γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging.

OBJECTIVES: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. METHODS: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. RESULTS: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. CONCLUSION: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. .

Impact of deep learning image reconstruction on volumetric accuracy and image quality of pulmonary nodules with different morphologies in low-dose CT.

BACKGROUND: This study systematically compares the impact of innovative deep learning image reconstruction (DLIR, TrueFidelity) to conventionally used iterative reconstruction (IR) on nodule volumetry and subjective image quality (IQ) at highly reduced radiation doses. This is essential in the context of low-dose CT lung cancer screening where accurate volumetry and characterization of pulmonary nodules in repeated CT scanning are indispensable. MATERIALS AND METHODS: A standardized CT dataset was established using an anthropomorphic chest phantom (Lungman, Kyoto Kaguku Inc., Kyoto, Japan) containing a set of 3D-printed lung nodules including six diameters (4 to 9 mm) and three morphology classes (lobular, spiculated, smooth), with an established ground truth. Images were acquired at varying radiation doses (6.04, 3.03, 1.54, 0.77, 0.41 and 0.20 mGy) and reconstructed with combinations of reconstruction kernels (soft and hard kernel) and reconstruction algorithms (ASIR-V and DLIR at low, medium and high strength). Semi-automatic volumetry measurements and subjective image quality scores recorded by five radiologists were analyzed with multiple linear regression and mixed-effect ordinal logistic regression models. RESULTS: Volumetric errors of nodules imaged with DLIR are up to 50% lower compared to ASIR-V, especially at radiation doses below 1 mGy and when reconstructed with a hard kernel. Also, across all nodule diameters and morphologies, volumetric errors are commonly lower with DLIR. Furthermore, DLIR renders higher subjective IQ, especially at the sub-mGy doses. Radiologists were up to nine times more likely to score the highest IQ-score to these images compared to those reconstructed with ASIR-V. Lung nodules with irregular margins and small diameters also had an increased likelihood (up to five times more likely) to be ascribed the best IQ scores when reconstructed with DLIR. CONCLUSION: We observed that DLIR performs as good as or even outperforms conventionally used reconstruction algorithms in terms of volumetric accuracy and subjective IQ of nodules in an anthropomorphic chest phantom. As such, DLIR potentially allows to lower the radiation dose to participants of lung cancer screening without compromising accurate measurement and characterization of lung nodules.

Genes or culture: are mitochondrial genes associated with tool use in bottlenose dolphins (Tursiops sp.)?

Some bottlenose dolphins use marine sponges as foraging tools ('sponging'), which appears to be socially transmitted from mothers mainly to their female offspring. Yet, explanations alternative to social transmission have been proposed. Firstly, the propensity to engage in sponging might be due to differences in diving ability caused by variation of mitochondrial genes coding for proteins of the respiratory chain. Secondly, the cultural technique of sponging may have selected for changes in these same genes (or other autosomal ones) among its possessors. We tested whether sponging can be predicted by mitochondrial coding genes and whether these genes are under selection. In 29 spongers and 54 non-spongers from two study sites, the non-coding haplotype at the HVRI locus was a significant predictor of sponging, whereas the coding mitochondrial genes were not. There was no evidence of selection in the investigated genes. Our study shows that mitochondrial gene variation is unlikely to be a viable alternative to cultural transmission as a primary driver of tool use in dolphins.

A large-scale multicentre study in Belgium of dose area product values and effective doses in interventional cardiology using contemporary X-ray equipment.

In this paper, a large-scale multicentre patient dose study performed in eight Belgian interventional cardiology departments is presented. Effective dose (E) was calculated based on a detailed dose-area product (DAP)-registration during each procedure and by using conversion coefficients generated by the Monte Carlo-based computer program PCXMC. Conversion coefficients were found to be 0.177 mSv Gycm(-2) for systems that do not use any additional copper filtration in cineradiography and 0.207 mSv Gycm(-2) for systems that use additional copper filtration in cineradiography. Mean E values of 9.6 and 15.3 mSv for diagnostic and therapeutic procedures, respectively, were obtained. DAP distributions were investigated in order to derive dose reference levels: 71 and 106 Gycm2 for diagnostic and therapeutic procedures, respectively, are proposed. Significant differences were observed in DAP distributions taking into account whether additional copper filtration was used in the cineradiography mode. Apart from the skin, the organs most at risk are lungs and heart. The probability of fatal cancer for the studied population amounted to 1.1x10(-4) and 2.1x10(-4) for diagnostic and therapeutic procedures, respectively, for the age distribution of the patients considered in this multicentre study.

Interventional cardiovascular procedures in Belgium: effective dose and conversion factors.

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P < 0.001), on filtration insertion (P < 0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P < 0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm(-2) was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P < 0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures.

INFLUENCE OF LOCALIZER AND SCAN DIRECTION ON THE DOSE-REDUCING EFFECT OF AUTOMATIC TUBE CURRENT MODULATION IN COMPUTED TOMOGRAPHY.

The purpose of this study was to investigate the influence of the localizer and scan direction on the dose-reducing efficacy of the automatic tube current modulation (ATCM) in computed tomography (CT). Craniocaudal and caudocranial chest CT scans, based on anterior-posterior (AP), posterior-anterior (PA), lateral (LAT) or dual AP/LAT localizers, of an anthropomorphic phantom containing thermoluminescent dosimeters (TLDs), were made on three Siemens systems. TLD readings were converted to lung and thyroid doses. A second dose estimation was performed based on Monte Carlo simulations. In addition, the ATCM behaviour of GE and Toshiba was evaluated based on AP, PA and LAT localizers. Compared with AP, tube currents of PA and AP/LAT scans were on average 20 % higher and 40 % lower, respectively, for the Siemens systems. Consequently, thyroid and lung doses increased with 60 % with a PA instead of an AP/LAT scan, with significant differences in image noise. Moreover, the thyroid dose halves by taking the scan in caudocranial direction. Noise values were not significantly different when changing scan direction.

Analysis of image quality in digital chest imaging.

An evaluation of the image quality of an amorphous silicon flat-panel detector system and a computed radiology system compared with a screen-film system was performed by means of contrast-detail phantom images. Hard and soft copy images were evaluated. Although patient dose at clinical settings was strongly decreased with the amorphous silicon system, the low-contrast visibility with this system was still significantly better than with the screen-film system. For the computed radiology system, low-contrast visibility was comparable to the screen-film system. Best results were obtained by soft copy reading at full resolution with adaptation of contrast and brightness. Changing tube voltage (102-133 kV), or additional filtration, did not significantly affect image quality. However, low-contrast visibility improved significantly with increasing exposure. It was clearly demonstrated that, in chest imaging, the amorphous silicon system has superior imaging characteristics compared to the screen-film and the computed radiology system.

Biodistribution and dosimetry study of 123I-rh-annexin V in mice and humans.

This study reports on the optimization of the labelling procedure of clinical grade 123I-rh-annexin V and on the investigation of the biodistribution and dosimetry of 123I-rh-annexin V, a tracer proposed for the study of apoptosis in mice and humans. Research grade 123I-rh-annexin V was prepared as described previously, whereas clinical grade 123I-rh-annexin V was prepared according to a modified IodoGen method. NMRI mice, 3-4 weeks of age, received research grade 123I-rh-annexin V (74.0+/-3.7 kBq/mouse) by intravenous (i.v.) injection and killed at preset time points. Afterwards, the collected organs, blood, urine and faeces were counted for radioactivity and determined as %ID/g tissue or %ID over time. Secondly, six volunteers with normal liver and kidney function underwent whole-body scans up to 21 h after i.v. injection of clinical grade 123I-rh-annexin V (345+/-38 MBq). Time-activity curves were generated for the organs of interest, e.g., thyroid, heart, liver, kidneys and whole body, by fitting the organ specific geometric mean counts, obtained from region of interest analysis of acquired images in humans. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Clinical grade 123I-rh-annexin V was obtained in radiochemical yields of 87.0+/-6.5% and radiochemical purities >98%. In mice, research grade 123I-rh-annexin V accumulated primarily in liver, kidney, stomach and lung tissue, limiting its usefulness for imaging of ongoing apoptosis in the abdominal and thoracic region. Clearance was predominantly urinary. In humans, acquired images with the clinical grade radioligand showed low lung uptake, resulting in good imaging conditions for the thoracic region. On the other hand, delayed imaging of the abdominal region was impeded due to extensive bowel activity. The highest absorbed doses were received by the thyroid, the kidneys, the heart wall, the liver and bone surfaces. The average effective dose of 123I-rh-annexin V was estimated to be 0.02 mSv.MBq-1. The amount of 123I-rh-annexin V required for in vivo imaging, results in an acceptable effective dose to the patient.

Intra-arterial radionuclide therapy for liver tumours: effect of selectivity of catheterization and 131I-Lipiodol delivery on tumour uptake and response.

Several authors have demonstrated the good tolerance of hepatic intra-arterial 131I-Lipiodol therapy and report survival rates of 21-25% after 1 year in inoperable patients. This study explored the possibility that more selective hepatic arterial instillation could be a strategy for increasing tumoural uptake and response of 131I-Lipiodol. Between June 1999 and September 2001 we selected 24 patients: 14 received a selective instillation of 131I-Lipiodol to the proper hepatic artery (SEL group); and 10 received a hyperselective instillation in the right or left hepatic artery (HYP-SEL group). The individual 131I-Lipiodol activity as a per cent of the injected activity per millilitre of tumour (%IA/ml tumour) was correlated with the selectivity of instillation in 28 tumours and with tumour response in 24 tumours. Differences in tumour response or tumour uptake between the SEL and HYP-SEL groups were not significant. In general, we observed a %IA/ml tumour of 0.05-2.6% for the uptake of 131I-Lipiodol. The uptake was significantly higher in responsive disease than in stable or progressive disease (P=0.002). A large tumour volume was invariably related to low uptake of 131I-Lipiodol and progressive disease (P=0.008). In conclusion, our study does not support the general use of hyper-selective or super-selective intra-arterial administration of 131I-Lipiodol. This result may be extrapolated to similar types of intra-arterial, loco-regional hepatic radionuclide therapy.

Establishment of trigger levels to steer the follow-up of radiation effects in patients undergoing fluoroscopically-guided interventional procedures in Belgium.

The accumulated dose to the skin of the patient during fluoroscopically-guided procedures can exceed the thresholds for tissue reactions. In practice, interventionalists have no direct information about the local procedure-related skin doses in their patient, causing suboptimal or delayed treatment. In current study, the accumulated Kerma-Area-Product (KAP) values were registered, as well as the reference air kerma (Ka,r) values, if available, for almost 200 cases undergoing seven different procedures. A sheet filled with 50 thermoluminescent dosemeters was wrapped around each patient to measure the peak skin dose. In a significant part of the Transjugular Intrahepatic Portosystemic Shunt (TIPSS) procedures, chemo-embolizations of the liver and cerebral embolizations, the threshold values for deterministic skin damage (2 Gy) were attained. Trigger values in terms of KAP, corresponding to a peak skin dose of 2 Gy, were determined. In general, our results comply reasonably well with the values proposed in the NCRP 168 report, with a KAP value of 425 Gy cm² and a Ka,r value of 3 Gy, corresponding to a peak skin dose of 3 Gy. Only for the TIPSS procedure a considerably lower value of 2 Gy was obtained at the published Ka,r and for the RF ablations we obtained a considerably lower value of 250 Gy cm² in terms of KAP.

[Fine-needle aspiration cytology of thyroid nodules: molecular diagnostics in a routine diagnostic setting]. / Feinnadelzytologie von Schilddrüsenknoten: Molekulare Diagnostik in der klinischen Routine.

BACKGROUND AND OBJECTIVE: Results for the detection of point mutations and rearrangements have thus far been obtained by fresh material of fine needle aspiration cytology (FNAC). After a first retrospective study we report on the diagnostic detection in routinely obtained, consecutive air-dried FNAC smears. METHODS: RNA and DNA was extracted from 154 consecutive routine air-dried FNAC smears: 80 with microfollicular proliferation (MFP), 45 with follicular neoplasia (FN), 26 with the cytological diagnosis of papillary carcinomas (PTC) and 3 which were suspicious for malignancy. PAX8/PPARG and RET/PTC3 rearrangements were detected by qPCR, while BRAF and RAS point mutations were detected by pyrosequencing. RESULTS: Only 0.7 % and 5.3 % of the routine air-dried FNAC samples did not allow analysis of a point mutation or rearrangements, respectively. NRAS mutations could be detected in 7 MFP smears, and in one of FN and PTC samples, respectively. HRAS mutations were detected in one MPF and one FN sample. A KRAS mutation was only detected in one FN sample, whereas BRAF mutations were detected in 20 samples with PTC (but in no other sample). PAX8/PPARG was detected in 2 MFP samples, while RET/PTC was detected in only one MFP sample. In total, 13.8 % MFP-FNAC, 6.7 % FN-FNAC, and 80.8 % PTC-FNAC samples harbored a mutation. CONCLUSION: These results demonstrate that rearrangements and point mutations can be detected in routinely obtained air-dried FNAC samples.

Rhenium-188 based radiopharmaceuticals for treatment of liver tumours.

Rhenium-188 (188Re) is a high energy beta-emitter with a physical half life of 17 hours. Various 188Re based radiopharmaceuticals were developed to treat liver malignancies. The vast majority of studies focus on patients suffering from hepatocellular carcinoma (HCC). Most radiopharmaceuticals are based on Lipiodol as a vehicle for the rhenium-188. The radiopharmaceutical that was tested clinically in detail is the 188Re-HDD/Lipiodol, developed by the Seoul University. Clinical data derived from several phase I and II studies using 188Re-HDD/Lipiodol suggest an excellent tolerance in patients with Child-Pugh A cirrhosis. A shortcoming in some trials was the occasional low labelling efficiency of 188Re-HDD/Lipiodol. Some newer 188Re based radiopharmaceuticals claim to have consistent high labelling efficiencies, however clinical data for these compounds are scarce or lacking at this moment. Hopefully, phase I clinical data will become available for promising radiopharmaceuticals such as 188Re-SSS-Lipiodol, developed by the group of Rennes, in the upcoming years. In Dresden a very different approach is used. They labelled human serum albumin microspheres with high activities of 188Re. In a small group of patients with liver metastasis and a few HCC patients, treatment proved safe. In the present clinical field, 188Re-based radiopharmaceuticals will have to proof firmly their strength and reliability in large patient groups if they want to compete with the commercially available yttrium-90 microspheres.

Does digital flat detector technology tip the scale towards better image quality or reduced patient dose in interventional cardiology?

As dynamic flat-panel detectors (FD) are introduced in interventional cardiology (IC), the relation between patient dose and image quality (IQ) needs to be reconsidered for this type of image receptor. On one hand this study investigates IQ of a FD system by means of a threshold contrast-detail analysis and compares it to an image intensifier (II) system on a similar X-ray setup. On the other hand patient dose for coronary angiography (CA) procedures on both systems is compared by Dose-Area Product (DAP)-registration of a patient population. The comparative IQ study was performed for a range of entrance dose rates (EDR) covering the fluoroscopy and cinegraphy working mode. In addition the IQ investigation was extended to a similar study under automatic brightness control (ABC). As well the systematic study of IQ as a function of EDR as the study performed under ABC point to a better IQ for FD in cinegraphy mode and no difference between both systems in fluoroscopy mode. The patient population study resulted in mean DAP values of 31Gycm(2) (II system) and 33Gycm(2) (FD system) (p=0.68) for CA procedures. As well total DAP as contributions of fluoroscopy and cinegraphy on both systems are not significantly different. To conclude, we could state that profit was taken from the intrinsic better performance of the FD for cinegraphy mode in producing higher quality images in this mode but without any effect on patient dose for CA procedures.

A large-scale multicentre study of patient skin doses in interventional cardiology: dose-area product action levels and dose reference levels.

For 318 patients in 8 different Belgian hospitals, the entire skin-dose distribution was mapped using a grid of 70 thermoluminescence dosimeters per patient, allowing an accurate determination of the maximum skin dose (MSD). Dose-area product (DAP) values, exposure parameters and geometry, together with procedure, patient and cardiologist characteristics, were also registered. Procedures were divided into two groups: diagnostic procedures (coronary angiography) and therapeutic procedures (dilatation, stent, combined procedures (e.g. coronary angiography + dilatation + stent)). The mean value of the MSD was 0.310 Gy for diagnostic and 0.699 Gy for therapeutic procedures. The most critical projection for receiving the MSD is the LAO90 (left anterior oblique) geometry. In 3% of cases, the MSD exceeded the 2 Gy dose threshold for deterministic effects. Action levels in terms of DAP values as the basis for a strategy for follow-up of patients for deterministic radiation skin effects were derived from measured MSD and cumulative DAP values. Two DAP action levels are proposed. A first DAP action level of 125 Gy cm(2) corresponding to the dose threshold of 2 Gy would imply an optional radiopathological follow-up depending on the cardiologist's decision. A second DAP action level of 250 Gy cm(2) corresponding to the 3 Gy skin dose would imply a systematic follow-up. Dose reference levels - 71.3 Gy cm(2) for diagnostic and 106.0 Gy cm(2) for therapeutic procedures - were derived from the 75 percentile of the DAP distributions. As a conclusion, we propose that total DAP is registered in patient's record file, as it can serve to improve the follow-up of patients for radiation-induced skin injuries.

Typetesting of physical characteristics of digital mammography systems: first experiences within the Flemish breast cancer screening programme.

To avoid the purchase of a digital mammography system by radiologists with intrinsic characteristics not able to fulfil the physical-technical quality requirements of the acceptance tests of the European guidance document, typetesting of digital equipment was introduced in the organisation and legislation of the Flemish breast cancer screening programme. Typetesting is performed for two types of instrumentation: systems for image capture and -processing and systems for image presentation. Typetesting is finalised or ongoing for eight DR systems and four CR systems. Eight workstations were or are submitted to the typetesting for image presentation. Experiences gained in typetesting of systems for image capture and -processing up to now show that the contrast-detail analysis of CDMAM phantom imaging and the homogeneity tests are most stringent. In general DR performs better than CR in imaging performance. Typetesting for image presentation has shown no difference in quality between CRT and LCD monitors. Furthermore, 3 MP monitors also pass the tests. However, to get the full resolution capabilities of the image capture system zooming in and scrolling over the image is necessary, which is time-consuming in clinical practice. Finally, we emphasize that typetesting involves also an evaluation of a set of clinical images by the working party of radiologists and that succeeding in typetesting does not mean that a particular system passes automatically the acceptance testing. A perfect tuning of the system and the coupling to a high quality X-ray system is necessary as well.

Optimised tracer-dependent dosage cards to obtain weight-independent effective doses.

PURPOSE: The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to determine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. METHODS: Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiopharmaceuticals were investigated using cluster analysis. RESULTS: Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA=7, nB=76, nC=12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodine-labelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. CONCLUSION: Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses.

Surface-emitting second-harmonic generation in a semiconductor vertical resonator.

We experimentally demonstrate a 240-fold increase in the efficiency of an AlGaAs/ALAs surface-emitting second-harmonic generation device by embedding the waveguide core in a monolithic vertical resonant cavity. Calculations indicate that conversion efficiencies of several percent per watt for second-harmonic generation of green or blue light may be expected in an optimized semiconductor resonant vertical-cavity surface emitter.

Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers.

In a randomized, double-blind, placebo-controlled study in 12 healthy volunteers pharmacokinetics, safety and impact on the faecal microflora of cefepime were determined. For eight days eight volunteers received cefepime 1000 mg bd by constant infusion over 30 min, four volunteers received placebo. Concentrations of cefepime in serum and urine were measured by bioassay and HPLC. The correlation between the two methods was good and the bioassay results were used for pharmacokinetic calculations. The faecal flora was analysed twice before the study, twice during the study and four times after cefepime administration. There were no significant differences in the pharmacokinetic parameters between days 1 and 8. The following values (mean +/- S.D.) represent day 1. The maximum concentration of 72.69 +/- 12.2 mg/L immediately after infusion decreased to 0.56 +/- 0.17 mg/L after 12 h. The mean 12 h recovery in urine was 93.69 +/- 2.14%. Pharmacokinetic parameters based on an open two-compartment model were as follows (mean +/- S.D.): area under the curve, 142.65 +/- 18.35 mg.h/L; elimination half-life 110.3 +/- 8.3 min; steady state volume of distribution 16.0 +/- 1.9 L/70 kg; total clearance, 107.0 +/- 16.0 mL/min; renal clearance 103.0 +/- 15.2 mL/min. No accumulation was observed during the eight day study period with cefepime at this dosage; trough levels on days 2-7 ranged from 0.52 +/- 0.26 mg/L to 0.90 +/- 0.33 mg/L. In the cefepime treated group the following side-effects were noted: headache (5), fatigue (4), nausea/stomach ache (2), soft stool (2), transient scotoma (1). Side-effects in the placebo group were: headache (2) fatigue (3), nausea/stomach-ache (1), soft stool (2) and photophobia (1). During cefepime administration a decrease in the number of Escherichia coli and bifidobacteria in faeces was observed, whereas Bacteroides spp. and clostridia showed a slight increase. The numbers of faecal bacteria returned to normal 20 to 48 days after the study was completed.