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灵活光谱光源扩展到FDA的试验中，该光源由NCI-IMAT倡议资助。SpectraLamp(Tm)设备能够在Brightfield(非基于荧光的)显微镜下对双重免疫染色样本进行自动化和定量分析，特别适用于血液病理学应用。临床上一个引人注目的领域是对急性白血病、骨髓增生异常综合征和慢性骨髓增生性疾病患者的骨髓活检标本中的恶性母细胞进行计数，以期对治疗效果进行分期和评估。目前的方法并不充分，原因是采样质量差(典型的骨髓抽吸物)或难以识别真正的原始细胞(骨髓活检和单色免疫组织化学表型分析)。双重免疫表型可以在很大程度上明确检测，但标准(非多光谱)彩色成像系统不支持这种标记策略。为了克服这一限制，我们将把我们的多光谱成像系统与高速载玻片扫描平台相结合，该平台可以在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母细胞，结合形态参数和双重甚至三重免疫表型，以确保准确性和精确度。在识别出原始细胞后，类似于流式细胞术的软件将以直方图和其他方式显示数据，允许用户对特定的细胞群体进行“选通”，并调出细胞图像面板进行确认。 时间表：与设备有关的最后任务将在第一年完成，仪器和软件功能的初步测试将在第二年进行，以及开发合格的免疫试剂面板和染色方案(通过DAKOCytomation)。FDA批准的临床试验将在第三年进行，导致提交510(K)批准的申请。

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.