Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct monte carlo methods.

Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS: The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION: This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation

Trafficking of High Avidity HER-2/neu-Specific T Cells into HER-2/neu-Expressing Tumors after Depletion of Effector/Memory-Like Regulatory T Cells

Cancer vaccines are designed to activate and enhance cancer-antigen-targeted T cells that are suppressed through multiple mechanisms of immune tolerance in cancer-bearing hosts. T regulatory cell (Treg) suppression of tumor-specific T cells is one barrier to effective immunization. A second mechanism is the deletion of high avidity tumor-specific T cells, which leaves a less effective low avidity tumor specific T cell repertoire available for activation by vaccines. Treg depleting agents including low dose cyclophosphamide (Cy) and antibodies that deplete CD25-expressing Tregs have been used with limited success to enhance the potency of tumor-specific vaccines. In addition, few studies have evaluated mechanisms that activate low avidity cancer antigen-specific T cells. Therefore, we developed high and low avidity HER-2/neu-specific TCR transgenic mouse colonies specific for the same HER-2/neu epitope to define the tolerance mechanisms that specifically affect high versus low avidity tumor-specific T cells.High and low avidity CD8(+) T cell receptor (TCR) transgenic mice specific for the breast cancer antigen HER-2/neu (neu) were developed to provide a purified source of naïve, tumor-specific T cells that can be used to study tolerance mechanisms. Adoptive transfer studies into tolerant FVB/N-derived HER-2/neu transgenic (neu-N) mice demonstrated that high avidity, but not low avidity, neu-specific T cells are inhibited by Tregs as the dominant tolerizing mechanism. High avidity T cells persisted, produced IFNγ, trafficked into tumors, and lysed tumors after adoptive transfer into mice treated with a neu-specific vaccine and low dose Cy to deplete Tregs. Analysis of Treg subsets revealed a Cy-sensitive CD4(+)Foxp3(+)CD25(low) tumor-seeking migratory phenotype, characteristic of effector/memory Tregs, and capable of high avidity T cell suppression.Depletion of CD25(low) Tregs allows activation of tumor-clearing high avidity T cells. Thus, the development of agents that specifically deplete Treg subsets should translate into more effective immunotherapies while avoiding autoimmunity

Identification of medium mass (A=60-80) ejectiles from 15 MeV/nucleon peripheral heavy-ion collisions with the MAGNEX large-acceptance spectrometer

An approach to identify medium-mass ejectiles from peripheral heavy-ion reactions in the energy region of 15 MeV/nucleon is developed for data obtained with a large acceptance magnetic spectrometer. This spectrometer is equipped with a focal plane multidetector, providing position, angle, energy loss and residual energy of the ions along with measurement of the time-of-flight. Ion trajectory reconstruction is performed at high order and ion mass is obtained with a resolution of better than 1/150. For the unambiguous particle identification however, the reconstruction of both the atomic number Z and the ionic charge q of the ions is critical and it is suggested, within this work, to be performed prior to mass identification. The new proposed method was successfully applied to MAGNEX spectrometer data, for identifying neutron-rich ejectiles related to multinucleon transfer generated in the 70Zn+ 64Ni collision at 15 MeV/nucleon. This approach opens up the possibility of employing heavy-ion reactions with medium-mass beams below the Fermi energy (i.e., in the region 15-25 MeV/nucleon) in conjunction with large acceptance ray tracing spectrometers, first, to study the mechanism(s) of nucleon transfer in these reactions and, second, to produce and study very neutron-rich or even new nuclides in previously unexplored regions of the nuclear landscape.Comment: 6 pages, 6figure

Characterization of a gas detector prototype based on Thick-GEM for the MAGNEX focal plane detector

A new gas detector prototype for the upgrade of the focal plane detector of the MAGNEX large-acceptance magnetic spectrometer has been developed and tested in view of the NUMEN project. It has been designed to operate at low gas pressure for detecting medium to heavy ions in the energy range between 15 and 60 AMeV. It is a drift chamber based on Multi-layer Thick-GEM (M-THGEM) as electron multiplication technology. Tests with two different M-THGEM layouts have been performed using both a radioactive $\alpha$-particle source and accelerated heavy-ion beams. The characterization of the detector in terms of measured currents that flow through the electrodes as a function of different parameters, including applied voltages, gas pressure and rate of incident particle, is described. The gain and ion backflow properties have been studied

Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS)

Purpose: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. Methods: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)—a prospective, multicenter study of infants (\u3c 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. Results: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. Conclusion: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment

Treatment of atypical central neurocytoma in a child with high dose chemotherapy and autologous stem cell rescue

The authors describe a 9 month old female with recurrent atypical central neurocytoma and leptomeningeal spread treated with high dose chemotherapy, autologous stem cell rescue, and adjuvant therapy. She had a complete response to therapy and was disease free at 4 years of age until a recurrence 6 months later. The use of intensive chemotherapy followed by autologous stem cell rescue for atypical neurocytoma may be considered as an adjunct to surgical therapy in young patients with atypical neurocytoma not amenable to radiation therapy

Background estimate in heavy-ion two-body reactions measured by the MAGNEX spectrometer

The MAGNEX magnetic spectrometer is nowadays used in the experimental measurements of rare quasi-elastic reactions between heavy ions at intermediate energy within the NUMEN project. The small cross sections involved in such processes under the large yields due to competitive reaction channels have motivated an accurate control of the background sources. In such view, the not ideal particle identification could introduce spurious contributions which have been identified and evaluated in the present analysis

One-neutron transfer reaction in the 18^{18}O + 48^{48}Ti collision at 275 MeV

The present article reports new data on the $^{48}$Ti($^{18}$O,$^{17}$O)$^{49}$Ti reaction at 275 MeV incident energy as part of the systematic research pursued within the NUMEN project. Supplementary measurements of the same reaction on $^{16}$O and $^{27}$Al targets were also performed in order to estimate the background arising from the use of a composite target (TiO$_{2}$ + $^{27}$Al). These data were analyzed under the same theoretical framework as those obtained with the titanium target in order to reinforce the conclusions of our analysis. Differential cross-section angular distribution measurements for the $^{17}$O$^{8+}$ ejectiles were performed in a wide angular range by using the MAGNEX large acceptance magnetic spectrometer. The experimental results were analyzed within the distorted-wave and coupled-channels Born Approximation frameworks. The optical potentials at the entrance and exit channels were calculated in a double folding approach adopting the S\~ao Paulo potential, and the spectroscopic amplitudes for the projectile and target overlaps were obtained from large-scale shell model calculations. The differential cross-sections are well-described by the theoretical calculations, where a weak coupling to collective excitations of projectile and target is inferred. The sensitivity of transfer cross-sections on different model spaces adopted in nuclear structure calculations, is also discussed