Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord

Lamanna, Jason J.; Urquia, Lindsey; Hurtig, Carl V.; Gutierrez, Juanmarco; Anderson, Cody; Piferi, Pete; Federici, Thais; Oshinski, John N.; Boulis, Nicholas M.

doi:10.1159/000448765

Cited by 17 publications

(10 citation statements)

References 39 publications

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“…A lumbar laminectomy was performed to expose the spinal cord and allow direct injection of PBNC-labeled MSCs into the tissue according to previous methods. 1 , 3 , 8 Up to

of PBNC-labeled MSCs suspended at

were directly injected into the spinal cord in vivo at a rate of

using a 33G syringe attached to an ultramicropump (World Precision Instruments). The needle remained in the spinal cord for 5-min postinjection to prevent reflux.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, stem cell therapies of the spinal cord could benefit from intra- and postoperative image guidance. 1 – 5 In a recent clinical study, amyotrophic lateral sclerosis patients received stem cell treatments through direct injection into the spinal cord, which is appealing due to better outcomes in spite of high risk associated with the invasive surgical procedure. 2 , 5 – 8 Real-time intraoperative image guidance of needle insertion is desired to improve procedure safety and guide stem cell delivery to the tissue target to validate success prior to completing the surgery.…”

Section: Introductionmentioning

confidence: 99%

“… 2 , 5 – 8 Real-time intraoperative image guidance of needle insertion is desired to improve procedure safety and guide stem cell delivery to the tissue target to validate success prior to completing the surgery. 1 , 3 , 4 Next, postoperative monitoring is valuable to track stem cell location and function over time to evaluate therapy progression.…”

Section: Introductionmentioning

confidence: 99%

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In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Kubelick

Emelianov

2020

Neurophoton.

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Significance: Stem cell therapies are of interest for treating a variety of neurodegenerative diseases and injuries of the spinal cord. However, the lack of techniques for longitudinal monitoring of stem cell therapy progression is inhibiting clinical translation. Aim: The goal of this study is to demonstrate an intraoperative imaging approach to guide stem cell injection to the spinal cord in vivo. Results may ultimately support the development of an imaging tool that spans intra-or postoperative environments to guide therapy throughout treatment. Approach: Stem cells were labeled with Prussian blue nanocubes (PBNCs) to facilitate combined ultrasound and photoacoustic (US/PA) imaging to visualize stem cell injection and delivery to the spinal cord in vivo. US/PA results were confirmed by magnetic resonance imaging (MRI) and histology. Results: Real-time intraoperative US/PA image-guided injection of PBNC-labeled stem cells and three-dimensional volumetric images of injection provided feedback necessary for successful delivery of therapeutics into the spinal cord. Postoperative MRI confirmed delivery of PBNClabeled stem cells. Conclusions: The nanoparticle-augmented US/PA approach successfully detected injection and delivery of stem cells into the spinal cord, confirmed by MRI. Our work demonstrated in vivo feasibility, which is a critical step toward the development of a US/PA/MRI platform to monitor regenerative spinal cord therapies.

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“…A lumbar laminectomy was performed to expose the spinal cord and allow direct injection of PBNC-labeled MSCs into the tissue according to previous methods. 1 , 3 , 8 Up to

of PBNC-labeled MSCs suspended at

were directly injected into the spinal cord in vivo at a rate of

using a 33G syringe attached to an ultramicropump (World Precision Instruments). The needle remained in the spinal cord for 5-min postinjection to prevent reflux.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Kubelick

Emelianov

2020

Neurophoton.

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“…Intraparenchymal delivery methods and devices applied to humans can range from free-hand injections with a blunt Hamilton or insulin syringe [3-7] to table-mounted [8-11] and patient-mounted stereotactic devices [12-21]. Minimally invasive drug delivery into specific locations of the spinal cord through image-guided approaches has yet to be fully validated [22, 23].…”

Section: Introductionmentioning

confidence: 99%

A Stereotactic Device for Intraparenchymal Spinal Cord Injections: Latest Developments for Practical Clinical Use

Federici

Hardcastle

Texakalidis

et al. 2021

Stereotact Funct Neurosurg

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This manuscript introduces the latest generation of a patient-mounted platform designed for segmental injections of therapeutics direct into the spinal cord parenchyma. It emphasizes its importance and it presents the rationale for developing this delivery methodology. It compares the newest with the previous generations, detailing how the modifications can streamline transportation, assembly, sterilization, and utilization of the platform by different surgeons. Finally, the illustrations depict the main alterations, as well as a cadaveric assessment of the device prototype in the cervical and thoracolumbar regions.

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“…More recently, a prototype of an MRIcompatible spinal derrick was used for MRI-guided insertion of injection needles through the interlaminar space. 13 The second spine-mounted stereotactic system was developed at the Mayo Clinic 9 for ISMS in pigs. The system anchors to the spine through eight MRI-compatible pedicle screws spanning four vertebral levels.…”

mentioning

confidence: 99%

Ultrasound-guided spinal stereotactic system for intraspinal implants

Toossi

Everaert

Seres³

et al. 2018

Journal of Neurosurgery: Spine

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OBJECTIVEThe overall goal of this study was to develop an image-guided spinal stereotactic setup for intraoperative intraspinal microstimulation (ISMS). System requirements were as follows: 1) ability to place implants in various segments of the spinal cord, targeting the gray matter with a < 0.5-mm error; 2) modularity; and 3) compatibility with standard surgical tools.METHODSA spine-mounted stereotactic system was developed, optimized, and tested in pigs. The system consists of a platform supporting a micromanipulator with 6 degrees of freedom. It is modular and flexible in design and can be applied to various regions of the spine. An intraoperative ultrasound imaging technique was also developed and assessed for guidance of electrode alignment prior to and after electrode insertion into the spinal cord. Performance of the ultrasound-guided stereotactic system was assessed both in pigs (1 live and 6 fresh cadaveric pigs) and on the bench using four gelatin-based surrogate spinal cords. Pig experiments were conducted to evaluate the performance of ultrasound imaging in aligning the electrode trajectory using three techniques and under two conditions. Benchtop experiments were performed to assess the performance of ultrasound-guided targeting more directly. These experiments were used to quantify the accuracy of electrode alignment as well as assess the accuracy of the implantation depth and the error in spatial targeting within the gray matter of the spinal cord. As proof of concept, an intraoperative ISMS experiment was also conducted in an additional live pig using the stereotactic system, and the resulting movements and electromyographic responses were recorded.RESULTSThe stereotactic system was quick to set up (< 10 minutes) and provided sufficient stability and range of motion to reach the ISMS targets reliably in the pigs. Transverse ultrasound images with the probe angled at 25°–45° provided acceptable contrast between the gray and white matter of the spinal cord. In pigs, the largest electrode alignment error using ultrasound guidance, relative to the minor axis of the spinal cord, was ≤ 3.57° (upper bound of the 95% confidence interval). The targeting error with ultrasound guidance in bench testing for targets 4 mm deep into the surrogate spinal cords was 0.2 ± 0.02 mm (mean ± standard deviation).CONCLUSIONSThe authors developed and evaluated an ultrasound-guided spinal stereotactic system for precise insertion of intraspinal implants. The system is compatible with existing spinal instrumentation. Intraoperative ultrasound imaging of the spinal cord aids in alignment of the implants before insertion and provides feedback during and after implantation. The ability of ultrasound imaging to distinguish between spinal cord gray and white matter also improves confidence in the localization of targets within the gray matter. This system would be suitable for accurate guidance of intraspinal electrodes and drug or cell injections.

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Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord

Cited by 17 publications

References 39 publications

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

A Stereotactic Device for Intraparenchymal Spinal Cord Injections: Latest Developments for Practical Clinical Use

Ultrasound-guided spinal stereotactic system for intraspinal implants

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