scholarly journals Transcranial MR-guided focused ultrasound sonothrombolysis in the treatment of intracerebral hemorrhage

2013 ◽  
Vol 34 (5) ◽  
pp. E14 ◽  
Author(s):  
Stephen J. Monteith ◽  
Neal F. Kassell ◽  
Oded Goren ◽  
Sagi Harnof
Keyword(s):  
Minimally Invasive ◽  
Intracerebral Hemorrhage ◽  
Focused Ultrasound ◽  
Focal Point ◽  
Disruptive Technology ◽  
Invasive Approach ◽  
Blood Clots ◽  
Volume Blood

Intracerebral hemorrhage remains a significant cause of morbidity and mortality. Current surgical therapies aim to use a minimally invasive approach to remove as much of the clot as possible without causing undue disruption to surrounding neural structures. Transcranial MR-guided focused ultrasound (MRgFUS) surgery is an emerging technology that permits a highly concentrated focal point of ultrasound energy to be deposited to a target deep within the brain without an incision or craniotomy. With appropriate ultrasound parameters it has been shown that MRgFUS can effectively liquefy large-volume blood clots through the human calvaria. In this review the authors discuss the rationale for using MRgFUS to noninvasively liquefy intracerebral hemorrhage (ICH), thereby permitting minimally invasive aspiration of the liquefied clot via a small drainage tube. The mechanism of action of MRgFUS sonothrombolysis; current investigational work with in vitro, in vivo, and cadaveric models of ICH; and the potential clinical application of this disruptive technology for the treatment of ICH are discussed.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance–guided focused ultrasound

2013 ◽  
Vol 118 (5) ◽  
pp. 1035-1045 ◽  
Author(s):  
Stephen J. Monteith ◽  
Sagi Harnof ◽  
Ricky Medel ◽  
Britney Popp ◽  
Max Wintermark ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Minimally Invasive ◽  
Intracerebral Hemorrhage ◽  
Focused Ultrasound ◽  
Safety Data ◽  
Surgical Techniques ◽  
Minimally Invasive Treatment ◽  
Swine Model ◽  
Invasive Treatment

Object Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. Methods and Results In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. Conclusions The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

scholarly journals Image-guided Control of Transgene Expression Based on Local Hyperthermia

2003 ◽  
Vol 2 (1) ◽  
pp. 153535002003021 ◽  
Author(s):  
E. Guilhon ◽  
B. Quesson ◽  
F. Moraud-Gaudry ◽  
H. de Verneuil ◽  
P. Canioni ◽  
...  
Keyword(s):  
Heat Shock ◽  
Transgene Expression ◽  
Focused Ultrasound ◽  
Fluorescent Protein ◽  
Focal Point ◽  
Feasibility Studies ◽  
Whole Body ◽  
Good Correspondence

Spatial and temporal control of transgene expression is one of the major prerequisites of efficient gene therapy. Recently, a noninvasive, physical approach has been presented based on local heat in combination with a heat-sensitive promoter. This strategy requires tight temperature control in vivo. Here, we use MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control on a whole-body clinical MRI system for a completely automatic execution of a predefined temperature-time trajectory in the focal point. Feasibility studies on expression control were carried out on subcutaneously implanted rat tumors. A stable modified C6 glioma cell line was used carrying a fused gene coding for thymidine kinase (TK) and green fluorescent protein (GFP) under control of the human heat-shock protein 70 (HSP70) promoter. In vitro studies showed strong induction of the TK-GFP gene expression upon heat shock under various conditions and localization of the protein product in the nucleus. In vivo tumors were subjected to a 3-min temperature elevation using MRI-FUS with a constant temperature, and were analysed 24 hr after the heat shock with respect to GFP fluorescence. Preliminary results showed strong local induction in regions heated above 40°C, and a good correspondence between temperature maps at the end of the heating period and elevated expression of TK-GFP.

scholarly journals Influence of Oxidative Stress on Time-Resolved Oxygen Detection by [Ru(Phen)3]2+ In Vivo and In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 485
Author(s):  
Veronika Huntosova ◽  
Denis Horvath ◽  
Robert Seliga ◽  
Georges Wagnieres
Keyword(s):  
Oxidative Stress ◽  
Tissue Oxygenation ◽  
Intact Cell ◽  
Molecular Probes ◽  
Stress Factors ◽  
Time Resolved ◽  
Invasive Approach ◽  
Oxygen Detection

Detection of tissue and cell oxygenation is of high importance in fundamental biological and in many medical applications, particularly for monitoring dysfunction in the early stages of cancer. Measurements of the luminescence lifetimes of molecular probes offer a very promising and non-invasive approach to estimate tissue and cell oxygenation in vivo and in vitro. We optimized the evaluation of oxygen detection in vivo by [Ru(Phen)3]2+ in the chicken embryo chorioallantoic membrane model. Its luminescence lifetimes measured in the CAM were analyzed through hierarchical clustering. The detection of the tissue oxygenation at the oxidative stress conditions is still challenging. We applied simultaneous time-resolved recording of the mitochondrial probe MitoTrackerTM OrangeCMTMRos fluorescence and [Ru(Phen)3]2+ phosphorescence imaging in the intact cell without affecting the sensitivities of these molecular probes. [Ru(Phen)3]2+ was demonstrated to be suitable for in vitro detection of oxygen under various stress factors that mimic oxidative stress: other molecular sensors, H2O2, and curcumin-mediated photodynamic therapy in glioma cancer cells. Low phototoxicities of the molecular probes were finally observed. Our study offers a high potential for the application and generalization of tissue oxygenation as an innovative approach based on the similarities between interdependent biological influences. It is particularly suitable for therapeutic approaches targeting metabolic alterations as well as oxygen, glucose, or lipid deprivation.

scholarly journals Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1207
Author(s):  
Andrea Vítečková Wünschová ◽  
Adam Novobilský ◽  
Jana Hložková ◽  
Peter Scheer ◽  
Hana Petroková ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Imaging Techniques ◽  
Barium Sulphate ◽  
Flow Conditions ◽  
Preclinical Imaging ◽  
Blood Clots ◽  
3D Printed

Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.

Impact of biomineralization on resin/biomineralized dentin bond longevity in a minimally invasive approach: An “in vitro” 18-month follow-up

2021 ◽  
Vol 37 (5) ◽  
pp. e276-e289
Author(s):  
Kelly Maria Moreira ◽  
Luiz Eduardo Bertassoni ◽  
Robert Phill Davies ◽  
Felipe Joia ◽  
José Francisco Höfling ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Minimally Invasive Approach ◽  
Invasive Approach

scholarly journals A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies

2018 ◽  
Vol 44 (2) ◽  
pp. E13 ◽  
Author(s):  
Goutam Ghoshal ◽  
Lucy Gee ◽  
Tamas Heffter ◽  
Emery Williams ◽  
Corinne Bromfield ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Minimally Invasive ◽  
Focused Ultrasound ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Rodent Model ◽  
Therapeutic Interventions ◽  
Porcine Liver

OBJECTIVEMinimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.METHODSUsing an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.RESULTSThermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.CONCLUSIONSThe authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

scholarly journals Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Hailong Yu ◽  
Xiang Cao ◽  
Wei Li ◽  
Pinyi Liu ◽  
Yuanyuan Zhao ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Connexin 43 ◽  
Nuclear Translocation ◽  
Neurological Deficits ◽  
Proximity Ligation Assay ◽  
Neuroprotective Effects ◽  
Cx43 Expression ◽  
Anti Inflammatory

Abstract Background In the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear. Methods Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins. Results In this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury. Conclusions This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

2009 ◽  
Vol 56 (6) ◽  
pp. 1189-1198 ◽  
Author(s):  
C. Damianou ◽  
K. Ioannides ◽  
V. Hadjisavvas ◽  
N. Mylonas ◽  
A. Couppis ◽  
...  
Keyword(s):  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound
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