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Greenhouse propagation of unrooted plant cuttings is characterized by short container cell height and high irrigation frequency. These conditions can result in high moisture level and low air content in soilless container substrates (“substrates”), causing delayed growth of adventitious roots and favoring root disease. The objective of this study was to quantify and compare substrate water and air relations for three propagation substrates (peat, rockwool, and phenolic foam) that varied widely in physical characteristics using four methods: 1) evaporation method with a tensiometer, 2) frozen column method, 3) gravimetric analysis, and 4) X-ray computed tomography (CT) analysis. Moisture retention curves based on evaporation (1) and the frozen column (2) resulted in differences for peat, but similar curves for rockwool and foam. The frozen column method was simple and low cost, but was constrained by column height for peat, which had a higher water potential compared with the other two substrates. Substrate porosity analysis at container capacity by gravimetric or CT methods were similar for volumetric water and air content (VWC and VAC) in rockwool and foam, but differed for peat for VWC and VAC. Gravimetric analysis was simple, rapid, and low cost for whole-cell analysis, but CT further quantified spatial water and air relations within the cell and allowed visualization of complex water and air relations in an image. All substrates had high water content at container capacity ranging from 67% to 91% VWC with 5% to 11% VAC in the short propagation cells, emphasizing the need for careful irrigation management.

The objective was to refine protocols to quantify rooting of plant cuttings and the water/air microenvironment of substrates using x-ray computed tomography (CT). Poinsettia (Euphorbia pulcherrima) cuttings were propagated in three substrates (peat, rockwool, and phenolic foam) at varied moisture levels. In Experiment 1, adventitious rooting occurred in cuttings grown in rockwool or foam from 12% to 86% volumetric water content (VWC) and 12% to 80% volumetric air content (VAC). The highest root growth occurred in rockwool at 59% VWC and 33% VAC. There was an advantage to quantifying root growth by CT in rockwool and foam, in contrast to peat, because of clear differences in material density between root and substrate during image processing. In Experiment 2, root growth was quantified in peat by two-dimensional image scans under similar growth chamber environments, with rapid root growth from 52% to 63% VWC and 16% to 26% VAC. In Experiment 3, CT was used to quantify the substrate microenvironment at 0.5 cm slices to further describe the environment at the base of the plant cutting. Rapid rooting occurred in microenvironments above 56% VWC and 14% VAC, whereas the low 3% VAC in foam at high moisture may limit root growth. Abbreviations: volumetric water content (VWC), volumetric air content (VAC), volumetric solid content (VSC)

Objectives To test the hypotheses that (a) the chairside/handheld dental scanner combined with a metrology software will measure clinical wear in vivo in agreement with measurements from X‐ray computed microtomography and; (b) polished monolithic zirconia does not cause accelerated wear of opposing enamel. Materials and methods Thirty single crowns were randomized to receive a monolithic zirconia or metal‐ceramic crown. Two non‐restored opposing teeth in the same quadrants were identified to serve as enamel controls. After cementation, quadrants were scanned using an intraoral dental scanner. Patients were recalled at 6‐months and 1‐year for re‐scanning. Scanned images were compared using a metrology software to determine maximum vertical wear of teeth. The accuracy of the scanning measurements from this new method was compared with X‐ray computed microtomography (micro‐CT) measurements. Statistical analysis was performed using Mann–Whitney U test to determine significant differences between wear of enamel against zirconia, metal‐ceramic or enamel. Linear regression analysis determined agreement between measurements obtained using intraoral scanning and micro‐CT. Results Regression analysis demonstrated that there is a quantitative agreement between depth and volume measurements produced using intraoral scanning and the micro‐CT methodologies. There was no significant difference between the wear of enamel against polished monolithic zirconia crowns and enamel against enamel. Conclusions Intraoral scanning combined with a matching software can accurately quantify clinical wear to verify that monolithic zirconia exhibited comparable wear of enamel compared with metal‐ceramic crowns and control enamel. Agreement between the intraoral scanner and the micro‐CT was 99.8%. Clinical Trials.gov NCT02289781.

Background Brainstem gliomas are aggressive and difficult to treat. Growth of these tumors may be characterized with MRI methods. Purpose To visualize longitudinal changes in tumor volume, vascular leakiness, and tissue microstructure in an animal model of brainstem glioma. Study type Prospective animal model. Animal model Male Sprague-Dawley rats (n = 9) were imaged with 9L gliosarcoma cells infused into the pontine reticular formation of the brainstem. The MRI tumor microenvironment was studied at 3 and 10 days postimplantation of tumor cells. Field strength/sequence Diffusion tensor imaging (DTI) and dynamic contrast-enhanced (DCE)-MRI were performed at 4.7T using spin-echo multislice echo planar imaging and gradient echo multislice imaging, respectively. Assessment Tumor leakiness was assessed by the forward volumetric transfer constant, Ktrans , estimated from DCE-MRI data. Tumor structure was evaluated with fractional anisotropy (FA) obtained from DTI. Tumor volumes, delineated by a T1 map, T2 -weighted image, FA, and DCE signal enhancement were compared. Statistical tests Changes in the assessed parameters within and across the groups (ie, rats 3 and 10 days post tumor cell implantation) were evaluated with Wilcoxon rank-sum tests. Results Day 3 tumors were visible mainly on contrast-enhanced images, while day 10 tumors were visible in both contrast-enhanced and diffusion-weighted images. Mean Ktrans at day 10 was 41% lower than at day 3 (P = 0.23). In day 10 tumors, FA was regionally lower in the tumor compared to normal tissue (P = 0.0004), and tumor volume, segmented based on FA map, was significantly smaller (P ≤ 0.05) than that obtained from other contrasts. Data conclusion Contrast-enhanced MRI was found to be more sensitive in detecting early-stage tumor boundaries than other contrasts. Areas of the tumor outlined by DCE-MRI and DTI were significantly different. Over the observed period of tumor growth, average vessel leakiness decreased with tumor progression. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:1322-1332.

Magnetic alginate microspheres are biocompatible due to their alginate matrix, and motion-controllable by applied magnetic fields due to their magnetic character. Therefore, they have the potential of being used as vessels to a broad variety of materials, including drugs and therapeutic agents, facilitating entry to biological systems in a relatively non-invasive manner. Here, magnetic alginate microspheres were prepared through an emulsification and ionic cross-linking process, where a mixture of alginate and iron oxide magnetic nanoparticles was initially dispersed in a continuous phase, followed by gelation of this dispersed phase into microspheres by cross-linking the dispersion with calcium ions. The resulting magnetic alginate microspheres were found to be superparamagnetic and to respond to applied magnetic fields by chain formation. The effect of shear rate, alginate concentration, and magnetic nanoparticle concentration on microsphere size was investigated with the aim to control the size of microspheres with respect to process and formulation parameters. Two of these parameters, shear rate and alginate concentration, were used to correlate experimental results with a theoretical model for the case where the dispersed phase is more viscous than the continuous phase.

Magnetic nanoparticles (MNPs) find applications in magnetic fluid hyperthermia (MFH), where the heat dissipated from the MNPs in the presence of an alternating magnetic field is used to treat cancer. However, upon systemic delivery MNPs are also readily phagocytosed by liver and spleen macrophages, leading to accumulation in these organs and thus resulting in nonspecific heating and damage to these healthy organs during MFH. A potential solution to this problem is using magnetic field gradients such as those used in magnetic particle imaging (MPI), a tracer imaging technology which makes the use of MNP's nonlinear magnetization response to a scanned field gradient to obtain the MNP distribution. The field gradient of MPI can be used to localize the region where MNPs dissipate heat, whereas its imaging capability can be utilized for real-time thermal therapy. In this chapter, we introduce and discuss this emerging field of image-guided thermal therapy using MPI and MFH.

Low tumor accumulation following systemic delivery remains a key challenge for advancing many cancer nanomedicines. One obstacle in engineering nanoparticles for high tumor accumulation is a lack of techniques to monitor their stability and mobility in situ. One way to monitor the stability and mobility of magnetic nanoparticles biological fluids in situ is through dynamic magnetic susceptibility measurements (DMS), which under certain conditions provide a measure of the particle's rotational diffusivity. For magnetic nanoparticles modified to have commonly used biomedical surface coatings, we describe a systematic comparison of DMS measurements in whole blood and tumor tissue explants. DMS measurements clearly demonstrated that stability and mobility changed over time and from one medium to another for each different coating. It was found that nanoparticles coated with covalently grafted, dense layers of PEG were the only ones to show good stability and mobility in all settings tested. These studies illustrate the utility of DMS measurements to estimate the stability and mobility of nanoparticles in situ, and which can provide insights that lead to engineering better nanoparticles for in vivo use.

The synthesis of well-defined nanoparticle materials has been an area of intense investigation, but size control in nanoparticle syntheses is largely empirical. Here, we introduce a general method for fine size control in the synthesis of nanoparticles by establishing steady state growth conditions through the continuous, controlled addition of precursor, leading to a uniform rate of particle growth. This approach, which we term the “extended LaMer mechanism” allows for reproducibility in particle size from batch to batch as well as the ability to predict nanoparticle size by monitoring the early stages of growth. We have demonstrated this method by applying it to a challenging synthetic system: magnetite nanoparticles. To facilitate this reaction, we have developed a reproducible method for synthesizing an iron oleate precursor that can be used without purification. We then show how such fine size control affects the performance of magnetite nanoparticles in magnetic hyperthermia.

BACKGROUND: Brainstem gliomas are aggressive and difficult to treat. Growth of these tumors may be characterized with MRI methods. PURPOSE: To visualize longitudinal changes in tumor volume, vascular leakiness and tissue microstructure in an animal model of brainstem glioma. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Male Sprague-Dawley rats (n = 9) were imaged with 9L gliosarcoma cells infused into the pontine reticular formation of the brainstem. The MRI tumor microenvironment was studied at 3- and 10-days post-implantation of tumor cells. FIELD STRENGTH/SEQUENCE: Diffusion tensor imaging (DTI) and dynamic contrast enhanced (DCE)-MRI were performed at 4.7T using spin-echo multi-slice echo planar imaging and gradient echo multi-slice imaging, respectively. ASSESSMENT: Tumor leakiness was assessed by the forward volumetric transfer constant, [Formula: see text] , estimated from DCE-MRI data. Tumor structure was evaluated with fractional anisotropy (FA) obtained from DTI. Tumor volumes, delineated by T(1) map, T(2)-weighted image, FA and DCE signal enhancement, were compared. STATISTICAL TESTS: Changes in the assessed parameters within and across the groups (i.e. rats 3- and 10-days post tumor cell implantation) were evaluated with Wilcoxon rank-sum tests. RESULTS: Day 3 tumors were visible mainly on contrast enhanced images, while day 10 tumors were visible in both contrast enhanced and diffusion weighted images. Mean [Formula: see text] at day 10 was 41% lower than at day 3 (p = 0.23). In day 10 tumors, FA was regionally lower in the tumor compared to normal tissue (p = 0.0004), and tumor volume, segmented based on FA map, was significantly smaller ([Formula: see text]) than that obtained from other contrasts. DATA CONCLUSION: Contrast enhanced MRI was found to be more sensitive in detecting early-stage tumor boundaries than other contrasts. Areas of the tumor outlined by DCE-MRI and DTI were significantly different. Over the observed period of tumor growth, average vessel leakiness decreased with tumor progression.

Novel magnetite-ammonium bisphosphonate graft ionic copolymer nanocomplexes (MGICs) have been developed for potential drug delivery, magnetic resonance imaging, and hyperthermia applications. The complexes displayed relatively uniform sizes with narrow size distributions upon self-assembly in aqueous media, and their sizes were stable under simulated physiological conditions for at least 7 days. The anticancer drugs, cisplatin and carboplatin, were loaded into the complexes, and sustained release of both drugs was observed. The transverse NMR relaxivities (r2s) of the complexes were 244 s−1 (mM Fe)−1 which is fast compared to either the commercial T2-weighted MRI agent Feridex IV® or our previously reported magnetite-block ionomer complexes. Phantom MRI images of the complexes demonstrated excellent negative contrast effects of such complexes. Thus, the bisphosphonate-bearing MGICs could be promising candidates for dual drug delivery and magnetic resonance imaging. Moreover, the bisphosphonate MGICs generate heat under an alternating magnetic field of 30 kA·m−1 at 206 kHz. The temperature of the MGIC dispersion in deionized water increased from 37 to 41°C after exposure to the magnetic field for 10 minutes, corresponding to a specific absorption rate of 77.0 W·g−1. This suggests their potential as hyperthermia treatment agents as well as the possibility of temperature-dependent drug release, making MGICs more versatile in potential drug delivery applications.

Growth factors or cytokines have demonstrated the potential to alter and manipulate the biological activity of cells via binding and activation of cell surface receptors. Changes induced by cytokines can range from simple changes in the cellular motility and proliferation to more complex biological actions, such as stem-cell differentiation. Transforming growth factor beta (TGF-β) exhibits the typical functionality of a growth factor, as it is pleiotropic and causes myriad responses in a number of cell types. This multifunctional nature gives the TGF-β a great potential for therapeutic applicationsparticularly in regenerative medicine. However, this multifunctionality till now has limited its usage in vivo, since upon injection, the cytokine may activate nefarious signaling pathways, such as those associated with tumor formation. In addition to this problem, the short half-lives of cytokines also places constraints on their delivery, as the majority of the injected biomolecule will not have a sufficient biological lifetime to reach the desired target location. Therefore, the methods of targeting the growth factors to specific sites in the body will prove crucial to their successful clinical implementation. Here, we describe a novel growth-factor targeting and activation strategy based on the delivery of energy from external alternating magnetic fields to magnetic nanoparticles to which a latent TGF-β has been conjugated. We demonstrate the successful conjugation of a latent TGF-β to the surface of poly(ethylene glycol)-coated iron oxide nanoparticles, and subsequent triggered release of an active TGF-β from its latent complex on the application of an external radio frequency magnetic field. This preliminary study highlights the potential of magnetic activation to remotely control the TGF-β activity in vivo, reducing the dangerous off-target side effects and offering a path to clinical implementation of this growth factor for regenerative medicine applications.

The rotational diffusion of polyethylene glycol coated magnetic nanoparticles in serum albumin solutions was investigated in a range spanning 0 mg mL−1 to 200 mg mL−1. Rotational diffusivities were determined from dynamic magnetic susceptibility measurements, which provide a non-optical means to probe rotation of nanoparticles in small volume samples. Experimental rotational diffusivities were compared to those estimated using the Stokes-Einstein relation and macroscopic measurements of the viscosity of the protein solutions. Excellent agreement was found between experimental measurements and theoretical predictions for serum albumin solutions buffered at physiological pH and for serum albumin solutions at acidic pH prepared using simple acids at physiological ionic strengths. For serum albumin solutions prepared using citrate buffer at acidic pH, we observed a discrepancy between the experimental rotational diffusivity and that predicted from the Stokes-Einstein relation. In contrast, when the pH was adjusted with a simple acid and salt at physiological ionic strength we observed agreement between the experimental rotational diffusivity and that predicted from the Stokes-Einstein relation. Because of the role of citrate ions in causing protein aggregation, we believe these observations suggest that dynamic magnetic susceptibility measurement of the rotational diffusivity of the nanoparticles is sensitive to gelation/crosslinking of proteins.

The use of dynamic magnetic susceptibility measurements is reported to study nanoparticle–protein interactions in situ. The technique consists of measuring the rotational diffusivity of thermally blocked magnetic nanoparticles (MNPs) in protein solutions. To illustrate the technique, the effect of nanoparticle zeta potential in carboxymethyl-dextran-coated MNPs and their interaction with model anionic and cationic proteins, such as bovine serum albumin (BSA), immunoglobulin G (IgG), fi brinogen (FIBR), apo-transferrin (TRANS), lysozyme (LYZ), and histone (HIS), in a range of protein concentrations is studied. Experiments indicate that interactions between the negatively charged particles and the negatively charged proteins BSA, IgG, FIBR, and TRANS are negligible. However, positively charged proteins LYZ and HIS readily absorb onto the nanoparticles, as evidenced by an increase in size and eventual aggregation of the particles. Onset of this effect seems to happen at a lower concentration of HIS compared with LYZ. The technique could be applied to other particle surface coatings and to particles in complex protein mixtures, such as whole blood and serum, allowing systematic in situ studies of nanoparticle–protein interactions.

Though the concepts of magnetic fluid hyperthermia (MFH) were originally proposed over 50 years ago, the technique has yet to be successfully translated into routine clinical application. Significant challenges must be addressed if the field is to progress and realise its potential as an option for treatment of diseases such as cancer. These challenges include determining the optimum fields and frequencies that maximise the effectiveness of MFH without significant detrimental off-target effects on healthy tissue, achieving sufficient concentrations of magnetic nanoparticles (MNPs) within the target tumour, and developing a better mechanistic understanding of MNP-mediated energy deposition and its effects on cells and tissue. On the other hand, emerging experimental evidence indicates that local thermal effects indeed occur in the vicinity of energy-dissipating MNPs. These findings point to the opportunity of engineering MNPs for the selective destruction of cells and/or intracellular structures without the need for a macroscopic tissue temperature rise, in what we here call magnetically mediated energy delivery (MagMED).

It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.

Magnetic Fluid Hyperthermia (MFH) uses heat generated by magnetic nanoparticles exposed to alternating magnetic fields to cause a temperature increase in tumors to the hyperthermia range (43-47 °C), inducing apoptotic cancer cell death. As with all cancer nanomedicines, one of the most significant challenges with MFH is achieving high nanoparticle accumulation at the tumor site. This motivates development of synthesis strategies that maximize the rate of energy dissipation of iron oxide magnetic nanoparticles, preferable due to their intrinsic biocompatibility. This has led to development of synthesis strategies that, although attractive from the point of view of chemical elegance, may not be suitable for scale-up to quantities necessary for clinical use. On the other hand, to date the aqueous co-precipitation synthesis, which readily yields gram quantities of nanoparticles, has only been reported to yield sufficiently high specific absorption rates after laborious size selective fractionation. This work focuses on improvements to the aqueous co-precipitation of iron oxide nanoparticles to increase the specific absorption rate (SAR), by optimizing synthesis conditions and the subsequent peptization step. Heating efficiencies up to 1,048 W/gFe (36.5 kA/m, 341 kHz; ILP = 2.3 nH·m2·kg-1) were obtained, which represent one of the highest values reported for iron oxide particles synthesized by co-precipitation without size-selective fractionation. Furthermore, particles reached SAR values of up to 719 W/gFe (36.5 kA/m, 341 kHz; ILP = 1.6 nH·m2·kg-1) when in a solid matrix, demonstrating they were capable of significant rates of energy dissipation even when restricted from physical rotation. Reduction in energy dissipation rate due to immobilization has been identified as an obstacle to clinical translation of MFH. Hence, particles obtained with the conditions reported here have great potential for application in nanoscale thermal cancer therapy.