Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease

Crohn’s disease(CD)is a chronic,non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease(IBD).CD is prone to relapse,and its incidence displays a persistent increase in developing countries.However,the pathogenesis of CD is poorly understood,with some studies emphasizing the link between CD and the intestinal microbiota.Specifically,studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD.Furthermore,investigations have shown whitematter lesions and neurologic deficits in patients with IBD.Based on these findings,brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging(BOLD-f MRI).BOLD-f MRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates.Therefore,biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients.To further study this phenomenon,brain changes of CD patients can be detected non-invasively,effectively and accurately by BOLD-f MRI combined with magnetic resonance spectroscopy(MRS).This approach can further shed light on the mechanisms of the occurrence and development of neurological CD.Overall,this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

In vivo magnetic resonance spectroscopy of liver tumors and metastases

Primary liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. The liver is also the second most common site for metastatic spread of cancer. To assist in the diagnosis of these liver lesions non-invasive advanced imaging techniques are desirable. Magnetic resonance (MR) is commonly used to identify anatomical lesions, but it is a very versatile technique and also can provide specific information on tumor pathophysiology and metabolism, in particular with the application of MR spectroscopy (MRS). This may include data on the type, grade and stage of tumors, and thus assist in further management of the disease. The purpose of this review is to summarize and discuss the available literature on proton, phosphorus and carbon-13-MRS as performed on primary liver tumors and metastases, with human applications as the main perspective. Upcoming MRSapproaches with potential applications to liver tumors are also included. Since knowledge of some technical background is indispensable to understand the results, a basic introduction of MRS and some technical issues of MRS as applied to tumors and metastases in the liver are described as well. In vivo MR spectroscopy of tumors in a metabolically active organ such as the liver has been demonstrated to provide important information on tumor metabolism, but it also is challenging as compared to applications on some other tissues, in particular in humans, mostly because of its abdominal location where movement may be a disturbing factor.

Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents

AIM To establish a threshold value for liver fat content between healthy children and those with nonalcoholic fatty liver disease(NAFLD) by using magnetic resonance imaging(MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel pointresolved 1H MR-Spectroscopy(1H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cutoff value. Lin coefficient test was used to evaluate thecorrelation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.

Importance of imaging and recent developments in diagnosis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is one of the most common causes of chronic liver disease and is a major public health problem worldwide.It is a spectrum that includes simple steatosis,nonalcoholic steatohepatitis(NASH),fibrosis and cirrhosis.Recently,NAFLD prevalence in children and adolescents has increased too.The increasing prevalence has resulted in NASH-related chronic liver disease.Therefore,early diagnosis and treatment is quite important.Although liver biopsy is still the gold standard for diagnosis and staging of NAFLD,particularly for the diagnosis of NASH,imaging methods such as ultrasonography,computed tomography,magnetic resonance imaging with chemical shift imaging and especially magnetic resonance spectroscopy and elastography have been increasingly approved as noninvasive alternative methods.The aim of this review is to analyze the diagnostic accuracy and limitations of the imaging methods and recent developments in the diagnosis of NAFLD.

Cerebellum and neurodegenerative diseases:Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases.While conventional magnetic resonance imaging(MRI) is widely used for brain and cerebellar morphologic evaluation,advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics.Volumetry,voxel-based morphometry,diffusion MRI based fiber tractography,resting state and task related functional MRI,perfusion,and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum.In the present review,after providing a brief description of each technique's advantages and limitations,we focus on their application to the study of cerebellar injury in major neurodegenerative diseases,such as multiple sclerosis,Parkinson's and Alzheimer's disease and hereditary ataxia.A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease,followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.

Potential role of imaging in assessing harmful effects on spermatogenesis in adult testes with varicocele

Varicocele is characterized by an abnormal dilatation and retrograde blood flow in the spermatic veins. Varicocele is the leading correctable cause of male infertility. Although it is highly prevalent in infertile men, it is also observed in individuals with normal fertility. Determining which men are negatively affected by varicocele would enable clinicians to better select those men who will benefit from treatment. To assess the functional status of the testes in men with varicocele, color Doppler sonographic parameters were evaluated. Testicular arterial blood flow was significantly reduced in men with varicocele, reflecting an impairment of spermatogenesis. An improvement in the testicular blood supply was found after varicocelectomy on spectral Doppler analysis. Testicular contrast harmonic imaging and elastography might improve our knowledge about the influence of varicocele on intratesticular microcirculation and tissue stiffness, respectively, providing possible information on the early damage of testicular structure by varicocele. Magnetic resonance imaging(MRI), with measurement of apparent diffusion coefficient has been used to assess the degree of testicular dysfunction and to evaluate the effectiveness of varicocele repair. Large prospective studies are needed to validate the possible role of functional sonography and MRI in the assessment of early defects of spermatogenesis in testes with varicocele.

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

"Personalized oncology" is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of "radiomics/radiogenomics". Diffusionweighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that "one size fits all". It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in "personalized oncology".

Cognitive dysfunction and hepatitis C virus infection

Cognitive dysfunction in patients with chronic hepatitis C virus(HCV) infection is a distinct form of minimal hepatic encephalopathy(MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging(MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism

Hepatic encephalopathy(HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events(i.e.,portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here,we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment,hyperammonaemia,electroencephalograph alterations,impaired neuropsychological performance,and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE,paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Functional magnetic resonance imaging and the brain: A brief review

Functional magnetic resonance imaging(fMRI) is em-ployed in many behavior analysis studies, with blood oxygen level dependent-(BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-contrast imaging in f MRI has been refined over the years, for example, the inclusion of a spin echo pulse and increased magnetic strength were shown to produce better recorded images. Taking careful precautions to control variables during measurement, comparisons between different specimen groups can be illustrated by f MRI imaging using both quantitative and qualitative methods. Differences have been observed in comparisons of active and resting, developing and aging, and defective and damaged brains in various studies. However, cognitive studies using f MRI still face a number of challenges in interpretation that can only be overcome by imaging large numbers of samples. Furthermore, f MRI studies of brain cancer, lesions and other brain pathologies of both humans and animals are still to be explored.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study

AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category(lamotrigine or levetiracetam, n=16), an "intermediate risk" category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a "high risk" category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Sustained attention in psychosis:Neuroimaging findings

To provide a systematic review of scientific literatureon functional magnetic resonance imaging(fMRI) stud-ies on sustained attention in psychosis. We searchedPubMed to identify fMRI studies pertaining sustainedattention in both affective and non-affective psycho-sis. Only studies conducted on adult patients using asustained attention task during fMRI scanning wereincluded in the final review. The search was conductedon September 10 th, 2013. 15 fMRI studies met our in-clusion criteria: 12 studies were focused on Schizophre-nia and 3 on Bipolar Disorder Type Ⅰ(BDI). Only halfof the Schizophrenia studies and two of the BDI stud-ies reported behavioral abnormalities, but all of themevidenced significant functional differences in brain re-gions related to the sustained attention system. Alteredfunctioning of the insula was found in both Schizophre-nia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlight-ing differences and similarities between Schizophrenia and BDI.