Background Volumetric modulated arc therapy (VMAT) has been shown feasible for radiosurgical treatment of multiple cranial lesions with a single isocenter. Objective To investigate whether equivalent radiosurgical plan quality and reduced delivery time could be achieved in VMAT for patients with multiple intracranial targets previously treated with Gamma Knife (GK) radiosurgery. Methods We identified 28 Gamma Knife treatments of multiple metastases. These were replanned for multi-arc (MA) and single-arc (SA), single-isocenter VMAT (RapidArc) in Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan was normalized for 100% prescription dose to 99–100% of target volume. Plan quality was analyzed by target conformity (RTOG, Paddick CI), dose fall-off (area under DVH curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other endpoints included beam-on and treatment time. Results Compared to Gamma Knife, multi-arc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; p<0.001) with no significant difference in median dose fall-off (p=0.269), 12Gy isodose volume (p=0.500), or low isodose spill (p=0.49). Multi-arc VMAT plans were associated with markedly reduced treatment time. A predictive model of the 12Gy isodose volume as a function of tumor number and volume was also developed. Conclusion For multiple target SRS, 4-arc VMAT produced clinically equivalent conformity, dose fall-off, 12 Gy isodose volume, and low isodose spill, and reduced treatment time compared to GK. Due to its similar plan quality and increased delivery efficiency, single-isocenter VMAT radiosurgery may constitute an attractive alternative to multi-isocenter radiosurgery for some patients.

The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca2+ channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca2+ oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.

We have implemented a three-dimensional dose calculation technique accounting for dose inhomogeneity within the liver and tumor of a patient treated with 90Y microspheres. Single-photon emission computed tomography (SPECT) images were used to derive the activity distribution within liver. A Monte Carlo calculation was performed to create a voxel dose kernel for the 90Y source. The activity distribution was convolved with the voxel dose kernel to obtain the three-dimensional (3D) radiation absorbed dose distribution. An automated technique was developed to accurately register the computed tomography (CT) and SPECT scans in order to display the 3D dose distribution on the CT scans. In addition, dose-volume histograms were generated to fully analyze the tumor and liver doses. The calculated dose-volume histogram indicated that although the patient was treated to the nominal whole liver dose of 110 Gy, only 16% of the liver and 83% of the tumor received a dose higher than 110 Gy. The mean tumor and liver doses were 163 and 58 Gy, respectively.

We propose a new method for selecting importance factors (for regions of interest like organs at risk) used to plan conformal radiotherapy. Importance factors, also known as weighting factors or penalty factors, are essential in determining the relative importance of multiple objectives or the penalty ratios of constraints incorporated into cost functions, especially in dealing with dose optimization in radiotherapy treatment planning. Researchers usually choose importance factors on the basis of a trial-and-error process to reach a balance between all the objectives. In this study, we used a genetic algorithm and adopted a real-number encoding method to represent both beam weights and importance factors in each chromosome. The algorithm starts by optimizing the beam weights for a fixed number of iterations then modifying the importance factors for another fixed number of iterations. During the first phase, the genetic operators, such as crossover and mutation, are carried out only on beam weights, and importance factors for each chromosome are not changed or 'frozen'. In the second phase, the situation is reversed: the beam weights are 'frozen' and the importance factors are changed after crossover and mutation. Through alternation of these two phases, both beam weights and importance factors are adjusted according to a fitness function that describes the conformity of dose distribution in planning target volume and dose-tolerance constraints in organs at risk. Those chromosomes with better fitness are passed into the next generation, showing that they have a better combination of beam weights and importance factors. Although the ranges of the importance factors should be set in advance by using this algorithm, it is much more convenient than selecting specific numbers for importance factors. Three clinical examples are presented and compared with manual plans to verify this method. Three-dimensional standard displays and dose-volume histograms are shown to demonstrate that this method is feasible, automatic and convenient.