Reprint of: Neuroimaging in acute liver failure

Acute liver failure (ALF) is frequently complicated by the development of brain edema that can lead to intracranial hypertension and severe brain injury. Neuroimaging techniques allow a none-invasive assessment of brain tissue and cerebral hemodynamics by means of transcranial Doppler ultrasonography, magnetic resonance and nuclear imaging with radioligands. These methods have been very helpful to unravel the pathogenesis of this process and have been applied to patients and experimental models. They allow monitoring the outcome of patients with ALF and neurological manifestations. The increase in brain water can be detected by observing changes in brain volume and disturbances in diffusion weighted imaging. Neurometabolic changes are detected by magnetic resonance spectroscopy, which provides a pattern of abnormalities characterized by an increase in glutamine and a decrease in myo-inositol. Disturbances in cerebral blood flow are depicted by SPECT or PET and can be monitored and the bedside by assessing the characteristics of the waveform provided by transcranial Doppler ultrasonography. Neuroimaging methods, which are rapidly evolving, will undoubtedly lead to future diagnostic and therapeutic progress that could be very helpful for patients with ALF.     

The functional anatomy of cerebral reorganisation after focal brain injury

Stroke is a major cause of disability in all age groups. Although the value of specific rehabilitative therapies is now acknowledged, the mechanisms of impairment and recovery are not well understood. There is growing interest in the role that central nervous system reorganisation might play in the recovery process, and in particular whether this reorganisation can be manipulated to provide clinical benefits for patients. The careful use of non-invasive techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation allows the study of the working human brain, and studies in humans suggest that functionally relevant adaptive changes occur in cerebral networks following stroke. An understanding of how these changes influence the recovery process will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and will allow the delivery of specific therapies to appropriately targeted patients suffering from stroke.     

Research advances in geriatric depression

Technical advances have facilitated the exploration of factors related to geriatric depression and have helped generate novel biological and psychosocial treatment approaches. This review summarizes the main advancements in epidemiology, clinical presentation and course, genetics, and other areas of biological research. Treatment interventions outlined in this paper include electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation, deep brain stimulatn, depression prophylaxis, multidisciplinary approaches to depression treatment, and psychotherapy. Forms of psychotherapy for geriatric depression summarized include interpersonal psychotherapy, supportive psychotherapy, cognitive-behavioral therapy, problem-solving therapy, and ecosystem-focused therapy. Neuroimaging techniques based on magnetic resonance imaging are discussed briefly, including volumetric brain studies, diffusion tensor imaging, fractional anisotropy, fiber tractography, magnetization transfer imaging, and blood-oxygenation-level-dependent functional magnetic resonance imaging. Finally, treatment effectiveness is addressed in a discussion of new models to improve access to and quality of care offered in the community.     

Fast scan magnetic resonance imaging and Doppler ultrasonography of uteroplacental hemodynamics in the rhesus monkey (Macaca mulatta)

Fast scan magnetic resonance imaging, color Doppler ultrasonography, and magnetic resonance angiography were used to demonstrate the uteroplacental hemodynamics in rhesus monkeys. “Jets” of maternal blood spurting into the placenta were observed with, or without, the use of a contrast medium from 114 days to the term of pregnancy. Cumulative intravenous doses of cocaine hydrochloride brought about changes in the sequences of imaging of the maternal blood inflow to the placenta. These methods appear suitable for non-invasive monitoring of the effects of drugs on placental function.     

Therapeutic hypothermia in the management of acute liver failure

A large body of experimental data and preliminary clinical studies point to the induction of mild hypothermia (32-35 °C) as a valuable approach to control the development of brain edema and intracranial hypertension in acute liver failure (ALF). The ability of hypothermia to affect multiple processes probably explains its efficacy to prevent these cerebral complications. Remarkably, mild hypothermia has been shown to prevent or attenuate most of the major alterations involved in the pathogenesis of the cerebral complications of ALF, including the accumulation of ammonia in the brain and the circulation, the alterations of brain glucose metabolism, the brain osmotic disturbances, the accumulation of glutamate and lactate in brain extracellular space, the development of inflammation and oxidative/nitrosative stress, and others. Limited information suggests that the systemic effects of hypothermia may also be beneficial for some peripheral complications of ALF. Translation of the beneficial effects of therapeutic hypothermia into standard clinical practice, however, needs to be confirmed in adequately designed clinical trials. Such trials will be important to determine the safety of therapeutic hypothermia, to identify which patients might benefit from it, and to provide the optimal guidelines for its use in patients with ALF.     

Neurological complications of acute liver failure: pathophysiological basis of current management and emerging therapies

One of the major causes of mortality in patients with acute liver failure (ALF) is the development of hepatic encephalopathy (HE) which is associated with increased intracranial pressure (ICP). High ammonia levels, increased cerebral blood flow and increased inflammatory response have been identified as major contributors to the development of HE and the related brain swelling. The general principles of the management of patients with ALF are straightforward. They include identifying the insult causing hepatic injury, providing organ systems support to optimize the patient's physical condition, anticipation and prevention of development of complications. Increasing insights into the pathophysiological mechanisms of ALF are contributing to better therapies. For instance, the evident role of cerebral hyperemia in the pathogenesis of increased ICP has led to a re-evaluation of established therapies such as hyperventilation, N-acetylcysteine, thiopentone sodium and propofol. The role of systemic inflammatory response in the pathogenesis of increased ICP has also gained importance supporting the concept that antibiotics given prophylactically reduce the risk of developing sepsis during the course of illness. Moderate hypothermia has also been established as a therapy able to reduce ICP in patients with uncontrolled intracranial hypertension and to prevent increases in ICP during orthopic liver transplantation. Ornithine phenylacetate, a new drug in the treatment of liver failure, and liver replacement therapies are still being investigated both experimentally and clinically. Despite many advances in the understanding of the pathophysiological basis and the management of intracranial hypertension in ALF, more clinical trials should be conducted to determine the best therapeutic management for this difficult clinical event.     

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.     

Neuropathology of acute liver failure

Cerebral edema has been identified in all forms of liver disease and is closely related to the development of hepatic encephalopathy. Cerebral edema is most readily recognized in acute liver failure (ALF), while the main cause of death in patients with ALF is multi-organ failure; brain herniation as a result of intracranial hypertension does remain a major cause of mortality. The mechanisms responsible for cerebral edema in ALF suggest both cytotoxic and vasogenic injury. This article reviews the gross and ultrastructural changes associated with cerebral edema in ALF. The primary cause of cerebral edema is associated with astrocyte swelling, mainly perivascular edema and ammonia still remains the primary neurotoxin involved in its pathogenesis. The astrocytic changes were confined to the gray matter. The other organelles involved in the pathogenesis of ALF include mitochondria, basement membrane, pericytes, microglial cells, blood-brain barrier (BBB) etc. Discrete neuronal changes have recently been reported. Recent studies in animal and humans have demonstrated the microglial changes which have the potential to cause neuronal dysfunction in ALF. The alterations in BBB still remain unclear though few studies have showed disruption of tight junction proteins indicating the involvement of BBB in cellular swelling.     

In vivo imaging of endogenous neural stem cells in the adult brain

The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3’-deoxy-3’-[¹⁸F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.     

Brain structural and functional characteristics in children with mental disorders and the possibilities of transcranial direct current stimulation

Analysis of the magnetic resonance imaging (MRI) data in children with mental disorders of perinatal origin showed that, in 70% of cases, pathological damage to the brain structures is absent, or only minimal residual changes are detected. At the same time, the EEG α-rhythm in the occipitoparietal areas was not regular in 77% of cases. The predominance of the signs of cerebral functional insufficiency allows efficacious use of the physiological methods of correction of mental disorders using transcranial direct current stimulation.     

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain''s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which ¹¹C-AcAc and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of ¹¹C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of ¹¹C-AcAc and ¹⁸F-FDG brain uptake (cerebral metabolic rate; μmol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer''s and Parkinson''s diseases.     

Imaging neurodegeneration in Parkinson's disease

Neuroimaging techniques have evolved over the past several years giving us unprecedented information about the degenerative process in Parkinson's disease (PD) and other movement disorders. Functional imaging approaches such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) have been successfully employed to detect dopaminergic dysfunction in PD, even while at a preclinical stage, and to demonstrate the effects of therapies on function of intact dopaminergic neurons within the affected striatum. PET and SPECT can also monitor PD progression as reflected by changes in brain levodopa and glucose metabolism and dopamine transporter binding. Structural imaging approaches include magnetic resonance imaging (MRI) and transcranial sonography (TCS). Recent advances in voxel-based morphometry and diffusion-weighted MRI have provided exciting potential applications for the differential diagnosis of parkinsonian syndromes. Substantia nigra hyperechogenicity, detected with TCS, may provide a marker of susceptibility to PD, probably reflecting disturbances of iron metabolism, but does not appear to correlate well with disease severity or change with disease progression. In the future novel radiotracers may help us assess the involvement of non-dopaminergic brain pathways in the pathology of both motor and non-motor complications in PD.     

In Vivo Measurements of Ethanol Concentration in Rabbit Brain by 1H Magnetic Resonance Spectroscopy

In vivo 1H magnetic resonance spectroscopy was used to measure the cerebral ethanol concentration in the rabbit after both intraarterial and intragastric administration. There was good agreement between cerebral and blood ethanol concentrations at all times after administration by either route. Cerebral ethanol levels, measured using in vivo 1H spectroscopy, agreed well with those measured in perchloric acid extracts of brain, analyzed by both high-resolution 1H spectroscopy and gas chromatography. Ethanol may be useful as an indicator to measure cerebral blood flow by 1H spectroscopy and chemical shift-selective magnetic resonance imaging.     

Observation of Cerebral Metabolites in an Animal Model of Acute Liver Failure In Vivo: A 1H and 31P Nuclear Magnetic Resonance Study

Acute liver failure was induced in rats by a single intragastric dose of carbon tetrachloride. This causes hepatic centrilobular necrosis, as indicated by histological examinations, and produces a large increase in the activity of serum alanine aminotransferase. The plasma NH4+ level (mean +/- SEM) was 123 +/- 10 microM in the control group and 564 +/- 41 microM in animals with acute liver failure (each n = 5). 31P nuclear magnetic resonance (NMR) was used to monitor brain cortical high-energy phosphate compounds, Pi, and intracellular pH. 1H NMR spectroscopy was utilised to detect additional metabolites, including glutamate, glutamine, and lactate. The results show that the forebrain is capable of maintaining normal phosphorus energy metabolite ratios and intracellular pH despite the metabolic challenge by an elevated blood NH4+ level. There was a significant increase in the brain glutamine level and a concomitant decrease in the glutamate level during hyperammonaemia. The brain lactate level increased twofold in rats with acute liver failure. The results indicate that 1H NMR can be used to detect cerebral metabolic changes in this model of hyperammonaemia, and our observations are discussed in relation to compartmentation of NH4+ metabolism.     

Increased cerebral activity in Parkinson’s disease patients carrying the DRD2 TaqIA A1 allele during a demanding motor task: a compensatory mechanism?

Previous studies suggest that neuroimaging techniques are useful for detecting the effects of functional genetic polymorphisms on brain function in healthy subjects or in patients presenting with psychiatric or neurodegenerative conditions. Former evidence showed that individuals carrying risk alleles displayed broader patterns of brain activity during behavioural and cognitive tasks, despite being clinically comparable to non-carriers. This suggests the presence of compensatory brain mechanisms. In the present study, we investigated this effect in Parkinson's disease (PD) patients carrying the DRD2 TaqIA A1 allelic variant. This variant may confer an increased risk of developing the disease and/or influence the clinical presentation. During a complex sequential motor task, we evidenced by functional magnetic resonance imaging that A1 allele carriers activated a larger network of bilateral cerebral areas than non-carriers, including cerebellar and premotor regions. Both groups had similar clinical and demographic measures. In addition, their motor performance during the functional magnetic resonance experiment was comparable. Therefore, our conclusions, pending replication in a larger sample, seem to reflect the recruitment of compensatory cerebral resources during motor processing in PD patients carrying the A1 allele.     

记忆训练联合电针疗法对全脑放疗患者认知功能、健康相关生命质量和颅脑磁共振灌注成像参数的影响

摘要 目的：探讨记忆训练联合电针疗法对全脑放疗患者认知功能、健康相关生命质量和颅脑磁共振灌注成像参数的影响。方法：选择江南大学附属医院2020年3月～2022年1月期间收治的全脑放疗患者94例,根据随机数字表法分为研究组（常规干预、记忆训练联合电针疗法）和对照组（常规干预）,各为47例。对比两组认知功能、健康相关生命质量和颅脑磁共振灌注成像参数的变化。结果：治疗1周、2周、3周、4周后,两组蒙特利尔认知功能检查量表（MoCA）和简易精神状态量表（MMSE）评分均较治疗前逐渐下降,但研究组各时间点MoCA、MMSE评分高于对照组（P<0.05）。治疗4周后,两组健康相关生命质量量表（HRQoL）各维度评分及总分均较治疗前升高,且研究组上述评分均高于对照组（P<0.05）。治疗4周后,两组颅脑平均脑血容量（CBV）值和平均脑血流量（CBF）值均较治疗前下降,但研究组上述值高于对照组（P<0.05）。结论：记忆训练联合电针疗法可减缓全脑放疗后导致的认知功能损害,并提升患者的健康相关生命质量,可能与调节脑血容量、脑血流量有关。     

Modulation of visual processing by attention and emotion: windows on causal interactions between human brain regions

Visual processing is not determined solely by retinal inputs. Attentional modulation can arise when the internal attentional state (current task) of the observer alters visual processing of the same stimuli. This can influence visual cortex, boosting neural responses to an attended stimulus. Emotional modulation can also arise, when affective properties (emotional significance) of stimuli, rather than their strictly visual properties, influence processing. This too can boost responses in visual cortex, as for fear-associated stimuli. Both attentional and emotional modulation of visual processing may reflect distant influences upon visual cortex, exerted by brain structures outside the visual system per se. Hence, these modulations may provide windows onto causal interactions between distant but interconnected brain regions. We review recent evidence, noting both similarities and differences between attentional and emotional modulation. Both can affect visual cortex, but can reflect influences from different regions, such as fronto-parietal circuits versus the amygdala. Recent work on this has developed new approaches for studying causal influences between human brain regions that may be useful in other cognitive domains. The new methods include application of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) measures in brain-damaged patients to study distant functional impacts of their focal lesions, and use of transcranial magnetic stimulation concurrently with fMRI or EEG in the normal brain. Cognitive neuroscience is now moving beyond considering the putative functions of particular brain regions, as if each operated in isolation, to consider, instead, how distinct brain regions (such as visual cortex, parietal or frontal regions, or amygdala) may mutually influence each other in a causal manner.     

Adult cerebral adrenoleukodystrophy and Addison's disease in a female carrier

We described a 38-year-old woman of rapidly progressive dementia with white matter encephalopathy and death. She had Addison's disease but the adrenal glands were hyperplastic. Brain magnetic resonance imaging revealed diffuse white matter lesion predominantly in the frontal lobe with band-like contrast enhancement. l-Methyl-11C-methionine positron emission tomography revealed accumulation of tracer in bilateral frontal lobes. Stereotactic biopsy demonstrated demyelination changes. A number of urinary organic acids were elevated. Adrenoleukodystrophy was diagnosed by elevated plasma very long chain fatty acid and ABCD1 gene mutation (C1544C/T). Adrenoleukodystrophy should be considered as a differential diagnosis in women with rapidly progressive white matter encephalopathy.     

Decreased Peripheral and Central Responses to Acupuncture Stimulation following Modification of Body Ownership

Acupuncture stimulation increases local blood flow around the site of stimulation and induces signal changes in brain regions related to the body matrix. The rubber hand illusion (RHI) is an experimental paradigm that manipulates important aspects of bodily self-awareness. The present study aimed to investigate how modifications of body ownership using the RHI affect local blood flow and cerebral responses during acupuncture needle stimulation. During the RHI, acupuncture needle stimulation was applied to the real left hand while measuring blood microcirculation with a LASER Doppler imager (Experiment 1, N = 28) and concurrent brain signal changes using functional magnetic resonance imaging (fMRI; Experiment 2, N = 17). When the body ownership of participants was altered by the RHI, acupuncture stimulation resulted in a significantly lower increase in local blood flow (Experiment 1), and significantly less brain activation was detected in the right insula (Experiment 2). This study found changes in both local blood flow and brain responses during acupuncture needle stimulation following modification of body ownership. These findings suggest that physiological responses during acupuncture stimulation can be influenced by the modification of body ownership.     

医学领域的磁共振成像革命——2003年诺贝尔生理及医学奖主要工作介绍

在磁场中 ,自旋的原子核会吸收频率与其自旋频率相同的电磁波 ,使自身能量增加 ,发生能级跃迁 ,当原子核迁移回原能级时 ,就会把多余的能量以电磁波的形式释放出来 ,称为核磁共振 (NMR) .磁共振成像(MRI)利用这一原理 ,依据所释放的能量在物质内部不同结构环境中不同的衰减 ,通过外加梯度磁场检测所发射出的电磁波 ,即可得知构成这一物体原子核的位置和种类 ,据此可以绘制成物体内部的结构图像 .将这种技术用于人体内部结构的成像 ,就产生出一种革命性的医学诊断工具 .快速变化的梯度磁场的应用 ,大大加快了磁共振成像的速度 ,使该技术在临床诊断、科学研究的应用成为现实 ,极大地推动了医学、神经生理学和认知神经科学的迅速发展