Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

Background:

Previous studies have indicated that the cognitive deficits in patients with Alzheimer''s disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

Methods:

Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and “small-world” property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz, and 0.11–0.25 Hz).

Results:

At lower-frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz), the global efficiency, the CC and the “small-world” properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11–0.25 Hz), the CpL was much longer, and the “small-world” property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

Conclusions:

This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.     

Amplitude of Low-frequency Oscillations in Parkinson's Disease: A 2-year Longitudinal Resting-state Functional Magnetic Resonance Imaging Study

Background:

Neuroimaging studies have found that functional changes exist in patients with Parkinson''s disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.

Methods:

Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.

Results:

Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).

Conclusions:

The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease''s progression in patients with PD.     

Frequency of cognitive impairment and depression in Parkinson's disease: A preliminary case-control study

Background:

This study aimed to determine the frequency of cognitive impairment and depression in our Parkinson''s Disease (PD) and their relationship with disease severity and disability.

Patients and Methods:

A total of 40 PD patients and 40 age-, sex-, and educationally matched controls were studied. The Unified Parkinson Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores and the Hoehn and Yahr (HY) stage were documented. Depression was assessed using the Zung Self-Rating Depression Scale (ZSDS), while cognition was evaluated using a composite score of the mini-mental state examination (MMSE) score and category fluency score.

Results:

A total of 55% (22/40) of PD and 10% (4 of 40) of controls had depression (P<0.001). A total of 60% of PD (24/40) and 5% of controls (2/40) had cognitive impairment (P<0.001). Both NMS coexisted in 16 of 40 PD (40%) compared with none of the controls (P<0.001). UPDRS (motor and ADL) scores and HY stage were significantly worse with impaired ZSDS scores - P 0.001. UPDRS ADL was significantly impaired by the presence of cognitive impairment. Coexisting depression and cognitive impairment were associated with significant worsening of all scores of severity and disability.

Conclusion:

Cognitive impairment and depression accompany our PD and are related to disability and worsening disease severity.     

Comparison of Magnetic Resonance Elastography and Diffusion-weighted Imaging for Staging Hepatic Fibrosis

Background:

To compare the diagnostic values of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) in staging hepatic fibrosis (HF) in an animal model.

Methods:

This study consisted of 44 rabbits served as HF group and 9 normal rabbits. HF group was divided into two subgroups: Group A (n = 32) and Group B (n = 12). Rabbits in Group B were served as a complementary group when rabbits in Group A suddenly died during the study. Rabbits from control and Group A underwent abdominal MR imaging (MRI), MRE, and DWI. In Group A, random eight rabbits underwent MRI examinations at 4, 5, 6, 10 weeks after carbon tetrachloride oil subcutaneous injection. Liver stiffness (LS) and apparent diffusion coefficient (ADC) values of liver parenchyma were measured. The diagnostic performance of MRE and DWI for staging HF was compared using the receiver operating characteristic curve analysis on the basis of the histopathological analysis of HF.

Results:

Significant differences of LS and DWI values were present among HF stages (P < 0.005). The LS values measured on MRE (r = 0.838, P < 0.001) were more strongly correlated with the HF stages than with ADC values (r = −0.527, P < 0.001). The area under the receiver operating characteristic curve values of LS were significantly larger than those of DWI were for discriminating two stages of HF (0.979 vs. 0.712 for ≥ S1, 0.922 vs. 0.699 for ≥ S2). MRE showed higher specificity for predicting all stages of HF compared to DWI.

Conclusions:

MRE more strongly correlated with the HF stages than DWI and is more specific in predicting all HF stages.     

Role of Quantitative Magnetic Resonance Imaging Parameters in the Evaluation of Treatment Response in Malignant Tumors

Objective:

To elaborate the role of quantitative magnetic resonance imaging (MRI) parameters in the evaluation of treatment response in malignant tumors.

Data Sources:

Data cited in this review were obtained mainly from PubMed in English from 1999 to 2014, with keywords “dynamic contrast-enhanced (DCE)-MRI,” “diffusion-weighted imaging (DWI),” “microcirculation,” “apparent diffusion coefficient (ADC),” “treatment response” and “oncology.”

Study Selection:

Articles regarding principles of DCE-MRI, principles of DWI, clinical applications as well as opportunity and aspiration were identified, retrieved and reviewed.

Results:

A significant correlation between ADC values and treatment response was reported in most DWI studies. Most quantitative DCE-MRI studies showed a significant correlation between K^trans values and treatment response. However, in different tumors and studies, both high and low pretreatment ADC or K^trans values were found to be associated with response rate. Both DCE-MRI and DWI demonstrated changes in their parameters hours to days after treatment, showing a decrease in K^trans or an increase in ADC associated with response in most cases.

Conclusions:

Combinations of quantitative MRI play an important role in the evaluation of treatment response of malignant tumors and hold promise for use as a cancer treatment response biomarker. However, validation is hampered by the lack of reproducibility and standardization. MRI acquisition protocols and quantitative image analysis approaches should be properly addressed prior to further testing the clinical use of quantitative MRI parameters in the assessment of treatments.     

Hyperbaric Oxygen and Ginkgo Biloba Extract Ameliorate Cognitive and Memory Impairment via Nuclear Factor Kappa-B Pathway in Rat Model of Alzheimer's Disease

Background:

Hyperbaric oxygen (HBO) and Ginkgo biloba extract (e.g., EGB 761) were shown to ameliorate cognitive and memory impairment in Alzheimer''s disease (AD). However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B (NF-κB) pathway.

Methods:

AD rats were induced by injecting β-amyloid 25–35 into the hippocampus. All animals were divided into six groups: Normal, sham, AD model, HBO (2 atmosphere absolute; 60 min/d), EGB 761 (20 mg·kg⁻¹·d⁻¹), and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats; TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues.

Results:

Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy (HBO/EGB 761) was superior to either HBO or EGB 761 alone. In line, reduced apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761.

Conclusions:

Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.     

Diagnostic Utility of Diffusion-weighted Magnetic Resonance Imaging in Differentiating Small Solid Renal Tumors (≤4 cm) at 3.0T Magnetic Resonance Imaging

Background:

The aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤4 cm).

Methods:

In this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm² and values compared via the Kruskal–Wallis and Mann–Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.

Results:

The tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10⁻³ mm²/s), ccRCCs ([1.53 ± 0.31] × 10⁻³ mm²/s) and the normal renal parenchyma ([2.22 ± 0.12] × 10⁻³ mm²/s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10⁻³ mm²/s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.

Conclusions:

DW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.     

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice

Background:

Early diagnosis assumes a vital role in an effective treatment of Alzheimer''s disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.

Methods:

A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(¹⁸ F) fluoro-D-glucose ([¹⁸ F]-FDG) uptake in the hippocampus and cerebral cortex.

Results:

With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (¹⁸ F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (¹⁸ F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.

Conclusions:

The decline of (¹⁸ F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.     

Semi-quantitative Assessment of Brain Maturation by Conventional Magnetic Resonance Imaging in Neonates with Clinically Mild Hypoxic-ischemic Encephalopathy

Background:

Mild hypoxic-ischemic encephalopathy (HIE) injury is becoming the major type in neonatal brain diseases. The aim of this study was to assess brain maturation in mild HIE neonatal brains using total maturation score (TMS) based on conventional magnetic resonance imaging (MRI).

Methods:

Totally, 45 neonates with clinically mild HIE and 45 matched control neonates were enrolled. Gestated age, birth weight, age after birth and postmenstrual age at magnetic resonance (MR) scan were homogenous in the two groups. According to MR findings, mild HIE neonates were divided into three subgroups: Pattern I, neonates with normal MR appearance; Pattern II, preterm neonates with abnormal MR appearance; Pattern III, full-term neonates with abnormal MR appearance. TMS and its parameters, progressive myelination (M), cortical infolding (C), involution of germinal matrix tissue (G), and glial cell migration bands (B), were employed to assess brain maturation and compare difference between HIE and control groups.

Results:

The mean of TMS was significantly lower in mild HIE group than it in the control group (mean ± standard deviation [SD] 11.62 ± 1.53 vs. 12.36 ± 1.26, P < 0.001). In four parameters of TMS scores, the M and C scores were significantly lower in mild HIE group. Of the three patterns of mild HIE, Pattern I (10 cases) showed no significant difference of TMS compared with control neonates, while Pattern II (22 cases), III (13 cases) all had significantly decreased TMS than control neonates (mean ± SD 10.56 ± 0.93 vs. 11.48 ± 0.55, P < 0.05; 12.59 ± 1.28 vs. 13.25 ± 1.29, P < 0.05). It was M, C, and GM scores that significantly decreased in Pattern II, while for Pattern III, only C score significantly decreased.

Conclusions:

The TMS system, based on conventional MRI, is an effective method to detect delayed brain maturation in clinically mild HIE. The conventional MRI can reveal the different retardations in subtle structures and development processes among the different patterns of mild HIE.     

Coronal Diffusion-weighted Magnetic Resonance Imaging of the Kidney: Agreement with Axial Diffusion-weighted Magnetic Imaging in Terms of Apparent Diffusion Coefficient Values

Background:

Coronal diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) values have gradually become applied (following conventional axial DW-MRI) in the renal analysis. To explore whether data obtained using coronal DW-MRI are comparable with those derived using axial DW-MRI, this preliminary study sought to assess the agreement in renal ADC values between coronal DW-MRI and axial DW-MRI.

Methods:

Thirty-four healthy volunteers were enrolled in the study; written consents were obtained. All subjects underwent respiratory-triggered axial and coronal DW-MRI using a 1.5-MR system with b values of 0 and 800 s/mm². The signal-to-noise ratios (SNRs) of the two DW-MRI sequences were measured and statistically compared using the paired t-test. The extent of agreement of ADC values of the upper pole, mid-pole, and lower pole of the kidney; the mean ADC values of the left kidney and right kidney; and the mean ADC values of the bilateral kidneys were evaluated via calculation of intraclass correlation coefficients (ICCs) or Bland–Altman method between the two DW-MRI sequences.

Results:

The SNR of coronal DW-MR images was statistically inferior to that of axial DW-MR images (P < 0.001). The ICCs of the ADC values of each region of interest, and the mean ADC values of bilateral kidneys, between the two sequences, were greater than 0.5, and the mean ADCs of the bilateral kidneys demonstrated the highest ICC (0.869; 95% confidence interval: 0.739–0.935). In addition, 94.1% (32/34), 94.1% (32/34), and 97.1% (31/34) of the ADC bias was inside the limits of agreement in terms of the mean ADC values of the left kidneys, right kidneys, and bilateral kidneys when coronal and axial DWI-MRI were compared.

Conclusions:

ADC values derived using coronal DW-MRI exhibited moderate-to-good agreement to those of axial DW-MRI, rendering the former an additional useful DW-MRI method, and causing the ADC values derived using the two types of DW-MRI to be comparable.     

Clinical and Magnetic Resonance Imaging Results of Arthroscopic Repair of Intratendinous Partial-thickness Rotator Cuff Tears

Background:

Partial-thickness rotator cuff tears (PTRCTs) are being diagnosed more often because of high-resolution magnetic resonance imaging (MRI). Compared with articular and bursal side tears, there have been few studies about evaluating the clinical and structural outcomes after intratendinous tear repair.

Methods:

From 2008 to 2012, 33 consecutive patients with intratendinous PTRCTs underwent arthroscopic repair. All of them were retrospectively evaluated. The University of California at Los Angeles (UCLA) and constant scores were evaluated before operation and at the final follow-up. Postoperative cuff integrity was determined using MRI according to Sugaya''s classification.

Results:

At the 2-year follow-up, the average UCLA score increased from 16.7 ± 1.9 to 32.5 ± 3.5, and the constant score increased from 66.2 ± 10.5 to 92.4 ± 6.9 (P < 0.001). Twenty seven patients received follow-up MRI examinations at an average of 15.2 months after surgery. Of these 27 patients, 22 (81.5%) had a healed tendon, and five patients had partial tears. There was no association between functional and anatomic results.

Conclusions:

For intratendinous PTRCT, clinical outcomes and tendon healing showed good results at a minimum 2-year after arthroscopic repair.     

Changes in the Vision-related Resting-state Network in Pituitary Adenoma Patients After Vision Improvement

Background:

The aim of this research was to investigate the changes in the vision-related resting-state network (V-RSN) in pituitary adenoma (PA) patients after vision improvement, which was induced by operative treatment.

Methods:

Ten PA patients with an improved visual acuity or/and visual field after transsphenoidal pituitary tumor resection were recruited and underwent a complete neuro-ophthalmologic evaluation, as well as an magnetic resonance imaging (MRI) protocol, including structural and resting-state functional MRI sequences before and after the operation. The regional homogeneity (ReHo) of the V-RSN was evaluated. Two sample t-test was performed to identify the significant differences in the V-RSN in the PA patients before and after transsphenoidal pituitary tumor resection.

Results:

Compared with the preoperation counterparts, the PA patients with improved vision after the operation exhibited reduced ReHo in the bilateral thalamus, globus pallidus, caudate nucleus, putamen nucleus, supplementary motor area, and left hippocampal formation, and increased ReHo in the bilateral cuneus gyrus, calcarine gyrus, right lingual gyrus, and fusiform gyrus.

Conclusions:

PA patients with improved vision exhibit increased neural activity within the visual cortex, but decreased neural activity in subareas of the multisensory and multimodal systems beyond the vision cortex.     

Improved Performance in Differentiating Benign from Malignant Sinonasal Tumors Using Diffusion-weighted Combined with Dynamic Contrast-enhanced Magnetic Resonance Imaging

Background:

Differentiating benign from malignant sinonsal lesions is essential for treatment planning as well as determining the patient''s prognosis, but the differentiation is often difficult in clinical practice. The study aimed to determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can improve the performance in differentiating benign from malignant sinonasal tumors.

Methods:

This retrospective study included 197 consecutive patients with sinonasal tumors (116 malignant tumors and 81 benign tumors). All patients underwent both DW and DCE-MRI in a 3-T magnetic resonance scanner. Two different settings of b values (0,700 and 0,1000 s/mm²) and two different strategies of region of interest (ROI) including whole slice (WS) and partial slice (PS) were used to calculate apparent diffusion coefficients (ADCs). A DW parameter with WS ADCs_b0,1000 and two DCE-MRI parameters (time intensity curve [TIC] and time to peak enhancement [Tpeak]) were finally combined to use in differentiating the benign from the malignant tumors in this study.

Results:

The mean ADCs of malignant sinonasal tumors (WS ADCs_b0,1000 = 1.084 × 10⁻³ mm²/s) were significantly lower than those of benign tumors (WS ADCs_b0,1000 = 1.617 × 10⁻³ mm²/s, P < 0.001). The accuracy using WS ADCs_b0,1000 alone was 83.7% in differentiating the benign from the malignant tumors (85.3% sensitivity, 81.2% specificity, 86.4% positive predictive value [PPV], and 79.5% negative predictive value [NPV]). The accuracy using DCE with Tpeak and TIC alone was 72.1% (69.1% sensitivity, 74.1% specificity, 77.5% PPV, and 65.1% NPV). Using DW-MRI parameter was superior than using DCE parameters in differentiation between benign and malignant sinonasal tumors (P < 0.001). The accuracy was 87.3% (90.5% sensitivity, 82.7% specificity, 88.2% PPV, and 85.9% NPV) using DW-MRI combined with DCE-MRI, which was superior than that using DCE-MRI alone or using DW-MRI alone (both P < 0.001) in differentiating the benign from the malignant tumors.

Conclusions:

Diffusion-weighted combined with DCE-MRI can improve imaging performance in differentiating benign from malignant sinonasal tumors, which has the potential to improve diagnostic accuracy and to provide added value in the management for these tumors.     

Application of Computed Tomography Virtual Noncontrast Spectral Imaging in Evaluation of Hepatic Metastases: A Preliminary Study

Objective:

The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography (CT) virtual noncontrast (VNC) spectral imaging in a retrospective analysis.

Methods:

Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast (TNC) and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial, portal venous, and equilibrium phases. The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial (VNCa), venous (VNCv), and equilibrium (VNCe) phase by the material decomposition process using water and iodine as a base material pair. The image quality and the contrast-to-noise ratio (CNR) of metastasis of the four groups were compared with ANOVA analysis. The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chi-square test.

Results:

There were no significant differences in image quality among TNC, VNCa and VNCv images (P > 0.05). The quality of VNCe images was significantly worse than that of other three groups (P < 0.05). The mean CNR of metastasis in the TNC and VNCs images was 1.86, 2.42, 1.92, and 1.94, respectively; the mean CNR of metastasis in VNCa images was significantly higher than that in other three groups (P < 0.05), while no statistically significant difference was observed among VNCv, VNCe and TNC images (P > 0.05). The metastasis detection rate of the four nonenhanced groups with no statistically significant difference (P > 0.05).

Conclusions:

The quality of VNCa and VNCv images is identical to that of TNC images, and the metastasis detection rate in VNC images is similar to that in TNC images. VNC images obtained from arterial phase show metastases more clearly. Thus, VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.     

A comparative study of whole body DWIBS MRI versus bone scan for evaluating skeletal metastases

Background

Skeletal metastases in oncology patients are identified by Bone scan and/Positron Emission Tomography (PET) scan. But developing countries in the world still lack adequate numbers of these imaging facilities.

Aims

Since Magnetic Resonance Imaging (MRI) is widely available as compared to bone scan or PET scan; a double blind study was undertaken to see if whole body imaging with MRI can give an idea of skeletal metastases.

Method

Diffusion weighted whole body Magnetic Resonance Imaging with background body signal suppression (DWIBS) was performed using 1.5 Tesla (T) MRI on histopathologically proven cases of carcinoma of breast within two months of mastectomy and followed up after a year of surgery. Similarly bone scan was also performed in these patients.

Results

DWIBS MRI demonstrated the presence and extent of bone metastases in 10 out of a total 18 patients included in study while bone scan could demonstrate them in only three cases. A highly significant difference between proportions of the skeletal metastases detected by whole body DWIBS-MRI than that by bone scan at one year follow-up. (i.e. p<0.01, z=2.66) was seen.

Conclusion

DWIBS MRI scores high in demonstrating skeletal metastases. Further comparative studies are necessary to evaluate if DWIBS can replace bone scan or PET scan.     

ApaI,BsmI, FokI,and TaqI Polymorphisms in the Vitamin D Receptor Gene and Parkinson's Disease

Background:

The vitamin D receptor (VDR) gene has been identified as a candidate gene for susceptibility to Parkinson''s disease (PD), but results from genetic association studies to date are inconsistent. Here, we conducted a meta-analysis of published case-control studies to evaluate the association of the extensively studied VDR ApaI (G/T), BsmI (G/A), FokI (C/T), and TaqI (T/C) gene polymorphisms with risk of PD.

Methods:

Electronic search at PubMed, EMBASE, EBSCO, China National Knowledge Infrastructure, Weipu database, and Wanfang database was conducted to identify all relevant studies. Odds ratio (OR) with 95% confidence interval (CI) values was applied to evaluate the strength of the association.

Results:

A total of seven studies with 2034 PD cases and 2432 controls were included in the meta-analysis following the inclusion and exclusion criteria. Overall, no significant association between ApaI, BsmI, and TaqI gene polymorphisms and PD susceptibility in all four genetic models was found (T vs. G: OR = 1.00, 95% CI: 0.89–1.12, P = 0.97; A vs. G: OR = 0.94, 95% CI: 0.77–1.15, P = 0.53; C vs. T: OR = 1.03, 95% CI: 0.85–1.25, P = 0.77) while a significant association between FokI (C/T) and PD risk was observed (C vs. T: OR = 1.41, 95% CI: 1.14–1.75, P = 0.001; CC vs. TT: OR = 2.45, 95% CI: 1.52–3.93, P = 0.0002; CT vs. TT: OR = 2.21, 95% CI: 1.38–3.52, P = 0.0009, CC vs. CT+TT: OR = 2.32, 95% CI: 1.49–3.61, P = 0.0002).

Conclusions:

Polymorphisms of ApaI, BsmI, and TaqI may not be associated with the susceptibility to PD while the FokI (C/T) polymorphism is possibly associated with increased PD risk. However, conclusions should be cautiously interpreted due to the relatively small number of studies included.     

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

Background:

Mitochondrial dysfunction is linked to the pathogenesis of Parkinson''s disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.

Methods:

Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.

Results:

Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082–0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030–0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112–11.523, P = 0.033), other haplogroups also did not show significant differences in the group.

Conclusions:

Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.     

Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

Background:

Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson''s disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

Methods:

The mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

Results:

The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

Conclusions:

DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.     

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study

Background:

Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH.

Methods:

Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups.

Results:

DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen.

Conclusion:

Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.