Hofstetter
Laboratory
University of Washington
Department of Neurological Surgery
OUR RESEARCH
Our laboratory focuses on the spinal cord. In particular, we target systems of the spinal cord that may have a direct positive impact on patient care at the University of Washington Medical Center. We have a variety of ongoing projects.
Ultrasound biomarkers for acute spinal cord injury
Traumatic Spinal Cord Injury
We are pioneering the use of advanced Ultrafast Contrast-Enhanced Ultrasound (CEUS) imaging to revolutionize assessment and prognostic capabilities following traumatic spinal cord injury (tSCI). Our cutting-edge approach combines high-frequency plane-wave ultrasound imaging with contrast agents, allowing us to visualize and measure spinal cord tissue perfusion, disruptions in vascular architecture, and changes in blood flow velocities with remarkable spatial and temporal precision.
Our recent studies have demonstrated that CEUS-derived metrics, including the perfusion area deficit (PAD) and the spinal perfusion index (SPI), strongly correlate with injury severity and long-term functional outcomes in both rodent models and our patients. This novel imaging modality provides unprecedented insight into tissue viability and has the potential to significantly enhance clinical decision-making immediately following injury. By enabling early identification of tissue at risk for secondary damage, this technology could substantially improve therapeutic interventions and patient recovery outcomes.
This innovative research is conducted in collaboration with Dr. Matthew Bruce at the University of Washington's Applied Physics Laboratory.
Advances In Spinal Cord Research
Spasticity Recovering after tSCI
We are developing electrical stimulation as a treatment for spasticity and functional recovery after spinal cord injury (SCI). Spasticity affects nearly two-thirds of people with traumatic SCI, causing involuntary muscle contractions that impair daily activities, such as grasping, eating, writing, and quality of life. Since no standard treatment exists, we first optimize the approach in animal models before translating it to humans. Dr. Sadeghi has developed unique devices to measure spasticity in rodents, enabling us to study stimulation effects. Collaborating with experts in the field, specifically Dr. Chet Moritz from the Department of Neurorehabilitation, and Dr. Steve Perlmutter from the Department of Biophysics and Physiology, we have shown that non-invasive spinal cord stimulation, combined with rehabilitation, reduces spasticity and improves motor control in chronic cervical SCI patients, with lasting benefits even after treatment ends.
Neuroprotective Effects of Spinal Cord Decompression in Traumatic Injury
Concept of Ceiling Effect
Acute traumatic spinal cord injury (tSCI) leads to secondary neuroglial cell death, which neuroprotective interventions like spinal decompression aim to reduce. This study examined whether the effectiveness of decompression varies with injury severity in a rat model. We found that in moderate spinal cord injuries, durotomy improved hindlimb function (p < 0.01), while myelotomy increased tissue preservation and motor neuron survival (p < 0.05). However, in severe injuries, neither intervention significantly improved outcomes (p > 0.05). Additionally, myelotomy resulted in greater tissue sparing compared to durotomy alone in moderate injuries (p < 0.01). These results suggest that spinal decompression is more beneficial in moderate tSCI but less effective in severe cases, highlighting the need for severity-specific personalized treatment approaches.
Botulinum Toxin A Preserves Bladder Integrity After Spinal Cord Injury
Bladder Chemo-denervation with Botulinum Toxin A
Following spinal cord injury, pathological reflexes lead to altered bladder function and detrusor hypertrophy. While bladder chemodenervation with botulinum toxin A (BoNT-A) is known to disrupt these reflexes, its effects on bladder tissue remain unclear. This study conducted by our lab used a rodent model of severe thoracic contusion spinal cord injury to examine the impact of early BoNT-A injections on bladder histopathology and collagen deposition. At eight weeks post-injury, BoNT-A-treated bladders weighed significantly less than saline-treated bladders (p < 0.05) and had thinner bladder walls (p < 0.0001). Spinal cord injury-induced detrusor hypertrophy and fibrosis were significantly reduced in BoNT-A-treated animals, with collagen organization resembling that of uninjured controls. These findings suggest that early detrusor chemodenervation with BoNT-A helps preserve bladder integrity by preventing fibrosis and excessive thickening.
Advancing Therapy Through Joint Research
The Hofstetter lab has expanded their research through a collaboration with Dr. Price at the University of Texas, focusing on single-cell RNA analysis of C1-2 DRGs from patients with acute or chronic neck pain. This work aims to uncover potential therapeutic targets and has been recognized by the NIH, earning a prestigious U19 grant to extend our research into chronic low back pain. The unwavering support from our esteemed surgeons, Drs. Karandikar, Khan and Amin, has been instrumental in driving forward our research initiatives and advancing clinical breakthroughs.
Read about the C1-2 and Chronic Lower Back Pain here
