Real-Time Ultrasound Image Fusion with FDG-PET/CT to Perform Fused Image-Guided Fine-Needle Aspiration in Neck Nodes: Feasibility and Diagnostic Value.

BACKGROUND AND PURPOSE: New imaging techniques such as hybrid imaging of ultrasound and FDG-PET/CT are available but not yet investigated for node staging. The aim of the study was to evaluate the feasibility and added diagnostic value of real-time image-fused ultrasound-guided fine-needle aspiration with FDG-PET/CT data for node staging. MATERIALS AND METHODS: Ninety-six patients who were referred for cervical lymph node staging with FDG-PET/CT before ultrasound were prospectively included. After routine ultrasound-guided fine-needle aspiration, all FDG-PET-positive nodes were marked on FDG-PET/CT, and real-time image fusing of ultrasound and FDG-PET/CT was performed using the electromagnetic navigation system PercuNav. Already-punctured nodes were confirmed to be PET-positive, and additional fused-ultrasound-guided fine-needle aspiration was performed in previously missed PET-positive nodes. RESULTS: Of 96 patients, 87 (91%) patients had suspicious nodes requiring fine-needle aspiration cytology. Ultrasound-guided fine-needle aspiration was performed in 175 nodes. Cytology was inconclusive in 9/175 (5%) nodes, and 85/166 (51%) nodes were malignant. Target planning was performed in 201 PET-positive nodes; 195/201 (97%) of those nodes were fused successfully. Twenty of 175 ultrasound-guided fine-needle aspiration nodes turned out to be FDG-PET-negative, and 149/175 (85%) of the fused ultrasound-guided fine-needle aspiration nodes were confirmed to be FDG-PET-positive. Of 201 PET-positive nodes, 46 (23%) were additionally identified, and fused ultrasound-guided fine-needle aspiration was performed. Cytology was inconclusive in 4/46 nodes (9%), and 13/42 (31%) nodes were malignant. CONCLUSIONS: Real-time ultrasound image fusion with FDG-PET-positive nodes is feasible in cervical lymph nodes, and fused ultrasound-guided fine-needle aspiration increases the number of malignant nodes detected.

Initial Bacterial Adhesion Properties of Anodically Oxidized Ti6Al4V.

This paper reports about the initial interaction of bacteria with anodically oxidized Ti6Al4V for the use as dental implant abutment surfaces. Ti6Al4V samples are anodically oxidized in hydrofluoric acid using different voltages. The resulting nanotopographies are characterized by atomic force microscopy, scanning electron microscopy and contact angle measurements. The topographies reach from micro-porous structures with small nanoporosities on top to fully hexagonally aligned nanotubes. For initial bacterial adhesion tests, Escherichia coli and Staphylococcus aureus are used. Samples are incubated for 2 h and afterwards non-adherent cells are washed off. The results of live/dead staining and cell counts are presented. Gram-negative and Gram-positive strains show different behavior in respect to total number of initially adherent cells on different micro/nanotopographies. The observed reduction of adhered microorganisms is mainly based on underlying microporous topographies.

Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.

Water scarcity hotspots travel downstream due to human interventions in the 20th and 21st century.

Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.

Municipal water reuse for urban agriculture in Namibia: Modeling nutrient and salt flows as impacted by sanitation user behavior.

Adequate sanitation, wastewater treatment and irrigation infrastructure often lacks in urban areas of developing countries. While treated, nutrient-rich reuse water is a precious resource for crop production in dry regions, excessive salinity might harm the crops. The aim of this study was to quantify, from a system perspective, the nutrient and salt flows a new infrastructure connecting water supply, sanitation, wastewater treatment and nutrient-rich water reuse for the irrigation of agriculture, from a system perspective. For this, we developed and applied a quantitative assessment method to understand the benefits and to support the management of the new water infrastructure in an urban area in semi-arid Namibia. The nutrient and salt flows, as affected by sanitation user behavior, were quantified by mathematical material flow analysis that accounts for the low availability of suitable and certain data in developing countries, by including data ranges and by assessing the effects of different assumptions in cases. Also the nutrient and leaching requirements of a crop scheme were calculated. We found that, with ideal sanitation use, 100% of nutrients and salts are reclaimed and the slightly saline reuse water is sufficient to fertigate 10 m(2)/cap/yr (90% uncertainty interval 7-12 m(2)/cap/yr). However, only 50% of the P contained in human excreta could be finally used for crop nutrition. During the pilot phase fewer sanitation users than expected used slightly more water per capita, used the toilets less frequently and practiced open defecation more frequently. Therefore, it was only possible to reclaim about 85% of nutrients from human excreta, the reuse water was non-saline and contained less nutrient so that the P was the limiting factor for crop fertigation. To reclaim all nutrients from human excreta and fertigate a larger agricultural area, sanitation user behavior needs to be improved. The results and the methodology of this study can be generalized and used worldwide in other semi-arid regions requiring irrigation for agriculture as well as urban areas in developing countries with inadequate sanitation infrastructure.

First Experimental Characterization of Microwave Emission from Cosmic Ray Air Showers.

We report the first direct measurement of the overall characteristics of microwave radio emission from extensive air showers. Using a trigger provided by the KASCADE-Grande air shower array, the signals of the microwave antennas of the Cosmic-Ray Observation via Microwave Emission experiment have been read out and searched for signatures of radio emission by high-energy air showers in the GHz frequency range. Microwave signals have been detected for more than 30 showers with energies above 3×10^{16} eV. The observations presented in this Letter are consistent with a mainly forward-directed and polarized emission process in the GHz frequency range. The measurements show that microwave radiation offers a new means of studying air showers at E≥10^{17} eV.

Neoadjuvant chemotherapy adaptation and serial MRI response monitoring in ER-positive HER2-negative breast cancer.

BACKGROUND: Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with 'luminal'-type breast cancer in whom the second half of neoadjuvant chemotherapy was selected based on the response to the first half. METHODS: Patients with oestrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer received three courses of neoadjuvant dose-dense doxorubicin and cyclophosphamide (ddAC). Three further courses of ddAC were administered in case of a 'favourable response' on the interim magnetic resonance imaging (MRI) and a switch to docetaxel and capecitabine (DC) was made in case of an 'unfavourable response', using previously published response criteria. The efficacy of this approach was evaluated by tumour size reductions on serial contrast-enhanced MRI, pathologic response and relapse-free survival. RESULTS: Two hundred and forty-six patients received three courses of ddAC. One hundred and sixty-four patients (67%) had a favourable response at the interim MRI, with a mean tumour size reduction of 31% after the first three courses and 34% after the second three courses. Patients with unfavourable responsive tumours had a mean tumour size reduction of 12% after three courses and received three courses of DC rather than ddAC. This led to a mean shrinkage of 27%. CONCLUSION: The tumour size reduction of initially less responsive tumours after treatment adaptation adds further evidence that a response-adapted strategy may enhance the efficacy of neoadjuvant chemotherapy.

Kneelike structure in the spectrum of the heavy component of cosmic rays observed with KASCADE-Grande.

We report the observation of a steepening in the cosmic ray energy spectrum of heavy primary particles at about 8×10(16) eV. This structure is also seen in the all-particle energy spectrum, but is less significant. Whereas the "knee" of the cosmic ray spectrum at 3-5×10(15) eV was assigned to light primary masses by the KASCADE experiment, the new structure found by the KASCADE-Grande experiment is caused by heavy primaries. The result is obtained by independent measurements of the charged particle and muon components of the secondary particles of extensive air showers in the primary energy range of 10(16) to 10(18) eV. The data are analyzed on a single-event basis taking into account also the correlation of the two observables.

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

Clinically and mammographically occult breast lesions: detection and classification with high-resolution sonography.

With recent significant advances in ultrasound technology, the potential of high-resolution sonography to improve the sensitivity of cancer diagnosis in women with dense breasts has become a matter of interest for breast imagers. To determine how often physician-performed high-resolution sonography can detect nonpalpable breast cancers that are not revealed by mammography, 8,970 women with breast density grades 2 through 4 underwent high-resolution sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by ultrasound-guided fine-needle aspiration, core-needle biopsy, or surgical biopsy. In 8,103 women with normal findings at mammography and physical examination, 32 cancers and 330 benign lesions were detected in 273 patients with sonography only. Eight additional cancers were found in 867 patients with a malignant (n = 5) or a benign (n = 3) palpable or mammographically detected index lesion. The overall prevalence of cancers detected with screening sonography was 0.41%, and the proportion of sonographically detected cancers to the total number of nonpalpable cancers was 22%. The mean size of invasive cancers detected only by sonography was 9.1 mm, and was not statistically different from the mean size of invasive cancers detected by mammography. The sensitivity of prospective sonographic classification for malignancy was 100%, and the specificity was 31%. In conclusion, the use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult cancers that are no different in size from nonpalpable mammographically detected cancers. Prospective classification of these lesions based on sonographic characteristics resulted in an acceptable benign-to-malignant biopsy rate of 6.3:1.

Incidental findings on sonography of the breast: clinical significance and diagnostic workup.

OBJECTIVE: The purpose of this study was to determine how often physician-performed high-resolution sonography can detect nonpalpable breast lesions not revealed by mammography. A sonographic classification scheme was tested for its accuracy in predicting malignancy of incidentally detected breast lesions. SUBJECTS AND METHODS: Six thousand one hundred thirteen asymptomatic women with breast density grades 2-4 and 687 patients with palpable or mammographically detected breast masses underwent sonography as an adjunct to mammography. All sonographically detected, clinically and mammographically occult breast lesions that were not simple cysts were prospectively classified into benign, indeterminate, or malignant categories. Diagnoses were confirmed by sonographically guided fine-needle aspiration or core needle biopsy. RESULTS: In 6113 asymptomatic women, 23 malignancies in 21 patients were detected with sonography only (prevalence, 0.31%). Five additional malignant lesions were found in patients with a malignant (n = 3) or a benign (n = 2) palpable or mammographically detected index lesion. The mean size of invasive malignancies detected only by sonography was 9.1 mm, which was not significantly different from the mean size of invasive cancers detected by mammography (p = .07). The sensitivity of the prospective sonographic classification for malignancy was 100%, and the specificity was 33.5%. CONCLUSION: The use of high-resolution sonography as an adjunct to mammography in women with dense breasts may lead to detection of a significant number of otherwise occult malignancies that are no different in size from nonpalpable mammographically detected lesions. Prospective classification of these lesions based on sonographic characteristics results in a significant reduction in number of unnecessary biopsies performed.

[Doppler ultrasound determination of average blood flow velocity and flow volume in transjugular intrahepatic portosystemic shunt (TIPS)]. / Dopplersonographische Bestimmung der mittleren Flussgeschwindigkeit und des Flussvolumens im Transjugulären Intrahepatischen Portosystemischen Shunt (TIPS).

AIM: To determine if duplex sonographic measured Time Average Motion (TAM) is an effective parameter for screening examination in routine follow-up after TIPS implantation. PATIENTS AND METHODS: 35 patients underwent duplex sonographic examination by a 3.5 MHz transducer with a follow-up for 12.4 months. RESULTS: A reduction of TAM about 60% from baseline proved with a sensitivity of 90% and a specificity of 93.7% the presence of a hemodynamic relevant stenosis, which was confirmed with angiography. We failed to establish a threshold which pointed out with acceptable accuracy the presence of shunt dysfunction. CONCLUSION: TAM is a good parameter in colour-duplex sonography which permits an objective view of TIPS-function. Angiography should be performed only in patients with suspect duplex-results or clinical worsening. A secondary sign of shunt dysfunction is increasing ascites.

[Value of MR tomography in inconclusive mammography findings]. / Der Stellenwert der MR-Tomographie beim unklaren Mammographiebefund.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging in the assessment of inconclusive findings at mammography, such as indeterminate focal or diffuse breast abnormalities, post-treatment breasts with extensive scarring, dense breasts, and findings suggesting multifocal or multicentric breast cancer. MATERIAL AND METHODS: 254 patients underwent mammography, sonography, and MRI of the breast. Dynamic MR imaging was done using a thin-section three-dimensional gradient-echo sequence (FLASH, TR = 11.8 ms; TE = 5 ms; flip angle = 25 degrees) which was applied in a dynamic fashion before and every 90 seconds after injection of gadopentetate dimeglumine. Diagnoses were confirmed at biopsy (n = 165) or by follow-up (n = 89). RESULTS: Among various breast anomalies, the highest proportion of breast cancers was associated with dense breast tissue (27.8%), architectural distortion (26.9%), and irregular scars (15.8%). Sensitivity of dynamic MR imaging was 93.7%, and specificity was 83.3%. As compared to mammography and sonography, MR detected 6 occult carcinomas, and showed additional malignant lesions in 19/63 women (30.2%) with biopsy-proven breast cancer. CONCLUSION: MR imaging of the breast may provide valuable additional information in indeterminate breast anomalies. However, because of its inherent limitations, it should not replace core needle biopsy in all lesions which are amenable to biopsy. Because of its high sensitivity in the detection of invasive carcinomas in any type of breast tissue, MR imaging is considered the modality of choice in the evaluation of dense breasts in high-risk patients or in patients with clinical suspicion of occult breast cancer, and for preoperative tumor staging.

Behavioural state dependency of renal artery and descending aorta velocimetry and micturition in the normal term fetus.

OBJECTIVE: To examine the behavioural state dependency of renal artery and descending aorta pulsatility index and hourly fetal urinary production rate (HFUPR) in the normal term fetus. DESIGN: An observational study. SUBJECTS: Twenty-three healthy women with a normal singleton pregnancy between 36 and 40 weeks gestation. MAIN OUTCOME MEASURES: Renal artery and descending aorta pulsatility indices were established using pulsed Doppler ultrasound. HFUPR (ml) was estimated using real-time ultrasound. Fetal behavioural states 1F (quiet sleep) and 2F (active sleep) were determined from combined recordings of fetal heart rate, eye movements and body movements. RESULTS: An inverse correlation between pulsatility index and fetal heart pattern was established for both the renal artery (r = 0.60; SD = 0.22; P = 0.0001) and the descending aorta (r = 0.73; SD = 0.16; P = 0.0001). The difference in mean pulsatility index between states 1F and 2F adjusted for fetal heart pattern was 0.09 (SD 0.23) for the renal artery (P = 0.02) and 0.26 (SD 0.19) for the descending aorta (P = 0.0001). Mean HFUPR was significantly higher (44.8%, P = 0.01) in state 1F (96 ml) compared with state 2F (54 ml). During the urinary filling phase, a poor correlation existed between renal artery pulsatility index and HFUPR (r = 0.04) and between descending aorta pulsatility index and HFUPR (r = 0.01). CONCLUSIONS: In the normal term fetus renal artery and descending aorta pulsatility indices are reduced during fetal behavioural state 2F, suggesting reduced downstream impedance at the fetal trunk and in particular at renal level. This behavioural state is, however, also associated with reduced micturition. No correlation exists between renal artery and descending aorta pulsatility indices and fetal urinary output.

Hourly fetal urinary production rate and blood velocity waveforms in the fetal renal artery relative to fetal heart rate pattern and fetal eye movements in normal pregnancies at 30-32 weeks of gestation.

In 14 normal pregnancies at 30-32 weeks of gestation, bloodflow velocity waveforms in the fetal renal artery and fetal micturition were studied in relation to fetal heart rate pattern (FHRP) and fetal eye movements. PI in the fetal renal artery was significantly lower in the presence of FHRP-B and eye movements separately and in combination compared with FHRP-A and absent eye movements separately and in combination. Fetal urinary output was higher in the absence of fetal eye movements. There was an inverse relationship between renal artery PI and fetal heart rate. However, since mean fetal heart rate in the various state variables was not essentially different, no standardization for heart rate was necessary. No correlation existed between renal artery PI and fetal urinary production rate. It can be concluded that in the normal fetus at 30-32 weeks of gestation, renal artery PI demonstrates a significant reduction in the presence of FHRP-B and fetal eye movements separately and in combination, suggesting reduced downstream impedance at renal level. However, the decrease in fetal micturition in the presence of fetal eye movements, suggests that reduced urinary output is determined by changes in fetal central nervous system activity rather than by changes in fetal renal perfusion.

Adrenergic receptors and sodium reabsorption in normotensive subjects as related to salt sensitivity.

We have studied proximal tubular sodium reabsorption as measured by lithium clearance, alpha-2 and beta-2 adrenergic receptors on circulating platelets and lymphocytes, respectively, and urinary aldosterone after variations of sodium intake in 24 normotensive volunteers. Fractional lithium clearance was 14.8% +/- 2.64 under a high salt diet of 200 mmol per day. After a low salt diet of 50 mmol/d for two weeks fractional lithium clearance did not change significantly (13.3% +/- 3.35). There were no correlations between alpha-2 adrenergic receptors, beta-2 adrenergic receptors or the alpha-2/beta-2 ratio and fractional lithium clearance, irrespective of the high or low salt diet. In contrast, a significant correlation was found between urinary aldosterone excretion and alpha-2 receptor densities under low salt diet (r = -0.55, n = 17, p less than 0.02). There were no correlations between beta-2 adrenoceptor density, alpha-2/beta-2 ratio and urinary aldosterone during high or low salt diet. Whereas our results are inconclusive about the value of lithium clearance determinations as a measure of proximal tubular sodium reabsorption during variations of sodium intake, we conclude, that alpha-adrenoceptor density, as measured on circulating blood cells, may possibly be representative for alpha-adrenergic equipment of the kidney. The inverse correlation between urinary aldosterone excretion in subjects equilibrated on a low salt diet of 50 mmol/d and alpha-2 adrenoceptor densities could be interpreted as an indirect evidence, that those subjects with a high alpha-2 adrenoceptor equipment show a high proximal tubular sodium reabsorption and thus can afford a low rate of aldosterone mediated distal tubular sodium reabsorption to maintain sodium balance. Our results are thus in accord with our previous hypothesis, that different receptor equipment of individual subjects may cause marked differences in sodium handling by the kidney. These differences may be responsible, at least in part, for the degree of salt sensitivity in individual subjects.

Up-regulation of alpha 2 adrenoceptors and down-regulation of beta 2 adrenoceptors by high-salt diet in normotensive men: enhanced up-regulation of operative (alpha 2:beta 2) adrenoceptor ratio predicts salt sensitivity.

In 24 normotensive male volunteers (age 20-25 years) reduction of sodium intake from 200 to 50 mmol/day over 2 weeks resulted in a 14% fall of alpha 2-adrenoceptors of platelets from 209.5 to 179.4 fmol/mg (P less than 0.01) and in a 16% rise of beta 2-adrenoceptors of lymphocytes from 13.3 to 16.2 fmol/mg (P less than 0.05) which was reversible by 2 weeks of high sodium intake. In contrast to the comparatively minor changes of alpha 2- and beta 2-adrenoceptor density, the functionally probably more relevant 'operative (alpha 2:beta 2) adrenoceptor ratio' decreased by 53% from 22.9 to 14.9 (P less than 0.01) during the low-salt diet. Although neither the individual changes of alpha 2- and of beta 2-adrenoceptor densities correlated with individual blood pressure changes induced by variations in sodium intake, there was a highly significant positive correlation (r = 0.55, n = 33; P less than 0.01) between the rises of the 'operative adrenoceptor ratio' and the rises of blood pressure induced by high salt intake. We conclude that the 'operative adrenoceptor ratio', although only determined on alpha 2- and beta 2- and not on alpha 1- and beta 1-adrenoceptors, and only on circulating blood cells, may be representative for sympathetic resistance vessel tone, at least as a function of variations of salt intake. Enhanced up-regulation of the 'operative adrenoceptor ratio' in the salt-sensitive part of the population may be one important early step in the development of essential hypertension.