scholarly journals MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study

2020 ◽  
Vol 7 ◽  
Author(s):  
Vlad Tereshenko ◽  
Irena Pashkunova-Martic ◽  
Krisztina Manzano-Szalai ◽  
Joachim Friske ◽  
Konstantin D. Bergmeister ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Peripheral Nerves ◽  
Proof Of Concept ◽  
Peripheral Nerve Injuries ◽  
Radiological Imaging ◽  
Nerve Injuries ◽  
Experimental Proof

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Chronic effects of muscle and nerve-directed stretching on tissue mechanics

2020 ◽  
Vol 129 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ricardo J. Andrade ◽  
Sandro R. Freitas ◽  
François Hug ◽  
Guillaume Le Sant ◽  
Lilian Lacourpaille ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Tissue Mechanics ◽  
Plantar Flexor ◽  
Chronic Effects ◽  
Flexor Muscles ◽  
Plantar Flexor Muscles

This study demonstrates that the mechanical properties of plantar flexor muscles and sciatic nerve can adapt mechanically to long-term stretching programs. Although interventions targeting muscular or nonmuscular structures are both effective at increasing maximal range of motion, the changes in tissue mechanical properties (stiffness) are specific to the structure being preferentially stretched by each program. We provide the first in vivo evidence that stiffness of peripheral nerves adapts to long-term loading stimuli using appropriate nerve-directed stretching.

Sonographic examination of peripheral nerve injuries at the hands of children

2014 ◽  
Vol 5 (3) ◽  
pp. 64-66
Author(s):  
Marina Nikolayevna Romanova ◽  
Nikolay Grigoryevich Zhila ◽  
Yelena Vladimirovna Sinelnikova
Keyword(s):  
Early Detection ◽  
Peripheral Nerve ◽  
Patient Outcomes ◽  
Ultrasound Imaging ◽  
Peripheral Nerves ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Sonographic Examination ◽  
Extent Of Damage ◽  
Improve Patient

Ultrasound imaging of peripheral nerves can accurately determine the level of damage, and also to assess the extent of damage to the structure of the nerve fiber. Early detection of the type of damage can significantly improve patient outcomes.

PEGylated Gd(OH)3 nanorods as metabolizable contrast agents for computed tomography imaging

2015 ◽  
Vol 39 (11) ◽  
pp. 8999-9005 ◽  
Author(s):  
Yingda Du ◽  
Ming Xing ◽  
Zhiman Li ◽  
Wei Guo
Keyword(s):  
Computed Tomography ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Computed Tomography Imaging ◽  
Hydrothermal Route ◽  
Tomography Imaging

PEGylated Gd(OH)3 nanorods have been efficiently prepared via a facile and green hydrothermal route and used as a metabolizable computed tomography contrast agent for in vivo imaging.

scholarly journals Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats

Neurosurgery ◽  
2017 ◽  
Vol 80 (3) ◽  
pp. 465-474 ◽  
Author(s):  
Francisco Gonzalez-Perez ◽  
Stefano Cobianchi ◽  
Claudia Heimann ◽  
James B. Phillips ◽  
Esther Udina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Standard Technique ◽  
Biologically Active ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Critical Gap ◽  
The Right

Abstract BACKGROUND: Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. OBJECTIVE: To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. METHODS: The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. RESULTS: Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. CONCLUSION: A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps.

Targeted tumor MRI with gadobutrol-loaded anti-HER2 immunoliposomes

2016 ◽  
Vol 58 (5) ◽  
pp. 573-580 ◽  
Author(s):  
Weicui Chen ◽  
Bo Liu ◽  
Jun Chen ◽  
Guoqing Liu ◽  
Xian Liu
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Signal To Noise Ratio ◽  
Cellular Level ◽  
Cancer Tissue ◽  
Post Injection ◽  
Specific Tumor ◽  
Noise Ratio ◽  
Targeted Contrast Agent

Background Immunoliposomes have been used to deliver MR contrast agents to cancer tissue by targeting tumor associated antigens, thus enabling the visualization of biological processes at the cellular level. Purpose To develop and evaluate the feasibility of specific HER2 targeted liposomal MR contrast agent. Material and Methods Gd-loaded anti-HER2 immunolipomes (Gd-ILs) and non-targeted PEGylated liposomes (Gd-NTLs) were prepared and characterized. Tumor bearing animals were randomized into three groups: Gd- ILs, Gd- NTLs and gadobutrol. Animals were imaged prior and 5, 15, 60, 120 and 180 min after i.v. injection of different contrast agents. The signal intensity enhancement percentage, signal- to- noise ratio and contrast- to –noise ratio was used to qualify tumor enhancement of different groups. After imaging, tumors were excised for histological examination. Results In vivo dynamic MR images, the specific targeted contrast agent bound to tumor tissue and result in a gradual and persisting enhancement for at least 3 hours in mice bearing tumor xenografts, reaching a maximum of 87.7% enhancement after 120 min post-injection. Gd-ILs demonstrated superior tumor enhancement over control non target contrast agent and gadobutrol in HER2 overexpressing tumors at 60, 120 and 180 min post- injection. The SNR and CNR of Gd-ILs in the tumors were significantly greater than that of Gd-NTLs at 60, 120, 180 min post- injection. Conclusion The results indicate the feasibility of Gd-ILs providing prolonged circulation, specific tumor enhancement and cancer cell recognition as targeted contrast agent.

Thermographic presentation of cutaneous sensory and vasomotor activity in the injured peripheral nerve

1985 ◽  
Vol 62 (5) ◽  
pp. 711-715 ◽  
Author(s):  
Kathleen L. Brelsford ◽  
Sumio Uematsu
Keyword(s):  
Elevated Temperature ◽  
Peripheral Nerve ◽  
Local Anesthesia ◽  
Peripheral Nerves ◽  
Peroneal Nerve ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Content Type ◽  
Vasomotor Activity ◽  
Fine Print

✓ Impaired function of cutaneous segments of monkey peripheral nerves experimentally blocked by lidocaine anesthesia was clearly visualized by means of elevated temperature measurements obtained on computerized color telethermography. Mean temperature elevations in the segments of anesthetized primate nerves were 2.40°C at the ulnar segment 17 minutes after nerve block, and 1.20°C at the peroneal nerve at 20 minutes. The vasomotor activity of specific nerves, recorded after local anesthesia and displayed by color telethermographic imaging, corresponded to the distribution of sensory segments identified by more cumbersome means. Telethermography is therefore shown to be a useful tool, both qualitatively and quantitatively, in mapping cutaneous distribution of peripheral nerves and for evaluation of peripheral nerve injuries.

The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries

2012 ◽  
Vol 117 (4) ◽  
pp. 787-794 ◽  
Author(s):  
Shin Ohtsubo ◽  
Masakazu Ishikawa ◽  
Naosuke Kamei ◽  
Yasumu Kijima ◽  
Osami Suzuki ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Peripheral Blood ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Group 4 ◽  
Group 1

Object CD133+ cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133+ cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133+ cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133+ cells to induce or enhance the repair of injured peripheral nerves. Methods Phosphate-buffered saline (PBS group [Group 1]), 105 fresh CD133+ cells (fresh group [Group 2]), 105 ex vivo expanded CD133+ cells (expansion group [Group 3]), or 104 fresh CD133+ cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed. Results After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3–fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133+ cell population contained 93.22% ± 0.30% CD133+ cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133+ cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1. Conclusions The authors' results show that ex vivo expanded CD133+ cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133+ cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133+ cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.

scholarly journals Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

2015 ◽  
Vol 112 (21) ◽  
pp. 6607-6612 ◽  
Author(s):  
Shenghui Xue ◽  
Hua Yang ◽  
Jingjuan Qiao ◽  
Fan Pu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agent ◽  
Therapeutic Interventions ◽  
Mri Contrast ◽  
Liver Cancers ◽  
Poor Treatment ◽  
Ratio Imaging ◽  
Metastatic Liver

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

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