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Biomedical subjects

B K Lind

Publications and source records attributed to B K Lind.

At least 19 recordsLinked to original sources
PubMed2006

Assessing the difference between planned and delivered intensity-modulated radiotherapy dose distributions based on radiobiological measures.

AIMS: Because of the highly conformal distributions that can be obtained with intensity-modulated radiotherapy (IMRT), any discrepancy between the intended and delivered distributions would probably affect the clinical outcome. Consequently, there is a need for a measure that would quantify those differences in terms of a change in the expected clinical outcome. MATERIALS AND METHODS: To evaluate such a measure, cancer of the cervix was used, where the bladder and rectum are proximal and partially overlapping with the internal target volume. A solid phantom simulating the pelvic anatomy was fabricated and a treatment plan was developed to deliver the prescribed dose to the phantom. The phantom was then irradiated with films positioned in several transverse planes. The racetrack microtron at 50 MV was used in the treatment planning and delivery processes. The dose distribution delivered was analysed based on the film measurements and compared against the treatment plan. The differences in the measurements were evaluated using both physical and biological criteria. Whereas the physical comparison of dose distributions can assess the geometric accuracy of delivery, it does not reflect the clinical effect of any measured dose discrepancies. RESULTS: It is shown how small inaccuracies in delivered dose can affect the treatment outcome in terms of complication-free tumour cure. CONCLUSIONS: With highly conformal IMRT, the accuracy of the patient set-up and treatment delivery are critical for the success of the treatment. A method is proposed to evaluate the precision of the delivered plan based on changes in complication and control rates as they relate to uncertainties in dose delivery.

Dose-Response Relationship, Radiation↗
PubMed2005

Dose and time dependent apoptotic response in a human melanoma cell line exposed to accelerated boron ions at four different LET.

The aim was to investigate and compare the influence of linear energy transfer (LET), dose and time on the induction of apoptosis in a human melanoma cell line exposed to accelerated light boron ((10)B) ions and photons. Cells were exposed in vitro to doses up to 6 Gy accelerated boron ions (40, 80, 125 and 160 eV nm(-1)) and up to 12 Gy photons (0.2 eV nm(-1)). The induction of apoptosis was measured up to 9 days after irradiation using morphological characterization of apoptotic cells and bodies. In parallel, measurements of cell-cycle distribution, monitored by DNA flow cytometry, and cell survival based on the clonogenic cell survival assay, were performed. In addition, the induction and repair of DNA double-strand breaks (DSB), using pulsed-field gel electrophoresis (PFGE) were studied. Accelerated boron ions induced a significant increase in apoptosis as compared with photons at all time points studied. At 1-5 h the percentage of radiation-induced apoptotic cells increased with both dose and LET. At the later time points (24-216 h) the apoptotic response was more complex and did not increase in a strictly LET-dependent manner. The early premitotic apoptotic cells disappeared at 24 h following exposure to the highest LET (160 eV nm(-1)). A postmitotic apoptotic response was seen after release of the dose-, time- and LET-dependent G2/M accumulations. The loss of clonogenic ability was dose- and LET-dependent and the fraction of un-rejoined DSB increased with increasing LET. Despite the LET-dependent clonogenic cell killing, it was not possible to measure quantitatively a LET-dependent apoptotic response. This was due to the different time course of appearance and disappearance of apoptotic cells.

Apoptosis↗
PubMed2003

Repairable-conditionally repairable damage model based on dual Poisson processes.

The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

Cell Line↗
PubMed2002

RBE of 50 MV scanned bremsstrahlung beams determined using clonogenic assay.

PURPOSE: In order to compare the biological effectiveness of a 50 MV scanned bremsstrahlung beam to (60)Co and 6 MV photons, the survival of Chinese hamster cells (V79-379A), human normal fibroblasts cells (GSH(+/+)) and human small cell lung cancer cells (U-1690) were analysed. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions in a plastic phantom. Dose to the cells was determined using ferrous sulphate and ionization chamber dosimetry. A number of cell survival models were fitted to the experimental data, including the standard LQ model with and without the induced repair. In particular, a new model treating damage and repair separately was used in combination with a new technique for accurate RBE determination. RESULTS: The measured RBE for the three cell lines were 0.988 (0.984-0.992), 0.999 (0.996-1.002) and 1.013 (1.009-1.016) for V79-379A, GSH(+/+) and U-1690 respectively and thus 50 MV scanned beams did not differ more than a fraction of a per cent from conventional therapy beams. CONCLUSIONS: The present study gives RBE consistent with previously calculated RBEs based on photonuclear reaction cross-sections of high-energy photons.

Animals↗
PubMed2002

Radiation response of hypoxic and generally heterogeneous tissues.

PURPOSE: Biologically based treatment optimisation can be based on the local mean values of the number of clonogenic cells and the cellular radiation response taken over macroscopic tissue voxels. Steep oxygen gradients in tumours may often lead to microscopic distributions of radiation resistance at the cellular level, far beyond the geometrical resolution of current diagnostic and radiotherapeutic methods. The present work focuses on quantifying the radiobiological effect of such microscopic distributions through tissue-oxygenation modelling and on calculating the corresponding radiation response on both micro- and macroscopic scales. MATERIALS AND METHODS: A simple model of tissue vasculature was developed with microvascular density and heterogeneity as its main parameters. New analytical expressions are presented for calculating the effective radiation response of tissues with generally heterogeneous radiation resistance and clonogen density. RESULTS: The oxygen distributions derived for different parameter sets agree very well with clinically measured oxygen distributions for both tumours and normal tissues. In addition to the vascular density, vascular heterogeneity is an important factor while estimating the hypoxic fraction in tissue. It is shown that both the local and global dose-response relation for tissues with heterogeneous radiation resistance can be accurately calculated from the effective initial clonogen number N(0,eff) and the effective radiation resistance D(0,eff). New equations are derived for calculating these quantities, for instance, from measured oxygen distributions. CONCLUSIONS: With the new methods presented here, existing techniques to measure the micro- and macroscopic oxygen distribution either using standard tumour-type or patient-specific oxygenation data can be used for biologically based treatment plan optimisation.

Cell Survival↗
PubMed2002

Relative biological effectiveness of boron ions on human melanoma cells.

PURPOSE: To compare the difference in relative biological effectiveness (RBE) between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. CONCLUSIONS: Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.

Apoptosis↗
PubMed2001

Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.

Associations between sleep-disordered breathing and cardiovascular disease (CVD) may be mediated by higher cardiovascular risk factor levels in those with sleep-disordered breathing. The authors examined these relations in the Sleep Heart Health Study, a multiethnic cohort of 6,440 men and women over age 40 years conducted from October 1995 to February 1998 and characterized by home polysomnography. In 4,991 participants who were free of self-reported CVD at the time of the sleep study, moderate levels of sleep-disordered breathing were common, with a median Respiratory Disturbance Index (RDI) of 4.0 (interquartile range, 1.25-10.7). The level of RDI was associated cross-sectionally with age, body mass index, waist-to-hip ratio, hypertension, diabetes, and lipid levels. These relations were more pronounced in those under age 65 years than in those over age 65. Women under age 65 years with RDI in the higher quartiles were more obese than men with similar RDI. Although the pattern of associations was consistent with greater obesity in those with higher RDI, higher body mass index did not explain all of these associations. If sleep-disordered breathing is shown in future follow-up to increase the risk for incident CVD events, part of the risk is likely to be due to the higher cardiovascular risk factors in those with higher RDI.

Adult↗
PubMed2001

Generalization of the normalized dose-response gradient to non-uniform dose delivery.

A generalization of the standard dose-response gradient to arbitrarily heterogeneous dose distributions has been developed. The generalized dose-response gradient is the scalar product of the vector representing the dose distribution and the gradient of the dose-response relation with respect to that dose vector. It is shown that, for a tumor, the individual gamma-values for each portion of the tumor divided by the corresponding local tumor control probability should be added to get the total value for the heterogeneously irradiated tumor. This corresponds to summing up the contributions of all tumor volumes so that the total value of the gradient is related to the logarithm of the total tumor clonogen number. General expressions are also derived for the change in the dose-response relation as a function of a change in the delivered dose distribution.

Dose Fractionation, Radiation↗
PubMed2001

Biologically effective uniform dose (D) for specification, report and comparison of dose response relations and treatment plans.

Developments in radiation therapy planning have improved the information about the three-dimensional dose distribution in the patient. Isodose graphs, dose volume histograms and most recently radiobiological models can be used to evaluate the dose distribution delivered to the irradiated organs and volumes of interest. The concept of a biologically effective uniform dose (D) assumes that any two dose distributions are equivalent if they cause the same probability for tumour control or normal tissue complication. In the present paper the D concept both for tumours and normal tissues is presented, making use of the fact that probabilities averaged over both dose distribution and organ radiosensitivity are more relevant to the clinical outcome than the expected number of surviving clonogens or functional subunits. D can be calculated in complex target volumes or organs at risk either from the 3D dose matrix or from the corresponding dose volume histograms of the dose plan. The value of the D concept is demonstrated by applying it to two treatment plans of a cervix cancer. Comparison is made of the D concept with the effective dose (Deff ) and equivalent uniform dose (EUD) that have been suggested in the past. The value of the concept for complex targets and fractionation schedules is also pointed out.

Dose Fractionation, Radiation↗
PubMed2000

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both. OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons. DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998. PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female). MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication. RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring. CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

Adult↗
PubMed2000

Comparison of conformal radiation therapy techniques within the dynamic radiotherapy project 'Dynarad'.

The objective of the dynamic radiotherapy project 'Dynarad' within the European Community has been to compare and grade treatment techniques that are currently applied or being developed at the participating institutions. Cervical cancer was selected as the tumour site on the grounds that the involved organs at risk, mainly the rectum and the bladder, are very close to the tumour and partly located inside the internal target volume. In this work, a solid phantom simulating the pelvic anatomy was used by institutions in Belgium, France, Greece, Holland, Italy, Sweden and the United Kingdom. The results were evaluated using both biological and physical criteria. The main purpose of this parallel evaluation is to test the value of biological and physical evaluations in comparing treatment techniques. It is demonstrated that the biological objective functions allow a much higher conformality and a more clinically relevant scoring of the outcome. Often external beam treatment techniques have to be combined with intracavitary therapy to give clinically acceptable results. However, recent developments can reduce or even eliminate this need by delivering more conformal dose distributions using intensity modulated external dose delivery. In these cases the reliability of the patient set-up procedure becomes critical for the effectiveness of the treatment.

European Union↗
PubMed1999

Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.

BACKGROUND: Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events. METHODS: We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke. RESULTS: There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves. CONCLUSIONS: Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.

Aged↗
PubMed1999

Complications caused by extramembranous placement of intrauterine pressure catheters.

A case report is described in which the inadvertent placement of a standard intrauterine pressure catheter in a laboring woman caused partial abruptio placentae and disseminated intravascular coagulation. Altering catheter placement technique and giving attention to aspects of placement can help avoid mishaps, and awareness of possible complications can lead to earlier diagnosis with increased appropriate intervention.

Abruptio Placentae↗
PubMed1999

Optimization of the dose level for a given treatment plan to maximize the complication-free tumor cure.

During the past decade, tumor and normal tissue reactions after radiotherapy have been increasingly quantified in radiobiological terms. For this purpose, response models describing the dependence of tumor and normal tissue reactions on the irradiated volume, heterogeneity of the delivered dose distribution and cell sensitivity variations can be taken into account. The probability of achieving a good treatment outcome can be increased by using an objective function such as P+, the probability of complication-free tumor control. A new procedure is presented, which quantifies P+ from the dose delivery on 2D surfaces and 3D volumes and helps the user of any treatment planning system (TPS) to select the best beam orientations, the best beam modalities and the most suitable beam energies. The final step of selecting the prescribed dose level is made by a renormalization of the entire dose plan until the value of P+ is maximized. The index P+ makes use of clinically established dose-response parameters, for tumors and normal tissues of interest, in order to improve its clinical relevance. The results, using P+, are compared against the assessments of experienced medical physicists and radiation oncologists for two clinical cases. It is observed that when the absorbed dose level for a given treatment plan is increased, the treatment outcome first improves rapidly. As the dose approaches the tolerance of normal tissues the complication-free cure begins to drop. The optimal dose level is often just below this point and it depends on the geometry of each patient and target volume. Furthermore, a more conformal dose delivery to the target results in a higher control rate for the same complication level. This effect can be quantified by the increased value of the P+ parameter.

Dose-Response Relationship, Radiation↗
PubMed1999

Stochastic optimization of intensity modulated radiotherapy to account for uncertainties in patient sensitivity.

The aim of the present work is to better account for the known uncertainties in radiobiological response parameters when optimizing radiation therapy. The radiation sensitivity of a specific patient is usually unknown beyond the expectation value and possibly the standard deviation that may be derived from studies on groups of patients. Instead of trying to find the treatment with the highest possible probability of a desirable outcome for a patient of average sensitivity, it is more desirable to maximize the expectation value of the probability for the desirable outcome over the possible range of variation of the radiation sensitivity of the patient. Such a stochastic optimization will also have to consider the distribution function of the radiation sensitivity and the larger steepness of the response for the individual patient. The results of stochastic optimization are also compared with simpler methods such as using biological response 'margins' to account for the range of sensitivity variation. By using stochastic optimization, the absolute gain will typically be of the order of a few per cent and the relative improvement compared with non-stochastic optimization is generally less than about 10 per cent. The extent of this gain varies with the level of interpatient variability as well as with the difficulty and complexity of the case studied. Although the dose changes are rather small (<5 Gy) there is a strong desire to make treatment plans more robust, and tolerant of the likely range of variation of the radiation sensitivity of each individual patient. When more accurate predictive assays of the radiation sensitivity for each patient become available, the need to consider the range of variations can be reduced considerably.

Dose-Response Relationship, Radiation↗
PubMed1998

Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group.

This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.

Electroencephalography↗
PubMed1998

An adaptive control algorithm for optimization of intensity modulated radiotherapy considering uncertainties in beam profiles, patient set-up and internal organ motion.

A new general beam optimization algorithm for inverse treatment planning is presented. It utilizes a new formulation of the probability to achieve complication-free tumour control. The new formulation explicitly describes the dependence of the treatment outcome on the incident fluence distribution, the patient geometry, the radiobiological properties of the patient and the fractionation schedule. In order to account for both measured and non-measured positioning uncertainties, the algorithm is based on a combination of dynamic and stochastic optimization techniques. Because of the difficulty in measuring all aspects of the intra- and interfractional variations in the patient geometry, such as internal organ displacements and deformations, these uncertainties are primarily accounted for in the treatment planning process by intensity modulation using stochastic optimization. The information about the deviations from the nominal fluence profiles and the nominal position of the patient relative to the beam that is obtained by portal imaging during treatment delivery, is used in a feedback loop to automatically adjust the profiles and the location of the patient for all subsequent treatments. Based on the treatment delivered in previous fractions, the algorithm furnishes optimal corrections for the remaining dose delivery both with regard to the fluence profile and its position relative to the patient. By dynamically refining the beam configuration from fraction to fraction, the algorithm generates an optimal sequence of treatments that very effectively reduces the influence of systematic and random set-up uncertainties to minimize and almost eliminate their overall effect on the treatment. Computer simulations have shown that the present algorithm leads to a significant increase in the probability of uncomplicated tumour control compared with the simple classical approach of adding fixed set-up margins to the internal target volume.

Algorithms↗