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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to monitor spinal cord health during surgery for individuals with chronic neck and upper back issues. It employs a special ultrasound using tiny bubbles (Definity Perflutren Lipid Microsphere Ultrasound Contrast) to observe blood flow changes in the spinal cord. The researchers aim to determine if this technique can predict and possibly prevent nerve damage during surgery. Eligible participants are those scheduled for specific neck and upper back surgeries due to nerve problems in those areas. As an unphased trial, this study allows participants to contribute to innovative research that could enhance surgical outcomes for future patients.

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 prior data suggests that this imaging technique is safe for spinal cord injury patients?

Research has shown that Definity Perflutren Lipid Microsphere, the ultrasound contrast agent used in this study, is safe. Testing has confirmed its safety for patients, including those with heart and lung issues. The FDA has approved it for other uses, such as heart and liver imaging, indicating general safety for people.

Studies have also found no major safety differences between older and younger patients using this contrast agent, suggesting it is well-tolerated across age groups. Although not yet approved specifically for spinal cord injury, its safety in other medical areas is reassuring. Patients should always consult their doctor with any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Definity Perflutren Lipid Microsphere Ultrasound Contrast for spinal cord injury because it offers a novel approach to diagnosis and monitoring. Unlike traditional imaging techniques, this contrast agent enhances ultrasound imaging, providing clearer, more detailed pictures of blood flow and tissue structure. This could potentially lead to earlier and more accurate assessments of spinal cord injuries, allowing for better-informed treatment decisions. Additionally, the non-invasive nature of ultrasound makes it a safer, more comfortable option for patients compared to more invasive procedures.

What evidence suggests that contrast enhanced ultrasound is effective for detecting spinal cord injury?

Research has shown that contrast-enhanced ultrasound (CEUS), which participants in this trial will receive, effectively detects changes in blood flow in spinal cord injuries. Animal studies demonstrated that CEUS can identify changes in blood movement through injured spinal cords. This is crucial because these changes can highlight areas of the spine not receiving enough blood, potentially leading to further injury. CEUS uses tiny bubbles to create clear images of blood flow without radiation. Although CEUS is already used for imaging the heart and liver, it holds promise for monitoring spinal cord health during surgery. ^{2 4 6 7 8}

Who Is on the Research Team?

Jessica Barley, PhD

Principal Investigator

Medical University of South Carolina

Brian Saway, MD

Principal Investigator

Medical University of South Carolina

Stephen Kalhorn, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06654804

Contrast-enhanced Ultrasound in the Treatment of Acute ... The investigators plan to use contrast-enhanced ultrasound (CEUS) to determine a decrease in the blood flow in the spinal cord at the site of injury, during the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11045808/

Contrast enhanced ultrasound for traumatic spinal cord injury Studies in animal models have shown CEUS to be an effective non-invasive imaging modality that can detect perfusion changes of injured spinal cords in real ...

3. withpower.com withpower.com/trial/contrast-enhanced-ultrasound-for-spinal-cord-injury-cf86a

Contrast-Enhanced Ultrasound for Spinal Cord Injury The research shows that contrast-enhanced ultrasound (CEUS) can effectively assess blood flow changes in spinal cord injuries, which is crucial for ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38664470/

Contrast enhanced ultrasound for traumatic spinal cord injury The objective of this review is to evaluate the current literature on the various applications and benefits of CEUS in traumatic spinal cord ...

5. definityimaging.com definityimaging.com/

DEFINITY® (Perflutren Lipid Microsphere) Diagnostic ... DEFINITY is a diagnostic ultrasound enhancing agent that uses advanced microbubble technology to opacify the left ventricular chamber.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/021064s025s029lbl.pdf

Definity - accessdata.fda.gov No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not ...

7. definityimaging.com definityimaging.com/safety

Safety Profile of DEFINITY® for Medical Imaging DEFINITY® is demonstrated to be safe in patients with a high prevalence of cardiopulmonary disease and pulmonary hypertension.

8. mayoclinic.org mayoclinic.org/drugs-supplements/perflutren-lipid-microsphere-intravenous-route/description/drg-20067608

Perflutren lipid microsphere (intravenous route) Perflutren lipid microsphere is an ultrasound contrast agent. ... Safety and efficacy have been established. Geriatric. Appropriate studies ...