CEUS for Spinal Cord Injury

Overseen By Brian F Saway, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Pregnancy, Hypersensitivity, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new imaging method called Contrast Enhanced Ultrasound (CEUS) to help doctors see blood flow changes in the spinal cord during surgery. It aims to help patients having surgery for chronic spinal cord pressure in the neck and upper back. The goal is to predict and prevent nerve damage by spotting blood flow issues early. CEUS has been used in various studies to visualize and assess blood flow in the spinal cord, including during surgery.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Definity Perflutren Lipid Microsphere Ultrasound Contrast for spinal cord injury?

Research using contrast-enhanced ultrasound (CEUS) in animal models, like monkeys and rodents, shows that CEUS can effectively visualize and measure blood flow changes in the spinal cord after injury. This suggests that CEUS might help assess and monitor spinal cord injuries in humans, potentially guiding treatment decisions. ^{1 2 3 4 5}

Is Definity (perflutren lipid microsphere) safe for use in humans?

Definity has been associated with serious heart and lung reactions, including some deaths, leading to a warning from the FDA. However, studies show that severe adverse reactions are uncommon, and it does not increase the risk of severe events during stress echocardiography. ^{6 7 8 9 10}

How does CEUS treatment differ from other treatments for spinal cord injury?

CEUS (contrast-enhanced ultrasound) is unique because it allows real-time visualization and quantification of blood flow changes in the spinal cord after injury, which is not possible with other imaging techniques. This method can help monitor the extent of injury and guide treatment by providing detailed information on blood flow and tissue perfusion. ^{1 2 3 5 11}

Research Team

Brian Saway, MD

Principal Investigator

Medical University of South Carolina

Stephen Kalhorn, MD

Principal Investigator

Medical University of South Carolina

Jessica Barley, PhD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for adults aged 18-80 who are scheduled for posterior cervicothoracic decompression surgery to treat spinal cord compression. It's not suitable for those allergic to perflutren lipid microsphere or its components, pregnant individuals, patients with prior surgery at the same spot, or anyone unable to consent due to physical/cognitive reasons.

Inclusion Criteria

I am between 18 and 80 years old.

I am scheduled for spine surgery to treat my nerve and spinal cord condition.

Exclusion Criteria

Patients with known hypersensitivity to perflutren lipid microsphere or its components, such as polyethylene glycol (PEG)

Patients with known hypersensitivity to ultrasound contrast

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intra-operative

Use of Contrast Enhanced Ultrasound to identify discreet areas of perfusion changes in the spinal cord during decompression surgery

Approximately 3 hours

Follow-up

Participants are monitored for neurologic and functional outcomes after surgery

12 months

Treatment Details

Interventions

• Definity Perflutren Lipid Microsphere Ultrasound Contrast

Trial Overview The study tests if a contrast agent called Definity Perflutren Lipid Microsphere Ultrasound Contrast can help visualize blood flow changes in the spine during surgery. The goal is to see if it predicts and shows recovery from spinal cord injuries better than current methods.

Participant Groups

Group I: Contrast Enhanced Ultrasound Arm Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

South Carolina Spinal Cord Injury Research Fund

Collaborator

Trials

1

Recruited

20+

Findings from Research

Using contrast-enhanced ultrasound (CEUS) at higher frequencies (15 MHz) allows for improved imaging of blood flow changes in the spinal cord after injury, revealing significant differences in perfusion deficits between moderate and severe injuries in a rodent model.

The study found that acute blood flow changes, such as delayed microbubble arrival times and morphological alterations in blood vessels, correlate with chronic outcomes in locomotive function and the amount of spared spinal cord tissue, highlighting the potential of CEUS in assessing spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound. Bruce, M., DeWees, D., Harmon, JN., et al.[2023]

This study utilized contrast-enhanced ultrasound (CEUS) to effectively measure spinal cord perfusion in rhesus monkeys with acute spinal cord injuries, revealing hypoperfusion at the injury epicenter and hyperperfusion in adjacent areas.

Quantitative analysis showed significant changes in perfusion parameters, with peak intensity decreasing at the injury site and increasing in surrounding regions, indicating that CEUS could be a valuable tool for real-time monitoring of spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury. Huang, L., Chen, K., Chen, FC., et al.[2018]

Ultrafast contrast-enhanced ultrasound (CEUS) imaging effectively visualizes and quantifies acute blood flow changes in a rat model of traumatic spinal cord injury, revealing significant loss of perfusion and structural alterations in the spinal vasculature immediately after injury.

CEUS demonstrated the ability to assess local tissue perfusion and blood flow velocities, suggesting its potential clinical application for determining the extent and severity of spinal cord injuries in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury. Khaing, ZZ., Cates, LN., Hyde, J., et al.[2020]

Real-time contrast enhanced ultrasound imaging (CEU) effectively assesses spinal cord blood flow (SCBF) changes in a rat model of spinal cord injury (SCI), providing a new method to evaluate neuroprotective therapies.

The study found critical ischemia at the injury epicenter 15 minutes post-SCI, while adjacent areas showed significantly reduced SCBF, highlighting the importance of targeting the ischemic penumbra zone for potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury. Dubory, A., Laemmel, E., Badner, A., et al.[2018]

Contrast-enhanced ultrasound (CEUS) effectively quantifies spinal cord perfusion changes in a porcine model of acute spinal cord injury, revealing hypoperfusion at the injury site and hyperperfusion in adjacent areas.

The study demonstrated significant alterations in blood flow patterns post-injury, with CEUS providing valuable insights into microcirculatory changes that correlate with neurological function deterioration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion. Huang, L., Lin, X., Tang, Y., et al.[2016]

In response to serious safety concerns, including 4 patient deaths and 190 serious reactions, the FDA issued a 'black box' warning for ultrasound contrast agents Definity and Optison, leading to a significant decline in their use in the US.

Recent safety data and discussions from the FDA Cardio-Renal panel indicate ongoing evaluation of these agents, with revised labeling aimed at improving safety protocols for contrast echocardiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. Main, ML., Goldman, JH., Grayburn, PA.[2022]

In a study involving 1,060 patients, Definity (perflutren lipid microsphere) was found to be well tolerated, with no deaths or serious adverse events reported during or within 30 minutes after administration.

The overall adverse event rate was 10.8%, with a low drug-related adverse event rate of 3.5%, indicating that most adverse events were mild or moderate, making Definity a safe option for patients with suboptimal echocardiograms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. Weiss, RJ., Ahmad, M., Villanueva, F., et al.[2022]

In a study involving 4,786 patients undergoing stress echocardiography, the use of perflutren-based contrast agents like Definity and Optison did not increase the risk of severe adverse events compared to patients who did not receive contrast.

The rates of serious complications, including death within 24 hours and cardiac arrest, were similar between those receiving contrast and those who did not, indicating that the use of these contrast agents is generally safe in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in stress echocardiography. Gabriel, RS., Smyth, YM., Menon, V., et al.[2015]

A study analyzing the FDA Adverse Event Reporting System found no significant new safety concerns or major cardiovascular events associated with perflutren ultrasound contrast agents, reinforcing their relative cardiovascular safety.

The most reported adverse events were back pain and flank pain, but these were not linked to serious cardiovascular issues, suggesting that while some discomfort may occur, the overall safety profile remains favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database. Hauben, M., Hung, EY., Hanretta, KC., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Ultrasound contrast agents: balancing safety versus efficacy. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of ultrasound contrast agents in stress echocardiography. [2015]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Influence of contrast ultrasonography with perflutren lipid microspheres on microvessel injury. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury. [2019]