Evidence for a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as a-lipoic acid and alpha-tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with alpha-lipoic acid and alpha-tocopherol, alone or in combination, prior to incubation with H2O2 or staurosporine. alpha-lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H2O2 and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with a-lipoic acid and/or a-tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of BcI-2, Bax, HSP70 or pERK1/2 or pJNK. alpha-lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with alpha-lipoic acid and alpha-tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of alpha-lipoic acid as an antioxidant.

A rheology study of high-energy radiolysis of a semicrystalline ethylene-propylene copolymer containing DOP mobilizer

The ractiolysis of a poly(ethylene-co-propylene), Elpro grade P 750 J, marketed by Thai Polypropylene Co. Ltd. for the manufacture of medical goods, was investigated at ambient temperature and melt rheology measured. The roles of calcium stearate, blended with the Elpro as a processing aid, and dioctyl phthalate (DOP), added in various amounts as a radical scavenger, were assessed. Following radiolysis, G' and the viscosity of the polymer melts at 453 K both decreased with increasing radiation dose, even when the mobilizer was present. The results indicated that although the DOP did scavenge radicals, it did not protect the polymer from net chain scission in a low-dose regimen. The value of (G(S) - 4G(X)) was approximately 0.6-0.7. (c) 2006 Wiley Periodicals, Inc.

Does chemotherapy improve survival in high-risk Stage I and II Merkel cell carcinoma of the skin?

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.

Population pharmacokinetics of single-dose intravenous paracetamol in children

Background To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children ≤15 yr of age. Methods After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3% at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM. Results One hundred and fifty-nine blood samples from 33 children aged 1.8–15 yr, weight 13.7–56 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V1 (central volume of distribution), Q (inter-compartmental clearance), and V2 (peripheral volume of distribution) were: 16.51×(WT/70)0.75, 28.4×(WT/70), 11.32×(WT/70)0.75, and 13.26×(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V1 and V2 in litres). Conclusions In children aged 1.8–15 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).

A high-fat meal induces low-grade endotoxemia:evidence of a novel mechanism of postprandial inflammation

Background: Bacterial endotoxin is a potently inflammatory antigen that is abundant in the human gut. Endotoxin circulates at low concentrations in the blood of all healthy individuals, although elevated concentrations are associated with an increased risk of atherosclerosis. Objective: We sought to determine whether a high-fat meal or smoking increases plasma endotoxin concentrations and whether such concentrations are of physiologic relevance. Design: Plasma endotoxin and endotoxin neutralization capacity were measured for 4 h in 12 healthy men after no meal, 3 cigarettes, a high-fat meal, or a high-fat meal with 3 cigarettes by using the limulus assay. Results: Baseline endotoxin concentrations were 8.2 pg/mL (interquartile range: 3.4–13.5 pg/mL) but increased significantly (P < 0.05) by ≈50% after a high-fat meal or after a high-fat meal with cigarettes but not after no meal or cigarettes alone. These results were validated by the observations that a high-fat meal with or without cigarettes, but not no meal or smoking, also significantly (P < 0.05) reduced plasma endotoxin neutralization capacity, which is an indirect measure of endotoxin exposure. Human monocytes, but not aortic endothelial cells, were responsive to transient (30 s) or low-dose (10 pg/mL) exposure to endotoxin. However, plasma from whole blood treated with as little as 10 pg endotoxin/mL increased the endothelial cell expression of E-selectin, at least partly via tumor necrosis factor-α–induced cellular activation. Conclusions: Low-grade endotoxemia may contribute to the postprandial inflammatory state and could represent a novel potential contributor to endothelial activation and the development of atherosclerosis.

Visual field severity indices demonstrate dose-dependent visual loss from Vigabatrin therapy

Purpose: The aims of this study were to develop an algorithm to accurately quantify Vigabatrin (VGB)-induced central visual field loss and to investigate the relationship between visual field loss and maximum daily dose, cumulative dose and duration of dose. Methods: The sample comprised 31 patients (mean age 37.9 years; SD 14.4 years) diagnosed with epilepsy and exposed to VGB. Each participant underwent standard automated static visual field examination of the central visual field. Central visual field loss was determined using continuous scales quantifying severity in terms of area and depth of defect and additionally by symmetry of defect between the two eyes. A simultaneous multiple regression model was used to explore the relationship between these visual field parameters and the drug predictor variables. Results: The regression model indicated that maximum VGB dose was the only factor to be significantly correlated with individual eye severity (right eye: p = 0.020; left eye: p = 0.012) and symmetry of visual field defect (p = 0.024). Conclusions: Maximum daily dose was the single most reliable indicator of those patients likely to exhibit visual field defects due to VGB. These findings suggest that high maximum dose is more likely to result in visual field defects than high cumulative doses or those of long duration.

Radiation Dose to the Lens of the Eye from Computed Tomography Scans of the Head

While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient’s medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods.

The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data.

The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult.

First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient’s head size.

Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study.

Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit.

The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group.

This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.

Accumulation de dose à partir de champs de déformation 4D appliqués aux traitements au CyberKnife et à l'IMRT

Le cancer pulmonaire est la principale cause de décès parmi tous les cancers au Canada. Le pronostic est généralement faible, de l'ordre de 15% de taux de survie après 5 ans. Les déplacements internes des structures anatomiques apportent une incertitude sur la précision des traitements en radio-oncologie, ce qui diminue leur efficacité. Dans cette optique, certaines techniques comme la radio-chirurgie et la radiothérapie par modulation de l'intensité (IMRT) visent à améliorer les résultats cliniques en ciblant davantage la tumeur. Ceci permet d'augmenter la dose reçue par les tissus cancéreux et de réduire celle administrée aux tissus sains avoisinants. Ce projet vise à mieux évaluer la dose réelle reçue pendant un traitement considérant une anatomie en mouvement. Pour ce faire, des plans de CyberKnife et d'IMRT sont recalculés en utilisant un algorithme Monte Carlo 4D de transport de particules qui permet d'effectuer de l'accumulation de dose dans une géométrie déformable. Un environnement de simulation a été développé afin de modéliser ces deux modalités pour comparer les distributions de doses standard et 4D. Les déformations dans le patient sont obtenues en utilisant un algorithme de recalage déformable d'image (DIR) entre les différentes phases respiratoire générées par le scan CT 4D. Ceci permet de conserver une correspondance de voxels à voxels entre la géométrie de référence et celles déformées. La DIR est calculée en utilisant la suite ANTs («Advanced Normalization Tools») et est basée sur des difféomorphismes. Une version modifiée de DOSXYZnrc de la suite EGSnrc, defDOSXYZnrc, est utilisée pour le transport de particule en 4D. Les résultats sont comparés à une planification standard afin de valider le modèle actuel qui constitue une approximation par rapport à une vraie accumulation de dose en 4D.

Time-resolved dosimetric verification of respiratory-gated radiotherapy exposures using a high-resolution 2D ionisation chamber array

The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS® SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of  <0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0  ±  0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates  >90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam.

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. Methods: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-a, IL-1b, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. Results: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-a, IL-1b and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. Conclusion: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines

Osteossarcoma, quimioterapia HDMTX e reflexos laboratoriais

O osteossarcoma ou sarcoma osteogénico (OS) é o tumor maligno primário mais comum de origem óssea que ocorre em crianças e adultos jovens. Este tumor surge a partir de células mesenquimais e é histologicamente caracterizado pela presença de células fusiformes e formação aberrante de osteóide. A incidência desta neoplasia apresenta uma distribuição bimodal, com um primeiro pico na adolescência e um segundo pico a ocorrer entre a 6ª e a 7ª década de vida. A maioria dos pacientes apresenta doença localizada à data do diagnóstico, e destes, aproximadamente 15 a 20% apresentam metástases detectáveis, em especial, pulmonares. A abordagem terapêutica ao OS engloba quimioterapia pré-operatória (neoadjuvante) seguida de ressecção cirúrgica do tumor primário e de todas as metástases visíveis e de quimioterapia pós-operatória (adjuvante). Historicamente, muitos agentes foram testados e usados no tratamento do OS, mas desde os anos 90 até à actualidade, o esquema de tratamento baseia-se na utilização de três agentes: Metotrexato (MTX), Doxorrubicina (A) e Ciclofosfamida (P), podendo ou não ser incluído um 4º agente, a Ifosfamida (I) ou o Ectopósido (E). Para surtir efeito, o MTX é administrado em alta dose, habitualmente de 12g/m2, podendo ir até 20g/m2, apresentando vários efeitos adversos. Como tal, outros agentes quimioterápicos têm sido testados, assim como outros tipos de tratamento e alvos, com o intuito de melhorar a performance e a sobrevida sem recorrência. A identificação de biomarcadores que permitam o diagnóstico, prognóstico e monitorização da terapia tem sido outra das principais linhas de investigação relacionadas com o OS. O objetivo deste trabalho centra-se na revisão da importância do tratamento neoadjuvante enquanto fator prognóstico do OS, e da monitorização laboratorial na utilização do MTX por forma a evitar efeitos secundários.

Osteossarcoma, quimioterapia HDMTX e reflexos laboratoriais

O osteossarcoma ou sarcoma osteogénico (OS) é o tumor maligno primário mais comum de origem óssea que ocorre em crianças e adultos jovens. Este tumor surge a partir de células mesenquimais e é histologicamente caracterizado pela presença de células fusiformes e formação aberrante de osteóide. A incidência desta neoplasia apresenta uma distribuição bimodal, com um primeiro pico na adolescência e um segundo pico a ocorrer entre a 6ª e a 7ª década de vida. A maioria dos pacientes apresenta doença localizada à data do diagnóstico, e destes, aproximadamente 15 a 20% apresentam metástases detectáveis, em especial, pulmonares. A abordagem terapêutica ao OS engloba quimioterapia pré-operatória (neoadjuvante) seguida de ressecção cirúrgica do tumor primário e de todas as metástases visíveis e de quimioterapia pós-operatória (adjuvante). Historicamente, muitos agentes foram testados e usados no tratamento do OS, mas desde os anos 90 até à actualidade, o esquema de tratamento baseia-se na utilização de três agentes: Metotrexato (MTX), Doxorrubicina (A) e Ciclofosfamida (P), podendo ou não ser incluído um 4º agente, a Ifosfamida (I) ou o Ectopósido (E). Para surtir efeito, o MTX é administrado em alta dose, habitualmente de 12g/m2, podendo ir até 20g/m2, apresentando vários efeitos adversos. Como tal, outros agentes quimioterápicos têm sido testados, assim como outros tipos de tratamento e alvos, com o intuito de melhorar a performance e a sobrevida sem recorrência. A identificação de biomarcadores que permitam o diagnóstico, prognóstico e monitorização da terapia tem sido outra das principais linhas de investigação relacionadas com o OS. O objetivo deste trabalho centra-se na revisão da importância do tratamento neoadjuvante enquanto fator prognóstico do OS, e da monitorização laboratorial na utilização do MTX por forma a evitar efeitos secundários.

Role of active and passive recovery in adaptations to high intensity training

It has been established that Wingate-based high-intensity training (HIT) consisting of 4 to 6 x 30-s all-out sprints interspersed with 4-min recovery is an effective training paradigm. Despite the increased utilisation of Wingate-based HIT to bring about training adaptations, the majority of previous studies have been conducted over a relatively short timeframe (2 to 6 weeks). However, activity during recovery period, intervention duration or sprint length have been overlooked. In study 1, the dose response of recovery intensity on performance during typical Wingate-based HIT (4 x 30-s cycle all-out sprints separated by 4-min recovery) was examined and active recovery (cycling at 20 to 40% of V̇O2peak) has been shown to improve sprint performance with successive sprints by 6 to 12% compared to passive recovery (remained still), while increasing aerobic contribution to sprint performance by ~15%. In the following study, 5 to 7% greater endurance performance adaptations were achieved with active recovery (40%V̇O2peak) following 2 weeks of Wingate-based HIT. In the final study, shorter sprint protocol (4 to 6 x 15-s sprints interspersed with 2 min of recovery) has been shown to be as effective as typical 30-s Wingate-based HIT in improving cardiorespiratory function and endurance performance over 9 weeks with the improvements in V̇O2peak being completed within 3 weeks, whereas exercise capacity (time to exhaustion) being increased throughout 9 weeks. In conclusion, the studies demonstrate that active recovery at 40% V̇O2peak significantly enhances endurance adaptations to HIT. Further, the duration of the sprint does not seem to be a driving factor in the magnitude of change with 15 sec sprints providing similar adaptations to 30 sec sprints. Taken together, this suggests that the arrangement of recovery mode should be considered to ensure maximal adaptation to HIT, and the practicality of the training would be enhanced via the reduction in sprint duration without diminishing overall training adaptations.

Are physical measures good indicators of image quality at low dose levels? A pilot study

Purpose: To evaluate if physical measures of noise predict image quality at high and low noise levels. Method: Twenty-four images were acquired on a DR system using a Pehamed DIGRAD phantom at three kVp settings (60, 70 and 81) across a range of mAs values. The image acquisition setup consisted of 14 cm of PMMA slabs with the phantom placed in the middle at 120 cm SID. Signal-to-noise ratio (SNR) and Contrast-tonoise ratio (CNR) were calculated for each of the images using ImageJ software and 14 observers performed image scoring. Images were scored according to the observer`s evaluation of objects visualized within the phantom. Results: The R2 values of the non-linear relationship between objective visibility score and CNR (60kVp R2 = 0.902; 70Kvp R2 = 0.913; 80kVp R2 = 0.757) demonstrate a better fit for all 3 kVp settings than the linear R2 values. As CNR increases for all kVp settings the Object Visibility also increases. The largest increase for SNR at low exposure values (up to 2 mGy) is observed at 60kVp, when compared with 70 or 81kVp.CNR response to exposure is similar. Pearson r was calculated to assess the correlation between Score, OV, SNR and CNR. None of the correlations reached a level of statistical significance (p>0.01). Conclusion: For object visibility and SNR, tube potential variations may play a role in object visibility. Higher energy X-ray beam settings give lower SNR but higher object visibility. Object visibility and CNR at all three tube potentials are similar, resulting in a strong positive relationship between CNR and object visibility score. At low doses the impact of radiographic noise does not have a strong influence on object visibility scores because in noisy images objects could still be identified.