T2 mapping as a predictor of nonperfused volume in MRgFUS treatment of desmoid tumors.

Objective: The objective of this study was to develop an alternative method of non-contrast monitoring of tissue ablation during focused ultrasound treatment. Desmoid tumors are benign but locally aggressive soft tissue tumors that arise from fibroblast cells. Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as an alternative to conventional therapies, showing promising results in reduction of tumor volume without significant side effects. The gold-standard assessment of the reduction of viable tumor volume post-treatment is non-perfused volume (NPV) and evaluation of NPV is typically performed with post-treatment gadolinium enhanced MR imaging. However, as gadolinium cannot be repeatedly administered during treatments, there is a need for alternative non-contrast monitoring of the tissue to prevent over and under treatment. Methods: Double-echo and multi-echo images were acquired before, during and after the MRgFUS treatment. T2 maps were generated with an exponential fit and T2 maps were compared to post-treatment post-contrast images.Results: In all five MRgFUS treatment sessions, T2 mapping showed excellent qualitative agreement with the post-contrast NPV.Conclusions: T2 mapping may be used to visualize the extent of ablation with focused ultrasound and can be used as a predictor of NPV prior to the administration of contrast during the post-treatment assessment.

Structural behavior of competitive temperature and pH-responsive tethered polymer layers.

Herein, we develop a molecular theory to examine a class of pH and temperature-responsive tethered polymer layers. The response of pH depends on intramolecular charge repulsion of weakly acidic monomers and the response of temperature depends on hydrogen bonding between polymer monomers and water molecules akin to the behavior of water-soluble polymers such as PEG (poly-ethylene glycol) or NIPAAm (n-isopropylacrylamide). We investigate the changes in structural behavior that result for various end-tethered copolymers: pH/T responsive monomers alone, in alternating sequence with hydrophobic monomers, and as 50/50 diblocks with hydrophobic monomers. We find that the sequence and location of hydrophobic units play a critical role in the thermodynamic stability and structural behavior of these responsive polymer layers. Additionally, the polymers exhibit tunable collapse when varying the surface coverage, location and sequence of hydrophobic units as a function of temperature and pH. As far as we know, our results present the first molecularly detailed theory for end-tethered polymers that are both pH and temperature-responsive via hydrogen bonding. We propose that this work holds predictive power for the guided design of future biomaterials.

Quantifying the Electron Donor and Acceptor Abilities of the Ketimide Ligands in M(N═C(t)Bu2)4 (M = V, Nb, Ta).

Addition of 4 equiv of Li(N═C(t)Bu2) to VCl3 in THF, followed by addition of 0.5 equiv of I2, generates the homoleptic V(IV) ketimide complex, V(N═C(t)Bu2)4 (1), in 42% yield. Similarly, reaction of 4 equiv of Li(N═C(t)Bu2) with NbCl4(THF)2 in THF affords the homoleptic Nb(IV) ketimide complex, Nb(N═C(t)Bu2)4 (2), in 55% yield. Seeking to extend the series to the tantalum congener, a new Ta(IV) starting material, TaCl4(TMEDA) (3), was prepared via reduction of TaCl5 with Et3SiH, followed by addition of TMEDA. Reaction of 3 with 4 equiv of Li(N═C(t)Bu2) in THF results in the isolation of a Ta(V) ketimide complex, Ta(Cl)(N═C(t)Bu2)4 (5), which can be isolated in 32% yield. Reaction of 5 with Tl(OTf) yields Ta(OTf)(N═C(t)Bu2)4 (6) in 44% yield. Subsequent reduction of 6 with Cp*2Co in toluene generates the homoleptic Ta(IV) congener Ta(N═C(t)Bu2)4 (7), although the yields are poor. All three homoleptic group 5 ketimide complexes exhibit squashed tetrahedral geometries in the solid state, as determined by X-ray crystallography. This geometry leads to a d(x(2)-y(2))(1) ((2)B1 in D(2d)) ground state, as supported by DFT calculations. EPR spectroscopic analysis of 1 and 2, performed at X- and Q-band frequencies (∼9 and 35 GHz, respectively), further supports the (2)B1 ground-state assignment, whereas comparison of 1, 2, and 7 with related group 5 tetra(aryl), tetra(amido), and tetra(alkoxo) complexes shows a higher M-L covalency in the ketimide-metal interaction. In addition, a ligand field analysis of 1 and 2 demonstrates that the ketimide ligand is both a strong π-donor and strong π-acceptor, an unusual combination found in very few organometallic ligands.

Immediate postoperative inferior vena cava stenting to improve hepatic venous outflow following orthotopic liver transplantation.

Orthotopic liver transplantation can be a surgically complex undertaking, with hepatic venous outflow obstruction occurring at a rate of 1%-6% due to inferior vena cava (IVC) torsion, compression, or anastomotic stenosis. In this report, we present 2 cases of immediate postoperative hepatic venous outflow obstruction in the setting of Budd-Chiari syndrome successfully treated with immediate IVC stenting. Although IVC stenting has been reported for management of long-term IVC anastomotic stenosis after orthotopic liver transplantation, use of stenting to address immediate postoperative caval outflow obstruction is less commonly described. We describe the potential utility of immediate stenting to improve outflow from the transplanted liver and highlight the value of this approach in addressing early postsurgical IVC pathology.

An iron ketimide single-molecule magnet [Fe4(N[double bond, length as m-dash]CPh2)6] with suppressed through-barrier relaxation.

Reaction of FeBr2 with 1.5 equiv. of LiN[double bond, length as m-dash]CPh2 and 2 equiv. of Zn, in THF, results in the formation of the tetrametallic iron ketimide cluster [Fe4(N[double bond, length as m-dash]CPh2)6] (1) in moderate yield. Formally, two Fe centers in 1 are Fe(i) and two are Fe(ii); however, Mössbauer spectroscopy and SQUID magnetometry suggests that the [Fe4]6+ core of 1 exhibits complete valence electron delocalization, with a thermally-persistent spin ground state of S = 7. AC and DC SQUID magnetometry reveals the presence of slow magnetic relaxation in 1, indicative of single-molecule magnetic (SMM) behaviour with a relaxation barrier of U eff = 29 cm-1. Remarkably, very little quantum tunnelling or Raman relaxation is observed down to 1.8 K, which leads to an open hysteresis loop and long relaxation times (up to 34 s at 1.8 K and zero field and 440 s at 1.67 kOe). These results suggest that transition metal ketimide clusters represent a promising avenue to create long-lifetime single molecule magnets.

Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm.

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

A thermoresponsive, citrate-based macromolecule for bone regenerative engineering.

There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to handle and apply to a surgical site, can fill and fully conform to the bone defect, and can promote the formation of new bone tissue. Thermoresponsive polymers that undergo liquid to gel transition at physiological temperature can potentially be used to meet these handling and shape-conforming requirements. However, there are no reports on their capacity to induce in vivo bone formation. The objective of this research was to investigate whether the functionalization of the thermoresponsive, antioxidant macromolecule poly(poly-ethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN), with strontium, phosphate, and/or the cyclic RGD peptide would render it a hydrogel with osteoinductive properties. We show that all formulations of functionalized PPCN retain thermoresponsive properties and can induce osteodifferentiation of human mesenchymal stem cells without the need for exogenous osteogenic supplements. PPCN-Sr was the most osteoinductive formulation in vitro and produced robust localized mineralization and osteogenesis in subcutaneous and intramuscular tissue in a mouse model. Strontium was not detected in any of the major organs. Our results support the use of functionalized PPCN as a valuable tool for the recruitment, survival, and differentiation of cells critical to the development of new bone and the induction of bone formation in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1743-1752, 2018.