Longitudinal Study of Gray Matter Changes in Parkinson Disease

BACKGROUND AND PURPOSE:The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis.MATERIALS AND METHODS:Longitudinal cognitive assessment and structural MR imaging of 89 patients with Parkinson disease (62 men) and 55 healthy controls (33 men) were from the Parkinson''s Progression Markers Initiative data base, including the initial baseline and 12-month follow-up data. Two-way analysis of covariance was performed with covariates of age, sex, years of education, imaging data from multiple centers, and total intracranial volume by using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra tool from SPM8 software.RESULTS:Gray matter volume changes for patients with Parkinson disease were detected with decreased gray matter volume in the frontotemporoparietal areas and the bilateral caudate, with increased gray matter volume in the bilateral limbic/paralimbic areas, medial globus pallidus/putamen, and the right occipital cortex compared with healthy controls. Progressive gray matter volume decrease in the bilateral caudate was found for both patients with Parkinson disease and healthy controls, and this caudate volume was positively associated with cognitive ability for both groups. The progressive gray matter volume increase specific to the patients with Parkinson disease was identified close to the left ventral lateral nucleus of thalamus, and a positive relationship was found between the thalamic volume and the tremor scores in a subgroup with tremor-dominant patients with Parkinson disease.CONCLUSIONS:The observed progressive changes in gray matter volume in Parkinson disease may provide new insights into the neurodegenerative process. The current findings suggest that the caudate volume loss may contribute to cognitive decline in patients with Parkinson disease and the progressive thalamus enlargement may have relevance to tremor severity in Parkinson disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra, with other neurons in the cortex and subcortical nuclei also affected during the course of the disease. This pathology might lead to morphologic brain changes.Voxel-based morphometry (VBM) analysis has been used to assess the cortical gray matter changes in patients with PD. Some cross-sectional studies were performed to compare the differences between patients with PD and healthy controls. However, these PD-VBM studies have not yet drawn any congruent conclusions. Some studies have shown distributed brain atrophy in cortical and subcortical regions, including the frontal lobe, temporal lobe, parietal lobe, occipital lobe, and the limbic/paralimbic areas.^1–8 On the other hand, 1 study reported an increase of GM in the thalamus in patients with PD with unilateral resting tremor compared with controls.⁹ A recent study has observed not only brain volume loss in the occipital region but also volume increase in the limbic/paralimbic system.¹⁰ In addition, some studies have failed to find any GM change.^11–14 In fact, few of these previous findings were wholly consistent with each other. These inconsistencies may result from the patient heterogeneity, such as the age, disease duration, disease severity, and variable covariates used in VBM analysis, which may confound the effect of results in between-group differences. Therefore, this issue of brain volume change in PD groups required further examination.To our knowledge, few studies have focused on the progression of regional volume changes in PD by using VBM. One longitudinal study showed a progressive gray matter volume (GMV) decrease in patients with PD with and without dementia with disease progression during a mean follow-up period of 25 months.¹⁵ In that study, a progressive GMV decrease in the limbic/paralimbic and temporo-occipital regions was observed in patients with PD, while in patients with dementia, the loss mainly involved the neocortical regions. However, in that study, no healthy matched controls were included. So far, the progressive GMV change across time specific to patients with PD compared with controls remains unclear.Thus, the main goals of the present study were to examine the GMV change in the PD group compared with healthy controls and to explore the progressive GMV change specific to patients with PD compared with controls with disease progression.     

Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis

BACKGROUND AND PURPOSE:Modifications of magnetic susceptibility have been consistently demonstrated in the subcortical gray matter of MS patients, but some uncertainties remain concerning the underlying neurobiological processes and their clinical relevance. We applied quantitative susceptibility mapping and longitudinal relaxation rate relaxometry to clarify the relative contribution of atrophy and iron and myelin changes to deep gray matter damage and disability in MS.MATERIALS AND METHODS:Quantitative susceptibility mapping and longitudinal relaxation rate maps were computed for 91 patients and 55 healthy controls from MR images acquired at 3T. Applying an external model, we estimated iron and myelin concentration maps for all subjects. Subsequently, changes of deep gray matter iron and myelin concentration (atrophy-dependent) and content (atrophy-independent) were investigated globally (bulk analysis) and regionally (voxel-based and atlas-based thalamic subnuclei analyses). The clinical impact of the observed MRI modifications was evaluated via regression models.RESULTS:We identified reduced thalamic (P < .001) and increased pallidal (P < .001) mean iron concentrations in patients with MS versus controls. Global myelin and iron content in the basal ganglia did not differ between the two groups, while actual iron depletion was present in the thalamus (P < .001). Regionally, patients showed increased iron concentration in the basal ganglia (P ≤ .001) and reduced iron and myelin content in thalamic posterior-medial regions (P ≤ .004), particularly in the pulvinar (P ≤ .001). Disability was predicted by thalamic volume (B = –0.341, P = .02), iron concentration (B = -0.379, P =  .005) and content (B = –0.406, P = .009), as well as pulvinar iron (B = –0.415, P = .003) and myelin (B = −0.415, P = .02) content, independent of atrophy.CONCLUSIONS:Quantitative MRI suggests an atrophy-related iron increase within the basal ganglia of patients with MS, along with an atrophy-independent reduction of thalamic iron and myelin correlating with disability. Absolute depletions of thalamic iron and myelin may represent sensitive markers of subcortical GM damage, which add to the clinical impact of thalamic atrophy in MS.

Along with atrophy,¹ several pathologic variations have been demonstrated in the deep gray matter (DGM) of MS patients by means of advanced MRI techniques.² Among these, recent quantitative susceptibility mapping (QSM) studies explored magnetic susceptibility alterations of subcortical GM,^3-5 because such changes might reflect iron accumulation and depletion, which play an important role in MS pathophysiology⁶ and seem to relate to motor and cognitive disability.^4,5Nonetheless, when drawing inferences on the relevance of DGM iron modifications in MS as measured by QSM, some considerations are needed. Indeed, brain magnetic susceptibility is also influenced by other molecules (primarily myelin, quantitatively assessable through the estimation of the longitudinal relaxation rate [R1]^7,8) whose spatial distribution remarkably overlaps with iron patterns.^9,10 Furthermore, susceptibility changes can differ across distinct subregions of DGM nuclei, which show intrinsic structural heterogeneity.¹¹ Finally, the observed modifications may partially reflect atrophy-related epiphenomena rather than actual increases of iron load.¹²Here we performed a multimodal (QSM and R1 relaxometry) investigation of DGM, computing in vivo iron- and myelin-specific maps to disentangle the contribution of atrophy and iron and myelin (concentration and content) abnormalities to subcortical GM damage in patients with MS at both global (bulk analysis) and regional (voxel-based and thalamic subnuclei ROI analyses) levels, simultaneously exploring their relationship with clinical disability.We hypothesized that: 1) modifications of DGM iron and myelin in MS would be partially accounted for by the presence of atrophy; 2) subregional analyses would show a heterogeneous spatial distribution of iron and myelin changes; 3) these alterations would predict clinical disability independent of atrophy.     

多发性硬化的深部灰质核团和边缘叶萎缩:基于体素的形态学研究

目的:采用基于体素的形态学(VBM)方法探讨多发性硬化患者的脑灰质变化.方法:应用3.0T MRI,对25例复发缓解型多发性硬化(RRMS)患者和22例正常志愿者进行3D T1WI扫描,通过基于体素的形态学分析全脑灰质和区域灰质核团的变化.结果:与正常对照组比较,多发性硬化的全脑灰质明显萎缩( 679.40±52.68...     

Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis Is Associated with White Matter Lesion Burden and Atrophy but Not with Cortical Atrophy: A Diffusion Tensor MRI Study

BACKGROUND AND PURPOSE:The association between subcortical deep gray matter, white matter, and cortical pathology is not well understood in MS. The aim of this study was to use DTI to investigate the subcortical deep gray matter alterations and their relationship with lesion burden, white matter, and cortical atrophy in patients with MS and healthy control patients.MATERIALS AND METHODS:A total of 210 patients with relapsing-remitting MS, 75 patients with progressive MS, and 110 healthy control patients were included in the study. DTI metrics in whole brain, normal-appearing white matter, normal-appearing gray matter, and subcortical deep gray matter structures were compared. The association between DTI metrics of the subcortical deep gray matter structures with lesion burden, normalized white matter volume, and normalized cortical volume was investigated.RESULTS:DTI measures were significantly different in whole brain, normal-appearing white matter, and normal-appearing gray matter among the groups (P < .01). Significant differences in DTI diffusivity of total subcortical deep gray matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity of total subcortical deep gray matter was significantly associated with normalized white matter volume (P < .001) and normalized cortical volume (P = .033) in healthy control patients. In both relapsing and progressive MS groups, the DTI subcortical deep gray matter measures were associated with the lesion burden and with normalized white matter volume (P < .001), but not with normalized cortical volume.CONCLUSIONS:These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.

Although in the past MS has been considered an inflammatory demyelinating disease affecting primarily the white matter of the central nervous system, currently, a substantial number of studies have established that gray matter is also involved in different stages of the disease.^1–5 Cortical and subcortical deep gray matter (SDGM) atrophy occurs also in the early stages of MS, and disability progression is significantly influenced by the neuronal loss of the gray matter.^6–8Atrophy of the SDGM structures is associated with disability progression and cognitive dysfunctions and can also predict the conversion to clinically definite MS.^9–12 An increasing body of evidence suggests that the atrophy of cortical and SDGM structures is associated with white matter lesion burden,¹³ but the underlying pathophysiologic processes remain poorly understood. Secondary Wallerian degeneration is certainly implicated in neuronal damage of gray matter structures; however, it seems unlikely to be the sole cause of gray matter pathology.^4,14DTI is an advanced MR imaging technique that has been used in a number of in vivo and ex vivo studies.^15,16 DTI measures are able to identify alterations outside the focal lesions in the so-called normal-appearing white matter and normal-appearing gray matter that remain largely undetected with conventional MR imaging in patients with MS.¹⁷There is a growing interest in studying the DTI alterations of the SDGM in the different stages of the MS disease process. Previous studies suggested that SDGM DTI abnormalities are also present in patients with clinically isolated syndrome^18,19 and are associated with disability progression as well as cognitive dysfunctions in patients with MS.^20–23Although different studies have investigated the associations between white matter lesions, brain atrophy, and DTI alteration in patients with MS,^24–26 the same relationships were not extensively investigated in healthy people whose pathophysiologic alteration of the brain cannot be attributable to the inflammatory process in the central nervous system. Therefore, in the current study, we aimed to investigate volumetric and DTI global, tissue-specific, and regional brain differences in a large cohort of healthy control (HC) patients, patients with relapsing-remitting MS (RRMS), and patients with progressive MS (PMS). We hypothesized that microstructural abnormalities of SDGM structures detected by DTI techniques are associated with lesion burden, and with white matter and gray matter volume alterations in patients with MS. Another aim was to explore the same associations in the HC group.     

应用全脑逐像素形态学自动分析方法研究阿尔茨海默氏病的灰质缺失

目的采用计算机处理核磁共振图像(magnetic resonance imaging,MRI),研究阿尔茨海默氏病(Alzheime's disease,AD)患者的灰质萎缩区域。方法采用逐像素形态学(voxeI-based morphometry,VBM)方法。结果和正常老年人对照组相比,AD病人的海马、海马旁回、内嗅皮层、杏仁体、尾状核头部、颞中回、扣带回、顶下小叶、岛叶和前额叶背外侧区双侧萎缩；右侧丘脑枕、颞上回、顶上小叶不同程度萎缩,而感觉运动皮层、小脑和枕叶相对保持完好。结论 VBM方法克服了以往使用人工勾画感兴趣区(ROI)方法的可重复性差,费时等缺点,可以客观、自动和全面地分析AD的灰质减少,具有良好的临床应用前景。     

基于体素的轻度阿尔茨海默病全脑灰质MRI成像分析

目的:利用磁共振T1 WI 3D成像研究轻度阿尔茨海默病患者相对于正常老年人灰质体积改变的特点.方法:对21例轻度AD患者及18例正常老年人进行三维T1WI扫描,利用基于SPM5的DARTEL工具箱对扫描获得的结构图像进行预处理,再对轻度AD组和对照组的令脑灰质体积进行基于体素的统计学比较.结果:轻度AD组的双侧海马、海马旁回及杏仁核、双侧丘脑、双侧颞枕叶皮质、双侧顶下小叶、双侧楔前叶、左侧中央后回、右侧额下回等结构与对照组的灰质密度差异具有统计学意义[P<0.05(FDR)].结论:基于体素的形态学研究能够发现轻度AD患者中大脑灰质广泛的及细微的结构萎缩,从而能够更加早期、全面、客观地反映轻度AD患者的脑结构改变.     

Decreased T1 Contrast between Gray Matter and Normal-Appearing White Matter in CADASIL

BACKGROUND AND PURPOSE:CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects.MATERIALS AND METHODS:Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score ≤ 1; mean age, 53.5 ± 11.1 years) and 30 age- and sex-matched controls.RESULTS:T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 ± 0.08 versus controls: 1.43 ± 0.04, P < 10⁻⁵). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities.CONCLUSIONS:Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease of the brain secondary to mutations of the NOTCH3 gene.¹ Conventional MR imaging markers have been repeatedly investigated in this disorder.^2–5 The impact of lacunar lesions detected on T1-weighted sequences seems more important than that of white matter lesions observed on FLAIR sequences.⁶ Recently, various measures of brain and cortical atrophy were shown to be related to clinical worsening.^7,8As reported in the context of Alzheimer disease,⁹ contrast between gray matter and normal-appearing white matter (NAWM) may be altered in CADASIL. This could have important implications for both image interpretation in the clinical setting and postprocessing in research studies. So far however, the alterations of MR imaging T1 contrast between GM and NAWM have not been evaluated in CADASIL. The aim of the present study was to assess potential contrast alterations between GM and NAWM on T1-weighted images in patients with CADASIL at the initial stage of the disease compared with age- and sex-matched individuals.     

Gray Matter Concentration Abnormality in Brains of Narcolepsy Patients

Objective

To investigate gray matter concentration changes in the brains of narcoleptic patients.

Materials and Methods

Twenty-nine narcoleptic patient with cataplexy and 29 age and sex-matched normal subjects (mean age, 31 years old) underwent volumetric MRIs. The MRIs were spatially normalized to a standard T1 template and subdivided into gray matter, white matter, and cerebrospinal fluid (CSF). These segmented images were then smoothed using a 12-mm full width at half maximum (FWHM) isotropic Gaussian kernel. An optimized voxel-based morphometry protocol was used to analyze brain tissue concentrations using SPM2 (statistical parametric mapping). A one-way analysis of variance was applied to the concentration analysis of gray matter images.

Results

Narcoleptics with cataplexy showed reduced gray matter concentration in bilateral thalami, left gyrus rectus, bilateral frontopolar gyri, bilateral short insular gyri, bilateral superior frontal gyri, and right superior temporal and left inferior temporal gyri compared to normal subjects (uncorrected p < 0.001). Furthermore, small volume correction revealed gray matter concentration reduction in bilateral nuclei accumbens, hypothalami, and thalami (false discovery rate corrected p < 0.05).

Conclusion

Gray matter concentration reductions were observed in brain regions related to excessive daytime sleepiness, cognition, attention, and memory in narcoleptics with cataplexy.     

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis

BACKGROUND AND PURPOSE:Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging–based iron-susceptibility measures.MATERIALS AND METHODS:Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions.RESULTS:Compared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition.CONCLUSIONS:Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

Cognitive problems occur in 40%–65% of individuals with multiple sclerosis, predominantly affecting information processing speed and episodic memory.¹ Subcortical atrophy, particularly in the thalamus, is well-known to predict cognitive deficits in MS.² Elevated levels of iron accumulation in deep gray matter (DGM) nuclei in MS have also been reported using different iron-sensitive MR imaging measures, with studies focusing particularly on the large basal ganglia nuclei (caudate, putamen, globus pallidus [GP]), and the thalamus).³ Excess iron catalyzes production of free radicals, promoting neurodegeneration. This affects the DGM in both healthy aging and different CNS disorders.⁴ DGM iron accumulation in MS may be an epiphenomenon of structural atrophy caused by cell death,⁵ but others reported no relationships between DGM iron, global/regional brain volumes, or lesion load, suggesting potentially independent pathologies.⁶ The functional implications of DGM iron accumulation relative to other DGM pathologies in MS need further examination. Previous studies have examined some aspects of cognitive functions and DGM iron in MS with 4 different MR techniques.^5,7–11 Among the MR imaging measures used, only the gradient-echo transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) have been validated against postmortem iron assessment, both in non-MS^12,13 and in MS populations.^14,15Three MS studies assessed different aspects of cognition along with R2*.^5,10,11 In Khalil et al,⁵ R2* in the basal ganglia (but not in the thalamus) was related to processing speed in patients with clinically isolated syndrome and those with MS. In Pinter et al,¹⁰ a neuropsychological composite score of cognitive efficiency/processing speed (but not memory) of patients with clinically isolated syndrome and patients with MS was reported. This was predicted by R2* relaxation rates averaged across basal ganglia nuclei, along with caudate volume and T2 lesion load. Schmalbrock et al¹¹ recently cross-examined QSM and R2* measures against performance in 2 inhibitory cognitive tasks (a Stroop Task and an Eriksen Flanker Task) in patients with relapsing-remitting MS, imaged at 7T. Inhibition in the Flanker Task (but not the Stroop Task) was related to caudate and anterior putamen iron assessed with QSM, but performance in neither task was related to R2* measures. Thus, only 1 study¹¹ directly compared the cognitive correlates of R2* and QSM-based iron measures in MS, but it did not control for atrophy in the same DGM regions.The objective of our study was to determine whether cognition in MS, measured by the Brief Repeatable Battery of Neuropsychological Tests, is related to DGM iron accumulation measured with R2* and QSM at a high field strength (4.7T). The core hypothesis was that iron (R2* and QSM) in DGM nuclei correlates with decreased cognitive performance in MS, irrespective of atrophy.     

A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

BACKGROUND AND PURPOSE:DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability.MATERIALS AND METHODS:Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects.RESULTS:T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation.CONCLUSIONS:Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

The era of quantitative MR imaging has arrived, allowing in vivo measurement of specific physical properties reflecting spinal cord (SC) microstructure and tissue damage.^1,2 Such measures have potential clinical applications, including improved diagnostic tools, objective monitoring for disease progression, and prediction of clinical outcomes.³ However, technical challenges such as artifacts, image distortion, and achieving acceptable SNR have led to limited reliability. Specialized pulse sequences and custom hardware have advanced the field but incur costs of increased complexity and acquisition time while creating barriers to portability and clinical adoption. Furthermore, quantitative MR imaging metrics often show wide ranges of normal values and confounding relationships with subject characteristics such as age,^4–8 for which most previous studies have not accounted.³Among the most promising SC quantitative MR imaging techniques are DTI and magnetization transfer (MT).^1–3 These provide measures of axonal integrity and myelin quantity that correlate with functional impairment in conditions such as degenerative cervical myelopathy (DCM)^5–7,9 and MS,^3,9 albeit with limited physiologic specificity (eg, fractional anisotropy [FA] reflects both demyelination and axonal injury).^10,11 SC cross-sectional area (CSA) computed from high-resolution anatomic images can measure atrophy (eg, in MS)¹² or the degree of SC compression in DCM.¹³ T2*-weighted imaging at 3T or higher field strengths offers high resolution and sharp contrast between SC WM and GM, allowing segmentation between these structures similar to that in phase-sensitive inversion recovery.^14,15 T2*WI also demonstrates hyperintensity in injured WM,^16–18 reflecting demyelination, gliosis, and increased calcium and nonheme iron concentrations.¹⁹ T2*WI signal intensity is not an absolute quantity, so we normalize its value in WM by the average GM signal intensity in each axial section, creating a novel measure of WM injury: T2*WI WM/GM ratio.²⁰We propose a multiparametric approach to cervical SC quantitative MR imaging with clinically feasible methods, including acceptable acquisition times, standard hardware/pulse sequences, and automated image analysis. Our protocol yields 4 measures of SC tissue injury (CSA, FA, MT ratio [MTR], and T2*WI WM/GM), for which this study establishes normative values in numerous ROIs. We characterize the variation of these metrics with age, sex, height, weight, cervical cord length, and rostrocaudal level and propose normalization methods. Finally, we assess test-retest reliability of FA, MTR, and T2*WI WM/GM and compare our DTI results against those with cardiac triggering.     

改良Webster症状评分量表评估帕金森病的手术疗效

目的：通过改良Ｗｓｂｓｔｅｒ记分量表评价电生理引导脑内核团毁损术治疗帕金森病的疗效。病人与方法：应用改良Ｗｅｂｓｔｅｒ症状评分表,对帕金森病人分别在手术前后进行１０组症状记分,１～１０分为轻度障碍;１１～２０分为中度障碍;２１～３０分为重度障碍;术后改善２５％以下为无效,２６％～５０％为有效,５１％～７５％为显效,７５％以上为特别显效。结果：术前评分为１９．９０±５．２７,术后评分１０．５７±６．１０,平均改善（８．９５±３．３７）分,差异非常显著,但无１例症状完全消除：其中特别显效４例（９．５％）;显效１７例（４０．５％）;有效１６例（３８．１％）,总有效率为８８．１％,单靶点毁损３４例,改善８．５９±３．５３,双靶点８例,改善（１０．００±４．１４）分,两组差别无统计学意义。分组统计结果表明,症状轻者术后改善的百分比较高。讨论：电生理引导脑内核团毁损术尚不能完全消除帕金森病的症状,但可使其明显改善;单侧双靶点毁损与单靶点毁损的疗效差别无显著意义,可能与病例数较少有关;症状较轻者术后改善明显。本文对手术适应症、禁忌症、并发症以及手术注意事项也进行了讨论。结论：对于药物疗效降低以及出现毒副作用的帕金森病患者     

MRI测量脑室、脑裂在Alzheimer病的应用研究

目的：定量评价Alzheimer病（alzheimer disease,AD)组，血管性痴呆（vascular dementia,VD)组、与年龄、性别相匹配的健康对照（health control,HC)组脑萎缩情况，有助于完善AD MRI的研究。资料与方法。使用Toshiba 1.5T超导MR扫描仪，对20例临床诊断为AD的患者、20例VD患者、20名HC者进行检查。对脑室、脑裂进行定量测量，并进行统计学处理。结果：AD、VD组侧脑室体部宽宽指数、侧脑室颞角宽度指数小于HC组，第三脑室宽度大于HC组，两侧外侧裂宽度指数、前绷裂宽度指数、两侧脉络膜裂宽度指数小于HC组。而AD与VD组以上测量指标除侧脑室颞角宽度以外无差别。结论：整体脑萎缩可提示痴呆的存在，但不能作为AD诊断的特异性指标，最好选择测量脑实质萎缩的指标进行AD的研究。     

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging,Focusing on Putaminal Change and Lesion Asymmetry

BACKGROUND AND PURPOSE:Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry.MATERIALS AND METHODS:This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values.RESULTS:The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001).CONCLUSIONS:3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Parkinsonism-predominant multiple system atrophy (MSA-p) is one of the Parkinson-plus syndromes that has a clinical manifestation similar to that of idiopathic Parkinson disease (IPD) and is often challenging to diagnose in its early stage. MR imaging plays a role in differentiating MSA-p from IPD and is included as an additional feature for the diagnosis of possible multiple system atrophy.¹ Various conventional and functional MR imaging findings regarding the putamen in MSA-p have been reported.^2–6 However, these findings had limited sensitivity and specificity.⁶An asymmetric presentation of clinical features is common for IPD in its early stage, while symmetric symptoms are more common in MSA-p than in IPD.^7,8 However, the clinical manifestation of parkinsonism develops asymmetrically in many patients with MSA-p, and it has been reported that approximately 40%–50% of patients with MSA-p present with initial asymmetric symptoms.^8,9 This presentation increases the difficulty of clinically differentiating IPD from MSA-p in the early stage of disease. However, to our knowledge, there are few previous reports that used imaging to examine the asymmetry of putaminal abnormalities in MSA-p.Susceptibility-weighted imaging (SWI), which was recently introduced and is now widely used in clinical brain imaging, reflects the physical magnetic properties of tissues because susceptibility changes in tissues, such as iron deposition, are very sensitive.¹⁰ In addition to the sensitivity of SWI to paramagnetic material, corrected phase images that are calculated to form final SWI can provide quantitative phase-shift values that reflect tissue iron content.¹¹ Recently published studies attempted to use SWI to differentiate movement disorders, including MSA-p,¹² and demonstrated different iron-deposition patterns between MSA-p and IPD by measuring phase-shift values by using corrected phase images of SWI sequences.¹³ However, most previous studies regarding SWI were performed on 1.5T or weaker main magnetic field MR imaging machines. When main magnetic field is increased to 3T, spins process at a higher frequency, which may result in phase shifts caused by susceptibility changes being more exaggerated on SWI.Thus, the purpose of the present study was to evaluate the imaging findings of 3T SWI for differentiating MSA-p from IPD, focusing on putaminal changes and lesion asymmetry.     

Subcortical Atrophy Is Associated with Cognitive Impairment in Mild Parkinson Disease: A Combined Investigation of Volumetric Changes,Cortical Thickness,and Vertex-Based Shape Analysis

BACKGROUND AND PURPOSE:The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction.MATERIALS AND METHODS:The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models.RESULTS:Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness.CONCLUSIONS:Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for Parkinson disease–mild cognitive impairment.

Parkinson disease (PD) has traditionally been considered a motor disorder. However, the presence of cognitive dysfunction is increasingly recognized and known to occur even at early stages, and most patients develop dementia during the course of the disease. Recently, it has emerged that patients with PD show a wide and variable spectrum of cognitive deficits involving multiple domains such as executive function, attention, memory, visuospatial, and, less frequently, language.^1,2 While traditionally believed to occur only in advanced stages of PD, recent studies suggest that approximately 30%–35% of patients with early PD experience cognitive disturbances,^3,4 which have been defined as mild cognitive impairment (MCI).⁵ The Movement Disorder Society (MDS) Task Force reported a mean prevalence of Parkinson disease with mild cognitive impairment (PD-MCI) at 27%, ranging from 19% to 38%.⁶ Furthermore, the impact of MCI and dementia in patients with PD at any given stage of the disease is substantial, with adverse consequences for functioning,⁷ psychiatric morbidity, caregiver burden,⁸ and mortality.⁹ At present, there is much to be elucidated with regard to the etiology of cognitive impairment in PD.Initially, dementia in PD was described as subcortical. Cognitive dysfunction in patients without dementia has also been attributed to dopaminergic depletion disrupting the frontostriatal circuit¹⁰ or dopamine-acetylcholine synaptic imbalance.¹¹ Nevertheless, recent investigations by using structural MR imaging suggest that specific cognitive deficits, such as memory deficits, and dementia in PD may also be accompanied by structural cerebral abnormalities. In this regard, MR imaging studies have demonstrated cortical atrophy in patients with PD with dementia. A recent meta-analysis revealed regional gray matter reductions of the medial temporal lobe and the basal ganglia,¹² while other areas, including the caudate,¹³ hippocampus,¹⁴ and amygdala,¹⁵ have also been implicated. However, present findings on GM atrophy in patients without dementia with PD are inconclusive. While a few studies have demonstrated atrophy in the medial temporal lobes,¹⁶ amygdala,¹⁷ and frontal and parietal regions,¹⁸ others have reported no significant GM reductions in PD populations without dementia.¹⁹In addition, cortical thinning in PD represents a relatively new area of research, and it has been reported to be more sensitive than voxel-based morphometry.²⁰ Recent studies have shown that cortical thinning occurs in PD without dementia.²¹ A longitudinal study also reported that patients with early PD presented with a more aggressive rate of cortical thinning in the frontotemporal regions compared with healthy controls.²²These mixed neuroimaging findings could be due, in part, to cognitively heterogeneous groups of patients, particularly in studies in which patients with MCI were not distinguished from those with normal cognition. Therefore, to systematically compare the pattern of GM atrophy in mild PD and its impact on specific cognitive domains, we used the recent MDS Task Force criteria to classify patients with PD with MCI or as cognitively normal (PD-NCI). We estimated the volumes of the amygdala, hippocampus, nucleus accumbens, caudate nucleus, putamen, pallidum, and thalamus in a cohort of patients with PD by using the FMRIB Integrated Registration and Segmentation Tool (FIRST; http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FIRST).Furthermore, we assessed differences in subcortical deep gray matter (SDGM) structures between PD-MCI and PD-NCI and further examined associations between individual structures and cognitive performances across multiple domains. Because vertex analysis directly measures changes in geometry without any smoothing of the image data, it might have the potential to more precisely detect regional alterations of the subcortical GM than the conventional voxel-based morphometry approach.²³ Therefore, we used a vertex-based shape-analysis method to investigate potential shape differences of SDGM structures between PD-MCI and PD-NCI. Last, vertex-wise cortical thickness analysis was performed by using FreeSurfer (http://surfer.nmr.mgh.harvard.edu) to assess and compare patterns of regional cortical alterations between both PD groups.     

Gray Matter Volume Reduction Is Associated with Cognitive Impairment in Neuromyelitis Optica

BACKGROUND AND PURPOSE:Whether gray matter impairment occurs in neuromyelitis optica is a matter of ongoing debate, and the association of gray matter impairment with cognitive deficits remains largely unknown. The purpose of this study was to investigate gray matter volume reductions and their association with cognitive decline in patients with neuromyelitis optica.MATERIALS AND METHODS:This study included 50 patients with neuromyelitis optica and 50 sex-, age-, handedness-, and education-matched healthy subjects who underwent high-resolution structural MR imaging examinations and a battery of cognitive assessments. Gray matter volume and cognitive differences were compared between the 2 groups. The correlations of the regional gray matter volume with cognitive scores and clinical variables were explored in the patients with neuromyelitis optica.RESULTS:Compared with healthy controls (635.9 ± 51.18 mL), patients with neuromyelitis optica (602.8 ± 51.03 mL) had a 5.21% decrease in the mean gray matter volume of the whole brain (P < .001). The significant gray matter volume reduction in neuromyelitis optica affected the frontal and temporal cortices and the right thalamus (false discovery rate correction, P < .05). The regional gray matter volumes in the frontal and temporal cortices were negatively correlated with disease severity in patients with neuromyelitis optica (Alphasim correction, P < .05). Patients with neuromyelitis optica had impairments in memory, information processing speed, and verbal fluency (P < .05), which were correlated with gray matter volume reductions in the medial prefrontal cortex and thalamus (Alphasim correction, P < .05).CONCLUSIONS:Gray matter volume reduction is present in patients with neuromyelitis optica and is associated with cognitive impairment and disease severity in this group.

Neuromyelitis optica (NMO) is an idiopathic, severe, demyelinating disease of the central nervous system that is characterized by optic neuritis and myelitis.^1,2 Although the brain is traditionally considered to be spared in NMO,³ recent studies have identified brain lesions in 60% of patients with this condition.⁴ In 10% of patients with NMO, the site of brain lesions on MR imaging coincides with high concentrations of the water channel aquaporin 4,^5,6 the target of NMO immunoglobulin G (NMO-IgG).Although several investigations have revealed gray matter impairment in NMO by comparing intergroup differences in the regional homogeneity,⁷ amplitude of low-frequency fluctuation,⁸ diffusivity,^9–11 perfusion,¹² and magnetization transfer ratio,¹³ whether GM structural impairment is a feature of NMO is an ongoing debate. Several studies have identified reductions in GM volume (GMV)^14–16 or cortical thickness¹⁷ in patients with NMO; however, 3 additional studies have failed to demonstrate reductions in the GMV^18,19 or cortical thickness in patients.²⁰ These conflicting outcomes may result from the low statistical power of the relatively small sample sizes (15–30 patients with NMO in previous studies). Studies with a large sample of patients with NMO may help clarify this issue.Cognitive impairment has been repeatedly reported in patients with NMO^{10,17,18,21–24} and is characterized by deficits in multiple cognitive domains, including memory, attention, and speed of information processing. The neural correlates of the cognitive impairment in NMO have been attributed to focal reductions in white matter volume and integrity.^10,18 A recent study found no correlation between cognitive impairment and cortical thinning in 23 patients with NMO.¹⁷ However, it remains unknown whether GMV reduction is associated with cognitive impairment in these patients.By recruiting a large sample of patients with NMO (n = 50), we aimed to clarify the GMV changes in NMO and the correlations of GMV changes with cognitive impairment and clinical variables in these patients.