Timelines of the "free-particle" and "fixed-particle" models of stone-formation: theoretical and experimental investigations

Two major theories on renal stone formation will be reviewed, the “free-particle” and “fixed-particle” mechanisms. These theories combine data on intrinsic factors (inborn metabolic errors), extrinsic factors (diet), renal cell responses and the physico-chemistry and biochemistry of urine into mechanisms of stone formation. This paper describes the specific role of time in both mechanisms. The timeline of crystal- and stone formation was deducted from literature data and was measured for two stones using radioisotope decay analysis. The stones of similar size and composition showed, respectively, a timeline of a few years and a development that took decades. In combination with data on stone architecture and patient characteristics these timelines are explained using the free-particle and fixed-particle mechanisms. Consideration of the timeline of stone formation has clinical implications. We conclude that the fixed-particle mechanism can be a slow process where decades pass between the first formation of a precipitate in the renal interstitium and the clinical presentation of the stone. Added to the fact that the mechanism of this initial precipitation is still ill defined, the conditions that started fixed-particle stone formation in an individual patient can be obscure. Blood and urine analysis in such patients does not necessarily reveal the individual’s risk for recurrence as lifestyle may have changed over time. This is in fact what defines the so-called idiopathic stoneformers. For these patients, prevention of outgrowth of previously formed precipitates, papillary plaques, may be more relevant than prevention of new plaque formation. In contrast, a patient who has formed a stone in a relatively short time through the free-particle mechanism is more likely to show abnormal values in blood and urine that explain the starting event of stone formation. In these patients, measurement of such values provides useful information to guide preventive measures. © 2016, The Author(s)

A randomized double-blind placebo-controlled trial to evaluate the value of a single bolus intravenous alfentanil in CT colonography

<p>Abstract</p> <p>Background</p> <p>Although CT colonography is a less invasive alternative for colonoscopy for the detection of colorectal polyps and cancer, procedural pain is common. In several studies, CT colonography pain and burden is higher than in colonoscopy. Apart from discomfort, anxiety and its related stress-induced peri- procedural side effects, this may influence the adherence for CT colonography as a possible screening tool for colorectal cancer. We hypothesize that a single bolus intravenous alfentanil will give a clinically relevant reduction in maximum pain defined as at least 1.3 point reduction on an 11-point numeric rating scale (NRS).</p> <p>Methods/Design</p> <p>A randomized double-blind placebo-controlled trial in which patients scheduled for elective CT colonography in a single tertiary centre are eligible for inclusion. The first 90 consenting patient will be block-randomized to either the alfentanil group or the placebo group. Before bowel insufflation, the alfentanil group receives a single bolus intravenous alfentanil 7.5 μg/kg dissolved in 0.9% NaCl, while the placebo group receives an intravenous bolus injection of pure 0.9% NaCl. For both groups an equal amount of fluid per kilogram (75 μL/kg) is injected. The primary outcome is the difference in maximum pain on an 11-point NRS. Secondary outcomes include: pain and burden of different CT colonography aspects, side effects, procedural time and recovery time. For the primary outcome an independent samples t-test is performed and a P value < 0.05 is considered statistically significant.</p> <p>Discussion</p> <p>This study will provide evidence whether a single bolus intravenous alfentanil gives a clinically relevant reduction in maximum pain during CT colonography.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC= NTR2902">NTR2902</a></p> <p><it>This trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The department of radiology of the Academic Medical Center of Amsterdam is responsible for the design and conduct of the trial</it>.</p

Children's spatial analysis of simple and complex Hierarchical Patterns in a Drawing Task

BACKGROUND: Primary tumor volume is as an important and independent prognostic factor in Ewing sarcoma. However, the observer variability of magnetic resonance imaging (MRI)-based primary tumor volume measurements in newly diagnosed Ewing sarcoma has never been investigated. Furthermore, it is unclear how MRI-based volume measurements compare to (18)F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-based volume measurements. This study aimed to determine the observer variability of simplified MRI-based primary tumor volume measurements in newly diagnosed treatment-naive Ewing sarcoma and to compare them to the actual primary tumor volume at MRI and the FDG-PET-based metabolically active tumor volume (MATV). MATERIAL AND METHODS: Twenty-nine newly diagnosed Ewing sarcoma patients with pretreatment MRI (of whom 11 also underwent FDG-PET) were included. Both exact and dichotomized (according to the proposed threshold of 200 mL) primary tumor volume measurements were analyzed. RESULTS: Mean inter- and intraobserver differences of MRI-based simplified tumor volume ± limits of agreement varied between 15-42 ± 155-204 mL and between 9-16 ± 64-250 mL, respectively. Inter- and intraobserver agreements of dichotomized MRI-based simplified tumor volume measurements was very good (κ = 0.827-1.000). Mean difference between simplified and actual tumor volumes at MRI ± limits of agreement was 60 ± 381 mL. Agreement between dichotomized simplified and actual tumor volumes at MRI was very good (κ = 0.839). Mean difference between MRI-based simplified tumor volume and MATV ± limits of agreement was 181 ± 549 mL and almost significantly different (p = .0581). Agreement between dichotomized MRI-based simplified tumor volume and MATV was moderate (κ = 0.560). CONCLUSIONS: Exact MRI-based simplified primary tumor volume measurements in Ewing sarcoma suffer from considerable observer variability, but observer agreement of dichotomized measurements (≤200 mL vs. >200 mL) is very good and generally matches MRI-based actual volume measurements. MRI-based primary tumor volume measurements poorly-moderately agree with and tend to be lower than the MATV

Image Quality and Activity Optimization in Oncologic F-18-FDG PET Using the Digital Biograph Vision PET/CT System

The first Biograph Vision PET/CT system (Siemens Healthineers) was installed at the University Medical Center Groningen. Improved performance of this system could allow for a reduction in activity administration or scan duration. This study evaluated the effects of reduced scan duration in oncologic 18F-FDG PET imaging on quantitative and subjective imaging parameters and its influence on clinical image interpretation. Methods: Patients referred for a clinical PET/CT scan were enrolled in this study, received a weight-based 18F-FDG injected activity, and underwent list-mode PET acquisition at 180 s per bed position (s/bp). Acquired PET data were reconstructed using the vendor-recommended clinical reconstruction protocol (hereafter referred to as "clinical"), using the clinical protocol with additional 2-mm gaussian filtering (hereafter referred to as "clinical+G2"), and-in conformance with European Association of Nuclear Medicine Research Ltd. (EARL) specifications-using different scan durations per bed position (180, 120, 60, 30, and 10 s). Reconstructed images were quantitatively assessed for comparison of SUVs and noise. In addition, clinically reconstructed images were qualitatively evaluated by 3 nuclear medicine physicians. Results: In total, 30 oncologic patients (22 men, 8 women; age: 48-88 y [range], 67 ± 9.6 y [mean ± SD]) received a single weight-based (3 MBq/kg) 18F-FDG injected activity (weight: 45-123 kg [range], 81 ± 15 kg [mean ± SD]; activity: 135-380 MBq [range], 241 ± 47.3 MBq [mean ± SD]). Significant differences in lesion SUVmax were found between the 180-s/bp images and the 30- and 10-s/bp images reconstructed using the clinical protocols, whereas no differences were found in lesion SUVpeak EARL-compliant images did not show differences in lesion SUVmax or SUVpeak between scan durations. Quantitative parameters showed minimal deviation (∼5%) in the 60-s/bp images. Therefore, further subjective image quality assessment was conducted using the 60-s/bp images. Qualitative assessment revealed the influence of personal preference on physicians' willingness to adopt the 60-s/bp images in clinical practice. Although quantitative PET parameters differed minimally, an increase in noise was observed. Conclusion: With the Biograph Vision PET/CT system for oncologic 18F-FDG imaging, scan duration or activity administration could be reduced by a factor of 3 or more with the use of the clinical+G2 or the EARL-compliant reconstruction protocol

Impact of partial-volume correction in oncological PET studies:A systematic review and meta-analysis

Purpose: Positron-emission tomography can be useful in oncology for diagnosis, (re)staging, determining prognosis, and response assessment. However, partial-volume effects hamper accurate quantification of lesions &lt;2–3× the PET system’s spatial resolution, and the clinical impact of this is not evident. This systematic review provides an up-to-date overview of studies investigating the impact of partial-volume correction (PVC) in oncological PET studies.Methods: We searched in PubMed and Embase databases according to the PRISMA statement, including studies from inception till May 9, 2016. Two reviewers independently screened all abstracts and eligible full-text articles and performed quality assessment according to QUADAS-2 and QUIPS criteria. For a set of similar diagnostic studies, we statistically pooled the results using bivariate meta-regression.Results: Thirty-one studies were eligible for inclusion. Overall, study quality was good. For diagnosis and nodal staging, PVC yielded a strong trend of increased sensitivity at expense of specificity. Meta-analysis of six studies investigating diagnosis of pulmonary nodules (679 lesions) showed no significant change in diagnostic accuracy after PVC (p = 0.222). Prognostication was not improved for non-small cell lung cancer and esophageal cancer, whereas it did improve for head and neck cancer. Response assessment was not improved by PVC for (locally advanced) breast cancer or rectal cancer, and it worsened in metastatic colorectal cancer.Conclusions: The accumulated evidence to date does not support routine application of PVC in standard clinical PET practice. Consensus on the preferred PVC methodology in oncological PET should be reached. Partial-volume-corrected data should be used as adjuncts to, but not yet replacement for, uncorrected data.</p

F-18-FDG-PET uptake in non-infected total hip prostheses

Background and purpose - F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used in the diagnostic work-up of a patient with suspected periprosthetic joint infection (PJI) but, due to a lack of accurate interpretation criteria, this technique is not routinely applied. Since the physiological uptake pattern of FDG around a joint prosthesis is not fully elucidated, we determined the physiological FDG uptake in non-infected total hip prostheses. Patients and methods - Patients treated with primary total hip arthroplasty (1995-2016) who underwent a FDG-PET/CT for an indication other than a suspected PJI were retrospectively evaluated. Scans were both visually and quantitatively analyzed. Semi-quantitative analysis was performed by calculating maximum and peak standardized uptake values (SUVmax and SUVpeak) by volume of interests (VOIs) at 8 different locations around the prosthesis. Results - 58 scans from 30 patients were analyzed. In most hips, a diffuse heterogeneous uptake pattern around the prosthesis was observed (in 32/38 of the cemented prostheses, and in 16/20 of the uncemented prostheses) and most uptake was located around the neck of the prosthesis. The median SUVmax in the cemented group was 2.66 (95% CI 2.51-3.10) and in the uncemented group 2.87 (CI 2.65-4.63) (Median difference = -0.36 [CI -1.2 to 0.34]). In uncemented prostheses, there was a positive correlation in time between the age of the prosthesis and the FDG uptake (r(s) = 0.63 [CI 0.26-0.84]). Interpretation - Our study provides key data to develop accurate interpretation criteria to differentiate between physiological uptake and infection in patients with a prosthetic joint.</p

Assessment of tumour size in PET/CT lung cancer studies: PET- and CT-based methods compared to pathology

BACKGROUND: Positron emission tomography (PET) may be useful for defining the gross tumour volume for radiation treatment planning and for response monitoring of non-small cell lung cancer (NSCLC) patients. The purpose of this study was to compare tumour sizes obtained from CT- and various more commonly available PET-based tumour delineation methods to pathology findings. METHODS: Retrospective non-respiratory gated whole body [(18)F]-fluoro-2-deoxy-D-glucose PET/CT studies from 19 NSCLC patients were used. Several (semi-)automatic PET-based tumour delineation methods and manual CT-based delineation were used to assess the maximum tumour diameter. RESULTS: 50%, adaptive 41% threshold-based and contrast-oriented delineation methods showed good agreement with pathology after removing two outliers (R(2)=0.82). An absolute SUV threshold of 2.5 also showed a good agreement with pathology after the removal of 5 outliers (R(2): 0.79), but showed a significant overestimation in the maximum diameter (19.8 mm, p<0.05). Adaptive 50%, relative threshold level and gradient-based methods did not show any outliers, provided only small, non-significant differences in maximum tumour diameter (<4.7 mm, p>0.10), and showed fair correlation (R(2)>0.62) with pathology. Although adaptive 70% threshold-based methods showed underestimation compared to pathology (36%), it provided the best precision (SD: 14%) together with good correlation (R(2)=0.81). Good correlation between CT delineation and pathology was observed (R(2)=0.77). However, CT delineation showed a significant overestimation compared with pathology (3.8 mm, p<0.05). CONCLUSIONS: PET-based tumour delineation methods provided tumour sizes in agreement with pathology and may therefore be useful to define the (metabolically most) active part of the tumour for radiotherapy and response monitoring purposes

Increased cerebral (R)-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI) and to relate these findings to glutamate release.</p> <p>Procedures</p> <p>Sequential dynamic <it>(R)</it>-[¹¹C]PK11195 PET scans were performed in rats 24 hours before (baseline), and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF) glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno)-histochemistry.</p> <p>Results</p> <p>Ten days after TBI, <it>(R)</it>-[¹¹C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p < 0.05). ECF glutamate values were increased immediately after TBI (27.6 ± 14.0 μmol·L^-1) as compared with the sham procedure (6.4 ± 3.6 μmol·L^-1). Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B.</p> <p>Conclusions</p> <p>Increased cerebral uptake of <it>(R)</it>-[¹¹C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.</p