Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.

AIM: To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). MATERIALS AND METHODS: Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. RESULTS: No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). CONCLUSION: In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts.

Dose heterogeneity correction for low-energy brachytherapy sources using dual-energy CT images.

Permanent seed implant brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose around brachytherapy sources is based on the AAPM TG-43 formalism, which generates the dose in a homogeneous water medium. Recently, AAPM TG-186 emphasized the importance of accounting for tissue heterogeneities. We have previously reported on a methodology where the absorbed dose in tissue can be obtained by multiplying the dose, calculated by the TG-43 formalism, by an inhomogeneity correction factor (ICF). In this work we make use of dual energy CT (DECT) images to extract ICF parameters. The advantage of DECT over conventional CT is that it eliminates the need for tissue segmentation as well as assignment of population based atomic compositions. DECT images of a heterogeneous phantom were acquired and the dose was calculated using both TG-43 and TG-43 [Formula: see text] formalisms. The results were compared to experimental measurements using Gafchromic films in the mid-plane of the phantom. For a seed implant configuration of 8 seeds spaced 1.5 cm apart in a cubic structure, the gamma passing score for 2%/2 mm criteria improved from 40.8% to 90.5% when ICF was applied to TG-43 dose distributions.

A Monte Carlo-based model of gold nanoparticle radiosensitization accounting for increased radiobiological effectiveness.

Radiosensitization using gold nanoparticles (AuNPs) has been shown to vary widely with cell line, irradiation energy, AuNP size, concentration and intracellular localization. We developed a Monte Carlo-based AuNP radiosensitization predictive model (ARP), which takes into account the detailed energy deposition at the nano-scale. This model was compared to experimental cell survival and macroscopic dose enhancement predictions. PC-3 prostate cancer cell survival was characterized after irradiation using a 300 kVp photon source with and without AuNPs present in the cell culture media. Detailed Monte Carlo simulations were conducted, producing individual tracks of photoelectric products escaping AuNPs and energy deposition was scored in nano-scale voxels in a model cell nucleus. Cell survival in our predictive model was calculated by integrating the radiation induced lethal event density over the nucleus volume. Experimental AuNP radiosensitization was observed with a sensitizer enhancement ratio (SER) of 1.21 ± 0.13. SERs estimated using the ARP model and the macroscopic enhancement model were 1.20 ± 0.12 and 1.07 ± 0.10 respectively. In the hypothetical case of AuNPs localized within the nucleus, the ARP model predicted a SER of 1.29 ± 0.13, demonstrating the influence of AuNP intracellular localization on radiosensitization.

A public image database to support research in computer aided diagnosis.

The Public Lung Database to address drug response (PLD) has been developed to support research in computer aided diagnosis (CAD). Originally established for applications involving the characterization of pulmonary nodules, the PLD has been augmented to provide initial datasets for CAD research of other diseases. In general, the best performance for a CAD system is achieved when it is trained with a large amount of well documented data. Such training databases are very expensive to create and their lack of general availability limits the targets that can be considered for CAD applications and hampers development of the CAD field. The approach taken with the PLD has been to make available small datasets together with both manual and automated documentation. Furthermore, datasets with special properties are provided either to span the range of task complexity or to provide small change repeat images for direct calibration and evaluation of CAD systems. This resource offers a starting point for other research groups wishing to pursue CAD research in new directions. It also provides an on-line reference for better defining the issues relating to specific CAD tasks.

Monte Carlo study of LDR seed dosimetry with an application in a clinical brachytherapy breast implant.

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.

Sci-Thurs PM: Delivery-03: Optical imaging of microscopic radiation dose gradients using a digital microscope.

Using superior localization and immobilization methods, stereotactic radiosurgery is capable of delivering spheres of dose as small as a few millimetres in diameter to intracranial targets. For targets abutting critical structures, the most conformal treatments minimize adverse radiation side effects and it is important, therefore, to ensure proper quality assurance prior to delivering high doses of radiation to eloquent brain locations in a single fraction. This work examines the capability of a digital microscope, with translation stage and associated software, to resolve dose gradients in Gafchromic EBT™ film at the micron level. In order to validate the microscope-film system from a radiation physics approach, films were irradiated to produce very steep penumbrae by using very small fields, lower photon energies and minimal geometric penumbra contribution. Orthovoltage film irradiations were done by placing films in phantom beneath pinhole collimators. The experimentally determined off-axis dose profiles were compared with Monte Carlo computer simulations which replicated the irradiation geometry and served to validate our measured data. The measured 80% - 20% penumbral widths were 46 µm ± 26 µm (100 kVp, 2 mm field size) and 69 µm ± 27 µm (300 kVp, 2 mm field size). In the energy range covered, the measured penumbral widths agreed with Monte Carlo computer simulations within experimental uncertainty. The effects of noise originating from both the film and the microscope system are discussed and improvements to this system suggested.

Hyperthermia (heat shock)-induced protein denaturation in liver, muscle and lens tissue as determined by differential scanning calorimetry.

Protein denaturation has been shown to occur in cells during heat shock and is closely correlated with the cellular responses to hyperthermia; however, little is known about protein denaturation in tissue. This study describes an analysis of endothermic transitions in the hyperthermic region using differential scanning calorimetry (DSC) in liver, white muscle, and lens tissue from Wistar rat, New Zealand white rabbit, and Rainbow trout. Complex DSC profiles consisting of several transitions were obtained for each tissue. Evidence is given that these transitions are due primarily to protein denaturation. Onset temperatures of denaturation (Tl) for rat liver, muscle, and lens are about 38, 39 and 48 degrees C, respectively. Thus, significant protein denaturation occurs in liver and muscle during mild hyperthermia (40-45 degrees C) with lens considerably more stable. The values of Tl for the same tissue from the different animals correlates well with body temperature (rabbit 39.4, rat 38.2, and trout grown at 11 degrees C); Tl increased in the same order as the body temperature for each tissue. Thus, there is correlation between the onset temperature for protein denaturation in these tissues and body temperature.

Imaging of HDR brachytherapy dose distributions using NMR Fricke-gelatin dosimetry.

The application of NMR Fricke-gelatin dosimetry to the imaging of dose distributions around high dose rate (HDR) radioactive Ir-192 seeds in brachytherapy is presented. The duration of the irradiations required to give changes of the Fricke-gelatin NMR characteristics, which were readily detected by the magnetic resonance imager, typically ranged from 4 to 25 min for single source and multiple source (33 source positions distributed among three catheters) geometries, respectively. A fast approach for determining radiation dose from MR image intensity using a calibration curve is described. NMR Fricke-gel dosimetry is shown to be a viable means of verifying the dose distributions from brachytherapy sources.