Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Differentiating benign from malignant cardiac tumors with cardiac magnetic resonance imaging

Background

The purpose of this analysis is to describe the differences in cardiac magnetic resonance characteristics between benign and malignant tumors, which would be helpful for surgical planning.

Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.
We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo . Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers.
This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.     

Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.     

经单根冠状动脉与冠状静脉窦同时灌注心肌保护的实验研究

目的探讨经单根冠状动脉和冠状静脉窦（CS）顺行性／逆行性同时心肌灌注（SARC）的效果。方法将离体猪心分别经左前降支（LAD）、左回旋支（LCX）或右冠状动脉（RCA）中的1支和CS行SARC，再依次向动、静脉灌注通路内注入磁共振造影剂[钆喷替酸葡甲胺（Gd-DTPA）]。应用磁共振成像（MRI）检测心肌内造影剂的分布以及对非灌注冠状动脉回流液进行分析，评估心肌灌注效果。结果SARC期间经单根冠状动脉注入Gd-DTPA不但使其支配区域磁共振信号增强，而且其余2根非灌注冠状动脉的支配区域信号也增强（包括右心室游离壁）；而SARC期间经CS注入Gd-DTPA只引起非灌注冠状动脉支配区变亮，灌注冠状动脉的支配区和右心室游离壁的信号强度无改变。SARC期间非灌注冠状动脉收集的回流液速度分别为：LAD 10．5～17．7ml／min，LCX 9．7～15．2ml／min，RCA 4．7～7．8ml／min。结论经单根冠状动脉和CS同时灌注可以提供全面均匀的心肌灌注，足以防止非灌注冠状动脉支配区发生心肌缺血损伤。     

骨内高压丹参治疗后骨髓微循环实验研究

目的:寻找中药对 Legg-Perthes 病及各种骨性关节炎等伴有骨内高压症的治疗方法并研究其治疗机理。方法:将18只骨内高压模型家兔随机分为相等的治疗组和对照组,分别肌肉注射等量的丹参注射液和生理盐水3周,然后分不同时期取材制作电镜标本进行研究。结果:发现治疗组早期骨髓微循环及造血组织病理状态即有显著恢复,晚期基本恢复正常,而对照组骨髓微循环及造血组织各期均呈现明显病理状态。结论:丹参能显著改善骨内高压下的骨髓微循环病理状态,从而降低骨内高压,为临床用中药治疗骨内高压症提供了理论依据。     

艾灸对30例健康人甲皱微循环及血液流变学的影响

目的：探讨艾灸对健康人甲皱微循环及血液流变学的影响。方法：选择健康学员及武警战士各30例，年龄20－22岁，应用江苏协达公司生产的XDM－1型微循环电脑检测仪及北京世帝科学仪器公司生产的LG－R－80血液粘度计，LG－B－190型红细胞变形／聚集测试仪。固定专人操作，分别于艾灸前及艾灸后，测试甲皱微循环及血液流变学各项指标的变化。结果：艾灸八邪及三阴交穴后，甲皱微循环各项指标均有明显变化，经统计学处理，红细胞聚集程度、血流速度、流态积分、管周积分均有显著性差异（P＜0．05），其余各项指标虽有不同程度的改变，但无统计学意义（P＞0．05）；血液流变学各项指标亦有明显变化，经统计学处理，全血低切相对粘度、全血低切还原粘度、红细胞刚性指数、红细胞聚集指数及血浆纤维蛋白原都有非常显著性差异（P＜0．01），全血高切相对粘度有显著性差异（P＜0．05），其余各项指标虽有不同程度的改变，但无统计学意义（P＞0．05）。结论：艾灸八邪及三阴交穴后可明显改善红细胞聚集程度，降低血液粘度，加快血流速度，降低外周血管阻力。     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.