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The use of pulsed high-intensity focused ultrasound (HIFU) with an ultrasound contrast agent (UCA) has been shown to disrupt the blood-brain barrier (BBB) noninvasively and reversibly in the targeted regions. This study evaluated the relative permeability of the blood-tumor barrier (BTB) after sonication by pulsed HIFU. Entry into the brain of chemotherapeutic agents is impeded by the BBB even though the permeability of this barrier may be partially reduced in the presence of a brain tumor. F98 glioma-bearing rats were injected intravenously with Evans blue (EB) with or without BTB disruption induced by pulsed HIFU. Sonication was applied at an ultrasound frequency of 1 MHz with a 5% duty cycle, and a repetition frequency of 1 Hz. The accumulation of EB in brain tumor and the tumor-to-contralateral brain ratio of EB were highest after pulsed HIFU exposure. Sonication followed by EB injection showed a tumor-to-contralateral brain ratio in the target tumors which was about 2 times that of the control tumors. This research demonstrates that pulsed HIFU enhances the relative permeability of the BTB in glioma- bearing rats. The results of this pilot study support the idea that further evaluation of other treatment strategies, such as HIFU exposure in addition to combined chemotherapy or repeated pulsed HIFU exposure to increase delivery of drugs into brain tumors, might be useful.

Purpose: To investigate the correlation between the contrast-enhanced magnetic resonance imaging (MRI) signal and the duration of blood-brain barrier (BBB) disruption induced by focused ultrasound (FUS).Materials and Methods: FUS was applied to 45 rat brains in the presence of microbubbles, and these rats were scanned on a 3T MRI system at several timepoints. The rat brains were then studied using contrast-enhanced spin echo T1-weighted images. At the same time, BBB disruption was evaluated based on Evans blue (EB) extravasation. The relationship between the normalized signal intensity change of the MRI and EB extravasation was analyzed by least-squares linear regression and the calculation of correlation coefficients.Results: When MRI enhancement was quantitatively evaluated by EB extravasation, a strong correlation between the normalized signal intensity change of the MRI and EB extravasation was identified during BBB disruption after sonication. However, the correlation coefficient decreased as BBB closure occurred after sonication ended. Conclusion:The contrast-enhanced MRI signal can potentially be used to evaluate the amount of chemotherapeutic agents entering the targeted tissue, but the accuracy of the assessment will be affected by the time interval since sonication.

Probabilistic constrained simulation optimization problems (PCSOP) are concerned with allocating limited resources to achieve a stochastic objective function subject to a probabilistic inequality constraint. The PCSOP are NP-hard problems whose goal is to find optimal solutions using simulation in a large search space. An efficient “Ordinal Optimization (OO)” theory has been utilized to solve NP-hard problems for determining an outstanding solution in a reasonable amount of time. OO theory to solve NP-hard problems is an effective method, but the probabilistic inequality constraint will greatly decrease the effectiveness and efficiency. In this work, a method that embeds ordinal optimization (OO) into tree–seed algorithm (TSA) (OOTSA) is firstly proposed for solving the PCSOP. The OOTSA method consists of three modules: surrogate model, exploration and exploitation. Then, the proposed OOTSA approach is applied to minimize the expected lead time of semi-finished products in a pull-type production system, which is formulated as a PCSOP that comprises a well-defined search space. Test results obtained by the OOTSA are compared with the results obtained by three heuristic approaches. Simulation results demonstrate that the OOTSA method yields an outstanding solution of much higher computing efficiency with much higher quality than three heuristic approaches.

Using multiple parameters (GA, BPD and HC) to estimate NBL is more accurate than using than using GA or BPD or HC alone, as indicated by the higher predictive value.