Molecular Ultrasound Imaging for the Detection of Neural Inflammation: A Longitudinal Dosing Pilot Study

Abstract

Molecular ultrasound imaging provides the ability to detect physiologic processes noninvasively by targeting a variety of biomarkers in vivo. The current study was performed by exploiting an inflammatory biomarker, P-selectin, known to be present following spinal cord injury. Using a murine model (n = 6), molecular ultrasound imaging was performed using contrast microbubbles modified to target and adhere to P-selectin, prior to spinal cord injury (0D), acute stage postinjury (7D), and chronic stage (42D). Additionally, two imaging sessions were performed on each subject at specific time points, using doses of 30 μL and 100 μL. Upon analysis, targeted contrast analysis parameters were appreciably increased during the 7D scan compared with the 42D scan, without statistical significance. When examining the dose levels, the 30-μL dose demonstrated greater values than the 100-μL dose but lacked statistical significance. These findings provide additional preclinical evidence for the use of molecular ultrasound imaging for the possible detection of inflammation.

Ultrasound in Traumatic Spinal Cord Injury: A Wide-Open Field

“…Using microbubbles augmented to target P-selectin, a potent mediator of acute inflammation, the authors successfully characterized the biomarker expression levels up to 42 d after SCI. 42 Diagnostic and prognostic utility of UMI will grow as more biomarkers of SCI and recovery become available. Photoacoustic imaging is another novel technique in which pulsed lasers generate sound waves in tissue that are detected by an ultrasound transducer, with imaging data often overlaid on co-registered structural ultrasound images.…”

“…Doppler, B-mode, or harmonic mode: In Vivo spinal cord blood flow monitoring [29][30][31][32][33][34][35][36][37][38][39][40] Molecular imaging: In Vivo biomarker monitoring of inflammatory or stem cell markers [42][43][44]46 Functional ultrasound: combine with epidural stimulation for adaptive neuromodulation 77 LIFU Permeability modulation, opening of blood-spinal cord barrier Therapeutics delivery 9,59,66-70 Neuromodulation 60,61,68,69 Neuroprotection: local upregulation of endogenous neuroprotective factors [60][61][62][63] Immunomodulation 74,75 HIFU Lesioning for SCI-related pain disorders 52,[55][56][57] Tumor ablation 49 Thermothrombolysis 51 Maintain CSF patency 50,58 CSF, cerebrospinal fluid; HIFU, high intensity focused ultrasound; LIFU, low intensity focused ultrasound; SCI, spinal cord injury.…”

“…Ultrasound molecular imaging (UMI) utilizes proteinspecific micro-and nanocontrast agents to perform realtime In Vivo biomarker detection and quantification. 41 As a proof of concept, Volz et al 42,43 used UMI to assess inflammatory biomarkers following SCI in mice. Using microbubbles augmented to target P-selectin, a potent mediator of acute inflammation, the authors successfully characterized the biomarker expression levels up to 42 d after SCI.…”