GigaFIBI; rapid, large-format histology-resolution imaging for Intraoperative assessment of breast lumpectomy margins

项目总结 保乳手术(BCS)，或肿块切除术，已成为治疗乳腺癌的标准手术。 BCS的目标是切除肿瘤和足够的周围组织，以减少肿瘤的发生机会 复发(边缘清晰)，但尽可能保留正常乳房外观。尽管BCS拥有 5-40%的病例术后病理检查发现肿瘤残留(切缘阳性)。 通常需要额外的手术，并有可能延误治疗、增加医疗成本、患者 焦虑，以及不理想的美容效果。在初次乳房手术时获得清晰的利润率 此外，肿瘤边缘状态是局部复发的主要决定因素，因此也可能导致肿瘤恶性。因此， 提供术中边缘评估的技术，其中最常见的是实时手术指导 与病理团队协调，有可能大幅减少额外手术的需要， 改善患者结局，增加医疗保健价值。 对于术中乳房边缘的评估，已经提出并评估了各种方法，包括 大体评价、冰冻切片分析、光学和非光学成像等。虽然这其中的每一个 与非引导手术相比，建议使用技术来降低正切缘率，它们还具有固有的 限制(例如，处理时间、成本、永久性组织变化)，具有不同程度的敏感性和 专一性。因此，单一的术中方法尚未被广泛接受到临床实践中 术后病理仍然是诊断和切缘评估的金标准。 术中BCS评估的理想工具将具有高度的敏感性，以检测所有 边缘肿瘤，与肿瘤类型无关，而且，由于诊断不是预期的结果，所以特异性 应该足够高，以限制假阳性和手术回报率。为此，我们建议 FIBI(荧光模拟亮场成像)用于快速、高质量地对BCS组织进行成像。我们将使用我们的 已经存在的FIBI技术来设计一种新的系统，Giga FIBI，能够评估大面积(UP 到100 x 100 mm2)的新鲜组织，不需要大量的处理或切片。通过一个 通过一系列验证研究，我们将证明Giga FIBI生成的显微图像具有与之相当的质量 在短短几分钟内从大表面到黄金标准的组织学。与其他现有的方法不同 Giga FIBI无需切片即可直接成像(无幻灯片技术)，是一种技术简单、成本低廉的 有效的解决方案，是非破坏性的，保持定向，并使组织可供下游使用 永久组织学或分子检测。 Giga FIBI提供的实用指导有望显著增强术中乳腺肿块 利润率评估，以最大限度地减少重复手术、局部复发，并改善患者预后。

PROJECT SUMMARY Breast-conserving surgery (BCS), or lumpectomy, has become standard for the treatment of breast cancers. The goal of BCS is to remove the cancer and enough surrounding tissue to reduce the chance of tumor recurrence (clear margins) but retain as much of the normal breast appearance as possible. Although BCS has many advantages, residual tumor (positive margins) are found on post-operative pathology in 5–40% of cases, often necessitating an additional surgery and potential for treatment delays, increased healthcare costs, patient anxiety, and suboptimal cosmetic outcomes. Obtaining clear margins at the time of the initial breast surgery also has implications for malignancy, as margin status is the chief determinant of local recurrence. Therefore, technologies providing intraoperative margin assessment, in which real-time surgical guidance is most often coordinated with the pathology team, has the potential to substantially reduce the need for additional surgeries, improve patient outcomes, and increase health care value. Various methods have been proposed and evaluated for intraoperative breast margin assessment, including gross evaluation, frozen section analysis, optical and non-optical imaging, and others. While each of these techniques are suggested to reduce positive margin rates over non-guided surgeries, they also have inherent limitations (e.g. processing time, cost, permanent tissue changes), with varying degrees of sensitivity and specificity. Accordingly, a single intraoperative method has yet to be widely accepted into clinical practice and post-operative pathology remains the gold-standard for diagnosis and margin evaluation. The ideal tool for intraoperative BCS assessments would have a high degree of sensitivity to detect all tumor in the margins, regardless of tumor type, and, since diagnosis is not the intended outcome, specificity should be high enough to both limit false positives and the rate of return surgeries. To this end, we propose FIBI (Fluorescence Imitating Brightfield Imaging) for rapid, high-quality imaging of BCS tissues. We will use our already existing FIBI technology to engineer a novel system, Giga FIBI, capable of assessing large areas (up to 100 x 100 mm2) of fresh tissue, eliminating the need for substantial processing or sectioning. Through a series of validation studies, we will show that Giga FIBI generates microscopic images at a quality comparable to gold-standard histology from large surfaces within just minutes. Unlike other existing methodologies for imaging tissue directly without sectioning (slide-free techniques), Giga FIBI is a technically simple and cost- effective solution that is non-destructive, preserves orientation, and leaves the tissue available for downstream permanent histology or molecular tests. The practical guidance provided by Giga FIBI is expected to markedly enhance intraoperative breast tumor margin assessment to minimize repeat surgeries, local recurrence, and improve patient outcomes.