Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Traumatic spinal cord injury (tSCI) causes an almost complete loss of blood flow at the site of injury (primary injury) as well as significant hypoperfusion in the penumbra of the injury. Hypoperfusion in the penumbra progresses after injury to the spinal cord and is likely to be a major contributor to progressive cell death of spinal cord tissue that was initially viable (secondary injury). Neuroprotective treatment strategies seek to limit secondary injury. Clinical monitoring of the temporal and spatial patterns of blood flow within the contused spinal cord is currently not feasible. The purpose of the current study was to determine whether ultrafast contrast-enhanced ultrasound (CEUS) Doppler allows for detection of local hemodynamic changes within an injured rodent spinal cord in real time.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>A novel ultrafast CEUS Doppler technique was developed utilizing a research ultrasound platform combined with a 15-MHz linear array transducer. Ultrafast plane-wave acquisitions enabled the separation of higher-velocity blood flow in macrocirculation from low-velocity flow within the microcirculation (tissue perfusion). An FDA-approved contrast agent (microbubbles) was used for visualization of local blood flow in real time. CEUS Doppler acquisition protocols were developed to characterize tissue perfusion both during contrast inflow and during the steady-state plateau. A compression injury of the thoracic spinal cord of adult rats was induced using iris forceps.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>High-frequency ultrasound enabled visualization of spinal cord vessels such as anterior spinal arteries as well as central arteries (mean diameter [± SEM] 145.8 ± 10.0 µm; 76.2 ± 4.5 µm, respectively). In the intact spinal cord, ultrafast CEUS Doppler confirmed higher perfusion of the gray matter compared to white matter. Immediately after compression injury of the thoracic rodent spinal cord, spinal cord vessels were disrupted in an area of 1.93 ± 1.14 mm<jats:sup>2</jats:sup>. Ultrafast CEUS Doppler revealed a topographical map of local tissue hypoperfusion with remarkable spatial resolution. Critical loss of perfusion, defined as less than 40% perfusion compared to the surrounding spared tissue, was seen within an area of 2.21 ± 0.6 mm<jats:sup>2</jats:sup>.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>In our current report, we introduce ultrafast CEUS Doppler for monitoring of spinal vascular structure and function in real time. Development and clinical implementation of this type of imaging could have a significant impact on the care of patients with tSCI.</jats:p></jats:sec>

Super-Resolution Ultrasound Localization Microscopy Through Deep Learning

“…After dissection of paraspinal muscles, a laminectomy was performed to expose the spinal cord from T6 to T10. A compression-type lesion was produced [29]. High-frame-rate CEUS acquisitions of the cord were performed with a Vantage ultrasound research platform (Verasonics, Seattle, WA, USA), using a linear array transducer (Vermon, Tours, France).…”

“…We proceed to apply Deep-ULM in-vivo, using a highframe-rate (400 Hz) CEUS scan of a rat spinal cord acquired with a Verasonics Vantage ultrasound research scanner [29]. We retrained the neural network based on an estimate of the PSF parameters of this system (obtained using the tool described earlier), and performed Deep-ULM on an 8-second acquisition to obtain a super resolved image.…”

“…Fig. 7 shows the application of Deep-ULM on a 12-second CEUS acquisition of a rat spinal cord following an injury [29], clearly depicting the resulting vascular deficit.…”

Physiopathology of Spinal Cord Injury

“…After a mechanical spinal cord injury (primary lesion), a series of self-destructive mechanisms (secondary lesion) is triggered that cause greater destruction of the spinal cord parenchyma with long-term sequela. Spinal cord injury is associated with mechanical damage, biochemical disorders, and hemodynamic changes [3]. The anatomic point where the primary lesion is exerted is known as the "epicenter," and the secondary mechanisms develop in a centrifugal form around the epicenter, expanding the injured area (Figure 1).…”

Implantable Osmotic Transport Device Can Reduce Edema After Severe Contusion Spinal Cord Injury

“…These initial studies suggest that spinal cord parenchymal swelling due to edema accumulation continues to expand radially until the tissue reaches the dura and can no long swell outward, despite routine decompressive laminectomy. This leads to an inevitable localized pressure build-up that causes the subarachnoid space to collapse at the epicenter and significant constriction of flow within local blood vessels (Soubeyrand et al, 2014a;Khaing et al, 2018;Saadoun and Papadopoulos, 2020). The collapsed blood vessels are no longer able to supply nutrients to the surrounding tissue and this creates local ischemia, further worsening tissue secondary injury (Gallagher et al, 2019).…”