Differentiation of brain tumor-related edema based on 3D T1rho imaging.

BACKGROUND AND PURPOSE: Cerebral edema associated with brain tumors is an important source of morbidity. Its type depends largely on the capillary ultra-structures of the histopathologic subtype of underlying brain tumor. The purpose of our study was to differentiate vasogenic edema associated with brain metastases and infiltrative edema related to diffuse gliomas using quantitative 3D T1 rho (T1ρ) imaging. MATERIALS AND METHODS: Preoperative MR examination including whole brain 3D T1ρ imaging was performed in 23 patients with newly diagnosed brain tumors (9 with metastasis, 8 with lower grade glioma, LGG, 6 with glioblastoma, GBM). Mean T1ρ values were measured in regions of peritumoral non-enhancing T2 signal hyperintensity, excluding both enhancing and necrotic or cystic component, and normal-appearing white matter. RESULTS: Mean T1ρ values were significantly elevated in the vasogenic edema surrounding intracranial metastases when compared to the infiltrative edema associated with either LGG or GBM (p=0.02 and <0.01, respectively). No significant difference was noted between T1ρ values of infiltrative edema between LGG and GBM (p=0.84 and 0.96, respectively). CONCLUSION: Our study demonstrates the feasibility and potential diagnostic role of T1ρ in the quantitative differentiation between edema related to intracranial metastases and gliomas and as a potentially complementary tool to standard MR techniques in further characterizing pathophysiology of vasogenic and infiltrative edema.

SU-E-T-568: Hippocampus and Neural Stemcell Sparing Using Proton Therapy in Whole Brain Irradiation.

PURPOSE: To investigate feasibility of using proton therapy (PT) in neural stemcell sparing and to compare its dosimetric advantage to IMRT. To investigate the robustness of the proton plan in hippocampus sparing by introducing translation and rotation errors in treatment plan. METHODS: Hippocampal neurogenesis directly correlates to memory and other cognitive functions. Compared to the traditional whole brain (WB) uniform irradiation, Photon Intensity-Modulated-Radiation-Therapy (IMRT) can reduce hippocampal dose somewhat but limited by its beam exit dose. Pinnacle and Eclipse were used, respectively, for IMRT and PT planning (30Gy in 10 fractions) for hippocampal neural stemcell sparing WB irradiation. Both hippocampus and neural stemcell regions were contoured as avoidance region. Similar to RTOG0933, the target was defined as the WB subtracted by 5 mm expansion of the avoidance region. Other organs-at- risk (OARs) includes lenses, eyes, optical chiasm, optical nerves, brainstem and parotids. Twelve coplanar beams were used in IMRT plans with 2.5mm MLC width. Objectives were specified to maximize target coverage and reduce dose to avoidance region and to other OARs. There were 9 non- coplanar proton beams that include 2 pairs of patch fields, 1 pair of match fields and 4 open fields. Distal blocking was used in 5 beams. RESULTS: Both plans' target coverage was scaled at 70% target covered by 30Gy. Plan comparison between proton and IMRT are, respectively, as follows: Target D2 (36.2, 37.3Gy); Mean dose to avoidance region (0.96, 5Gy); mean doses to left-lens (0.21, 3.35Gy); mean doses to right-lens (0.25, 3.57Gy); mean dose to left-parotid (0.82, 9.57Gy) and right-parotid (0.11, 11.6Gy). Similar dose distribution found in brainstem, eyes and optical nerves and chiasm for both proton and IMRT plans. CONCLUSIONS: Proton plan demonstrated dosimetric advantage in neural stemcell and hippocampus sparing than IMRT plan. The proton plan is robust from translation and rotation setup errors.

SU-E-T-446: Effect of Dose Calculation Grid Size Variability on the Specification of Spinal Cord Dose Tolerance for Spinal Stereotactic Body Radiation Therapy.

PURPOSE: To investigate the effect of the dose grid resolution variability on the spinal cord dose for spinal SBRT treatments. METHOD: 10 CyberKnife plans were selected for the proximity of the PTV to the spinal cord. All dose distributions were calculated with Monte Carlo using high spatial resolution and minimal relative uncertainty. The plans were renormalized to a 16 Gy prescription dose and to ensure a target coverage > 95% in order to compare the calculated dose distributions. Each dose matrix was resampled 12 times, covering a grid resolution range of 0.95 mm to 13.52 mm. The spinal cord DVHs were generated for each resampled dose grid. The variations of the maximum point dose (DmaxCord) and dose-coverage to partial volumes (D[V]) up to 5 cc were investigated against the grid resolution. RESULTS: The mean variation of DmaxCord with grid resolution is characterized by an inverse power law, with a sharp initial decrease leading to potentially large underestimates of DmaxCord (24%, 40% and 55% at resolutions of 2 mm, 4 mm and 8 mm). The variability of mean D[V] values decreases from smaller to larger grid resolutions, however large disparities are observed between patient plans. We introduced the variability threshold volume (Vth) as a constraint to express the dose coverage independently from the grid resolution. For resolutions up to 8 mm, the mean Vth value is (0.96±0.10) cc with a corresponding dose coverage of (26± 12) % relative to the initial DmaxCord value. CONCLUSIONS: Dose distributions calculated with grid resolutions larger than 2 mm could Result in significant underestimates of DmaxCord. Furthermore, the sensitivity of the dose coverage to grid resolution variability is patient dependent. Consequently, a specified cord dose tolerance should be quoted at a particular grid resolution uniformly adopted between institutions; 2 mm or less is an appropriate value.

A two-step optimization method for improving multiple brain lesion treatments with robotic radiosurgery.

Planning robotic radiosurgery treatments for multiple (n > 3) metastatic brain lesions is challenging due to the need of satisfying a large number of dose-volume constraints and the requirement of prescribing different dose levels to individual targets. In this study, we developed a sequential two-step optimization technique to improve the planning quality of such treatments. In contrast to the conventional approach of where all targets are simultaneously planned, we have developed a two-step optimization method. In this method, the first step was to create treatment plans for individual targets. In the second step, the 3D dose matrices associated with each plan were exported to Dicom-RT digital files and subsequently optimized. For the optimization, a singular-value-decomposition (SVD) algorithm was implemented to minimize the dose interferences among different targets. Finally, we compared the optimized treatment plans with the treatment plans created using the conventional method to determine the effectiveness of the new method. Large improvements in target dose distributions as well as normal brain sparing were found for the two-step optimization treatment plans as compared with the conventional treatment plans. The two-step optimization significantly lowered the volume of normal brain receiving relatively low doses. For example, the normal brain volume receiving 12-Gy was reduced by averaged 42% (range 34%-47%) with the two-step optimization. Such improvements generally enlarged with increasing number of targets being treated regardless of target sizes. Of note, normal brain dose was found to increase non-linearly with increasing number of targets. In summary, a two-step optimization technique is demonstrated to significantly improve the treatment plan quality as well as reduce the planning effort for multi-target robotic radiosurgery.

A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: a radiobiological modeling study.

A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.

Nature of the chromophore binding site of bacteriorhodopsin: the potential role of Arg82 as a principal counterion.

The nature of the chromophore binding site of light-adapted bacteriorhodopsin is analyzed by using modified neglect of differential overlap with partial single and double configuration interaction (MNDO-PSDCI) molecular orbital theory to interpret previously reported linear and nonlinear optical spectroscopic measurements. We conclude that in the absence of divalent metal cations in close interaction with Asp85 and Asp212, a positively charged amino acid must be present in the same vicinity. We find that models in which Arg82 is pointed upward into the chromophore binding site and directly stabilizes Asp85 and Asp212 are successful in rationalizing the observed one-photon and two-photon properties. We conclude further that a water molecule is strongly hydrogen bonded to the chromophore imine proton. The chromophore "1Bu*+" and "1Ag*-" states, despite extensive mixing, exhibit significantly different configurational character. The lowest-lying "1Bu*+" state is dominated by single excitations, whereas the second-excited "1Ag*-" state is dominated by double excitations. We can rule out the possibility of a negatively charged binding site, because such a site would produce a lowest-lying "1Ag*-" state, which is contrary to experimental observation. The possibility that Arg82 migrates toward the extracellular surface during the photocycle is examined.