Non-invasive assessment of graft vs host disease using optoacoustic imaging

异基因造血干细胞移植(HSCT)仍然是治疗急性髓系白血病的唯一方法 侵袭性恶性血液病和许多非恶性血液病患者 疾病(遗传疾病和免疫缺陷疾病)。移植物抗宿主病(GVHD)是 异基因造血干细胞移植的主要并发症及无复发死亡原因。GVHD是 可归因于供者T细胞对受体同种异体抗原的识别，常见于皮肤、肝脏 胃肠道(GI-GVHD)。GI-GVHD的最初临床怀疑是由以下症状引起的 体重严重减轻，大便排泄量增加，每天500cc(500-1500)，没有其他原因 已确认身份。GI-GVHD与化疗/感染性结肠炎(CI-GVHD)的临床诊断 结肠炎)需要结肠镜/内窥镜检查，然后进行活检，但有60%的专家 病理诊断的变异性。为了克服这些在诊断GI-GVHD方面的局限性，我们 建议：1)检验临床MSOT检测氧合/脱氧血红蛋白的安全性， GI-GVHD患者的总血红蛋白、胶原对比和2)评估 临床MSOT对GI-GVHD与化疗/感染性结肠炎的鉴别价值 (结肠炎)最终提高诊断准确率、降低患者风险并缩短时间 去接受治疗。 根据我们在造血干细胞移植和患者自身免疫反应方面的经验，以及 多光谱光声断层扫描的经验，这些建议的研究旨在评估 MSOT成像在区分移植物抗宿主病和CI-结肠炎中的潜力 为患者提供一种经腹无创、准确、客观的方法 针对个别患者识别疾病，支持个性化用药。我们 假设临床MSOT成像对免疫功能低下的患者是安全的 系统和临床MSOT可以区分移植物抗宿主病和CI结肠炎 含氧和脱氧的血红蛋白和胶原蛋白的结合。我们将通过以下方式验证这一假设 目的如下：1)评估GI-GVHD患者MSOT临床特征的安全性 或CI-结肠炎；以及2)评估临床MSOT对GI-GVHD的识别和分层的潜力 HSCT患者。我们的研究将是第一个在HSCT患者中测试临床MSOT的研究 建议使用MSOT来鉴别临床表现相似但 截然不同的治疗方法。

Allogeneic hematopoietic stem cell transplant (HSCT) remains the only curative modality for patients with aggressive hematologic malignancies and many nonmalignant hematologic disorders (genetic disorders and immunodeficiency disorders). Graft vs host disease (GVHD) is the major complication and cause of non-relapse mortality in allogeneic HSCT. GVHD is attributable to donor T cell recognition of recipient alloantigen, presenting commonly in skin, liver and gastrointestinal (GI-GVHD). Initial clinical suspicion of GI-GVHD is made by symptoms of severe weight loss and increased stool output >500cc (500->1500)per day, without other cause identified. Clinical diagnosis of GI-GVHD separately from chemotherapy/infectious colitis (CI- Colitis) requires colonoscopy/endoscopy followed by biopsy, but has < 60% intra-expert variability of pathological diagnosis. To overcome these limitations in diagnosis of GI-GVHD, we propose to: 1) test the safety of Clinical MSOT detecting oxy-/deoxy-hemoglobin, total hemoglobin, and collagen contrast in patients with GI-GVHD and to 2) evaluate the potential of clinical MSOT to differentiate GI-GVHD from chemotherapy/infectious colitis (CI-Colitis) to ultimately increase diagnostic accuracy, decrease patient risk, and decrease time to therapy. Building upon our experience in HSCT and autoimmune responses in patients, as well as experience with multispectral optoacoustic tomography, these proposed studies aim to assess the potential of MSOT imaging to differentiate GVHD from CI-Colitis with the ultimate goal to provide patients a transabdominal non-invasive, accurate and objective method to identify disease for individual patients in support of personalized medicine. We hypothesize that clinical MSOT imaging is safe for patients with compromised immune systems and that clinical MSOT can distinguish GVHD from CI-Colitis based upon a combination of oxy- and deoxy-hemoglobin and collagen. We will test this hypothesis by the following Aims: 1) Assess safety of clinical features of MSOT in patients with GI-GVHD or CI-Colitis; and 2) Evaluate potential of clinical MSOT to identify and stratify GI-GVHD in HSCT patients. Our study will be the first to test clinical MSOT in HSCT patients and the first proposed study to use MSOT differentiate diseases of similar clinical presentation but radically different therapies.