Brainstem proton magnetic resonance spectroscopy in idopathic REM sleep behavior disorder

STUDY OBJECTIVES: Rapid-eye-movement (REM) sleep behavior disorder (RBD) is thought to result from a dysfunction of the brainstem structures that regulate physiologic REM sleep muscle atonia. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive method that allows detection of in vivo neuronal dysfunction in localized brain areas. The aim of our study was to investigate whether 1H-MRS can detect brainstem abnormalities in patients with idiopathic RBD. DESIGN: 1H-MRS centered on the midbrain and the pontine tegmentum was acquired in 15 patients with idiopathic RBD and 15 control subjects matched for age and sex. SETTING: University hospital sleep laboratory center. PARTICIPANTS: Fifteen untreated patients with chronic RBD diagnosed by history and video-polysomnography, normal neurologic examination, and normal cranial MRI. Fifteen healthy controls with no sleep complaints and normal polysomnography and brain MRI. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The metabolic peaks detectable with 1H-MRS, N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), choline-containing compounds (Cho) and myoinositol (mI), and the ratios of NAA, Cho and ml to Cr were evaluated both in the midbrain and pontine tegmentum. No significant differences in N-acetylaspartate/creatine, choline/creatine and myoinosito/creatine ratios were found between patients and controls. CONCLUSIONS: The results do not suggest that marked mesopontine neuronal loss or 1H-MRS detectable metabolic disturbances occur in idiopathic RBD.     

Magnetic resonance imaging using hemagglutinating virus of Japan-envelope vector successfully detects localization of intra-cardially administered microglia in normal mouse brain

Although the therapeutic use of microglia has received some attention for the treatment of brain diseases, few non-invasive techniques exist for monitoring the cells after administration. Here, we present a technique using magnetic resonance imaging (MRI) to track microglia injected intra-cardially. We labeled microglia expressing enhanced green fluorescent protein with superparamagnetic iron oxide (Resovist) using the hemagglutinating virus of Japan-envelope vector. We injected labeled microglia into the left ventricle of the heart of mice. After monitoring exogenously administered microglia in the mouse brain in vivo using T(2)*-weighted MRI at a magnetic field of 7T, we compared the MR images with histochemical localization of exogenous microglia in vitro. MRI revealed clear signal changes attributable to Resovist-containing microglia in the mouse brain. Histochemistry demonstrated the presence of exogenous microglia in the brain at the same locations shown by MRI. This study demonstrates the usefulness of MRI for non-invasive monitoring of exogenous microglia, and suggests a promising future for microglia/macrophages as therapeutic tools for brain disease.     

Magnetic resonance spectroscopy of the brain under mild hypothermia indicates changes in neuroprotection-related metabolites

Brain hypothermia has demonstrated pronounced neuroprotective effect in patients with cardiac arrest, ischemia and acute liver failure. However, its underlying neuroprotective mechanisms remain to be elucidated in order to improve therapeutic outcomes. Single voxel proton magnetic resonance spectroscopy (¹H-MRS) was performed using a 7 Tesla MRI scanner on normal Sprague–Dawley rats (N = 8) in the same voxel under normothermia (36.5 °C) and 30 min mild hypothermia (33.5 °C). Levels of various brain proton metabolites were compared. The level of lactate (Lac) and myo-inositol (mI) increased in the cortex during hypothermia. In the thalamus, taurine (Tau), a cryogen in brain, increased and choline (Cho) decreased. These metabolic alterations indicated the onset of a number of neuroprotective processes that include attenuation of energy metabolism, excitotoxic pathways, brain osmolytes and thermoregulation, thus protecting neuronal cells from damage. These experimental findings demonstrated that ¹H-MRS can be applied to investigate the changes of specific metabolites and corresponding neuroprotection mechanisms in vivo noninvasively, and ultimately improve our basic understanding of hypothermia and ability to optimize its therapeutic efficacy.     

非人灵长类动物超高场磁共振脑成像技术进展

非人类灵长类动物是神经科学研究中的重要动物模型,可以兼容多种侵入式和非侵入式神经信号探测和神经活动调控方法.结合侵入式和非侵入式方法的非人灵长类动物的神经科学研究,有助于将大量基于动物模型的基础研究成果进行临床转化.其中磁共振脑成像技术是目前最主要的非侵入式大脑神经信号探测手段.非人灵长类动物磁共振脑成像研究,对于深入...     

Seizures are associated with brain injury severity in a neonatal model of hypoxia–ischemia

Hypoxia–ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O₂) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), ¹H-MR spectroscopy (¹H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in ¹H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals; this difference was not apparent on MRI or ¹H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.     

Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease

Maple syrup urine disease (MSUD) is associated with increased branched-chain amino acids (BCAA), their keto acids (BCKA), and acute or chronic encephalopathy. Aim of treatment is to reduce BCAA and BCKA to prevent or minimize brain dysfunction. We investigated 14 juvenile and adult patients with MSUD by means of cerebral magnetic resonance imaging (MRI) and correlated MRI changes to biochemical control measured as median plasma BCAA concentrations over 6-36 months prior to investigation. Abnormalities consisted of an increased signal in the white matter on T2-weighted images which is compatible with a disturbed water content of the white matter and dysmyelination. Areas affected most commonly were mesencephalon, brain stem, thalamus and globus pallidus; supratentorial lesions seem to be restricted to severe cases. No patient with white matter changes had acute neurological/encephalopathic symptoms indicating that the severity of dysmyelination does not correlate to acute neurotoxicity.     

New evidence from magnetic resonance imaging of brain changes after climbs at extreme altitude

The aim of the present study was to look for anatomical changes in climbers' brains, using magnetic resonance imaging (MRI), after extremely high-altitude climbs and to relate them to possible associated risk factors. Clinical history, neurological examinations and MRI were carried out on a group of nine climbers before and after climbing to over 7500 m without the use of supplementary oxygen. None of the subjects showed any neurological dysfunctions. In five climbers MRI abnormalities (high signal areas, cortical atrophy) were observed before the expedition. After the descent, two of them showed new high intensity signal areas recorded by MRI. Both subjects suffered severe neurological symptoms during the climb. The present study suggested that the brain changes observed by MRI could be related to the severity of clinical events at high altitude. However, we do not know the exact meaning of such MRI findings or the reason for their location, predominantly in posterior regions of the brain. The new evidence that a high percentage of climbers show MRI brain abnormalities, and especially the appearance of changes after the ascent, reinforces the possibility of a potential neurological risk in high-altitude climbing.     

Simulated dive in rats lead to acute changes in cerebral blood flow on MRI, but no cerebral injuries to grey or white matter

In this study, the effect of a simulated dive on rat brain was investigated using several magnetic resonance imaging (MRI)-methods and immunohistochemistry. Rats were randomly assigned to a dive- or a control group. The dive group was exposed to a simulated air dive to 600 kPa for 45 min. Pulmonary artery was monitored for vascular gas bubbles by ultrasound. MRI was performed 1 h after decompression and at one and 2 weeks after the dive with a different combination of MRI sequences at each time point. Two weeks after decompression, rats were sacrificed and brains were prepared for histology. Dived rats had a different time-curve for the dynamic contrast-enhanced MRI signal than controls with higher relative signal intensity, a tendency towards longer time to peak and a larger area under the curve for the whole brain on the acute MRI scan. On MRI, 1 and 2 weeks after dive, T₂-maps showed no signal abnormalities or morphological changes. However, region of interest based measurements of T₂ showed higher T₂ in the brain stem among decompressed animals than controls after one and 2 weeks. Microscopical examination including immunohistochemistry did not reveal apparent structural or cellular injuries in any part of the rat brains. These observations indicate that severe decompression does not seem to cause any structural or cellular injury to the brain tissue of the rat, but may cause circulatory changes in the brain perfusion in the acute phase.     

磁共振波谱评价大脑半球代谢物的偏侧优势

为了利用无创性的磁共振波谱成像技术研究大脑半球代谢物的非对称性,本研究对56例正常成年人行磁共振波谱成像,主要对双侧大脑半球的4个解剖区域:额叶、颞叶、枕叶及顶叶的代谢物天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)进行测量,并以Cr为内参照物比较NAA和Cho相对含量(NAA/Cr、Cho/Cr)的侧别差异。结果表明:双侧额叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异;在双侧颞叶之间,这2种比值均存在显著性差异;双侧枕叶之间Cho/Cr存在显著性差异,而NAA/Cr无显著性差异;双侧顶叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异。本研究结果提示双侧大脑半球的代谢物存在偏侧优势。     

Wavelet Analysis as a Tool for Investigating Movement-Related Cortical Oscillations in EEG-fMRI Coregistration

Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) identifies blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG events. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 12 subjects during eyes-closed condition inside a three T magnetic resonance (MR) scanner using an MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. For EEG data analysis we used a time–frequency approach to measure time by varying the energy in a signal at a given frequency band by the convolution of the EEG signal with a wavelet family in the alpha and beta bands. The correlation between the BOLD signal associated with the EEG regressor provides that sensory motor region is a source of the EEG. We conclude that combined EEG-fMRI can be used to investigate movement-related oscillations of the human brain inside an MRI scanner and wavelet analysis adds further details on the EEG changes. The movement-related changes in the EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.     

散发型Creutzfeldt-Jakob病的临床、脑电图及头颅磁共振DWI影像特点研究

目的:探讨散发型Creutzfeldt-Jakob病（sCJD）的临床、脑电图、弥散加权成像（DWI）特点及诊断价值。方法:对2例sCJD患者的临床特征、脑电图改变和头颅磁共振DWI异常信号进行分析。结果:2例患者脑电图均有特征性改变--周期性同步放电（periodic synchronous discharge,PSD）,反复多次动态检查有利于提高阳性率;DWI病变主要分布于皮层及纹状体,DWI对于早期发现特异的皮层和基底节高信号优于传统磁共振的T₁WI、T₂WI及FLAIR技术。结论:脑电图及头颅磁共振DWI技术具有无创、快捷优点,有助于sCJD早期诊治。     

Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease

We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage.     

精神分裂症患者一级亲属脑组织磁共振质子波谱成像的初步研究

目的 探讨精神分裂症患者一级亲属及正常对照组脑组织磁共振质子波谱分析(1H-MRS)的结果间是否存在差异.方法首先对精神分裂症患者一级亲属36人、正常对照组21人进行左侧前额叶、丘脑、海马、桥脑的1H-MRS分析,之后对所得结果进行独立样本t检验.结果 精神分裂症患者一级亲属与正常对照组在左侧前额叶、丘脑、海马、桥脑的...     

Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.     

瘤周区多体素磁共振波谱在脑肿瘤鉴别诊断中的应用

目的评价脑肿瘤周围区域多体素氢质子磁共振波谱(1H-MRS)在脑肿瘤诊断及鉴别诊断中的应用价值。方法搜集行常规MRI及多体素1H-MRS检查的脑肿瘤病变患者38例,包括胶质瘤15例、转移瘤9例、脑膜瘤14例(均为良性)。再根据WHO2000年分类标准,将脑胶质瘤分为低级别组(Ⅰ～Ⅱ级)8例,高级别组(Ⅲ～Ⅳ级)7例。所有患者检查前均未接受过化疗或放疗,没有脑外伤或/和脑手术史。常规扫描后增强前采用定点分辨磁共振波谱序列(PRESS)扫描,根据病灶的特征选定感兴趣区(ROI),ROI的大小既要包括肿瘤实质区、肿瘤周围区,也要尽可能涵盖对侧正常脑组织,又要避开骨骼、脑室、血管、坏死、囊变、出血、气体及钙化等区域。后处理应用MR机附带的波谱分析软件自动完成。计算脑胶质瘤、转移瘤及脑膜瘤实质区、周围区及对侧正常脑组织区代谢产物比值的平均值,进行组内、组间比较。P<0.05有统计学意义。结果多体素1H-MRS显示不同脑肿瘤的肿瘤实质区NAA/Cr、Cho/Cr和NAA/Cho平均值与对侧正常脑组织区比较有显著性差异(P<0.05);脑胶质瘤周围区与脑膜瘤、转移瘤的周围区以及高、低级别胶质瘤肿瘤周围区域多组代谢物比值具统计学差异(P<0.05)),高级别与低级别脑胶质瘤肿瘤周围区Glx/Cr的比值有显著性差异(P<0.05)。结论多体素1H-MRS技术可无创观察脑肿瘤患者脑代谢改变,有助于脑肿瘤的诊断、鉴别诊断、预测侵袭性病变的浸润范围以及脑胶质瘤的分级诊断等。     

Serial evaluation of patients with brain tumors using volume MRI and 3D 1H MRSI.

Patients with brain tumors are routinely monitored for tumor progression and response to therapy using magnetic resonance imaging (MRI). Although serial changes in gadolinium enhancing lesions provide valuable information for making treatment decisions, they do not address the fate of non-enhancing lesions and are unable to distinguish treatment induced necrosis from residual or recurrent tumor. The introduction of a non-invasive methodology, which could identify an active tumor more reliably, would have a major impact upon patient care and evaluation of new therapies. There is now compelling evidence that magnetic resonance spectroscopic imaging (MRSI) can provide such information as an add-on to a conventional MRI examination. We discuss data acquisition and analysis procedures which are required to perform such serial MRI-MRSI examinations and compare their results with data from histology, contrast enhanced MRI, MR cerebral blood volume imaging and FDG-PET. Applications to the serial assessment of response to therapy are illustrated by considering populations of patients being treated with brachytherapy and gamma knife radiosurgery.     

EEG and fMRI Coregistration to Investigate the Cortical Oscillatory Activities During Finger Movement

Electroencephalography combined with functional magnetic resonance imaging (EEG-fMRI) may be used to identify blood oxygenation level dependent (BOLD) signal changes associated with physiological and pathological EEG event. In this study we used EEG-fMRI to determine the possible correlation between topographical movement-related EEG changes in brain oscillatory activity recorded from EEG electrodes over the scalp and fMRI-BOLD cortical responses in motor areas during finger movement. Thirty-two channels of EEG were recorded in 9 subjects during eyes-open condition inside a 1.5 T magnetic resonance (MR) scanner using a MR-compatible EEG recording system. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during␣fMRI acquisition. For EEG data analysis we used the event-related-synchronization/desynchronization (ERS/ERD) approach to investigate where movement-related decreases in alpha and beta power are located. For image statistical analysis we used a general linear model (GLM) approach. There was a significant correlation between the positive-negative ratio of BOLD signal peaks and ERD values in the electrodes over the region of activation. We conclude that combined EEG-fMRI may be used to investigate movement-related oscillations of the human brain inside an MRI scanner and the movement-related changes in the EMG or EEG signals are useful to identify the brain activation sources responsible for BOLD-signal changes.     

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.     

Evidence for Metabolic Hypothalamo-Amygdala Dysfunction in Narcolepsy

Study Objectives:

Proton resonance spectroscopy (¹H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (mI), a glial marker and second messenger involved in the regulation of intracellular calcium. One ¹H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, “regions of interest,” thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae.

Design:

We performed ¹H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios.

Setting:

The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich.

Participants:

¹H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning.

Measurements and Results:

No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (mI)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and mI/Cr in the right amygdala (r = −0.89, P < 0.001), between mI/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = −63, P < 0.05) and between mI/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = −0.69, P < 0.05).

Conclusion:

Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.

Citation:

Poryazova R; Werth E; Khatami R; Dydak U; Meier D; Boesiger P; Bassetti CL. Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy. SLEEP 2009;32(5):607-613.     

Effect of posterior temporal-parietal hematoma on orbital frontal chemistry in relation to a cognitive and anxiety state: a combined 1H-MRS and neuropsychological study of an unusual case as compared with 16 healthy subjects

The authors report the unusual case of a 58-year-old woman (MJP) suffering from left temporal throbbing headache, associated with confusion. Magnetic resonance imaging showed a 5 x 3 x 2 cm hematoma at the left posterior temporal--parietal junction (PTPJ). Repeated MRI of MJP's brain performed during a 4-month follow-up period showed decrease in hematoma size (2.3 x 1.5 x 1) with evidence for development of encephalomalacia and resorption of blood products involving the area of hemorrhage. MJP had mild transcortical sensory aphasia characterized by difficulty with reading and processing, with semantic paraphasic errors while speaking and some difficulty with repetition. MJP had remained normotensive and seizure free, on Vasotec therapy and Dilantin prophylaxis. An in vivo proton magnetic resonance spectroscopy (1H-MRS) performed during an 8-month follow-up period showed reduced concentration for N-acetyl aspartate (NAA) by 19.3% (F=4.09, P<0.04), and myo-inositol by 32.0% (F=5.16, P<0.02) in the left orbital frontal cortex (OFC) as compared with 16 healthy subjects (age- and sex-matched). Cognitive tests (the Wechsler abbreviated scale of intelligence (WASI) and the Stroop color--word interference) showed a significant impairment suggesting involvement of higher-order cognitive functioning (memory, learning, and general intelligence) and attentional system. The Spielberger state-trait anxiety inventory (STAI) showed increased anxiety at the moment of the current examination and decreased tendency to be anxious over a long period of time. The Beck Anxiety and Depression Inventory revealed minimal anxiety and mild to moderate levels of depression. It is hypothesized that the PTPJ hematoma triggered long-distance pathways linking PTPJ area and frontal lobe, including OFC, which resulted in abnormal chemical changes in the left OFC and in cognitive tests impairment, and in long-term anxiety state changes.