The authors would like to thank Richard Raghoo for providing the PET images shown in Figure 1.

All procedures performed involving human participants were in accordance with the ethical standards of the internal review board (IRB) of the Radboud university medical center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The ORG algorithm is a vendor specific product and is available on the Siemens Biograph mCT PET/CT scanner family and newer PET/CT models.
1. Patient preparation
<ol>
	<li>Patient anamnesis
	<ol>
		<li>Check the patient&#82...

<ol>
	<li>Kostakoglu, L., Agress, H., Goldsmith, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+Role+of+FDG+PET+in+Evaluation+of+Cancer+Patients.">Clinical Role of FDG PET in Evaluation of Cancer Patients.</a> Radiographics. 23 (2), 315-340 (2003).</li><li>Grootjans, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+in+the+management+of+locally+advanced+and+metastatic+NSCLC.">PET in the management of locally advanced and metastatic NSCLC.</a> Nature Reviews Clinical Oncology. 12 (7), 395-407 (2015).</li><li>Croteau, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PET+Metabolic+Biomarkers+for+Cancer.">PET Metabolic Biomarkers for Cancer.</a> Biomarkers in Cancer. 8, 61-69 (2016).</li><li>Vlenterie, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+Metabolic+Response+as+a+Predictor+of+Treatment+Outcome+in+Patients+With+Metastatic+Soft+Tissue+Sarcomas.">Early Metabolic Response as a Predictor of Treatment Outcome in Patients With Metastatic Soft Tissue Sarcomas.</a> Anticancer Research. 39 (3), 1309-1316 (2019).</li><li>Barrington, S. F., Meignan, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+to+prepare+for+risk+adaptation+in+lymphoma+by+standardising+measurement+of+metabolic+tumour+burden.">Time to prepare for risk adaptation in lymphoma by standardising measurement of metabolic tumour burden.</a> Journal of Nuclear Medicine. 60 (8), 1096-1102 (2019).</li><li>Grootjans, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Performance+of+automatic+image+segmentation+algorithms+for+calculating+total+lesion+glycolysis+for+early+response+monitoring+in+non-small+cell+lung+cancer+patients+during+concomitant+chemoradiotherapy.">Performance of automatic image segmentation algorithms for calculating total lesion glycolysis for early response monitoring in non-small cell lung cancer patients during concomitant chemoradiotherapy.</a> Radiotherapy and Oncology. 119 (3), 473-479 (2016).</li><li>Grootjans, W., Geus-Oei, L. F., Bussink, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Image-guided+adaptive+radiotherapy+in+patients+with+locally+advanced+non-small+cell+lung+cancer:+the+art+of+PET.">Image-guided adaptive radiotherapy in patients with locally advanced non-small cell lung cancer: the art of PET.</a> Quarterly Journal of Nuclear Medicine and Molecular Imaging. 62 (4), 369-384 (2018).</li><li>Everitt, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+radiation+oesophagitis+associated+with+2-deoxy-2-[18F]fluoro-d-glucose+uptake+on+positron+emission+tomography/CT+during+chemo-radiation+therapy+in+patients+with+non-small-cell+lung+cancer.">Acute radiation oesophagitis associated with 2-deoxy-2-[18F]fluoro-d-glucose uptake on positron emission tomography/CT during chemo-radiation therapy in patients with non-small-cell lung cancer.</a> Journal of Medical Imaging and Radiation Oncology. 61 (5), 682-688 (2017).</li><li>Castillo, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-radiotherapy+FDG+PET+predicts+radiation+pneumonitis+in+lung+cancer.">Pre-radiotherapy FDG PET predicts radiation pneumonitis in lung cancer.</a> Radiation Oncology. 74 (9), 1-10 (2014).</li><li>Lee, J. W., Seo, K. H., Kim, E. S., Lee, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+18F-fluorodeoxyglucose+uptake+of+bone+marrow+on+PET/CT+in+predicting+clinical+outcomes+in+non-small+cell+lung+cancer+patients+treated+with+chemoradiotherapy.">The role of 18F-fluorodeoxyglucose uptake of bone marrow on PET/CT in predicting clinical outcomes in non-small cell lung cancer patients treated with chemoradiotherapy.</a> European Radiology. 27 (5), 1912-1921 (2017).</li><li>Aide, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EANM/EARL+harmonization+strategies+in+PET+quantification:+from+daily+practice+to+multicentre+oncological+studies.">EANM/EARL harmonization strategies in PET quantification: from daily practice to multicentre oncological studies.</a> European Journal of Nuclear Medicine and Molecular Imaging. 44, 17-31 (2017).</li><li>Grootjans, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amplitude-based+optimal+respiratory+gating+in+positron+emission+tomography+in+patients+with+primary+lung+cancer.">Amplitude-based optimal respiratory gating in positron emission tomography in patients with primary lung cancer.</a> European Radiology. 24 (12), 3242-3250 (2014).</li><li>Dawood, M., B&#252;ther, F., Lang, N., Schober, O., Sch&#228;fers, K. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+gating+in+positron+emission+tomography:+A+quantitative+comparison+of+different+gating+schemes.">Respiratory gating in positron emission tomography: A quantitative comparison of different gating schemes.</a> Medical Physics. 34 (7), 3067 (2007).</li><li>Fayad, H., Lamare, F., Thibaut, M., Visvikis, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motion+correction+using+anatomical+information+in+PET/CT+and+PET/MR+hybrid+imaging.">Motion correction using anatomical information in PET/CT and PET/MR hybrid imaging.</a> Quarterly Journal of Nuclear Medicine and Molecular Imaging. 60 (1), 12-24 (2016).</li><li>Nehmeh, S. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+respiratory+tracking+system+for+smart-gated+PET+acquisition.">A novel respiratory tracking system for smart-gated PET acquisition.</a> Medical Physics. 38 (1), 531-558 (2011).</li><li>Boucher, L., Rodrigue, S., Lecomte, R., B&#233;nard, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+Gating+for+3-Dimensional+PET+of+the+Thorax:+Feasibility+and+Initial+Results.">Respiratory Gating for 3-Dimensional PET of the Thorax: Feasibility and Initial Results.</a> Journal of Nuclear Medicine. 45 (2), 214-229 (2004).</li><li>Kokki, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Linear+relation+between+spirometric+volume+and+the+motion+of+cardiac+structures:+MRI+and+clinical+PET+study.">Linear relation between spirometric volume and the motion of cardiac structures: MRI and clinical PET study.</a> Journal of Nuclear Cardiology. 23 (3), 475-485 (2016).</li><li>van Elmpt, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+gating+compared+to+3D+and+4D+PET+reconstruction+for+characterization+of+lung+tumours.">Optimal gating compared to 3D and 4D PET reconstruction for characterization of lung tumours.</a> European Journal of Nuclear Medicine and Molecular Imaging. 38 (5), 843-855 (2011).</li><li>Tsutsui, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Accuracy+of+amplitude-based+respiratory+gating+for+PET/CT+in+irregular+respirations.">Accuracy of amplitude-based respiratory gating for PET/CT in irregular respirations.</a> Annals of Nuclear Medicine. 28 (8), 770-779 (2014).</li><li>Grootjans, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+respiratory+gated+positron+emission+tomography+on+clinical+staging+and+management+of+patients+with+lung+cancer.">The impact of respiratory gated positron emission tomography on clinical staging and management of patients with lung cancer.</a> Lung Cancer. 90 (2), 217-223 (2015).</li><li>Van Der Gucht, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+a+new+respiratory+amplitude-based+gating+technique+in+evaluation+of+upper+abdominal+PET+lesions.">Impact of a new respiratory amplitude-based gating technique in evaluation of upper abdominal PET lesions.</a> European Journal of Radiology. 83 (3), 509-515 (2014).</li><li>Wijsman, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluating+the+use+of+optimally+respiratory+gated+18F-FDG-PET+in+target+volume+delineation+and+its+influence+on+radiation+doses+to+the+organs+at+risk+in+non-small-cell+lung+cancer+patients.">Evaluating the use of optimally respiratory gated 18F-FDG-PET in target volume delineation and its influence on radiation doses to the organs at risk in non-small-cell lung cancer patients.</a> Nuclear Medicine Communications. 37 (1), 66-73 (2016).</li><li>Grootjans, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Impact+of+Optimal+Respiratory+Gating+and+Image+Noise+on+Evaluation+of+Intratumor+Heterogeneity+on+18F-FDG+PET+Imaging+of+Lung+Cancer.">The Impact of Optimal Respiratory Gating and Image Noise on Evaluation of Intratumor Heterogeneity on 18F-FDG PET Imaging of Lung Cancer.</a> Journal of Nuclear Medicine. 57 (11), 1692-1698 (2016).</li><li>Smeets, E. M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+respiratory-gated+[18F]FDG+PET/CT+significantly+impacts+the+quantification+of+metabolic+parameters+and+their+correlation+with+overall+survival+in+patients+with+pancreatic+ductal+adenocarcinoma.">Optimal respiratory-gated [18F]FDG PET/CT significantly impacts the quantification of metabolic parameters and their correlation with overall survival in patients with pancreatic ductal adenocarcinoma.</a> European Journal of Nuclear Medicine and Molecular Imaging Research. 9 (1), 1-10 (2019).</li><li>B&#252;ther, F., Vehren, T., Sch&#228;fers, K. P., Sch&#228;fers, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+Data-driven+Respiratory+Gating+in+Clinical+PET.">Impact of Data-driven Respiratory Gating in Clinical PET.</a> Radiology. 281 (1), 229-238 (2016).</li><li>Feng, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-Gating:+An+Adaptive+Center-of-Mass+Approach+for+Respiratory+Gating+in+PET.">Self-Gating: An Adaptive Center-of-Mass Approach for Respiratory Gating in PET.</a> IEEE Transactions on Medical Imaging. 37 (5), 1140-1148 (2018).</li><li>Schleyer, P. J., O'Doherty, M. J., Marsden, P. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extenstion+of+a+data-driven+gating+technique+to+3D,+whole+body+PET+studies.">Extenstion of a data-driven gating technique to 3D, whole body PET studies.</a> Physics in Medicine &amp; Biology. 56 (13), 3953-3965 (2011).</li><li>Lamare, F., Fayad, H., Fernandez, P., Visvikis, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+respiratory+motion+correction+for+PET/CT+imaging:+Application+to+lung+cancer.">Local respiratory motion correction for PET/CT imaging: Application to lung cancer.</a> Medical Physics. 42 (10), 5903-5912 (2015).</li><li>Lamare, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=List-mode-based+reconstruction+for+respiratory+motion+correction+in+PET+using+non-rigid+body+transformations.">List-mode-based reconstruction for respiratory motion correction in PET using non-rigid body transformations.</a> Physics in Medicine &amp; Biology. 52 (17), 5187-5204 (2007).</li><li>Manber, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+Impact+of+Respiratory+Motion+Correction+in+Simultaneous+PET/MR,+Using+a+Joint+PET/MR+Predictive+Motion+Model.">Clinical Impact of Respiratory Motion Correction in Simultaneous PET/MR, Using a Joint PET/MR Predictive Motion Model.</a> Journal of Nuclear Medicine. 59 (9), 1467-1473 (2018).</li><li>Rank, C. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+motion+compensation+for+simultaneous+PET/MR+based+on+highly+undersampled+MR+data.">Respiratory motion compensation for simultaneous PET/MR based on highly undersampled MR data.</a> Medical Physics. 43 (12), 6234-6245 (2016).</li><li>K&#252;stner, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR-based+respiratory+and+cardiac+motion+correction+for+PET+imaging.">MR-based respiratory and cardiac motion correction for PET imaging.</a> Medical Image Analysis. 42, 129-144 (2017).</li><li>Fayad, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+a+generalized+reconstruction+by+inversion+of+coupled+systems+(GRICS)+approach+for+generic+respiratory+motion+correction+in+PET/MR+imaging.">The use of a generalized reconstruction by inversion of coupled systems (GRICS) approach for generic respiratory motion correction in PET/MR imaging.</a> Physics in Medicine &amp; Biology. 60 (6), 2529-2546 (2015).</li><li>van der Vos, C. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+the+Spatial+Alignment+in+PET/CT+Using+Amplitude-Based+Respiration-Gated+PET+and+Respiration-Triggered+CT.">Improving the Spatial Alignment in PET/CT Using Amplitude-Based Respiration-Gated PET and Respiration-Triggered CT.</a> Journal of Nuclear Medicine. 56 (12), 1817-1822 (2015).</li><li>van der Vos, C. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+a+Free-Breathing+CT+and+an+Expiratory+Breath-Hold+CT+with+Regard+to+Spatial+Alignment+of+Amplitude-Based+Respiratory-Gated+PET+and+CT+Images.">Comparison of a Free-Breathing CT and an Expiratory Breath-Hold CT with Regard to Spatial Alignment of Amplitude-Based Respiratory-Gated PET and CT Images.</a> Journal of Nuclear Medicine Technology. 42 (4), 269-273 (2014).</li><li>van der Vos, C. S., Meeuwis, A. P. W., Grootjans, W., de Geus-Oei, L. F., Visser, E. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+the+spatial+alignment+in+PET/CT+using+amplitude-based+respiratory-gated+PET+and+patient-specific+breathing-instructed+CT.">Improving the spatial alignment in PET/CT using amplitude-based respiratory-gated PET and patient-specific breathing-instructed CT.</a> Journal of Nuclear Medicine Technology. 47 (2), 154-159 (2018).</li><li>Houdu, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Why+harmonization+is+needed+when+using+FDG+PET/CT+as+a+prognosticator:+demonstration+with+EARL-compliant+SUV+as+an+independent+prognostic+factor+in+lung+cancer.">Why harmonization is needed when using FDG PET/CT as a prognosticator: demonstration with EARL-compliant SUV as an independent prognostic factor in lung cancer.</a> European Journal of Nuclear Medicine and Molecular Imaging. 46 (2), 421-428 (2019).</li><li>Kaalep, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EANM/EARL+FDG-PET/CT+accreditation+-+summary+results+from+the+first+200+accredited+imaging+systems.">EANM/EARL FDG-PET/CT accreditation - summary results from the first 200 accredited imaging systems.</a> European Journal of Nuclear Medicine and Molecular Imaging. 45 (3), 412-422 (2018).</li></ol>

In the nuclear medicine community, the deteriorating effects of respiratory motion artefacts in PET imaging have been well-recognized for a long time. It has been shown in many studies that the blurring effect of respiratory motion artefacts can significantly influence image quantification and lesion detectability. Although several respiratory gating methods have been developed, respiratory gating is currently not widely being used in clinical practice. This is particularly due to a resulting variable image quality, unac...

Positron Emission Tomography (PET) in combination with X-ray computed tomography (CT) is a widely accepted imaging tool in clinical practice for accurate diagnosis and clinical staging of a variety of diseases1. The advantage of PET imaging is the ability to visualize and quantify a myriad of biological processes in vivo with high sensitivity and accuracy2. This is achieved through intravenously administering a radioactively labelled compound, also known as a radiotracer, to the patient. Depending on the radiotracer being used, tissue characteristics such as glucose metabolism, cellular proliferation, degree of hypoxia, amino acid transport, and expression of proteins and receptors, can be visualized and quantified2.
Although several radiotracers have been developed, validated, and used in clinical practice, the radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used radiotracer in clinical practice. Given that FDG predominantly accumulates in cells with an elevated glycolytic rate (i.e., cells with elevated glucose uptake and conversion to pyruvate for energy production), it is possible to discriminate tissues with different metabolic states. Similar to glucose, the first step of FDG uptake is transport from the extra-cellular space over the plasma membrane to the intra-cellular space, which is facilitated by glucose transporters (GLUT)3. Once the FDG is in the intra-cellular space, phosphorylation by hexokinases will result in the generation of FDG-6-phosphate. However, in contrast to glucose-6-phosphate, FDG-6-phosphate cannot enter the Krebs cycle for further aerobic dissimilation due to the absence of a hydroxyl (OH) group at the second (2&#8217;) carbon position. Given that the reverse reaction, the dephosphorylation of FDG-6-phosphate back to FDG, hardly occurs in most tissues, the FDG-6-phosphate is trapped intracellularly3. Therefore, the degree of FDG uptake is dependent on the expression of the GLUT (in particular GLUT1 and GLUT3) on the plasma membrane, and the intracellular enzymatic activity of hexokinases. The concept of this continuous uptake and trapping of FDG is referred to as metabolic trapping. The fact that FDG preferentially accumulates in tissues with an elevated metabolic activity is shown in Figure 1a, demonstrating the physiological distribution of FDG in a patient. This FDG-PET image shows higher uptake in heart, brain, and liver tissues, which are known to be metabolically active organs under normal conditions.
The high sensitivity for detecting differences in the metabolic state of tissues makes FDG an excellent radiotracer for discriminating normal from diseased tissues, given that an altered metabolism is an important hallmark for many diseases. This is readily depicted in Figure 1b, showing an FDG-PET image of a patient with stage IV non-small cell lung cancer (NSCLC). There is increased uptake in the primary tumor as well as in metastatic lesions. In addition to visualization, quantification of radiotracer uptake plays an important role in clinical management of patients. Quantitative indices derived from PET images reflecting the degree of radiotracer uptake, such as the standardized uptake value (SUV), metabolic volumes, and total lesion glycolysis (TLG), can be used to provide important prognostic information and measure treatment response for different patient groups4,5,6. In this regard, FDG-PET imaging is increasingly being used to personalize radiotherapy and systemic treatment in oncology patients7. Furthermore, the use of FDG-PET for monitoring acute treatment induced toxicity, such as radiation induced esophagitis8, pneumonitis9 and systemic inflammatory responses10, has been described and provides important information for making image-guided treatment decisions.
Given the important role of PET for clinical management of patients, image quality and quantitative accuracy is important for appropriately guiding treatment decisions based on PET images. However, there are numerous technical factors that can compromise quantitative accuracy of PET images11. An important factor that can significantly influence image quantification in PET is related to the longer acquisition times of PET compared to other radiological imaging modalities, typically several minutes per bed position. As a consequence, patients are usually instructed to breath freely during PET imaging. The result is that PET images suffer from respiratory induced motion, which can lead to significant blurring of organs located within the thorax and upper abdomen. This respiratory-induced motion blurring can significantly impair adequate visualization and quantitative accuracy of radiotracer uptake, which can affect clinical management of patients when using PET images for diagnosis and staging, target volume definition for radiation treatment planning applications, and monitoring of therapy response12.
Several respiratory gating methods have been developed in an attempt to correct PET images for respiratory motion artefacts13. These methods can be categorized into prospective, retrospective, and data-driven gating strategies. Prospective and retrospective respiratory gating techniques typically rely on the acquisition of a respiratory surrogate signal during PET imaging14. These respiratory surrogate signals are used to track and monitor the patient&#8217;s respiratory cycle. Examples of respiratory tracking devices are detection of chest wall excursion using pressure sensors12 or optical tracking systems (e.g., video cameras)15, thermocouples to measure the temperature of breathed air16, and spirometers to measure airflow and thereby indirectly estimating volume changes in the patient&#8217;s lungs17.
Respiratory gating is then typically accomplished by continuously and simultaneously recording a surrogate signal (designated S(t)), with the PET data during image acquisition. Using the surrogate signal acquired, PET data corresponding to a particular respiratory phase or amplitude range (amplitude-based gating) can be selected12,13,18. Phase-based gating is performed by dividing each respiratory cycle into a fixed number of gates, as depicted in Figure 2a. Respiratory gating is then performed by selecting data acquired at a particular phase during the patient&#8217;s respiratory cycle to be used for image reconstruction. Similarly, amplitude-based gating relies on defining an amplitude range of the respiratory signal, as shown in Figure 2b. When the value of the respiratory signal falls within the set amplitude range, the corresponding PET listmode data will be used for image reconstruction. For retrospective gating approaches, all data is collected and re-binning of the PET data is performed after image acquisition. Although prospective respiratory gating methods use the same concepts as retrospective gating approaches for re-binning of PET data, these methods rely on collecting data prospectively during image acquisition. When a sufficient amount of PET data is collected, image acquisition will be finalized. The difficulty of such prospective and retrospective gating approaches is maintaining acceptable image quality without significantly prolonging image acquisition times when irregular breathing occurs13. In this regard, phase-based respiratory gating methods are particularly sensitive to irregular breathing patterns13,19, where significant amounts of PET data can be discarded due to rejection of inappropriate triggers, resulting in considerable reduction of image quality or unacceptable lengthening of image acquisition time. Additionally, when inappropriate triggers are accepted, the performance of the respiratory gating algorithm and thereby the effectiveness of motion rejection from the PET images can be reduced due to the fact that respiratory gates are defined at different phases of the respiratory cycle, as depicted in Figure 2a. Indeed, it has been reported that amplitude-based respiratory gating is more stable than phase-based approaches in case of irregularities in the respiratory signal13. Though amplitude-based respiratory gating algorithms are more robust in the presence of irregular breathing frequencies, these algorithms are more sensitive to baseline drifting of the respiratory signal. Drifting of the baseline signal can occur due to numerous reasons when the patient&#8217;s muscle tension (i.e., transition of a patient into a more relaxed state during image acquisition) or breathing pattern changes. In order to prevent such baseline drifting of the signal, care should be taken to securely attach tracking sensors to the patient and perform regular monitoring of the respiratory signal.
Although these problems are known, traditional respiratory gating algorithms only allow limited control over image quality and usually require significant lengthening of image acquisition time or increased amounts of radiotracer to be administered to the patient. These factors resulted in limited adoption of such protocols in clinical routine. In order to circumvent these problems related to the variable quality of the respiratory gated images , a specific type of amplitude-based gating algorithm, also known as optimal respiratory gating (ORG), has been proposed18. Respiratory gating with ORG permits the user to specify image quality of the respiratory gated images by providing a duty cycle as input to the algorithm. The duty cycle is defined as a percentage of the acquired PET list-mode data that is used for image reconstruction. In contrast to many other respiratory gating algorithms, this concept permits the user to directly determine image quality of the reconstructed PET images. Based on the duty cycle specified, an optimal amplitude range is calculated, which takes the specific characteristics of the entire respiratory surrogate signal into account18. The optimal amplitude range for a specific duty cycle will be calculated by starting with a selection of different values for the lower amplitude limit, designated (L), of the respiratory signal. For each selected lower limit, the upper amplitude limit, designated (U), is adjusted in such a way that the sum of the selected PET data, defined as data acquired when the respiratory signal falls within the amplitude range (L&#60;S(t)&#60;U), is equal to the specified duty cycle. For example, for a duty cycle of 50% and six minutes of acquired PET listmode data, the amplitude range is adapted to include three minutes (50%) of PET data. The optimal amplitude range (W) is defined as the smallest amplitude range used for respiratory gating that still contains the required amount of PET data (i.e., ArgMax([U-L])), as depicted in Figure 2c12. Thus, by specifying the duty cycle, the user makes a trade-off between the amount of noise and the degree of residual motion residing in the ORG PET images. Lowering the duty cycle will increase the amount of noise, though this will also reduce the amount of residual motion in the PET images (and vice versa). Although the concepts and effects of ORG have been described in previous reports, the purpose of this manuscript is to provide clinicians with details on the specific protocols when using ORG in clinical practice. Therefore, the use of ORG in a clinical imaging protocol is described. Several practical aspects, including patient preparation, image acquisition and reconstruction protocols will be provided. Furthermore, the manuscript will cover the user interface of the ORG software and specific choices that can be made when performing respiratory gating during PET imaging. Lastly, the effect of ORG on lesion detectability and image quantification, as shown in previous studies, are discussed.

<table>
	<tbody>
		<tr>
			<td>Sensor Port, sensor, black box, wave deck, elastic band, load cell sensor (complete set)</td>
			<td>anzai medical co.</td>
			<td>respiratory gating system AZ-733V</td>
			<td>http://www.anzai-med.co.jp/en/product/item/az733v</td>
		</tr>
	</tbody>
</table>

management of respiratory motion artefacts in 18f-fluorodeoxyglucose positron emission tomography using an amplitude-based optimal respiratory gating algorithm

Positron emission tomography (PET) combined with X-ray computed tomography (CT) is an important molecular imaging platform that is required for accurate diagnosis and clinical staging of a variety of diseases. The advantage of PET imaging is the ability to visualize and quantify a myriad of biological processes in vivo with high sensitivity and accuracy. However, there are multiple factors that determine image quality and quantitative accuracy of PET images. One of the foremost factors influencing image quality in PET imaging of the thorax and upper abdomen is respiratory motion, resulting in respiration-induced motion blurring of anatomical structures. Correction of these artefacts is required for providing optimal image quality and quantitative accuracy of PET images.
Several respiratory gating techniques have been developed, typically relying on acquisition of a respiratory signal simultaneously with PET data. Based on the respiratory signal acquired, PET data is selected for reconstruction of a motion-free image. Although these methods have been shown to effectively remove respiratory motion artefacts from PET images, the performance is dependent on the quality of the respiratory signal being acquired. In this study, the use of an amplitude-based optimal respiratory gating (ORG) algorithm is discussed. In contrast to many other respiratory gating algorithms, ORG permits the user to have control over image quality versus the amount of rejected motion in the reconstructed PET images. This is achieved by calculating an optimal amplitude range based on the acquired surrogate signal and a user-specified duty cycle (the percentage of PET data used for image reconstruction). The optimal amplitude range is defined as the smallest amplitude range still containing the amount of PET data required for image reconstruction. It was shown that ORG results in effective removal of respiration-induced image blurring in PET imaging of the thorax and upper abdomen, resulting in improved image quality and quantitative accuracy.

The use of ORG in PET results in an overall reduction of respiratory-induced blurring of the images. For example, in a clinical evaluation of patients with non-small cell lung cancer (NSCLC), ORG resulted in detection of more pulmonary lesions and hilar/mediastinal lymph nodes20. This is readily demonstrated in Figure 8 and Figure 9, showing non-gated and ORG PET images of patients with NSCLC.
In particular, OR...

Watch this Scientific Journal Video about Management of Respiratory Motion Artefacts in 18F-fluorodeoxyglucose Positron Emission Tomography using an Amplitude-Based Optimal Respiratory Gating Algorith

Management of Respiratory Motion Artefacts in 18F-fluorodeoxyglucose Positron Emission Tomography using an Amplitude-Based Optimal Respiratory Gating Algorithm

Amplitude-based optimal respiratory gating (ORG) effectively removes respiratory-induced motion blurring from clinical 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images. Correction of FDG-PET images for these respiratory motion artefacts improves image quality, diagnostic and quantitative accuracy. Removal of respiratory motion artefacts is important for adequate clinical management of patients using PET.

Management of Respiratory Motion Artefacts in 18F-fluorodeoxyglucose Positron Emission Tomography using an Amplitude-Based Optimal Respiratory Gating Algorithm

Positron emission tomography (PET) combined with X-ray computed tomography (CT) is an important molecular imaging platform that is required for accurate ...

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5.4K vistas.  Leiden University Medical Centre. Los efectos deteriorados de los artefactos de movimiento respiratorio en las imágenes PET/CT han sido reconocidos durante mucho tiempo. El gating respiratorio óptimo es un método utilizado para corregir imágenes PET/CT para estos artefactos de movimiento. Mantener una calidad de imagen suficiente es problemático para la mayoría de los algoritmos de medición respiratoria.El algoritmo de medición respiratoria óptima permite al usuario mantener y definir una calidad de imagen suf...

Video: Management of Respiratory Motion Artefacts in 18F-fluorodeoxyglucose Positron Emission Tomography using an Amplitude-Based Optimal Respiratory Gating Algorithm