algorithm, FreeSurfer, and SIENAX, respectively. In contrast, registration-based algorithms showed better reproducibility, with a low mean difference of 0.45% for BBSI, KN-BSI and JI, and a mean length agreement interval of 1.55%. If SIENA obtained a lower mean difference of 0.12%, its agreement interval of 3.29% was wider. CONCLUSIONS: If brain atrophy estimation remains an open issue, future investigations of the accuracy and reliability of the brain volume quantification algorithms are needed to measure the slow and small brain volume changes occurring in MS.

Diffusion tensor-MRI evidence for extra-axonal neuronal degeneration in caudate and thalamic nuclei of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: MS is an inflammatory demyelinating disease affecting both WM and GM. While WM lesions are easily visualized by conventional MR imaging, the detection of GM alterations remains challenging. This diffusion tensor MR imaging study aimed to detect and characterize diffuse microscopic alterations in 2 deep GM structures, the caudate nucleus and the thalamus, in patients with RR and SP MS. The relationship between diffusivity markers, and atrophy of the caudate and the thalamus, as well as brain lesion load and clinical status of the patients was also explored. MATERIALS AND METHODS: Twenty-three RR and 18 SP patients, along with 27 healthy controls, underwent MR imaging examination including anatomic and DTI acquisitions. Volumes, mean FA, and MD of the caudate and the thalamus, as well as WM lesion volumes, were assessed. RESULTS: FA was significantly (P < .001) increased in the caudate and the thalamus of patients with MS compared with controls, and was higher in SP compared with RR patients. Increased FA was associated with volume decreases of caudate (r = -0.712; P < .001) and thalamus (r = -0.407; P < .01) in patients with MS. WM T2 lesion load was significantly associated with caudate (r = 0.611; P < .001) and thalamic (r = 0.354; P < .05) FA. Caudate FA, and, to a lesser extent, thalamic FA, were associated with functional deficits, as measured by EDSS and MSFC. CONCLUSIONS: Increased FA in the caudate and the thalamus may constitute a sensitive marker of MS pathologic processes, such as loss of dendrites and/or swelling of neuronal cell bodies.

Analysis of Cone-Beam Artifacts in off-Centered Circular CT for Four Reconstruction Methods.

Cone-beam (CB) acquisition is increasingly used for truly three-dimensional X-ray computerized tomography (CT). However, tomographic reconstruction from data collected along a circular trajectory with the popular Feldkamp algorithm is known to produce the so-called CB artifacts. These artifacts result from the incompleteness of the source trajectory and the resulting missing data in the Radon space increasing with the distance to the plane containing the source orbit. In the context of the development of integrated PET/CT microscanners, we introduced a novel off-centered circular CT cone-beam geometry. We proposed a generalized Feldkamp formula (α-FDK) adapted to this geometry, but reconstructions suffer from increased CB artifacts. In this paper, we evaluate and compare four different reconstruction methods for correcting CB artifacts in off-centered geometry. We consider the α-FDK algorithm, the shift-variant FBP method derived from the T-FDK, an FBP method based on the Grangeat formula, and an iterative algebraic method (SART). The results show that the low contrast artifacts can be efficiently corrected by the shift-variant method and the SART method to achieve good quality images at the expense of increased computation time, but the geometrical deformations are still not compensated for by these techniques.

Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study.

BACKGROUND AND PURPOSE: Aging is recognized to originate from a diversity of mechanisms that blur the limits between normal and pathologic processes. The purpose of this study was to determine the early effect of normal aging on the regional distribution of brain metabolite concentrations, including N-acetylaspartate (NAA), a major neuronal marker, choline (Cho), and creatine (Cr). METHODS: Thirty-two healthy participants, ages 21 to 61 years, were examined by proton MR spectroscopic (1H MRS) imaging. 1H MRS imaging acquisitions were performed in two brain locations: the centrum semiovale and the temporal lobe. Thirty voxels were selected in four cerebral regions, cortical, semioval, temporal, and hippocampal, and 1H MR spectra were processed to determine the metabolite ratios. RESULTS: With advancing age of the participants, the ratios of %NAA, NAA:Cho, and NAA:Cr were significantly decreased, whereas the ratios of %Cho and %Cr were significantly increased in the cortical, semioval, and temporal regions. On the basis of the significant metabolic difference determined by cluster analysis, two groups of 16 participants with ages ranging from 21 to 39 years (younger group) and 40 to 61 years (older group) were compared. Repeated measures analysis of variance tests, with multiple comparison procedures between the two age groups and among the four brain region groups, showed significant decreases of the %NAA, NAA:Cho, and NAA:Cr ratios in the semioval and temporal regions of the older group compared with the younger group. When compared with other cerebral regions, %NAA and %Cho ratios were significantly decreased in the hippocampal and cortical regions, respectively. CONCLUSION: These metabolic changes suggest that brain aging is characterized by a reduction in neuronal viability or function associated with an accelerated membrane degradation and/or an increase in glial cell numbers.

A constrained Gauss-Seidel method for correction of point spread function effect in MR spectroscopic imaging.

Magnetic resonance spectroscopic imaging is limited by a low signal-to-noise ratio, so a compromise between spatial resolution and examination time is needed in clinical application. The reconstruction of truncated signal introduces a Point Spread Function that considerably affects the spatial resolution. In order to reduce spatial contamination, three methods, applied after Fourier transform image reconstruction, based on deconvolution or iterative techniques are tested to decrease Point Spread Function contamination. A Gauss-Seidel (GS) algorithm is used for iterative techniques with and without a non-negative constraint (GS+). Convergence and noise dependence studies of the GS algorithm have been done. The linear property of contamination was validated on a point sample phantom. A significant decrease of contamination without broadening the spatial resolution was obtained with GS+ method compared to a conventional apodization. This post-processing method can provide a contrast enhancement of clinical spectroscopic images without changes in acquisition time.

Phosphorus and proton magnetic resonance spectroscopy in episodic ataxia type 2.

Localized phosphorus (31P) and proton (1H) magnetic resonance spectroscopy was performed in the cerebellum and the occipital lobe of 6 patients with episodic ataxia type 2. From use of 31P magnetic resonance spectroscopy, untreated patients showed decreased high-energy phosphate ratios in the cerebrum, and increased pH in the cerebellum and cerebrum, which normalized under acetazolamide. 1H magnetic resonance spectra demonstrated high lactate peaks in 3 of the 6 patients. These metabolic alterations, probably induced by the calcium channelopathy, may characterize episodic ataxia type 2.

A metabolism study of human masseter muscle by 31P magnetic resonance spectroscopy during long periods of exercise and recovery.

The metabolism of the human masseter muscle was investigated using phosphorus (31p) magnetic resonance spectroscopy (MRS) during long periods of exercise and recovery. Eleven subjects aged 19 to 28 yr were examined by 31p MRS during four consecutive periods of 13 min each: rest, exercise, recovery 1 and 2. For each subject, a biting force equal to 20% of maximum voluntary biting force was applied and controlled during the exercise period to produce maximum fatigue. 31p MR spectra were localized from a 24 cm3 volume of interest using an image selected in vivo spectroscopy (ISIS) sequence and a 6 cm diameter surface coil placed on the left masseter. Compared to the resting level, the phosphocreatine (PCr) content decreased by 26% during exercise, while the inorganic phosphate (Pi) concentration increased by 65%. During the two recovery periods, the Pi content remained decreased compared with the resting level by 36% and 30%, respectively. The Pi/PCr ratio was increased from 0.30+/-0.04 at rest to 0.63+/-0.13 during exercise while the adenosine triphosphate (ATP)/Pi ratio was decreased. The pH decreased from 7.02+/-0.03 to 6.93+/-0.04 during exercise and returned to control level (7.09+/-0.08) only during the second recovery period. These results suggest that the masseter muscle is characterized by high ATP turnover and, therefore, high oxidative phosphorylative activity in agreement with its constitution of predominantly fatigue resistant type I fibers.

[Anatomical study with MRI of a small muscle: the masseter]. / Etude anatomique par IRM d'un muscle de petite dimension: le masséter.

Magnetic resonance imaging (MRI) provides functional information in an anatomic presentation allowing to distinguish soft tissues with high sensitivity. The goal of this study was to investigate the normal anatomy of the major masticatory muscle, the masseter, both at rest or during contraction by using three dimensional (3D) MRI. Eighteen subjects aged from 19 to 28 years, all in good health, were studied. Several experiments were first realized on phantoms to test the 3D-MRI technique. After reconstruction and segmentation processing, 3D acquisition, enabled obtaining data on the masseter anatomy. The normal anatomical position of the masseter was reported to the skin plan as the mean internal distance (7.9 +/- 0.42 mm) and external distance (15.2 +/- 0.41 mm). While there was no difference between internal distance, for sex or side, the external distance was significantly (p = 0.02) shorter in male (7.7 +/- 0.5 mm) than in female (8.8 +/- 0.4 mm) for both sides. The mean volume for all subjects and both sides (20.3 +/- 1.1 cm3) did not change significantly between rest and exercise. The masseter volume was significantly (p < 0.00001) greater in male (24.2 +/- 2.0 cm3) than in female (16.4 +/- 3.6 cm3) groups. These physiological references may be useful for further MRI investigations of masticatory system pathologies.

In vivo hippocampal (31)P NMR metabolites in Alzheimer's disease and ageing.

Memory loss is the most common early symptom of Alzheimer's disease (AD). For this study, we chose the hippocampi as regions of interest. The hippocampus, which is closely associated with memory processing, is known to be vulnerable to damage in the early stage of AD. We considered both inter-group (patients vs controls) and intra-group (right vs left hippocampus) comparisons. We examined seven patients meeting the DSM-III-R criteria of senile dementia and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS - ADRDA) criteria of probable AD, and II aged controls. This study focused on the measurement of phosphorus 31 ((31)P) Nuclear Magnetic Resonance (NMR) spectroscopy metabolites in each hippocampus. We found significant differences in phosphorus metabolites for both intra-group comparison (pH shifted towards relative alkalosis in the left hippocampus of patients) and inter-group consideration (reduced phosphodiesters [Pde]and elevated gamma adenosine triphosphate (ATP) in the right hippocampus, higher inorganic phosphate (pHi) in the left hippocampus for patients as compared to controls). We suggest energy failure and membrane functional breakdown in patients compared to aged controls.

Automated detection of the left ventricular region in gated nuclear cardiac imaging.

An approach to automated outlining the left ventricular contour and its bounded area in gated isotopic ventriculography is proposed. Its purpose is to determine the ejection fraction (EF), an important parameter for measuring cardiac function. The method uses a modified version of the fuzzy C-means (MFCM) algorithm and a labeling technique. The MFCM algorithm is applied to the end diastolic (ED) frame and then the (FCM) is applied to the remaining images in a "box" of interest. The MFCM generates a number of fuzzy clusters. Each cluster is a substructure of the heart (left ventricle,...). A cluster validity index to estimate the optimum clusters number present in image data point is used. This index takes account of the homogeneity in each cluster and is connected to the geometrical property of data set. The labeling is only performed to achieve the detection process in the ED frame. Since the left ventricle (LV) cluster has the greatest area of the cardiac images sequence in ED phase, a framing operation is performed to obtain, automatically, the "box" enclosing the LV cluster. THe EF assessed in 50 patients by the proposed method and a semi-automatic one, routinely used, are presented. A good correlation between the two methods EF values is obtained (R = 0.93). The LV contour found has been judged very satisfactory by a team of trained clinicians.

Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites.

We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter. Chronic alcohol consumption was associated with reduced white matter concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) were associated with reduced concentrations of PDE and PCr, compared with both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV interactions were detected, the effects of HIV infection and alcohol abuse were cumulative. This is reflected in a successive decrease of white matter PDE and PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+ light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations were lower in ARC/AIDS alcoholics than in HIV- light/nondrinking individuals. These findings suggest altered brain phospholipid metabolites and energy metabolites with alcohol abuse and HIV infection. They demonstrate that the adverse metabolic effects of HIV on the brain are augmented by chronic alcohol abuse.

Hypoglycemia prevents increase in lactic acidosis during reperfusion after temporary cerebral ischemia in rats.

Sequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N-acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p < or = 0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p = 0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis.

Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities.

A modified ISIS method, for image-selected localized proton magnetic resonance spectroscopy (1H MRS), was used to determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities (WMSH). First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly (P less than 0.05) increased from 0.23 +/- 0.02 (mean +/- SE), 0.20 +/- 0.01, and 0.05 +/- 0.01, respectively in the normal group to 0.39 +/- 0.08, 0.37 +/- 0.05, and 0.48 +/- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +/- 0.02 in the normal group to 0.64 +/- 0.05 in the WMSH group. Third, in normal white matter, the concentration of N-acetyl aspartate, choline, and lactate was estimated to 11.5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM.

Increased pH and inorganic phosphate in temporal seizure foci demonstrated by [31P]MRS.

To investigate alterations of brain metabolism associated with temporal lobe epilepsy, [31P]MRS studies were performed on the anterotemporal lobes of patients with medically refractory complex partial seizures. Interictally, the pH was significantly more alkaline in the temporal lobe ipsilateral to the seizure focus (7.25 vs. 7.08, p less than 0.05), and the inorganic phosphorous concentration was greater on the side of the epileptogenic focus (1.9 vs. 1.1 mM, p less than 0.05). These changes in pH and inorganic phosphate may represent metabolic alterations secondary to seizures. Alternatively, because alkalosis enhances neural excitability and may enhance seizure activity, the increased pH of the seizure focus may provide insight into the pathophysiologic mechanism of epileptic seizures.

Effect of photic stimulation on human visual cortex lactate and phosphates using 1H and 31P magnetic resonance spectroscopy.

Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.

Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging.

Areas of high signal intensity in white matter are identified on brain magnetic resonance (MR) imaging studies in 25%-50% of elderly subjects. The authors used phosphorus-31 MR spectroscopy to characterize the metabolic status of hemispheric white matter brain volumes in 30 elderly subjects with white matter areas of high signal intensity at MR imaging. Compared with white matter volumes with no or minimal areas of high intensity, white matter volumes with extensive areas of high intensity evidenced a 26% decrease in the adenosine triphosphate (ATP)/inorganic phosphate (Pi) ratio (P = .03) and a 21% decrease in the ATP concentration (P = .05), with the Pi level unchanged. A pilot P-31 spectroscopic imaging study in a subject with a large, coalescing white matter area of high signal intensity demonstrated large reductions in metabolite concentrations in the high-signal-intensity area. These results suggest that extensive white matter areas of high signal intensity indicate a process that affects white matter cellular energy metabolism.