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Magnetic particle imaging (MPI) is able to assess the delivery efficiency of different methods. (A) Experimental setup showing how the aerosol is delivered by controlled ventilation to the rodent. (B) MPI assessment of the delivery efficiency of three different methods. Method 1 uses a slow controlled ventilation rate. This enables the aerosol to be more evenly distributed in the lung. Method 2 uses a fast, controlled ventilation rate, resulting in more inertial impaction of the aerosol in the central conducting airways as opposed to the finer airways in the lung periphery. Method 3 increases the size of the aerosol droplets and therefore significantly increases the probability of inertial impaction in the central airways, resulting in poor delivery to lung periphery.
Source publication
Pulmonary delivery of therapeutics is attractive due to rapid absorption and non-invasiveness but it is challenging to monitor and quantify the delivered aerosol or powder. Currently, single-photon emission computed tomography (SPECT) is used but requires inhalation of radioactive labels that typically have to be synthesized and attached by hot che...
Contexts in source publication
Context 1
... of the experimental groups are shown in Figure 4 and the inhalation hardware setup was constructed as shown in Figure 5. In short, the nebulizer was connected in line between the y-junction and the output of the rodent ventilator device to inject the aerosol into the ventilation airstream to be inhaled by the rodent. ...
Context 2
... MPI was performed as described in the animal imaging section with a scan field-of-view (FOV) of 14.2 cm × 4.7 cm × 4.0 cm and scan duration of approximately 2 min. The normalized MPI signal, normalized DOX HCl fluorescence signal and aerosol mass are plotted in the correlation graphs in Figure 3 and Figure 5. Because the SPIONs concentration was dilute (0.17 mg iron / mL) with respect to DOX HCl (1 mg/mL) and low concentrations were maintained while total aerosol deposited was varied, there was no observable quenching of the DOX HCl fluorescence signal by the iron oxide in the experiment. ...
Context 3
... of the key applications of radioaerosols is the in vivo evaluation of aerosol delivery efficiency [9]. Here, we show that MPI is similarly able to visualize the efficiency of different delivery methods for Group A rats ( Figure 5). It is well known from prior literature that drug-aerosol deposition depends on many factors. ...
Context 4
... prior literature, rapid inhalation increases the chance of impaction in the oropharynx and large conducting airways, while slow, steady inhalation increases the chance of penetration to the lung periphery [58]. Figure 5B shows that MPI can visualize this effect. With fast ventilation rate as controlled by the ventilator piston stroke rate (stroke volume and rest of ventilation setup is kept the same), we observed a much larger fraction of aerosol deposited in the central, large conducting airways and lesser aerosol in the peripheral parts of the lung. ...
Similar publications
Pulmonary delivery of therapeutics is attractive due to rapid absorption and non-invasiveness but it is challenging to monitor and quantify the delivered aerosol or powder. Currently, single-photon emission computed tomography (SPECT) is used but requires inhalation of radioactive labels that typically have to be synthesized and attached by hot che...
Citations
... The crucial aspect of this methodology lies in the capacity to accurately identify and monitor aerosols in vivo (eg, assessing the efficacy and uniformity of aerosol delivery and tracking the initial nebulized treatment deposition in vivo), effectively addressing the limitations of SPIO imaging of the lungs because of the difficulty in imaging the lungs with MRI ( Figure 10B). 164 However, although there is extensive research on SPIO, the imaging technique of SPIO has been observed to result in a decrease in the resolution of soft tissues owing to artifacts produced by superparamagnetism. Moreover, the human body releases iron during apoptosis and lysis, and iron can be phagocytosed by microglia or macrophages, leading to false-positive imaging results. ...
Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.
... Magnetic particle imaging (MPI) (Gleich and Weizenecker 2005, Tobias et al 2017, Yin et al 2022 is an emerging imaging technology in medical tomography that has high sensitivity, high spatial resolution, and high temporal resolution, make it promising for clinical applications such as dynamic measurements (Gleich et al 2008, Weizenecker et al 2009, monitoring of endovascular intervention devices (Rahmer et al 2017, Ahlborg et al 2022, Tong et al 2021, angioplasty (Salamon et al 2016, Herz et al 2018, cellular tracking (Jung et al 2018, Huang et al 2023, Zhuo et al 2023, and drug delivery and monitoring (Tay et al 2018). ...
Objective:
Real-time reconstruction of magnetic particle imaging (MPI) shows promising clinical applications. However, prevalent reconstruction methods are mainly based on serial iteration, which causes large delay in real-time reconstruction. In order to achieve lower latency in real-time MPI reconstruction, we propose a parallel method for accelerating the speed of reconstruction methods.
Approach:
The proposed method, named adaptive multi-frame parallel iterative method (AMPIM), enables the processing of multi-frame signals to multi-frame MPI images in parallel. To facilitate parallel computing, we further propose an acceleration strategy for parallel computation to improve the computational efficiency of our AMPIM.
Main results:
OpenMPIData was used to evaluate our AMPIM, and the results show that our AMPIM improves the reconstruction frame rate per second of real-time MPI reconstruction by two orders of magnitude compared to prevalent iterative algorithms including the Kaczmarz algorithm, the conjugate gradient normal residual algorithm, and the alternating direction method of multipliers algorithm. The reconstructed image using AMPIM has high contrast-to-noise with reducing artifacts.
Significance:
The AMPIM can parallelly optimize least squares problems with multiple right-hand sides by exploiting the dimension of the right-hand side. AMPIM has great potential for application in real-time MPI imaging with high imaging frame rate.
... Its response time may only be suitable for low response time applications such as tumor imaging [31], monitoring cell-based treatment [32], intraoperative navigation [33]. At its current stage, this proposed system is still quite far away from real-time applications such as perfusion imaging [34], tracking targeted drug [35]. The main issue restricting the temporal resolution is due to the implemented hardware problem currently at its limit. ...
... First described in 2005 1 , magnetic particle imaging (MPI) has recently emerged as a pre-clinical small animal alternative to MRI for cell tracking [2][3][4][5] . MPI directly detects the nonlinear magnetization of superparamagnetic iron oxide (SPIO) particles as a signal hot-spot, as opposed to MRI which indirectly detects SPIO as regions of signal loss from its effect on proton relaxation. ...
Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide (SPIO) labeled cells. We have used MPI to detect SPIO-labeled dendritic cells (DC) migrated to the popliteal lymph nodes (pLN) after injection into the hind footpads. However, in some cases the low pLN signal could not be resolved from nearby higher footpad signal where window leveling to pLN signal oversaturated the footpad signal. The same limitation occurs when SPIO is injected intravenously, accumulates in the liver, and prevents isolation of regions of interest with lower signals. Previous studies have reported on the issue of resolving a wide range of differing iron concentration. A small focused field of view (FOV), to exclude high sources of nearby signal cannot be performed with the standard reconstruction algorithm equipped on the MomentumTM MPI scanner because it is assumed that there is no signal at the edge of the FOV and these values are set to zero for each line along the transmit axis. However, when there is signal at the FOV edge, an inverted negative artifact is created. The multichannel joint reconstruction method uses an iterative reconstruction technique to recover edge information using information from an orthogonal axis, preventing this artifact and allowing the user to prescribe a small FOV on the region of interest. Here we describe the implementation of this method to isolate and quantify low regions of MPI signal from higher regions.
... Magnetic Particle Imaging (MPI) is particularly useful in imaging and diagnosis of tissues such as the GI tract and lungs. (A) MPI is by far the most sensitive modality for detecting the GI bleed[4] and (B) MPI images of tracer distribution in the lung, also known as lung ventilation assessment[5]. ...
Various diseases and immune-related issues have been associated with the gastrointestinal system’s health. Gastrointestinal permeability - a measure of transport across the GI tract’s cell lining from the lumen - is a functional parameter that is affected and is a viable factor in GI health assessment. Current diagnosis of GI-related disease involves the use of invasive exploratory surgery to minimally invasive colonoscopy. Magnetic particle imaging (MPI) is a non-radioactive and highly sensitive tracer imaging modality. The nanoparticle tracers used for MPI are FDA approved and can readily be translated into the clinic. In this research, we provide the first proof-of-concept using MPI to evaluate GI permeability in an in vitro model of the epithelial barrier lining of the GI tract.
... Most of the studies proposed the use of MRI [70][71][72][73] as a monitoring technique, and some recent reports mention Magnetic Particle Imaging (MPI) as a promising alternative. As SPION tracers are exogenous, this imaging technique has nearly no background in comparison with contrast-modified MRI [74,75]. The signal arising from SPION can be processed to reflect their spatial location and concentration, opening the doors for quantitative imaging with good spatial resolution (≈1 mm) and sensitivity (≈100 µM Fe) [10,76]. ...
Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response
when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy. This review provides a comprehensive description of the fundamental aspects of SPION formulation and highlights various recent approaches regarding in vivo applications in the field of cancer therapy.
... 33 The stability of probes is crucial for in vivo diagnosis as well. Researchers developed the hybrid ICG−SPION approach through simple mixing 34,35 or non-covalent encapsulation 36,37 for multimodal imaging. However, ICG can leak out of those particles, complicating the interpretation of imaging results. ...
Breast cancer is the leading cause of cancer-associated deaths among women. Techniques for non-invasive breast cancer detection and imaging are urgently needed. Multimodality breast cancer imaging is attractive since it can integrate advantages from several modalities, enabling more accurate cancer detection. In order to accomplish this, indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoworm (NW-ICG) has been synthesized as a contrast agent. When evaluated in a spontaneous mouse breast cancer model, NW-ICG gave a large tumor to normal tissue contrasts in multiple imaging modalities including magnetic particle imaging, near-infrared fluorescence imaging, and photoacoustic imaging, providing more comprehensive detection and imaging of breast cancer. Thus, NW-ICGs are an attractive platform for non-invasive breast cancer diagnosis.
... As a tracing agent, the lung deposition of an inhaled particle can be detected due to the nature of the particle; for example, Technetium-99m ( 99m Tc) emits gamma-ray, which can be detected by SPECT, resulting in an image of the lung [13]. On the other side, the contrast agent can alter the result of existing imaging methods (CT and MRI), providing brighter or darker regions for better diagnosis or interpretation [16][17][18]. ...
... To date, 38 tracing and contrast agents have been approved for commercial use [30][31][32], and the development of new agents is underway to improve the safety aspect and image quality [17,18,23,33,34]. This review aimed to Table 1 Detection mechanism in lung imaging AgNP, silver-based nanoparticle; AuNP, gold-based nanoparticle; CA, contrast agent; CT, computed Tomography; FeNP, iron-based nanoparticle; 68 Ga, Gallium-68; I-CA, iodonated-based contrast agent; MnNP, manganese nanoparticle; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, Single photon emission computed tomography; SPIONs, super paramagnetic iron oxide nanoparticles; T1, longitudinal; T2, transverse; 99m Tc, Technetium-99m Detection source Imaging method Advantages Disadvantages ...
... Pulmonary delivery for contrast or tracing agent administration route has provided an image for lung disease diagnosis for decades [13]. Furthermore, an attempt to discover new inhalable particles with increased image quality and safety profile has also been reported in recent years [17,18,23,33,34]. For instance, Silva et al. reported the development of a dual-modality contrast agent consisting of Fe and gold (Au) for detection using MRI and CT, respectively [20]. ...
Purpose:
The application of contrast and tracing agents is essential for lung imaging, as indicated by the wide use in recent decades and the discovery of various new contrast and tracing agents. Different aerosol production and pulmonary administration methods have been developed to improve lung imaging quality. This review details and discusses the ideal characteristics of aerosol administered via pulmonary delivery for lung imaging and the methods for the production and pulmonary administration of dry or liquid aerosol.
Methods:
We explored several databases, including PubMed, Scopus, and Google Scholar, while preparing this review to discover and obtain the abstracts, reports, review articles, and research papers related to aerosol delivery for lung imaging and the formulation and pulmonary delivery method of dry and liquid aerosol. The search terms used were "dry aerosol delivery", "liquid aerosol delivery", "MRI for lung imaging", "CT scan for lung imaging", "SPECT for lung imaging", "PET for lung imaging", "magnetic particle imaging", "dry powder inhalation", "nebuliser", and "pressurised metered-dose inhaler".
Results:
Through the literature review, we found that the critical considerations in aerosol delivery for lung imaging are appropriate lung deposition of inhaled aerosol and avoiding toxicity. The important tracing agent was also found to be Technetium-99m (99mTc), Gallium-68 (68Ga) and superparamagnetic iron oxide nanoparticle (SPION), while the essential contrast agents are gold, iodine, silver gadolinium, iron and manganese-based particles. The pulmonary delivery of such tracing and contrast agents can be performed using dry formulation (graphite ablation, spark ignition and spray dried powder) and liquid aerosol (nebulisation, pressurised metered-dose inhalation and air spray).
Conclusion:
A dual-imaging modality with the combination of different tracing or contrast agents is a future development of aerosolised micro and nanoparticles for lung imaging to improve diagnosis success.
Graphical abstract:
... Overall, the research in MNPs will not provide further development of the medical field but exciting applications of MNPs in related areas. This review gives an overview of various applications of MNPs in medicine including drug delivery, magnetic resonance and magnetic particle imaging, sensing, biomarker detection, antimicrobial agents, and regenerative medicine (Moradiya et al. 2019;Tay et al. 2018;Richard et al. 2017;. The overall applications of MNPs are given in Fig. 24.1. ...
The geriatric population is escalating globally, and the need for treating infectious and non-infectious diseases in elderly patients is also correspondingly increasing worldwide. In clinical trials and under doctor’s office settings, the drug dosages are generally computed on mg/kg body wt. basis in young adults and middle-aged men and women (<40 years). It is well recognized that in comparison with the younger age counterparts, the geriatric subjects are more susceptible to drug-mediated adverse reactions due to the reduced activity in cytochrome P450 coenzymes and glucuronidation/sulfation mechanisms. Since the body mass in elderly patients, especially frail elders, is markedly reduced due to sarcopenia, progressive loss in body fat, and osteoporosis, hence, drug doses based on mg/kg body wt. usually cannot be applied in this group of patients as is done in relatively young adults. Most of the physiological functions, including drug metabolizing and excretory capacity declines in the elderly, consequently cause significant alterations in the metabolic disposition as well as changes in the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of administered drugs in elderly subjects as opposed to the younger individuals. Innumerable studies have shown wide differences in xenobiotic responses due to inter-individual variation, demographics, age, gender, ethnicity, and race. These differences are attributed to a wide array of factors such as pharmacogenetics variations, gastrointestinal and microbial metabolism of drugs, bioavailability, and first-step metabolism in the liver and renal excretion. Elderly individuals are one of the most vulnerable age groups to adverse drug reactions (ADRs) due to multiple comorbidities, co-medications, and declining functions of the gastrointestinal-hepatic-renal systems. Age-related debilitating conditions tend to enhance the incidence to ADRs and hospital readmissions due to cognitive impairment, inappropriate drug use, and drug-drug, drug-diet, and drug-herbal interactions. Collectively, all these situations make it highly challenging for the physicians, nurses, pharmacists, and surgeons to make drug dose adjustment decisions for the geriatric patients. Healthcare providers should always ask their patients about herbal and dietary supplements’ use and discourage concomitant ingestion of botanical products and fruit juices, especially grape fruit juice, with prescription drugs. Systematic research by various scientific groups and pharmaceutical companies has helped in the computation of drug dose adjustments and decision-making easier for drug administration in elderly and frail patients. Appropriate guidelines, equations, and formulas are available for calculating drug dosages for frail elderly patients based on serum creatinine or cystatin-C clearance or some other biomarkers. It is important that elderly patients should be enrolled in clinical trials for understanding the pharmacometabolomics and assessment of safety, efficacy, and optimal dose schedules of new drugs. The focus of this review is to address the age-related physiological, pharmacological, and toxicological changes in elderly humans as well as age-related alterations in the absorption, distribution, metabolism, and excretion (ADME) of drugs administered orally or by other routes. We will also describe the characteristics of drug molecules that influence the bioavailability, PK, PD, and potential interactions of prescription drugs or over-the-counter medications taken simultaneously with fruit juices and herbal remedies. In this review, we have selected examples of potential risks associated with the psychotherapeutic class of drugs because the antidepressant, antianxiety, and insomnia-treating medications are some of the most frequently used categories of drugs by elderly men and women.
... Overall, the research in MNPs will not provide further development of the medical field but exciting applications of MNPs in related areas. This review gives an overview of various applications of MNPs in medicine including drug delivery, magnetic resonance and magnetic particle imaging, sensing, biomarker detection, antimicrobial agents, and regenerative medicine (Moradiya et al. 2019;Tay et al. 2018;Richard et al. 2017;. The overall applications of MNPs are given in Fig. 24.1. ...
Besides synthetic drugs, a wide variety of medicinal plants have been used for the prevention and management of various liver disorders. Generally, plant therapies are well tolerated due to their lesser side effects. The aims and objectives of this review are to describe the drug therapies used for treating liver disorders as well as the most commonly used hepatoprotective plant-derived bioactive ingredients and their formulations employed for treating various liver pathologies. The extensive literature review was conducted using different databases such as ScienceDirect, SciFinder Scholar, Wiley Online Library, PubMed, ResearchGate, Google Scholar and Chemical Abstracts (until March 2021). Our literature searches showed that a wide array of plant products or plant extracts have been used in the folklore and traditional remedies for the prevention and management of liver disorders. The complex chemical structures of many isolated plant ingredients such as flavonoids, polyphenols, and steroid-type compounds have been determined using sophisticated analytical techniques. While the pharmacological and toxicological activities of many plant products have been tested in animal models, their underlying mechanism of action remains unknown. In this review, we will describe the hepatoprotective actions of the following plants and their bioactive components: Allium sativum, Allium hirtifolium, Andrographis paniculata, Apium graveolens, Asparagus racemosus, Berberis vulgaris, Curcuma longa, Emblica officinalis, Glycyrrhiza glabra, Marrubium vulgare, Nigella sativa, Phyllanthus niruri, Picrorhiza kurroa, Solanum nigrum, Swertia chirayita, Taraxacum officinale, oleanolic acid, Cliv-92, ursolic acid, berberine, proanthocyanidins, naringenin, silymarin, andrographolide, glycyrrhizin, curcumin, rhein, geniposide and resveratrol. There are challenges and opportunities for understanding the mechanism of action of the phytotherapies used for curing liver diseases as well as discovering new drug molecules useful for targeting different liver ailments. Combinations of traditional herbal remedies found to be safe and effective are also suggested as a possible cost-effective therapeutic tool to be tested in future researches aiming to unveil novel options to treat liver disorders in humans. However, well-designed, randomized, placebo-controlled, multicentre trials are needed to establish the long-term safety and efficacy as well the optimal dose schedules required for treating different liver disorders in humans.
