Dose-effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization.

PURPOSE: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([166Ho]-radioembolization). MATERIALS AND METHODS: Single center, retrospective study included patients with NELM that received [166Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (Dt) and whole liver healthy tissue (Dh) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS). RESULTS: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean Dt in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a Dt of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached. CONCLUSION: This study confirms the safety and efficacy of [166Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a Dt of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

Identification of sampling patterns for high-resolution compressed sensing MRI of porous materials: 'learning' from X-ray microcomputed tomography data.

There exists a strong motivation to increase the spatial resolution of magnetic resonance imaging (MRI) acquisitions so that MRI can be used as a microscopy technique in the study of porous materials. This work introduces a method for identifying novel data sampling patterns to achieve undersampling schemes for compressed sensing MRI (CS-MRI) acquisitions, enabling 3D spatial resolutions of 17.6 µm to be achieved. A data-driven learning approach is used to derive k-space undersampling schemes for 3D MRI acquisitions from 3D X-ray microcomputed tomography (µCT) datasets acquired at a higher spatial resolution than can be acquired using MRI. The performance of the new sampling approach was compared to other, well-established sampling strategies using simulated MRI data obtained from high-resolution µCT images of rock core plugs. These simulations were performed for a range of different k-space sampling fractions (0.125-0.375) using images of Ketton limestone. The method was then extended to consideration of imaging Estaillades limestone and Fontainebleau sandstone. The results show that the new sampling approach performs as well as or better than conventional variable density sampling and without need for time-consuming parameter optimisation. Further, a bespoke sampling pattern is produced for each rock type. The novel undersampling strategy was employed to acquire 3D magnetic resonance images of a Ketton limestone rock at spatial resolutions of 35 and 17.6 µm. The ability of the k-space sampling scheme produced using the new approach in enabling reconstruction of the pore space characteristics of the rock was then demonstrated by benchmarking against the pore space statistics obtained from high-resolution µCT data. The MRI data acquired at 17.6 µm resolution gave excellent agreement with the pore size distribution obtained from the X-ray microcomputed tomography dataset, while the pore coordination number distribution obtained from the MRI data was slightly skewed to lower coordination numbers. This approach provides a method of producing a k-space undersampling pattern for MRI acquisition at a spatial resolution for which a fully sampled acquisition at that spatial resolution would be impractically long. The approach can be easily extended to other CS-MRI techniques, such as spatially resolved flow and relaxation time mapping. LAY DESCRIPTION: Magnetic resonance imaging (MRI) is widely used to study the microstructure of, and fluid transport phenomena in porous media relevant for engineering applications. A major application is the study of water and hydrocarbon transport in porous sedimentary rocks, which typically have pore sizes smaller than 100 µm. The spatial resolution of routine MRI acquisitions, however, is limited to several hundred µm due to the relatively low sensitivity of the magnetic resonance method. Therefore, there exists a strong motivation to increase the spatial resolution of MRI by one to two orders of magnitude to be able to study these rocks at a pore scale. This work reports the initial step towards achieving this. Three-dimensional images of rock pore structure are acquired at both 35 and 17.6 µm spatial resolution. In ongoing work, these methods are now being incorporated into magnetic resonance velocity imaging methods, thereby enabling imaging of both pore structure and hydrodynamics at these much higher spatial resolutions than were hitherto possible. Although X-ray microcomputed tomography (µCT) produces high spatial resolution images, it is far more limited in being able to spatially map transport processes (i.e. flow) in porous media. This work reports a strategy for accelerating the image acquisition time such that sufficient signal-to-noise ratio (SNR) is achieved to increase the spatial resolution, that is, the voxel size within which there is sufficient SNR within the resulting image. To achieve this, a technique known as compressed sensing is used which exploits undersampling of the acquired data relative to the standard fully sampled image. In MRI, data are acquired in so-called k-space and Fourier transformed to yield the real space image. The challenge, when undersampling, is to optimise the specific points in k-space that are acquired because these will influence the quality of the resulting image. This work reports a straightforward, robust strategy for identifying the optimal sets of k-space points to acquire. The method introduced uses simulated MRI images calculated from high-resolution µCT images of the rocks of interest, from which optimised MRI sampling patterns are obtained. The method does not require any optimisation of parameters for its implementation, which is a significant advantage compared to other strategies. Moreover, we show that the pore space characteristics of the acquired MRI images are in excellent agreement with the same characteristics obtained from a high-resolution µCT image.

In the critically ill patient, diabetes predicts mortality independent of statin therapy but is not associated with acute lung injury: a cohort study.

OBJECTIVES: Patients with diabetes mellitus form 23%-30% of published cohorts of critically ill patients. Conflicting published evidence links diabetes mellitus to both higher and lower mortality. Other cohort studies suggest that diabetes mellitus protects against acute lung injury. We hypothesized that diabetes mellitus is an independent risk factor for mortality. We further hypothesized that diabetes mellitus is a risk factor for cardiac overload and not for acute lung injury. DESIGN: Retrospective cohort study. SETTING: The intensive care unit of a tertiary referral hospital. PATIENTS: From November 1, 2004, to October 1, 2007, a cohort of patients admitted ≥48 hrs to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,013 patients, 317 had diabetes mellitus. Ninety-day mortality was higher in the diabetes mellitus patients compared to patients without diabetes mellitus (hazard ratio 1.53, 95% confidence interval 1.29-1.80). This association strengthened after adjusting for confounders and for medication (hazard ratio 1.53, 95% confidence interval 1.07-2.17).We found no association between diabetes mellitus and acute lung injury (relative risk ratio 1.01, 95% confidence interval 0.78-1.32; adjusted relative risk ratio 0.99, 95% confidence interval 0.75-1.31), but diabetes mellitus was a risk factor for cardiac overload (relative risk ratio 1.91, 95% confidence interval 1.30-2.81; adjusted relative risk ratio 1.45, 95% confidence interval 0.97-2.18). Statins were associated with both a reduced risk of mortality (hazard ratio 0.74, 95% confidence interval 0.63-0.87; adjusted hazard ratio 0.53, 95% confidence interval 0.44-0.64) and a decreased risk of developing acute lung injury (relative risk ratio 0.71, 95% confidence interval 0.56-0.89; adjusted relative risk ratio 0.61, 95% confidence interval 0.47-0.79). CONCLUSIONS: Diabetes mellitus is an independent risk factor for mortality in critically ill patients and failure to adjust for statins underestimates the size of this association. Diabetes mellitus is not associated with acute lung injury but is associated with cardiac overload. A diagnosis of cardiac overload excludes a diagnosis of acute lung injury. Investigators who do not account for cardiac overload as a competing alternative outcome may therefore falsely conclude that diabetes mellitus protects from acute lung injury.

Use of statins is associated with an increased risk of rheumatoid arthritis.

OBJECTIVES: Statins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case-control study using the Netherlands Information Network of General Practice database. METHODS: The authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001-2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease-modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis. RESULTS: Cases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found. CONCLUSIONS: Statin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies.

[A male with a suprapatellar mass]. / Een man met een zwelling boven de knie.

This case describes a 52-year-old man who presents with a suprapatellar mass, that gradually increased over a period of several years. His medical history describes an episode of gout 12 years previously, for which he never used medication. Extensive imaging and histopathologic examination confirm the presence of a gout tophus.

The predictive value of phase angle on long-term outcome after ICU admission.

INTRODUCTION: The use of severity of illness scoring systems, including the Acute Physiology and Chronic Health Evaluation (APACHE) III score, has made it possible to compare groups of patients and evaluate treatment strategies. Phase angle, derived from bio-impedance analysis, reflects tissue quality and quantity in which cell mass, membrane integrity and hydration state are represented. We hypothesized that phase angle on ICU admission may serve as a proxy for physical frailty and as such can be used as an additional predictor of long-term mortality after ICU admission. METHODS: A single-center prospective observational cohort study with consecutive patients, admitted to the ICU between June 2018 and June 2019. Demographic data, APACHE III, comorbidity, and phase angle in the first 6 h after ICU admission were collected and the ICU, hospital, and 1-year survival were registered. RESULTS: Of all 1023 patients, 115 (11%) died within a year after ICU admission. Nonsurvivors had higher APACHE III scores than survivors [86 (65-119) vs. 55 (46-67), p < 0.001]. Phase angle was significantly higher in survivors than in nonsurvivors [5.4 (4.7-6.4) vs. 4.7 (3.9-6.0), p < 0.001]. Univariate analysis showed an association between mortality and admission type, sepsis, presence of malignancy, APACHE III, and PhA. Multivariate logistic regression analysis using these variables confirmed low PhA to be an independent predictor of 1-year mortality (OR: 1.81; CI: 1.09-2.97; p = 0.02), in addition to presence of malignancy (OR: 2.30; CI: 1.31-4.02; p = 0.004) and APACHE III score (OR: 1.03; CI: 1.02-1.04; p < 0.001). CONCLUSION: In this single center study, low phase angle was independently associated with 1-year all-cause mortality after ICU admission. CLINICALTRIALS: gov number: NCT0444976.

Detection of Early Ischemic Changes with Virtual Noncontrast Dual-Energy CT in Acute Ischemic Stroke: A Noninferiority Analysis.

BACKGROUND AND PURPOSE: Dual-energy virtual NCCT has the potential to replace conventional NCCT to detect early ischemic changes in acute ischemic stroke. In this study, we evaluated whether virtual NCCT is noninferior compared with standard linearly blended NCCT, a surrogate of conventional NCCT, regarding the detection of early ischemic changes with ASPECTS. MATERIALS AND METHODS: Adult patients who presented with suspected acute ischemic stroke and who underwent dual-energy NCCT and CTA and brain MR imaging within 48 hours were included. Standard linearly blended images were reconstructed to match a conventional NCCT. Virtual NCCT images were reconstructed from CTA. ASPECTS was evaluated on conventional NCCT, virtual NCCT, and DWI, which served as the reference standard. Agreement between CT assessments and the reference standard was evaluated with the Lin concordance correlation coefficient. Noninferiority was assessed with bootstrapped estimates of the differences in ASPECTS between conventional and virtual NCCT with 95% CIs. RESULTS: Of the 193 included patients, 100 patients (52%) had ischemia on DWI. Compared with the reference standard, the ASPECTS concordance correlation coefficient for conventional and virtual NCCT was 0.23 (95% CI, 0.15-0.32) and 0.44 (95% CI, 0.33-0.53), respectively. The difference in the concordance correlation coefficient between virtual and conventional NCCT was 0.20 (95% CI, 0.01-0.39) and did not cross the prespecified noninferiority margin of -0.10. CONCLUSIONS: Dual-energy virtual NCCT is noninferior compared with conventional NCCT for the detection of early ischemic changes with ASPECTS.

Feasibility of bone density evaluation using plain digital radiography.

OBJECTIVE: For the radiographic evaluation of subchondral bone changes (sclerosis) in osteoarthritis (OA), bone density (BD) is commonly subjectively assessed. BD evaluation using plain digital radiography might be influenced by acquisition and post-processing (PP) settings. Objective of this study was to evaluate the effects of these settings on the measurement of BD using digital radiographs. METHODS: A bone density standard (BDS) of hydroxyapatite (HA) mimicked a BD range of 1.0-5.75 g/cm(2). Digital radiographs were acquired with variation in acquisition settings, and with clinical and minimal PP. An aluminum step wedge served as an internal reference to express the gray values of the BDS in mm aluminum equivalents (mmAl). The relation (R(2)) between actual BD and BD normalized to the reference wedge was evaluated with linear regression analyses for radiographs with variations in PP and acquisition settings. Precision of BD measurement of the BDS was evaluated for application in clinical practice. RESULTS: The correlation between actual BD and BD normalized to the reference was improved by changing PP from clinical (R(2)=0.96) to minimal (R(2)=0.98). Higher tube voltage [kilovolt (kV)] improved the correlation further. Even for clinical PP, average standard deviation (SD) was 0.97 mmAl, much smaller than the change of 2.51 mmAl clinically observed in early OA, which implies the feasibility of BD measurements on digital radiographs. CONCLUSION: Changing PP and acquisition settings in clinical practice can have profound effect on outcome. If done with care, accurate BD measurement is feasible using plain digital radiography.

Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.

FISH applications for genomics and plant breeding strategies in tomato and other solanaceous crops.

This paper describes the use of advanced fluorescence in situ hybridization (FISH) technologies for genomics and breeding of tomato and related Solanum species. The first part deals with the major determinants of FISH technology: (1) spatial resolution, which depends on the diffraction limit of the microscope and the type of chromosome, chromatin or isolated DNA fibres as target for the hybridisation; (2) the detection sensitivity, which is limited by the sensitivity and dynamic range of the CCD camera and the quality of the microscope, and the amplification system of the weak signals from tiny probe molecules; (3) simultaneous detection of multiple probes labelled directly or indirectly with up to 5 different fluorophores, whether or not in different combinations and/or mixed at different ratios. The power and usability of such multicolour FISH is indispensable when large numbers of bacterial artificial chromosomes (BACs) or other vectors with genomic DNA are available. Mapping of multiple BACs on chromosomes are powerful instruments confirming their assumed genetic position, whereas pooled BACs for a given chromosome arm will reveal the gaps between the BACs or derived contigs of their physical maps. Tandem and dispersed repeats, which are abundant in the genomes of most species, can be analysed in repeat bar coding FISH, showing the major blocks of repeats in heterochromatin and euchromatin areas. Repeat-rich areas of the chromosomes can also be demonstrated by hybridisation of probed Cot fractions of sheared genomic DNA; a powerful method to elucidate the heterochromatin domains for genomic studies. In addition, unlabelled Cot DNA, as blocking agent in BAC-FISH painting, suppresses repetitive sequences from the BACs to hybridise on the chromosomes. Cross-species BAC-FISH painting with labelled probes from tomato and potato BACs and hybridised on the chromosomes of related species, under appropriate conditions, is a powerful instrument to demonstrate chromosomal rearrangements, including inversions and translocations. The technology not only supports phylogenetic studies between the taxa under study but can also be helpful in breeding programs with crops containing introgressed regions from related species when linkage drag or meiotic pairing disturbances between the homoeologues are assumed. In the next steps in comparative genomics, we now can detect smaller chromosomal and DNA rearrangements, diminutions and amplifications of repeats and changes of the epigenetic status of introgressed regions.

Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis.

OBJECTIVES: To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis. METHODS: Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls. RESULTS: Peptides representing amino acid regions 16-39 and 263-282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263-282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263-282 of PG suggesting a possibility of molecular mimicry in these patients. CONCLUSIONS: These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis.

Holmium-166 poly(L-lactic acid) microsphere radioembolisation of the liver: technical aspects studied in a large animal model.

OBJECTIVE: To assess the accuracy of a scout dose of holmium-166 poly(L-lactic acid) microspheres ((166)Ho-PLLA-MS) in predicting the distribution of a treatment dose of (166)Ho-PLLA-MS, using single photon emission tomography (SPECT). METHODS: A scout dose (60 mg) was injected into the hepatic artery of five pigs and SPECT acquired. Subsequently, a 'treatment dose' was administered (540 mg) and SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) of the total dose performed. The two SPECT images of each animal were compared. To validate quantitative SPECT an ex vivo liver was instilled with (166)Ho-PLLA-MS and SPECT acquired. The liver was cut into slices and planar images were acquired, which were registered to the SPECT image. RESULTS: Qualitatively, the scout dose and total dose images were similar, except in one animal because of catheter displacement. Quantitative analysis, feasible in two animals, tended to confirm this similarity (r(2) = 0.34); in the other animal the relation was significantly better (r(2) = 0.66). The relation between the SPECT and planar images acquired from the ex vivo liver was strong (r(2) = 0.90). CONCLUSION: In the porcine model a scout dose of (166)Ho-PLLA-MS can accurately predict the biodistribution of a treatment dose. Quantitative (166)Ho SPECT was validated for clinical application.

The influence of self-absorption on PET and PET/CT shielding requirements.

PURPOSE: The high energy (511 keV) annihilation photons used in positron emission tomography (PET) imaging generally require a substantial amount of lead to protect personnel and the general public from ionizing radiation. A cost-effective design of the PET facility that ensures radiation does not exceed formal dose limits requires accurate estimation of the necessary PET shielding. The American Association of Physicists in Medicine (AAPM) Task Group 108 recently published broad beam transmission factors based on Monte Carlo calculations of 511 keV photons. In this work, an extension to the AAPM model is presented, based on Monte Carlo simulations including the effects of self-absorption on the photon energy spectrum. METHODS: Monte Carlo calculations were performed using MCNPX. The photon energy spectrum after self-absorption was computed by simulating a normal 18FDG activity distribution in an anthropomorphic phantom. This spectrum was used to calculate the dose rate transmission factors for various wall thicknesses of lead, concrete, and iron. The method was validated by measurement and corresponding simulation of the transmission factors of an 18FDG source in air and in PMMA. Furthermore, a method to generate 3D area dose rate maps of PET facilities incorporating the calculated transmission tables is presented and applied to several shielding situations. RESULTS: The calculated self-absorption correction factor and the broad beam transmission factors resulting from Monte Carlo simulations of a monoenergetic point source emitting 511 keV photons were in excellent agreement with the results of the AAPM publication (0.66 vs 0.64 and R2 = 0.999, respectively). However, when all radiation physics, i.e., also the effect of self-absorption on the photon energy spectrum, is included in the Monte Carlo calculations, a substantial reduction in required shielding material was found. For example, including all radiation physics leads to 13.3 mm of lead required to obtain a typical transmission factor of 0.1, instead of 16.0 mm of lead when the AAPM data including only the self-absorption correction factor are used. These findings were confirmed by the experimental measurements. The transmission factors produced in this work can be applied in the same manner as those estimated by AAPM to allow for a cost-effective design of PET and PET/CT facilities without violating radiation safety regulations. CONCLUSIONS: Taking into account the effect of self-absorption on the photon energy spectrum results in more accurate and cost-effective shielding requirement estimations.

Simultaneous 166Ho/99mTc dual-isotope SPECT with Monte Carlo-based downscatter correction for automatic liver dosimetry in radioembolization.

BACKGROUND: Intrahepatic dosimetry is paramount to optimize radioembolization treatment accuracy using radioactive holmium-166 microspheres (166Ho). This requires a practical protocol that combines quantitative imaging of microsphere distribution with automated and robust delineation of the volumes of interest. To this end, we propose a dual isotope single photon emission computed tomography (SPECT) protocol based on 166Ho therapeutic microspheres and technetium-99 m (99mTc) stannous phytate, which accumulates in healthy liver tissue. This protocol may allow accurate and automatic estimation of tumor-absorbed dose and healthy liver-absorbed dose. The current study focuses on a Monte Carlo-based reconstruction framework that inherently corrects for scatter crosstalk between the 166Ho and 99mTc imaging. To demonstrate the feasibility of the method, it is evaluated with realistic phantom experiments and patient data. METHODS: The Utrecht Monte Carlo System (UMCS) was extended to include detailed modeling of crosstalk interactions between 99mTc and 166Ho. First, 99mTc images were reconstructed including energy window-based corrections for 166Ho downscatter. Next, 99mTc downscatter in the 81-keV 166Ho window was Monte Carlo simulated to allow quantitative reconstruction of the 166Ho images. The accuracy of the 99mTc-downscatter modeling was evaluated by comparing measurements with simulations. In addition, the ratio between 99mTc and 166Ho yielding the best 166Ho dose estimates was established and the quantitative accuracy was reported. RESULTS: Given the same level of activity, 99mTc contributes twice as many counts to the 81-keV window than 166Ho, and four times as many counts to the 140-keV window, applying a 166Ho/99mTc ratio of 5:1 yielded a high accuracy in both 166Ho and 99mTc reconstruction. Phantom experiments revealed that the accuracy of quantitative 166Ho activity recovery was reduced by 10% due to the presence of 99mTc. Twenty iterations (8 subsets) of the SPECT/CT reconstructions were considered feasible for clinical practice. Applicability of the proposed protocol was shown in a proof-of-concept case. CONCLUSION: A novel 166Ho/99mTc dual-isotope protocol for automatic dosimetry compensates accurately for downscatter and allows for the addition of 99mTc without compromising 166Ho SPECT image quality.

Feasibility of CT quantification of intratumoural 166Ho-microspheres.

BACKGROUND: Microspheres loaded with radioactive 166Ho (166Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of ß radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging. This phantom study investigated the feasibility of CT quantification of 166Ho-MS. METHODS: CT quantification was performed on a phantom with various concentrations of HoCl and Ho-MS to investigate the CT sensitivity and calibrate the CT recovery. 166Ho-MS were injected into ex vivo tissues, in VX-2 cancer-bearing rabbits, and in patients with head-neck cancer, to demonstrate sensitivity and clinical visibility. The amount of Ho-MS was determined by CT scanning, using a density-based threshold method and compared with a validated 166Ho SPECT quantification method. RESULTS: In the phantom, a near perfect linearity (least squares R2 > 0.99) between HU values and concentration of 166Ho was found. Ex vivo tissue experiments showed an excellent correlation (r = 0.99, p < 0.01) between the dose calibrator, SPECT, and CT imaging. CT recovery was on average 86.4% ex vivo, 76.0% in rabbits, and 99.1% in humans. CONCLUSION: This study showed that CT-based quantification of Ho microspheres is feasible and is a high-resolution alternative to SPECT-based determination of their local distribution.

Oesophageal acid hypersensitivity is not a contraindication to Nissen fundoplication.

BACKGROUND: The Rome III criteria classify patients with a positive relationship between symptoms and reflux episodes but a physiological oesophageal acid exposure time as having gastro-oesophageal reflux disease (GORD) with an acid hypersensitive oesophagus. The long-term outcome of antireflux surgery in these patients was investigated. METHODS: Outcomes of Nissen fundoplication in 28 patients with GORD refractory to proton-pump inhibitors (PPIs) and oesophageal acid hypersensitivity (group 1) were compared with those of 126 patients with pathological acid exposure (group 2). RESULTS: Fundoplication had a similar effect in both groups. Three months after surgery, total acid exposure time and the prevalence of oesophagitis had decreased, whereas mean lower oesophageal pressure had increased. The percentage of patients using PPIs was reduced from 83 to 4 per cent in group 1 and from 86.1 to 7.4 per cent in group 2 (both P < 0.001). Quality of life measured on a scale from 0 to 100 improved from 52 to 69 (P = 0.009) and 64 (P < 0.001) respectively. The percentage of patients with resolved or improved symptoms at 5 years was similar. CONCLUSION: Patients with oesophageal acid hypersensitivity benefit from Nissen fundoplication as much as those with pathological acid exposure.

An atomic force microscope operating at hypergravity for in situ measurement of cellular mechano-response.

We present a novel atomic force microscope (AFM) system, operational in liquid at variable gravity, dedicated to image cell shape changes of cells in vitro under hypergravity conditions. The hypergravity AFM is realized by mounting a stand-alone AFM into a large-diameter centrifuge. The balance between mechanical forces, both intra- and extracellular, determines both cell shape and integrity. Gravity seems to be an insignificant force at the level of a single cell, in contrast to the effect of gravity on a complete (multicellular) organism, where for instance bones and muscles are highly unloaded under near weightless (microgravity) conditions. However, past space flights and ground based cell biological studies, under both hypogravity and hypergravity conditions have shown changes in cell behaviour (signal transduction), cell architecture (cytoskeleton) and proliferation. Thus the role of direct or indirect gravity effects at the level of cells has remained unclear. Here we aim to address the role of gravity on cell shape. We concentrate on the validation of the novel AFM for use under hypergravity conditions. We find indications that a single cell exposed to 2 to 3 x g reduces some 30-50% in average height, as monitored with AFM. Indeed, in situ measurements of the effects of changing gravitational load on cell shape are well feasible by means of AFM in liquid. The combination provides a promising technique to measure, online, the temporal characteristics of the cellular mechano-response during exposure to inertial forces.

A method to measure PET scatter fractions for daily quality control.

PURPOSE: Regular monitoring of PET scanner performance is mandatory to assure quality of acquired data. While extensive performance measurements include many scanner characteristics such as resolution, count rate, uniformity, sensitivity, and scatter fraction (SF), most daily QC protocols are limited to uniformity and sensitivity measurements. These measurements may be too insensitive to detect more subtle drifts in detector gains that could lead to reduced detection of primary and increased detection of scattered events. Current methods to measure SF, such as those prescribed by the NEMA protocols (SF-NEMA), however, require specially designed phantoms and are too cumbersome to be performed on a daily basis. METHODS: In this study, a simple and versatile method to determine SF is described. This method (SF-DAILY) does not require additional measurements, making it suitable for daily QC. The method was validated for four different scanners by comparing results with those obtained with the NEMA 1994 protocol. RESULTS: For all scanner types and acquisition modes, excellent agreement was found between SF-NEMA and SF-DAILY. CONCLUSIONS: The proposed method is a very practical and valuable addition to current daily QC protocols. In addition, the method can be used to accurately measure SF in phantoms with other dimensions than the NEMA phantom.

Dose of CT protocols acquired in clinical routine using a dual-layer detector CT scanner: A preliminary report.

PURPOSE: To assess the radiation dose associated with always-on dual-energy acquisitions in clinical practice over a broad range of clinical protocols using a dual-layer detector CT (DLCT; IQon spectral CT, Philips Healthcare) as compared to an otherwise technically equivalent single-layer detector CT (SLCT; Brilliance iCT, Philips healthcare). MATERIALS AND METHODS: Dose-length-product data for consecutive examinations over a six-month period acquired with DLCT were retrospectively collected and compared to consecutive examinations from an SLCT. Imaging protocols were optimized for diagnostic image quality for each system prior to data collection. Dose reports of CT protocols that were used at least 50 times on both systems were collected. After exclusion of statistical outliers, protocols were evaluated with regard to reported dose levels. RESULTS: In total, 4536 dose reports for DLCT and 5783 reports for SLCT were collected. All DLCT examinations were acquired at 120 kVp, enabling dual-energy analysis. With SLCT, 79% of examinations were acquired at 120 kVp, and 21% at 100/80 kVp. Protocols for 15 indications were used more than 50 times on both scanners. For seven protocols there was no significant difference between the two scanners (p > 0.05), whereas seven protocols were acquired with higher dose levels on SLCT compared to the DLCT (p < 0.03). For one protocol, the DLCT dose was significantly higher (p < 0.005) compared to the SLCT. CONCLUSION: Dual-layer detector CT enables acquisition of dual-energy information over a broad range of clinical indications without increasing radiation dose when compared to a conventional single-layer detector CT.

An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial.

OBJECTIVES: The primary objective of this trial was to assess safety and anti-inflammatory effects of an add-on training program involving breathing exercises, cold exposure, and meditation in patients with axial spondyloarthritis. METHODS: This study was an open-label, randomised, one-way crossover clinical proof-of-concept trial. Twenty-four patients with moderately active axial spondyloarthritis(ASDAS >2.1) and hs-CRP ≥5mg/L were included and randomised to an intervention (n = 13) and control group (n = 11) group that additionally received the intervention after the control period. The intervention period lasted for 8 weeks. The primary endpoint was safety, secondary endpoints were change in hs-CRP, serum calprotectin levels and ESR over the 8-week period. Exploratory endpoints included disease activity measured by ASDAS-CRP and BASDAI, quality of life (SF-36, EQ-5D, EQ-5D VAS), and hospital anxiety and depression (HADS). RESULTS: We found no significant differences in adverse events between groups, with one serious adverse event occurring 8 weeks after end of the intervention and judged 'unrelated'. During the 8-week intervention period, there was a significant decline of ESR from (median [interquartile range] to 16 [9-26.5] to 9 [5-23] mm/hr, p = 0.040, whereas no effect was found in the control group (from 14 [8.3-27.3] to 16 [5-37] m/hr, p = 0.406). ASDAS-CRP declined from 3.1 [2.5-3.6] to 2.3 [1.9-3.2] in the intervention group (p = 0.044). A similar trend was observed for serum calprotectin (p = 0.064 in the intervention group versus p = 0.182 in the control group), but not for hs-CRP. CONCLUSIONS: This proof-of-concept study in axial spondyloarthritis met its primary endpoint with no safety signals during the intervention. There was a significant decrease in ESR levels and ASDAS-CRP upon the add-on training program in the intervention group. These findings warrant full-scale randomised controlled trials of this novel therapeutic approach in patients with inflammatory conditions. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02744014.