Diffraction tomography for accurate digital pathology on a portable microscope

便携式显微镜上的衍射断层扫描可实现精确的数字病理学

• 批准号: 10257624
• 负责人: Pratik Bokadia
• 金额: $ 24.9万
• 依托单位: AIRILABS LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-04 至 2024-03-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10257624
• 关键词: 3-Dimensional; Accident and Emergency department; Address; Agreement; Algorithms; Anemia; Area; Blood; Blood Cell Count; Blood Cells; Blood Tests; Cell Count; Cell Volumes; Cells; Cellular Morphology; Chemicals; Clinic; Clinical; Complete Blood Count; Complex; Computational Technique; Computer Systems; Data; Detection; Devices; Diagnosis; Disease; Elements; Erythrocytes; Etiology; Future; Gold; Grant; Health; Hematology; Hemoglobin; Hospitals; Human Resources; Image; Imaging Techniques; Infrastructure; Laboratories; Lighting; Machine Learning; Maps; Measurement; Measures; Mechanics; Methods; Microscope; Morphology; Optics; Outcome; Pathologic; Patient Monitoring; Patients; Phase; Play; Primary Health Care; Procedures; Prognosis; Property; Refractive Indices; Reporting; Resolution; Role; Sampling; Scanning; Sickle Cell Anemia; Slide; Source; Specimen; Surface; Symptoms; System; Systems Development; Testing; Thick; Three-Dimensional Imaging; Time; Training and Infrastructure; Trauma; Uncertainty; Universities; Virus Diseases; Width; base; chemical property; cost; data acquisition; digital pathology; experience; high resolution imaging; imaging capabilities; imaging system; improved; indexing; instrument; lens; leukemia; mean corpuscular volume observed; medical schools; microscopic imaging; new technology; novel; peripheral blood; point of care; portability; programs; quantitative imaging; reconstruction; tomography; validation studies

Title: Diffraction tomography for accurate digital pathology on a portable microscope Abstract: Complete blood cell count (CBC) and peripheral blood smear (PBS) analysis are the most ubiquitous blood tests ordered to help understand the underlying pathological condition of a patient. Currently, two separate instruments are typically used to conduct these tests, and both require dedicated lab personnel to operate. As a result of this, the reach of these tests is limited to centralized lab facilities in hospitals or independent labs with the required infrastructure. This ‘limited’ access extends to primary care centers as well as emergency rooms in the hospital, where patients experience longer turnaround times, uncertainty around their symptoms, and multiple follow-ups between tests and doctor’s prognosis. To address these challenges there have been several recent efforts to develop a portable system for CBC and PBS analysis, based on high-resolution imaging with an optical microscope. Unfortunately, due to the challenge of high-resolution imaging over a large volume, these systems cannot successfully address this problem. Also, parameters of CBC such as Mean Cell Volume (MCV), Mean Cellular Hemoglobin (MCH), and Hemoglobin (Hb) cannot be obtained from the standard intensity images of the microscope. Instead, a 3D “tomographic” imaging system is needed to accurately obtain these parameters from a PBS, but commercial tomographic systems are bulky, expensive, and can only image a small area of the sample. In this proposal, we will use a 3D microscopic imaging technique termed Fourier ptychographic tomography (FPT) to generate complete PBS and CBC parameters such as MCV and MCH from the resulting refractive index and the cell thickness measurements. Our FPT setup simply requires an LED array placed beneath the sample plane of a standard microscope, resulting in a compact, portable, and generally low-cost instrument. Its additional tomographic information also improves the detection of blood cell morphological conditions such as sickle cell anemia or Leukemia. In this Phase-1 grant, we will develop the world’s first portable tomographic microscope and demonstrate its utility for automated hematology (i.e., CBC and PBS analysis) at point-of-care, which will pave the way for future clinical tests of our new instrument in Phase II.

标题：便携式显微镜上精确数字病理学的衍射断层扫描 翻译后摘要：全血细胞计数（CBC）和外周血涂片（PBS）分析是最 为了帮助了解病人潜在的病理状况而进行的普遍的血液检查。 目前，通常使用两种单独的仪器来进行这些测试，并且两者都需要 专门的实验室人员进行操作。因此，这些测试的范围仅限于集中的 医院的实验室设施或具有所需基础设施的独立实验室。这种“有限”的访问 延伸到初级保健中心以及医院的急诊室， 更长的周转时间，围绕他们的症状的不确定性，以及测试之间的多次随访， 医生的预测为了应对这些挑战，最近做出了一些努力， 用于CBC和PBS分析的便携式系统，基于光学高分辨率成像 显微镜不幸的是，由于在大体积上进行高分辨率成像的挑战，这些 系统不能成功地解决这个问题。此外，CBC参数，如平均细胞体积 (MCV)、平均细胞血红蛋白（MCH）和血红蛋白（Hb）无法从标准品中获得 显微镜的强度图像。相反，需要3D“断层”成像系统来 精确地从PBS获得这些参数，但是商业层析成像系统体积庞大， 昂贵，并且只能对样品的小区域成像。在本提案中，我们将使用3D 显微成像技术称为傅立叶重叠关联断层扫描（FPT），以生成完整的 PBS和CBC参数，如MCV和MCH，来自所得折射率和细胞 厚度测量我们的FPT设置只需在样品下方放置一个LED阵列 平面的标准显微镜，导致在紧凑，便携式，一般低成本的仪器。 其附加的断层信息也提高了血细胞形态的检测 镰状细胞性贫血或白血病。在第一阶段，我们将开发世界上 第一个便携式断层摄影显微镜并证明其用于自动血液学（即，CBC 和PBS分析），这将为我们的新仪器的未来临床测试铺平道路 在第二阶段。