Ultrasound-guided photoacoustic imaging and tracking of stem cells in the spinal cord

超声引导光声成像和脊髓干细胞追踪

基本信息

批准号：
9978212
负责人：
STANISLAV Y EMELIANOV
金额：
$ 43.4万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9978212
关键词：
3-Dimensional Abbreviations Address Amyotrophic Lateral Sclerosis Apoptosis Apoptotic Area Autopsy BODIPY Biological CASP3 gene Cell Count Cell Survival Cell Transplantation Cells Clinical Clinical Engineering Clinical Trials Contrast Media Development Disadvantaged Disease Engraftment Feedback Foundations Glossary Goals Gold Histologic Histology Imaging Techniques Immune Implant In Vitro Injections Ionizing radiation Label Location Magnetic Resonance Imaging Mesenchymal Stem Cells Monitor Operative Surgical Procedures Optics Patients Penetration Positron-Emission Tomography Postoperative Period Procedures Protocols documentation Rattus Research Research Personnel Risk Rodent Scientist Signal Transduction Spinal Cord Spinal Cord Diseases Spinal cord injury Stem cell transplant System Techniques Technology Therapeutic Time Tissue Sample Tissues Translations Transplantation Treatment Efficacy Ultrasonography Work X-Ray Computed Tomography base clinical imaging clinically relevant cost effective effective therapy high risk image guided imaging approach imaging platform imaging study imaging system in vivo in vivo imaging migration minimal risk nanorod novel photoacoustic imaging portability post-transplant preclinical study programs real-time images sensor serial imaging spinal cord imaging stem cell fate stem cell therapy stem cells success

项目摘要

ABSTRACT Stem cells, including mesenchymal stem cells (MSCs) have proven to be an exciting and promising thera- peutic for the treatment of numerous diseases and disorders of the spinal cord, such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Positive results in preclinical studies have led to an increase in transla- tion of stem cell therapies. However, upon reaching clinical trials, many stem cell therapeutics fail. In search for answers, the clinicians and researchers are missing critical information; the fate of the cells once implanted. Therefore, there is a definite and urgent clinical need for a technique that is capable of accurate real-time guid- ance of quantitative stem cell delivery to target areas, noninvasive longitudinal in vivo tracking of stem cell loca- tion, and assessment of stem cell viability over time after the delivery. This project is based on a hypothesis that stem cells can be effectively labeled with a photoacoustic imaging contrast agent and a photoacoustic apoptosis sensor to visualize cell localization and ascertain their viability, respectively; and ultrasound-guided photoacous- tic (USPA) imaging system and approach can be developed for longitudinal, quantitative, and noninvasive track- ing of double-labeled stem cells and their fate in vivo. The overall goal of this research program is to develop a novel cell labeling system and corresponding USPA imaging approach allowing real time image guidance for precise and accurate injection of the stem cells, and longitudinal tracking both the location and viability of stem cells in vivo in the spinal cord. First, a PA sensitive tracker will be developed, which will allow for real time feedback on the location of the stem cells during and immediately after injection, as well as post-operative tracking the location of the transplanted cells over time. Second, a PA sensor of apoptosis will be developed. This sensor will provide a unique PA signal in cells which are undergoing apoptosis, allowing us to ascertain the cells viability. The combination of both PA tracker and apoptotic sensor to double label stem cells is critical for real time imaged guided delivery of cells, and tracking viable and apoptotic cells longitudinally in vivo. The USPA imaging double-labeled cells will provide highly valu- able information of the fate of stem cells in vivo, which can be used to refine and advance the field of stem cell transplantation in the spinal cord. If successful, this work will lay foundation for in vivo real-time intra-operative and then longitudinal USPA imaging of transplanted cells within the spinal cord – the technology needed by both scientists and clinicians.

抽象的干细胞，包括间充质干细胞（MSC），已被证明是一种令人兴奋且有前途的治疗方法。用于治疗多种脊髓疾病和病症，例如脊髓损伤 (SCI) 临床前研究的积极结果导致了肌萎缩侧索硬化症（ALS）的增加。然而，许多干细胞疗法在进入临床试验后都失败了。答案是，新来者和研究人员缺少关键信息；细胞植入后的命运。因此，临床迫切需要一种能够准确实时引导的技术。定量干细胞递送到目标区域的能力，干细胞定位的无创纵向体内跟踪和评估分娩后一段时间内干细胞的活力。该项目基于以下假设：可以用光声成像造影剂和光声凋亡有效地标记干细胞传感器分别可视化细胞定位并确定其活力；以及超声波引导光声 tic (USPA) 成像系统和方法可以开发用于纵向、定量和非侵入性跟踪双标记干细胞的形成及其体内命运。该研究项目的总体目标是开发一种新型细胞标记系统和相应的USPA 成像方法允许实时图像引导以精确准确地注射干细胞，以及纵向追踪脊髓体内干细胞的位置和活力首先，PA 敏感。将开发跟踪器，这将允许实时反馈干细胞在过程中和过程中的位置注射后立即进行，以及术后跟踪移植细胞随时间的位置。其次，将开发细胞凋亡的PA传感器。该传感器将在细胞中提供独特的PA信号。正在经历细胞凋亡，使我们能够确定 PA 追踪器和细胞活力的组合。双标记干细胞的凋亡传感器对于实时成像引导的细胞递送和跟踪至关重要 USPA 成像双标记细胞可在体内纵向观察活细胞和凋亡细胞。体内干细胞命运的丰富信息，可用于完善和推进干细胞领域如果成功，这项工作将为体内实时术中移植奠定基础。然后对脊髓内移植细胞进行纵向 USPA 成像——这是两者都需要的技术科学家和信徒。