Micro-CT based characterisation of changes to the vascular network following closed soft tissue trauma and cryotherapy

This project has investigated how the architecture of the blood vessels supplying nutrients to skeletal muscles is affected by muscle contusion injuries, and how it changes during healing with or without initial treatment of the injury by icing. In order to do this, we used contrast agents to visualise blood vessels in 3D with micro-computed tomography imaging. This research significantly contributes to the fields of orthopaedics, traumatology and sports medicine, as it improves our understanding of muscle contusion injuries. Furthermore, the methods developed in this thesis may help to improve the diagnosis and monitoring of these injuries.

Synthesis and characterization of Fe- and Co-based ferrite nanoparticles and study of the T-1 and T-2 relaxivity of chitosan-coated particles

In pursuit of newer and more effective contrast agents for magnetic resonance imaging, we report in this article the use of biocompatible chitosan-coated ferrite nanoparticles of different kinds with a view to determine their potential applications as the contrast agents in the field of nuclear magnetic resonance. The single-phase ferrite particles were synthesized by chemical co-precipitation (CoFe2O4 and Fe3O4) and by applying ultrasonic vibration (CoFe2O4 and Co0.8Zn0.2Fe2O4). Although magnetic anisotropy of CoFe2O4 nanoparticle leads to finite coercivity even for nanoensembles, it has been reduced significantly to a minimum level by applying ultrasonic vibration. Fe3O4 synthesized by chemical co-precipitation yielded particles which already possess negligible coercivity and remanence. Substitution of Co by Zn in CoFe2O4 increases the magnetization significantly with a small increase in coercivity and remanence. Particles synthesized by the application of ultrasonic vibration leads to the higher values of T-2 relaxivities than by chemical coprecipitation. We report that the T-2 relaxivities of these particles are of two orders of magnitude higher than corresponding T-1 relaxivities. Thus, these particles are evidently suitable as contrast agent for T-2 weighted MR images.

Photocytotoxic lanthanide complexes

Lanthanide complexes have recently received considerable attention in the field of therapeutic and diagnostic medicines. Among many applications of lanthanides, gadolinium complexes are used as magnetic resonance imaging (MRI) contrast agents in clinical radiology and luminescent lanthanides for bioanalysis, imaging and sensing. The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin. Photodynamic therapy (PDT) is a non-invasive treatment modality of cancer using a photosensitizer drug and light. This review primarily focuses on different aspects of the chemistry of lanthanide complexes showing photoactivated DNA cleavage activity and cytotoxicity in cancer cells. Macrocyclic texaphyrin-lanthanide complexes are known to show photocytotoxicity with the PDT effect in near-IR light. Very recently, non-macrocyclic lanthanide complexes are reported to show photocytotoxicity in cancer cells. Attempts have been made in this perspective article to review and highlight the photocytotoxic behaviour of various lanthanide complexes for their potential photochemotherapeutic applications.

Synthesis, Characterization, and Nuclear Magnetic Resonance Study of Chitosan-Coated Mn1-xZnxFe2O4 Nanocrystals

Ultra-fine crystallites of Mn1-xZnxFe2O4 series (0 <= x <= 1) were synthesized through wet chemical co- precipitation method followed by calcination at 200 degrees C for 4 hours. Formation of ferrites was confirmed by X-ray diffraction, TEM selected area diffraction (SAD) and Fourier Transform Infra-red Spectroscopy (FTIR). Nanocrystallites of different compositions in the series were coated with biocompatible chitosan in order to investigate their possible application as contrast agent for magnetic resonance imaging (MRI). Chitosan coating examined by FTIR, revealed a strong bonding of chitosan molecules to the surface of the ferrite nanocrystallites. Spin-spin, tau(2) relaxivities of nuclear spins of hydrogen protons of the solutions for different ferrites were measured from concentration dependence of relaxation time by nuclear magnetic resonance (NMR). All the compositions of Mn1-xZnxFe2O4 series possess higher values of tau(2) relaxivity thus making them suitable as contrast agents for tau(2) weighted imaging by MRI.

Size Control and Magnetic Property Trends in Cobalt Ferrite Nanoparticles Synthesized Using an Aqueous Chemical Route

Cobalt ferrite (CoFe2O4) is an engineering material which is used for applications such as magnetic cores, magnetic switches, hyperthermia based tumor treatment, and as contrast agents for magnetic resonance imaging. Utility of ferrites nanoparticles hinges on its size, dispersibility in solutions, and synthetic control over its coercivity. In this work, we establish correlations between room temperature co-precipitation conditions, and these crucial materials parameters. Furthermore, post-synthesis annealing conditions are correlated with morphology, changes in crystal structure and magnetic properties. We disclose the synthesis and process conditions helpful in obtaining easily sinterable CoFe2O4 nanoparticles with coercive magnetic flux density (H-c) in the range 5.5-31.9 kA/m and M-s in the range 47.9-84.9 A.m(2)Kg(-1). At a grain size of similar to 54 +/- 2 nm (corresponding to 1073 K sintering temperature), multi-domain behavior sets in, which is indicated by a decrease in H-c. In addition, we observe an increase in lattice constant with respect to grain size, which is the inverse of what is expected of in ferrites. Our results suggest that oxygen deficiency plays a crucial role in explaining this inverse trend. We expect the method disclosed here to be a viable and scalable alternative to thermal decomposition based CoFe2O4 synthesis. The magnetic trends reported will aid in the optimization of functional CoFe2O4 nanoparticles

Design and synthesis of biofunctional magnetic/fluorescent glyco-nanoparticles and quantum dots and their application as specific molecular imaging probes

206 p.

Acoustic radiation force of a Bessel beam on a porous sphere.

The possibility of using acoustic Bessel beams to produce an axial pulling force on porous particles is examined in an exact manner. The mathematical model utilizes the appropriate partial-wave expansion method in spherical coordinates, while Biot's model is used to describe the wave motion within the poroelastic medium. Of particular interest here is to examine the feasibility of using Bessel beams for (a) acoustic manipulation of fine porous particles and (b) suppression of particle resonances. To verify the viability of the technique, the radiation force and scattering form-function are calculated for aluminum and silica foams at various porosities. Inspection of the results has shown that acoustic manipulation of low porosity (<0.3) spheres is similar to that of solid elastic spheres, but this behavior significantly changes at higher porosities. Results have also shown a strong correlation between the backscattered form-function and the regions of negative radiation force. It has also been observed that the high-order resonances of the particle can be effectively suppressed by choosing the beam conical angle such that the acoustic contribution from that particular mode vanishes. This investigation may be helpful in the development of acoustic tweezers for manipulation of micro-porous drug delivery carrier and contrast agents.

新型靶向性磁共振成像造影剂的合成及性质研究

磁共振成像(magnetic resonance imaging, MRI)以其分辨率高、对人体无电离辐射损伤、多参数成像等优点而得到迅速发展和广泛应用。目前，MRI已从单一形态学向分子影像学的深度发展，对医学临床和医学研究产生了巨大影响。为了提高病变部位与正常组织间信号的对比度，约30%~40%的诊断需要使用磁共振成像造影剂。它是一类能缩短成像时间、提高成像对比度和清晰度、显示组织器官功能状态的诊断用药。下一代磁共振成像造影剂的设计目标将集中在对特定组织或器官具有选择性或靶向性、高弛豫性能和减少用药剂量等方面。本论文在此领域的研究内容可归纳如下： (1) 以多糖为载体的MRI造影剂 设计合成了阿拉伯半乳聚糖修饰的Gd-DTPA配合物(Gd-DTPA-CMAG-An)和葡聚糖修饰的Gd-DTPA配合物(Gd-DTPA-CMDn-Cyst)。通过体外弛豫时间测试和体内磁共振成像实验研究了Gd-DTPA-CMAG-An弛豫性能、器官选择性、体内滞留时间和代谢情况，结合体外稳定性综合评价了其应用于临床的可能性。研究结果表明，Gd-DTPA-CMAG-An配合物在水溶液中弛豫性能为Gd-DTPA的1.4倍左右，Gd-DTPA-CMAG-A2对肝脏信号的增强效果是Gd-DTPA的2.0倍左右，并且能在较长时间内产生良好稳定的增强效果。这与肝脏表面的去唾液酸糖蛋白受体的专一性识别有关。Gd-DTPA-CMAG-A2良好的肝脏选择性和肾脏代谢能力，有望成为有前景的肝脏选择性造影剂。通过小鼠MRI实验初步评价了Gd-DTPA-CMDn-Cyst配合物造影剂对血管信号的增强作用。Gd-DTPA-CMD4-Cyst对血管产生了良好的增强效果，并且能在较长时间内对血管产生良好稳定的增强，从而有充分的时间优化成像窗口获得理想的成像效果。但造影剂在体内的分布和代谢是一个非常复杂的过程，Gd-DTPA-CMD4-Cyst在血液中的滞留情况及能否用于血管造影仍需进一步的实验证实。 (2) MnNaY 型分子筛作为胃肠道MRI造影剂 离子交换法制备了Mn2+交换的NaY分子筛MnNaY，从对造影剂的一般要求出发，对其酸性水溶液中的稳定性和离子交换选择性、体外弛豫性能和体内成像等方面进行研究，并对器官的选择性及体内滞留时间和代谢情况进行了分析，从而对其应用于临床的可能性进行了探讨。研究结果表明，MnNaY悬浮液能长时间在较低的酸性条件下保持良好的稳定性，其弛豫效率高于目前临床所用造影剂Gd-DTPA，随Mn2+的含量在NaY分子筛中的增加(3.2%~5.2%)，弛豫效率反而降低。MnNaY (3.2% Mn)对胃部具有良好的增强效果，并且能在较长时间内产生良好稳定的增强效果，有利于获得理想的成像效果。它是一种比较好的潜在口服胃肠道造影剂。 (3) 甘草酸为载体的MRI造影剂 合成了甘草酸为载体的配合物GL-(A-Gd-DTPA)3，对其体外弛豫性能和体内成像等方面进行了研究，结果表明，其在水中的弛豫效率约为目前临床所用造影剂Gd-DTPA的1.4倍，体内成像表明它能在较长时间内对大鼠肝脏产生良好稳定的增强效果，这是由于肝(实质)细胞膜表面存在GL和GA受体，Gd-DTPA 以GL为载体后具有良好的趋肝性与肝细胞靶向性。 (4) 中性的Gd-DTPA双酰胺衍生物 合成了两种中性的Gd-DTPA双酰胺衍生物Gd-DTPA-BBA和Gd-DTPA-BtBA，其弛豫效率与Gd-DTPA相近，对肝脏和肾脏具有较好的增强效果，由于这两种配合物均为电中性化合物，这样配合物溶液的渗透压值与血液的渗透压值较接近，可能更易为生物体所接受。

新型选择性磁共振成像造影剂的设计、合成及性质

近年来，随着磁共振血管造影（magnetic resonance angiography，MRA）、功能磁共振成像（fuectional MRI）、灌注磁共振成像中erfusion MRI）、扩散加权磁共振成像（diffusion weigllted MRI）等新M班技术的发展和在临床诊断应用中的普及，磁共振成像造影剂的研究和开发已经成为一个日益重要的研究领域。其中大分子造影剂由于具有弛豫效率高、在血池中停留时间长及可能的组织、器官选择性等特点更是受到MRI造影剂研究者的广泛关注。论文工作围绕新型MRI造影剂的研制进行了较系统的研究，主要实验结果归纳如下：（1）以天然多糖为载体的M斑造影剂设计合成了四种天然多糖修饰的Gd-DTPA配合物：AG-（Gd-DTPA）n、PQPS-（Gd-DTPA）n、GAPS-（Gd-DTPA）n和EAPS-（Gd-DTPA）。通过体外弛豫时间测试和体内磁共振成像实验研究其弛豫性能、器官选择性、体内滞留时间和代谢情况，结合体外稳定性和溶血性综合评价了其应用于临床的可能性。研究结果表明，不同类型多糖Gd-DTPA配合物在水溶液中弛豫性能相近，为Gd-DTPA的1.5-2.0倍，对肝脏信号的增强效果是Gd-DTPA的3.0倍左右，并且能在较长时间内产生稳定良好的增强效果。肝脏信号的增强效果随多糖Gd-DTPA配合物分子量的增加基本呈现出升高趋势，表明分子量影响其肝脏分布，分子量越大越易于在肝脏积累。其中，AG-（GdDTPA）n表现出了良好的肝脏选择性和肾脏代谢性能，有望成为有前景的肝脏选择性造影剂。而EAPS-（Gd-DTPA）n在肾脏中的代谢速率较慢，这一特性在磁共振血管造影及灌注磁共振成像的研究中极有帮助。（2）稀土杂多配合物M班造影剂设计合成了三种夹心型稀土杂多配合物：K13［Gd（Siw11O39）］、K11H6［Gd3O3（SiWgO34）2］及K17［Gd（PZW17O61）2］，通过体外弛豫性能、稳定性、溶血性及体内急性毒性、磁共振成像实验，对其体外体内的增强效果和安全性进行了较全面的评价。K13［Gd（SIWllO39）2］和K17〔Gd（PZwl7o61）2］在水溶液中的弛豫效率略高于Gd-DTPA，而K11H6［Gd3O3（SiW9O34）2］在水溶液中的弛豫效率是Gd-DTPA的3.5倍左右。磁共振成像实验表明：K13［Gd（SIWll。动2］、K11H6［Gd3O3（siwgo34）2」和K17［Gd（P ZwI7o61）2］对肝脏产生的增强效果分别为Gd-DTPA的1.5、2.5和3.5倍左右，对肾脏的增强效果不及Gd-DTPA。通过与磷钨杂多配合物的比较发现，具有相同构型的稀土杂多配合物对肝脏和肾脏产生的增强效果相近，肝脏信号增强的顺序为Gd（凡wl7）2＞Gd3（XW9）2＞Gd（XW11）2，肾脏信号增强的顺序为Gd3（XW9）2≈Gd（XW11）2＞Gd（X2W17）2。总体来说，稀土杂多配合物在体内的分布和代谢是由其构型、离子大小、所带负电荷等因素决定的，受结构中的杂原子影响不大。

Novel Near-Infrared Luminescent Hybrid Materials Covalently Linking with Lanthanide [Nd(III), Er(III), Yb(III), and Sm(III)] Complexes via a Primary beta-Diketone Ligand: Synthesis and Photophysical Studies

A series of novel, colorless, and transparent sot-gel derived hybrid materials Ln-DBM-Si covalently grafted with Ln(DBM-OH)(3)center dot 2H(2)O (where DBM-OH = o-hydroxydibenzoylmethane, Ln = Nd, Er, Yb, and Sin) were prepared through the primary beta-diketone ligand DBM-OH. The structures and optical properties of Ln-DBM-Si were studied in detail. The investigation results revealed that the lanthanide complexes were successfully in situ grafted into the corresponding hybrids Ln-DBM-Si. Upon excitation at the maximum absorption of ligands, the resultant materials displayed excellent near-infrared luminescence.

Study of alpha-, beta- and gamma-cyclodextrin/C-60 supramolecular complexes: Influence of the cavity dimension toward the host-guest complexes

Herein we report the spectroscopic, electrochemical, TEM and DLS characterizations Of C-60 supramolecular inclusion complexes with alpha-, beta- and gamma-cyclodextrins prepared using anionic C-60. The results indicate that the cyclodextrin itself has little effect on the encapsulated C-60 or on the properties of the inclusion complex. Instead, the cyclodextrin has a significant influence on the aggregation behavior of individual complex in aqueous solution, which in turn affects the property of the supramolecular complex of cyclodextrin and C-60 greatly, As the cavity dimension of cyclodextrin becomes smaller as it changes from gamma-CD to beta-CD, and finally to alpha-CD, it is observed that more aggregation occurs for the corresponding inclusion complex in aqueous solution.

Studies on the solution structures of lanthanide(III) complexes of DTPA-BIN by NMR

The solution structures of diamagnetic lanthanide (III) complexes of DTPA-BIN (Ln = La, Y, Lu, Sc) have been investigated by H-1 NMR, C-13 NMR and 2D NMR. For each complex, two or more species of asymmetric conformations with little distinction were identified at room temperature. And their solution structures vary with the radius of the central metals. NMR spectra support the hypothesis that Sc3+ with smaller radius formed an eight-coordinated structure with DTPA-BIN, La3+ with larger radius formed nine- or ten-coordinated structures with DTPA-BIN, and Y (DTPA-BIN) and Lu (DTPA-BIN) had nine-coordinated solution structures. The solution structure of Gd (DTPA-BIN) was obtained from the similarity of radius between Gd3+ and Y3+, which is a nine-coordinated structure formed by three nitrogens, three acetate oxygens, two acetyl oxygens, one water molecule and a gadolinium(III) cation.

NMR studies of Gd(DTPA-BIN) in human serum albumin solution

Stable gadolinium complexes, such as Gd(DTPA) and Gd(DOTA), are usually used as the contrast agents for magnetic resonance imaging(MRI). Reported here are the enhanced relaxation properties of a novel gadolinium complex, diethylene-triaminopentaacetate Lis (isoniazid) [Gd(DTPA-BIN)], in aqueous and in human serum albumin(HSA) solution, which indicates that (1) two Gd(DTPA-BIN) can integrate non-covalently with one HSA with an equilibrium constant of 0. 02 mmol(-2) . L-2 ; (2) the relaxivities are 3. 28 and 4. 92 mmol(-1) . L . s(-1) for the free Gd(DTPA-BIN) and the [Gd(DTPA-BIN)](2), HSA conjugator, respectively; (3) the rotational correlation time of protein conjugator is notably higher than that of the free complex, The above results may imply that Gd(DTPA-BIN) has a higher tissue selectivity than that of its parent Gd(DTPA).

Synthesis and solvent enhanced relaxation property of water-soluble endohedral metallofullerenols

Gadolinium fullerenols, as novel and potential contrast agents for magnetic resonance imaging, were synthesized, which showed excellent efficiency in enhancing water proton relaxation with a relaxivity of 47.0+/-1.0 mM(-1).s(-1).

H-1 NMR Titration Studies of Two Novel DTPA Derivatives

Polyaminopolycarboxylate gadolinium (III) complexes have been studied intensively in recent years because of their potential uses as contrast agents for magnetic resonance imaging (MHI)([1]). The research interests are mainly focussed on Gd3+ complexes of DTPA, DOTA and their various derivatives. Four kinds of Gd3+ complexes can be used presently in clinical MRI, which are GD(DTPA)([2]), Gd(DOTA)([3]), Gd(DTPA-BMA)([4]) and Gd(HP-DO3A)([5]). Here report two new DTPA bis (amide) derivatives-diethylenetriaminepentaacetic acid-N, N ''-bis (dimethylamide) (DTPA-BDMA) and -bis (diethylamide) (DTPA-BDEA).