Development and validation of lens-free polarized microscopy to identify mono-sodium urate and calcium pyrophosphate crystals from synovial fluid

开发和验证无透镜偏光显微镜以识别滑液中的尿酸钠和焦磷酸钙晶体

• 批准号: 9761457
• 负责人: JOHN D FITZGERALD
• 金额: $ 17.16万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-09 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761457
• 关键词: Affect; Agreement; Algorithms; Arthritis; Automation; Birefringence; Calcium Pyrophosphate; Calcium pyrophosphate deposition disease; Characteristics; Clinical; Consumption; Crystallization; Data; Databases; Deposition; Detection; Development; Devices; Diagnosis; Diagnostic; Examinations and Diagnoses; Gold; Gout; Image; Inflammatory Arthritis; Joints; Light Microscope; Methodology; Methods; Microscope; Microscopic; Microscopy; Modality; Optics; Patients; Polarization Microscopy; Process; Property; Pseudogout; Resolution; Sampling; Scanning; Synovial Fluid; System; Technology; Testing; Time; Urate; Validation; Work; arthropathies; clinical application; cost; experience; image processing; improved; instrument; instrumentation; lens; particle; polarized light; screening

ABSTRACT Crystal arthropathy is the most common type of inflammatory arthritis, caused by the deposition of either monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPP) crystals in or around joints, clinically recognized as either gout or pseudogout. Diagnosis of crystal arthropathy can be established by identifying MSU or CPPD crystals in the synovial fluid with a compensated polarized light microscope (CPLM). CPLM has been the gold- standard diagnostic instrument for crystal arthropathy since 1961. However, given the limited field of view (FOV) of CPLM, examination for crystals can be laborious. Furthermore, the sensitivity of CPLM can be affected by crystal concentration, size, and birefringent properties (particularly for CPP crystals), as well as technician experience. There exists the need to develop an inexpensive high-resolution, wide-FOV polarized microscopic device for synovial fluid screening, with improved sensitivity. Lens-free on-chip microscopy has developed in the past decade. The advantages of the lens-free microscope include high-resolution, wide FOV, low cost and compact instrumentation. However, lens-free technology has not been adapted to perform polarized imaging due to a fundamental difference in its imaging principle. We have developed a way to overcome this challenge and have preliminary data showing the ability of our system to accurately detect both MSU and CPP crystals. The proposed lens-free polarized on-chip microscope will enable the rapid screening and sensitive detection of birefringent crystals in synovial fluid samples of patients, greatly improving the sensitivity and efficiency of gout and pseudogout diagnosis.

摘要 水晶性关节病是最常见的炎性关节炎类型，由 临床上关节内或关节周围的尿酸一钠(MSU)或二水焦磷酸钙(CPP)晶体 被识别为痛风或假性痛风。晶状体关节病的诊断可以通过识别 用补偿偏光显微镜观察滑液中的MSU或CPPD晶体。CPLM有 自1961年以来一直是水晶关节病的黄金标准诊断仪器。然而，鉴于有限的 在CPLM的视场(FOV)中，对晶体的检查可能很费力。此外，CPLM的灵敏度 也会受到晶体浓度、大小和双折射特性的影响(特别是对于CPP晶体) 作为技术员的经验。存在开发廉价的高分辨率、宽视场的需求 用于滑液筛查的偏光显微镜设备，具有更高的灵敏度。 无透镜片上显微镜是在过去的十年中发展起来的。无透镜显微镜的优势 包括高分辨率、宽视场、低成本和紧凑仪器。然而，无镜头技术具有 由于成像原理的根本不同，不适合进行偏振成像。我们 已经开发出了一种克服这一挑战的方法，并有初步数据表明我们系统的能力 以准确检测MSU和CPP晶体。 提出的无透镜偏振片上显微镜将能够快速筛选和灵敏地检测 患者滑液样本中的双折射晶体，大大提高了痛风的敏感性和效率 和伪基因诊断。

项目成果

Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis.

• DOI: 10.1038/srep28793
• 发表时间: 2016-06-30
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Zhang Y;Lee SY;Zhang Y;Furst D;Fitzgerald J;Ozcan A
• 通讯作者: Ozcan A

Pathological crystal imaging with single-shot computational polarized light microscopy.

• DOI: 10.1002/jbio.201960036
• 发表时间: 2020-01
• 期刊: Journal of biophotonics
• 影响因子: 2.8
• 作者: Bai B;Wang H;Liu T;Rivenson Y;FitzGerald J;Ozcan A
• 通讯作者: Ozcan A

Diagnostic advances in synovial fluid analysis and radiographic identification for crystalline arthritis.

结晶性关节炎滑液分析和放射学鉴定的诊断进展。

• DOI: 10.1097/bor.0000000000000582
• 发表时间: 2019
• 期刊: Current opinion in rheumatology
• 影响因子: 5.1
• 作者: Zell,Monica;Zhang,Dawen;FitzGerald,John
• 通讯作者: FitzGerald,John

Deep Learning-Based Holographic Polarization Microscopy.

• DOI: 10.1021/acsphotonics.0c01051
• 发表时间: 2020-11-18
• 期刊: ACS photonics
• 影响因子: 7
• 作者: Liu T;de Haan K;Bai B;Rivenson Y;Luo Y;Wang H;Karalli D;Fu H;Zhang Y;FitzGerald J;Ozcan A
• 通讯作者: Ozcan A