Magnetic resonance imaging measurements of vascular permeability and extracellular volume fraction of breast tumors by dynamic Gd-DTPA-enhanced relaxometry

Vascular permeability (k(ep), min(-1)) and extracellular volume fraction (v(e)) are tissue parameters of great interest to characterize malignant tumor lesions. Indeed, it is well known that tumors with high blood supply better respond to therapy than poorly vascularized tumors, and tumors with large extracellular volume tend to be more malignant than tumors showing lower extracellular volume. Furthermore, the transport of therapeutic agents depends on both extracellular volume fraction and vessel permeability. Thus, before treatment, these tissue parameters may prove useful to evaluate tumor aggressiveness and to predict responsiveness to therapy and variations during cytotoxic therapies could allow to assess treatment efficacy and early modified therapy schedules in case of poor responsiveness. As a consequence, there is a need to develop methods that could be routinely used to determine these tissue parameters. In this work, blood-tissue permeability and extracellular volume fraction information were derived from magnetic resonance imaging dynamic longitudinal relaxation rate (R(1)) mapping obtained after an intravenous bolus injection of Gd-DTPA in a group of 92 female patients with breast lesions, 68 of these being histologically proven to be with carcinoma. For the sake of comparison, 24 benign lesions were studied. The measurement protocol based on two-dimensional gradient echo sequences and a monoexponential plasma kinetic model was that validated in the occasion of previous animal experiments. As a consequence of neoangiogenesis, results showed a higher permeability in malignant than in benign lesions, whereas the extracellular volume fraction value did not allow any discrimination between benign and malignant lesions. The method, which can be easily implemented whatever the imaging system used, could advantageously be used to quantify lesion parameters (k(ep) and v(e)) in routine clinical imaging. Because of its large reproducibility, the method could be useful for intersite comparisons and follow-up studies.     

Numerical simulation of magnetic fluid hyperthermia based on multiphysics coupling and recommendation on preferable treatment conditions

In this study, we established a multiphysics coupling model of magnetic fluid hyperthermia (MFH), using complex magnetic permeability to solve the magnetic losses of magnetic nanoparticles (MNPs). The experiments were performed to verify the validity of numerical coupling method. The optimal treatment time (OTT) was regarded as the time required for the lowest temperature point of the tumor to attain the damage criteria. The OTT increased by about 42 s as the tumor radius increased by 1 cm, and decreased by 10 s for the increase in MNP dose per gram of tumor by 1 mg. To achieve cost-effective therapies under moderate treatment conditions, the preferable ranges of external magnetic field intensity H₀ and frequency f, MNP radius R and volume fraction $?$ are 3–11 kA/m, 200–500 kHz, 8–10 nm, and 5%–10%, respectively. It is greatly encouraged to adopt the combination of higher H₀ (8–11 kA/m) and lower f (200–300 kHz), and the conjunction of higher R and $?$. There was a slight thermal damage to normal tissues due to eddy current loss. In conclusion, MFH can provide an excellent therapeutic effect for deep tumors.     

Enhanced MRI of tumors utilizing a new nitroxyl spin label contrast agent

Nitroxyl spin labels have been shown to be effective in vivo contrast agents for magnetic resonance imaging (MRI) of the central nervous system, myocardium, and urinary tract. A new pyrrolidine nitroxyl contrast agent (PCA) with better resistance to in vivo metabolic inactivation than previously tested agents was studied for its potential to enhance subcutaneous neoplasms in an animal model. Twenty-two contrast enhancement trials were performed on a total of 15 animals 4-6 weeks after implantation with human renal adenocarcinoma. Spin echo imaging was performed using a .35 T animal imager before and after intravenous administration of PCA in doses ranging from 0.5 to 3mM/kg. The intensity of tumor tissue in the images increased an average of 35% in animals receiving a dose of 3 mM/kg. The average enhancement with smaller doses was proportionately less. Tumor intensity reached a maximum within 15 min of injection. The average intensity difference between tumor and adjacent skeletal muscle more than doubled following administration of 3 mM/kg of PCA. Well-perfused tumor tissue was more intensely enhanced than adjacent poorly perfused and necrotic tissue.     

白细胞介素治疗肿瘤的临床疗效观察及微量元素变化的研究

观察了白细胞介素－２和白细胞介素－６治疗恶性肿瘤３６例疗效及微量元素锌（Ｚｕ）和铜（Ｃｕ）的变化,经治疗后,其中部分缓解８例,好转１６例,稳定７例,发展５例。治疗后３６例恶性肿瘤患者血清Ｚｎ含量和Ｚｎ／Ｃｕ比值明显升高,而Ｃｕ含量明显降低,结果提示,Ｚｎ／Ｃｕ比值对恶性肿瘤的疗效和预后有一定的参考价值。     

碳离子均匀扫描治疗与光子IMRT治疗颅底恶性肿瘤的剂量学比较研究

比较分析国产重离子加速器均匀扫描与光子调强放疗(IMRT)治疗计划在颅底恶性肿瘤治疗中的剂量学差异。回顾分析国产重离子设备(Heavy Ion Medical Machine, HIMM)采用均匀扫描方式治疗8例颅底恶性肿瘤的患者治疗计划,包括7例脊索瘤、1例软骨肉瘤。碳离子治疗(Carbon Ion Radiotherapy, CIRT)计划采用兰州科近泰基公司的ciPlan计划系统(V1.0)进行计划设计,处方剂量为计划靶区57.6~60.8 Gy (RBE),16分次,单次3.6~3.8 Gy(RBE)。治疗使用多叶准直器(Multi Leaf Collimator, MLC)调节射束横向适形度,脊形过滤器(Ridge Filter, RF)展宽Bragg峰,补偿器(Bolus)调节射束远端的适形度。使用90°固定水平治疗头,采取床角为0°,及转床90°或180°实现两野交角照射或对穿照射。光子IMRT计划采用美国Varian公司的Eclipse计划系统(V13.5)设计5野固定野调强计划,处方剂量和CIRT计划一致。所有计划在满足危及器官(Organ At Risk, OAR)限量的基础上进行剂量评估,相关剂量学参数包括: 靶区覆盖、适形度指数(CI)、均匀性指数(HI)、以及危及器官受量。PTV的V95两者之间比较无统计学差异(P=0.106),D_mean、CI、HI均有统计学差异, IMRT计划优于CIRT计划(P值分别为0.048, 0.031和0.024)。OAR受量方面,大部分OAR的CIRT计划比IMRT计划的小,但没有统计学差异,而视交叉、左晶体、右晶体的最大剂量及脑干、右侧视神经的平均剂量有统计学差异(P值分别为0.034, 0.000, 0.047, 0.008和0.030)。OAR与靶区的距离,使用最小hausdorff距离(HD_min)来描述,当HD_min>7.1 mm时,CIRT计划明显优于IMRT计划。均匀扫描方式的碳离子治疗计划在靶区均匀度及适形度方面劣于光子IMRT计划,但在OAR受量方面,均匀扫描碳离子治疗计划优于IMRT计划。剂量学优势能否转化为临床获益有待于通过临床研究进一步验证。