Purpose: The deterministic Acuros XB (AXB) algorithm was recently implemented in the Eclipse treatment planning system. The goal of this study was to compare AXB performance to Monte Carlo (MC) and two standard clinical convolution methods: the anisotropic analytical algorithm (AAA) and the collapsed-cone convolution (CCC) method. Methods: Homogeneous water and multilayer slab virtual phantoms were used for this study. The multilayer slab phantom had three different materials, representing soft tissue, bone, and lung. Depth dose and lateral dose profiles from AXB v10 in Eclipse were compared to AAA v10 in Eclipse, CCC in Pinnacle 3 , and EGSnrc MC simulations for 6 and 18 MV photon beams with open fields for both phantoms. In order to further reveal the dosimetric differences between AXB and AAA or CCC, three-dimensional (3D) gamma index analyses were conducted in slab regions and subregions defined by AAPM Task Group 53. Results: The AXB calculations were found to be closer to MC than both AAA and CCC for all the investigated plans, especially in bone and lung regions. The average differences of depth dose profiles between MC and AXB, AAA, or CCC was within 1.1, 4.4, and 2.2%, respectively, for all fields and energies. More specifically, those differences in bone region were up to 1.1, 6.4, and 1.6%; in lung region were up to 0.9, 11.6, and 4.5% for AXB, AAA, and CCC, respectively. AXB was also found to have better dose predictions than AAA and CCC at the tissue interfaces where backscatter occurs. 3D gamma index analyses (percent of dose voxels passing a 2%/2 mm criterion) showed that the dose differences between AAA and AXB are significant (under 60% passed) in the bone region for all field sizes of 6 MV and in the lung region for most of field sizes of both energies. The difference between AXB and CCC was generally small (over 90% passed) except in the lung region for 18 MV 10 Â 10 cm 2 fields (over 26% passed) and in the bone region for 5 Â 5 and 10 Â 10 cm 2 fields (over 64% passed). With the criterion relaxed to 5%/2 mm, the pass rates were over 90% for both AAA and CCC relative to AXB for all energies and fields, with the exception of AAA 18 MV 2.5 Â 2.5 cm 2 field, which still did not pass. Conclusions: In heterogeneous media, AXB dose prediction ability appears to be comparable to MC and superior to current clinical convolution methods. The dose differences between AXB and AAA or CCC are mainly in the bone, lung, and interface regions. The spatial distributions of these differences depend on the field sizes and energies.

Glutamate-induced excitotoxicity has been implicated in the etiology of stroke, epilepsy, and neurodegenerative diseases. NMDA receptors (NMDARs) play a pivotal role in excitotoxic injury; however, clinical trials testing NMDAR antagonists as neuroprotectants have been discouraging. The development of novel neuroprotectant molecules is being vigorously pursued. Here, we report that downstream regulatory element antagonist modulator (DREAM) significantly inhibits surface expression of NMDARs and NMDAR-mediated current. Overexpression of DREAM showed neuroprotection against excitotoxic neuronal injury, whereas knockdown of DREAM enhanced NMDA-induced toxicity. DREAM could directly bind to the C0 domain of the NR1 subunit. Although DREAM contains multiple binding sites for the NR1 subunit, residues 21-40 of the N terminus are the main binding site for the NR1 subunit. Thus, 21-40 residues might relieve the autoinhibition conferred by residues 1-50 and derepress the DREAM core domain by a competitive mechanism. Intriguingly, the cell-permeable TAT-21-40 peptide, constructed according to the critical binding site of DREAM to the NR1 subunit, inhibits NMDARmediated currents in primary cultured hippocampal neurons and has a neuroprotective effect on in vitro neuronal excitotoxic injury and in vivo ischemic brain damage. Moreover, both pretreatment and posttreatment of TAT-21-40 is effective against excitotoxicity. In summary, this work reveals a novel, negative regulator of NMDARs and provides an attractive candidate for the treatment of excitotoxicity-related disease.

AXB was found to be satisfactorily accurate when compared to measurements in the RPC H&N phantom. Compared with AAA, AXB results were equal to or better than those obtained with film measurements for IMRT and VMAT plans. The AXB_D(m,m) reporting mode was found to be closer to TLD and film measurements than was the AXB_D(w,m) mode. AXB calculation time was found to be significantly shorter (× 4) than AAA for VMAT.

Purpose:The novel deterministic radiation transport algorithm, Acuros XB (AXB), has shown great potential for accurate heterogeneous dose calculation. However, the clinical impact between AXB and other currently used algorithms still needs to be elucidated for translation between these algorithms. The purpose of this study was to investigate the impact of AXB for heterogeneous dose calculation in lung cancer for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Methods: The thorax phantom from the Radiological Physics Center (RPC) was used for this study. IMRT and VMAT plans were created for the phantom in the Eclipse 11.0 treatment planning system. Each plan was delivered to the phantom three times using a Varian Clinac iX linear accelerator to ensure reproducibility. Thermoluminescent dosimeters (TLDs) and Gafchromic EBT2 film were placed inside the phantom to measure delivered doses. The measurements were compared with dose calculations from AXB 11.0.21 and the anisotropic analytical algorithm (AAA) 11.0.21. Two dose reporting modes of AXB, dose-to-medium in medium (D m,m ) and dose-to-water in medium (D w,m ), were studied. Point doses, dose profiles, and gamma analysis were used to quantify the agreement between measurements and calculations from both AXB and AAA. The computation times for AAA and AXB were also evaluated. Results: For the RPC lung phantom, AAA and AXB dose predictions were found in good agreement to TLD and film measurements for both IMRT and VMAT plans. TLD dose predictions were within 0.4%-4.4% to AXB doses (both D m,m and D w,m ); and within 2.5%-6.4% to AAA doses, respectively. For the film comparisons, the gamma indexes (±3%/3 mm criteria) were 94%, 97%, and 98% for AAA, AXB_D m,m , and AXB_D w,m , respectively. The differences between AXB and AAA in dosevolume histogram mean doses were within 2% in the planning target volume, lung, heart, and within 5% in the spinal cord. However, differences up to 8% between AXB and AAA were found at lung/soft tissue interface regions for individual IMRT fields. AAA was found to be 5-6 times faster than AXB for IMRT, while AXB was 4-5 times faster than AAA for VMAT plan. Conclusions: AXB is satisfactorily accurate for the dose calculation in lung cancer for both IMRT and VMAT plans. The differences between AXB and AAA are generally small except in heterogeneous interface regions. AXB D w,m and D m,m calculations are similar inside the soft tissue and lung regions. AXB can benefit lung VMAT plans by both improving accuracy and reducing computation time.