Low-Cost, Handheld Light Sheet Microscope for Guiding Anal Cancer Diagnosis
用于指导肛门癌诊断的低成本手持式光片显微镜
基本信息
- 批准号:10382361
- 负责人:
- 金额:$ 17.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-15 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptionAlgorithmic AnalysisAnusArchitectureBenignBiological MarkersBiopsyCellular MorphologyCervicalCervical Cancer ScreeningClinicalClinical ResearchComplicationConfocal MicroscopyCore BiopsyCytologyCytoplasmDetectionDevicesDiagnosisDiagnosticEarly DiagnosisEpithelialGoalsGoldHIV SeropositivityHistologyHomosexualsImageIncidenceLamina PropriaLateralLesionLightLightingMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of anusMalignant neoplasm of cervix uteriMicroscopeMicroscopyMorbidity - disease rateMucous MembraneNeedlesNuclearOperative Surgical ProceduresOptical Coherence TomographyOpticsOralPainPap smearPerformanceProceduresProgram AppropriatenessResolutionScanningScreening procedureSensitivity and SpecificitySeveritiesSignal TransductionSkinSkin CancerSourceSpecificityStandardizationSurgical marginsTechnologyThickTimeTissuesVisualizationaccurate diagnosisautomated image analysisbasecancer diagnosiscancer preventioncellular imagingclinical applicationcostdesigndiagnostic accuracydiagnostic criteriafeasibility testingfluorescence imaginghistological imagehuman imagingimaging capabilitiesimaging probeimprovedin vivomenmicroscopic imagingmortalityprototypequality assurancescreening programtooltumor
项目摘要
Project Summary/Abstract
Anal cancer incidence has been increasing, by four times over the last three decades. The incidence rate is
unacceptably high among HIV-positive homosexual men, 131 per 100,000. The main challenge in anal cancer
diagnosis and prevention is the lack of a standardized screening program. In vivo optical microscopy
technologies such as confocal microscopy and optical coherence tomography have the potential to visualize
cellular morphologic changes associated with the anal malignancy, but their clinical adaptation has been
challenging. In this Trailblazer R21 project, we propose to develop a low-cost, scattering-based light sheet
microscopy (sLSM) device that can aid accurate diagnosis of anal cancer, with the goal of ultimately reducing
the anal cancer-associated morbidity and mortality. Our sLSM device will uniquely address the unmet needs in
existing in vivo microscopy technologies (e.g., CM, OCT), simultaneously achieving i) high lateral resolution (1-
2 µm) for examining cellular nuclear features in the epithelium, ii) large FOV (~2.5 mm), iii) visualization of the
entire epithelial thickness in a single image, and iv) low device cost (~$2,000). We expect that the sLSM device
will reveal the key diagnostic cellular features in vivo, which will facilitate detection of early-stage anal
malignancy and timely initiation of adequate treatment. The sLSM device will also guide the biopsy to
malignant lesions with high sensitivity and specificity to increase the biopsy yield and reduce the morbidity and
complication caused by the unnecessary biopsy of benign lesions. As the first step towards this goal, we will
develop the prototype handheld sLSM device and evaluate the accuracy of diagnosing anal malignancy in the
following aims: In Aim 1, we will develop a handheld sLSM probe for imaging anal mucosa. The sLSM device
will provide cellular resolution in the epithelium and reveal architectural details in deeper regions in a single
image. We will optimally design the illumination and detection optics to achieve the 1.4 µm lateral resolution
over a 2.5-mm FOV, 6.5 ± 0.9 µm axial resolution for the epithelium, and 18 ± 8 µm axial resolution for the
superficial lamina propria. In Aim 2, we will conduct a clinical study of imaging human anal tissues with the
handheld sLSM device. One hundred anal biopsies concerning for anal cancer will be first imaged with the
sLSM device. sLSM images will be compared with the corresponding histologic images to identify cellular and
architectural features visualized in sLSM images and to develop the sLSM diagnostic criteria. The sensitivity
and specificity of the sLSM for diagnosing anal malignancy will be evaluated. Automated image analysis
algorithms will be developed to quantitatively evaluate the cellular and architectural features. In addition to
providing a low-cost microscopy tool that aids accurate diagnosis of anal malignancy, the sLSM technology
can be used for in vivo diagnosis of other cancers (e.g., cervical, oral, skin cancers), intra-operative
assessment of the surgical margin, and quality assurance during the core needle biopsy.
项目概要/摘要
肛门癌的发病率一直在增加,在过去三十年中增加了四倍。发病率为
在艾滋病毒呈阳性的男同性恋者中,这一比例高得令人难以接受,每 10 万人中有 131 人感染艾滋病毒。肛门癌的主要挑战
诊断和预防的关键是缺乏标准化的筛查方案。体内光学显微镜
共焦显微镜和光学相干断层扫描等技术具有可视化的潜力
细胞形态学变化与肛门恶性肿瘤相关,但其临床适应已被证实
具有挑战性的。在这个 Trailblazer R21 项目中,我们建议开发一种低成本、基于散射的光片
显微镜 (sLSM) 设备可以帮助准确诊断肛门癌,目标是最终减少
肛门癌相关的发病率和死亡率。我们的 sLSM 设备将独特地解决以下领域未满足的需求:
现有的体内显微镜技术(例如 CM、OCT),同时实现 i) 高横向分辨率(1-
2 µm) 用于检查上皮细胞核特征,ii) 大视场 (~2.5 mm),iii) 可视化
单个图像中的整个上皮厚度,以及 iv) 设备成本低(约 2,000 美元)。我们期望 sLSM 装置
将揭示体内关键的诊断细胞特征,这将有助于早期肛门疾病的检测
恶性肿瘤并及时开始适当的治疗。 sLSM 设备还将引导活检
具有高敏感性和特异性的恶性病变,以提高活检产量并降低发病率和
对良性病变进行不必要的活检而引起的并发症。作为实现这一目标的第一步,我们将
开发原型手持式 sLSM 设备并评估诊断肛门恶性肿瘤的准确性
以下目标:在目标 1 中,我们将开发一种用于肛门粘膜成像的手持式 sLSM 探头。 sLSM装置
将提供上皮细胞分辨率,并在一次中揭示更深区域的结构细节
图像。我们将优化设计照明和检测光学器件以实现 1.4 µm 横向分辨率
在 2.5 mm FOV 上,上皮细胞的轴向分辨率为 6.5 ± 0.9 µm,上皮细胞的轴向分辨率为 18 ± 8 µm
固有层浅层。在目标 2 中,我们将进行一项利用人体肛门组织成像的临床研究
手持式 sLSM 设备。首先将使用 100 个与肛门癌有关的肛门活检进行成像
sLSM 装置。 sLSM 图像将与相应的组织学图像进行比较,以识别细胞和
sLSM 图像中可视化的建筑特征并制定 sLSM 诊断标准。灵敏度
并将评估 sLSM 诊断肛门恶性肿瘤的特异性。自动图像分析
将开发算法来定量评估细胞和架构特征。此外
sLSM 技术提供了一种低成本的显微镜工具,有助于准确诊断肛门恶性肿瘤
可用于其他癌症(例如宫颈癌、口腔癌、皮肤癌)的体内诊断、术中诊断
手术切缘的评估以及空心针活检期间的质量保证。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Dongkyun Kang其他文献
Dongkyun Kang的其他文献
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Low-Cost, Handheld Light Sheet Microscope for Guiding Anal Cancer Diagnosis
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Low-Cost, Handheld Light Sheet Microscope for Guiding Anal Cancer Diagnosis
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