Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

[Cerebral lesions of DWI hyperintensity in patients with subacute stroke assessed by intravoxel incoherent motion technique].

OBJECTIVE: To investigate the cerebral lesions of diffusion weighted imaging (DWI) hyperintensity in patients with subacute stroke with intravoxel incoherent motion (IVIM) technique. METHODS: The clinical data of 20 patients with ischemic stroke (3 to 7 d after onset) who underwent DWI and IVIM scanning between June 2014 and July 2015, were retrospectively analyzed. The parameters from IVIM including slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) were processed. DWI hyperintensity was segmented by its signal intensity greater than the mean+2 standard deviations of the value in the homologous contralateral region. Then, DWI hyperintensity was classified into two regions of interest (ROIs): infarction core and peri-core with the ADC threshold of 0.55 × 10⁻³ mm²/s. The mirrored ROIs of infarction core and peri-core were also obtained. Then, we measured the values of ADC and D, D(*) and f in these ROIs. The ratios of ADC (rADC), D (rD), D(*) (rD(*)) and f (rf) were also calculated (e.g., rADC=ADCinfarction core/ADCmirrored region). RESULTS: Compared with mirrored region, ADC, D and f in the infarction core region decreased by 45% (P<0.001), 42% (P<0.001) and 32% (P<0.001), respectively; while ADC, D and f in the peri-core region decreased by 22% (P<0.001), 32% (P<0.001) and 8% (P=0.009), respectively. The values of rADC, rD, rD(*) and rf in the infarction core region were significantly lower than those in the peri-core region (all P<0.001). Pearson analysis showed that rADC was positively correlated with rf in the peri-core region (r=0.467, P=0.038). CONCLUSION: During subacute stage of stroke, compared to the infarction core region within DWI hyperintensity, D and f increase in the peri-core region of DWI hyperintensity, reflecting the increased water diffusion in microstructure and perfusion volume in microvasculature. This result shows that the potential reason for the heterogeneous ADC signal is associated with the disappearance of cellular edema and microvascular compensatory with increased blood volume.

Effects of APOE ε2 allele on basal forebrain functional connectivity in mild cognitive impairment.

BACKGROUND: Basal forebrain cholinergic system (BFCS) dysfunction is associated with cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Apolipoprotein E (APOE) ε2 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on APOE. OBJECTIVE: We investigated the effect of the APOE ε2 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients. METHOD: We included 60 MCI patients with APOE ε3/ε3, 18 MCI patients with APOE ε2/ε3, 73 CN subjects with APOE ε3/ε3, and 36 CN subjects with APOE ε2/ε3 genotypes who had resting-state functional magnetic resonance imaging data from the Alzheimer's disease Neuroimaging Initiative. We used BFCS subregions (Ch1-3 and Ch4) as seeds and calculated the FC with other brain areas. Using a mixed-effect analysis, we explored the interaction effects of APOE ε2 allele × cognitive status on BFCS-FC. Furthermore, we examined the relationships between imaging metrics, cognitive abilities, and AD pathology markers, controlling for sex, age, and education as covariates. RESULTS: An interaction effect on functional connectivity was found between the right Ch4 (RCh4) and left insula (p < 0.05, corrected), and between the RCh4 and left Rolandic operculum (p < 0.05, corrected). Among all subjects and APOE ε2 carriers, RCh4-left Insula FC was associated with early tau deposition. Furthermore, no correlation was found between imaging metrics and amyloid burden. Among all subjects and APOE ε2 carriers, FC metrics were associated with cognitive performance. CONCLUSION: The APOE ε2 genotype may play a protective role during BFCS degeneration in MCI.

Characterizing mild cognitive impairment in prodromal Parkinson's disease: A community-based study in China.

OBJECTIVE: The International Parkinson and Movement Disorder Society (MDS) has published research criteria for prodromal Parkinson's disease (pPD), which includes cognitive impairment as a prodromal marker. However, the clinical features of mild cognitive impairment (MCI) in pPD remain unknown. Our study aimed to evaluate the frequency and clinical features of mild cognitive impairment of pPD in the elderly in China. METHODS: The cross-sectional community-based study recruited 2688 participants aged ≥50 years. Subjects were diagnosed with pPD according to the MDS criteria. Overall, 39 pPD and 22 healthy controls underwent comprehensive clinical and neuropsychological assessment. MCI was also diagnosed by the MDS criteria. Next, we investigated the relationship between clinical factors and cognition. RESULTS: Among the 2,663 dementia-free and Parkinson disease (PD)-free participants, 55 met the criteria for pPD (2.1%) and 23 pPD met the criteria for MCI. Memory, attention/working memory, and executive function were the most frequent impaired domains, and amnestic MCI multidomain phenotype was the most frequent MCI subtype (69.57%) in pPD. Additionally, correlation analysis revealed that the global cognitive performance was negatively related to UPDRS-III score (r = -0.456, p = 0.004). CONCLUSION: MCI, specifically impairment in memory, attention/working memory, and executive domain, is present at the prodromal stage of PD. In addition, cognitive performance is correlated with motor symptoms in pPD. Our results reflect that cognitive profile, combined with motor symptoms, can help clinicians to identify individuals with pPD early, as those would be the optimal candidates for neuroprotective therapy.

A multiple-tissue-specific magnetic resonance imaging model for diagnosing Parkinson's disease: a brain radiomics study.

Brain radiomics can reflect the characteristics of brain pathophysiology. However, the value of T1-weighted images, quantitative susceptibility mapping, and R2* mapping in the diagnosis of Parkinson's disease (PD) was underestimated in previous studies. In this prospective study to establish a model for PD diagnosis based on brain imaging information, we collected high-resolution T1-weighted images, R2* mapping, and quantitative susceptibility imaging data from 171 patients with PD and 179 healthy controls recruited from August 2014 to August 2019. According to the inclusion time, 123 PD patients and 121 healthy controls were assigned to train the diagnostic model, while the remaining 106 subjects were assigned to the external validation dataset. We extracted 1408 radiomics features, and then used data-driven feature selection to identify informative features that were significant for discriminating patients with PD from normal controls on the training dataset. The informative features so identified were then used to construct a diagnostic model for PD. The constructed model contained 36 informative radiomics features, mainly representing abnormal subcortical iron distribution (especially in the substantia nigra), structural disorganization (e.g., in the inferior temporal, paracentral, precuneus, insula, and precentral gyri), and texture misalignment in the subcortical nuclei (e.g., caudate, globus pallidus, and thalamus). The predictive accuracy of the established model was 81.1 ± 8.0% in the training dataset. On the external validation dataset, the established model showed predictive accuracy of 78.5 ± 2.1%. In the tests of identifying early and drug-naïve PD patients from healthy controls, the accuracies of the model constructed on the same 36 informative features were 80.3 ± 7.1% and 79.1 ± 6.5%, respectively, while the accuracies were 80.4 ± 6.3% and 82.9 ± 5.8% for diagnosing middle-to-late PD and those receiving drug management, respectively. The accuracies for predicting tremor-dominant and non-tremor-dominant PD were 79.8 ± 6.9% and 79.1 ± 6.5%, respectively. In conclusion, the multiple-tissue-specific brain radiomics model constructed from magnetic resonance imaging has the ability to discriminate PD and exhibits the advantages for improving PD diagnosis.

High-resolution computed tomography findings independently predict epidermal growth factor receptor mutation status in ground-glass nodular lung adenocarcinoma.

BACKGROUND: For lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation, small molecule tyrosine kinase inhibitors are more effective. Some patients could not obtain enough histological specimens for EGFR gene mutation detection. Specific imaging features can predict EGFR mutation status to a certain extent. AIM: To assess the associations of EGFR mutations with high-resolution computerized tomography (HRCT) features in ground-glass nodular lung adenocarcinoma. METHODS: This study retrospectively assessed patients with ground-glass nodular lung adenocarcinoma diagnosed between January 2011 and March 2017. EGFR gene mutations in exons 18-21 were detected. The patients were classified into mutant EGFR and wild-type groups, and general data and HRCT image characteristics were assessed. RESULTS: Among 98 patients, 31 (31.6%) and 67 (68.4%) had mutated and wild-type EGFR in exons 18-21, respectively. Gender, age, smoking history, location of lesions, morphology, edges, borders, pleural indentations, and associations of nodules with bronchus and blood vessels were comparable in both groups (all P > 0.05). Patients with mutant EGFR had larger nodules than those with the wild-type (17.19 ± 6.79 and 14.37 ± 6.30 mm, respectively; P = 0.047). Meanwhile, the vacuole/honeycomb sign was more frequent in the mutant EGFR group (P = 0.011). The logistic regression prediction model included the combination of nodule size and vacuole/honeycomb sign (OR = 1.120, 95%CI: 1.023-1.227, P = 0.014) revealed a sensitivity of 83.9%, a specificity of 52.2% and an AUC of 0.698 (95%CI: 0.589-0.806; P = 0.002). CONCLUSION: Nodule size and vacuole/honeycomb features could independently predict EGFR mutation status in ground-glass nodular lung adenocarcinoma.

Cardiorespiratory arrest after iso-osmolar iodinated contrast injection: A case report of contrast-induced encephalopathy following contrast-enhanced computed-tomography.

RATIONALE: Contrast-induced encephalopathy (CIE) is a rare complication caused by administration of intravascular contrast media and characterized by acute reversible neurological disturbance. Most of the CIE cases are reported after arterial administration of contrast media such as during cerebral or coronary angiographies, yet only a few articles have reported CIE secondary to intravenous contrast. A case of CIE secondary to intravenous contrast administration is reported here. PATIENT CONCERNS: A 68-year-old man was admitted to our hospital for contrast-enhanced chest computed-tomography (CT) examination due to suspected pulmonary nodules. After CT examination, the patient lost consciousness and experienced a cardiorespiratory arrest. An emergency plain brain CT was done immediately which showed abnormal cortical contrast enhancement and cerebral sulci hyperdensity. DIAGNOSES: After excluding other differential diagnoses such as electrolytes imbalance, hypo/hyperglycemia, cardiogenic pathologies and other neurological emergencies such as cerebral hemorrhage, cerebral infarction, the final diagnosis of CIE was made. INTERVENTIONS: The patient was admitted to the intensive care unit for further management. A series of supportive treatments were arranged. OUTCOMES: Follow-up visits at the outpatient clinic showed no lasting neurological deficits. LESSONS: CIE should be considered as 1 of the differential diagnoses for a patient with acute neurologic symptoms after iodinate contrast administration. Neuroradiological imaging examinations are essential to rule out other etiologies such as acute cerebral infarction or intracranial hemorrhage.

[Functional MR study of hepatic fibrosis].

The accurate diagnosis and staging of hepatic fibrosis is crucial for treatment and prognosis of liver disease. The current gold standard is liver biopsy, but it cannot be used in population-based screening, and has well known drawbacks if used for monitoring of disease progression or treatment results. Functional MR, as a non-invasive method, is increasingly used in hepatic fibrosis and became the current hot spot. Most recently available functional MR imaging techniques including diffusion weighted imaging, perfusion weighted imaging and MR spectroscopy can detect cirrhosis or fibrosis reasonably accurately. However, to date only MR elastography has been able to stage fibrosis or diagnose mild disease. MR diffusion weighted appears next most promising.

[Magnetic resonance signal features of superparamagnetic iron oxide with different particle size and concentration].

OBJECTIVE: To investigate the magnetic resonance (MR) signal features of superparamagnetic iron oxide (SPIO) with different particle size and concentration. METHODS: The superparamagnetic iron oxide with different concentration and particle size was scanned by magnetic resonance; T1, T2 and T2(*) values of each group were recorded to evaluate the features of MR signals. RESULTS: The T1 value of SPIO with different particle size had negative linear relationship with concentration. In low concentration the T2 and T2(*) values were elevated markedly with the particle size decreased; while in high concentration the T2 and T2(*)values were elevated gently with particle size decreased. lg(T2), particle size and concentration of SPIO had linear relationship. CONCLUSIONS: SPIO affects magnetic resonance signal mainly with effect on T1 and T2. T2 value can be regarded as the major detection index in the magnetic resonance scan of SPIO. There is a linear relationship among particle size, SPIO concentration and lg(T2) value.

[Magnetic resonance signal detection of superparamagnetic iron oxide nanoparticles and its biological effects on endothelial cells].

OBJECTIVE: To investigate the magnetic resonance (MR) signal changes of superparamagnetic iron oxide (SPIO) and its biological effects on endothelial cells. METHODS: The citric-acid coated SPIO was synthesized by co-precipitation method. The human umbilical vein endothelial cells (HUVECs) were incubated with SPIO for 24 h in culture medium at iron concentration of 0.01, 0.05, 0.10, 0.15 mg/ml (experimental groups), and the cells incubated without SPIO served as control groups. The uptake efficiency of intracellular iron was measured by Prussian blue staining, and the cell viability was monitored by Calcein-AM method. The cell cytoskeleton (F-actin and tubulin), adherence and migration capacity were measured by immunofluorescence staining. The iron oxide nanoparticles distribution and the cellular organelle change were monitored by transmission electron microscopy (TEM). Quantification of particle uptake was measured by atomic absorption spectrometry. The MR signal of endothelial cells after labeling was monitored by Philips 3.0 T MR scanner. RESULTS: SPIO was uptaken by HUVECs in a concentration-dependence manner. Compared with the control group, cell viability was decreased along with the increase of iron concentration. Compared with the control group, the cell cytoskeleton was markedly disorganized and the FAK spot was bigger and sparser.The nanoparticles were mainly existed in lysosomes, and the higher concentration of SPIO, the more lysosomes and vacuoles presented in the cells. The iron content per cell was (55.86 +/-9.935) pg when the SPIO concentration was 0.15 mg/ml. The MR image showed that the cells labeled with SPIO resulted in the decrease of MR signal. CONCLUSION: The cells labeled with SPIO can be detected by MR. The cell viability, cytoskeleton, adherence and migration capacity of HUVECs are affected by citric-acid coated SPIO in a concentration-dependent manner.

[Evaluation of kidney oxygen bioavailability in acute renal failure by blood oxygen level dependent magnetic resonance imaging].

OBJECTIVE: To assess the kidney oxygen bioavailability in acute renal failure using blood oxygen level dependent (BOLD) magnetic resonance (MR) imaging. METHODS: Twenty-one patients with acute renal failure, including 18 patients with oliguric renal failure, 1 nonoliguric acute renal failure and 2 functional renal failure were enrolled in the study; 20 healthy subjects served as controls. All subjects received renal functional MR examination. BOLD MR imaging with 16 gradient-recalled-echoes on a 1.5-T scanner were performed. R2(*)(1/sec) values of the cortex and medulla and R2(*) ratio of the medulla to cortex (R2(*) ratio of M/C) of the renal were recorded respectively. RESULTS: The R2(*) values of the medulla was higher than those of the cortex in controls (17.64 +/-1.86/sec vs 13.73 +/-0.49/sec, P<0.00). The R2(*) ratio of M/C in controls was 1.28 +/-0.06. The R2(*) values of the medulla (13.31 +/-4.28/sec) and cortex (12.25 +/-2.41/sec) and the R2(* ) ratio of M/C (1.01 +/-0.25) in oliguric renal failure were lower than those in controls (P <0.05). Patients with functional renal failure and nonoliguric acute renal failure had higher R2(*) values in cortex and medulla and higher R2(*) ratio of M/C than those of controls. CONCLUSION: BOLD MRI demonstrates that decreased R2(*) values of cortex and medulla suggest lower oxygen bioavailability in acute renal failure and decreased R2(*)ratio of M/C suggests the disappearance of a steep cortico-medullary gradient of oxygen.

[Value of diffusion-weighted MR imaging in diagnosis of acute rejection after renal transplantation].

OBJECTIVE: To evaluate the feasibility of MR diffusion-weighted imaging (DWI) in diagnosis of acute rejection after renal transplantation. METHODS: Sixty-nine patients who underwent renal transplantation were enrolled in the study. According to the clinical features and renal biopsy, 26 patients were designated in rejection group and 43 in non-rejection group. Patients in non-rejection group underwent MR DWI scan at 2 to 3 weeks after operation, and those in rejection group underwent scan at 5 d before or after renal biopsy. Then the apparent diffusion coefficient (ADC) values of transplanted kidneys were measured with high diffusion sensitivity gradient factors (b values). RESULTS: Patients with acute rejection had significantly lower ADC (P <0.04) than non-rejection patients with all the different b values (b=200, 400, 600, 800, 1,000 s/mm(2)). The ROC curves showed that sensitivity and specificity were best when b value was 800 s/mm(2). CONCLUSION: DWI is a potential and reliable non-invasive method for the diagnosis of the acute rejection after renal transplantation.

[MRI scan of striatum volume in healthy adults].

OBJECTIVE: To examine the age, sex, and hemispheric differences in volume of the striatum by MRI in healthy adults. METHODS: The volumes of the bilateral caudate nucleus and putamen were measured on MR images in 100 healthy right-handed adults (18-70 y). RESULTS: The volume of bilateral caudate nucleus and putamen in healthy adults was (8.42 +/-0.88) cm(3) and (8.90 +/-0.89) cm(3), which were decreased with aging (for caudate nucleus r=-0.727, P<0.001; for putamen r=-0.709, P<0.001). The average annual shrinkage rate was 0.52 % in the caudate nucleus and 0.50 % in the putamen. There were no gender differences in the volume of the striatum, however, the age-related shrinkage of the striatum was more evident in men than that in women. The volume of the left caudate nucleus (t=4.43, P<0.001) and the putamen (t=4.88, P<0.001) was greater than that of its right counterpart. CONCLUSION: Bilateral age-related shrinkage of the striatum is found in healthy adults, which is more evident in men than that in women. In both sexes, significant leftward asymmetry in volume of the caudate nucleus and the putamen is found.

[Role of activated brain regions during tactile stimulation in early Parkinson's disease: a preliminary fMRI study].

OBJECTIVE: To investigate the role of activated brain regions in Parkinson's disease (PD) during tactile stimulation. METHODS: Twenty-one patients with early PD[mean age (60.43 +/-9.65)y] and twenty-two age-matched healthy controls [mean age (59.23 +/-11.12)y] were enrolled in the study. All the patients were tested by the United Parkinson Disease Rating Scale (UPDRS) as the evaluation of the disease severity. A block design was used when the finger tactile stimulation was given to the subjects. The hypoactive and hyperactive regions of PD patients were confirmed first, which were identified as regions of interest (ROI). ROI analysis was performed to quantify BOLD signal changes when subjects were under tactile stimulation. The correlations of signal changes with disease severity, and correlations of hyperactive with hypoactive regions were analyzed. RESULTS: Right primary sensory and motor cortex, right supplementary motor area (SMA), bilateral caudates, bilateral precuneus, bilateral occipital visual cortex and left middle temporal gyrus were hypoactivated in PD, while right prefrontal cortex (PFC) and right caudate were hyperactivated. The hypoactivation of right SMA was negatively correlated with disease severity. All the hypoactive and hyperactive regions were positively correlated with activation of caudates. There was a positive correlation between hyperactive PFC and hypoactive regions. CONCLUSIONS: The signal change of SMA is directly related to disease severity in early PD, and caudates may play a significant role in PD tactile processing. The hyperactivation of PFC may be not a compensation but a pathophysiological change related to PD neural dysfunction.

[Biochemical metabolic changes detected by phosphorus-31 MR spectroscopy in liver of fasting rabbits].

OBJECTIVE: To investigate the biochemical metabolic changes detected by phosphorus-31 MR spectroscopy ((31)P MRS) with pathologic changes in the liver of fasting rabbits. METHODS: A total of 22 rabbits were under the starvation up to death to establish animal models. Hepatic (31)P MRS was performed in different period of 10 rabbits including normal condition, over-starvation, agonal condition and death after 30 min. Other 9 rabbits were divided into three type including over-starvation, agonal condition and death group with 3 rabbits in each group, and 3 healthy rabbits served as controls. All the 12 rabbits were sacrificed for the hepatic pathological examination. The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. RESULTS: All the relative quantification of phosphorus metabolites were changed significantly from starvation to death (X(2)=23.13-35.41, P<0.01). The relative quantifications of ATP of normal condition, over-starvation, agonal condition and death were 2.54 +/-0.53, 1.73 +/-0.14, 0.88 +/-0.23 and 0.05 +/-0.08, respectively (rs=1.0, P<0.01). The relative quantifications of PDE from normal to death were 1.25 +/-0.54, 2.76 +/-0.23, 3.33 +/-0.49 and 3.87 +/-0.43, respectively, and those of Pi were 0.42 +/-0.02, 0.65 +/-0.05, 0.89 +/-0.15 and 0.99 +/-0.08, respectively (rs=1.0, P <0.01). The relative quantifications of PME were also significantly changed (rs=0.4, P=0.6). The pathologic changes of normal condition, over-starvation, agonal condition and death: decreased size of hepatocytes, loss of cell number, cellular swelling, degeneration and cell necrosis or hepatic hemorrhage became more and more pronounced. CONCLUSION: (31)P MRS can monitor dynamic changes of relative quantification of phosphorus metabolites, which are correlated with the pathological severity of acute hepatic injury by fasting.

[Evaluation of biochemical metabolites by 31P MR spectroscopy in leukemic infiltration of liver].

OBJECTIVE: To evaluate the changes of phosphorus metabolites in leukemic infiltration of liver (LIL) with two-dimensional chemical shift imaging(2D CSI)(31)phosphorus MR spectroscopy ((31)P MRS). METHODS: Fifteen patients with LIL and 12 healthy subjects (control group) were scanned with liver 2D CSI(31)P MRS by a 1.5T MR Scanner(Sonata, Siemens Corporation). Relative quantification of phosphorus metabolites including phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE) and beta-adenosine- triphosphate (beta-ATP) were detected and after calibrated with model factor, the ratios of PME/PDE, PME/(PME+PDE), PME/ATP, PDE/ATP and Pi/ATP were analyzed. RESULTS: Compared with control group, the PME value, PME/PDE ratio, PME/(PME+PDE) ratio and PME/ATP ratio were increased in LIL group (1.992 +/-0.876 Compared with 1.167 +/-0.427, P <0.05), (0.551 +/-0.339 Compared with 0.254 +/-0.059,P <0.01), (0.326 +/-0.13 Compared with 0.199 +/-0.049, P <0.01)and (1.402 +/-0.654 Compared with 0.792 +/-0.232, P <0.01) respectively. CONCLUSION: (31)P MRS examination can be used as a non-invasive procedure to evaluate the changes of phosphorus metabolites of leukemic infiltration of liver. The increase of PME value and its ratios to PDE, ATP and PME+PDE may indicate leukemic infiltration of liver.

Progressive brain atrophy in Parkinson's disease patients who convert to mild cognitive impairment.

AIMS: Cognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins. METHODS: Ninety-four patients with PD and 32 controls were included in this study. Neuropsychological tests were performed at baseline and after 28 months to identify which patients had normal cognition and which ones developed PD-MCI after follow-up ("converters"). Gray matter atrophy was assessed in cross-sectional and longitudinal analyses, respectively. The associations between altered GMV with dopamine transporter (DAT) results and the level of CSF proteins were assessed. RESULTS: Among the 94 patients with normal cognition at baseline, 24 (mean age, 63.1 years) developed PD-MCI after 28 months of follow-up, and 70 (mean age, 62.3 years) remained nonconverters. The converters showed significant right temporal atrophy at baseline and extensive atrophy in temporal lobe at follow-up. Progressive bilateral frontal lobe atrophy was found in the converters. Baseline right temporal atrophy was correlated with the striatal dopaminergic degeneration in the converters. No correlation was found between the right temporal atrophy and the alterations of CSF proteins. CONCLUSION: Early atrophy in temporal lobes and progressive atrophy in frontal lobes might be a biomarker for developing multidomain impairment of cognition and converting to PD-MCI. Furthermore, cognition-related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD-MCI.

[Hard nut to crack in diagnosis of pituitary hyperplasia secondary to primary hypothyroidism and reasons of misdiagnosis].

OBJECTIVE: To analyze the difficulty in diagnosis of pituitary hyperplasia secondary to primary hypothyroidism and reasons of misdiagnosis. METHODS: Ten patients with clinical manifestations of primary hypothyroidism, 3 males and 7 females, aged 7 - 26, underwent MR imaging and serum hormone examination before and after thyroid hormone replacement therapy. T1-weighted images without and with contrast material enhancement in sagittal and coronal planes were obtained. Serum free triiodothyronine, free thyroxine, thyrotropic-stimulating hormone and prolactin (PRL) levels were measured. RESULTS: Obvious symmetrical enlargement of the pituitary gland with homogeneous signal intensity was revealed by MRI in all the patients. The height of the pituitary ranged 1.2 - 2.2 cm. The pituitary glands appeared homogeneously enhanced after Gd-DTPA administration. After 3 - 6 months of L-thyroxin replacement therapy, follow-up MRI showed that the pituitary glands reduced in size markedly in 9 cases, and the plasma thyroxine, TSH, and PRL levels of these 9 cases turned normal. One patient was misdiagnosed as with macroadenoma and was treated with gamma knife, resulting in permanence hypothyroidism. CONCLUSION: Symmetrical enlargement of pituitary gland with homogeneously enhancement on MRI has great diagnostic value in pituitary hyperplasia with primary hypothyroidism. Thyroid hormone replacement therapy can cause regression of the enlarged pituitary, thus avoiding unnecessary surgery.

Whole-tumor perfusion CT using texture analysis in unresectable stage IIIA/B non-small cell lung cancer treated with recombinant human endostatin.

BACKGROUND: To observe the dynamic changes of blood perfusion with whole-tumor computed tomography (CT) perfusion imaging using texture analysis in patients with unresectable stage IIIA/B non-small cell lung cancer (NSCLC) treated with recombinant human endostatin (Endostar). METHODS: This phase II clinical trial recruited 11 patients diagnosed with stage IIIA/B NSCLC. Histological examination prior to treatment revealed squamous cell carcinoma in 4 cases and adenocarcinoma in 7 cases. All patients underwent contrast-enhanced perfusion CT at baseline and a second CT scan 1 week after treatment initiation with Endostar. CT perfusion images including blood flow (BF), blood volume (BV), and permeability (PMB) were imported into OmniKinetics software to quantitatively assess the texture features. Skewness, kurtosis, and entropy were calculated at baseline and after anti-angiogenic therapy. Changes in tumor were analyzed using Wilcoxon signed-rank test. The association of parameters with survival was evaluated using Cox proportional hazards regression model. RESULTS: There were no statistical differences in the mean values of BF, BV, and PMB before and after treatment (P=0.594, 0.477 and 0.328, respectively). The skewness on BF images demonstrated significant differences at baseline and after treatment (0.6±2.7 vs. 1.0±2.6, P=0.010), while skewness of BV and PMB showed no significant variation (P=0.477 and 0.213, respectively). The kurtosis and entropy for BF, BV and PMB showed no significant differences (all P>0.05). In adenocarcinoma, the mean BF showed no significant differences at baseline and after treatment (76.5±25.7 vs. 101.2±46.4, P=0.398), while skewness for BF was significantly higher after treatment than at baseline (-0.19±3.3 vs. 0.59±3.2, P=0.028). No significant associations were found between perfusion CT imaging parameters and progression-free survival. CONCLUSIONS: These results suggested that blood perfusion showed improvement with whole-tumor perfusion CT using texture analysis in patients with stage IIIA/B NSCLC treated by Endostar.

Oscillation-specific nodal alterations in early to middle stages Parkinson's disease.

BACKGROUND: Different oscillations of brain networks could carry different dimensions of brain integration. We aimed to investigate oscillation-specific nodal alterations in patients with Parkinson's disease (PD) across early stage to middle stage by using graph theory-based analysis. METHODS: Eighty-eight PD patients including 39 PD patients in the early stage (EPD) and 49 patients in the middle stage (MPD) and 36 controls were recruited in the present study. Graph theory-based network analyses from three oscillation frequencies (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; slow-3: 0.073-0.198 Hz) were analyzed. Nodal metrics (e.g. nodal degree centrality, betweenness centrality and nodal efficiency) were calculated. RESULTS: Our results showed that (1) a divergent effect of oscillation frequencies on nodal metrics, especially on nodal degree centrality and nodal efficiency, that the anteroventral neocortex and subcortex had high nodal metrics within low oscillation frequencies while the posterolateral neocortex had high values within the relative high oscillation frequency was observed, which visually showed that network was perturbed in PD; (2) PD patients in early stage relatively preserved nodal properties while MPD patients showed widespread abnormalities, which was consistently detected within all three oscillation frequencies; (3) the involvement of basal ganglia could be specifically observed within slow-5 oscillation frequency in MPD patients; (4) logistic regression and receiver operating characteristic curve analyses demonstrated that some of those oscillation-specific nodal alterations had the ability to well discriminate PD patients from controls or MPD from EPD patients at the individual level; (5) occipital disruption within high frequency (slow-3) made a significant influence on motor impairment which was dominated by akinesia and rigidity. CONCLUSIONS: Coupling various oscillations could provide potentially useful information for large-scale network and progressive oscillation-specific nodal alterations were observed in PD patients across early to middle stages.