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Molecular Ultrasound Imaging for the Detection of Neural Inflammation

Volz, Kevin R
http://rave.ohiolink.edu/etdc/view?acc_num=osu1460728270

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Health and Rehabilitation Sciences.
Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound’s capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was performed while targeting three early inflammatory markers (P-selectin, VCAM-1, ICAM-1). Imaging protocols and outcome measures of previous TCEUS investigations of inflammation were replicated to aid in comparisons of outcomes. Signal intensity data was used to generate time intensity curves for qualitative and quantitative analysis of contrast agent temporal behavior. A proof of principle study established preclinical evidence to support the ability of TCEUS to detect acute neural inflammation. Substantial increases in signal intensities were observed while targeting inflammatory markers compared to controls. Further investigations consisted of examining molecular ultrasound sensitivity, and were accomplished by examining targeted contrast agent dosing parameters, and the ability of TCEUS to longitudinally evaluate neural inflammation. Qualitative analysis of TCEUS imaging performed with both administered doses revealed marked increases in signal intensities during acute inflammation, where inflammatory marker expression was presumably at its highest. This was in comparison to measures obtained in the absence of, and during, chronic inflammation. This research contributes much needed empirical evidence to the molecular ultrasound body of literature, and represents the first steps towards advancing this TCEUS application to clinical practice. Future studies are necessary to further these findings and effectively build upon this evidence. Increasing evidence of TCEUS use for the detection of neural inflammation will aid in its eventual clinical translation, where it will likely have a positive impact on patient care.
Kevin Evans, PhD (Advisor)
John Buford, PhD (Committee Member)
Carolyn Sommerich, PhD (Committee Member)
Miriam Freimer, MD (Committee Member)
259 p.
Health Sciences; Medical Imaging; Nanotechnology; Neurology; Radiology

Recommended Citations

Citations

  • Volz, K. R. (2016). Molecular Ultrasound Imaging for the Detection of Neural Inflammation [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1460728270

    APA Style (7th edition)

  • Volz, Kevin. Molecular Ultrasound Imaging for the Detection of Neural Inflammation. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1460728270.

    MLA Style (8th edition)

  • Volz, Kevin. "Molecular Ultrasound Imaging for the Detection of Neural Inflammation." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1460728270

    Chicago Manual of Style (17th edition)

osu1460728270
432
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This open access ETD is published by The Ohio State University and OhioLINK.