Hard X-ray imaging and tomography at the Biomedical Imaging and Therapy beamlines of Canadian Light Source.

The Biomedical Imaging and Therapy facility of the Canadian Light Source comprises two beamlines, which together cover a wide X-ray energy range from 13 keV up to 140 keV. The beamlines were designed with a focus on synchrotron applications in preclinical imaging and veterinary science as well as microbeam radiation therapy. While these remain a major part of the activities of both beamlines, a number of recent upgrades have enhanced the versatility and performance of the beamlines, particularly for high-resolution microtomography experiments.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia.

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model.

Pelvic Pseudotumor Associated With a Ceramic Bearing Total Hip.

Pseudotumors have been well documented to occur most frequently in metal-metal bearing total hip arthroplasties and less frequently in metal-polyethylene bearings. There are few cases in the literature of pseudotumors occurring in ceramic-ceramic articulations. We report a case of a large pelvic pseudotumor in a patient with a ceramic-ceramic bearing articulation in a 67-year-old man.

Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia.

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1-34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER).

Direct Assessment of Rabbit Cortical Bone Basic Multicellular Unit Longitudinal Erosion Rate: A 4D Synchrotron-Based Approach.

Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER.

Fragmentation of hunting bullets observed with synchrotron radiation: Lighting up the source of a lesser-known lead exposure pathway.

Bullet fragments have been previously observed in the remains and edible portions of big game animals that were harvested using rifles. The fragmentation issue has attracted attention because traditional hunting bullets are more than 70% lead, which is toxic to humans and scavengers in the ecosystem. We prepared gunshot wounds in ballistic gelatin blocks, and then applied synchrotron X-ray imaging technology to the bullet fragmentation process for the first time.

Developing a Microbubble-Based Contrast Agent for Synchrotron Multiple-Image Radiography.

Purpose: Multiple-image radiography (MIR) is an analyzer-based synchrotron X-ray imaging approach capable of dissociating absorption, refraction, and scattering components of X-ray interaction with the material. It generates additional image contrast mechanisms (besides absorption), especially in the case of soft tissues, while minimizing absorbed radiation dose. Our goal is to develop a contrast agent for MIR using ultrasound microbubbles by carrying out a systematic assessment of size, shell material, and concentration.

Developing a Microbubble-Based Contrast Agent for Synchrotron In-Line Phase Contrast Imaging.

Objective: X-ray phase contrast imaging generates contrast from refraction of X-rays, enhancing soft tissue contrast compared to conventional absorption-based imaging. Our goal is to develop a contrast agent for X-ray in-line phase contrast imaging (PCI) based on ultrasound microbubbles (MBs), by assessing size, shell material, and concentration.

Methods: Polydisperse perfluorobutane-core lipid-shelled MBs were synthesized and size separated into five groups between 1 and 10 μm.

Cortical Bone Porosity in Rabbit Models of Osteoporosis.

Cortical bone porosity is intimately linked with remodeling, is of growing clinical interest, and is increasingly accessible by imaging. Thus, the potential of animal models of osteoporosis (OP) to provide a platform for studying how porosity develops and responds to interventions is tremendous. To date, rabbit models of OP have largely focused on trabecular microarchitecture or bone density; some such as ovariectomy (OVX) have uncertain efficacy and cortical porosity has not been extensively reported.

Biodistribution of strontium and barium in the developing and mature skeleton of rats.

Bone acts as a reservoir for many trace elements. Understanding the extent and pattern of elemental accumulation in the skeleton is important from diagnostic, therapeutic, and toxicological perspectives. Some elements are simply adsorbed to bone surfaces by electric force and are buried under bone mineral, while others can replace calcium atoms in the hydroxyapatite structure.

Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats.

Synthetic parathyroid hormone (PTH) is clinically indicated for the treatment of osteoporosis, through its anabolic effects on parathyroid hormone receptors (PTHRs), located on osteoblast cells. However, the bioavailability of PTH for bone cells is restricted by the short half-life of PTH and the widespread distribution of PTHRs in non-skeletal tissues. To impart affinity for mineralized bone surfaces, bisphosphonate (BP)-mediated PTH analogues were synthesized, characterized, and evaluated in vitro and in vivo.

La(iii) biodistribution profiles from intravenous and oral dosing of two lanthanum complexes, La(dpp) and La(XT), and evaluation as treatments for bone resorption disorders.

Trivalent lanthanum (La) has the potential to treat bone resorption disorders (such as osteoporosis) by eliciting a bone-building response in the cells which control skeletal remodelling. Because La suffers from extremely poor intestinal absorption, specifically designed chelators are required in order that a biologically active form of lanthanum can be administered orally. Two such chelators, 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdpp) and bis-{[bis(carboxymethyl)amino]methy}phosphinic acid (HXT), have previously been the subjects of extensive physical, in vitro, and in vivo testing as the tris- and mono-lanthanum(iii) complexes La(dpp) and La(XT), respectively.

Spectral K-edge subtraction imaging of experimental non-radioactive barium uptake in bone.

Purpose: To evaluate the feasibility of using non-radioactive barium as a bone tracer for detection with synchrotron spectral K-edge subtraction (SKES) technique.

Methods: Male rats of 1-month old (i.e.

On-chip synthesis of fine-tuned bone-seeking hybrid nanoparticles.

Aims: Here we report a one-step approach for reproducible synthesis of finely tuned targeting multifunctional hybrid nanoparticles (HNPs).

Materials & Methods: A microfluidic-assisted method was employed for controlled nanoprecipitation of bisphosphonate-conjugated poly(D,L-lactide-co-glycolide) chains, while coencapsulating superparamagnetic iron oxide nanoparticles and the anticancer drug Paclitaxel.

Results: Smaller and more compact HNPs with narrower size distribution and higher drug loading were obtained at microfluidic rapid mixing regimen compared with the conventional bulk method.

3-D localization of non-radioactive strontium in osteoarthritic bone: Role in the dynamic labeling of bone pathological changes.

The study objective was to visualize regions of bone that undergo pathological mineralization and/or remodeling during pathogenesis of osteoarthritis, by employing non-radioactive strontium as a dynamic tracer of bone turnover. Post traumatic osteoarthritis was surgically induced in skeletally mature rats, followed by in vivo micro-CT imaging for 12 weeks to assess bone micro-structural changes. Rats either received strontium ranelate daily for the entire course of study or only last 10 days before euthanization.

Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties.

Objective: We sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA.

Methods: Post-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment.

Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges.

Introduction: Bearing in mind that many promising drug candidates have the problem of reaching their target site, the concept of advanced drug delivery can play a significant complementary role in shaping modern medicine. Among other nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential in nanomedicine. The intrinsic properties of SPIONs, such as inherent magnetism, broad safety margin and the availability of methods for fabrication and surface engineering, pave the way for diverse biomedical applications.

Synthesis, characterization and biodistribution studies of (125)I-radioiodinated di-PEGylated bone targeting salmon calcitonin analogue in healthy rats.

Purpose: The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical.

Methods: HPLC was used for isolation of sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible PEGylation sites by trypsin digestion. Stability of the compound over time, bone mineral affinity using hydroxyapatite, and biodistribution in normal rats after radiolabeling of sCT-2(PEG-BP) or control sCT with (125)I was evaluated.

Synthesis and in vitro evaluation of bone-seeking superparamagnetic iron oxide nanoparticles as contrast agents for imaging bone metabolic activity.

In this article, we report the synthesis and in vitro evaluation of a new class of nonionizing bone-targeting contrast agents based on bisphosphonate-conjugated superparamagnetic iron oxide nanoparticles (SPIONs), for use in imaging of bone turnover with magnetic resonance imaging (MRI). Similar to bone-targeting (99m)Technetium medronate, our novel contrast agent uses bisphosphonates to impart bone-seeking properties, but replaces the former radioisotope with nonionizing SPIONs which enables their subsequent detection using MRI. Our reported method is relatively simple, quick and cost-effective and results in BP-SPIONs with a final nanoparticle size of 17 nm under electron microscopy technique (i.

Synthesis of pseudopolyrotaxanes-coated Superparamagnetic Iron Oxide Nanoparticles as new MRI contrast agent.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized and coated with pseudopolyrotaxanes (PPRs) and proposed as a novel hybrid nanostructure for medical imaging and drug delivery. PPRs were prepared by addition of α-cyclodextrin rings to functionalized polyethylene glycol (PEG) chain with hydrophobic triazine end-groups. Non-covalent interactions between SPIONs and PPRs led to the assembly of SPIONs@PRs hybrid nanomaterials.

Three dimensional mapping of strontium in bone by dual energy K-edge subtraction imaging.

The bones of many terrestrial vertebrates, including humans, are continually altered through an internal process of turnover known as remodeling. This process plays a central role in bone adaptation and disease. The uptake of fluorescent tetracyclines within bone mineral is widely exploited as a means of tracking new tissue formation.

Potential mechanism of alendronate inhibition of osteophyte formation in the rat model of post-traumatic osteoarthritis: evaluation of elemental strontium as a molecular tracer of bone formation.

Objective: To employ elemental Strontium as a tracer of bone turnover, in the presence (or absence) of the bisphosphonate drug Alendronate, in order to spatially map osteophytogenesis and other bone turnover in rats developing post-traumatic secondary osteoarthritis (PTOA).

Methods: PTOA was induced in rats by medial meniscectomy surgery. We utilized in-vivo microfocal computed tomography (CT) to follow bony adaptations in groups for 8 weeks after surgery, either with or without alendronate treatment.