Ionization chamber radial response deconvolution in megavoltage photon beam.

The aim of this paper is to study a radial response model as a method, to correct output factor results gathered with ionization chambers of different size and shape in cone collimated RT fields. An enhanced version of a non-parametric super-resolution deconvolution method able to model a radial response function of a small cylinder symmetric ionization chamber is described and demonstrated. The radial response of four ionization chambers with different geometry and radius are estimated using 6 MV photon beam in water at the isocentre plane. Finally the validity of the estimates is tested by applying the response functions to the output factor measurements of 4-20 mm conical collimators. The enhanced method is demonstrated by obtaining the response function characteristics with a spatial uncertainty smaller than 0.1 mm when the distance from chamber axis is larger than 0.5 mm. In all studied ionization chambers, a significant local response maximum is found close to the air cavity boundary. The agreement between the output factor results of different chambers is promising, the largest difference (max-min) in output factor is 4% obtained for the smallest 4 mm cone size.

Fast voxel-level dosimetry for (177)Lu labelled peptide treatments.

In peptide receptor radionuclide therapy (PRRT), voxel-level radiation absorbed dose calculations can be performed using several different methods. Each method has it strengths and weaknesses; however, Monte Carlo (MC) simulation is presently considered the most accurate method at providing absorbed dose distributions. Unfortunately MC simulation is time-consuming and often impractical to carry out in a clinical practice. In this work, a fast semi-Monte Carlo (sMC) absorbed dose calculation method for (177)Lu PRRT dosimetry is presented. The sMC method is based on a local electron absorption assumption and fast photon MC simulations. The sMC method is compared against full MC simulation code built on PENELOPE (vxlPen) using digital phantoms to assess the accuracy of these assumptions.Due to the local electron absorption assumption of sMC, the potential errors in cross-fire dose from electrons and photons emitted by (177)Lu were first evaluated using an ellipsoidal kidney model by comparing vxlPen and sMC. The photon cross-fire dose from background to kidney and kidney to background with varying kidney-to-background activity concentration ratios were calculated. In addition, kidney to kidney photon and electron cross-dose with different kidney to kidney distances were studied. Second, extended cardiac-torso (XCAT) phantoms were created with liver lesions and with realistic activity distributions and tissue densities. The XCAT phantoms were used to simulate SPECT projections and 3D activity distribution images were reconstructed using an OSEM algorithm. Image-based dose rate distributions were calculated using vxlPen and sMC. Total doses and dose rate volume histograms (DrVH) produced by the two methods were compared.The photon cross-fire dose from the kidney increased the background's absorbed dose by 5% or more up to 5.8 cm distance with 20 : 1 kidney to background activity concentration ratio. On the other hand, the photon cross-fire dose from the background to the kidney volume was negligible. The vxlPen results showed that the cross fire dose between two similar kidney volumes relative to the source kidney's self-dose were 0.5% and 0.02% for photon and electrons, respectively, when source and target kidneys were modelled next to each other. The photon cross-dose decreased as function of distance, and electron doses were zero at distances larger than 4 mm. The difference between sMC and vxlPen kidney total doses in the XCAT phantom study was -0.4% while the electron dose DrVHs were identical between the methods. There was a systematic 5% difference in photon doses in soft tissue between the codes due to different simulations parameters. However, the photons produced only 4% of the kidney's total dose, thus the difference was not considered significant for total dose calculations.The comparison studies show that the absorbed doses calculated using the sMC differ only slightly from dedicated MC simulator results, while the dose estimates can be obtained in a fraction of the dedicated simulator's calculation time. Results imply that there is no need for electron MC simulation for (177)Lu absorption calculations with current SPECT systems. However, the photon cross-fire dose should be taken into account in healthy tissues, which have a relatively low uptake especially in cases where there are high uptake volumes are nearby.

The addition of entropy-based regularity parameters improves sleep stage classification based on heart rate variability.

The work considers automatic sleep stage classification, based on heart rate variability (HRV) analysis, with a focus on the distinction of wakefulness (WAKE) from sleep and rapid eye movement (REM) from non-REM (NREM) sleep. A set of 20 automatically annotated one-night polysomnographic recordings was considered, and artificial neural networks were selected for classification. For each inter-heartbeat (RR) series, beside features previously presented in literature, we introduced a set of four parameters related to signal regularity. RR series of three different lengths were considered (corresponding to 2, 6, and 10 successive epochs, 30 s each, in the same sleep stage). Two sets of only four features captured 99 % of the data variance in each classification problem, and both of them contained one of the new regularity features proposed. The accuracy of classification for REM versus NREM (68.4 %, 2 epochs; 83.8 %, 10 epochs) was higher than when distinguishing WAKE versus SLEEP (67.6 %, 2 epochs; 71.3 %, 10 epochs). Also, the reliability parameter (Cohens's Kappa) was higher (0.68 and 0.45, respectively). Sleep staging classification based on HRV was still less precise than other staging methods, employing a larger variety of signals collected during polysomnographic studies. However, cheap and unobtrusive HRV-only sleep classification proved sufficiently precise for a wide range of applications.

Monitoring nocturnal heart rate with bed sensor.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". OBJECTIVES: The aim of this study is to assess the reliability of the estimated Nocturnal Heart Rate (HR), recorded through a bed sensor, compared with the one obtained from standard electrocardiography (ECG). METHODS: Twenty-eight sleep deprived patients were recorded for one night each through matrix of piezoelectric sensors, integrated into the mattress, through polysomnography (PSG) simultaneously. The two recording methods have been compared in terms of signal quality and differences in heart beat detection. RESULTS: On average, coverage of 92.7% of the total sleep time was obtained for the bed sensor, testifying the good quality of the recordings. The average beat-to-beat error of the inter-beat intervals was 1.06%. These results suggest a good overall signal quality, however, considering fast heart rates (HR > 100 bpm), performances were worse: in fact, the sensitivity in the heart beat detection was 28.4% while the false positive rate was 3.8% which means that a large amount of fast beats were not detected. CONCLUSIONS: The accuracy of the measurements made using the bed sensor has less than 10% of failure rate especially in periods with HR lower than 70 bpm. For fast heart beats the uncertainty increases. This can be explained by the change in morphology of the bed sensor signal in correspondence of a higher HR.

Super-resolution non-parametric deconvolution in modelling the radial response function of a parallel plate ionization chamber.

The signal of the dosimetric detector is generally dependent on the shape and size of the sensitive volume of the detector. In order to optimize the performance of the detector and reliability of the output signal the effect of the detector size should be corrected or, at least, taken into account. The response of the detector can be modelled using the convolution theorem that connects the system input (actual dose), output (measured result) and the effect of the detector (response function) by a linear convolution operator. We have developed the super-resolution and non-parametric deconvolution method for determination of the cylinder symmetric ionization chamber radial response function. We have demonstrated that the presented deconvolution method is able to determine the radial response for the Roos parallel plate ionization chamber with a better than 0.5 mm correspondence with the physical measures of the chamber. In addition, the performance of the method was proved by the excellent agreement between the output factors of the stereotactic conical collimators (4-20 mm diameter) measured by the Roos chamber, where the detector size is larger than the measured field, and the reference detector (diode). The presented deconvolution method has a potential in providing reference data for more accurate physical models of the ionization chamber as well as for improving and enhancing the performance of the detectors in specific dosimetric problems.

SU-E-J-54: Bone Detection in MR Images and Absorbed Dose in a Material Behind Bones in Radiotherapy.

PURPOSE: To determine whether bones could be localized accurately by using MR images only in radiotherapy treatment planning. Furthermore, to measure absorbed dose in a material behind different parts of the bone, and to evaluate dose calculation error in a pseudo-CT image by assuming a single electron density for the bones. METHODS: A dedicated phantom was constructed using fresh deer bones and gelatine. The accuracy of the bone edge location and the bone diameter in MR images were evaluated by comparing those in the images with the actual measures. The absorbed dose behind the bones was measured by a matrix detector at 6 and 15 MV. Thedose calculation error in the bulk density pseudo-CT image was quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00, Elekta CMS Software). RESULTS: The examination of bone position revealed that the bones can be localized within a 1-mm-pixel-size in the MR images. The measured dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15 MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations illustrated that the bulk density pseudo-CT image used causes errors up to nearly 2% to the dose behind the middle part, but also, the edge of the femur. CONCLUSIONS: This research ascertains that the bone localization is not a restrictive issue for radiotherapy treatment planning by using MR imageonly. The work indicates also that the decrease in absorbed dose is not necessarily dependent on the diameter of the bone. Future research shouldinvestigate the generation of more complex pseudo-CT images and the dosecalculations by using these. Supported by Elekta.

Sleep-wake detection based on respiratory signal acquired through a pressure bed sensor.

This study proposes an automatic method for the sleep-wake staging in normal and pathologic sleep based only on respiratory effort acquired from a Pressure Bed Sensor (PBS). Motion and respiratory movements were obtained through a PBS and sleep-wake staging was evaluated from those time series. 20 all night polysomnographies, with annotations, used as gold standard and the time series coming from the PBS were used to develop and to evaluate the automatic wake-sleep staging. The database was built up by: 10 healthy subjects and 10 patients with severe sleep apnea. The agreement of the statistical measures between the automatic classification and the human scoring were: 83.59 ± 6.79 of sensitivity, 83.60 ± 15.13 of specificity and 81.91 ± 6.36 of accuracy. These results suggest that some important indexes, such as sleep efficiency, could be computed through a contactless technique.

Epithermal neutron beam interference with cardiac pacemakers.

In this paper, a phantom study was performed to evaluate the effect of an epithermal neutron beam irradiation on the cardiac pacemaker function. Severe malfunction occurred in the pacemakers after substantially lower dose from epithermal neutron irradiation than reported in the fast neutron or photon beams at the same dose rate level. In addition the pacemakers got activated, resulting in nuclides with half-lives from 25 min to 115 d. We suggest that BNCT should be administrated only after removal of the pacemaker from the vicinity of the tumor.

Surgical management of radiation-associated cutaneous breast angiosarcoma.

The purpose of this study was to investigate the surgical management of radiation-associated cutaneous breast angiosarcoma with an emphasis on surgical margins and choice of reconstruction. Nine cases of angiosarcoma were identified in patients earlier treated with radiotherapy for breast cancer. Breast angiosarcoma was diagnosed a median of 5.25 years following radiotherapy. Median age at diagnosis was 60 years. Surgical treatment consisted of radical mastectomy (four cases), simple mastectomy (two cases) and wide local excision (three cases). Defect reconstruction involved three latissimus dorsi flap reconstructions and four skin grafts. Clear histological margins were achieved in all cases. Median follow-up was 81 months. Six patients were alive and disease-free at the end of the study period. Aggressive surgical resection with wide margins is essential to reduce local recurrence and improve survival.

Tracheal sound parameters of respiratory cycle phases show differences between flow-limited and normal breathing during sleep.

The objective of the present work was to develop new computational parameters to examine the characteristics of respiratory cycle phases from the tracheal breathing sound signal during sleep. Tracheal sound data from 14 patients (10 males and 4 females) were examined. From each patient, a 10 min long section of normal and a 10 min section of flow-limited breathing during sleep were analysed. The computationally determined proportional durations of the respiratory phases were first investigated. Moreover, the phase durations and breathing sound amplitude levels were used to calculate the area under the breathing sound envelope signal during inspiration and expiration phases. An inspiratory sound index was then developed to provide the percentage of this type of area during the inspiratory phase with respect to the combined area of inspiratory and expiratory phases. The proportional duration of the inspiratory phase showed statistically significantly higher values during flow-limited breathing than during normal breathing and inspiratory pause displayed an opposite difference. The inspiratory sound index showed statistically significantly higher values during flow-limited breathing than during normal breathing. The presented novel computational parameters could contribute to the examination of sleep-disordered breathing or as a screening tool.

Intelligent methods for identifying respiratory cycle phases from tracheal sound signal during sleep.

We present two methods for identifying respiratory cycle phases from tracheal sound signal during sleep. The methods utilize the Hilbert transform in envelope extraction. They determine automatically a patient-specific amplitude threshold to be used in the detection. The core of one method is designed to be amplitude-independent whereas the other method uses solely the amplitude information. The methods provided average sensitivities of 98% and 99%, respectively, and positive prediction values of 100% on the total of 1434 respiratory cycles analysed from six different patients. The developed methods seem promising as such or as tools for analysing sleep disordered breathing.

High frequency components of tracheal sound are emphasized during prolonged flow limitation.

A nasal pressure transducer, which is used to study nocturnal airflow, also provides information about the inspiratory flow waveform. A round flow shape is presented during normal breathing. A flattened, non-round shape is found during hypopneas and it can also appear in prolonged episodes. The significance of this prolonged flow limitation is still not established. A tracheal sound spectrum has been analyzed further in order to achieve additional information about breathing during sleep. Increased sound frequencies over 500 Hz have been connected to obstruction of the upper airway. The aim of the present study was to examine the tracheal sound signal content of prolonged flow limitation and to find out whether prolonged flow limitation would consist of abundant high frequency activity. Sleep recordings of 36 consecutive patients were examined. The tracheal sound spectral analysis was performed on 10 min episodes of prolonged flow limitation, normal breathing and periodic apnea-hypopnea breathing. The highest total spectral amplitude, implicating loudest sounds, occurred during flow-limited breathing which also presented loudest sounds in all frequency bands above 100 Hz. In addition, the tracheal sound signal during flow-limited breathing constituted proportionally more high frequency activities compared to normal breathing and even periodic apnea-hypopnea breathing.

New tracheal sound feature for apnoea analysis.

Sleep apnoea syndrome is common in the general population and is currently underdiagnosed. The aim of the present work was to develop a new tracheal sound feature for separation of apnoea events from non-apnoea time. Ten overnight recordings from apnoea patients containing 1,107 visually scored apnoea events totalling 7 h in duration and 72 h of non-apnoea time were included in the study. The feature was designed to describe the local spectral content of the sound signal. The median, maximum and mean smoothing of different time scales were compared in the feature extraction. The feature was designed to range from 0 to 1 irrespective of tracheal sound amplitudes. This constant range could offer application of the feature without patient-specific adjustments. The overall separation of feature values during apnoea events from non-apnoea time across all patients was good, reaching 80.8%. Due to the individual differences in tracheal sound signal amplitudes, developing amplitude-independent means for screening apnoea events is beneficial.

Improved computational fronto-central sleep depth parameters show differences between apnea patients and control subjects.

All-night EEG recordings from 12 male apnea patients and 12 age-matched healthy control subjects were studied in the present work. The spectral mean frequency was used to provide computational sleep depth curves from two frontopolar and two central EEG channels. Our previously presented computational parameters quantifying the properties of the sleep depth curves were improved. The resulting light sleep percentage (LS%) values were higher in apnea patients than in control subjects in the right central brain position (P = 0.028), in concordance to our previous work. Moreover, apnea patients showed higher LS% values in the right frontopolar position (P = 0.008). Also, apnea patients showed a smaller anteroposterior sleep depth difference than control subjects on the right hemisphere (P = 0.002). These are interesting new findings, achieved by the present methodology. Thus, the developed computational parameters were able to quantify, at least to some degree, the disruption of sleep process caused by the recurrent apneic events.

Diffuse sleep spindles show similar frequency in central and frontopolar positions.

The objective of the present work was to examine fronto-central spindle frequency. A previously validated spindle detector, providing an electroencephalographic (EEG) amplitude independent spindle detection, was used to detect bilateral sleep spindles from sleep EEG recordings of ten healthy subjects with a time resolution of 0.33-s. A bilateral spindle detected centrally and frontopolarly simultaneously is called here a diffuse spindle. A bilateral spindle detected only frontopolarly or centrally at a given time is called a pure frontopolar and a pure central spindle, respectively. Spindle frequency was obtained with zero-padded discrete Fourier transform (DFT). Waveform phase angle of diffuse spindles was also examined. A total of 1230 diffuse spindles and 5316 pure central and 2595 pure frontopolar spindles were detected. The difference of median spindle frequency between central and frontopolar brain positions was clearly smaller in diffuse spindles than in pure spindles. Moreover, 34% of the diffuse spindles showed a similar frequency in central and frontopolar locations. This figure was up to 50.9% when including the 700 diffuse spindles fulfilling a strict anteroposterior (AP) timing criteria. The timing criteria selection in diffuse spindle analysis is a new functionality, enabled by the present spindle analysis method. Diffuse spindles showed coherent spindle oscillation in a large fronto-central area. Pure frontopolar spindles might be special cases of diffuse spindles, both of them seem to be generated in the nucleus medialis dorsalis (NMD) of the thalamus.

Detection of compressed tracheal sound patterns with large amplitude variation during sleep.

The objective of the present work was to develop automated methods for the compressed tracheal breathing sound analysis. Overnight tracheal breathing sound was recorded from ten apnoea patients. From each patient, three different types of tracheal sound deflection pattern, each of 10 min duration, were visually scored, viewing the compressed tracheal sound curve. Among them, high deflection patterns are of special interest due to the possible correlation with apnoea-hypopnoea sequences. Three methods were developed to detect patterns with high deflection, utilizing nonlinear filtering in local characterization of tracheal sounds. Method one comprises of local signal maximum, the second method of its local range, and the third of its relative range. The three methods provided 80% sensitivity with 57, 91 and 93% specificity, respectively. Method three provided an amplitude-independent approach. The nonlinear filtering based methods developed here offer effective means for analysing tracheal sounds of sleep-disordered breathing.

Beneficial effects of antiepileptic medication on absence seizures and cognitive functioning in children.

In this prospective clinical study, the effects on cognitive functioning of absence seizures, epileptiform EEG discharges, and their abolishment by antiepileptic medication were evaluated in patients newly diagnosed with childhood absence epilepsy or juvenile absence epilepsy. Eleven children in the study group and ten age- and gender-matched controls with mild asthma underwent combined video/EEG and neurocognitive assessment (IQ, fine-motor fluency, attention, visual and spatial memory). The neuropsychological assessment was repeated after the introduction of antiepileptic medication. Ten children with absence epilepsy became clinically seizure free. The study group improved in attention, fine-motor fluency, and visual memory. The controls improved only in fine-motor and attention skills. Duration of generalized 3-Hz spike-wave discharges and clinical absence seizures was negatively correlated with performance on the visual memory task. Cessation of seizures induced by antiepileptic medication may support neurocognitive functioning in children.

Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology.

Different modalities for imaging cancer-bearing breast tissue samples are described and compared. The images include clinical mammograms and computed tomography (CT) images, CT images with partly coherent synchrotron radiation (SR), and CT and radiography images taken with SR using the diffraction enhanced imaging (DEI) method. The images are evaluated by a radiologist and compared with histopathological examination of the samples. Two cases of lobular carcinoma are studied in detail. The indications of cancer are very weak or invisible in the conventional images, but the morphological changes due to invasion of cancer become pronounced in the images taken by the DEI method. The strands penetrating adipose tissue are seen clearly in the DEI-CT images, and the histopathology confirms that some strands contain the so-called 'Indian file' formations of cancer cells. The radiation dose is carefully measured for each of the imaging modalities. The mean glandular dose (MGD) for 50% glandular breast tissue is about 1 mGy in conventional mammography and less than 0.25 mGy in projection DEI, while in the clinical CT imaging the MGD is very high, about 45 mGy. The entrance dose of 95 mGy in DEI-CT imaging gives rise to an MGD of 40 mGy, but the dose may be reduced by an order of magnitude, because the contrast is very large in most images.

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

Analysis of depth profiling data obtained by confocal Raman microspectroscopy.

The nominal depth resolution achieved in confocal Raman microscopy is on the order of a few micrometers. Often, however, the depth resolution is decreased by light refraction at the sample surface. The problem can be avoided with the use of an immersion objective and index matching oils. Through this intervention the instrument point-spread function (PSF) can be assumed to be independent of the depth of focus in the sample, and spatially invariant depth profiles can be acquired. In this work the instrument PSF was determined by measuring a depth profile of a thick uniform sample and calculating the first derivative of the depth profile curve. The first-derivative method was also used to determine sample thickness. Convolution with the PSF makes it possible to simulate the behavior of the instrument with different sample functions. It is also possible to use the instrument PSF to deconvolve depth-profiling data. Deconvolution reduces the blurring effect of the instrument and increases the depth resolution. Deconvolution can also be used in analysis of the sample surface position and in layer structure analysis. In this paper we show how the convolution integral can be used with the immersion sampling technique to determine the PSF and how the sample thickness can be determined.