Transcutaneous contrast-enhanced ultrasound imaging of the posttraumatic spinal cord

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Study design

Experimental animal study.


The current study aims to test whether the blood flow within the contused spinal cord can be assessed in a rodent model via the acoustic window of the laminectomy utilizing transcutaneous ultrasound.


Department of Neurological Surgery, University of Washington, Seattle WA.


Long-Evans rats (n = 12) were subjected to a traumatic thoracic spinal cord injury (SCI). Three days and 10 weeks after injury, animals underwent imaging of the contused spinal cord using ultrafast contrast-enhanced ultrasound with a Vantage ultrasound research system in combination with a 15 MHz transducer. Lesion size and signal-to-noise ratios were estimated via transcutaneous, subcutaneous, or epidural ultrasound acquisition through the acoustic window created by the original laminectomy.


Following laminectomy, transcutaneous and subcutaneous contrast-enhanced ultrasound imaging allowed for assessment of perfusion and vascular flow in the contused rodent spinal cord. An average loss of 7.2 dB from transcutaneous to subcutaneous and the loss of 5.1 dB from subcutaneous to epidural imaging in signal-to-noise ratio (SNR) was observed. The hypoperfused injury center was measured transcutaneously, subcutaneously and epidurally (5.78 ± 0.86, 5.91 ± 0.53, 5.65 ± 1.07 mm2) at 3 days post injury. The same animals were reimaged again at 10 weeks following SCI, and the area of hypoperfusion had decreased significantly compared with the 3-day measurements detected via transcutaneous, subcutaneous, and epidural imaging respectively (0.69 ± 0.05, 1.09 ± 0.11, 0.95 ± 0.11 mm2, p < 0.001).


Transcutaneous ultrasound allows for measurements and longitudinal monitoring of local hemodynamic changes in a rodent SCI model.

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Fig. 1: Illustration of experiment setup.
Fig. 2: CEUS imaging detects tissue perfusion and vascular flow within the spinal cord in a rodent.
Fig. 3: CEUS imaging performed through the acoustic window subacutely.
Fig. 4: CEUS imaging performed through the original acoustic window chronically.
Fig. 5: Transcutaneous CEUS imaging detects area of tissue perfusion deficit after SCI.
Fig. 6: Extent of  spared tissue estimated with CEUS imaging correlates with histological measurements.

Data availability

The datasets generated during this study are available from the corresponding author on reasonable request.


  1. 1.

    Ducker TB, Assenmacher DR. Microvascular response to experimental spinal cord trauma. Surg Forum. 1969;20:428–30.

  2. 2.

    Guha A, Tator CH, Rochon J. Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. Stroke. 1989;20:372–7.

  3. 3.

    Mautes AE, Weinzierl MR, Donovan F, Noble LJ. Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther. 2000;80:673–87.

  4. 4.

    Fehlings MG, Vaccaro A, Wilson JR, Singh A, WC D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PloS ONE. 2012;7:e32037.

  5. 5.

    Furlan JC, Noonan V, Cadotte DW, Fehlings MG. Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma. 2011;28:1371–99.

  6. 6.

    Wilson JR, Singh A, Craven C, Verrier MC, Drew B, Ahn H, et al. Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal Cord. 2012;50:840–3.

  7. 7.

    Wyndaele JJ. The impact of early versus late surgical decompression on neurological recovery after traumatic spinal cord injury (SCI). Spinal Cord. 2012;50:789.

  8. 8.

    Walters BC, Hadley MN, Hurlbert RJ, Aarabi B, Dhall SS, Gelb DE, et al. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery 2013;60 (Suppl 1):82–91.

  9. 9.

    Werndle MC, Saadoun S, Phang I, Czosnyka M, Varsos GV, Czosnyka ZH, et al. Monitoring of spinal cord perfusion pressure in acute spinal cord injury: initial findings of the injured spinal cord pressure evaluation study. Crit Care Med. 2014;42:646–55.

  10. 10.

    Phang I, Papadopoulos MC. Intraspinal pressure monitoring in a patient with spinal cord injury reveals different intradural compartments: injured spinal cord pressure evaluation (ISCoPE) study. Neurocrit Care. 2015;23:414–8.

  11. 11.

    Inoue T, Manley GT, Patel N, Whetstone WD. Medical and surgical management after spinal cord injury: vasopressor usage, early surgerys, and complications. J Neurotrauma. 2014;31:284–91.

  12. 12.

    Khaing ZZ, Cates LN, Fischedick AE, McClintic AM, Mourad PD, Hofstetter CP. Temporal and spatial evolution of raised intraspinal pressure following traumatic spinal cord injury. J Neurotrauma. 2017;34:645–51.

  13. 13.

    Khaing ZZ, Ehsanipour A, Hofstetter CP, Seidlits SK. Injectable hydrogels for spinal cord repair: a focus on swelling and intraspinal pressure. Cells Tissues Organs. 2016;202:67–84.

  14. 14.

    Kogler AS, Bilfinger TV, Galler RM, Mesquita RC, Cutrone M, Schenkel SS, et al. Fiber-optic monitoring of spinal cord hemodynamics in experimental aortic occlusion. Anesthesiology. 2015;123:1362–73.

  15. 15.

    Rashnavadi T, Macnab A, Cheung A, Shadgan A, Kwon BK, Shadgan B. Monitoring spinal cord hemodynamics and tissue oxygenation: a review of the literature with special focus on the near-infrared spectroscopy technique. Spinal Cord. 2019;57:617–25.

  16. 16.

    Busch DR, Davis J, Kogler A, Galler RM, Parthasarathy AB, Yodh AG, et al. Laser safety in fiber-optic monitoring of spinal cord hemodynamics: a preclinical evaluation. J Biomed Opt. 2018;23:1–9.

  17. 17.

    Soubeyrand M, Badner A, Vawda R, Chung YS, Fehlings MG. Very high resolution ultrasound imaging for real-time quantitative visualization of vascular disruption after spinal cord injury. J Neurotrauma. 2014;31:1767–75.

  18. 18.

    Soubeyrand M, Laemmel E, Dubory A, Vicaut E, Court C, Duranteau J. Real-time and spatial quantification using contrast-enhanced ultrasonography of spinal cord perfusion during experimental spinal cord injury. Spine. 2012;37:E1376–82.

  19. 19.

    Dubory A, Laemmel E, Badner A, Duranteau J, Vicaut E, Court C, et al. Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury. J Vis Exp. 2015;7:e52536.

  20. 20.

    Bruce M, Hannah A, Hammond R, Khaing ZZ, Tremblay-Darveau C, Burns PN, et al. High frequency nonlinear Doppler contrast-enhanced ultrasound imaging of blood flow. IEEE Trans Ultrason Ferroelectr Freq Control. 2020, in press.

  21. 21.

    Khaing ZZ, Cates LN, DeWees DM, Hannah A, Mourad P, Bruce M, et al. Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury. J Neurosurg Spine. 2018;29:306–13.

  22. 22.

    Tremblay-Darveau C, Williams R, Milot L, Bruce M, Burns PN. Combined perfusion and doppler imaging using plane-wave nonlinear detection and microbubble contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control. 2014;61:1988–2000.

  23. 23.

    Tremblay-Darveau C, Williams R, Sheeran PS, Milot L, Bruce M, Burns PN. Concepts and tradeoffs in velocity estimation with plane-wave contrast-enhanced Doppler. IEEE Trans Ultrason Ferroelectr Freq Control. 2016;63:1890–905.

  24. 24.

    McGraw KO, Wong SP. Forming inferences about some intraclass correlation coefficients. Psychol Methods. 1996;1:30–46.

  25. 25.

    Cao Q, Zhang YP, Iannotti C, DeVries WH, Xu XM, Shields CB, et al. Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat. Exp Neurol. 2005;191 Suppl 1:S3–S16.

  26. 26.

    Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991;75:15–26.

  27. 27.

    Guest JD, Moore SW, Aimetti AA, Kutikov AB, Santamaria AJ, Hofstetter CP, et al. Internal decompression of the acutely contused spinal cord: differential effects of irrigation only versus biodegradable scaffold implantation. Biomaterials. 2018;185:284–300.

  28. 28.

    Chen S, Smielewski P, Czosnyka M, Papadopoulos MC, Saadoun S. Continuous monitoring and visualization of optimum spinal cord perfusion pressure in patients with acute cord injury. J Neurotrauma. 2017;34:2941–9.

  29. 29.

    Jobsis FF. What is a molecular oxygen sensor? What is a transduction process? Adv Exp Med Biol. 1977;78:3–18.

  30. 30.

    Murkin JM. NIRS: a standard of care for CPB vs. an evolving standard for selective cerebral perfusion? J Extra Corpor Technol. 2009;41:P11–4.

  31. 31.

    Suehiro K, Funao T, Fujimoto Y, Mukai A, Nakamura M, Nishikawa K. Transcutaneous near-infrared spectroscopy for monitoring spinal cord ischemia: an experimental study in swine. J Clin Monit Comput. 2017;31:975–9.

  32. 32.

    Nilsson GE, Tenland T, Oberg PA. Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow. IEEE Trans Biomed Eng. 1980;27:597–604.

  33. 33.

    Carlson GD, Gorden CD, Nakazawa S, Wada E, Smith JS, LaManna JC. Sustained spinal cord compression: part II: effect of methylprednisolone on regional blood flow and recovery of somatosensory evoked potentials. J Bone Jt Surg Am. 2003;85:95–101.

  34. 34.

    Horn EM, Theodore N, Assina R, Spetzler RF, Sonntag VK, Preul MC. The effects of intrathecal hypotension on tissue perfusion and pathophysiological outcome after acute spinal cord injury. Neurosurg Focus. 2008;25:E12.

  35. 35.

    Hamamoto Y, Ogata T, Morino T, Hino M, Yamamoto H. Real-time direct measurement of spinal cord blood flow at the site of compression: relationship between blood flow recovery and motor deficiency in spinal cord injury. Spine. 2007;32:1955–62.

  36. 36.

    Westergren H, Farooque M, Olsson Y, Holtz A. Spinal cord blood flow changes following systemic hypothermia and spinal cord compression injury: an experimental study in the rat using Laser-Doppler flowmetry. Spinal Cord. 2001;39:74–84.

  37. 37.

    Griffiths IR, Rowan JO, Crawford RA. Spinal cord blood flow measured by a hydrogen clearance technique. J Neurol Sci. 1975;26:529–44.

  38. 38.

    Elmore JR, Gloviczki P, Harper CM,Jr, Murray MJ, Wu QH, Bower TC, et al. Spinal cord injury in experimental thoracic aortic occlusion: investigation of combined methods of protection. J Vasc Surg. 1992;15:789–98.

  39. 39.

    Santamaria AJ, Benavides FD, Padgett KR, Guada LG, Nunez-Gomez Y, Solano JP, et al. Dichotomous locomotor recoveries are predicted by acute changes in segmental blood flow after thoracic spinal contusion injuries in pigs. J Neurotrauma. 2019;36:1399–415.

  40. 40.

    Quencer RM. The injured spinal cord. Evaluation with magnetic resonance and intraoperative sonography. Radio Clin N Am. 1988;26:1025–45.

  41. 41.

    Badner A, Vawda R, Laliberte A, Hong J, Mikhail M, Jose A, et al. Early intravenous delivery of human brain stromal cells modulates systemic inflammation and leads to vasoprotection in traumatic spinal cord injury. Stem Cells Transl Med. 2016;5:991–1003.

  42. 42.

    Badner A, Vidal PM, Hong J, Hacker J, Fehlings MG. Endogenous Interleukin-10 deficiency exacerbates vascular pathology in traumatic cervical spinal cord injury. J Neurotrauma. 2019;36:2298–307.

  43. 43.

    Goertz DE, Cherin E, Needles A, Karshafian R, Brown AS, Burns PN, et al. High frequency nonlinear B-scan imaging of microbubble contrast agents. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52:65–79.

  44. 44.

    Tremblay-Darveau C, Williams R, Milot L, Bruce M, Burns PN. Visualizing the tumor microvasculature with a nonlinear plane-wave doppler imaging scheme based on amplitude modulation. IEEE Trans Med Imaging. 2016;35:699–709.

  45. 45.

    Mende U, Zoller J, Drommer R, Born IA, Poepel B. Realtime sonography. ZWR 1989;98:526–32.

  46. 46.

    Horii SC, Raghavendra BN. Transcutaneous sonography of the postoperative spine. Neuroradiology. 1986;28:599–607.

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This work was supported by awards from the Craig Neilsen Foundation, DoD CDMRP Translational Award (W81XWH-18-1-0753), and Department of Neurological Surgery.

Author information

ZZK, MB and CPH designed experiments, ZZK, MB and LNC performed experiments and recorded data, ZZK, MB, LNC, JEH and RH analyzed data, ZZK, MB and CPH wrote the paper and all authors reviewed and approved the paper.

Correspondence to Christoph P. Hofstetter.

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The authors declare that they have no conflict of interest.


All work performed in this study was approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Washington (Protocol Number: 4362-01). We certify that all applicable institutional and governmental regulations concerning the ethical use of vertebrate animals were followed during the course of this research.

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Khaing, Z.Z., Cates, L.N., Hyde, J.E. et al. Transcutaneous contrast-enhanced ultrasound imaging of the posttraumatic spinal cord. Spinal Cord (2020).

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