Diffusion MRI detects basal forebrain cholinergic abnormalities in the 3xTg-AD mouse model of Alzheimer's disease

Degeneration of the basal forebrain (BF) is detected early in the course of Alzheimer's disease (AD). Reduction in the number of BF cholinergic (ChAT) neurons associated with age-related hippocampal cholinergic neuritic dystrophy is described in the 3xTg-AD mouse model; however, no prior diffusion MRI (dMRI) study has explored the presence of BF alterations in this model. Here we investigated the ability of diffusion MRI (dMRI) to detect abnormalities in BF microstructure for the 3xTg-AD mouse model, along with related pathology in the hippocampus (HP) and white matter (WM) tracks comprising the septo-hippocampal pathway. 3xTg-AD and normal control (NC) mice were imaged in vivo using the specific dMRI technique known as diffusional kurtosis imaging (DKI) at 2, 8, and 15 months of age, and 8 dMRI parameters were measured at each time point. Our results revealed significant lower dMRI values in the BF of 2 months-old 3xTg-AD mice compared with NC mice, most likely related to the increased number of ChAT neurons seen in this AD mouse model at this age. They also showed significant age-related dMRI changes in the BF of both groups between 2 and 8 months of age, mainly a decrease in fractional anisotropy and axial diffusivity, and an increase in radial kurtosis. These dMRI changes in the BF may be reflecting the complex aging and pathological microstructural changes described in this region. Group differences and age-related changes were also observed in the HP, fimbria (Fi) and fornix (Fx). In the HP, diffusivity values were significantly higher in the 2 months-old 3xTg-AD mice, and the HP of NC mice showed a significant increase in axial kurtosis after 8 months, reflecting a normal pattern of increased fiber density complexity, which was not seen in the 3xTg-AD mice. In the Fi, mean and radial diffusivity values were significantly higher, and fractional anisotropy, radial kurtosis and kurtosis fractional anisotropy were significantly lower in the 2 months-old 3xTg-AD mice. The age trajectories for both NC and TG mice in the Fi and Fx were similar between 2 and 8 months, but after 8 months there was a significant decrease in diffusivity metrics associated with an increase in kurtosis metrics in the 3xTg-AD mice. These later HP, Fi and Fx dMRI changes probably reflect the growing number of dystrophic neurites and AD pathology progression in the HP, accompanied by WM disruption in the septo-hippocampal pathway. Our results demonstrate that dMRI can detect early cytoarchitectural abnormalities in the BF, as well as related aging and neurodegenerative changes in the HP, Fi and Fx of the 3xTg-AD mice. Since DKI is widely available on clinical scanners, these results also support the potential of the considered dMRI parameters as in vivo biomarkers for AD disease progression.     

Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice

Background

Several transgenic animal models genetically predisposed to develop Alzheimer's disease (AD)-like pathology have been engineered to facilitate the study of disease pathophysiology and the vetting of potential disease-modifying therapeutics. The triple transgenic mouse model of AD (3xTg-AD) harbors three AD-related genetic loci: human PS1^M146V, human APP^swe, and human tau^P301L. These mice develop both amyloid plaques and neurofibrillary tangle-like pathology in a progressive and age-dependent manner, while these pathological hallmarks are predominantly restricted to the hippocampus, amygdala, and the cerebral cortex the main foci of AD neuropathology in humans. This model represents, at present, one of the most advanced preclinical tools available and is being employed ever increasingly in the study of mechanisms underlying AD, yet a detailed regional and temporal assessment of the subtleties of disease-related pathologies has not been reported.

Methods and results

In this study, we immunohistochemically documented the evolution of AD-related transgene expression, amyloid deposition, tau phosphorylation, astrogliosis, and microglial activation throughout the hippocampus, entorhinal cortex, primary motor cortex, and amygdala over a 26-month period in male 3xTg-AD mice. Intracellular amyloid-beta accumulation is detectable the earliest of AD-related pathologies, followed temporally by phospho-tau, extracellular amyloid-beta, and finally paired helical filament pathology. Pathology appears to be most severe in medial and caudal hippocampus. While astrocytic staining remains relatively constant at all ages and regions assessed, microglial activation appears to progressively increase temporally, especially within the hippocampal formation.

Conclusion

These data fulfill an unmet need in the ever-widening community of investigators studying 3xTg-AD mice and provide a foundation upon which to design future experiments that seek to examine stage-specific disease mechanisms and/or novel therapeutic interventions for AD.     

基于磁共振图像和改进的UNet++模型区分阿尔茨海默症患者和健康人群

阿尔茨海默症（Alzheimer's Disease,AD）是一种神经退行性疾病,高效准确的早期诊断对其治疗至关重要．本文提出了一种融合多语义级别的深度卷积神经网络结构,基于磁共振图像,用于区分AD患者与正常受试者的方法．首先,在传统UNet++网络的基础上改进了深度监督整合算法;然后,构建了一种新的特征融合结构,进一步细化了不同语义级别的特征;最后,基于不同组织区域（白质、灰质和脑脊液）的磁共振图像,使用本文所提出的方法区分AD患者和正常受试者,并探究了从不同组织获得的信息对分类准确率的影响．实验结果表明,使用本文提出的方法区分两类人群的最高准确率为98.74%,平均准确率为98.47%,高于目前文献报道的其他方法．     

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

Background  

The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss.     

Multiple sclerosis: Benefits of q-space imaging in evaluation of normal-appearing and periplaque white matter

Introduction

Diffusion tensor imaging (DTI) reveals white matter pathology in patients with multiple sclerosis (MS). A recent non-Gaussian diffusion imaging technique, q-space imaging (QSI), may provide several advantages over conventional MRI techniques in regard to in vivo evaluation of the disease process in patients with MS. The purpose of this study is to investigate the use of root mean square displacement (RMSD) derived from QSI data to characterize plaques, periplaque white matter (PWM), and normal-appearing white matter (NAWM) in patients with MS.

Methods

We generated apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps by using conventional DTI data from 21 MS patients; we generated RMSD maps by using QSI data from these patients. We used the Steel–Dwass test to compare the diffusion metrics of regions of interest in plaques, PWM, and NAWM.

Results

ADC differed (P < 0.05) between plaques and PWM and between plaques and NAWM. FA differed (P < 0.05) between plaques and NAWM. RMSD differed (P < 0.05) between plaques and PWM, plaques and NAWM, and PWM and NAWM.

Conclusion

RMSD values from QSI may reflect microstructural changes and white-matter damage in patients with MS with higher sensitivity than do conventional ADC and FA values.     

Bi-exponential diffusion signal decay in normal appearing white matter of multiple sclerosis

Purpose

Our aim was to characterize bi-exponential diffusion signal changes in normal appearing white matter of multiple sclerosis (MS) patients.

Methods

Diffusion parameters were measured using mono-exponential (0–1000 s/mm²) and bi-exponential (0–5000 s/mm²) approaches from 14 relapsing-remitting subtype of MS patients and 14 age- and sex-matched controls after acquiring diffusion-weighted images on a 3T MRI system. The results were analyzed using parametric or nonparametric tests and multiple linear regression models.

Results

Mono-exponential apparent diffusion coefficient (ADC) slightly increased in controls (P=.09), but decreased significantly in MS as a function of age, nonetheless an elevated ADC was observed with increasing lesion number in patients. Bi-exponential analyses showed that the increased ADC is the result of decreased relative volume fraction of slow diffusing component (f_s). However, the fast and slow diffusion components (ADC_f, ADC_s) did not change as a function of either age in controls or lesion number and age in MS patients.

Conclusions

These data demonstrated that the myelin content of the white matter affects diffusion in relapsing-remitting subtype of multiple sclerosis that is possibly a consequence of the shift between different water fractions.     

Clinical 3.0 T Magnetic Resonance Scanner to Be Used for Imaging of Mouse Atherosclerotic Lesions

Magnetic resonance imaging (MRI) is a useful tool for non-invasive identification and characterization of atherosclerotic plaques in both basic science and clinical practice. To date, the reported studies on in vivo vascular MRI of small animals, such as mice and rats, are mainly performed on high-field micro-MR scanners, which are not always available in many academic institutions and basic research units. This study aimed to explore the possibility of generating high-resolution MR images of the atherosclerotic aortic walls/plaques of mice using a clinical 3.0 T MR scanner with a dedicated solenoid mouse coil. An atherosclerotic mouse model was first generated by feeding 8 ApoE⁻/⁻ mice an atherogenic diet. MR images of the ascending aortas of these mice were then achieved using a three-dimensional black-blood turbo spin-echo sequence (repetition time TR = 4 heart echo time TE = 10 ms). The MRI displayed a clear view of the aortic lumens and the atherosclerotic lesions, which correlated significantly well with subsequent histological confirmations (linear regression analysis, r = 0.73, P = 0.04). This study demonstrated that a clinical 3.0 T MR scanner can be used for high-resolution imaging of mouse atherosclerotic lesions to some extent.     

White matter abnormalities in children and adolescents with temporal lobe epilepsy

Background and Purpose

The widespread propagation of synchronized neuronal firing in seizure disorders may affect cortical and subcortical brain regions. Diffusion tensor imaging (DTI) can noninvasively quantify white matter integrity. The purpose of this study was to investigate the abnormal changes of white matter in children and adolescents with focal temporal lobe epilepsy (TLE) using DTI.

Materials and Methods

Eight patients with clinically diagnosed TLE and eight age- and sex-matched healthy controls were studied. DTI images were obtained with a 3-T magnetic resonance imaging scanner. The epileptic foci were localized with magnetoencephalography. Fractional anisotropy (FA), mean diffusivity (MD), parallel (λ_||) and perpendicular (λ_⊥) diffusivities in the genu of the corpus callosum, splenium of the corpus callosum (SCC), external capsule (EC), anterior limbs of the internal capsule (AIC), and the posterior limbs of the internal capsule (PIC) were calculated. The DTI parameters between patients and controls were statistically compared. Correlations of these DTI parameters of each selected structure with age of seizure onset and duration of epilepsy were analysed.

Results

In comparison to controls, both patients' seizure ipsilateral and contralateral had significantly lower FA in the AIC; PIC and SCC and higher MD, λ_|| and λ_⊥ in the EC, AIC, PIC and SCC. The MD, λ_|| and λ_⊥ were significantly correlated with age of seizure onset in the EC and PIC. λ_|| was significantly correlated with the duration of epilepsy in the EC and PIC.

Conclusion

The results of the present study indicate that children and adolescents with TLE had significant abnormalities in the white matter in the hemisphere with seizure foci. Furthermore, these abnormalities may extend to the other brain hemisphere. The age of seizure onset and duration of epilepsy may be important factors in determining the extent of influence of children and adolescents TLE on white matter.     

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T₁-weighted, T₂-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T₁ and T₂ weighted images were collected in UUO mice on day 0 (~ 3 h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p < 0.05) changes in thickness of cortex and outer medulla, and regional changes in T₂ signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical–medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression.     

Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer’s disease

We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.     

Magnetization transfer MRI of mouse brain reveals areas of high neural density

Extending applications of magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) of the human central nervous system, this work quantitatively describes MTC of the murine brain. As a novel finding, complementing T₁- and T₂-weighted MRI, MTC allows for the distinction of densely packed gray matter from normal gray and white matter. Examples include the Purkinje cell layer and the granular cell layer in the mouse cerebellum as well as the delineation of the CA3 subfield of the hippocampus relative to surrounding hippocampal gray matter and white matter tracts such as the hippocampal fimbria. Using a kainate lesion model, the CA3 hyperintensities in MTC and T₁-weighted MRI are assigned to the densely packed somata of pyramidal cells.     

基于高夹角分辨率扩散磁振造影神经径路追踪的人脑语言机率路径图谱

大脑皮质内部的联系神经束,对于大脑皮质之间的信息传递担任非常重要的角色.传统的语言模型理论提出人类的2个主要语言中枢分别位于大脑皮质的左侧额下回的布罗卡区域(Broca’s area,BA44andBA45)以及颞上回处的维尼基区域(Wernicke’s area,BA22),而联系这2个区域的纤维束,也就是弓状束(arcuate fasciculus).另外,近期研究也发现下顶叶(inferior parietal cortex,BA39and BA40)在语音处理历程具重要性.扩散磁振造影(Diffu-sionMRI)可以提供大脑白质精细的组织结构,配合神经径路追踪(tractography)便能撷取出复杂的神经纤维连结路径.该研究利用扩散磁振影像中的高夹角分辨率扩散磁振造影(high angular resolution diffusion imaging)与神经径路追踪技术,呈现与语言相关的大脑机率神经连结路径(probabilistic language pathway).     

Co-registration of the distribution of wall shear stress and 140 complex plaques of the aorta

Previous studies provide evidence that atherosclerosis develops in vascular regions exposed to low wall shear stress (WSS) and high oscillatory shear index (OSI). 4D flow MRI was analyzed in 70 stroke patients with complex plaques (≥ 4 mm thickness, ulcerated or superimposed thrombi) and in 12 young healthy volunteers. The segmental distribution of peak systolic WSS_systole and OSI was quantified in analysis planes positioned directly at the location of 140 complex plaques found in the 70 patients. In addition, WSS_systole and OSI were evaluated in 8 standard analysis planes distributed along the aorta. Complex plaques were predominantly found at the inner curvature of the aortic arch and of the descending aorta. High OSI was co-located with the segments mostly affected by complex plaque while WSS_systole demonstrated a homogenous distribution. In standard analysis planes, patients demonstrated significantly (p < 0.01) altered distribution of wall parameters compared to volunteers (reduced WSS_systole in 91% of aortic wall segments, increased OSI in 48% of segments). OSI distribution was asymmetric with higher values at the inner curvature of the aorta. While WSS and OSI showed expected changes in patients compared to healthy controls, their distribution pattern at complex plaques indicated a more complex and heterogeneous relationship than previously anticipated.     

Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study

ObjectiveTo assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD).MethodsForty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD.ResultsAfter a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate + glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%.ConclusionEither MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.     

Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging

G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains. High field MRM of actively-stained mouse brains from GIT1-KO and wild type (WT) controls (n = 6 per group) allowed segmenting 37 regions, based on co-registration to the Waxholm Space atlas. Overall brain size in GIT1-KO mice was ~32% smaller compared to WT controls. After correcting for brain size, several regions were significantly different in GIT1-KO mice relative to WT, including the gray matter of the ventral thalamic nuclei and the rest of the thalamus, the inferior colliculus, and pontine nuclei. GIT1-KO mice had reduced volume of white matter tracts, most notably in the anterior commissure (~26% smaller), but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, the basal ganglia appeared enlarged in GIT1-KO mice, including the globus pallidus, caudate putamen, and particularly the accumbens - supporting a possible vulnerability to addiction. Volume based morphometry based on high-resolution MRM (21.5 μm isotropic voxels) was effective in detecting overall, and local differences in brain volumes in GIT1-KO mice, including in white matter tracts. The reduced relative volume of specific brain regions suggests a critical, but not uniform, role for GIT1 in brain development, conducive to brain microcephaly, and aberrant connectivity.     

Anti-PrP<Superscript>C</Superscript> monoclonal antibody infusion as a novel treatment for cognitive deficits in an alzheimer's disease model mouse

Background  

Alzheimer's Disease (AD) is the most common of the conformational neurodegenerative disorders characterized by the conversion of a normal biological protein into a β-sheet-rich pathological isoform. In AD the normal soluble Aβ (sAβ) forms oligomers and fibrils which assemble into neuritic plaques. The most toxic form of Aβ is thought to be oligomeric. A recent study reveals the cellular prion protein, PrP^C, to be a receptor for Aβ oligomers. Aβ oligomers suppress LTP signal in murine hippocampal slices but activity remains when pretreated with the PrP monoclonal anti-PrP antibody, 6D11. We hypothesized that targeting of PrP^C to prevent Aβ oligomer-related cognitive deficits is a potentially novel therapeutic approach. APP/PS1 transgenic mice aged 8 months were intraperitoneally (i.p.) injected with 1 mg 6D11 for 5 days/week for 2 weeks. Two wild-type control groups were given either the same 6D11 injections or vehicle solution. Additional groups of APP/PS1 transgenic mice were given either i.p. injections of vehicle solution or the same dose of mouse IgG over the same period. The mice were then subjected to cognitive behavioral testing using a radial arm maze, over a period of 10 days. At the conclusion of behavioral testing, animals were sacrificed and brain tissue was analyzed biochemically or immunohistochemically for the levels of amyloid plaques, PrP^C, synaptophysin, Aβ40/42 and Aβ oligomers.     

Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques

White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named ‘Multispectral Coloring Modulation and Variance Identification’ (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T₁-, T₂-, T₂?- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland–Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique.     

Ocular integrity following manganese labeling of the visual system for MRI

Injection of manganese into the eye will enhance the contrast of visual system neuronal pathways imaged by MRI (MEMRI). The present study was undertaken to determine the effect of a range of MnCl₂ doses upon the integrity of various ocular structures. Anesthetized mice received ocular anterior chamber injections of 50–500 nmol of MnCl₂. One week later, the eyes were fixed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Additional animals received 50 nmol of MnCl₂ injected into the anterior chamber and were later imaged using T1-weighted 7 T MRI. Following 500 and 300 nmol MnCl₂, the corneal stroma and endothelium were degenerated, the anterior chamber contained a dense fibrin matrix with extensive inflammatory cell infiltration, a plaque often formed on the anterior lens, and significant retinal degeneration was observed. Following 100 nmol MnCl₂, retinal preservation of ocular structures was significantly better than at higher doses. In addition, there was no difference from vehicle control retina in cell counts within the ganglion cell layer, or in the width of the inner nuclear layer or outer nuclear layer. Also, there was no difference in the thickness of the inner plexiform layer. However, there was thinning of the peripheral outer plexiform layer, as well as in the outer segment layer. Visual system elements labeled in MRI of mice that received 100 nmol MnCl₂ included the retina, optic nerve, lateral geniculate nucleus, and superior colliculus. The preservation of ganglion cell layer cell counts and inner plexiform layer thickness following 100 nmol MnCl₂ suggests there was negligible injury to RGCs following this dose. These results support using 100 nmol MnCl₂ in mouse eyes for in vivo assessment of the integrity of RGC projections to target neurons in the brain.     

Diffusion tensor parameters and principal eigenvector coherence: Relation to b-value intervals and field strength

Diffusion-weighted MRI images acquired at b-value greater than 1000 s mm^− 2 measure the diffusion of a restricted pool of water molecules. High b-value images are accompanied by a reduction in signal-to-noise ratio (SNR) due to the application of large diffusion gradients. By fitting the diffusion tensor model to data acquired at incremental b-value intervals, we determined the effect of SNR on tensor parameters in normal human brains, in vivo. In addition, we also investigated the impact of field strength on the diffusion tensor model. Data were acquired at 1.5 and 3 T, at b-values 0, 1000, 2000 and 3000 s mm^− 2 in twenty diffusion-sensitised directions. Fractional anisotropy (FA), mean diffusivity (MD) and principal eigenvector coherence (κ) were calculated from diffusion tensors fitted between datasets with b-values 0–1000, 0–2000, 0–3000, 1000–2000 and 2000–3000 s mm^− 2. Field strength and b-value effects on diffusion parameters were analysed in white and grey matter regions of interest. Decreases in FA, κ and MD were found with increasing b-value in white matter. Univariate analysis showed a significant increase in FA with increasing field strength in highly organised white matter. These results suggest there are significant differences in diffusion parameters at 1.5 and 3 T and that the optimal results, in terms of the highest values of FA in white matter, are obtained at 3 T with a maximum b = 1000 s mm^− 2.     

Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy

Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy (¹H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel ¹H-MRS (TR: 2000 ms, TE: 30 ms) was performed at 3.0 T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.