EPI, Echo planar imaging

Epi,回波平面成像
  • 文章类型: Journal Article
    在1.5T全身DWIBS中使用不同的呼吸方案和多波段(MB)组合前瞻性地比较睾丸I期癌症患者的伪影和图像质量。使用反转恢复(IR)脂肪饱和度的背景身体信号抑制(DWIBS)的扩散加权全身成像是肿瘤全身MRI的基石,但实施受到较长收购时间的限制。新的多频带(MB)技术减少了扫描时间,可以重新投资于呼吸补偿。
    纳入30例睾丸癌I期患者。测试了全身DWIBS的三种变体:标准自由呼吸(FB)-DWIBS,FB-MB-DWIBS和呼吸触发(RT)-MB-DWIBS。使用Likert量表评估b=800s/mm2图像的伪影和图像质量。未发现病理。在健康志愿者中计算SNR。
    在胸部(p<0.001)和腹部(p<0.001)中,RT-MB-DWIBS的评分明显优于FB-DWIBS,但不在骨盆(p=0.569)。在所有位置,FB-MB-DWIBS均显著低于FB-DWIBS(p<0.001)和RT-MB-DWIBS(p<0.001)。然而,FB-MB-DWIBS在一半的时间内扫描,但没有低于“令人满意”。很少遇到人工制品。低强度组织的信噪比相似,但是FB-DWIBS的高强度和易呼吸组织(脾脏)的SNR略低于其他序列。
    由序列产生的图像是相似的。MB使得能够使用呼吸触发器或可用于产生具有可接受的图像质量的非常快速的自由呼吸DWI。
    UNASSIGNED: To prospectively compare artefacts and image quality in testicular stage I cancer patients using different combinations of breathing schemes and Multi-band (MB) in whole-body DWIBS at 1.5 T.Diffusion-Weighted whole-body Imaging with Background body signal Suppression (DWIBS) using inversion recovery (IR) fat saturation is a cornerstone in oncologic whole-body MRI, but implementation is restrained by long acquisition times. The new Multi-Band (MB) technique reduces scan time which can be reinvested in respiratory compensation.
    UNASSIGNED: Thirty testicular cancer stage I patients were included. Three variations of whole-body DWIBS were tested: Standard free Breathing (FB)-DWIBS, FB-MB-DWIBS and Respiratory triggered (RT)-MB-DWIBS. Artefacts and image quality of b = 800 s/mm2 images were evaluated using a Likert scale. No pathology was revealed. SNR was calculated in a healthy volunteer.
    UNASSIGNED: RT-MB-DWIBS was rated significantly better than FB-DWIBS in the thorax (p < 0.001) and abdomen (p < 0.001), but not in the pelvis (p = 0.569). FB-MB-DWIBS was ranked significantly lower than both FB-DWIBS (p < 0.001) and RT-MB-DWIBS (p < 0.001) at all locations. However, FB-MB-DWIBS was scanned in half the time without being less than \"satisfactory\". Few artefacts were encountered. SNR was similar for low-intensity tissues, but the SNR in high-intensity and respiratory-prone tissue (spleen) was slightly lower for FB-DWIBS than the other sequences.
    UNASSIGNED: Images produced by the sequences were similar. MB enables the use of respiratory trigger or can be used to produce very fast free-breathing DWI with acceptable image quality.
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  • 文章类型: Journal Article
    •需要了解帕金森病的表型异质性。性别和遗传学决定帕金森病的表现和进展。•帕金森病中改变的情绪处理是男性患者特有的。•这受到两种性别的内分泌和遗传因素的影响。•这一发现可能会影响新出现的临床特征的诊断和治疗。
    帕金森病(PD)被认为对男性和女性有不同的影响。神经精神症状在PD中常见且致残。然而,以往关注PD患者情绪识别的研究忽视了性别的混淆,缺乏关于潜在内分泌和遗传机制的证据.此外,虽然有许多关于PD情绪处理的影像学研究,性别相关的神经数据分析很少。因此,我们旨在探索命名因素对PD中情感识别和处理的相互作用。
    对51名非痴呆的PD患者(26名男性)和44名年龄和性别匹配的健康对照(HC;25名男性)进行了临床和神经心理检查,包括情绪识别任务(Ekman60faces测试)。对25名患者和31名HC的子样本进行了基于任务的功能磁共振成像(fMRI),其中包括情绪面部表情的视频。为了研究激素和遗传学对情绪处理的影响,血液样本用于内分泌(睾酮,雌二醇,孕酮)和基因检测(5-HTTLPR,Val158MetCOMT多态性)。
    在认知能力方面没有出现群体或性别差异。男性而非女性PD患者在识别情绪愤怒时表现出局限性障碍,伴随着对面部表情的神经反应减弱(例如,在壳核和脑岛中)。内分泌,女性患者的恐惧认知与雌激素水平呈正相关,而在遗传水平上,我们发现Val158MetCOMT基因型对PD患者的恐惧识别有影响。
    我们的研究提供了证据表明,PD患者的情绪处理受损会特别影响男性患者,激素和遗传学有助于情绪识别表现。对潜在神经的进一步研究,PD中特定症状的内分泌和遗传机制具有临床意义,因为它可以提高我们对疾病的现象学和病理学的理解,并可能允许更个性化的医学。
    •Understanding of the phenotypic heterogeneity of Parkinson\'s disease is needed.•Gender and genetics determine manifestation and progression of Parkinson\'s disease.•Altered emotion processing in Parkinson\'s disease is specific to male patients.•This is influenced by endocrinal and genetic factors in both genders.•This finding may impact the diagnosis and treatment of emerging clinical features.
    Parkinson\'s disease (PD) has been suggested to affect males and females differently. Neuropsychiatric symptoms are common and disabling in PD. However, previous studies focusing on emotion recognition in PD have neglected the confounder of gender and lack evidence on the underlying endocrinal and genetic mechanisms. Moreover, while there are many imaging studies on emotion processing in PD, gender-related analyses of neural data are scarce. We therefore aimed at exploring the interplay of the named factors on emotion recognition and processing in PD.
    51 non-demented PD patients (26 male) and 44 age- and gender-matched healthy controls (HC; 25 male) were examined clinically and neuropsychologically including an emotion recognition task (Ekman 60faces test). A subsample of 25 patients and 31 HC underwent task-based functional magnetic resonance imaging (fMRI) comprised of videos of emotional facial expressions. To examine the impact of hormones and genetics on emotion processing, blood samples were taken for endocrinal (testosterone, estradiol, progesterone) and genetic testing (5-HTTLPR, Val158Met COMT polymorphisms).
    No group or gender differences emerged regarding cognitive abilities. Male but not female PD patients exhibited confined impairments in recognizing the emotion anger accompanied by diminished neural response to facial expressions (e.g. in the putamen and insula). Endocrinologically, fear recognition was positively correlated with estrogen levels in female patients, while on the genetic level we found an effect of Val158Met COMT genotype on the recognition of fear in PD patients.
    Our study provides evidence that impaired emotion processing in PD specifically affects male patients, and that hormones and genetics contribute to emotion recognition performance. Further research on the underlying neural, endocrinological and genetic mechanisms of specific symptoms in PD is of clinical relevance, as it can improve our understanding of the phenomenology and pathobiology of the disease and may allow a more personalized medicine.
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  • 文章类型: Journal Article
    最常见的线粒体DNA(mtDNA)突变之一,碱基对3243的A到G的转变与大脑的变化有关,除了常见的听力问题,糖尿病和肌病。然而,到目前为止,尚未提供m.3243A>G患者大脑的详细定量描述。在这项研究中,7T的超高场MRI以及基于体积和表面的数据分析方法用于突出形态(即萎缩)-,患者(N=22)和健康对照(N=15)之间的微观结构(即髓鞘和铁浓度)和代谢(即脑血流量)相关差异。在7T时使用定量MRI使我们能够以高精度和灵敏度检测大脑中生物物理过程的细微变化,除了通常评估的病变和萎缩。此外,在患者人群中评估了血液和尿液上皮细胞中m.3243A>G突变负荷对这些MRI测量的影响,并揭示了血液水平最能指示大脑状态和疾病严重程度,基于MRI和神经心理学数据。形态MRI数据显示皮质广泛减少,皮质下和小脑灰质体积,除了明显扩大的心室。此外,基于表面的分析揭示了皮层厚度(例如听觉皮层)的大脑区域特异性变化,在T1,T2*和脑血流量中,作为突变负荷的函数,这通常与m.3243A>G相关的临床症状(例如听力障碍)有关。此外,与注意力控制相关的几个区域(例如额叶中回),感觉运动网络(例如中央沟库)和默认模式网络(例如前突)的特征在于皮质厚度的变化,T1、T2*和/或脑血流量,这在以前的MRI研究中没有描述。最后,几个假设,基于血管,m.3243A>G突变的代谢或星形胶质影响,讨论了可能解释潜在病理生物学的原因。最后,这是首个7T,也是针对该患者人群的最大MRI研究,该研究提供了m.3243A>G突变的宏观脑相关性,提示线粒体疾病的潜在MRI生物标志物,并可能指导未来(纵向)研究广泛追踪神经病理学和临床变化.
    One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients\' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N = 22) and healthy controls (N = 15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain\'s state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.
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  • 文章类型: Journal Article
    Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries.
    Infants (n = 65, included in final analyses: n = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age.
    Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course.
    fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.
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  • 文章类型: Journal Article
    Diagnosis of amyotrophic lateral sclerosis (ALS) depends on clinical evidence of combined upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, although ALS patients can present with features predominantly of one or the other. Some UMN-predominant patients show hyperintense signal along the intracranial corticospinal tract (CST) on T2- and proton density (PD)-weighted images (ALS-CST +), and appear to have faster disease progression when compared to those without CST hyperintensity (ALS-CST -). The reason for this is unknown. We hypothesized that diffusion tensor tractography (DTT) would reveal differences in DTI abnormalities along the intracranial CST between these two patient subgroups. Clinical DTI scans were obtained at 1.5T in 14 neurologic controls and 45 ALS patients categorized into two UMN phenotypes based on clinical measures and MRI. DTT was used to quantitatively assess the CST in control and ALS groups. DTT revealed subcortical loss (\'truncation\') of virtual motor CST fibers (presumably) projecting from the precentral gyrus (PrG) in ALS patients but not in controls; in contrast, virtual fibers (presumably) projecting to the adjacent postcentral gyrus (PoG) were spared. No significant differences in virtual CST fiber length were observed between controls and ALS patients. However, the frequency of CST truncation was significantly higher in the ALS-CST + subgroup (9 of 21) than in the ALS-CST - subgroup (4 of 24; p = 0.049), suggesting this finding could differentiate these ALS subgroups. Also, because virtual CST truncation occurred only in the ALS patient group and not in the control group (p = 0.018), this DTT finding could prove to be a diagnostic biomarker of ALS. Significantly shorter disease duration and faster disease progression rate were observed in ALS patients with CST fiber truncation than in those without (p < 0.05). DTI metrics of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were also determined in four regions of interest (ROIs) along the CST, namely: cerebral peduncle (CP), posterior limb of internal capsule (PLIC), centrum semiovale at top of lateral ventricle (CSoLV) and subcortical to primary motor cortex (subPMC). Of note, FA values along the left hemisphere virtual CST tract were significantly different between controls and ALS-CST + patients (p < 0.05) only at the PLIC level, but not at the CSoLV or subPMC level. Also, no significant differences in FA values were observed between ALS subgroups or between control and ALS-CST - groups (p > 0.05) in any of the ROIs. In addition, comparing FA values between ALS patients with CST truncation and those without in the aforementioned four ROIs, revealed no significant differences in either hemisphere. However, visual evaluation of DTT was able to identify UMN degeneration in patients with ALS, particularly in those with a more aggressive clinical disease course and possibly different pathologic processes.
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  • 文章类型: Journal Article
    Current imaging diagnostic techniques are often insensitive to the underlying pathological changes following mild traumatic brain injury (TBI) or concussion so much so that the explicit definition of these uncomplicated mild brain injuries includes the absence of radiological findings. In the US military, this is complicated by the natural tendency of service members to down play symptoms for fear of removal from their unit particularly in combat making it challenging for clinicians to definitively diagnose and determine course of treatment. Questions remain regarding the long-term impact of these war-time brain injuries. The objective of the current study was to evaluate the long-term imaging sequelae of blast concussion in active-duty US military and leverage previous longitudinal data collected in these same patients to identify predictors of sustained DTI signal change indicative of chronic neurodegeneration. In total, 50 blast TBI and 44 combat-deployed controls were evaluated at this 5-year follow up by advanced neuroimaging techniques including diffusion tensor imaging and quantitative volumetry. While cross-sectional analysis of regions of white matter on DTI images did not reveal significant differences across groups after statistical correction, an approach flexible to the heterogeneity of brain injury at the single-subject level identified 74% of the concussive blast TBI cohort to have reductions in fractional anisotropy indicative of chronic brain injury. Logistic regression leveraging clinical and demographic data collected in the acute/sub-acute and 1-year follow up to determine predictors of these long-term imaging changes determined that brain injury diagnosis, older age, verbal memory and verbal fluency best predicted the presence of DTI abnormalities 5 years post injury with an AUC of 0.78 indicating good prediction strength. These results provide supporting evidence for the evolution not resolution of this brain injury pathology, adding to the growing body of literature describing imaging signatures of chronic neurodegeneration even after mild TBI and concussion.
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  • 文章类型: Journal Article
    OBJECTIVE: The added value of perfusion MRI for decision-making in vestibular schwannoma (VS) patients is unknown. MRI offers two perfusion methods: the first employing contrast agent (dynamic susceptibility contrast (DSC)-MRI) that provides information on cerebral blood volume (CBV) and cerebral blood flow (CBF), the second by magnetic labeling of blood (arterial spin labeling (ASL)-MRI), providing CBF-images. The goal of the current study is to investigate whether DSC and ASL perfusion MRI provides complimentary information to current anatomical imaging in treatment selection process of VS.
    METHODS: Nine patients with growing VS with extrameatal diameter >9 mm were included (>2 mm/year and 20% volume expansion/year) and one patient with 23 mm extrameatal VS without growth. DSC and ASL perfusion MRI were obtained on 3 T MRI. Perfusion in VS was scored as hyperintense, hypointense or isointense compared to the contralateral region.
    RESULTS: Seven patients showed hyperintense signal on DSC and ASL sequences. Three patients showed iso- or hypointense signal on at least one perfusion map (1 patient hypointense on both DSC-MRI and ASL; 1 patient isointense on DSC-CBF; 1 patient isointense on ASL). All patients showed enhancement on post-contrast T1 anatomical scan.
    CONCLUSIONS: Perfusion MR provides additional information compared to anatomical imaging for decision-making in VS.
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  • 文章类型: Journal Article
    在运动神经元障碍患者的几项研究中发现静息状态网络中功能连通性增加,尽管扩散张量成像研究一致显示白质完整性丧失。为了理解结构连通性和功能连通性之间的关系,我们检查了原发性侧索硬化症(PLS)患者功能连接改变的区域之间的结构连接,长寿的运动神经元疾病。根据16例PLS患者的静息状态fMRI构建连接矩阵,以识别患者和健康对照之间不同连接的区域。使用概率纤维跟踪来检查不同连接性的区域之间的结构连接。与对照组相比,PLS患者有12个区域的功能连通性增加,大脑-小脑连接占优势。小脑和皮质运动区域之间以及小脑与额叶和颞叶皮质之间的功能连通性增强。光纤跟踪检测到功能连接增加的区域之间的连接没有差异。我们得出的结论是,功能连通性变化并不强烈基于结构连通性。增加的功能连接可能是由共同的输入,或者通过减少皮质激活的选择性,这可能是由于皮质传入完整时皮质内抑制的丧失。
    Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.
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  • 文章类型: Journal Article
    特发性帕金森病(IPD)是第二常见的神经退行性疾病,然而,仍然缺乏有效的疾病改善治疗。神经变性涉及多种相互作用的病理途径。涉及神经血管机制的程度在IPD中尚未明确定义。我们的目的是确定新的磁共振成像(MRI)技术,包括脑灌注的动脉自旋标记(ASL)量化,可以揭示IPD中神经血管状态(NVS)的改变。14名IPD参与者(平均±SD年龄65.1±5.9岁)和14名年龄和心血管危险因素匹配的对照参与者(平均±SD年龄64.6±4.2岁)接受了3TMRI扫描方案。之前收集了ASL图像,在6分钟高碳酸血症挑战期间和之后。FLAIR图像用于确定白质病变评分。从静息和高碳酸血症期间的ASL数据计算脑血流量(CBF)和动脉到达时间(AAT)的定量图像。计算脑血管反应性(CVR)图像,描绘了CBF和AAT相对于潮气末CO2变化的变化。与对照组(平均±SD年龄1335±165ms)相比,IPD参与者(平均±SD年龄1532±138ms)观察到全脑平均基线AAT显着(p=0.005)增加。体素分析显示,这种情况在整个大脑中普遍存在。然而,白质病变评分无统计学差异,CBF,或患者和对照组之间的CVR。区域CBF,但不是AAT,在IPD组中发现与蒙特利尔认知评估(MoCA)评分呈正相关.这些发现提供了IPD中NVS改变的进一步证据。
    Idiopathic Parkinson\'s disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.
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  • 文章类型: Journal Article
    There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson\'s disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results. To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes. We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10(- 3) mm(2)/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I(2) = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I(2) = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = - 0.5, p = 0.22, I(2) = 28%). The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson\'s disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker.
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