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

异基因造血干细胞移植（HSCT）仍然是唯一的治疗方式， 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） 异基因造血干细胞移植的主要并发症和非复发死亡原因。GVHD是 由于供体T细胞识别受体同种异体抗原，通常在皮肤、肝脏 和胃肠道（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，每天排便量增加> 500 cc（500->1500），无其他原因 鉴定GI-GVHD的临床诊断与化疗/感染性结肠炎（CI-10）分开 结肠炎）需要结肠镜检查/内窥镜检查，然后进行活检，但专家内 病理诊断的变异性。为了克服GI-GVHD诊断中的这些局限性，我们 建议：1）测试临床MSOT检测氧合/脱氧血红蛋白的安全性， 总血红蛋白和胶原蛋白对比，并2）评估 临床MSOT区分GI-GVHD与化疗/感染性结肠炎的潜力 （CI-结肠炎），以最终提高诊断准确性，降低患者风险，并缩短时间 接受治疗 基于我们在HSCT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，这些拟议的研究旨在评估 MSOT成像区分GVHD和CI-结肠炎的潜力，最终目标是 为患者提供一种经腹无创、准确、客观的方法， 为个别病人确定疾病，以支持个性化医疗。我们 假设临床MSOT成像对于免疫功能受损患者是安全的， 临床MSOT可以根据一个特定的免疫系统将GVHD与CI-结肠炎区分开来， 氧合血红蛋白和脱氧血红蛋白以及胶原蛋白的组合。我们将通过以下方式检验这一假设： 以下目的：1）评估MSOT在GI-GVHD患者中的临床特征的安全性 或CI-结肠炎;以及2）评价临床MSOT在以下患者中识别和分层GI-GVHD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， 拟议的研究使用MSOT区分具有相似临床表现的疾病， 完全不同的疗法

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.