Single-voxel 1H Magnetic Resonance Research Articles

P6203Intramyocellular lipid saturation as a new metabolic biomarker

Abstract Background Endurance trained athletic healthy volunteers (Athl-HV) and type 2 diabetes patients (T2D) have higher levels of lipids in their skeletal myocytes compared to healthy controls. Despite apparently similar metabolic storage, they are at opposite ends of insulin sensitivity and cardio-metabolic risk. Purpose We investigated if the degree of saturation of the IntraMyoCellular Lipids (IMCL) will differentiate Athl-HV from T2D; and explored if an exercise intervention will induce changes in the IMCL saturation. Methods Male, age matched Athl-HV and T2D were enrolled (n=25/group). Athl-HV had ≥5 years endurance training, T2D were sedentary. Subjects were studied at baseline and after an exercise intervention (4 week deconditioning in Athl-HV and supervised bike training at ≥65% of peakVO2, 5 hours/week x 8 weeks in T2D). All subjects underwent cardio-pulmonary exercise testing (CPET), blood sampling for insulin sensitivity (QUICKI*) and single voxel 1H-magnetic resonance spectroscopy (1H-MRS) of the right vastus lateralis. 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression and analysed in LCModel. We derived fractional lipid mass (fLM) and fractions of saturated (fSL) and unsaturated (fUL) lipids. Data were analysed by t tests, shown as mean±SEM, statistical significance p<0.05. Results CPET and insulin sensitivity are presented in Table 1. T2D had higher fLM in the skeletal muscle compared to Athl-HV, at baseline (p=0.003) and after the exercise intervention (p=0.009), Figure 1A. At baseline, T2D had a different phenotype with a lower fSL and higher fUL compared to Athl-HV (82±3 vs 88±1% and 18±3 vs 12±1%, p=0.02 for both). Whilst deconditioning did not attract any significant changes in either fSL or fUL in Athl-HV (88±1 to 86±1% and 12±1 to 14±1, p=0.2), in contrast, with exercise training T2D significantly increased fSL (82±3 to 88±1%) and decreased their fUL (18±3 to 12±1%) (both p=0.01). Figure 1B and 1C. CPET and insulin sensitivity results Athl-HV Baseline Athl-HV Deconditioning p value T2D Baseline T2D After Training p value VO2 peak, (mL/kg/min) 45.0±0.9† 41.7±0.9‡ <0.0001 23.6±0.6† 30.3±0.6‡ <0.0001 QUICKI* 0.346±0.002† 0.343±0.003‡ 0.2 0.308±0.004† 0.317±0.004‡ 0.02 *QUICKI: Quantitative Insulin Sensitivity Check Index; †Athl-HV vs T2D at baseline p≤0.001, ‡Athl-HV vs T2D after exercise intervention p≤0.001. Figure 1 Conclusion We demonstrate for the first time, in vivo, significant differences in the IMCL amount and saturation between Athl-HV and T2D. IMCL saturation was changed by exercise training in T2D to mirror the phenotype seen in Athl-HV uncovering a new, independent biomarker of improved cardio-metabolic health. Acknowledgement/Funding British Heart Foundation Project Grant no. PG/15/88/31780

Diurnal stability and long-term repeatability of neurometabolites using single voxel 1H magnetic resonance spectroscopy

PurposeThis study was designed to evaluate the diurnal stability and long-term repeatability and reliability of one-dimensional (1D) hydrogen magnetic resonance spectroscopy (1H-MRS) in vitro and in vivo at 3 T. Material and methodA standard brain phantom was used for in vitro study. In vivo diurnal evaluation involved ten healthy subjects, while repeatability study involved six subjects. MRS was acquired from posterior cingulate gyrus (PCG), and processed with LCModel. Diurnal effects were assessed with repeated measures ANOVAs, repeatability was evaluated using coefficient of variation (CV), while reliability was assessed with standard error measurement (SEM) and intra-class correlation coefficient (ICC). ResultsDiurnal metabolic changes in vitro were non-significant. The intra/inter-in vitro CVs for the major metabolites; N-acetylaspartate (NAA), creatine (Cr), myo-inositol (mI), glutamate + glutamine (Glx) and total choline (tCho) were 1−3%/2−6%, respectively. Statistically significant in vivo diurnal effects were only seen for glycerophosphocholine (GPC, +10%, F = 10.6, p = 0.001) and Glx (+6%, F = 5.1, p = 0.018). The intra/inter-subject CVs for the major metabolites ranged from 2−5%/ 5−9%, respectively. The major metabolites displayed ICC ranging from 0.5−0.7 and low SEM (0.001−0.078) reflecting high reliability in detecting neurometabolites. The inter-week interval for in vivo measurements had minimal effect on metabolite ratios (F = 1.4, p = 0.09). ConclusionIn vitro MRS showed no diurnal effects and minimal variation in metabolite levels. Most PCG metabolites are not altered diurnally. The low in vivo variability of metabolite concentration supports the use of localised MRS on clinical 3 T scanners for reliable neurometabolic profiling of the brain.

Evaluation of the Braak staging of brain pathology with 1 H-MRS in patients with Parkinson’s disease

The Braak staging of Parkinson's disease (PD) pathology is usually based on the brain autopsy, which has not been confirmed in living patients of PD. In this study, we investigated the metabolites of medulla oblongata, substantia nigra (SN), putamen, and motor cortex by measuring N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) in 22 patients of PD and 15 age-matched healthy controls, using single-voxel 1H-magnetic resonance spectroscopy (1H-MRS). The results showed that NAA/Cr in SN was lower in PD group than that in control group (p=0.006), however, there was no difference for NAA/Cr and Cho/Cr between PD group and control group in other regions. In SN, NAA/Cr was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) (r=-0.743, p=0.002) and Hoehn-Yahr staging (r=-0.714, p=0.003), while Cho/Cr was positively correlated with UPDRS (r=0.850, p<0.001) and Hoehn-Yahr staging (r=0.647, p=0.009). In PD group, the variance of NAA/Cr in SN was significantly larger than that in other regions (p=0.005), but there was no difference for the variance of Cho/Cr among regions of interesting (ROIs) (p=0.267). These results indicate that SN is the most seriously injured region in PD, and the metabolites in SN measured by 1H-MRS is correlated with the severity of PD. However, the Braak staging of PD pathology is not validated by 1H-MRS.

Higher visceral fat is associated with lower cerebral N-acetyl-aspartate ratios in middle-aged adults.

Excessive adipose tissue, particularly with a central distribution, consists of visceral fat, which is metabolically active and could impinge upon central nervous system functioning. The aim of the current study was to examine levels of visceral adiposity in relation to key cerebral metabolite ratios localized in the occipitoparietal grey matter. Seventy-three adults, aged between 40 and 60years, underwent structural magnetic resonance imaging and single voxel 1H Magnetic Resonance Spectroscopy (1H MRS). Visceral fat was assessed using Dual Energy X Ray Absorptiometry (DXA). Individuals with higher visceral fat mass and volume had significantly lower ratios of N-acetyl-aspartate to total creatine (phosphocreatine+creatine, PCr+Cr) (NAA/PCr+Cr) (β=-0.29, p=0.03, β=-0.28, p=0.04). They also had significantly higher ratios of myo-inositol to total creatine (mI/PCr+Cr ) (β=0.36, p=0.01, β=0.36, p=0.01). Visceral fat mass and volume were not significantly related to ratios of glutamate to total creatine (Glu/PCr+Cr). While future studies are necessary, these results indicate central adiposity is associated with metabolic changes that could impinge upon the central nervous system in middle age.

Application of Single Voxel 1H Magnetic Resonance Spectroscopy in Hepatic Benign and Malignant Lesions

BackgroundTo quantify the metabolite changes in hepatic tumors by single-voxel 1H magnetic resonance spectroscopy (MRS) at 3.0 T and explore the application value of 1HMRS in the diagnosis of hepatic benign and malignant lesions.Material/MethodsA total of 45 patients (55 lesions) diagnosed with hepatic lesions by ultrasound and/or computer topography (CT) from November 2006 to March 2007 were included in this study. All patients underwent 3D-dynamic enhanced scan with liver acquisition with acceleration volume acquisition (LAVA) sequence and single-voxel 1HMRS imaging with PRESS (point-resolved spectroscopy) sequence. The metabolite concentrations such as choline (Cho) and lipids (Lip) were measured.ResultsThere was significant difference regarding the occurrence rate of the obvious elevated Cho peaks between benign and malignant tumors (7/27 vs. 21/28, p=0.000). There was statistical significant differences regarding the Cho/Lip ratios in hepatic benign (0.0686±0.0283, 95% CI: 0.0134–0.1245) and malignant (0.1266±0.1124, 95% CI: 0.0937–0.2203) lesions (p<0.05). When compared with the pathological results, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 85.7% (24/28), 92.6% (25/27), 92.3% (24/26), 86.2% (25/29), and 89.1% (49/55) respectively for the MRI assessment, and 92.6% (26/28), 88.9% (24/27), 89.7 (26/29), 92.3 (24/26), and 90.9% (50/55) respectively for 1HMRS combined with MRI assessment.ConclusionsSingle Cho peaks or Lip peaks cannot be used for the diagnosis of hepatic benign and malignant lesions. Combined use of 1HMRS and MRI can greatly improve the application value of MRI assessment in the diagnosis of hepatic benign and malignant lesions with a higher sensitivity, negative predictive value, and overall accuracy.

Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term.

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis.

Manifold Learning in MR spectroscopy using nonlinear dimensionality reduction and unsupervised clustering.

To investigate whether nonlinear dimensionality reduction improves unsupervised classification of (1) H MRS brain tumor data compared with a linear method. In vivo single-voxel (1) H magnetic resonance spectroscopy (55 patients) and (1) H magnetic resonance spectroscopy imaging (MRSI) (29 patients) data were acquired from histopathologically diagnosed gliomas. Data reduction using Laplacian eigenmaps (LE) or independent component analysis (ICA) was followed by k-means clustering or agglomerative hierarchical clustering (AHC) for unsupervised learning to assess tumor grade and for tissue type segmentation of MRSI data. An accuracy of 93% in classification of glioma grade II and grade IV, with 100% accuracy in distinguishing tumor and normal spectra, was obtained by LE with unsupervised clustering, but not with the combination of k-means and ICA. With (1) H MRSI data, LE provided a more linear distribution of data for cluster analysis and better cluster stability than ICA. LE combined with k-means or AHC provided 91% accuracy for classifying tumor grade and 100% accuracy for identifying normal tissue voxels. Color-coded visualization of normal brain, tumor core, and infiltration regions was achieved with LE combined with AHC. The LE method is promising for unsupervised clustering to separate brain and tumor tissue with automated color-coding for visualization of (1) H MRSI data after cluster analysis.

Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: A 1H magnetic resonance spectroscopy study

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel 1H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system.

Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study

We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.

Brain dynamic neurochemical changes in dystonic patients: A magnetic resonance spectroscopy study

Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Non-invasive diagnosis of lung tuberculosis in children by single voxel 1H-magnetic resonance spectroscopy

Our previous study showed that (1)H-magnetic resonance spectroscopy ((1)H-MRS) can detect lipid peaks characteristic for Mycobacterium tuberculosis infection in cerebral lesions of young children; therefore, we aimed to extend and validate the application of (1)H-MRS for the diagnosis of active pulmonary tuberculosis lesions in three adolescent patients. Here, we document lipid peaks characteristic for M. tuberculosis infection by (1)H-MRS from lung tissue surrounding lung cavities of two patients whose sputum samples were positive for acid-fast bacilli by microscopy and positive for M. tuberculosis by genetic testing, indicating active tuberculosis. A similar lipid peak was found also in the pleural effusion of a third patient with concurrent lung cavity compatible with active tuberculosis. However, in a patient with a pyogenic pulmonary abscess, (1)H-MRS of the drained pus displayed different characteristic peaks but no lipid peak at all. Our findings further validate (1)H-MRS as a rapid, non-invasive, and specific diagnostic tool for active tuberculosis in children with microbiologically documented infection outside the central nervous system, specifically in the lungs.

Metabolic dysfunction and relationship in human frontoparietal cortex in severe traumatic brain injury: Single-voxel 1H magnetic resonance spectroscopy study

(1)H-magnetic resonance spectroscopy revealed that apparently normal (from the data of magnetic resonance imaging) human brain frontoparietal cortex in the subacute stage of traumatic brain injury is characterized by decreased level of N-acetylaspartate (NAA) and increase in levels of myoinositol, choline-containing compounds (Cho), and creatine/phosphocreatine (Cr). Correlations between Cr, Cho, and NAA were established. We propose a scheme of neuronal metabolic processes that joins these substances.

Real‐time dynamic frequency and shim correction for single‐voxel magnetic resonance spectroscopy

Subject motion during brain magnetic resonance spectroscopy acquisitions generally reduces the magnetic field (B₀) homogeneity across the volume of interest or voxel. This is the case even if prospective motion correction ensures that the voxel follows the head. We introduce a novel method for rapidly mapping linear variations in B₀ across a small volume using two-dimensional excitations. The new field mapping technique was integrated into a prospectively motion-corrected single-voxel ¹H magnetic resonance spectroscopy sequence. Interference with the magnetic resonance spectroscopy measurement was negligible, and there was no penalty in scan time. Frequency shifts were also measured continuously, and both frequency and first-order shim corrections were applied in real time. Phantom experiments and in vivo studies demonstrated that the resulting motion- and shim-corrected sequence is able to mitigate line broadening and maintain spectral quality even in the presence of large-amplitude subject motion.

Effect of Cell Therapy on Metabolite Content in Brain Structures of Children with Consequences of Severe Brain Injury: 1H Magnetic Resonance Spectroscopy Study

The effect of intravenous injection of human umbilical cord blood cells on the levels of N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, glutamine and glutamate, and myoinositol in morphologically intact areas of the cortex, white matter, and hippocampus of children with consequences of traumatic brain injury was studied by single voxel 1H magnetic resonance spectroscopy. It was shown that cell therapy increases the content of N-acetylaspartate, a marker of functional integrity of neurons, in the white matter and in the cortex at the boundary between the frontotemporal and parietal lobes and reduces neurological deficit.

Short echo time single voxel 1H magnetic resonance spectroscopy in the diagnosis and characterisation of pineal tumours in children

Magnetic resonance spectroscopy (MRS) has been successful in characterising a range of brain tumours and is a useful aid to non-invasive diagnosis. The pineal region poses considerable surgical challenges and a major surgical resection is not required in the management of all tumours. Improved non-invasive assessment of pineal region tumours would be of considerable benefit. Single voxel MRS (TE 30 ms, TR 1500, 1.5 T) was performed on 15 pineal tumours: 5 germinomas, 1 non-germinomatous secreting germ cell tumour (GCT), 2 teratomas, 5 pineoblastomas, 1 pineal parenchymal tumour (PPT) of intermediate differentiation and 1 pineocytoma. Two germinomas outside the pineal gland were also studied. Metabolite, lipid and macromolecule concentrations were determined with LCModel™. Germ cell tumours had significantly higher lipid and macromolecule concentrations than other tumours (t-test; P < 0.05). The teratomas had significantly lower total choline and creatine levels than germinomas (z test; P < 0.05). Taurine was convincingly detected in germinomas as well as PPTs. Magnetic resonance spectroscopy is useful for characterising pineal region tumours, aiding the non-invasive diagnosis and giving additional biological insight.

495 Clinical and pathological prognostic characteristic of breast cancer patients with brain metastases

A clinical and radiologic diagnosis of acute disseminated encephalomyelitis was made in two children: a 6-month-old female who presented with focal seizures and thalamic and cerebral white matter lesions, and a 4.5-year-old male who presented with tremor and dystonia and had bilateral basal ganglia lesions, without evidence of active brain infection. Serial clinical and laboratory evaluations were supplemented by neuroimaging including routine magnetic resonance imaging and 1H magnetic resonance spectroscopy. They were treated symptomatically, without using steroids or intravenous immunoglobulin, and both children recovered. Single voxel 1H magnetic resonance spectroscopy data were acquired from the involved areas and from normal-appearing white matter. Abnormalities in N-acetyl-aspartate, choline, and lactate peaks were evident during the symptomatic phase, and persistence of low N-acetyl-aspartate was observed during recovery. These spectroscopic findings are consistent with neuropathologic findings of neuronal dysfunction, cellular membrane turnover, cellular infiltration, and metabolic stress in the acute phase, and with neuronal loss in the chronic phase. Gabis LV, Panasci DJ, Andriola MR, Huang W. Acute disseminated encephalomyelitis: An MRI/MRS longitudinal study.

Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by 1H magnetic resonance spectroscopy

Background Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity. Aims and methods Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel 1H magnetic resonance spectroscopy (MRS) at 3 T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified. Results HCL as assessed by 1H MRS linearly correlated ( r = 0.70, p < 0.001) with histological evaluation of liver biopsies and was in agreement with histological steatosis staging in 65% of the patients. Biochemically assessed hepatic triglyceride contents correlated with HCL measured with 1H MRS ( r = 0.63, p < 0.03) and allowed discriminating between none or mild steatosis versus moderate or severe steatosis. Patients infected with hepatitis C virus genotype 3 had a higher prevalence of steatosis (62%) which was not explained by differences in body mass or whole body insulin resistance. When these patients were excluded from correlation analysis, hepatic fat accumulation positively correlated with insulin resistance in the remaining hepatitis C patients (HCL vs. HOMA-IR, r = 0.559, p < 0.020, n = 17). Conclusion Localized 1H MRS is a valid and useful method for quantification of HCL content in patients with chronic hepatitis C and can be easily applied to non-invasively monitoring of steatosis during repeated follow-up measurements in a clinical setting.

Biochemical abnormalities of the medial temporal lobe and medial prefrontal cortex in late-life depression

We utilized single-voxel 1H magnetic resonance spectroscopy (MRS) to investigate biochemical abnormalities related to late-life depression in the medial prefrontal cortex and medial temporal lobe. Fourteen elderly subjects whose depression responded to treatment and 12 nondepressed subjects were enrolled. Subjects were scanned using a GE 3.0 Tesla whole body MR scanner. Metabolite concentrations were quantified using the LC Model software and adjusted for CSF and ratio of gray to white matter. ANCOVA models tested for group differences while controlling for age and sex. Older previously depressed individuals showed significantly reduced concentrations of total N-acetyl aspartate (NAA), choline, and creatine in the prefrontal cortex and significantly elevated left medial temporal lobe concentrations of NAA and myo-inositol. There were no significant group differences in right temporal metabolite concentrations. The prefrontal cortex observations suggest that reduced neuronal, phospolipid, and energy metabolism is present even in clinically improved depression. In contrast, elevated NAA and myo-inositol concentrations in the left medial temporal lobe could be associated with neuronal and glial cell changes in the amygdala.

Magnetic Resonance Imaging of Alzheimer's Pathology in the Brains of Living Transgenic Mice: A New Tool in Alzheimer's Disease Research

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Cardinal pathologic features of AD are amyloid plaques and neurofibrillary tangles, and most in the field believe that the initiating events ultimately leading to clinical AD center on disordered metabolism of amyloid beta protein. Mouse models of AD have been created by inserting one or more human mutations associated with disordered amyloid metabolism and that cause early onset familial AD into the mouse genome. Human-like amyloid plaque formation increases dramatically with age in these transgenic mice. Amyloid reduction in humans is a major therapeutic objective, and AD transgenic mice allow controlled study of this biology. Recent work has shown that amyloid plaques as small as 35 μm can be detected using in vivo magnetic resonance microimaging (MRMI) at high magnetic field (9.4 T). In addition, age-dependent changes in metabolite concentration analogous to those that have been identified in human AD patients can be detected in these transgenic mice using single-voxel 1H magnetic resonance spectroscopy (1H MRS) at high magnetic field. These MR-based techniques provide a new set of tools to the scientific community engaged in studying the biology of AD in transgenic models of the disease. For example, an obvious application is evaluating therapeutic modification of disease progression. Toward the end of this review, the authors include results from a pilot study demonstrating feasibility of using MRMI to detect therapeutic modification of plaque progression in AD transgenic mice.

Preliminary assessment of benign maxillofacial and neck lesions with in vivo single-voxel 1H magnetic resonance spectroscopy

The purpose of this study was to assess the potential roles of in vivo single-voxel hydrogen 1 (1H) magnetic resonance (MR) spectroscopy in differentiation of benign maxillofacial and neck lesions. Fifty-five benign maxillofacial and neck lesions were selected for this study. Both localization techniques for single-voxel 1H MR spectroscopy, long TE (144 ms) point-resolved spectroscopy (PRESS), and short TE (30 ms) stimulated echo acquisition mode (STEAM) were utilized. Choline (Cho) signals were regarded as the criterion to evaluate the differences among the benign lesions. Choline signals were detected in 25 of 55 (45.5%) lesions with PRESS versus 12 of 55 (21.8%) lesions with STEAM (P = .015). On the PRESS, 8 out of 11 (72.7%) neurogenic tumors, 5 of 7 (71.5%) Warthin tumors, and 4 of 5 (80%) sarcoidosis and sinus histiocytosis were detected with Cho signals, whereas 16 of 19 (84.2%) fluid-filled lesions (hemangiomas, lymphangiomas, and cysts) had no Cho signals. Statistically, a significant difference of Cho signals remained between the fluid-filled lesions and the solid lesions (P = .003). In vivo 1H MR spectroscopy might provide information in differentiating fluid-filled lesions from solid lesions in the maxillofacial and neck regions. Most neurogenic tumors, Warthin tumors, sarcoidosis, and sinus histiocytosis were detected with Cho signals.