Neuroimaging of mitochondrial disease

Mitochondrial disease represents a heterogeneous group of genetic disorders that require a variety of diagnostic tests for proper determination. Neuroimaging may play a significant role in diagnosis. The various modalities of nuclear magnetic resonance imaging (MRI) allow for multiple independent detection procedures that can give important anatomical and metabolic clues for diagnosis. The non-invasive nature of neuroimaging also allows for longitudinal studies. To date, no pathonmonic correlation between specific genetic defect and neuroimaging findings have been described. However, certain neuroimaging results can give important clues that a patient may have a mitochondrial disease. Conventional MRI may show deep gray structural abnormalities or stroke-like lesions that do not respect vascular territories. Chemical techniques such as proton magnetic resonance spectroscopy (MRS) may demonstrate high levels of lactate or succinate. When found, these results are suggestive of a mitochondrial disease. MRI and MRS studies may also show non-specific findings such as delayed myelination or non-specific leukodystrophy picture. However, in the context of other biochemical, structural, and clinical findings, even non-specific findings may support further diagnostic testing for potential mitochondrial disease. Once a diagnosis has been established, these non-invasive tools can also aid in following disease progression and evaluate the effects of therapeutic interventions.     

Brain MR Imaging and Proton MR Spectroscopy in Female Mice with Pyruvate Dehydrogenase Complex Deficiency

Pyruvate dehydrogenase complex (PDC) deficiency is an inborn metabolic disorder that causes neurological abnormalities. In this report, a murine model of PDC deficiency was analyzed using histology, magnetic resonance (MR) imaging and MR spectroscopy (MRS) and the results compared to PDC-deficient female patients. Histological analysis of brains from PDC-deficient mice revealed defects in neuronal cytoarchitecture in grey matter and reduced size of white matter structures. MR results were comparable to previously published clinical MR findings obtained from PDC-deficient female patients. Specifically, a 15.4% increase in relative lactate concentration, 64.4% loss of N-acetylaspartate concentration and a near complete loss of discernable glutamine plus glutamate concentration were observed in a PDC deficient mouse compared to wild-type control. Lower apparent diffusion coefficients (ADCs) were observed within the brain consistent with atrophy. These results demonstrate the usefulness of this murine model to systematically evaluate the beneficial effects of dietary and pharmacological interventions. Special issue dedicated to John P. Blass. Lioudmila Pliss and Richard Mazurchuk are two investigators who contributed equally.     

High-Field Proton Magnetic Resonance Spectroscopy of a Swine Model for Axonal Injury

Abstract: A miniature swine model for diffuse brain injury has recently been developed that replicates the inertial loading conditions associated with rotational acceleration during automotive accidents. The swine model induces diffuse axonal pathology without macroscopic injury such as contusions and hematomas, thus affording a unique opportunity to study axonal injury with noninvasive techniques such as magnetic resonance imaging (MRI) and spectroscopy (MRS). In the present study, we evaluated this diffuse injury model with proton MRS, in vivo, using a high-field (4.0-T) MR scanner, since MRS has been demonstrated as a sensitive probe for detecting neurochemical abnormalities. Our study examined a region of the swine brain at timepoints before and after brain injury. Spectroscopic results indicate that N -acetylaspartate/creatine is diminished by at least 20% in regions of confirmed axonal pathology, whereas conventional MRI did not detect any abnormalities. These findings suggest that MRS has high sensitivity in diagnosing microscopic pathology following diffuse brain injury.     

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.     

Hyperpolarized MRI,functional MRI,MR spectroscopy and CEST to provide metabolic information in vivo

Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.     

Changes in Diffusion Kurtosis Imaging and Magnetic Resonance Spectroscopy in a Direct Cranial Blast Traumatic Brain Injury (dc-bTBI) Model

Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1–14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14–19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS.     

PEGylation of protein-based MRI contrast agents improves relaxivities and biocompatibilities

Magnetic resonance imaging (MRI) has emerged as a leading diagnostic technique in clinical and preclinical settings. However, the application of MRI to assess specific disease markers for diagnosis and monitoring drug effect has been severely hampered by the lack of desired contrast agents with high relaxivities, and optimized in vivo retention time. We have reported the development of protein-based MRI contrast agents (ProCA1) by rational design of Gd^3 + binding sites into a stable protein resulting in significantly increased longitudinal (r₁) and transverse (r₂) relaxivities compared to Gd-DTPA. Here, we report a further improvement of protein contrast agents ProCA1 for in vivo imaging by protein modification with various sizes of polyethylene glycol (PEG) chain. PEGylation results in significant increases of both r₁ and r₂ relaxivities (up to 200%), and these high relaxivities persist even at field strengths up to 9.4 T. In addition, our experimental results demonstrate that modified contrast agents have significant improvement of in vivo MR imaging and biocompatibilities including dose efficiency, protein solubility, blood retention time and decreased immunogenicity. Such improvement can be important to the animal imaging and pre-clinical research at high or ultra-high field where there is an urgent need for molecular imaging probes and optimized contrast agent.     

Magnetic resonance spectroscopy and measurement of tau epitopes of autopsy proven sporadic Creutzfeldt-Jakob disease in a patient with non-specific initial EEG, MRI and negative 14-3-3 immunoblot

Limited potential of electroencephalogram (EEG), magnetic resonance images (MRI) and cerebrospinal fluid (CSF) test for 14-3-3 protein in the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) resulted in developments in diagnostic premortem tehniques. Recent studies provided evidence that magnetic resonance spectroscopy (MRS) and measurement of total-tau (T-tau) and phospho-tau (P-tau) may be useful to identify patients with CJD. We combined detected metabolic changes in the brain by MRS and measured T-tau and tau-pT181 by ELISA, and tau-pT231 by Westernblot in a patient with autopsy proven sCJD. Our results show that in contrast to negative CSF 14-3-3 protein, nonspecific EEG and MRI, MRS revealed metabolic alterations in regions of the brain that has appeared normal on MRI, and tau tests has shown measurable levels of phosphorylated and non-phosphorylated isoforms in CSF. We conclude that rapidly progressive dementia with negative 14-3-3 test and non-specific initial EEG and MRI must still be considered in the differential diagnosis of the sCJD. Combination of serial functional MRI along with MRS study and measurement of tau ratio could improve the early diagnosis of sCJD. The current case is the first attempt to study results of the use of MRS and tau tests in a case of sCJD with diagnostic dilemma.     

Magnetic resonance imaging findings in the brains of rabbits infected with Angiostrongylus cantonensis: a long-term investigation

Because magnetic resonance (MRI) imaging is a superior technique in delineating pathological changes in cerebral angiostrongyliasis, it should also be an optimal imaging modality in monitoring long-term changes in the brains of animals infected with Angiostrongylus cantonensis. In this study, MRI and histological techniques were used to observe the changes in the brains of 7 rabbits infected with the third-stage larvae of A. canronensis. Changes were monitored by MRI from day 0 to day 207 postinfection (PI). Hyperintense lesions on T2-weighted MR brain images were first observed on day 22 PI and hallmarks of abnormalities were noted on day 35 PI. Hyperintensities on brain MR images remained up to day 207 PI. Histological examination from days 108 to 207 PI revealed meningeal congestion, choroid plexus inflammation, infarction, granuloma with embedded larva, gliosis, and hemorrhage in the brain tissues. These findings suggest that hosts infected with A. cantonensis may undergo pathological changes in the brain tissues for more than 200 days PI. Moreover, severe abnormalities may occur as early as the fifth week PI.     

Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging.

Despite striking advances in functional brain imaging, the cellular and molecular mechanisms that underlie the signals detected by these techniques are still largely unknown. The basic physiological principle of functional imaging is represented by the tight coupling existing between neuronal activity and the associated local increase in both blood flow and energy metabolism. Positron emission tomography (PET) signals detect blood flow, oxygen consumption and glucose use associated with neuronal activity; the degree of blood oxygenation is currently thought to contribute to the signal detected with functional magnetic resonance imaging, while magnetic resonance spectroscopy (MRS) identifies the spatio-temporal pattern of the activity-dependent appearance of certain metabolic intermediates such as glucose or lactate. Recent studies, including those of neurotransmitter-regulated metabolic fluxes in purified preparations and analyses of the cellular localization of enzymes and transporters involved in energy metabolism, as well as in vivo microdialysis and MRS approaches have identified the neurotransmitter glutamate and astrocytes, a specific type of glial cell, as pivotal elements in the coupling of synaptic activity with energy metabolism. Astrocytes are ideally positioned to sense increases in synaptic activity and to couple them with energy metabolism. Indeed they possess specialized processes that cover the surface of intraparenchymal capillaries, suggesting that astrocytes may be a likely site of prevalent glucose uptake. Other astrocyte processes are wrapped around synaptic contacts which possess receptors and reuptake sites for neurotransmitters. Glutamate stimulates glucose uptake into astrocytes. This effect is mediated by specific glutamate transporters present on these cells. The activity of these transporters, which is tightly coupled to the synaptic release of glutamate and operates the clearance of glutamate from the extracellular space, is driven by the electrochemical gradient of Na+. This Na(+)-dependent uptake of glutamate into astrocytes triggers a cascade of molecular events involving the Na+/K(+)-ATPase leading to the glycolytic processing of glucose and the release of lactate by astrocytes. The stoichiometry of this process is such that for one glutamate molecule taken up with three Na+ ions, one glucose molecule enters an astrocyte, two ATP molecules are produced through aerobic glycolysis and two lactate molecules are released. Within the astrocyte, one ATP molecule fuels one 'turn of the pump' while the other provides the energy needed to convert glutamate to glutamine by glutamine synthase. Evidence has been accumulated from structural as well as functional studies indicating that, under aerobic conditions, lactate may be the preferred energy substrate of activated neurons. Indeed, in the presence of oxygen, lactate is converted to pyruvate, which can be processed through the tricarboxylic acid cycle and the associated oxidative phosphorylation, to yield 17 ATP molecules per lactate molecule. These data suggest that during activation the brain may transiently resort to aerobic glycolysis occurring in astrocytes, followed by the oxidation of lactate by neurons. The proposed model provides a direct mechanism to couple synaptic activity with glucose use and is consistent with the notion that the signals detected during physiological activation with 18F-deoxyglucose (DG)-PET may reflect predominantly uptake of the tracer into astrocytes. This conclusion does not question the validity of the 2-DG-based techniques, rather it provides a cellular and molecular basis for these functional brain imaging techniques.     

In Vivo NMR Studies of Neurodegenerative Diseases in Transgenic and Rodent Models

In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide unique quality to attain neurochemical, physiological, anatomical, and functional information noninvasively. These techniques have been increasingly applied to biomedical research and clinical usage in diagnosis and prognosis of diseases. The ability of MRS to detect early yet subtle changes of neurochemicals in vivo permits the use of this technology for the study of cerebral metabolism in physiological and pathological conditions. Recent advances in MR technology have further extended its use to assess the etiology and progression of neurodegeneration. This review focuses on the current technical advances and the applications of MRS and MRI in the study of neurodegenerative disease animal models including amyotrophic lateral sclerosis, Alzheimer's, Huntington's, and Parkinson's diseases. Enhanced MR measurable neurochemical parameters in vivo are described in regard to their importance in neurodegenerative disorders and their investigation into the metabolic alterations accompanying the pathogenesis of neurodegeneration.     

Biochemical characterization of breast tumors by in vivo and in vitro magnetic resonance spectroscopy (MRS)

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have evolved as sensitive tools for anatomic and metabolic evaluation of breast cancer. In vivo MRS studies have documented the presence of choline containing compounds (tCho) as a reliable biochemical marker of malignancy and also useful for monitoring the tumor response to therapy. Recent studies on the absolute quantification of tCho are expected to provide cut-off values for discrimination of various breast pathologies. Addition of MRS investigation was also reported to increase the specificity of MRI. Further, ex vivo and in vitro MRS studies of intact tissues and tissue extracts provided several metabolites that were not be detected in vivo and provided insight into underlying biochemistry of the disease processes. In this review, we present briefly the role of various ¹H MRS methods used in breast cancer research and their potential in relation to diagnosis, monitoring of therapeutic response and metabolism.     

In vivo assessment of nodularin-induced hepatotoxicity in the rat using magnetic resonance techniques (MRI, MRS and EPR oximetry)

Acute nodularin-induced hepatotoxicity was assessed in vivo, in rats using magnetic resonance (MR) techniques, including MR imaging (MRI), MR spectroscopy (MRS), and electron paramagnetic resonance (EPR) oximetry. Nodularin is a cyclic hepatotoxin isolated from the cyanobacterium Nodularia spumigena. Three hours following the intraperitoneal (i.p.) administration of nodularin (LD50), a region of 'damage', characterized by an increase in signal intensity, was observed proximal to the porta hepatis (PH) region in T2-weighted MR images of rat liver. Image analysis of these regions of apparent 'damage' indicated a statistically significant increase in signal intensity around the PH region following nodularin administration, in comparison with controls and regions peripheral to the PH region. An increase in signal intensity was also observed proximal to the PH region in water chemical shift selective images (CSSI) of nodularin-treated rat livers, indicating that the increased signal observed by MRI is an oedematous response to the toxin. Microscopic assessment (histology and electron microscopy) and serum liver enzyme function tests (aminotransferase (ALT) and aspartate ALT (AST)) confirmed the nodularin-induced tissue injury observed by MRI. In vivo and in vitro MRS was used to detect alterations in metabolites, such as lipids, Glu+Gln, and choline, during the hepatotoxic response (2-3 h post-exposure). Biochemical assessment of perchloric acid extracts of nodularin-treated rat livers were used to confirm the MRS results. In vivo EPR oximetry was used to monitor decreasing hepatic pO2 (approximately 2-fold from controls) 2-3 h following nodularin exposure. In vivo MR techniques (MRI, MRS and EPR oximetry) are able to highlight effects that may not have been evident in single end point studies, and are ideal methods to follow tissue injury progression in longitudinally, increasing the power of a study through repeated measures, and decreasing the number of animals to perform a similar study using histological or biochemical techniques.     

Application of Magnetic Resonance Spectroscopy in metabolic research

The etiology of metabolic disease in humans is far from understood, and even though potential pathways are identified in animal models and cell studies, it is often difficult to determine their relevance in humans, as the possibilities of tissue sampling are limited. The application of non-invasive imaging techniques can provide essential metabolic information and this mini review focuses on the opportunities of Magnetic Resonance Spectroscopy (MRS) to add to our understanding of the metabolic processes during health and disease. MRS is a volatile technique that can give us information about the concentrations of endogenous metabolites in a completely non-invasive way. In this mini review we discuss the opportunities that MRS is giving us by describing how the investigation of ectopic fat depots has gained a lot of attention and has really taken off after ¹H-MRS for quantification of lipid content became widely available. We furthermore discuss how other MRS techniques, such as ³¹P-MRS and ¹³C-MRS can add valuable information and especially highlight the strength of MRS to be applied dynamically and therefore monitor metabolic changes during physiological challenges such as exercise or meal tests.     

Contrast-Enhanced FLAIR (Fluid-Attenuated Inversion Recovery) for Evaluating Mild Traumatic Brain Injury

Purpose

To evaluate whether adding a contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence to routine magnetic resonance imaging (MRI) can detect additional abnormalities in the brains of symptomatic patients with mild traumatic brain injury.

Materials and Methods

Fifty-four patients with persistent symptoms following mild closed head injury were included in our retrospective study (M∶F = 32∶22, mean age: 59.8±16.4, age range: 26–84 years). All MRI examinations were obtained within 14 days after head trauma (mean: 3.2±4.1 days, range: 0.2–14 days). Two neuroradiologists recorded (1) the presence of traumatic brain lesions on MR images with and without contrast-enhanced FLAIR images and (2) the pattern and location of meningeal enhancement depicted on contrast-enhanced FLAIR images. The number of additional traumatic brain lesions diagnosed with contrast-enhanced FLAIR was recorded. Correlations between meningeal enhancement and clinical findings were also evaluated.

Results

Traumatic brain lesions were detected on routine image sequences in 25 patients. Three additional cases of brain abnormality were detected with the contrast-enhanced FLAIR images. Meningeal enhancement was identified on contrast-enhanced FLAIR images in 9 cases while the other routine image sequences showed no findings of traumatic brain injury. Overall, the additional contrast-enhanced FLAIR images revealed more extensive abnormalities than routine imaging in 37 cases (p<0.001). In multivariate logistic regression analysis, subdural hematoma and posttraumatic loss of consciousness showed a significant association with meningeal enhancement on contrast-enhanced FLAIR images, with odds ratios 13.068 (95% confidence interval 2.037 to 83.852), and 15.487 (95% confidence interval 2.545 to 94.228), respectively.

Conclusion

Meningeal enhancement on contrast-enhanced FLAIR images can help detect traumatic brain lesions as well as additional abnormalities not identified on routine unenhanced MRI. Therefore contrast-enhanced FLAIR MR imaging is recommended when a contrast MR study is indicated in a patient with a symptomatic prior closed mild head injury.     

Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia

A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the "Membrane Hypothesis of Schizophrenia." The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (31P MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. 31P MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying 31P MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia.     

Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

Background and Aim

High tidal volume (V_T) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs.

Methods

Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, V_T 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH₂O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: V_T 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm³, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman''s correlations.

Results

No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups.

Conclusion

Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury.     

^H磁共振波谱在脑胶质瘤的应用进展

磁共振波谱（magnetic resonance spectroscopy,MRS）技术的出现使活体检测组织的代谢和生化信息成为可能,随着其技术的不断成熟,其在临床的应用范围日益扩大。脑胶质瘤具有与正常脑组织不同的代谢特征,借助MRS技术一方面可以反映其代谢特征,另外可将其与正常脑组织区分,因此MRS技术特别是^1H-MRS在脑胶质瘤的诊断、鉴别诊断、分级及预后评估中应用日益广泛。本文就相关进展进行综述。     

The cerebro-morphological fingerprint of a progeroid syndrome: white matter changes correlate with neurological symptoms in xeroderma pigmentosum

Background

Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid syndrome. It has recently been shown that the underlying DNA repair defect plays a central role in the aging process. In addition to skin symptoms, various premature neurological abnormalities have been reported.

Methodology/Principal Findings

We present the clinical neurological phenotype in 14 XP patients (seven subtypes), in seven of these patients together with conventional and multiparametric advanced MRI data to assess the macrostructural and microstructural cerebral morphology in comparison to controls, including volumetric measurements, MR spectroscopy (¹H MRS), and diffusion tensor imaging (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and mild cognitive deficits. DTI demonstrated significantly reduced WM directionality in all regions investigated, i.e. the thalamus, the corticospinal tracts and the dorsal corpus callosum. Single patients showed a marked relative hippocampal volume reduction, but the patients were not different from controls in the volumetric measurements of hippocampal and whole brain volumes at group level. However, ¹H MRS demonstrated that the hippocampal formation was metabolically altered.

Conclusions

The most prominent feature was the white matter affectation, as assessed by DTI, with volume and directionality reductions of the fiber projections involving both the craniocaudal fibers and the interhemispheric connections. These findings, although heterogeneous among the study sample, could be correlated with the clinico-neurological symptoms. The imaging findings support the position that myelin structures degrade prematurely in the brain of XP patients.     

Biofilm shows spatially stratified metabolic responses to contaminant exposure

Biofilms are core to a range of biological processes, including the bioremediation of environmental contaminants. Within a biofilm population, cells with diverse genotypes and phenotypes coexist, suggesting that distinct metabolic pathways may be expressed based on the local environmental conditions in a biofilm. However, metabolic responses to local environmental conditions in a metabolically active biofilm interacting with environmental contaminants have never been quantitatively elucidated. In this study, we monitored the spatiotemporal metabolic responses of metabolically active Shewanella oneidensis MR‐1 biofilms to U(VI) (uranyl, UO₂ ²⁺) and Cr(VI) (chromate, CrO₄ ^2?) using non‐invasive nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) approaches to obtain insights into adaptation in biofilms during biofilm‐contaminant interactions. While overall biomass distribution was not significantly altered upon exposure to U(VI) or Cr(VI), MRI and spatial mapping of the diffusion revealed localized changes in the water diffusion coefficients in the biofilms, suggesting significant contaminant‐induced changes in structural or hydrodynamic properties during bioremediation. Finally, we quantitatively demonstrated that the metabolic responses of biofilms to contaminant exposure are spatially stratified, implying that adaptation in biofilms is custom‐developed based on local microenvironments.