Brain biochemistry and personality: a magnetic resonance spectroscopy study

To investigate the biochemical correlates of normal personality we utilized proton magnetic resonance spectroscopy ((1)H-MRS). Our sample consisted of 60 subjects ranging in age from 18 to 32 (27 females). Personality was assessed with the NEO Five-Factor Inventory (NEO-FFI). We measured brain biochemistry within the precuneus, the cingulate cortex, and underlying white matter. We hypothesized that brain biochemistry within these regions would predict individual differences across major domains of personality functioning. Biochemical models were fit for all personality domains including Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. Our findings involved differing concentrations of Choline (Cho), Creatine (Cre), and N-acetylaspartate (NAA) in regions both within (i.e., posterior cingulate cortex) and white matter underlying (i.e., precuneus) the Default Mode Network (DMN). These results add to an emerging literature regarding personality neuroscience, and implicate biochemical integrity within the default mode network as constraining major personality domains within normal human subjects.     

Molecular aspects of magnetic resonance imaging and spectroscopy

Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.     

Postnatal changes in functional activities of the pig's brain: a combined functional magnetic resonance imaging and immunohistochemical study

Developmental changes in brain activation after pain stimulation and after passive movement of the hind paw were assessed by functional magnetic resonance imaging (fMRI) in pigs of postnatal ages 2, 4 and 6 months. Response patterns were correlated with histological maturation parameters. At 2 months, fMRI failed to detect brain activation after pain stimulation and revealed weak, but widespread activation after passive movement. At 4 months, strong reaction of numerous cortical areas on the contralateral side was seen after pain stimulation. Following passive movement, activation was weaker but more widespread, and the brainstem was also involved. By 6 months, cortical activation became more restricted to the contralateral sensory cortex and brainstem after pain stimulation and to the contralateral sensory and ipsilateral premotor and motor cortices after passive movement. Neocortical synaptophysin immunoreaction increased significantly between 2 and 4 months and slightly decreased by 6 months. The density of GABA-immunoreactive neurons and fibers significantly increased, reaching a maximum at 6 months. Our studies indicate that remodeling of synapses and development of inhibitory GABA neurons last until 6 months postnatally, when the fMRI response of the pig's brain also attains its mature adult pattern.     

Magnetic resonance imaging and magnetic resonance spectroscopy in a patient with amyotrophic lateral sclerosis and frontotemporal dementia

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have been investigated in a single neurodegenerative disease manifesting as either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) alone, but have not been examined in combined disorders such as ALS with FTD (ALS-FTD). To our knowledge, this study is the first attempt to demonstrate relationship between MRI abnormalities and MR spectroscopic metabolite changes of the motor cortex, frontal white matter and corticospinal tract in a patient with the diagnosis of ALS with probable upper motor neuron signs (ALS-PUMNS) and FTD. Patient presented underwent MRI of the brain and MRS. The ratio of N-acetylaspartate (NAA) to creatine (Cr), choline to Cr, myo-inositol (ml) to Cr and glutamate-glutamine (Glx) to Cr were derived from peak area measurement. Spectra from the right motor cortex, frontal white matter and corticospinal tract were obtained. MR images were evaluated for sulcus centralis enlargement, corticospinal tract hyperintensity and frontal lobes atrophy. Spectra showed reduced NAA/Cr and Glx/Cr ratio, yet the ratio of Cho/Cr exhibited significant elevation. MR images revealed sulcus centralis enlargement, high signal intensity of corticospinal tract and atrophy of both frontal lobes. Proton spectroscopic metabolic changes in a current patient fully correlate with previously reported MRS metabolic changes in ALS alone. Surprisingly, normal ml (glial marker) values have been found in almost all measured voxels of interest except in the frontal white matter. These findings differ from the previous findings in ALS or FTD alone. In conclusion, these findings support the concept that ALS, FTD and ALS-FTD may represent different manifestations of a single pathological continuum.     

Three-dimensional reconstruction of brain surface anatomy based on magnetic resonance imaging diffusion-weighted imaging: A new approach

Fifty normal noninfarct patients and 12 cases with infarcts of the cerebrum were examined with routine magnetic resonance imaging and echo-planar diffusion-weighted imaging. The diffusion-weighted three-dimensional images were reconstructed with volume-rendering processing on workstation. Precentral gyrus, post-central gyrus, superior parietal lobule, superior frontal gyrus, precentral sulcus, central sulcus, postcentral sulcus, intraparietal sulcus and superior frontal sulcus were best shown of all structures with an arbitrary score of 2.61–2.77. Supramarginal gyrus, middle frontal gyrus, inferior frontal gyrus and lateral sulcus were clearly shown in the majority of the cerebra with average scores of 2.0–2.49; angular gyrus, inferior frontal sulcus and superior temporal gyrus were not demonstrated satisfactorily and their average scores were 1.67–1.89. Middle temporal gyrus, inferior temporal gyrus, superior temporal sulcus and inferior temporal sulcus were difficult to identify, and thus had average scores of 0.87–1.26. Brain surface structures were better displayed in the older group of individuals than in the younger group. The structures in the 12 cases with acute or chronic cerebrum infarcts were also satisfactorily demonstrated with this new technique.     

Evidence of morphological and functional abnormalities in the hypothalamus of growth-hormone-deficient children: a combined magnetic resonance imaging and endocrine study

Fifty-seven children with growth hormone deficiency and 15 healthy age-matched controls were studied by magnetic resonance imaging (MRI). Of the patients, 36 (63%) had isolated GH deficiency (IGHD) and 21 (37%) multiple pituitary hormone deficiency (MPHD). MRI studies showed a marked reduction in pituitary volume in all patients in comparison with normal controls. Moreover, a striking morphological abnormality with the apparent absence of the pituitary stalk and an ectopic posterior pituitary lobe was detected in 34 of the patients (59%). This pituitary stalk abnormality was detected in 95% of the MPHD patients and in 39% of the IGHD patients. All but one of the patients with a normal pituitary stalk had IGHD. Endocrine evaluation showed no correlation with MRI data: in particular patients with an apparent anatomical interruption of the hypothalamic-pituitary axis showed a variety of patterns of hormonal responses. In conclusion, our study shows a high frequency of hypothalamic-pituitary anomalies in patients with GH deficiency, particularly related with MPHD. However, further studies are needed to improve our understanding of the relationship between MRI and endocrine data.     

Comparative anatomy of rabbit and human achilles tendons with magnetic resonance and ultrasound imaging

We sought to describe the comparative anatomy of the Achilles tendon in rabbits and humans by using macroscopic observation, magnetic resonance imaging, and ultrasonography. The calcaneus-Achilles tendon-gastrocnemius-soleus complexes from 18 New Zealand white rabbits underwent ultrasound (US) and magnetic resonance (MR) imaging and gross anatomic sectioning; these results were compared with those from a cadaveric gastrocnemius-soleus-Achilles tendon-calcaneus specimen from a 68-y-old human male. The medial and lateral gastrocnemius muscle tendons merged 5.2 +/- 0.6 mm proximal to the calcaneal insertion macroscopically, at 93% of their course, different from the gastrocnemius human tendons, which merged at 23% of their overall course. The rabbit flexor digitorum superficialis tendon, corresponding to the flexor digitorum longus tendon in human and comparable in size with the gastrocnemius tendons, was located medial and anterior to the medial gastrocnemius tendon proximally and rotated dorsally and laterally to run posterior to the Achilles tendon-calcaneus insertion. In humans, the flexor digitorum longus tendon tracks posteriorly to the medial malleolus. The soleus muscle and tendon are negligible in the rabbit; these particular comparative anatomic features in the rabbit were confirmed on the MR images. Therefore the rabbit Achilles tendon shows distinctive gross anatomical and MR imaging features that must be considered when using the rabbit as a research model, especially for mechanical testing, or when generalizing results from rabbits to humans.     

Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy

ABSTRACT: Improvements in neuroimaging technologies, and greater access to their use, have generated a plethora of data regarding male/female differences in the developing brain. Examination of these differences may shed light on the pathophysiology of the many illnesses that differ between the sexes and ultimately lead to more effective interventions. In this review, we attempt to synthesize the anatomic magnetic resonance imaging (MRI) literature of male/female brain differences with emphasis on studies encompassing adolescence -- a time of divergence in physical and behavioral characteristics. Across all ages total brain size is consistently reported to be about 10 % larger in males. Structures commonly reported to be different between sexes include the caudate nucleus, amygdala, hippocampus, and cerebellum -- all noted to have a relatively high density of sex steroid receptors. The direction and magnitude of reported brain differences depends on the methodology of data acquisition and analysis, whether and how the subcomponents are adjusted for the total brain volume difference, and the age of the participants in the studies. Longitudinal studies indicate regional cortical gray matter volumes follow inverted U shaped developmental trajectories with peak size occurring one to three years earlier in females. Cortical gray matter differences are modulated by androgen receptor genotyope and by circulating levels of hormones. White matter volumes increase throughout childhood and adolescence in both sexes but more rapidly in adolescent males resulting in an expanding magnitude of sex differences from childhood to adulthood.     

The multisensory attentional consequences of tool use: a functional magnetic resonance imaging study

Background

Tool use in humans requires that multisensory information is integrated across different locations, from objects seen to be distant from the hand, but felt indirectly at the hand via the tool. We tested the hypothesis that using a simple tool to perceive vibrotactile stimuli results in the enhanced processing of visual stimuli presented at the distal, functional part of the tool. Such a finding would be consistent with a shift of spatial attention to the location where the tool is used.

Methodology/Principal Findings

We tested this hypothesis by scanning healthy human participants'' brains using functional magnetic resonance imaging, while they used a simple tool to discriminate between target vibrations, accompanied by congruent or incongruent visual distractors, on the same or opposite side to the tool. The attentional hypothesis was supported: BOLD response in occipital cortex, particularly in the right hemisphere lingual gyrus, varied significantly as a function of tool position, increasing contralaterally, and decreasing ipsilaterally to the tool. Furthermore, these modulations occurred despite the fact that participants were repeatedly instructed to ignore the visual stimuli, to respond only to the vibrotactile stimuli, and to maintain visual fixation centrally. In addition, the magnitude of multisensory (visual-vibrotactile) interactions in participants'' behavioural responses significantly predicted the BOLD response in occipital cortical areas that were also modulated as a function of both visual stimulus position and tool position.

Conclusions/Significance

These results show that using a simple tool to locate and to perceive vibrotactile stimuli is accompanied by a shift of spatial attention to the location where the functional part of the tool is used, resulting in enhanced processing of visual stimuli at that location, and decreased processing at other locations. This was most clearly observed in the right hemisphere lingual gyrus. Such modulations of visual processing may reflect the functional importance of visuospatial information during human tool use.     

Potential of albumin labeled with nitroxides as a contrast agent for magnetic resonance imaging and spectroscopy

The biological and physical properties of albumin and nitroxides make them attractive candidates as special purpose MRI contrast agents which could be used to study the intravascular compartment or specific targets in tissues. In this study, albumin-nitroxide complexes were prepared by reduction and alkylation of the disulfide bonds of the protein and characterized by electron spin resonance and ultraviolet absorption spectroscopy. An average of six nitroxides were bound covalently to each molecule of human serum albumin. The water proton relaxivity of the protein-bound nitroxide (at 20 MHz and 37 degrees C) was 4-fold greater than that of the free nitroxide. The digestion of the nitroxide-albumin complexes by cells or by trypsin decreased the relaxivity of the nitroxide-protein complex. The rate of reduction of albumin-bound nitroxide by cells was much slower than that of the free nitroxide but still was oxygen-sensitive (2-3-fold increase in the rate of reduction in the absence of oxygen).     

Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.     

Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism

Rett syndrome, a neurodevelopmental X-linked disorder, represents the most important genetic cause of severe mental retardation in the female population and results from a mutation in the gene encoding methyl-CpG-binding protein 2 (MECP2). We report here the first characterization of Mecp2-null mice, by in vivo magnetic resonance imaging and spectroscopy, delineating the cerebral phenotype associated with the lack of Mecp2. We performed a morphometric study that revealed a size reduction of the whole brain and of structures involved in cognitive and motor functions (cerebellum and motor cortex). Significant metabolic anomalies, including reduced N-acetylaspartate, myo-inositol, and glutamine plus glutamate, and increased choline levels were evidenced. These findings indicate that not only neuronal but also glial metabolism is affected in Mecp2-null mice. Furthermore, we uncovered an important reduction of brain ATP level, a hitherto undetected anomaly of energy metabolism that may reflect and contribute to cerebral injury and dysfunction.     

Analysis of CHO-K1 cell growth in a fixed bed bioreactor using magnetic resonance spectroscopy and imaging

Non-invasive magnetic resonance imaging and spectroscopy techniques have been used to monitor the growth and distribution of Chinese hamster ovary K1 cells growing in a fixed bed bioreactor composed of macroporous carriers. Diffusion-weighted 1H magnetic resonance spectroscopy was used to monitor the volume fraction of the bioreactor occupied by the cells and diffusion-weighted 1H magnetic resonance imaging was used to map cell distribution. The imaging measurements demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the surface of the carriers. The increase in the volume fraction occupied by the cells during cell growth showed a close correlation with bioreactor ATP content measured using 31P magnetic resonance spectroscopy. These magnetic resonance measurements, in conjunction with measurements of bioreactor glucose consumption, allowed estimation of the specific glucose consumption rate. This declined during the culture, in parallel with medium glucose concentration. This revised version was published online in July 2006 with corrections to the Cover Date.     

A new horizon of DNP technology: application to in-vivo 13C magnetic resonance spectroscopy and imaging

Dynamic nuclear polarization (DNP) is an emerging technique for increasing the sensitivity (>10,000-fold) of magnetic resonance spectroscopy and imaging (MRSI), in particularly for low-γ nuclei. DNP methodology is based on polarizing nuclear spins in an amorphous solid state at low temperature (ca. 1 K) through coupling of the nuclear spins with unpaired electron spins that are added to the sample via an organic free radical. In an amorphous solid state, the high electron spin polarization can be transferred to the nuclear spins by microwave irradiation. While this technique has been utilized in solid-state research for many years, it is only recently that dissolution methods and the required hardware have been developed to produce the high nuclear polarization provided by DNP to produce injectable hyperpolarized solutions suitable for in vivo studies. It has been applied to a number of ¹³C-labeled cell metabolites in biological systems and their real-time metabolic conversion has been imaged. This review focuses briefly on the DNP methodology and the significant molecules investigated to date in preclinical cancer models, in terms of their downstream metabolism in vivo or the biological processes that they can probe. In particular, conversion between hyperpolarized ¹³C-labeled pyruvate and lactate, catalyzed by lactate dehydrogenase, has been shown to have a number of potential applications such as diagnosis, staging tumor grade, and monitoring therapy response. Strategies for making this technique more viable to use in clinical settings have been discussed.     

Functional magnetic resonance imaging: imaging techniques and contrast mechanisms.

Functional magnetic resonance imaging (fMRI) is a widely used technique for generating images or maps of human brain activity. The applications of the technique are widespread in cognitive neuroscience and it is hoped they will eventually extend into clinical practice. The activation signal measured with fMRI is predicated on indirectly measuring changes in the concentration of deoxyhaemoglobin which arise from an increase in blood oxygenation in the vicinity of neuronal firing. The exact mechanisms of this blood oxygenation level dependent (BOLD) contrast are highly complex. The signal measured is dependent on both the underlying physiological events and the imaging physics. BOLD contrast, although sensitive, is not a quantifiable measure of neuronal activity. A number of different imaging techniques and parameters can be used for fMRI, the choice of which depends on the particular requirements of each functional imaging experiment. The high-speed MRI technique, echo-planar imaging provides the basis for most fMRI experiments. The problems inherent to this method and the ways in which these may be overcome are particularly important in the move towards performing functional studies on higher field MRI systems. Future developments in techniques and hardware are also likely to enhance the measurement of brain activity using MRI.     

Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy

Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.     

Ribosome-chloramphenicol interactions: a nuclear magnetic resonance study

Proton magnetic resonance line broadening of chloramphenicol resonances has been employed to study the binding of this inhibitor of protein synthesis to the Escherichia coli 70 S ribosome. Temperature dependence measurements of the resonance line widths show that chloramphenicol is in fast exchange with the ribosome. Differential broadening of the various drug resonances suggests that it binds in its receptor site in essentially the same conformation that exists free in solution. Thus, even though the drug possesses a fair degree of structural flexibility, this is not necessary for its interaction with the ribosome. The recognition is most likely of the classic lock and key type, with the ribosomal site being essentially an open gate for the fitting of the drug. From the proton line-width measurements and ¹⁹F spectra of a derivative, it has been possible to propose a model for the geometry of chloramphenicol when it resides on the ribosome which is consistent with established structure-activity relationships for the drug.     

How doctors generate diagnostic hypotheses: a study of radiological diagnosis with functional magnetic resonance imaging

Background

In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life.

Methodology and Principal Findings

To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI) using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals) embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs) and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14) seconds and 1.23 (SD ±0.13) seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds). The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals.

Conclusions

Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar brain systems.