Disruption of the Blood-Spinal Cord Barrier Using Low-Intensity Focused Ultrasound in a Rat Model

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise ...

Johns Hopkins University School of Medicine

Elastography is an imaging technology capable of measuring tissue stiffness and consistency. The technology has achieved widespread use in the workup and management of diseases of the liver, breast, thyroid, and prostate. Although elastography is increasingly being applied in neurosurgery, it has not yet achieved widespread adoption and many clinicians remain unfamiliar with the technology. Therefore, we sought to summarize the range of applications and elastography modalities available for neurosurgery, report its effectiveness in comparison with conventional imaging methods, and offer recommendations. All full-text English-language manuscripts on the use of elastography for neurosurgical procedures were screened using the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science databases. Thirty-two studies were included with 990 patients, including 21 studies on intracranial tumors, 5 on hydrocephalus, 4 on epilepsy, 1 on spinal cord compression, and 1 on adolescent scoliosis. Twenty studies used ultrasound elastography (USE) whereas 12 used magnetic resonance elastography (MRE). MRE studies were mostly used in the preoperative setting for assessment of lesion stiffness, tumor-brain adherence, diagnostic workup, and operative planning. USE studies were performed intraoperatively to guide resection of lesions, determine residual microscopic abnormalities, assess the tumor-brain interface, and study mechanical properties of tumors. Elastography can assist with resection of brain tissue, detection of microscopic lesions, and workup of hydrocephalus, among other applications under investigation. Its sensitivity often exceeds that of conventional MRI and ultrasound for identifying abnormal tissue and lesion margins.

Applications of elastography in operative neurosurgery: A systematic review.

Spinal cord injury (SCI) is a devastating disease with limited effective treatment options. Animal paradigms are vital for understanding the pathogenesis of SCI and testing potential therapeutics. The porcine model of SCI is increasingly favored because of its greater similarity to humans. However, its adoption is limited by the complexities of care and range of testing parameters. Researchers need to consider swine selection, injury method, post-operative care, rehabilitation, behavioral outcomes, and histology metrics. Therefore, we systematically reviewed full-text English-language articles to evaluate study characteristics used in developing a porcine model and summarize the interventions that have been tested using this paradigm. A total of 63 studies were included, with 33 examining SCI pathogenesis and 30 testing interventions. Studies had an average sample size of 15 pigs with an average weight of 26 kg, and most used female swine with injury to the thoracic cord. Injury was most commonly induced by weight drop with compression. The porcine model is amenable to testing various interventions, including mean arterial pressure augmentation ( = 7), electrical stimulation ( = 6), stem cell therapy ( = 5), hypothermia ( = 2), biomaterials ( = 2), gene therapy ( = 2), steroids ( = 1), and nanoparticles ( = 1). It is also notable for its clinical translatability and is emerging as a valuable pre-clinical study tool. This systematic review can serve as a guideline for researchers implementing and testing the porcine SCI model.

Porcine Model of Spinal Cord Injury: A Systematic Review.

Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood-brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.

Kelly Jiang

Department of Neurosurgery

Johns Hopkins University School of Medicine

Disruption of the Blood-Spinal Cord Barrier Using Low-Intensity Focused Ultrasound in a Rat Model

Kelly Jiang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurosurgery

Johns Hopkins University School of Medicine

Disruption of the Blood-Spinal Cord Barrier Using Low-Intensity Focused Ultrasound in a Rat Model

Department of Neurosurgery