Saeed Usman, Lang Anthony E, Masellis Mario
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Front Neurol. 2020 Oct 15;11:572976. doi: 10.3389/fneur.2020.572976. eCollection 2020.
Parkinson's disease (PD) and atypical Parkinsonian syndromes are progressive heterogeneous neurodegenerative diseases that share clinical characteristic of parkinsonism as a common feature, but are considered distinct clinicopathological disorders. Based on the predominant protein aggregates observed within the brain, these disorders are categorized as, (1) α-synucleinopathies, which include PD and other Lewy body spectrum disorders as well as multiple system atrophy, and (2) tauopathies, which comprise progressive supranuclear palsy and corticobasal degeneration. Although, great strides have been made in neurodegenerative disease research since the first medical description of PD in 1817 by James Parkinson, these disorders remain a major diagnostic and treatment challenge. A valid diagnosis at early disease stages is of paramount importance, as it can help accommodate differential prognostic and disease management approaches, enable the elucidation of reliable clinicopathological relationships ideally at prodromal stages, as well as facilitate the evaluation of novel therapeutics in clinical trials. However, the pursuit for early diagnosis in PD and atypical Parkinsonian syndromes is hindered by substantial clinical and pathological heterogeneity, which can influence disease presentation and progression. Therefore, reliable neuroimaging biomarkers are required in order to enhance diagnostic certainty and ensure more informed diagnostic decisions. In this article, an updated presentation of well-established and emerging neuroimaging biomarkers are reviewed from the following modalities: (1) structural magnetic resonance imaging (MRI), (2) diffusion-weighted and diffusion tensor MRI, (3) resting-state and task-based functional MRI, (4) proton magnetic resonance spectroscopy, (5) transcranial B-mode sonography for measuring substantia nigra and lentiform nucleus echogenicity, (6) single photon emission computed tomography for assessing the dopaminergic system and cerebral perfusion, and (7) positron emission tomography for quantifying nigrostriatal functions, glucose metabolism, amyloid, tau and α-synuclein molecular imaging, as well as neuroinflammation. Multiple biomarkers obtained from different neuroimaging modalities can provide distinct yet corroborative information on the underlying neurodegenerative processes. This integrative "multimodal approach" may prove superior to single modality-based methods. Indeed, owing to the international, multi-centered, collaborative research initiatives as well as refinements in neuroimaging technology that are currently underway, the upcoming decades will mark a pivotal and exciting era of further advancements in this field of neuroscience.
帕金森病（PD）和非典型帕金森综合征是渐进性的异质性神经退行性疾病，它们都具有帕金森症的临床特征，但被认为是不同的临床病理障碍。根据在大脑中观察到的主要蛋白质聚集体，这些疾病可分为两类：（1）α-突触核蛋白病，包括帕金森病和其他路易体谱系障碍以及多系统萎缩；（2）tau蛋白病，包括进行性核上性麻痹和皮质基底节变性。尽管自1817年詹姆斯·帕金森首次对帕金森病进行医学描述以来，神经退行性疾病研究取得了很大进展，但这些疾病仍然是主要的诊断和治疗挑战。在疾病早期阶段进行准确诊断至关重要，因为它有助于采取不同的预后和疾病管理方法，理想情况下在疾病前驱期阐明可靠的临床病理关系，还能促进对临床试验中新型疗法的评估。然而，帕金森病和非典型帕金森综合征早期诊断的探索受到显著的临床和病理异质性的阻碍，这会影响疾病的表现和进展。因此，需要可靠的神经影像学生物标志物来提高诊断的确定性，并确保做出更明智的诊断决策。在本文中，我们将从以下几种模式对成熟的和新兴的神经影像学生物标志物进行更新介绍：（1）结构磁共振成像（MRI）；（2）扩散加权和扩散张量MRI；（3）静息态和基于任务的功能MRI；（4）质子磁共振波谱；（5）用于测量黑质和豆状核回声的经颅B型超声检查；（6）用于评估多巴胺能系统和脑灌注的单光子发射计算机断层扫描；（7）用于量化黑质纹状体功能、葡萄糖代谢、淀粉样蛋白、tau蛋白和α-突触核蛋白分子成像以及神经炎症的正电子发射断层扫描。从不同神经影像学模式获得的多种生物标志物可以提供关于潜在神经退行性过程的不同但相互佐证的信息。这种综合的“多模式方法”可能优于基于单一模式的方法。事实上，由于目前正在进行的国际多中心合作研究计划以及神经影像学技术的改进，未来几十年将是神经科学领域进一步取得重大进展的关键且令人兴奋 的时代。
