Spectral imaging for automated malignant blast counting

描述（由申请人提供）： 我们建议将我们成功开发的用于光学显微镜的敏捷光谱光源（通过NCI-IMAT计划资助）扩展到FDA试验中。SpectraLamp（tm）设备能够在明场（非荧光）显微镜中对双重免疫染色样品进行自动化和定量分析，特别适用于血液病理学应用。一个临床上令人信服的领域是计数恶性原始细胞的骨髓活检标本的急性白血病，骨髓增生异常综合征和慢性骨髓增生性疾病的分期和评估治疗反应的目的。目前的方法是不够的，由于穷人的采样（典型的骨髓穿刺）或难以识别真正的母细胞（骨髓活检和单色免疫组织化学表型）。双免疫分型允许在很大程度上明确的检测，但这种标记策略不支持标准（非多光谱）彩色成像系统。为了克服这一局限性，我们将联合收割机与我们的多光谱成像系统相结合，高速载玻片扫描平台可以在3分钟内以高分辨率扫描整个骨髓活检。机器学习软件工具和光谱成像将识别原始细胞，结合形态学参数和双重甚至三重免疫表型，以确保准确性和精确性。在识别出胚细胞后，流式细胞仪软件将以直方图和其他方式呈现数据，允许用户“门控”特定的细胞群，并调出细胞图像面板进行确认。 时间表：第一年将完成与设备相关的最终任务，第二年将对仪器和软件功能进行初步测试，并开发合格的免疫试剂和染色方案（由DAKOCytomation开发）。FDA批准的临床试验将在第三年进行，并提交510（k）许可申请。

DESCRIPTION (provided by applicant): We propose to extend our successful development of an agile spectral light source for light microscopy, funded through the NCI-IMAT initiative, into FDA trials. The SpectraLamp(tm) device enables the automated and quantitative analysis of double-immunostained samples in brightfield (non-fluorescence-based) microscopy, with particular utility for hematopathology applications. A clinically compelling area is the enumeration of malignant blasts in bone marrow biopsy specimens of patients with acute leukemias, myelodysplastic syndromes and chronic myleloproliferative diseases for the purpose of staging and evaluating therapeutic responses. Current methods are inadequate due to poor sampling (typical of bone marrow aspirates) or difficulty in identifying true blasts (bone marrow biopsies and single-color immunohistochemical phenotyping). Double-immunophenotyping permits largely unambiguous detection, but such labeling strategies are not supported by standard (non-multispectral) color imaging systems. To overcome this limitation, we will combine our multispectral imaging system with a high-speed slide-scanning platform that can scan an entire bone-marrow biopsy at high resolution in under 3 minutes. Machine-learning software tools and spectral imaging will identify blasts, combining morphology parameters and double or even triple immunophenotyping to ensure accuracy and precision. After blasts are identified, flow-cytometrylike software will present the data in histograms and other modalities, allowing the user to "gate" on particular cellular populations and pull up panels of cell images for confirmation. Time-line: Final equipment-related tasks will be accomplished in the first year and preliminary testing of the instrumentation and software features will occur in the second year, as will development of qualified panels of immunoreagents and staining protocols (by DAKOCytomation). FDA-sanctioned clinical trials will be conducted in the third year, leading to submission of an application for a 510(k) clearance.