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The aim of this study was to assess synovitis by (18)F-FDG PET in an individual joint analysis and in a global analysis of rheumatoid arthritis (RA) disease activity and to compare (18)F-FDG PET parameters with clinical, biologic, and sonographic (US) rheumatoid parameters. Three hundred fifty-six joints were assessed in 21 patients with active RA: the knees in all subjects and either wrists as well as metacarpophalangeal and proximal interphalangeal joints in 13 patients, or ankles and the first metatarsophalangeal joints in the remaining 8 patients. PET analysis consisted of a visual identification of (18)F-FDG uptake in the synovium and measurements of standardized uptake values (SUVs). Independent assessors performed the clinical and US examinations. PET positivity was found in 63% of joints, whereas 75%, 79%, and 56% were positive for swelling, tenderness, and US analysis, respectively. Both the rate of PET-positive joints and the SUV increased with the number of positive parameters present (swelling, tenderness, US positivity) and with the synovial thickness. The mean SUV was significantly higher in joints where a power Doppler signal was found. In a global PET analysis, the number of PET-positive joints and the cumulative SUV were significantly correlated with the swollen and tender joint counts, the patient and physician global assessments, the erythrocyte sedimentation rate and C-reactive protein serum levels, the disease activity score and the simplified disease activity index, the number of US-positive joints, and the cumulative synovial thickness. (18)F-FDG PET is a unique imaging technique that can assess the metabolic activity of synovitis and measure the disease activity in RA.

Guidelines for SPECT myocardial perfusion imaging (MPI) traditionally recommend a fixed tracer dose. Yet, clinical practice shows degraded image quality in heavier patients. The aim was to optimize and validate the tracer dose and scan time to obtain a constant image quality less dependent on patients’ physical characteristics. 125 patients underwent Cadmium Zinc Telluride (CZT)-SPECT stress MPI using a fixed Tc-99m-tetrofosmin tracer dose. Image quality was scored by three physicians on a 4-point grading scale and related to the number of photon counts normalized to tracer dose and scan time. Counts were correlated with various patient-specific parameters dealing with patient size and weight to find the best predicting parameter. From these data, a formula to provide constant image quality was derived, and subsequently tested in 92 new patients. Degradation in image quality and photon counts was observed for heavier patients for all patients’ specific parameters (P < .01). We found body weight to be the best-predicting parameter for image quality and derived a new dose formula. After applying this new body weight-depended tracer dose and scan time in a new group, image quality was found to be constant (P > .19) in all patients. Also in CZT SPECT image quality decreases with weight. The use of a tracer dose and scan time that depends linearly on patient’s body weight corrected for the varying image quality in CZT-SPECT MPI. This leads to better radiation exposure justification.

The purpose of this study was to assess the efficiency of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the characterisation and primary staging of suspicious renal masses, in comparison with computed tomography, the current standard imaging modality. Fifty-three FDG PET studies were performed within the framework of a prospective study: 35 for both characterisation and staging of a suspicious mass, and 18 for staging early after surgical removal of a renal cancer. In the characterisation of renal masses, a high rate of false negative results was observed, leading to a sensitivity, specificity and accuracy of 47%, 80% and 51% respectively, versus 97%, 0/5 and 83% respectively for CT. FDG PET detected all the sites of distant metastasis revealed by CT, as well as eight additional metastatic sites, leading to an accuracy of 94% versus 89% for CT. However, 36/53 patients (68%) did not have any distant metastasis on either CT or on PET. All but one of these patients had a low Fuhrman histological grade and a limited local stage (< or =pT2). We conclude that FDG PET does not offer any advantage over CT for the characterisation of renal masses but that it appears to be an efficient tool for the detection of distant metastasis in renal cancer. However, our data suggest that a selection process could be implemented to determine which patients should undergo PET. FDG PET could be performed in the event of a solitary metastasis or doubtful images on CT. Selection could also be based on adverse histological findings from nephrectomy specimens in order to perform staging early after nephrectomy.

With the advantages of the increased sensitivity of fully 3-dimensional (3D) PET for whole-body imaging come the challenges of more complicated quantitative corrections and, in particular, an increase in the number of random coincidences. The most common method of correcting for random coincidences is the real-time subtraction of a delayed coincidence channel, which does not add bias but increases noise. An alternative approach is the postacquisition subtraction of a low-noise random coincidence estimate, which can be obtained either from a smoothed delayed coincidence sinogram or from a calibration scan or directly estimated. Each method makes different trade-offs between noise amplification, bias, and data-processing requirements. These trade-offs are dependent on activity injected, the local imaging environment (e.g., near the bladder), and the reconstruction algorithm. Using fully 3D whole-body simulations and phantom studies, we investigate how the gains in noise equivalent count (NEC) rates from using a noiseless random coincidence estimation method are translated to improvements in image signal-to-noise ratio (SNR). The image SNR, however, depends on the image reconstruction method and the local imaging environment. We show that for fully 3D whole-body imaging using a particular set of scanners and clinical protocols, a low-noise estimate of random coincidences improves sinogram and image SNRs by approximately 15% compared with online subtraction of delayed coincidences. A 15% improvement in image SNR arises from a 32% increase in the NEC rate. Thus, scan duration can be reduced by 25% while still maintaining a constant total acquired NEC.

Dosimetric comparisons between RapidArc (RA) and conventional Intensity-Modulated Radiation Therapy (IMRT) techniques for nasopharyngeal carcinoma (NPC) were performed to address differences in dose coverage of the target, sparing of organs-at-risk (OARs), delivery of monitor units (MUs) and time, to assess whether the RA technique was more beneficial for treatment of NPC. Eight NPC patients (Stages I–IV), who had completed RA treatment, were selected for this study. Computed tomography data sets were re-planned using 7-fields fixed beam IMRT. Quantitative measurements of dose-endpoint values on the dose-volume histograms were carried out for evaluation of: (i) dose homogeneity (D5% – D95%); (ii) degree of conformity (CI95%); (iii) tumor control probability (TCP); (iv) doses to OARs; (v) normal tissue complication probability (NTCP); (vi) treatment time; and (vii) MUs. RA plans achieved better dose conformity and TCP in planning target volumes (PTVs). Target dose homogeneity was not as high as for IMRT plans. Doses to tempero-mandibular joints, clavicles, parotid glands and posterior neck, and their NTCPs were significantly lower in RA plans (P < 0.05). Mean doses to the brainstem and spinal cord were slightly lower in IMRT plans. RA plans allowed for a mean reduction in MUs by 78% (P = 0.006), and a four-fold reduction in treatment delivery times, relative to IMRT plans. RA plans showed superior, or comparable, target coverage and dose conformity in PTVs, but at the expense of inferior dose homogeneity. RA plans also achieved significant improvements in dose reduction to OARs and healthy tissue sparing. A significant reduction in treatment delivery time for RA treatment technique was also noted.

Quantitative measurement of adipose tissue (AT) compartments in the entire body and of lipids in muscle and liver cells by means of MRI and MRS. Assessment of age and gender related differences in AT compartments and determination of cross-correlations between AT compartments in a heterogeneous cohort at increased risk for metabolic diseases. One hundred and fifty healthy volunteers with increased risk to type 2 diabetes were examined. T1-weighted MRI was applied for whole-body adipose tissue quantification. Adipose tissue compartments were subdivided in lower extremities, trunk (abdominal subcutaneous (SCAT) and visceral (VAT) adipose tissue), and upper extremities. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) in tibialis anterior and soleus muscle were determined by volume selective MRS. Females are characterized by lower %VAT (2.8+/-1.3% vs. 4.6+/-1.4%, p<0.001) and higher %SCAT (14.7+/-3.9% vs. 9.3+/-2.9%, p<0.001). There is a strong correlation between %VAT and age (r=0.64/0.60 for females/males), whereas %SCAT remained virtually unchanged in males (r=-0.09) and was only slightly increaseding in females (r =0.30, p<0.01). For IHCL, age related differences were observed in females with significantly increased IHCL in the older women, but not in males. IMCL contents in both muscles were found almost independent of age in both, males and females. Furthermore, VAT and IHCL show significant correlations in both groups. Assessed age and gender related differences, especially the age related significant increase of VAT and IHCL, as well as cross-correlations between different lipid compartments might contribute to a better understanding of the lipid metabolism under normal and pathologic metabolic conditions in humans.

In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is compared with step-and-shoot IMRT (SSIMRT) of the prostate gland by measuring the dose distribution within patients' lymphocytes. In this prospective study, blood was taken from 20 patients before and 10 min after their first irradiation fraction for each technique. The isolated leukocytes were fixed 2 h after radiation. DNA double-stranded breaks in lymphocyte nuclei were stained immunocytochemically using anti-gamma-H2AX antibodies. Gamma-H2AX foci distribution in lymphocytes was determined for each patient. Using a calibration line, dose distributions in patients' lymphocytes were determined by studying the gamma-H2AX foci distribution, and these data were used to generate a cumulative dose–lymphocyte histogram (DLH). Measured in vivo (DLH), significantly fewer lymphocytes indicated low-dose exposure (<40% of the applied dose) during TOMO compared with SSIMRT. The dose exposure range, between 45 and 100%, was equal with both radiation techniques. The mean number of gamma-H2AX foci per lymphocyte was significantly lower in the TOMO group compared with the SSIMRT group. In radiotherapy of the prostate gland, TOMO generates a smaller fraction of patients' lymphocytes with low-dose exposure relative to the whole body compared with SSIMRT. Differences in the constructional buildup of the different linear accelerator systems, e.g. the flattening filter, may be the cause thereof. The influence of these methods on the incidence of secondary malignancy should be investigated in further studies.

Background Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). Results The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96–100%) and chromatin mark QTL (≥87–92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. Conclusions Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application ( https://github.com/molgenis/systemsgenetics/tree/master/Decon2 ) and as a web tool ( www.molgenis.org/deconvolution ).

Enteral nutrition (EN) is a ubiquitous intervention in ICU patients but there is uncertainty regarding the optimal dose, timing and importance for patient-centered outcomes during critical illness. Our research group has previously found an improved protein balance during normocaloric versus hypocaloric parenteral nutrition in neurosurgical ICU patients. We now wanted to investigate if this could be demonstrated in a general ICU population with established enteral feeding, including patients on renal replacement therapy. Six patients completed the full protocol. During feeding with 100% EN all patients received >1.2 g/kg/day of protein. Mean whole-body protein balance increased from -6.07 to 2.93 [micro]mol phenylalanine/kg/h during 100% EN as compared to 50% (p = 0.044). The oxidation rate of phenylalanine was unaltered (p = 0.78). It is possible to assess whole-body protein turnover using a stable isotope technique in critically ill patients during enteral feeding and renal replacement therapy. Our results also suggest a better whole-body protein balance during full dose as compared to half dose EN. As the sample size was smaller than anticipated, this finding should be confirmed in larger studies.

Exposure to ionizing radiation from nuclear devices, spaceflights or terrorist attacks represents a major threat to human health and public security. After a radiological incident, noninvasive biomarkers that can facilitate rapid assessment of exposure risk in the early stages are urgently needed for optimal medical treatment. Serum microRNAs (miRNAs) are ideal biomarkers because they are stable in response to environmental changes, they are common among different species and are easily collected. Here, we performed miRNA PCR arrays to analyze miRNA expression profiles at 24 h postirradiation. Blood samples were collected from animals that received 0.5–2 Gy total-body carbon-ion irradiation. A specific signature with 12 radiosensitive miRNAs was selected for further validation. After exposure to 0.1–2 Gy of carbon-ion, iron-ion or X-ray radiations, five miRNAs that showed a significant response to these radiation types were selected for further observation of dose- and time-dependent changes: miR-183-5p, miR-9-3p, miR-200b-5p, miR-342-3p and miR-574-5p. We developed a universal model using these five miRNAs to predict the degree of exposure to different radiation types with high sensitivity and specificity. In conclusion, we have identified a set of miRNAs that are quite sensitive to different radiation types in the early stages after exposure, demonstrating their potential use as effective indicators to predict the degree of exposure.