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Project

Ultrafast Contrast-enhanced Ultrasound to Measure Local Blood Flow after SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 287 K
Funding amount
Abstract
Traumatic spinal cord injury (tSCI) develops in 2 phases. The first phase consists of the primary injury where cell death results from direct mechanical destruction of tissue. In the second phase, secondary injury results in cell death expanding into the area surrounding the primary injury. Ischemia, inadequate blood supply, is likely a key factor responsible for secondary injury. Indeed, after traumatic brain injury, careful management of perfusion pressure has resulted in significantly improved clinical outcomes. While current spine trauma guidelines recommend maintenance of a mean arterial pressure of greater than 85 mmHg, strict management and maintenance of local spinal perfusion is currently not feasible. This is in part due to the lack of technology to measure tissue perfusion directly within the injured spinal cord.Therefore, development of clinical and preclinical techniques that can accurately assess the vascular system following spinal cord after trauma are needed. We propose to develop ultrafast contrast-enhanced ultrasound (CEUS) Doppler at elevated frequencies (>15MHz) for measurement of blood flow changes following tSCI in a rat model. Ultrasound contrast agents have been in clinical use for over 20 years to detect perfusion deficits ranging from ischemia in the heart, trauma in the abdomen, to tumors. Here, we propose to develop ultrafast CEUS Doppler enabling for the first time simultaneous imaging of tissue perfusion and blood flow dynamics in spine vasculature. We will first develop ultrafast CEUS Doppler to visualize changes in both vascular structure and blood flow dynamics of spinal vessels (>50-80µm) arising from tSCI. Blood flow dynamics estimated by ultrafast CEUS Doppler will be validated by comparing the data with measurements obtained from conventional Doppler device in both in vitro and in vivo studies. Next, we will develop ultrafast CEUS Doppler’s capability to visualize perfusion changes resulting from tSCI. CEUS-based measurements of tissue perfusion will be compared with those obtained from microsphere deposition method, considered to be a gold standard. Finally, we seek to identify hemodynamic characteristics and perfusion thresholds that can best predict lesion severity and tissue at risk for secondary injury. Successful completion of our proposed studies has the potential to culminate in a novel CEUS-based biomarker able to identify the tissue at risk for secondary injury resulting from tSCI. Thus, the proposed work could lay the foundation to develop objective inclusion criteria for neuroprotective spinal cord injury trials and to validate our preclinical tSCI models. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1102 Cardiorespiratory Medicine and Haematology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Cardiovascular

  • RCDC

    Bioengineering

  • RCDC

    Neurosciences

  • RCDC

    Diagnostic Radiology

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Cardiovascular

  • HRCS RAC

    4.1 Discovery and preclinical testing of markers and technologies

  • HRCS RAC

    4.2 Evaluation of markers and technologies

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science