Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases

Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics is immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. From the Clinical Editor Many nervous system disorders remain unresolved clinical problems. In many cases, drug agents simply cannot cross the blood-brain barrier (BBB) into the nervous system. The advent of nanomedicines can enhance the delivery of biologically active molecules for targeted therapy and imaging. This review focused on the use of nanotechnology for degenerative, inflammatory, and infectious diseases in the nervous system

Photoacoustic tomography and sensing in biomedicine

Photoacoustics has been broadly studied in biomedicine, for both human and small animal tissues. Photoacoustics uniquely combines the absorption contrast of light or radio frequency waves with ultrasound resolution. Moreover, it is non-ionizing and non-invasive, and is the fastest growing new biomedical method, with clinical applications on the way. This review provides a brief recap of recent developments in photoacoustics in biomedicine, from basic principles to applications. The emphasized areas include the new imaging modalities, hybrid detection methods, photoacoustic contrast agents and the photoacoustic Doppler effect, as well as translational research topics

Standardization of research methods employed in assessing the interaction metallic-based nanoparticles and the blood-brain barrier: present and future perspectives

peer-reviewedThe full text of this article will not be available until the embargo expires on the 18/01/2020.Treating diseases of the central nervous system (CNS) is complicated by the presence of the blood-brain barrier (BBB), a semipermeable boundary layer protecting the CNS from toxins and homeostatic disruptions. However, this layer also excludes almost 100% of therapeutics, impeding the treatment of CNS diseases. The advent of nanoparticles, in particular metallic-based nanoparticles, presents the potential to overcome this barrier and transport drugs into the CNS. Recent interest in metallic-based nanoparticles has generated an immense array of information pertaining to nanoparticles of different materials, sizes, morphologies, and surface properties. Nanoparticles with different physico-chemical properties lead to distinct nanoparticle-host interactions; yet, comprehensive characterization is often not completed. Similarly, in vivo testing has involved a mixed evaluation of parameters, including: BBB permeability, integrity, biodistribution, and toxicity. The methods applied to assess these parameters are inconsistent; this complicates the comparison of different nanoparticle-host system responses. A systematic review was conducted to investigate the methods by which metallic-based nanoparticles are characterized and assessed in vivo. The introduction of a standardized approach to nanoparticle characterization and in vivo testing is crucial if research is to transition to a clinical setting. The approach suggested, herein, is based on equipment and techniques that are accessible and informative to facilitate the routine incorporation of this standardized, informative approach into different research settings. Thorough characterization could lead to improved interpretation of in vivo responses, which could clarify nanoparticle properties that result in favorable in vivo outcomes whilst exposing nanoparticle-specific weaknesses. Only then will researchers successfully identify nanoparticles capable of delivering life-saving therapeutics across the blood-brain barrier

Targeted Magnetite Tissue Delivery for Antiretroviral Pharmacokinetics

Pharmacokinetics and pharmacodynamics studies are required for bench to bedside translation of any new drug, formulation or device. Multifunctional magnetite nanocarriers enable magnetic resonance imaging tracking of nanomaterial encased antiretroviral drugs serving to improve the effectiveness of formulation developments. Targeting ligands used to deliver nanoparticles to HIV harboring cells can be tested using multifunctional magnetite nanocarriers. To this end, two types of magnetite nanocarriers were developed. These included small magnetite antiretroviral therapy particles. The second were ALN-PEG coated magnetite particles for testing macrophages targeting ligands. Overall, these works should serve to speed the development of long acting nanoformulated ART to improve access and effectiveness of treatment regimens for the infected human host

Long-axial field-of-view PET/CT: perspectives and review of a revolutionary development in nuclear medicine based on clinical experience in over 7000 patients.

Recently introduced long-axial field-of-view (LAFOV) PET/CT systems represent one of the most significant advancements in nuclear medicine since the advent of multi-modality PET/CT imaging. The higher sensitivity exhibited by such systems allow for reductions in applied activity and short duration scans. However, we consider this to be just one small part of the story: Instead, the ability to image the body in its entirety in a single FOV affords insights which standard FOV systems cannot provide. For example, we now have the ability to capture a wider dynamic range of a tracer by imaging it over multiple half-lives without detrimental image noise, to leverage lower radiopharmaceutical doses by using dual-tracer techniques and with improved quantification. The potential for quantitative dynamic whole-body imaging using abbreviated protocols potentially makes these techniques viable for routine clinical use, transforming PET-reporting from a subjective analysis of semi-quantitative maps of radiopharmaceutical uptake at a single time-point to an accurate and quantitative, non-invasive tool to determine human function and physiology and to explore organ interactions and to perform whole-body systems analysis. This article will share the insights obtained from 2 years' of clinical operation of the first Biograph Vision Quadra (Siemens Healthineers) LAFOV system. It will also survey the current state-of-the-art in PET technology. Several technologies are poised to furnish systems with even greater sensitivity and resolution than current systems, potentially with orders of magnitude higher sensitivity. Current barriers which remain to be surmounted, such as data pipelines, patient throughput and the hindrances to implementing kinetic analysis for routine patient care will also be discussed

Development of High-speed Photoacoustic Imaging technology and Its Applications in Biomedical Research

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of this dissertation is to develop high-speed PA microscopy (PAM) technologies. Novel optical scanning, ultrasonic detection, and laser source techniques are introduced in this dissertation to advance the performance of PAM systems. These upgrades open up new avenues for PAM to be applicable to address important biomedical challenges and enable fundamental physiological studies.First, we investigated the feasibility of applying high-speed PAM to the detection and imaging of circulating tumor cells (CTCs) in melanoma models, which can provide valuable information about a tumor’s metastasis potentials. We probed the melanoma CTCs at the near-infrared wavelength of 1064 nm, where the melanosomes absorb more strongly than hemoglobin. Our high-speed PA flow cytography system successfully imaged melanoma CTCs in travelling trunk vessels. We also developed a concurrent laser therapy device, hardware-triggered by the CTC signal, to photothermally lyse the CTC on the spot in an effort to inhibit metastasis.Next, we addressed the detection sensitivity issue in the previous study. We employed the stimulated Raman scattering (SRS) effect to construct a high-repetition-rate Raman laser at 658 nm, where the contrast between a melanoma CTC and the blood background is near the highest. Our upgraded PA flow cytography successfully captured sequential images of CTCs in mouse melanoma xenograft model, with a significantly improved contrast-to-noise ratio compared to our previous results. This technology is readily translatable to the clinics to extract the information of a tumor’s metastasis risks.We extended the Raman laser technology to the field of brain functional studies. We developed a MEMS (micro-electromechanical systems) scanner for fast optical scanning, and incorporated it to a dual-wavelength functional PAM (fPAM) for high-speed imaging of cerebral hemodynamics in mouse. This fPAM system successfully imaged transient changes in blood oxygenation at cerebral micro-vessels in response to brief somatic stimulations. This fPAM technology is a powerful tool for neurological studies.Finally, we explored some approaches of reducing the size the PAM imaging head in an effort to translate our work to the field of wearable biometric monitors. To miniaturize the ultrasonic detection device, we fabricated a thin-film optically transparent piezoelectric detector for detecting PA waves. This technology could enable longitudinal studies on free-moving animals through a wearable version of PAM

NASA technology utilization applications

The work is reported from September 1972 through August 1973 by the Technology Applications Group of the Science Communication Division (SCD), formerly the Biological Sciences Communication Project (BSCP) in the Department of Medical and Public Affairs of the George Washington University. The work was supportive of many aspects of the NASA Technology Utilization program but in particular those dealing with Biomedical and Technology Application Teams, Applications Engineering projects, new technology reporting and documentation and transfer activities. Of particular interest are detailed reports on the progress of various hardware projects, and suggestions and criteria for the evaluation of candidate hardware projects. Finally some observations about the future expansion of the TU program are offered

Photoacoustic tomography and sensing in biomedicine

Photoacoustics has been broadly studied in biomedicine, for both human and small animal tissues. Photoacoustics uniquely combines the absorption contrast of light or radio frequency waves with ultrasound resolution. Moreover, it is non-ionizing and non-invasive, and is the fastest growing new biomedical method, with clinical applications on the way. This review provides a brief recap of recent developments in photoacoustics in biomedicine, from basic principles to applications. The emphasized areas include the new imaging modalities, hybrid detection methods, photoacoustic contrast agents and the photoacoustic Doppler effect, as well as translational research topics

Assessing pulmonary ventilation and perfusion properties with 19F-MRI

PhD ThesisPulmonary imaging with conventional MRI remains challenging, owing to the low proton density of lung tissue and magnetic susceptibility gradients that exist at ubiquitous air-tissue interfaces. The use of exogenous gas agents can overcome these challenges by direct visualisation of inhaled gases within the airways, facilitating assessment of regional ventilation properties. To date, this has largely been achieved in research settings using hyperpolarised-gas MRI, a well-established technique that is capable of providing clinically useful metrics of lung function (e.g. the percentage ventilated lung volume, %VV). However, the requirement for specialised gas polarising equipment and expertise remains a barrier to widespread clinical adoption. Recently, 19F-MRI of inhaled perfluoropropane (PFP) has emerged as a viable approach to human ventilation imaging, offering an alternative to hyperpolarisation with potential for translation to clinical practice. This thesis presents methods for performing human 19F-MR ventilation imaging, focussing on the application of novel scan procedures in healthy volunteers, patients with asthma, and patients with chronic obstructive pulmonary disease (COPD). Initial experiments were conducted within the framework of a dual-centre study (LIFT), enabling the establishment of reproducible imaging methods in healthy volunteers for the evaluation of static %VV measurements across different study sites. The utility of these methods to quantify ventilation defects in patients with asthma and COPD, including bronchodilator response, is reported and discussed. In addition, this thesis explores the feasibility of performing dynamic ventilation and perfusion imaging, employing 19F-MRI of inhaled PFP in combination with a widely used intravenous gadolinium-based contrast agent. Experiments were conducted within the framework of two small feasibility studies (VQ MRI and LungGas). Initial results of these studies are presented, alongside a discussion of the wider implications for future assessment of regional pulmonary ventilation/perfusion properties. This work supports the use of 19FMRI as a novel imaging modality for the assessment of respiratory disease

IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)

Magnetoencephalography (MEG) records weak magnetic fields outside the human head and thereby provides millisecond-accurate information about neuronal currents supporting human brain function. MEG and electroencephalography (EEG) are closely related complementary methods and should be interpreted together whenever possible. This manuscript covers the basic physical and physiological principles of MEG and discusses the main aspects of state-of-the-art MEG data analysis. We provide guidelines for best practices of patient preparation, stimulus presentation, MEG data collection and analysis, as well as for MEG interpretation in routine clinical examinations. In 2017, about 200 whole-scalp MEG devices were in operation worldwide, many of them located in clinical environments. Yet, the established clinical indications for MEG examinations remain few, mainly restricted to the diagnostics of epilepsy and to preoperative functional evaluation of neurosurgical patients. We are confident that the extensive ongoing basic MEG research indicates potential for the evaluation of neurological and psychiatric syndromes, developmental disorders, and the integrity of cortical brain networks after stroke. Basic and clinical research is, thus, paving way for new clinical applications to be identified by an increasing number of practitioners of MEG. (C) 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.Peer reviewe