Effect of sonication parameters on the efficacy of focused ultrasound and microbubble-mediated blood-spinal cord barrier opening using short-burst, phase keying exposures

2020 ◽  
Vol 148 (4) ◽  
pp. 2799-2799
Author(s):  
Stecia-Marie P. Fletcher ◽  
Min Choi ◽  
Ranjith Ramesh ◽  
Meaghan O'Reilly
Keyword(s):  
Spinal Cord ◽  
Focused Ultrasound ◽  
Short Burst ◽  
Burst Phase ◽  
Barrier Opening ◽  
Blood Spinal Cord Barrier ◽  
Sonication Parameters

scholarly journals Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Focused Ultrasound ◽  
Healthy Tissue ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Intense Staining ◽  
Her2 Breast Cancer ◽  
Sprague Dawley Rats ◽  
Blood Spinal Cord Barrier

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

scholarly journals A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening

Theranostics ◽  
2020 ◽  
Vol 10 (17) ◽  
pp. 7758-7774
Author(s):  
Stecia-Marie P. Fletcher ◽  
Min Choi ◽  
Natalia Ogrodnik ◽  
Meaghan A. O'Reilly
Keyword(s):  
Spinal Cord ◽  
Porcine Model ◽  
Barrier Opening ◽  
Blood Spinal Cord Barrier

Ultrasound-Induced Blood–Spinal Cord Barrier Opening in Rabbits

2019 ◽  
Vol 45 (9) ◽  
pp. 2417-2426
Author(s):  
Anne-Sophie Montero ◽  
Franck Bielle ◽  
Lauriane Goldwirt ◽  
Adrien Lalot ◽  
Guillaume Bouchoux ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Barrier Opening ◽  
Blood Spinal Cord Barrier

scholarly journals Magnetic resonance imaging-guided focused ultrasound to increase localized blood-spinal cord barrier permeability

2017 ◽  
Vol 12 (12) ◽  
pp. 2045 ◽  
Author(s):  
DonnaJ Cross ◽  
AllisonH Payne ◽  
GregoryW Hawryluk ◽  
Yoshimi Anzai ◽  
Henrik Odéen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Focused Ultrasound ◽  
Resonance Imaging ◽  
Barrier Permeability ◽  
Blood Spinal Cord Barrier

scholarly journals Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christian Blume ◽  
M. F. Geiger ◽  
M. Müller ◽  
H. Clusmann ◽  
V. Mainz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurological Status ◽  
Consecutive Series ◽  
Inflammatory Reactions ◽  
Immune Mediated ◽  
Elisa Testing ◽  
Cord Injury ◽  
Blood Spinal Cord Barrier ◽  
Angiopoietin 2

AbstractEndogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

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