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：可移植显微镜上精确数字病理学的衍射断层扫描 摘要：完整的血细胞计数（CBC）和外周血涂片（PBS）分析最多 无处不在的血液检查有序有助于了解患者的潜在病理状况。 目前，通常使用两种单独的仪器进行这些测试，并且都需要 专用实验室人员进行操作。因此，这些测试的范围仅限于集中式 具有所需基础设施的医院或独立实验室的实验室设施。此“有限”访问 延伸到医院的初级保健中心以及医院的急诊室 较长的周转时间，症状周围的不确定性以及测试和测试之间的多次随访 医生的预后。为了应对这些挑战，最近有几项努力来开发 基于光学的高分辨率成像，用于CBC和PBS分析的便携式系统 显微镜。不幸的是，由于大量高分辨率成像的挑战，这些 系统无法成功解决此问题。另外，CBC的参数，例如平均细胞体积 （MCV），平均细胞血红蛋白（MCH）和血红蛋白（Hb）无法从标准中获得 显微镜的强度图像。相反，需要3D“断层扫描”成像系统 准确地从PBS获得了这些参数，但是商业断层系统很大， 昂贵，并且只能为样品的一小部分图像。在此提案中，我们将使用3D 微观成像技术称为傅立叶ptychographic层析成像（FPT），以生成完整 PBS和CBC参数，例如来自最终折射率的MCV和MCH和MCH 厚度测量。我们的FPT设置仅需要放置在样品下方的LED阵列 标准显微镜的平面，导致紧凑，便携式和通常低成本的仪器。 它的其他断层扫描信息还改善了血细胞形态学的检测 镰状细胞贫血或白血病等疾病。在这一阶段1赠款中，我们将发展世界的 首次便携式断层造影显微镜并演示其自动血液学的实用性（即CBC 和PBS分析）在护理点，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。