Sports concussions and aging: a neuroimaging investigation.

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

Neurometabolic and microstructural alterations following a sports-related concussion in female athletes.

BACKGROUND: Sports-related concussions are a major public health concern affecting millions of individuals annually. Neurometabolic and microstructural alterations have been reported in the chronic phase following a concussion in male athletes, while no study has investigated these alterations in female athletes. METHODS: Neurometabolic and microstructural alterations following a concussion were investigated by comparing 10 female athletes with a concussion and 10 control female athletes, using magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI). Athletes with concussion were scanned at least 7 months post-concussion (mean = 18.9 months). RESULTS: MRS revealed a significant lower level of myo-inositol in the hippocampus and the primary motor cortices (M1) bilaterally. DTI analysis using Tract-Based Spatial Statistics (TBSS) showed no difference in fractional anisotropy (FA) while higher level of mean diffusivity (MD) in athletes with concussion was detected in large white matter tracts including the forceps minors, inferior/superior longitudinal fasciculi, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, anterior thalamic radiations and corticospinal tract. Moreover, a region of interest approach for the corpus callosum revealed a significant lower level of FA in the segment containing fibres projecting to M1. CONCLUSIONS: This study demonstrates persistent neurometabolic and microstructural alterations in female athletes suffering a sports-related concussion.

Simultaneous assessment of liver volume and whole liver fat content: a step towards one-stop shop preoperative MRI protocol.

OBJECTIVE: The purpose of this study was to evaluate the ability of a whole liver volume (WLV) segmentation algorithm to measure fat fraction (FF). METHODS: Twenty consecutive patients with histologically proven fatty liver disease underwent dual-echo in-phase/out-of-phase MRI and magnetic resonance spectroscopy (MRS) at 1.5 T. Two readers independently performed semiautomatic 3D liver segmentation on the out-of-phase sequences using an active contour model. FF was calculated for voxels, segments and WLV. Segmentation inter-observer reproducibility was assessed by intra-class correlation coefficient (ICC) for WLV and FF. Fat fraction correlation and agreement as determined by histology, MRS and MRI were determined. RESULTS: ICC was 0.999 (95% CI: 0.999-1, P < 0.001) for WLV FF calculation and 0.996 (95% CI: 0.990-0.998, P < 0.001) for whole liver volume calculations. Strong correlations were found between FF measured by histology, MRS and WLV-MRI. A Bland-Altman analysis showed a good agreement between FF measured by MRS and WLV-MRI. No systematic variations of FF was found between segments when analyzed by ANOVA (F = 1.78, P = 0.096). CONCLUSION: This study shows that a reproducible whole liver volume segmentation method to measure fat fraction can be performed. This strategy may be integrated to a "one-stop shop" protocol in liver surgery planning.

Metabolic changes in concussed American football players during the acute and chronic post-injury phases.

BACKGROUND: Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations. METHODS: The present study investigated the effects of sports concussion on brain metabolism using 1H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years) and education (mean: 16 years) within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI. RESULTS: Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase. CONCLUSIONS: These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.

Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods.

The purpose was to evaluate the ability of three magnetic resonance (MR) techniques to detect liver steatosis and to determine which noninvasive technique (MR, bioassays) or combination of techniques is optimal for the quantification of hepatic fat using histopathology as a reference. Twenty patients with histopathologically proven steatosis and 24 control subjects underwent single-voxel proton MR spectroscopy (MRS; 3 voxels), dual-echo in phase/out of phase MR imaging (DEI) and diffusion-weighted MR imaging (DWI) examinations of the liver. Blood or urine bioassays were also performed for steatosis patients. Both MRS and DEI data allowed to detect steatosis with a high sensitivity (0.95 for MRS; 1 for DEI) and specificity (1 for MRS; 0.875 for DEI) but not DWI. Strong correlations were found between fat fraction (FF) measured by MRS, DEI and histopathology segmentation as well as with low density lipoprotein (LDL) and cholesterol concentrations. A Bland-Altman analysis showed a good agreement between the FF measured by MRS and DEI. Partial correlation analyses failed to improve the correlation with segmentation FF when MRS or DEI data were combined with bioassay results. Therefore, FF from MRS or DEI appear to be the best parameters to both detect steatosis and accurately quantify fat liver noninvasively.

Diffusion-weighted imaging and magnetization transfer imaging of tardive and edentulous orodyskinesia.

Oral dyskinesias occur in elderly individuals in relation to drug use (tardive dyskinesia, TD) or edentulousness (edentulous orodyskinesia, EOD) but their characterization remains incomplete. Our aim was to investigate whether magnetic resonance techniques such as diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) of the brain could be used to differentiate dyskinetic patients from control subjects. Eight drug-treated patients with TD, 12 EOD patients, 8 drug-treated patients without TD, and 10 control subjects were recruited and examined by DWI and MTI. Measurements in the caudate nucleus, putamen, and globus pallidus yielded globally different apparent diffusion coefficient (ADC) values between drug treated patients with TD and control subjects but the magnetization transfer ratios showed no significant variations. The discrimination between dyskinetic patients and control subjects offered by ADC values was however slightly poorer than the discrimination offered by the previously published choline/creatine ratios measured by MR spectroscopy in the basal ganglia. The results are consistent with the pathophysiological hypothesis of damage to cholinergic interneurons.

Quantitative MRS study of Baló's concentric sclerosis lesions.

Baló's concentric sclerosis (BCS) lesions display specific metabolite changes detected by magnetic resonance spectroscopy (MRS). We report on two cases of BCS lesions examined by MRS; the first case was evaluated 36 days after the onset of symptoms, whereas the second case was evaluated 9 days after the onset of symptoms. MRS data were obtained from single voxels located in the lesion and in the contralateral region. Relative to the creatine/phosphocreatine peak, BCS lesions displayed decreases of N-acetyl aspartate and increases of choline, myo-inositol (mI), glutamine/glutamate (Glx), lactate and lipid+macromolecule signals, in agreement with previous reports. In addition, previously unreported decreases of mI (-19% to -29%) and increases of Glx (+55% to +198%) were measured; these could be useful in characterizing BCS lesions.

Cognitive function and cerebral assessment in patients who have Cushing's syndrome.

Cushing's syndrome (CS) is a relevant model to better understand the effects of glucocorticoid (GC) excess on the human brain. The importance of GC excess on the central nervous system is highlighted by the high prevalence of neuropsychiatric disorders such as depression and cognitive impairment in patients who have CS. In addition, there is a high incidence of apparent diffuse loss of brain volume in patients who have CS. Recent studies indicate at least partial reversibility of these abnormalities following correction of hypercortisolism.

(1)H magnetic resonance spectroscopy of autosomal ataxias.

Multiple forms of autosomal ataxia exist which can be identified by genetic testing. Due to their wide variety, the identification of the appropriate genetic test is difficult but could be aided by magnetic resonance data. In this study, magnetic resonance spectroscopy (MRS) and imaging (MRI) data were recorded for 20 ataxia patients of six different types and compared to 20 normal subjects. Spectra were acquired in the pons, left frontal lobe, left basal ganglia, left cerebellar hemisphere and vermis. Both metabolite spectra and absolute metabolite concentrations were determined. Differences in metabolite levels were observed between ataxia patients and control subjects and between ataxia patients of different types. A number of correlations were found between metabolite ratios, atrophy levels, number of repeats on the small and large allele, age at examination, symptoms duration and age at symptoms onset for ataxia patients. These MR characteristics are expected to be useful for the identification of the ataxia type.

Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer disease.

CONTEXT: The staging of Alzheimer disease (AD) dementia could be improved by a neurometabolic analysis using magnetic resonance spectroscopy. OBJECTIVE: To examine the correlation between regional cerebral metabolic alterations measured by proton magnetic resonance spectroscopy and neuropsychological dysfunctions in patients with early AD. DESIGN: A case-control study. SETTING: University hospital neurology clinic and radiology department. PARTICIPANTS: A cohort of 14 patients with mild AD and 14 control subjects paired for age and sex. INTERVENTIONS: Single-voxel proton magnetic resonance spectroscopic brain examination (60 minutes) and a comprehensive battery of psychometric tests (2 hours). MAIN OUTCOME MEASURES: Metabolite ratios relative to unsuppressed water were calculated for magnetic resonance spectroscopic metabolites (N-acetylaspartate, choline, creatine-phosphocreatine, and myo-inositol) in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs), and frontal cortices of both hemispheres. Correlations were examined between metabolic changes in an area and psychometric scores of its known regional function: MTL and verbal memory, PTC and language and visuoconstructional abilities, and frontal cortices and executive functions. RESULTS: A significant reduction of N-acetylaspartate/water (H2O) in the left MTL and of choline/H2O in both MTLs, as well as a significant increase of myo-inositol/H2O in the right PTC were observed. Metabolic alterations in the left MTL were correlated with a loss of verbal memory, in the left PTC with language impairment, and in the right PTC with a loss of visuoconstructional abilities in the group with AD. CONCLUSION: These findings are consistent with regional distribution of neuropathologic changes and cognitive symptoms characterizing early phases of AD, and with the pattern of lateralization of normal brain function.

Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease.

Structures of the medial temporal lobes are recognized to play a central role in memory processing and to be the primary sites of deterioration in Alzheimer disease (AD). Mild cognitive impairment (MCI) represents potentially an intermediate state between normal aging and AD. Proton magnetic resonance spectroscopy (MRS) was used to examine brain metabolic changes in patients with AD and MCI in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs) and prefrontal cortices (PFCs). Fourteen patients with MCI, 14 patients with mild AD and 14 age- and sex-matched control subjects were studied. Patients with AD and MCI demonstrated significant reductions of NAA/H(2)O and Cho/H(2)O in the left MTL relative to control subjects. Patients with AD showed mI/H(2)O increases relative to patients with MCI and control subjects in all six regions investigated, and a statistically significant mI/H(2)O increase was measured in the right PTC. Patients with AD and MCI demonstrated the same metabolic pattern in the left MTL, suggesting a similar pathological process underlying memory impairment. Increased mI signal appears to be a neurochemical abnormality associated mostly with AD and the dementia process. Some interhemispheric metabolite asymmetries were increased in AD patients.

Characterization of ataxias with magnetic resonance imaging and spectroscopy.

A wide variety of autosomal transmitted ataxias exist and their ultimate characterization requires genetic testing. Common clinical characteristics among different ataxia types complicate the choice of the appropriate genetic test. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) generally show cerebellar or cerebral atrophy and perturbed metabolite levels which differ between ataxias. In order to help the clinician accurately identify the ataxia type, reported MRI and MRS data in different brain regions are summarized for more than 60 different types of autosomal inherited and sporadic ataxias.

A follow-up study of neurometabolic alterations in female concussed athletes.

Athletes who sustain a concussion demonstrate a variety of symptoms and neuropsychological alterations that could be brought on by neurometabolic abnormalities. However, no study has yet investigated these aspects in female athletes using magnetic resonance spectroscopy. The present study investigated the neurometabolic and -psychological effects of a concussion in the acute (7-10 days postinjury) and chronic (6 months postinjury) phases after injury. Eleven female concussed athletes and 10 female control athletes were scanned at both time points in a 3T magnetic resonance imaging scanner. Neuropsychological and symptomatic evaluations were completed at each time point. Neuropsychological alterations and a higher severity of symptoms were found in the acute phase in concussed athletes, relative to controls, but showed recovery in the chronic phase. Concussed athletes showed neurometabolic impairment in prefrontal and motor cortices characterized by a pathological increase of glutamine/glutamate and creatine (Cr) only in the chronic phase. Also, a significant decrease in N-acetyl-aspartate/Cr ratio was observed in control athletes at the second time point. Concussed female athletes showed acute cognitive alterations and higher severity of symptoms that do not appear to be underlied by neurometabolic abnormalities, which are only present in the chronic postinjury phase.

Early detection of liver steatosis by magnetic resonance imaging in rats infused with glucose and intralipid solutions and correlation to insulin levels.

OBJECTIVE: Magnetic resonance (MR) techniques allow noninvasive fat quantification. We aimed to investigate the accuracy of MR imaging (MRI), MR spectroscopy (MRS) and histological techniques to detect early-onset liver steatosis in three rat phenotypes assigned to an experimental glucolipotoxic model or a control group. MATERIALS AND METHODS: This study was approved by the institutional committee for the protection of animals. Thirty-two rats (13 young Wistar, 6 old Wistar and 13 diabetic Goto-Kakizaki rats) fed a standard diet were assigned to a 72h intravenous infusion of glucose and Intralipid fat emulsion or a saline infusion. Plasma insulin levels were measured. Steatosis was quantified in ex vivo livers with gradient-recalled multi-echo MRI, MRS and histology as fat fractions (FF). RESULTS: A significant correlation was found between multi-echo MRI-FF and MRS-FF (r=0.81, p<0.01) and a weaker correlation was found between histology and MRS-FF (r=0.60, p<0.01). MRS and MRI accurately distinguished young Wistar and Goto-Kakizaki rats receiving the glucose+Intralipid infusion from those receiving the saline control whereas histology did not. Significant correlations were found between MRI or MRS and insulin plasma level (r=0.63, p<0.01; r=0.57, p<0.01), and between MRI or MRS and C-peptide concentration (r=0.54, p<0.01; r=0.44, p<0.02). CONCLUSIONS: Multi-echo MRI and MRS may be more sensitive to measure early-onset liver steatosis than histology in an experimental glucolipotoxic rat model.

MRS study of the effects of minocycline on markers of neuronal and microglial integrity in ALS.

OBJECTIVE: Magnetic resonance spectroscopy (MRS) allows to monitor brain metabolites noninvasively in amyotrophic lateral sclerosis (ALS). The objective of this study was to use MRS to monitor the effect of minocycline treatment (200 mg/day) over a short period (6 weeks) on the brain metabolites in the precentral gyrus and brainstem in newly diagnosed ALS patients. METHODS: Ten ALS patients (not on riluzole treatment) were recruited and submitted to single-voxel proton MRS longitudinal examinations (1) before minocycline treatment, (2) 3 weeks and (3) 6 weeks after initiation of treatment. RESULTS: Results did not show the expected decrease of N-acetylaspartate/creatine (NAA/Cr) in the precentral gyrus, and an increased NAA/Cr ratio in the brainstem suggested neuronal recovery. The myo-inositol (mI)/Cr ratio was unchanged in the precentral gyrus, but increased in the brainstem, indicating a glial reaction. CONCLUSIONS: MRS results suggest that minocycline treatment could be beneficial in the early stages of ALS.

Neurometabolic changes in the acute phase after sports concussions correlate with symptom severity.

Sports concussion is a major problem that affects thousands of people in North America every year. Despite negative neuroimaging findings, many athletes display neurophysiological alterations and post-concussion symptoms such as headaches and sensitivity to light and noise. It is suspected that neurometabolic changes may underlie these changes. In this study we investigated the effects of sports concussion on brain metabolism using (1)H-MR spectroscopy by comparing a group of 12 non-concussed athletes with a group of 12 concussed athletes of the same age (mean 22.5 years) and education (mean 16 years). All athletes were scanned 1-6 days post-concussion in a 3T Siemens MRI, and were administered a symptom scale to evaluate post-concussion symptomatology. Participants also completed a neuropsychological test battery to assess verbal memory, visual memory, information processing speed, and reaction time, and no group differences were detected relative to controls. Concussed athletes showed a higher number of symptoms than non-concussed athletes, and they also showed a significant decrease in glutamate in the primary motor cortex (M1), as well as significant decreases in N-acetylaspartate in the prefrontal and primary motor cortices. No changes were observed in the hippocampus. Furthermore, the metabolic changes in M1 correlated with self-reported symptom severity despite equivalent neuropsychological performance. These results confirm cortical neurometabolic changes in the acute post-concussion phase, and demonstrate for the first time a correlation between subjective self-reported symptoms and objective physical changes that may be related to increased vulnerability of the concussed brain.

Proton magnetic resonance spectroscopy study of dyskinesia patients.

Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (-13%, P = 0.020) and SOD patients (-12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (-11%, P = 0.079). All other metabolite ratios (N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction.

Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides.

Many neurodegenerative diseases are related to an abnormal expansion of the CAG trinucleotide that produces polyglutamine segments in several proteins. However, the pathogenesis of these neurodegenerative states is not yet well understood. Thus, to evaluate the molecular mechanisms leading to those diseases, suitable research tools such as synthetic polyglutamine peptides are required. The synthesis and purification of such peptides are usually difficult because of poor solubility, which leads to low coupling and/or deblocking reactivity. After exploring many synthesis, solubilization and purification approaches, a protocol allowing the production of polyglutamines in good yield and high purity was developed. With this protocol, peptides of 10-30 glutamine residues were synthesized using a linear solid-phase strategy combined with a maximal side-chain protection scheme using fluorenylmethyloxycarbonyl (Fmoc) chemistry. After cleavage of the peptide from the polymeric support, the crude material was treated with glacial acetic acid and lyophilized. This treatment significantly improved the solubility of the polyglutamine peptides thus allowing their dissolution in aqueous conditions and purification through reverse-phase high performance liquid chromatography. These solubilization and purification conditions led to the formation of N-pyroglutamyl peptide derivatives that were easily isolated. These N-pyroglutamylated compounds also appear as useful research tools because data from the literature suggest that N-terminal modification of polyglutamine segments might play a role in their pathogenic properties.

Comparison of 17beta-estradiol structures from x-ray diffraction and solution NMR.

The NMR-derived structure of estrogen (17beta-estradiol, E2), the drug of choice for postmenopausal women, was compared with a recent literature crystal x-ray structure of Fab-bound E2. 1H and 13C NMR spectra of E2 were acquired in DMSO-d6. Assignments were obtained from an analysis of DQF-COSY, TOCSY, HETCOR, HMQC and HMBC 2D NMR spectra. The 1H and 13C NMR assignments are the first reported for E2 in DMSO-d6. Two solution structures, S1 and S2, were obtained with molecular modeling using NOE constraints. S1 overlaps with the crystal structure for all rings. S2 shows prominent differences in the C-ring (C9--C11--C12--C13) segment, which deviates from a chair conformation, and excellent overlap in the A-, B- and D-rings of E2. The C-ring in S2 adopts a boat conformation as opposed to a chair conformation in the x-ray and S1 structures. The S2 structure is about 6 degrees more twisted than the bound x-ray and S1 models. The S1, S2 and x-ray structures had ring bowing values of 10.1 +/- 0.3, 11 +/- 1 and 10.37 degrees , respectively. Of the 100 solution conformers generated, 83 had S1 conformation and 17 had S2 conformation, with average internal energies of 112 +/- 2 and 141 +/- 2 kcal mol(-1), respectively. The 100 S1- and S2- derived conformers showed a r.m.s.d. of 0.72 A for all atoms. The x-ray, S1 and S2 C18--O17 distances were 2.93, 2.92 +/- 0.01 and 2.93 +/- 0.01 A, respectively, and the O3--O17 distances were 11.06, 11.18 +/- 0.12, and 10.89 +/- 0.05 A, respectively.

Feasibility of magnetic resonance imaging-guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma.

PURPOSE: To evaluate the feasibility of treating breast neoplasms with use of magnetic resonance (MR) imaging-guided focused ultrasound (US) surgery. MATERIALS AND METHODS: Twenty-four female patients, each with a single biopsy-proven breast carcinoma, who were considered to be at increased surgical risk or who had refused surgery underwent MR imaging-guided focused US surgery as an adjunct to their chemotherapeutic regimen of tamoxifen. Follow-up included routine studies to rule out metastatic disease and MR studies with and without contrast material infusion in the treated breast (10 days and 1, 3, and 6 months after the treatment session). Percutaneous biopsy was performed after 6-month follow-up, and if residual tumor was present, a second MR imaging-guided focused US surgery treatment session was performed, followed by repeat biopsy 1 month later. RESULTS: Twenty-three of 24 patients completed the protocol, with only one minor complication associated with the treatment sessions (second-degree skin burn resolved with local treatment). Follow-up MR studies demonstrated a varying hypointense treatment margin (range, 1-11 mm), which represents destruction of tissue beyond the visible tumor. Absence of enhancement may be an indicator of tumor destruction (18 of 19 patients with negative biopsy results) whereas persistent enhancement suggested tumor residue (three of five patients with residual tumor). Overall, 19 of 24 patients (79%) had negative biopsy results after one or two treatment sessions. CONCLUSION: MR imaging-guided focused US surgery of breast tumors is a safe, repeatable, and promising method of focal tumor destruction.