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.     

Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern France.

AIMS: To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with > or = 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated. METHODS: Four hundred and forty-seven consecutive patients who underwent stress MPI were prospectively followed for 2.1 [0.5-4.1] years for the subsequent occurrence of hard CE (myocardial infarction and sudden or coronary death) and soft CE (unstable angina and ischaemic heart failure requiring hospitalization). Re-vascularization procedures performed as a result of the screening protocol were not included in the analysis. RESULTS: Follow-up was successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline. Medical therapy was intensified in all subjects and especially in those with abnormal MPI. Twenty-three patients with abnormal MPI underwent a re-vascularization procedure. CEs occurred in 14 patients, including six of 71 patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds ratio (OR) (95% CI) = 5.6 (1.7-18.5)]. Low-density lipoprotein cholesterol > or = 3.35 mmol/l [OR (95% CI) = 7.3; 1.5-34.7] and age > median [OR (95% CI) = 6.0 (1.2-28.6)] were additional independent predictors for CE. The independent predictors for abnormal MPI were male gender, plasma triglycerides > or = 1.70 mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the strongest [OR (95% CI) = 4.0 (1.8-8.8)]. CONCLUSIONS: Asymptomatic patients with diabetes in this study had a very low hard cardiac event rate over an intermediate period. This could be explained by the effects of intervention or by the low event rate in the background population. Randomized studies of cardiac heart disease screening are required in asymptomatic subjects with diabetes to determine the effectiveness of this intervention.     

动脉灌注灭活再植治疗骨肉瘤的体会

本组１２例骨肉瘤均采用动脉区域灌注灭活再植及术后化疗方法，术后２年存活率平均为７５％，１例因经验不足致局部复发，仅占８．３％，表明在化疗保障下，采用此种方法即能保肢，又能获得与截肢治疗相同的手术效果，优于单纯行灭活再植术后中方法。     

深低温停循环逆行脑灌注脑组织自由基变化的实验研究

研究深低温停循环（ＤＨＣＡ）与逆行脑灌注（ＲＣＰ）时脑组织自由基的变化。健康杂种犬１４只，随机等分为ＤＨＣＡ组和ＲＣＰ组，在停循环前（Ａ点）、ＤＨＣＡ／ＲＣＰ３０分（Ｂ点）、ＤＨＣＡ／ＲＣＰ６０分（Ｃ点）ＤＨＣＡ／ＲＣＰ９０分（Ｄ眯）和复温再灌注３０分（Ｅ点）取脑皮层ｌｇ，检测丙二醛（ＭＤＡ）和超氧化物歧化酶（ＳＯＤ）水平。结果见两组在Ａ点ＭＤＡ和ＳＯＤ无差别。在Ｂ、Ｃ、Ｄ、Ｅ点，ＤＨＣＡ组ＭＤＡ     

Minimizing macrovessel signal in cerebral perfusion imaging using independent component analysis.

The pronounced susceptibility effect of macrovessels in MR bolus-tracking studies induces spots of artificially high blood flow and volume in perfusion parameter images. These high-intensity regions impede the detection of perfusion changes and lead to elevated perfusion parameters in adjacent tissues. The purpose of this work was to explore postprocessing methods to reduce the influence of macrovessel signal in dynamic MRI. After data reduction was performed with the use of a principal component analysis (PCA), an independent component analysis (ICA) was applied to separate signal components of different compartments. Based on this decomposition, the dynamic time series were reconstructed with minimized contributions of macrovessel signal and noise. The influence of the temporal resolution and signal-to-noise ratio (SNR) of the source data were investigated by means of a simulation study. A region-of-interest (ROI)-based analysis of corrected and uncorrected in vivo data demonstrated that the influence of arteries and veins was reduced at least by 50%, while gray matter (GM) and white matter (WM) tissues were nearly unaffected by the correction process. Hemodynamic parameter images of the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated from corrected and uncorrected scans. The corrected parameter images showed a clearly reduced macrovessel signal and an improved perceptibility of microvascular perfusion changes compared to the uncorrected ones.     

有效控制与控制不佳的MRI阴性的GTCS病人发作间期SPECT对照研究

目的:利用单光子发射计算机断层摄影(SPECT)半定量分析有效控制与控制不良的MRI阴性的全面性强直阵挛发作癫(GTCS)病人的局部脑血流差异,探讨脑血流灌注与其预后的关系.材料和方法:对29例有效控制的和12例控制不佳的MRI阴性的GTCS病人进行发作间期99mTc-ECD-SPECT脑血灌流显像,10例年龄匹配的健康人作对照,用感兴趣区(ROI)的不对称指数(%AI)进行半定量分析.将SPECT分析结果与病人的临床表现与EEG相比较.结果:①控制不佳组与有效控制组在丘脑和基底节区的%AI存在显著性差异(P<0.05);②控制不佳组SPECT脑显像的异常率(83.3%,10/12)明显高于有效控制组的异常率(17.2%,5/29),两组具有显著性差异(P<0.01);而两组病人的EEG异常率分别为58.3%、44.8%(7/12、13/29),无显著性差异(P>0.05).结论:控制不佳的MRI阴性的GTCS病人往往存在发作间期的低血流灌注脑区,提示癫的难治性;而控制良好的病人多无明显异常发现,可能预后较好.     

Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects.

Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter- and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P = 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P = 0.02) in females compared to males.     

High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging.

An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution=234 x 468 microm2) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the study of small rodents at high fields.     

Quantification of perfusion fMRI using a numerical model of arterial spin labeling that accounts for dynamic transit time effects.

A new approach to modeling the signal observed in arterial spin labeling (ASL) experiments during changing perfusion conditions is presented in this article. The new model uses numerical methods to extend first-order kinetic principles to include the changes in arrival time of the arterial tag that occur during neuronal activation. Estimation of the perfusion function from the ASL signal using this model is also demonstrated. The estimation algorithm uses a roughness penalty as well as prior information. The approach is demonstrated in numerical simulations and human experiments. The approach presented here is particularly suitable for fast ASL acquisition schemes, such as turbo continuous ASL (Turbo-CASL), which allows subtraction pairs to be acquired in less than 3 s but is sensitive to arrival time changes. This modeling approach can also be extended to other acquisition schemes.