Low-molecular-weight heparin adherence and effects on survival within a randomised phase III lung cancer trial (RASTEN).

BACKGROUND: Coagulation activation is a hallmark of cancer, and anticoagulants have shown tumour-inhibiting properties. However, recent trials have failed to demonstrate improved survival with low-molecular-weight heparin (LMWH) in cancer populations. This has raised the question of suboptimal adherence as a possible explanation for the lack of benefit. Still, there is no standardised method to directly monitor LMWH in patient plasma. Here, we directly determine LMWH levels in patients using the Heparin Red assay to objectively assess adherence and how this associates with the patient outcome in the RASTEN trial. METHODS: RASTEN is a multicentre, randomised phase III trial investigating if the addition of LMWH to standard therapy can improve survival in small-cell lung cancer. LMWH was measured in plasma (N = 258) by the Heparin Red assay and compared with the anti-factor Xa (anti-FXa) activity assay. RESULTS: Both methods could differentiate patients in the LMWH arm from the control arm and patients receiving therapeutic LMWH owing to thrombosis. Receiver Operating Characteristic (ROC) analysis yielded adherence rates of 85% for anti-FXa and 68% for Heparin Red. No survival benefits were found in the adherent subgroup compared with the control arm (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.95-1.67; P = 0.105 and HR: 1.19; 95% CI: 0.89-1.60; P = 0.248 for anti-FXa and Heparin Red, respectively). Heparin Red could define patients with high probability of adherence to LMWH treatment, which warrants prospective studies for further validation. Our finding that the LMWH-adherent subpopulation did not show improved survival excludes that the negative outcome of RASTEN was due to poor adherence.

Disparities in Obesity, Physical Activity Rates, and Breast Cancer Survival.

The significantly higher breast cancer (BCa) mortality rates of African-American (AA) women compared to non-Hispanic (NHW) white women constitute a major US health disparity. Investigations have primarily focused on biological differences in tumors to explain more aggressive forms of BCa in AA women. The biology of tumors cannot be modified, yet lifestyle changes can mitigate their progression and recurrence. AA communities have higher percentages of obesity than NHWs and exhibit inefficient access to care, low socioeconomic status, and reduced education levels. Such factors are associated with limited healthy food options and sedentary activity. AA women have the highest prevalence of obesity than any other racial/ethnic/gender group in the United States. The social ecological model (SEM) is a conceptual framework on which interventions could be developed to reduce obesity. The SEM includes intrapersonal factors, interpersonal factors, organizational relationships, and community/institutional policies that are more effective in behavior modification than isolation from the participants' environmental context. Implementation of SEM-based interventions in AA communities could positively modify lifestyle behaviors, which could also serve as a powerful tool in reducing risk of BCa, BCa progression, and BCa recurrence in populations of AA women.

Prostatic artery embolization: radiation exposure to patients and staff.

The aim of this study was to evaluate the radiation doses to patients and staff received from the first cases of prostatic artery embolization (PAE) conducted in a public hospital in Recife, Brazil. Five PAE procedures for 5 men diagnosed with benign prostatic hyperplasia were investigated. In order to characterize patient exposure, dosimetric quantities, such as the air kerma-area product (P KA), the cumulative air kerma at the interventional reference point (Ka,r), the number of images, etc, were registered. To evaluate the possibility for deterministic effects, the peak skin dose (PSD) was measured using radiochromic films. For evaluation of personal dose equivalent and effective dose to the medical staff, thermoluminescent dosemeters (TLD-100) were used. The effective dose was estimated using the double dosimetry alghoritm of von Boetticher. The results showed that the mean patient's PSD per procedure was 2674.2 mGy. With regard to the medical staff, the mean, minimum and maximum effective doses estimated per procedure were: 18 µSv, 12 µSv and 21 µSv respectively. High personal equivalent doses were found for the feet, hands and lens of the eye, due to the use of multiple left anterior oblique projections and the improper use of the suspended lead screen and the lead curtain during procedures.

Evaluation of staff, patient and foetal radiation doses due to endoscopic retrograde cholangiopancreatography (ERCP) procedures in a pregnant patient.

The use of endoscopic retrograde cholangiopancreatography (ERCP) in pregnant patients is not rare. Most studies on the safety and efficacy of these procedures report short- and long-term pregnancy outcomes and but not foetal absorbed doses. This investigation reports on an ERCP procedure for a 40-y-old woman who was 32-34 weeks pregnant. Thermoluminescent dosemeters (TLD 100) were used to measure doses received by the patient and the staff. Additionally, Monte Carlo calculations were performed using a 3D computational phantom representing a 9-month pregnant patient to estimate the foetal absorbed dose. The results show that the spleen of the mother received the largest absorbed dose of 12.18 mGy since it was closer to the source than other internal organs. For the foetus and uterus, the lowest absorbed dose was found to be 0.01 mGy to the foetal brain, while the largest absorbed dose was estimated to be 0.13 mGy to the placenta.

ErbB3 upregulation by the HNSCC 3D microenvironment modulates cell survival and growth.

Head and neck squamous carcinomas (HNSCC) present as dense epithelioid three-dimensional (3D) tumor nests that can mediate signals via the human epidermal growth factor receptor (ErbB) tyrosine kinase family to promote intratumoral survival and growth. We examined the role of the tumor microenvironment on ErbB receptor family expression and found that the status of intercellular organization altered the receptor profile. We showed that HNSCC cells forced into tumor island-like 3D aggregates strongly upregulated ErbB3 at the level of transcription. Not only was the elevated ErbB3 responsive to HRG-ß1-induced enhanced signaling mechanism, but also analysis by siRNA-knockdown and kinase inhibitor strategies revealed that the ErbB3/AKT signaling pathway was sufficient to enhance tumor cell survival and growth potential. Elevated ErbB3 expression in the high-density 3D culture system was strongly associated with hypoxia-induced HIF-1α. Hypoxia-regulated ErbB3 expression was mediated by the HIF-1α-binding consensus sequence in the ErbB3 proximal promoter. The findings show that the local 3D tumor microenvironment can trigger reprograming and switching of ErbB family members and thereby influence ErbB3-driven tumor growth.

[Evaluation of Cutaneous Microcirculation at the Dorsum of the Hand within Different Age Groups - Implications for Wound Healing in Hand Surgery?]. / Evaluation der kutanen Mikrozirkulation des Handrückens im Alter - Implikationen für die Wundheilung in der Handchirurgie?

BACKGROUND: Cutaneous microcirculation has shown to play a key role in wound healing. Although healing disorders are still one of the most common complications in hand surgery, there still exists a lack of scientific research on possible age-related changes in cutaneous microcirculation at the dorsum of hand. HYPOTHESIS: Cutaneous microcirculation at the dorsum of the hand differs significantly between different age groups. METHODS: 53 healthy subjects were divided into 2 groups by age (Group A:<40 years, n=31 vs. Group B≥40 years, n=22). All subjects underwent measurement of the microcirculation at the dorsum of the hand with combined laser-Doppler and photo spectrometry. RESULTS: Cutaneous oxygen saturation was significantly higher in Group A than in Group B (A: 64.7±9.9% vs. B: 58.3±12.6%; p=0,044). In contrast, blood flow velocity was significantly higher in Group B (A: 43±19.6 AU vs. B: 56.7±21.1 AU; p=0.019). CONCLUSION: The hypothesis of this study was confirmed. This is the first study to show significant differences of cutaneous microcirculation at the dorsum of the hand within different age groups. Further clinical trials are needed in order to examine if delayed wound healing can be correlated to impaired cutaneous microcirculation at the dorsum of the hand.

Estimation of organ doses to patients undergoing hepatic chemoembolization procedures.

The aim of this study is to evaluate organ and tissue absorbed doses to patients undergoing hepatic chemoembolization procedures performed in two hospitals in the city of Recife, Brazil. Forty eight patients undergoing fifty hepatic chemoembolization procedures were investigated. For the 20 cases with PA projection only, organs and tissues dose to KAP conversion coefficients were calculated using the mesh-based anthropometric phantom series FASH and MASH coupled to the EGSnrc Monte Carlo code. Clinical, dosimetric and irradiations parameters were registered for all patients. The maximum organ absorbed doses found were 2.4 Gy, 0.85 Gy, 0.76 Gy and 0.44 Gy for skin, kidneys, adrenals and liver, respectively.

[Viability and Particle Size of Fat Grafts Obtained with WAL and PAL Techniques]. / Vitalität und Partikelgröße bei der autologen Fetttransplantation mit der WAL und der PAL Technik.

BACKGROUND: Water jet-assisted liposuction (WAL) and power-assisted liposuction (PAL) are used for autologous fat grafting. This study analyses the viability and particle sizes of fat grafts obtained by these techniques. PATIENTS, MATERIAL AND METHODS: The WAL and PAL techniques were applied in 9 female patients in identical body regions. In order to analyse cell viability, fat grafts were tested via the WST-8 assay and DNA quantification immediately after liposuction. Furthermore, in order to determine particle size, an optically evaluable water-fat emulsion was analysed by macroscopic inspection and light microscopy. RESULTS: The WST-8 assay showed significantly lower extinction values (OD) for use of the WAL technique - corresponding to a lower metabolical activity - compared to PAL liposuction: WAL 1.85±0.56 OD, PAL 2.25±0.57 OD. The quotient of extinction values and cell DNA concentration determined by DNA quantification also indicated statistically significant differences between both systems of liposuction in favour of using power-assisted systems: WAL 0.061±0.023 OD/µg, PAL 0.083±0.029 OD/µg. On the other hand, microscopic and macroscopic analyses showed significantly greater diameters (d) for fat grafts obtained with the PAL technique than by WAL liposuction: dmakroWAL=0.8 mm and dmakroPAL=1.1 mm or, respectively, dmikroWAL 0.89 mm and dmikroPAL=0.93 mm. CONCLUSION: Power-assisted liposuction obtains fat grafts with a higher metabolical activity than water jet-assisted liposuction. A falsification of extinction values within the WST-8 assay due to diversity of the number of cells was eliminated by additionally implemented DNA quantification. According to the current scientific debate, the particle size of obtained fat grafts is also considered as an important criterion for the success of autologous fat grafting. For clinical use, one should favour techniques which provide the smallest and most viable fat grafts as possible. In our opinion, the significantly lower size of WAL particles compared to the higher viability of PAL grafts indicates a necessity of analysing viability as well as particle size in order to evaluate liposuction systems. Data solely about in vitro viability of fat grafts fail to offer a recommendation for the use of a specific technique.

Radiation exposure to patients and medical staff in hepatic chemoembolisation interventional procedures in Recife, Brazil.

The purpose of this study was to evaluate patient and medical staff absorbed doses received from transarterial chemoembolisation of hepatocellular carcinoma, which is the most common primary liver tumour worldwide. The study was performed in three hospitals in Recife, capital of the state of Pernambuco, located in the Brazilian Northeastern region. Two are public hospitals (A and B), and one is private (C). For each procedure, the number of images, irradiation parameters (kV, mA and fluoroscopy time), the air kerma-area product (PKA) and the cumulative air kerma (Ka,r) at the reference point were registered. The maximum skin dose (MSD) of the patient was estimated using radiochromic film. For the medical staff dosimetry, thermoluminescence dosemeters (TLD-100) were attached next to the eyes, close to the thyroid (above the shielding), on the thorax under the apron, on the wrist and on the feet. The effective dose to the staff was estimated using the algorithm of von Boetticher. The results showed that the mean value of the total PKA was 267.49, 403.83 and 479.74 Gy cm(2) for Hospitals A, B and C, respectively. With regard to the physicians, the average effective dose per procedure was 17 µSv, and the minimum and maximum values recorded were 1 and 41 µSy, respectively. The results showed that the feet received the highest doses followed by the hands and lens of the eye, since the physicians did not use leaded glasses and the equipment had no lead curtain.

A rapid method for breath analysis in cystic fibrosis patients.

For easy handling and speed of lung diseases diagnostics, approaches based on volatile organic compounds (VOCs), including those emitted by pathogenic microorganisms, are considered but currently require considerable sampling efforts. We tested whether easy-to-handle and fast detection of lung infections is possible using solid-phase microextraction (SPME) of 100 ml of exhaled breath. An analytical procedure for the detection of VOCs from the headspace of epithelial lung cells infected with four human pathogens was developed. The feasibility of this method was tested in a cystic fibrosis (CF) outpatient clinic in vivo. Exhaled breath was extracted by SPME and analyzed by gas chromatography-mass spectrometry (GC-MS). The compositions of VOCs released in the infection model were characteristic for all individual pathogens tested. Exhaled breath of CF patients allowed clear distinction of CF patients and controls by their VOC compositions using multivariate analyses. Interestingly, the major specific VOCs detected in the exhaled breath of infected CF patients in vivo differed from those monitored during bacterial in vitro growth. SPME extraction of VOCs from 100 ml of human breath allowed the distinction between CF patients and healthy probands. Our results highlight the importance of assessing the entire pattern of VOCs instead of selected biomarkers for diagnostic purposes, as well as the need to use clinical samples to identify reliable biomarkers. This study provides the proof-of-concept for the approach using the composition of exhaled VOCs in human breath for the rapid identification of infectious agents in patients with lower respiratory tract infections.

Monitoring hydroquinone-quinone redox cycling by single molecule fluorescence spectroscopy.

Current research in the field of single-molecule chemistry is increasingly focused on the development of reliable experimental approaches for investigating chemical processes on a molecular level using single-molecule fluorescence spectroscopy (SMFS). Herein, we report on single-molecule observations of the copper(II)/air mediated oxidation of fluorescently labeled hydroquinone-based probe molecules followed by their reduction with cysteine. The redox cycle is signaled by quenching/recovery of fluorescence emission after addition of the oxidant/reductant, respectively. The experiments were realized by immobilizing the probe on a glass cover slide to allow single-molecule observation by means of total-internal-reflection fluorescence microscopy. Besides detection of successful oxidation and reduction events on single probe molecules, individual molecular intensity trajectories revealed dynamic processes and formation of intermediate states upon reaction. For the experimental design presented, we envision further reaction studies of catalytic redox-processes of single hydroquinone-moieties by means of SMFS.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

BACKGROUND: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. METHODS: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. RESULTS: In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). CONCLUSION: Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice.

Skeletal dosimetry based on µCT images of trabecular bone: update and comparisons.

Two skeletal dosimetry methods using µCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic­periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use µCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 µm thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the µCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger µCT images of TB.

Electron absorbed fractions of energy and S-values in an adult human skeleton based on µCT images of trabecular bone.

When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on µCT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 µm thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters (14)C, (59)Fe, (131)I, (89)Sr, (32)P and (90)Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 µm endosteum and the previously recommended 10 µm endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by ∼20% when the beta emitters are in marrow.

Dose to medium versus dose to water as an estimator of dose to sensitive skeletal tissue.

The purpose of this study is to determine whether dose to medium, D(m), or dose to water, D(w), provides a better estimate of the dose to the radiosensitive red bone marrow (RBM) and bone surface cells (BSC) in spongiosa, or cancellous bone. This is addressed in the larger context of the ongoing debate over whether D(m) or D(w) should be specified in Monte Carlo calculated radiotherapy treatment plans. The study uses voxelized, virtual human phantoms, FAX06/MAX06 (female/male), incorporated into an EGSnrc Monte Carlo code to perform Monte Carlo dose calculations during simulated irradiation by a 6 MV photon beam from an Elekta SL25 accelerator. Head and neck, chest and pelvis irradiations are studied. FAX06/MAX06 include precise modelling of spongiosa based on microCT images, allowing dose to RBM and BSC to be resolved from the dose to bone. Modifications to the FAX06/MAX06 user codes are required to score D(w) and D(m) in spongiosa. Dose uncertainties of approximately 1% (BSC, RBM) or approximately 0.5% (D(m), D(w)) are obtained after up to 5 days of simulations on 88 CPUs. Clinically significant differences (>5%) between D(m) and D(w) are found only in cranial spongiosa, where the volume fraction of trabecular bone (TBVF) is high (55%). However, for spongiosa locations where there is any significant difference between D(m) and D(w), comparisons of differential dose volume histograms (DVHs) and average doses show that D(w) provides a better overall estimate of dose to RBM and BSC. For example, in cranial spongiosa the average D(m) underestimates the average dose to sensitive tissue by at least 5%, while average D(w) is within approximately 1% of the average dose to sensitive tissue. Thus, it is better to specify D(w) than D(m) in Monte Carlo treatment plans, since D(w) provides a better estimate of dose to sensitive tissue in bone, the only location where the difference is likely to be clinically significant.

Differential epidermal growth factor receptor signaling regulates anchorage-independent growth by modulation of the PI3K/AKT pathway.

Tumor cells are capable of surviving loss of nutrients and anchorage in hostile microenvironments. Under these conditions, adapting to specific signaling pathways may shift the balance between growth and cellular dormancy. Here, we report a mechanism by which epidermal growth factor receptor (EGFR) differentially modulates the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway in cellular stress conditions. When carcinoma cells were cultured as multicellular aggregates (MCA), cyclin D1 was induced through a serum-dependent EGFR activating pathway, triggering cell proliferation. The expression of cyclin D1 required both EGFR-mediated ERK and AKT activation. In serum-starved MCAs, EGFR activation was associated with active ERK1/2, but not AKT, and failed to induce cyclin D1. Analysis revealed that, under serum-starved conditions, EGFR-Y1086 residue was poorly autophosphorylated and this correlated with failure to phosphorylate Gab1. Accordingly, the EGFR activation failed to induce EGFR/PI3K complex formation or AKT activation, preventing cyclin D1 induction. Furthermore, we show that in serum-starved MCA, expression of constitutively active AKT re-established cyclin D1 expression and induced proliferation in an EGFR-dependent manner. Thus, modulation of the PI3K/AKT pathway by context-dependent EGFR signaling may regulate tumor cell growth and dormancy.

FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations.

Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon exposure showed good agreement between FASH/MASH and REGINA/REX, but large differences between FASH/MASH and the mesh-based RPI_AM and the RPI_AF phantoms, developed at the Rensselaer Polytechnic Institute (RPI).

Skeletal dosimetry for external exposures to photons based on microCT images of spongiosa: consideration of voxel resolution, cluster size, and medullary bone surfaces.

Skeletal dosimetry based on microCT images of trabecular bone has recently been introduced to calculate the red bone marrow (RBM) and the bone surface cell (BSC) equivalent doses in human phantoms for external exposure to photons. In order to use the microCT images for skeletal dosimetry, spongiosa voxels in the skeletons were replaced at run time by so-called micromatrices, which have exactly the size of a spongiosa voxel and contain segmented trabecular bone and marrow micro-voxels. A cluster (=parallelepiped) of 2 x 2 x 2 = 8 micromatrices was used systematically and periodically throughout the spongiosa volume during the radiation transport calculation. Systematic means that when a particle leaves a spongiosa voxel to enter into a neighboring spongiosa voxel, then the next micromatrix in the cluster will be used. Periodical means that if the particle travels through more than two spongiosa voxels in a row, then the cluster will be repeated. Based on the bone samples available at the time, clusters of up to 3 x 3 x 3 = 27 micromatrices were studied. While for a given trabecular bone volume fraction the whole-body RBM equivalent dose showed converging results for cluster sizes between 8 and 27 micromatrices, this was not the case for the BSC equivalent dose. The BSC equivalent dose seemed to be very sensitive to the number, form, and thickness of the trabeculae. In addition, the cluster size and/or the microvoxel resolution were considered to be possible causes for the differences observed. In order to resolve this problem, this study used a bone sample large enough to extract clusters containing up to 8 x 8 x 8 = 512 micro-matrices and which was scanned with two different voxel resolutions. Taking into account a recent proposal, this investigation also calculated the BSC equivalent dose on medullary surfaces of cortical bone in the arm and leg bones. The results showed (1) that different voxel resolutions have no effect on the RBM equivalent dose but do influence the BSC equivalent dose due to voxel effects by up to 5% for incident photon energies up to 200 keV, (2) that the whole-body BSC equivalent dose calculated with a cluster with 2 x 2 x 2 = 8 micromatrices is consistent with results received with clusters of up to 8 x 8 x 8 = 512 micromatrices, and (3) that for external whole-body exposure the inclusion of the BSC on medullary surfaces of cortical bone has a negligible effect on the whole-body BSC equivalent dose.

Skeletal dosimetry in cone beam computed tomography.

Cone beam computed tomography (CBCT) is a relatively new patient imaging technique that has proved invaluable for treatment target verification and patient positioning during image-guided radiotherapy (IGRT). It has been shown that CBCT results in additional dose to bone that may amount to 10% of the prescribed dose. In this study, voxelized human phantoms, FAX06 (adult female) and MAX06 (adult male), are used together with phase-space data collected from a realistic model of a CBCT imager to calculate dose in the red bone marrow (RBM) and bone surface cells (BSCs), the two organs at risk within the bone spongiosa, during simulated head and neck, chest and pelvis CBCT scans. The FAX06/MAX06 phantoms model spongiosa based on micro-CT images, filling the relevant phantom voxels, which are 0.12 x 0.12 x 0.12 cm3, with 17 x 17 x 17 microm3 microvoxels to form a micromatrix of trabecular bone and bone marrow. FAX06/ MAX06 have already been implemented in an EGSnrc-based Monte Carlo code to simulate radiation transport in the phantoms; however, this study required significant modifications of the code to allow use of phase-space data from a simulated CBCT imager as a source and to allow scoring of total dose, RBM dose and BSC dose on a voxel-by-voxel basis. In simulated CBCT scans, the BSC dose is significantly greater than the dose to other organs at risk. For example, in a simulated head and neck scan, the average BSC dose is 25% higher than the average dose to eye lens (approximately 8.3 cGy), and 80% greater than the average dose to brain (5.7 cGy). Average dose to RBM, on the other hand, is typically only approximately 50% of the average BSC dose and less than the dose to other organs at risk (54% of the dose to eye lens and 76% of dose to brain in a head and neck scan). Thus, elevated dose in bone due to CBCT results in elevated BSC dose. This is potentially of concern when using CBCT in conjunction with radiotherapy treatment.