scholarly journals In vivo contactless brain stimulation via non-invasive and targeted delivery of magnetoelectric nanoparticles

2020 ◽  
Author(s):  
Tyler Nguyen ◽  
Jianhua Gao ◽  
Ping Wang ◽  
Abhignyan Nagesetti ◽  
Peter Andrews ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Brain Stimulation ◽  
Targeted Delivery ◽  
Brain Region ◽  
Magnetic Field Gradient ◽  
Latency Period ◽  
Global Network ◽  
Invasive Technique ◽  
Non Invasive

AbstractNon-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in humans. However, the current technologies usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) can be navigated to a targeted brain region with a magnetic field and is highly efficient in converting an externally applied magnetic wave into local electric fields for neuronal activity modulation. Here we developed a new method to fabricate MENs of CoFe2O4-BaTiO3 core-shell structure that had excellent magneto-electrical coupling properties. Using calcium imaging of organotypic and acute cortical slices from GCaMP6s transgenic mice, we demonstrated their efficacy in reliably evoking neuronal responses with a short latency period. For in vivo non-invasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and guided to pass through the blood brain barrier to a targeted brain region by applying a magnetic field gradient. A magnetic field (∼450 Oe at 10 Hz) applied to mouse brain was able to reliably evoke cortical activities, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. This study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of contactless deep brain stimulation that may have great potential for translation.

In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

2021 ◽  
Author(s):  
Tyler Nguyen ◽  
Jianhua Gao ◽  
Ping Wang ◽  
Abhignyan Nagesetti ◽  
Peter Andrews ◽  
...  
Keyword(s):  
Brain Stimulation ◽  
Targeted Delivery ◽  
Non Invasive

Spectroscopic imaging of human disease

1996 ◽  
Vol 54 ◽  
pp. 884-885
Author(s):  
D.J. Meyerhoff
Keyword(s):  
Magnetic Field ◽  
Magnetic Resonance ◽  
Field Gradient ◽  
Human Disease ◽  
Morphological Changes ◽  
Magnetic Field Gradient ◽  
Spectroscopic Imaging ◽  
Resonance Spectroscopy ◽  
Tissue Water

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),

scholarly journals Multiplexed Non-invasive in vivo Imaging to Assess Metabolism and Receptor Engagement in Tumor Xenografts

2019 ◽  
Author(s):  
Alena Rudkouskaya ◽  
Nattawut Sinsuebphon ◽  
Marien Ochoa ◽  
Joe E. Mazurkiewicz ◽  
Xavier Intes ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Metabolic Response ◽  
Imaging Modalities ◽  
Wide Field ◽  
Receptor Ligand ◽  
Non Invasive ◽  
Intracellular Drug Delivery

AbstractFollowing an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. To date, non-invasive quantitative imaging modalities that can comprehensively assess simultaneous cellular drug delivery efficacy and therapeutic response are lacking. In this regard, Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in vivo and subsequent intracellular internalization, which is critical to assess the delivery efficacy of targeted therapeutics. However, implementation of multiplexing optical imaging with FRET in vivo is challenging to achieve due to spectral crowding and cross-contamination. Herein, we report on a strategy that relies on a dark quencher that enables simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700) using in vitro NIR FLI microscopy and in vivo wide-field MFLI imaging. Second, we report on simultaneous in vivo imaging of the metabolic probe IRDye 800CW 2-deoxyglucose (2-DG) and MFLI-FRET imaging of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

scholarly journals Optical coherence tomography imaging of oral mucosa bullous diseases: a preliminary study

2020 ◽  
Vol 49 (2) ◽  
pp. 20190071
Author(s):  
Dario Di Stasio ◽  
Dorina Lauritano ◽  
Francesca Loffredo ◽  
Enrica Gentile ◽  
Fedora Della Vella ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Oral Mucosa ◽  
Statistical Power ◽  
Pemphigus Vulgaris ◽  
Invasive Technique ◽  
Optical Coherence ◽  
Non Invasive ◽  
Bullous Diseases ◽  
Subepithelial Layer

Objectives: Optical coherence tomography (OCT) is a non-invasive technique based on optical imaging with a micrometre resolution. The purpose of this study is to investigate the potential role of OCT in evaluating oral mucosa bullous diseases. Methods: two patients with bullous pemphigoid (BP) and one patient with pemphigus vulgaris (PV) were examined and images of their oral lesions were performed using OCT. Results: In OCT images, the BP blister has a clearly different morphology from the PV one compared to the blistering level. Conclusion: This exploratory study suggests that the OCT is able to distinguish epithelial and subepithelial layer in vivo images of healthy oral mucosa from those with bullous diseases, assisting the clinicians in differential diagnosis.The presented data are in accordance with the scientific literature, although a wider pool of cases is needed to increase statistical power. Histological examination and immunofluorescence methods remain the gold standard for the diagnosis of oral bullous diseases. In this context, the OCT can provide the clinician with a valuable aid both as an additional diagnostic tool and in the follow up of the disease.

scholarly journals Confocal Raman spectroscopy: Evaluation of a non-invasive technique for the detection of topically applied ketorolac tromethamine in vitro and in vivo

2019 ◽  
Vol 570 ◽  
pp. 118641 ◽  
Author(s):  
Christian J.F. Bertens ◽  
Shuo Zhang ◽  
Roel J. Erckens ◽  
Frank J.H.M. van den Biggelaar ◽  
Tos T.J.M. Berendschot ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Invasive Technique ◽  
Ketorolac Tromethamine ◽  
Confocal Raman Spectroscopy ◽  
Non Invasive ◽  
Confocal Raman

Extracranial Carotid Artery Disease Assessed By Indium-111 Labelled Platelets In Man

1981 ◽  
Author(s):  
M Goldman ◽  
D Simpson ◽  
R J Hawker ◽  
Z Drolc ◽  
C N McCollum
Keyword(s):  
Gamma Camera ◽  
Ex Vivo ◽  
Carotid Artery Disease ◽  
Objective Assessment ◽  
Diagnostic Methods ◽  
Invasive Technique ◽  
Platelet Activity ◽  
Transient Ischaemic Attacks ◽  
Non Invasive

Platelet microemboli have been implicated in the aetiology of transient ischaemic attacks and strokes. Current non-invasive diagnostic methods are restricted to assessing blood flow. Arteriography may demonstrate non-occluding atheromatous ulcers but carries a significant morbidity.111-In labelled platelets and gamma camera imaging of diseased carotid vessels have therefore been evaluated.Eight patients proceeding to unilateral carotid endarterectomy received an injection of autologous platelets labelled with 111-In-oxine 48 hours preoperatively. Gamma camera images were taken at 4 and 24 hours. Operative endarterectomy specimens were collected and gamma emissions were measured.The scintigraphic images were independently assessed by two observers. Nine abnormal vessels were identified by platelet accumulation. In 5 cases the observers combined assessment was in complete accord with previous bilateral angiography. Individually each observer identified the symptomatic side in 6 patients. Activity in the endarterectomy specimens measured ex vivo varied from 1.22-84.5 times greater than background activity. The ratio of specimen activity to 5 ml blood samples simultaneously taken varied from 0.017 to 0.360 (mean 0.089).This non-invasive technique allows localisation of platelet activity in the extracranial cerebral circulation. Objective assessment in vivo is hindered by the relatively small amount of activity on the diseased vessels by comparison with circulating blood activity.

scholarly journals 4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation

2020 ◽  
Vol 4 (s1) ◽  
pp. 11-11
Author(s):  
Tyler Nguyen ◽  
Zoe Vriesman ◽  
Peter Andrews ◽  
Sehban Masood ◽  
M Stewart ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Post Treatment ◽  
Calcium Signals ◽  
Whole Brain ◽  
Non Invasive ◽  
Cortical Regions

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.

scholarly journals Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography

2021 ◽  
Vol 22 (5) ◽  
pp. 2440
Author(s):  
Rocío Benítez-Fernández ◽  
Carolina Melero-Jerez ◽  
Carmen Gil ◽  
Enrique J. de la Rosa ◽  
Ana Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Invasive Technique ◽  
Optic Coherence Tomography ◽  
Non Invasive ◽  
Disease Modifying ◽  
Orally Bioavailable ◽  
Ms Therapy

The need for remyelinating drugs is essential for healing disabling diseases such as multiple sclerosis (MS). One of the reasons for the lack of this class of therapies is the impossibility to monitor remyelination in vivo, which is of utmost importance to perform effective clinical trials. Here, we show how optical coherence tomography (OCT), a cheap and non-invasive technique commonly used in ophthalmology, may be used to assess remyelination in vivo in MS patients. Our pioneer approach validates OCT as a technique to study remyelination of the optic nerve and reflects what is occurring in non-accessible central nervous system (CNS) structures, like the spinal cord. In this study we used the orally bioavailable small molecule VP3.15, confirming its therapeutical potential as a neuroprotective, anti-inflammatory, and probably remyelinating drug for MS. Altogether, our results confirm the usefulness of OCT to monitor the efficacy of remyelinating therapies in vivo and underscore the relevance of VP3.15 as a potential disease modifying drug for MS therapy.

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