While the enhanced permeability and retention effect may promote the preferential accumulation of nanoparticles into well-vascularized primary tumors, it is ineffective in the case of metastases hidden within a large population of normal cells. Due to their small size, high dispersion to organs, and low vascularization, metastatic tumors are less accessible to targeted nanoparticles. To tackle these challenges, we designed a nanoparticle for vascular targeting based on an αvβ3 integrin-targeted nanochain particle composed of four iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped nanoparticles enabled enhanced ‘sensing’ of the tumor-associated remodeling of the vascular bed offering increased likelihood of specific recognition of metastatic tumors. Compared to spherical nanoparticles, the chain-shaped nanoparticles resulted in superior targeting of αvβ3 integrin due to geometrically enhanced multivalent docking. We performed multimodal in vivo imaging (Fluorescence Molecular Tomography and Magnetic Resonance Imaging) in a non-invasive and quantitative manner, which showed that the nanoparticles targeted metastases in the liver and lungs with high specificity in a highly aggressive breast tumor model in mice.

Parkinson's disease (PD) is characterized by the progressive loss of select neuronal populations, but the prodeath genes mediating the neurodegenerative processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a stress-induced gene with proapoptotic activity that was previously described as highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA) cellular model of PD. Here, we report that Trib3 immunostaining is elevated in dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD patients. Trib3 protein is also upregulated in cellular models of PD, including neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6-OHDA, 1-methyl-4-phenylpyridinium (MPP

Tumors present numerous biobarriers to the successful delivery of nanoparticles. Decreased blood flows and high interstitial pressures in tumors dictate the degree of resistance to extravasation of nanoparticles. To understand how a nanoparticle can overcome these biobarriers, we developed a multimodal in vivo imaging methodology, which enabled the non-invasive measurement of microvascular parameters and deposition of nanoparticles at the microscopic scale. To monitor the spatiotemporal progression of tumor vasculature and its vascular permeability to nanoparticles at the microcapillary level, we developed a quantitative in vivo imaging method using an iodinated liposomal contrast agent and a micro-CT. Following perfusion CT for quantitative assessment of blood flow, small animal fluorescence molecular tomography was used to image the in vivo fate of cocktails containing liposomes of different sizes labeled with different NIR fluorophores. The animal studies showed that the deposition of liposomes depended on local blood flow. Considering tumor regions of different blood flow, the deposition of liposomes followed a size-dependent pattern. In general, the larger liposomes effectively extravasated in fast flow regions, while smaller liposomes performed better in slow flow regions. We also evaluated whether the tumor retention of nanoparticles is dictated by targeting them to a receptor overexpressed by the cancer cells. Targeting of 100-nm liposomes showed no benefits at any flow rate. However, active targeting of 30-nm liposomes substantially increased their deposition in slow flow tumor regions (~12-fold increase), which suggested that targeting prevented the washout of the smaller nanoparticles from the tumor interstitium back to blood circulation.

Ankle impingement syndromes encompass a broad spectrum of post-traumatic and chronic degenerative changes that present with pain on specific movements about the ankle joint. Both amateur and professional athletes are disproportionately affected by these conditions, and while conservative measures can potentially treat an impingement syndrome, definitive therapy is often alleviated surgically. Imaging (including conventional radiography, ultrasound, CT and MRI) plays an invaluable role in the diagnosis and pre-surgical work-up. An anatomically based classification system is useful in these syndromes, as the aetiology, sites of pathology and preferred treatment methods are similarly based on anatomic locations about the ankle. This review focuses on the anatomic locations, pathophysiology, imaging considerations and brief discussion of therapies for each of the major anatomic ankle impingement syndromes.

Introduction: Evidence suggests that toxic iron is involved in haemophilic joint destruction. Aim:To determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease. Methods: Adults with haemophiliaA or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results.Results: MRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (r s = −0.81, P < 0.001) and MRI scores (r s = −0.52, P = 0.037). This was unexpected since UTE-T2* values decrease with better joint status in patients with osteoarthritis, suggesting that iron was present and responsible for the effects.Histological analysis of cartilage confirmed iron deposition within chondrocytes, associated with low UTE-T2* values. Conclusions: Iron accumulation can occur in cartilage (not only in synovium) andshows a clear association with joint health. Cartilage iron is a novel biomarker which, if quantifiable with innovative joint-specific MRI T2* sequences, may guide treatment optimization.