NEMA characterization of the SAFIR prototype PET insert

Background: The SAFIR prototype insert is a preclinical Positron Emission Tomography (PET) scanner built to acquire dynamic images simultaneously with a 7 T Bruker Magnetic Resonance Imaging (MRI) scanner. The insert is designed to perform with an excellent coincidence resolving time of 194 ps Full Width Half Maximum (FWHM) and an energy resolution of 13.8% FWHM. These properties enable it to acquire precise quantitative images at activities as high as 500 MBq suitable for studying fast biological processes within short time frames (&lt; 5 s). In this study, the performance of the SAFIR prototype insert is evaluated according to the NEMA NU 4-2008 standard while the insert is inside the MRI without acquiring MRI data.Results: Applying an energy window of 391–601 keV and a coincidence time window of 500 ps the following results are achieved. The average spatial resolution at 5 mm radial offset is 2.6 mm FWHM when using the Filtered Backprojection 3D Reprojection (FBP3DRP) reconstruction method, improving to 1.2 mm when using the Maximum Likelihood Expectation Maximization (MLEM) method. The peak sensitivity at the center of the scanner is 1.06%. The Noise Equivalent count Rate (NECR) is 799 kcps at the highest measured activity of 537 MBq for the mouse phantom and 121 kcps at the highest measured activity of 624 MBq for the rat phantom. The NECR peak is not yet reached for any of the measurements. The scatter fractions are 10.9% and 17.8% for the mouse and rat phantoms, respectively. The uniform region of the image quality phantom has a 3.0% STD, with a 4.6% deviation from the expected number of counts per voxel. The spill-over ratios for the water and air chambers are 0.18 and 0.17, respectively.Conclusions: The results satisfy all the requirements initially considered for the insert, proving that the SAFIR prototype insert can obtain dynamic images of small rodents at high activities (∼ 500 MBq) with a high sensitivity and an excellent count-rate performance.</p

NEMA characterization of the SAFIR prototype PET insert

Background The SAFIR prototype insert is a preclinical Positron Emission Tomography (PET) scanner built to acquire dynamic images simultaneously with a 7 T Bruker Magnetic Resonance Imaging (MRI) scanner. The insert is designed to perform with an excellent coincidence resolving time of 194 ps Full Width Half Maximum (FWHM) and an energy resolution of 13.8% FWHM. These properties enable it to acquire precise quantitative images at activities as high as 500 MBq suitable for studying fast biological processes within short time frames (< 5 s). In this study, the performance of the SAFIR prototype insert is evaluated according to the NEMA NU 4-2008 standard while the insert is inside the MRI without acquiring MRI data. Results Applying an energy window of 391–601 keV and a coincidence time window of 500 ps the following results are achieved. The average spatial resolution at 5 mm radial offset is 2.6 mm FWHM when using the Filtered Backprojection 3D Reprojection (FBP3DRP) reconstruction method, improving to 1.2 mm when using the Maximum Likelihood Expectation Maximization (MLEM) method. The peak sensitivity at the center of the scanner is 1.06%. The Noise Equivalent count Rate (NECR) is 799 kcps at the highest measured activity of 537 MBq for the mouse phantom and 121 kcps at the highest measured activity of 624 MBq for the rat phantom. The NECR peak is not yet reached for any of the measurements. The scatter fractions are 10.9% and 17.8% for the mouse and rat phantoms, respectively. The uniform region of the image quality phantom has a 3.0% STD, with a 4.6% deviation from the expected number of counts per voxel. The spill-over ratios for the water and air chambers are 0.18 and 0.17, respectively. Conclusions The results satisfy all the requirements initially considered for the insert, proving that the SAFIR prototype insert can obtain dynamic images of small rodents at high activities (∼ 500 MBq) with a high sensitivity and an excellent count-rate performance

MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care

Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids. Based on that microRNA expression for serum samples of sulfur mustard patients were examined, to establish specific microRNA patterns as a basis for diagnostic use and insight into affected molecular pathways. Patients were categorized based on their long-term complications into three groups and microRNA serum levels were measured. The differentially regulated microRNAs and their corresponding gene targets were identified. Cell cycle arrest, ageing and TGF-beta signaling pathways showed up to be the most deregulated pathways. The candidate microRNA miR-143-3p could be validated on all individual patients. In a ROC analysis miR-143-3p turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Further microRNAs which might own a link to the biology of the sulfur mustard patients are miR-365a-3p, miR-200a-3p, miR-663a. miR-148a-3p, which showed up only in a validation study, might be linked to the airway complications of the sulfur mustard patients. All the other candidate microRNAs do not directly link to COPD phenotype or lung complications. In summary the microRNA screening study characterizes several molecular differences in-between the clinical categories of the sulfur mustard exposure groups and established some useful microRNA biomarkers. qPCR raw data is available via the Gene Expression Omnibus https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110797

MicroRNA expression in serum samples of sulfur mustard veterans as a diagnostic gateway to improve care

<div><p>Sulfur mustard is a vesicant chemical warfare agent, which has been used during Iraq-Iran-war. Many veterans and civilians still suffer from long-term complications of sulfur mustard exposure, especially in their lung. Although the lung lesions of these patients are similar to Chronic Obstructive Pulmonary Disease (COPD), there are some differences due to different etiology and clinical care. Less is known on the molecular mechanism of sulfur mustard patients and specific treatment options. microRNAs are master regulators of many biological pathways and proofed to be stable surrogate markers in body fluids. Based on that microRNA expression for serum samples of sulfur mustard patients were examined, to establish specific microRNA patterns as a basis for diagnostic use and insight into affected molecular pathways. Patients were categorized based on their long-term complications into three groups and microRNA serum levels were measured. The differentially regulated microRNAs and their corresponding gene targets were identified. Cell cycle arrest, ageing and TGF-beta signaling pathways showed up to be the most deregulated pathways. The candidate microRNA miR-143-3p could be validated on all individual patients. In a ROC analysis miR-143-3p turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Further microRNAs which might own a link to the biology of the sulfur mustard patients are miR-365a-3p, miR-200a-3p, miR-663a. miR-148a-3p, which showed up only in a validation study, might be linked to the airway complications of the sulfur mustard patients. All the other candidate microRNAs do not directly link to COPD phenotype or lung complications. In summary the microRNA screening study characterizes several molecular differences in-between the clinical categories of the sulfur mustard exposure groups and established some useful microRNA biomarkers. qPCR raw data is available via the Gene Expression Omnibus <a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110797" target="_blank">https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE110797</a>.</p></div

The SAFIR experiment: Concept, status and perspectives

The SAFIR development represents a novel Positron Emission Tomography (PET) detector, conceived for preclinical fast acquisitions inside the bore of a Magnetic Resonance Imaging (MRI) scanner. The goal is hybrid and simultaneous PET/MRI dynamic studies at unprecedented temporal resolutions of a few seconds. The detector relies on matrices of scintillating LSO-based crystals coupled one-to-one with SiPM arrays and readout by fast ASICs with excellent timing resolution and high rate capabilities. The paper describes the detector concept and the initial results in terms of simulations and characterisation measurements

Graphical abstract.

<p>Graphical abstract.</p

The 9 top affected cellular pathways influenced from the 29 microRNAs of the normal-severe comparison.

<p>The 9 top affected cellular pathways influenced from the 29 microRNAs of the normal-severe comparison.</p

Validation of miR-143-3p expression.

<p>(A) Increased expression of miR-143-3p in either 'mild' and 'severe' group. miR-143-3p expression was up-regulated in both mild and severe groups with a fold change of 3.9 and 7.0 respectively (p = 0.005 and p = 0.1*10⁻⁶). The graph shows the mean values of all validated patients. The number of patients in the individual validation is slightly different from the number of patients in the pool samples. On the y axis the fold change is denoted. The star on top of the horizontal brackets indicate a significant difference. n is giving the sample number of all individually validated patients. The standard deviation is given by the top indicators. (B) The receiver-operator characteristic curve for miR-143-3p suggests this microRNA for being a suitable biomarker. miR-143-3p is able to discriminate SMV patients from control samples by an AUC of 0.87 (p = 0.0004). The x and y axis denote the percentage values of the performance parameters 'specificity' and 'sensitivity' over the full range from 0 to 100 percent.</p

Differential microRNAs (15) of the normal-mild group.

<p>The values shown here are from the right part of the workflow in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194530#pone.0194530.g002" target="_blank">Fig 2</a>. dCt: delta Ct, FC: fold change and sampling p: sampling p value which was finally considered.</p