Diffusion weighted magnetic resonance imaging of liver: Principles, clinical applications and recent updates

Diffusion-weighted imaging(DWI), a functional imaging technique exploiting the Brownian motion of water molecules, is increasingly shown to have value in various oncological and non-oncological applications. Factors such as the ease of acquisition and ability to obtain functional information in the absence of intravenous contrast, especially in patients with abnormal renal function, have contributed to the growing interest in exploring clinical applications of DWI. In the liver, DWI demonstrates a gamut of clinical applications ranging from detecting focal liver lesions to monitoring response in patients undergoing serial follow-up after loco-regional and systemic therapies. DWI is also being applied in the evaluation of diffuse liver diseases such as non-alcoholic fatty liver disease, hepatic fibrosis and cirrhosis. In this review, we intend to review the basic principles, technique, current clinical applications and future trends of DW-MRI in the liver.

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.

Quantitative diffusion-weighted magnetic resonance enterography in ileal Crohn’s disease: A systematic analysis of intra and interobserver reproducibility

BACKGROUND Magnetic resonance enterography(MRE) is increasingly attractive as a noninvasive and radiation-free tool for assessing Crohn’s disease(CD). Diffusionweighted imaging(DWI) is recommended as an optional MRE sequence for CD by the European Society of Gastrointestinal and Abdominal Radiology, and has shown a superb potential as a quantitative modality for bowel inflammation evaluation. However, the measurement reproducibility of quantitative DWI analysis in MRE has not been ascertained so far. To facilitate the application of quantitative diffusion-weighted MRE in the clinical routine, systematic investigations of the intra and interobserver reproducibility of DWI quantitative parameters should be performed.AIM To evaluate the intra and interobserver reproducibility of quantitative analysis for diffusion-weighted MRE(DW-MRE) in ileal CD.METHODS Forty-four subjects(21 with CD and 23 control subjects) who underwent ileocolonoscopy and DW-MRE(b = 800 s/mm2) within one week were included.Two radiologists independently measured apparent diffusion coefficients(ADC)of the terminal ileum and signal intensity ratio(SR) of the terminal ileum to ipsilateral psoas muscle on DWI images(b = 800 s/mm2). Between-and withinreader agreements were assessed using intraclass correlation coefficients(ICC),coefficients of variation(CoV), and 95% limits of agreement of Bland-Altman plots(BA-LA LoA). Diagnostic performances of ADC and SR for identifying inflamed terminal ileum from the normal were evaluated by receiver operating characteristic(ROC) curve analysis.RESULTS There were no significant differences in ADC or SR values between the two sessions or between the two radiologists either in the CD or control group(paired t-test, P > 0.05). The intra and interobserver reproducibility of ADC(ICC: 0.952-0.984;CoV: 3.73-6.28%;BA-LA LoA: ±11.27% to ±15.88%) and SR(ICC: 0.969-0.989;CoV: 3.51%-4.64%;BA-LA LoA: ±10.62% to ±15.45%) was excellent for CD.Agreement of ADC measurements was slightly less in control subjects(ICC:0.641-0.736;CoV: 10.47%-11.43%;BA-LA LoA: ± 26.59% to ± 30.83%). SR of normal terminal ileum demonstrated high intra and interobserver reproducibility(ICC: 0.944-0.974;CoV: 3.73%-6.28%;BA-LA LoA: ± 18.58% to ± 24.43%). ADC and SR of two readers had outstanding diagnostic efficiencies(area under the ROC curve: 0.923-0.988).CONCLUSION Quantitative parameters derived from DW-MRE have good to excellent intra and interobserver agreements with high diagnostic accuracy, and can serve as robust and efficient quantitative biomarkers for CD evaluation.

Magnetic resonance imaging markers for early diagnosis of Parkinson's disease

Parkinson＇s disease （PD） is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called ＂prodromal＂, where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging （MRI） and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.

Morphological and functional evaluation of chronic kidney disease using magnetic resonance imaging

X-ray computed tomography(CT),ultrasonography(US)and radionuclide scanning are important clinical methods for evaluating morphology of the kidney.These modalities are also applicable for estimating kidney function with time lapse analysis using proper contrastmedia as may be necessary.In the case of US,it can estimate kidney function based on the measurement of blood flow using the Doppler effect.Formerly,magnetic resonance imaging(MRI)was an inappropriate diagnostic imaging technique for abdominal organs because of their respiratory displacements.However,MRI is now actively used for kidney as well as liver or other parenchymal organs,in tandem with the technological advances.Unlike unenhanced X-ray CT,"conventional"MRI can distinguish the border between cortex and medulla in T1 or T2 weighted images.It was known that the border blurred with decreasing kidney function.Moreover,several other particular imaging methods were introduced in recent years,and these could be called"functional"MRI.In this review,the following are discussed:functional MRI for chronic kidney disease,which include blood oxygenation level-dependent MRI for evaluation of hypoxia,diffusion-weighted imagingfor evaluation of fibrosis,diffusion tensor imaging for evaluation of microstructure,and arterial spin labeling to evaluate the amount of organ perfusion,accompanied with several related articles.The ultimate goal of functional MRI is to provide useful in vivo information repeatedly for daily medical treatment non-invasively.

Application Progress of Intravoxel Incoherent Motion Diffusion Weighted Magnetic Resonance Imaging in Pancreatic Cancer

Intravoxel incoherent motion imaging (IVIM), on the traditional diffusion weighted imaging (DWI) technology, uses the biexponential model and adopts the multi-b-value analysis to obtain the perfusion information of water molecule diffusion and microcirculation without the use of contrast agent. It is more and more used in pancreatic diseases, which is of great significance for the diagnosis and identification of pancreatic cancer. This article will review the principles of IVIM imaging and its application in pancreatic diseases, especially in pancreatic cancer diagnosis, the prediction of pathological grade of pancreatic ductal adenocarcinoma, the judgment of lymph node metastasis, and differentiation of pathological classification.

Differentiating between Alzheimer’s disease, amnestic mild cognitive impairment, and normal aging via diffusion kurtosis imaging

Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer’s disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer’s disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer’s disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer’s disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer’s disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer’s disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6).

Progress of intravoxel incoherent motion diffusion-weighted imaging in liver diseases

Traditional magnetic resonance(MR)diffusion-weighted imaging(DWI)uses a single exponential model to obtain the apparent diffusion coefficient to quantitatively reflect the diffusion motion of water molecules in living tissues,but it is affected by blood perfusion.Intravoxel incoherent motion(IVIM)-DWI utilizes a double-exponential model to obtain information on pure water molecule diffusion and microcirculatory perfusion-related diffusion,which compensates for the insufficiency of traditional DWI.In recent years,research on the application of IVIM-DWI in the diagnosis and treatment of hepatic diseases has gradually increased and has achieved considerable progress.This study mainly reviews the basic principles of IVIM-DWI and related research progress in the diagnosis and treatment of hepatic diseases.

Diffusion tensor imaging of the brain in patients with Alzheimer's disease and cerebrovascular lesions

Background:Recent autopsy study showed a high incidence of cerebrovascular lesions in Alzheimer's disease(AD).To assess the impact of cerebrovascular pathology in AD,we used diffusion tensor imaging(DTI) to study AD patients with and without cerebrovascular lesions.Materials and Methods:Conventional and DTI scans were obtained from 10 patients with probable AD,10 AD/V patients(probable AD with cerebrovascular lesions) and ten normal controls.Mean diffusivity(D) and fractional anisotropy(FA) values of some structures involved with AD pathology were measured.Results:D value was higher in AD patients than in controls in hippocampus and the cingulate gyrus.In AD/V patients,increased D value was found in the same structures and also in the thalamus and basal ganglia compared to controls.There was a significant difference of D value between AD and AD/V patients.FA value reduced in the white matter of left inferior temporal gyrus and in the bilateral middle cingulate gyrus in patients with AD/V compared with controls.The MMSE(mini-mental state examination) score significantly correlated with FA value in the right hippocampus(r=0.639,P<0.019),in the right anterior cingulate gyrus(r=0.587,P<0.035) and in left parahippocampal gyrus(r=0.559,P<0.047).Conclusion:Cerebrovascular pathology had stronger impact on the D value than the AD pathology alone did.Elevated D value in thalamic and basal ganglia may contribute to cognitive decline in AD/V patients.Reduced FA values in AD/V patients may indicate that cerebrovascular pathology induced more severe white matter damage than the AD pathology alone did.

Detecting dopaminergic neuronal degeneration using diffusion tensor imaging in a rotenone-induced rat model of Parkinson's disease: fractional anisotropy and mean diffusivity values

Dopamine content in the basal ganglia is strongly associated with the degree of dopaminergic neuron loss in the substantia nigra pars com- pacta. Symptoms of Parkinson＇s disease might not arise until more than 50% of the substantia nigra pars compacta is lost and the dopamine content in the basal ganglia is reduced by more than 80%. Greater diagnostic sensitivity and specificity would allow earlier detection of Parkinson＇s disease. Diffusion tensor imaging is a recently developed magnetic resonance imaging technique that measures mean diffusiv- ity and fractional anisotropy, and responds to changes in brain microstructure. When the microscopic barrier （including cell membranes, microtubules and other structures that interfere with the free diffusion of water） is destroyed and extracellular fluid volume accumulates, the mean diffusivity value increases; when the integrity of the microstructure （such as myelin） is destroyed, fractional anisotropy value decreases. However, there is no consensus as to whether these changes can reflect the early pathological alterations in Parkinson＇s disease. Here, we established a rat model of Parkinson＇s disease by injecting rotenone （or sunflower oil in controls） into the right suhstantia nigra. Diffusion tensor imaging results revealed that in the stages of disease, at 1, 2, 4, and 6 weeks after rotenone injection, fiactional anisotropy value decreased, but mean diffusivity values increased in the right substantia nigra in the experimental group. Fractional anisotropy values were lower at 4 weeks than at 6 weeks in the right substantia nigra of rats from the experimental group. Mean diffusivity values were mark- edly greater at 1 week than at 6 weeks in the right corpus striatum of rats from the experimental group. These findings suggest that mean diffusivity and fractional anisotropy values in the brain of rat models of Parkinson＇s disease 4 weeks after model establishment can reflect early degeneration of dopaminergic neurons. ＇The change in fractional anisotropy values after destruction of myelin integrity is likely to be of greater early diagnostic significance than the change in mean diffusivity values.

Diffusion-weighted imaging and fluid-attenuated inversion recovery sequence in sporadic Creutzfeldt-Jakob disease:One-case report

The diagnosis of sporadic Creutzfeldt-Jakob disease （sCJD） is extremely difficult. Diffusion-weighted imaging has been shown to be the most sensitive technique for the detection of signal alterations in sCJD patients. The present study analyzed the diagnostic value of diffusion-weighted imaging and fluid-attenuated inversion recovery sequence in the early stage of sCJD in one female patient and correlated the clinical symptoms during disease course and magnetic resonance manifestations. Thalamic and basal ganglia hyperintensities were observed on magnetic resonance images in a very early stage, i.e., when the clinical typical manifestations of the disease were not present. With the progression of the disease, cortical and basal ganglia hyperintensities were observed on magnetic resonance images, showing an obvious cerebral atrophy. These findings suggest that diffusion-weighted imaging and fluid-attenuated inversion recovery sequence are helpful in diagnosing sCJD.

Diffusion-weighted magnetic resonance imaging in diagnosis of Creutzfeldt-Jakob disease

Background Creutzfeldt-Jakob disease （CJD）, a rare disease, is uncharacterized by computed tomography （CT） and magnetic resonance imaging （MRI）. This study was aimed to evaluate the diffusion-weighted MRI （DWI） manifestations of CJD and to discuss their diagnostic value. Methods The findings of T1-weighted MR/（T1WI）, T2-weighted MRI（T2WI）, DWI and post-contrast MRI in 5 patients （3 patients with biopsy-proven CJD and 2 patients with clinically-proven CJD） were retrospectively analyzed in this study. Results Four out of the 5 patients had cerebral atrophy of various degrees. One patient showed symmetric high signal intensity at the bilateral globus pallidus and the head of the caudate nucleus, with very high signal in the cerebral cortex on the DWI. This patient only had symmetric slightly high signal at the bilateral globus pallidus and putamen on T2WI. One patient had high signal intensity at the basal ganglia and cerebral cortex on DWI, but abnormal T2 signal intensity at the bilateral paraventricular white matter on MRI. Two patients presented with widely gyri-like high signal intensity at the cortex on DWI, but routine MRI showed bilateral paraventricular long T2 signal intensity in 1 patient and no abnormal findings in another. No abnormalities were shown by both routine MRIand DWI in the last patient. Conclusions DWI is more sensitive than its conventional counterpart in the depiction of CJD. DWI is more sensitive to detect cortical abnormal signal intensity in CJD not detected by T2WI.

Brain imaging of mild cognitive impairment and Alzheimer's disease

The rapidly increasing prevalence of cognitive impairment and Alzheimer＇s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer＇s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and AIzheimer＇s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer＇s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer＇s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

A Study on Clinical Characteristics and Magnetic Resonance Imaging Manifestations on Systemic Rosai-Dorfman Disease

Background： Rosai-Dorfman disease （RDD） is typically characterized by painless bilateral and symmetrical cervical lymphadenopathy, with associated fever and leukocytosis. The aim of the current study was to summarize the clinical features and imaging characteristics of RDD, in an effort to improve its diagnostic accuracy. Methods： The study was analyzed from 32 patients between January 2011 and December 2017; of these, 16 patients had pathologically diagnosed RDD, eight had pathologically diagnosed meningioma, and eight pathologically diagnosed lymphoma. All patients underwent computed tomography and magnetic resonance imaging （MRI）. Clinical features and imaging characteristics of RDD were analyzed retrospectively. The mean apparent diffusion coefficient （ADC） values of lesions at different sites were measured, and one-way analysis of variance and the least significant difference t-test were used to compare the differences between groups and draw receiver operating characteristic curves. The tumors were excised for biopsy and analyzed using immunohistochemistry. Results： The mean ADCs were （0.81 ± 0.10） × 10^-3mm^2/s for intercranial RDD, （0.73 ± 0.05） × 10^-3mm^2/s for nasopharyngeal RDD, （0.74 ± 0.11） × 10^-3mm2/s for bone RDD, and （0.71 ± 0.04） × 10^-3mm2/s for soft-tissue RDD. The optimum ADC to distinguish intracranial RDD from lymphoma was 0.79 × 10^-3mm2/s （62.5% sensitivity and 100% specificity） and to distinguish meningioma from intracranial RDD was 0.92 × 10^-3mm^2/s （62.5% sensitivity and 100% specificity）. Levels of C-reactive protein, erythrocyte sediment rate and D-dimer were significantly elevated （81%, 87%, and 75%, respectively）. On immunohistochemistry, RDD was positive for both S-100 and CD68 proteins but negative for CD1a. Conclusions： Conventional MRI, combined with diffusion-weighted imaging and ADC mapping, is an important diagnostic tool in evaluating RDD patients. An accurate diagnosis of RDD should consider the clinical features, imaging characteristics, and the pathological findings.

Marchiafava-Bignami disease:A case report

Rationale:Clinicians encounter multiple alcohol-related illnesses in practice,and Marchiafava-Bignami disease is a rare and devastating entity among them.It is a toxic-demyelinating disease and seen in chronic alcoholics,although it may be occasionally observed in chronically malnourished teetotalers.The clinical presentations are diverse.The symptoms and signs are non-specific,and the onset can be acute or chronic.Patient’s concerns:A 45-year-old right-handed patient suffered from alcohol use disorder with multiple non-specific neuropsychiatric manifestations.Diagnosis:Marchiafava-Bignami disease.Interventions:Thiamine,folate,vitamin B12,and steroid therapy.Outcome:The patient’s behaviour was significantly improved but dysarthria and pyramidal signs persisted.He was left with permanent cognitive impairment.Lessons:Though prompt therapy may halt the demyelinating process in this disease,the treatment remains a challenge in clinical practice.The recognition of the neuro-radiologic features is crucial to establish an early diagnosis.

Microstructural damage pattern of vascular cognitive impairment: a comparison between moyamoya disease and cerebrovascular atherosclerotic disease

Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China(approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.

Diffusion-weighted MRI in a liver protocol: Its role in focal lesion detection

AIM: To evaluate the role of diffusion-weighted imaging (DWI) in the detection of focal liver lesions (FLLs), using a conventional magnetic resonance imaging (MRI) protocol. METHODS: Fifty-two patients (22 males, average age 55.6 years, range: 25-82 years), studied using a 1.5 Tesla magnetic resonance scanner, were retrospectively analyzed; detection of FLLs was evaluated by considering the number of lesions observed with the following sequences: (1) respiratory-triggered diffusion-weighted single-shot echo-planar (DW SS-EP) sequences; (2) fat-suppressed fast spin-echo (fs-FSE) T2 weighted sequences; (3) steady-state free precession (SSFP) images; and (4) dynamic triphasic gadolinium-enhanced images, acquired with three-dimensional fast spoiled gradient-echo (3D FSPGR). Two radiologists independently reviewed the images: they were blinded to their respective reports. DW SS-EP sequences were compared to fs-FSE, SSFP and dynamic gadolinium-enhanced acquisitions using a t -test. Pairs were compared for the detection of: (1) all FLLs; (2) benign FLLs; (3) malignant FLLs; (4) metastases; and (5) hepatocellular carcinoma (HCC). RESULTS: Interobserver agreement was very good (weighted = 0.926, CI = 0.880-0.971); on the consensus reading, 277 FLLs were detected. In the comparison with fs-FSE, DW SS-EP sequences had a significantly higher score in the detection of all FLLs, benign FLLs, malignant FLLs and metastases; no statistical difference was observed in the detection of hepatocellular carcinoma (HCCs). In the comparison with SSFP sequences, DW SS-EP had significantly higher scores (P < 0.05) in the detection of all lesions, benign lesions, malignant lesions, metastases and HCC. All FLLs were better detected by dynamic 3D FSGR enhanced acquisition, with P = 0.0023 for reader 1 and P = 0.0086 for reader 2 in the comparison with DW SS-EP sequences; with reference to benign FLLs, DW SS-EP showed lower values than 3D FSPGR enhanced acquisition (P < 0.05). No statistical differences were observed in the detection of malignant lesions and metastases; considering HCCs, a very slight difference was reported by reader 1 (P = 0.049), whereas no difference was found by reader 2 (P = 0.06). CONCLUSION: In lesion detection, DWI had higher scores than T2 sequences; considering malignant FLLs, no statistical difference was observed between DWI and dynamic gadolinium images.

Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson＇s disease models

Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson＇s disease animal models.They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra,but also satisfy the requirements for iron deposition.However,few studies have compared the characteristics of these two models by magnetic resonance imaging.In this study,rat models of Parkinson＇s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra.At 1,2,4,and 6 weeks after injection,coronal whole-brain T2-weighted imaging,transverse whole-brain T2-weighted imaging,and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2＊ values at the injury site.The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group.In the 6-hydroxydopamine group,the fractional anisotropy value was decreased,but T2＊ values were increased on the right side of the substantia nigra at 1 week.Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods,while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson＇s disease over long periods.

Why psychosis is frequently associated with Parkinson's disease?

Psychosis is a common non-motor symptom of Parkinson’s disease whose pathogenesis remains poorly understood. Parkinson’s disease in conjunction with psychosis has been shown to induce injury to extracorticospinal tracts as wel as within some cortical areas. In this study, Parkinson’s disease patients with psychosis who did not receive antipsychotic treatment and those without psychosis underwent diffusion tensor imaging. Results revealed that in Parkinson’s disease patients with psychosis, damage to the left frontal lobe, bilateral occipital lobe, left cingulated gyrus, and left hippocampal white-matter fibers were greater than damage to the substantia nigra or the globus pal idus. Damage to white-matter fibers in the right frontal lobe and right cingulate gyrus were also more severe than in the globus pal idus, but not the substantia nigra. Damage to frontal lobe and cingulate gyrus white-matter fibers was more apparent than that to occipital or hippocampal fiber damage. Compared with Parkinson’s disease patients without psychosis, those with psychosis had significantly lower fractional anisotropy ratios of left frontal lobe, bilateral occipital lobe, left cingu-lated gyrus, and left hippocampus to ipsilateral substantia nigra or globus pal idus, indicating more severe damage to white-matter fibers. These results suggest that psychosis associated with Par-kinson’s disease is probably associated with an imbalance in the ratio of white-matter fibers be-tween brain regions associated with psychiatric symptoms （frontal lobe, occipital lobe, cingulate gyrus, and hippocampus） and those associated with the motor symptoms of Parkinson’s disease （the substantia nigra and globus pal idus）. The relatively greater damage to white-matter fibers in psychiatric symptom-related brain regions than in extracorticospinal tracts might explain why psy-chosis often occurs in Parkinson’s disease patients.

Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology

AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical limitations.RESULTS: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected variables. The most relevant findings using metabolomics indicate increased levels of triglyceride and monounsaturated fatty acids in severe steatosis but those results were accompanied by a significant depletion of diglycerides, polyunsaturated fatty acids, glucose-6-phosphate and the ATP/AMP ratio. Combined data indicated the coordinated action on mitochondrial fat oxidation and glucose transport activity and may support the consideration of NAFLD as a likely mitochondrial disease. This concept may helpto explain the dissociation between excess lipid storage in adipose tissue and NAFLD and may direct the search for plasma biomarkers and novel therapeutic strategies. A limitation of our study is that data were obtained in a relatively low number of patients.CONCLUSION: MRI is sufficient to stage NAFLD in obese patients and to assess the improvement after bariatric surgery. Other data were superfluous for this purpose.