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

使用光声成像对移植物抗宿主疾病进行无创评估

基本信息

批准号：
10578012
负责人：
Jennifer Lin Holter Chakrabarty
金额：
$ 16.95万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10578012
关键词：
Abdomen Adverse event Alloantigen Allogenic Anesthesia procedures Autoimmune Responses Biological Markers Biopsy Body Weight decreased Caring Categories Clinical Clinical Research Clinical Trials Colitis Collagen Colonoscopy Complication Contrast Media Crohn&apos s disease Data Deposition Diagnosis Diagnostic tests Disease Dose Endoscopy Feces Genetic Diseases Goals Hematologic Neoplasms Hematopoietic Stem Cell Transplantation Hemoglobin Human Image Immune Immune system Immunocompromised Host Immunologic Deficiency Syndromes Infectious colitis Intervention Intestines Liver Methods Modality Molecular Mus Muscular Dystrophies Non-Neoplastic Hematologic and Lymphocytic Disorder Output Oxyhemoglobin Pathologic Patient risk Patients Pharmaceutical Preparations Phase Physicians Pilot Projects Refractory Risk Schedule Skin Skin Temperature Solid Neoplasm Steroids Symptoms T-Lymphocyte Testing Therapeutic Time Transplant Recipients Weight Gain chemotherapy clinical diagnosis clinical efficacy deoxyhemoglobin diagnostic accuracy experience gastrointestinal graft vs host disease high risk histological stains improved individual patient mortality optoacoustic tomography patient stratification personalized medicine photoacoustic imaging safe patient safety assessment safety testing

项目摘要

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.

异基因造血干细胞移植（HSCT）仍然是唯一的治疗方法患有侵袭性血液系统恶性肿瘤和许多非恶性血液系统疾病的患者疾病（遗传性疾病和免疫缺陷性疾病）。移植物抗宿主病（GVHD）是异基因 HSCT 的主要并发症和非复发死亡原因。移植物抗宿主病是归因于供体 T 细胞识别受体同种抗原，常见于皮肤、肝脏和胃肠道（GI-GVHD）。胃肠道移植物抗宿主病 (GI-GVHD) 的初步临床怀疑是由以下症状引起的：体重严重减轻，排便量增加>500cc（500->1500）每天，无其他原因确定。 GI-GVHD 的临床诊断与化疗/感染性结肠炎分开（CI- 结肠炎）需要结肠镜检查/内窥镜检查，然后进行活检，但专家内部的诊断率< 60% 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， GI-GVHD 患者的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）最终提高诊断准确性、降低患者风险并缩短时间来治疗。基于我们在 HSCT 和患者自身免疫反应方面的经验，以及根据多光谱光声断层扫描的经验，这些拟议的研究旨在评估 MSOT 成像具有区分 GVHD 和 CI 结肠炎的潜力，最终目标是为患者提供经腹无创、准确、客观的方法识别个体患者的疾病以支持个性化医疗。我们假设临床 MSOT 成像对于免疫功能低下的患者是安全的系统，并且临床 MSOT 可以根据以下指标区分 GVHD 和 CI-结肠炎：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个假设目标如下： 1) 评估 GI-GVHD 患者 MSOT 临床特征的安全性或 CI-结肠炎； 2) 评估临床 MSOT 识别和分层 GI-GVHD 的潜力造血干细胞移植患者。我们的研究将是第一个在 HSCT 患者中测试临床 MSOT 的研究，也是第一个拟议的研究使用 MSOT 区分具有相似临床表现的疾病，但完全不同的疗法。