MR-Guided Focused Ultrasound: A New Generation Treatment of Parkinson's Disease, Essential Tremor and Neuropathic Pain

The application of high intense focused ultrasound (HIFU) is currently the subject of many experimental and clinical trials. The combination of HIFU with MRI guidance known as MR-guided focused ultrasound (MRgFUS) appears to be particularly promising to ablate tissues located deep in the brain. The method can be the beginning of interventional neurology and an important alternative to neurosurgery. Studies conducted to date show the effectiveness of the method both in chronic diseases and in emergency cases. The safety and effectiveness of this method have been observed in parkinsonian and essential tremor as well as in neuropathic pain. The procedure does not require anaesthesia. Ionizing radiation is not used and there is no risk of cumulative dose. Such advantages may result in low complication rates and medical justification for further development of MRgFUS.

Download Full-text

Mechanics Of Ultrasonic Neuromodulation In A Mouse Subject

10.1101/2021.09.23.461613 ◽

2021 ◽

Author(s):

Hossein Salahshoor ◽

Hongsun Guo ◽

Mikhail G. Shapiro ◽

Michael Ortiz

Keyword(s):

Pressure Wave ◽

Focused Ultrasound ◽

Shear Waves ◽

Element Model ◽

Wave Pattern ◽

Promising Tool ◽

Sensory Effects ◽

The Subject ◽

Sensory Responses ◽

The Brain

AbstractUltrasound neuromodulation (UNM), where a region in the brain is targeted by focused ultrasound (FUS), which, in turn, causes excitation or inhibition of neural activity, has recently received considerable attention as a promising tool for neuroscience. Despite its great potential, several aspects of UNM are still unknown. An important question pertains to the off-target sensory effects of UNM and their dependence on stimulation frequency. To understand these effects, we have developed a finite-element model of a mouse, including elasticity and viscoelasticity, and used it to interrogate the response of mouse models to focused ultrasound (FUS). We find that, while some degree of focusing and magnification of the signal is achieved within the brain, the induced pressure-wave pattern is complex and delocalized. In addition, we find that the brain is largely insulated, or ‘cloaked’, from shear waves by the cranium and that the shear waves are largely carried away from the skull by the vertebral column, which acts as a waveguide. We find that, as expected, this waveguide mechanism is strongly frequency dependent, which may contribute to the frequency dependence of UNM effects. Our calculations further suggest that off-target skin locations experience displacements and stresses at levels that, while greatly attenuated from the source, could nevertheless induce sensory responses in the subject.

Download Full-text

Faculty Opinions recommendation of A pilot study of focused ultrasound thalamotomy for essential tremor.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718075956.793489765 ◽

2014 ◽

Author(s):

Leo Verhagen ◽

Brandon Barton

Keyword(s):

Pilot Study ◽

Essential Tremor ◽

Focused Ultrasound

Download Full-text

The Obesity-associated Risk in Open and Endovascular Repair of Abdominal Aortic Aneurysm

Current Pharmaceutical Design ◽

10.2174/1381612825666190710112844 ◽

2019 ◽

Vol 25 (18) ◽

pp. 2033-2037 ◽

Cited By ~ 2

Author(s):

Djordje Radak ◽

Slobodan Tanaskovic ◽

Mihailo Neskovic

Keyword(s):

Risk Factor ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Treatment Option ◽

Morbidly Obese ◽

Complication Rates ◽

Obese Patients ◽

Invasive Treatment ◽

Abdominal Aortic ◽

The Subject

: The rising pandemic of obesity in modern society should direct attention to a more comprehensive approach to abdominal aortic aneurysm (AAA) treatment in the affected population. Although overweight patients are considered prone to increased surgical risk, studies on the subject did not confirm or specify the risks well enough. : Associated comorbidities inevitably lead to a selection bias leaning towards endovascular abdominal aortic repair (EVAR), as a less invasive treatment option, which makes it hard to single out obesity as an independent risk factor. The increased technical difficulty often results in prolonged procedure times and increased blood loss. Several smaller studies and two analyses of national registries, including 7935 patients, highlighted the advantages of EVAR over open repair (OR) of abdominal aortic aneurysm, especially in morbidly obese population (relative risk reduction up to 47%). On the other hand, two other studies with 1374 patients combined, concluded that EVAR might not have an advantage over OR in obese patients (P = 0.52). Obesity is an established risk factor for wound infection after both EVAR and OR, which is associated with longer length of stay, subsequent major operations, and a higher rate of graft failure. Percutaneous EVAR technique could present a promising solution to reducing this complication. : EVAR seems like a more feasible treatment option than OR for obese patients with AAA, due to lower overall morbidity and mortality rates, as well as reduced wound-related complication rates. However, there is a clear lack of high-quality evidence on the subject, thus future prospective trials are needed to confirm this advantage.

Download Full-text

Naphthoquinone Derivatives Isolated from Plants: Recent Advances in Biological Activity

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200818212020 ◽

2020 ◽

Vol 20 (19) ◽

pp. 2019-2035

Author(s):

Esmaeil Sheikh Ahmadi ◽

Amir Tajbakhsh ◽

Milad Iranshahy ◽

Javad Asili ◽

Nadine Kretschmer ◽

...

Keyword(s):

Clinical Trials ◽

Biological Activity ◽

Small Molecules ◽

Anticancer Activity ◽

Clinical Significance ◽

Phase Ii ◽

Biological Activities ◽

Phase Ii Clinical Trials ◽

Naturally Occurring ◽

The Subject

Naturally occurring naphthoquinones (NQs) comprising highly reactive small molecules are the subject of increasing attention due to their promising biological activities such as antioxidant, antimicrobial, apoptosis-inducing activities, and especially anticancer activity. Lapachol, lapachone, and napabucasin belong to the NQs and are in phase II clinical trials for the treatment of many cancers. This review aims to provide a comprehensive and updated overview on the biological activities of several new NQs isolated from different species of plants reported from January 2013 to January 2020, their potential therapeutic applications and their clinical significance.

Download Full-text

Revision Targeted Muscle Reinnervation Improves Secondary Pain Insult in an Upper Extremity Amputee: A Case Report

Hand ◽

10.1177/1558944721992467 ◽

2021 ◽

pp. 155894472199246

Author(s):

David D. Rivedal ◽

Meng Guo ◽

James Sanger ◽

Aaron Morgan

Keyword(s):

Neuropathic Pain ◽

Peripheral Nerves ◽

Nerve Biopsy ◽

Sensory Cortex ◽

Denervated Muscle ◽

Unique Case ◽

Targeted Muscle Reinnervation ◽

Muscle Reinnervation ◽

And Function ◽

The Brain

Targeted muscle reinnervation (TMR) has been shown to improve phantom and neuropathic pain in both the acute and chronic amputee population. Through rerouting of major peripheral nerves into a newly denervated muscle, TMR harnesses the plasticity of the brain, helping to revert the sensory cortex back toward the preinsult state, effectively reducing pain. We highlight a unique case of an above-elbow amputee for sarcoma who was initially treated with successful transhumeral TMR. Following inadvertent nerve biopsy of a TMR coaptation site, his pain returned, and he was unable to don his prosthetic. Revision of his TMR to a more proximal level was performed, providing improved pain and function of the amputated arm. This is the first report to highlight the concept of secondary neuroplasticity and successful proximal TMR revision in the setting of multiple insults to the same extremity.

Download Full-text

Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery

Scientific Reports ◽

10.1038/s41598-021-81046-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Danielle Weber-Adrian ◽

Rikke Hahn Kofoed ◽

Joseph Silburt ◽

Zeinab Noroozian ◽

Kairavi Shah ◽

...

Keyword(s):

Gene Delivery ◽

Intravenous Injection ◽

Viral Vectors ◽

Focused Ultrasound ◽

Fluorescent Protein ◽

Gfp Expression ◽

Peripheral Organs ◽

Neuronal Expression ◽

Green Fluorescent ◽

The Brain

AbstractNon-surgical gene delivery to the brain can be achieved following intravenous injection of viral vectors coupled with transcranial MRI-guided focused ultrasound (MRIgFUS) to temporarily and locally permeabilize the blood–brain barrier. Vector and promoter selection can provide neuronal expression in the brain, while limiting biodistribution and expression in peripheral organs. To date, the biodistribution of adeno-associated viruses (AAVs) within peripheral organs had not been quantified following intravenous injection and MRIgFUS delivery to the brain. We evaluated the quantity of viral DNA from the serotypes AAV9, AAV6, and a mosaic AAV1&2, expressing green fluorescent protein (GFP) under the neuron-specific synapsin promoter (syn). AAVs were administered intravenously during MRIgFUS targeting to the striatum and hippocampus in mice. The syn promoter led to undetectable levels of GFP expression in peripheral organs. In the liver, the biodistribution of AAV9 and AAV1&2 was 12.9- and 4.4-fold higher, respectively, compared to AAV6. The percentage of GFP-positive neurons in the FUS-targeted areas of the brain was comparable for AAV6-syn-GFP and AAV1&2-syn-GFP. In summary, MRIgFUS-mediated gene delivery with AAV6-syn-GFP had lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.

Download Full-text

Medicinal Plants and Mushrooms with Immunomodulatory and Anticancer Properties—A Review on Hong Kong’s Experience

Molecules ◽

10.3390/molecules26082173 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2173

Author(s):

Grace Gar-Lee Yue ◽

Clara Bik-San Lau ◽

Ping-Chung Leung

Keyword(s):

Clinical Trials ◽

Medicinal Plants ◽

Infection Control ◽

Immune Modulation ◽

Evidence Based ◽

Medicinal Mushroom ◽

Immunomodulatory Effects ◽

Anticancer Properties ◽

Further Development ◽

Insight Into

The immune modulating effects of selected herbs deserve careful studies to gain evidence-based support for their further development. We have been working hard on many items of medicinal herbs to gain insight into their immunomodulatory effects relevant to cancer treatment in particular, while infection control is not excluded. Nine of them have been selected to give the results of our exploration on their biological, particularly immunomodulatory activities. Since Hong Kong people especially favor one medicinal mushroom, viz. Coriolus versicolor, a number of clinical trials using Coriolus for cancer-related studies are included in this review. While immune modulation platforms are being built for relevant studies, a brief account on the research targets and related procedures are given.

Download Full-text

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Vaccines ◽

10.3390/vaccines9040359 ◽

2021 ◽

Vol 9 (4) ◽

pp. 359

Author(s):

Thai Thanh Hoang Thi ◽

Estelle J. A. Suys ◽

Jung Seok Lee ◽

Dai Hai Nguyen ◽

Ki Dong Park ◽

...

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Physicochemical Properties ◽

Solid Lipid Nanoparticles ◽

Drug Delivery Systems ◽

Lipid Nanoparticles ◽

Therapeutic Vaccines ◽

Cancer Nanomedicine ◽

Fundamental Research ◽

Further Development

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

Download Full-text