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&#8217;s name and date of birth. Inclusion criteria are similar to routine non-gated PET scanning. No additional in- or exclusion criteria are required.</li>
		<li>Check the label delivered with the syringe containing the radiotracer (name, date of birth and amount of activity). 
		NOTE: The amount of activity administered to the patient is dependent on the patient&#8217;s body mass and can vary between institutions&#160;(in this protocol an amount of 3.2 MBq/kg is suggested).</li>
		<li>Ensure that the clinical information on the application form is correct by interviewing the patient. Ask the patient whether there were any recent relevant changes in treatment or medication.</li>
		<li>Ask the patient whether he or she has diabetes mellitus (DM). In case the patient has DM, ask whether he or she followed appropriate preparation (i.e., no administration of short working insulin less than 4 hours prior to the PET scan, or use of blood glucose lowering agents (such as metformin).</li>
		<li>Ask the patient whether he or she has any allergies or uses anticoagulants.</li>
		<li>Measure the patient&#8217;s blood glucose by applying a drop of blood obtained by pricking the side of the fingertip of the patient on a dedicated test strip (the serum glucose should not exceed 11.0 mmol/L).</li>
		<li>Explain the patient preparation and imaging procedures to the patient.</li>
	</ol>
	</li>
	<li>Administration of the radiotracer
	<ol>
		<li>Secure venous access to the patient by inserting a peripheral venous cannula in one of the antecubital veins.</li>
		<li>Attach a three way stop cock system with Luer lock to a 20 mL syringe containing saline (this is the secondary syringe).</li>
		<li>Flush the three way stop cock system with saline (for the purpose of deaeration).</li>
		<li>Attach the three way stop cock with syringe to the end of the venous cannula.</li>
		<li>Check whether the venous cannula is patent by carefully flushing 10 mL of saline through the cannula (ask the patient whether he or she has any complaints during flushing).</li>
		<li>Attach the syringe containing the radiotracer (primary syringe) to the three way stop cock. Turn the valves of the three way stop cock so that the flow direction of fluid through the system runs from the syringe containing the radiotracer to the peripheral venous cannula. Administer the radiotracer by slowly pushing the plunger of the syringe (the syringe containing the tracer is placed in a special lead shielded container).</li>
		<li>Turn the valves of the three way stop cock in such a way that the syringe containing saline is connected to the primary syringe (that contained the radiotracer) and flush the syringe to rinse any residual radiotracer from the syringe.</li>
		<li>Turn the valves of the three way stop cock and push the plunger of the primary syringe to administer any residual radiotracer remaining in the syringe to the patient.</li>
		<li>Repeat step 1.2.7. and 1.2.8. three times.</li>
		<li>Turn the three way stop cock (to prevent backflow of blood from the patient&#8217;s vein) and detach the primary syringe. Attach a third syringe containing furosemide, turn the three way stop cock again and administer 0.5 g/Kg of furosemide (with a maximum amount of 10 mg) by pushing the plunger of the syringe. Remove the peripheral&#160; venous cannula and apply pressure to the puncture site using a sterile bandage. Check whether there is no significant bleeding and from the puncture site and fix the bandage using medical tape.</li>
	</ol>
	</li>
	<li>Patient incubation
	<ol>
		<li>Let the patient rest in a comfortable position, preferably in a dimly lit room,&#160;for 50 minutes.</li>
		<li>After 50 minutes, instruct the patient to void their bladder.</li>
		<li>At 55 minutes, escort the patient to the scanner and position the patient supine with the arms up on the scanner bed. Use appropriate arm support to make it as comfortable as possible for the patient. If the patient is not able to elevate his or her arms, scanning can be performed with the arms position alongside the patient.</li>
		<li>Observe the patient&#8217;s breathing pattern and secure the respiratory belt around the patient&#8217;s thorax (usually, the position just beneath the rib cage is optimal). Ensure that the sensor is placed at a location where abdominal wall excursion is identified after visual inspection (usually 5-7 cm from the midline). Secure the belt around the patient by using the Velcro-based closing system.</li>
		<li>Check on the scanner display whether the respiratory signal remains within bounds of the minimum and maximum range (if the respiratory signal is clipping, fasten or tighten the belt appropriately).</li>
		<li>Tip: Make sure the belt is fastened tight enough around the patient&#8217;s chest. Given that patients enter a more relaxed state after some time, the respiratory signal tends to drop (baseline drift of the signal). This prevents the signal from going out of bounds, thus maintaining a high quality of surrogate signal that is being used for respiratory gating.</li>
		<li>Start scanning at 60 minutes after incubation time.</li>
	</ol>
	</li>
</ol>
2. Image acquisition and reconstruction
<ol>
	<li>Protocol selection
	<ol>
		<li>Select the whole-body protocol on the scanner. This can be done by moving the cursor over the appropriate protocol category (indicated by the circles next to the patient icon in the examination card), and click on the appropriate protocol (Figure 3).</li>
		<li>The ORG acquisition protocol will start with a scout scan (topogram) of the patient. To initiate acquisition of the topogram, press the scanner start key (yellow round key with a radiation sign) on the scanner control box (Figure 4). To halt or abort acquisition of the topogram, press the suspend or stop key respectively.</li>
		<li>Start by planning the PET bed positions on the topogram. This can be done by clicking the left mouse button on the topogram and setting the scan range.</li>
		<li>Select the bed positions which to be corrected for respiratory motion (Figure 5). 
		NOTE: These are the &#8216;gated&#8217; bed positions that cover the thorax. The &#8216;gated&#8217; bed positions are recorded in listmode. Depending on the clinical indication, bed positions covering the upper abdomen can also be gated (for example when imaging is indicated for liver or pancreatic lesions). For the non-gated bed positions, it is only necessary to record the sinograms for image reconstruction.</li>
		<li>Set image recording time for the PET bed positions (Figure 5). 
		NOTE: Depending on the amount of injected activity, scan duration of the non-gated&#160;bed positions has to be adapted to yield sufficient image quality. Additionally, the recording time of the non-gated bed positions in combination with the duty cycle being used for image reconstruction of the gated bed positions, the recording time of the gated bed positions is determined. For example, for a duty cycle of 35%, lengthening the scan by factor 3 yields approximately similar statistics for gated and non-gated bed positions. Suggested imaging protocol at the Radboud University Medical Center is a recording time for non-gated bed positions of 2 minutes, whilst for gated bed positions recording time is 6 minutes using a duty cycle of 35%</li>
		<li>After setting up the acquisition parameters, press and hold the start key (yellow round button with a radiation sign) on the scanner control box and wait until the scanner bed has moved back to the starting position. Press the start key again to acquire a low dose CT scan from the patient (head to feet). After acquiring the CT scan, press the start key to initiate the PET scan.</li>
		<li>During image acquisition, regularly check on the patient and the quality of the respiratory signal (adjust the respiratory belt if required). 
		NOTE: Adjustment of the belt should only be performed when no respiratory gated bed positions are acquired. Therefore, adjustments should be done before or after these bed positions are acquired. Adjustment of the belt during acquisition of the gated bed position will affect the quality of the ORG images. Careful observation of the respiratory signal and possible adjustment of the respiratory belt before acquisition of the gated bed positions is required to counteract any significant baseline drifting of the signal during PET scanning.</li>
	</ol>
	</li>
	<li>Image reconstruction
	<ol>
		<li>Review the respiratory signal that has been acquired and select the appropriate duty cycle for the gated bed positions (Figure 6). 
		NOTE: The amplitude range used for respiratory gating is superimposed on the respiratory signal). Check for inconstancies or baseline drifts in the respiratory signal that can influence quality of the respiratory gating.</li>
		<li>Select image reconstruction protocol optimized for viewing (Figure 7). This is usually a high-resolution image reconstruction protocol with smaller voxel sizes for detection of small lesions. It is of importance to realize that the ORG algorithm will calculate the optimal amplitude range by using the entire respiratory signal of the selected bed positions. Though different duty cycles can be used for different bed positions (for example to correct for a varying quality respiratory signal), using different duty cycles for different bed positions is not advised given that this will introduce variations in image quality between different bed positions. 
		NOTE: Here is an example image reconstruction protocol for viewing:
		<ul>
			<li>Algorithm: TrueX + TOF (UltraHD PET)</li>
			<li>Number of iterations:3</li>
			<li>Number of subsets: 21</li>
			<li>Matrix size: 400 &#215; 400</li>
			<li>Post-reconstruction filtering, kernel (3D Gaussian), full width half maximum (FWHM): 3.0 mm</li>
			<li>Duty cycle 35%</li>
		</ul>
		</li>
		<li>Furthermore, reconstruct the PET images with an protocol compliant to the Research4Life (EARL) initiative for quantitative PET imaging. These are usually lower resolution images with specific post-reconstruction filtering applied. 
		NOTE: Here is an example image reconstruction protocol for image quantification:
		<ul>
			<li>Algorithm: TrueX + TOF (UltraHD PET)</li>
			<li>Number of iterations: 3</li>
			<li>Number of subsets: 21</li>
			<li>Matrix size: 256</li>
			<li>Post-reconstruction filtering, kernel (3D Gaussian), full width half maximum (FWHM): 8.0 mm</li>
			<li>Duty cycle 35%</li>
		</ul>
		</li>
		<li>Send the reconstructed images to the PACS archive. The images are now ready to be evaluated by the nuclear medicine physician</li>
	</ol>
	</li>
</ol>

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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>

The authors declare no conflict of interest.

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...

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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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5.5K Views.  Leiden University Medical Centre. De verslechterende effecten van respiratoire bewegingsartefacten in PET/CT-beeldvorming zijn al lang goed erkend. Optimale ademhalingsgating is een methode die wordt gebruikt om PET / CT-beelden te corrigeren voor deze bewegingsartefacten. Het handhaven van een voldoende beeldkwaliteit is problematisch voor de meeste ademhalingsgating algoritmen.Het optimale ademhalingsgating algoritme stelt de gebruiker in staat om een voldoende beeldkwaliteit te behouden en te definiëren. Respiratoi...

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

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time &#177;4 cm pan-and-tilt action. Robot-driven &#177;60&#176; pivots of an integrated &#177;185&#176; rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-&#7429;-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Stereotactic ablative body radiation therapy (SBRT) involves the precise delivery of high-dose radiation to cancer tumor targets. A novel SBRT platform offers a first-of-its-kind gimbaled radiation accelerator mounted within a pivoting O-ring gantry capable of dynamic image-guided tumor tracking. Here, we describe dynamic tumor tracking for lung targets.

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable ...

Medicine

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For inoperable patients, local ablation therapies, such as stereotactic body radiotherapy (SBRT), can provide effective local tumor control with minimal toxicity. Because of its high precision and accuracy, SBRT delivers a higher radiation dose per fraction, is more effective, and targets smaller irradiation volumes than does conventional radiotherapy. In addition, steep dose gradients from target lesions to surrounding normal tissues are achieved using SBRT; thus, SBRT provides more effective tumor control and exhibits fewer side effects than conventional radiotherapy. The use of SBRT is prevalent for treating intracranial lesions (known as stereotactic radiosurgery); however, it is now also used for treating spinal and adrenal metastases. Because of advancements in image-guided assistance and respiratory motion management, several studies have investigated the use of SBRT for treating lung or liver tumors, which move as a patient breathes. The results of these studies have suggested that SBRT favorably controls tumors in the case of moving lesions.
Four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) is clinically convenient for effective respiratory motion management. Because this method is noninvasive and allows free breathing, its use reduces complications. Furthermore, patients consider this method convenient. Moreover, it is considered more efficient than other methods of respiratory motion management by physicians and therapists. The use of 4D-CT with an AC for treating pulmonary lesions has also been widely investigated, and the technique is gaining acceptance for treating hepatic lesions. However, the protocols for using 4D-CT with an AC for treating hepatic lesions are different from those used for treating pulmonary lesions. In this article, we describe a new protocol for SBRT with 4D-CT and an AC for treating liver metastases.

Stereotactic body radiotherapy (SBRT) requires rigorous accuracy and precision for delivering high radiation doses per fraction to small treatment volumes to improve tumor control and simultaneously reduce toxicity. Herein, we present a noninvasive and clinically convenient respiratory motion management protocol for SBRT for liver metastases.

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the recognized standard-of-care for blood flow quantification based on phase contrast MRI. While such measurement of blood flow has been possible in adults for decades, methods to extend this capability to fetal blood flow have only recently been developed.
Fetal blood flow quantification in major vessels is important for monitoring fetal pathologies such as congenital heart disease (CHD) and fetal growth restriction (FGR). CHD causes alterations in the cardiac structure and vasculature that change the course of blood in the fetus. In FGR, the path of blood flow is altered through the dilation of shunts such that the oxygenated blood supply to the brain is increased. Blood flow quantification enables assessment of the severity of the fetal pathology, which in turn allows for suitable&#160;in utero&#160;patient management and planning for postnatal care.
The primary challenges of applying phase contrast MRI to the human fetus include small blood vessel size, high fetal heart rate, potential MRI data corruption due to maternal respiration, unpredictable fetal movements, and lack of conventional cardiac gating methods to synchronize data acquisition. Here, we describe recent technical developments from our lab that have enabled the quantification of fetal blood flow using phase contrast MRI, including advances in accelerated imaging, motion compensation, and cardiac gating.

Here we present a protocol for measuring fetal blood flow rapidly with MRI and retrospectively performing motion correction and cardiac gating.

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the ...

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents.
OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4-min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided.
As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

The assessment of microvascular function by oxygenation-sensitive cardiac magnetic resonance imaging in combination with vasoactive breathing maneuvers is unique in its ability to assess rapid dynamic changes in myocardial oxygenation in vivo and, thus, may serve as a critically important diagnostic technique for coronary vascular function.

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of ...

High-Resolution Cardiac Positron Emission Tomography/Computed Tomography for Small Animals

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding cardiac function and metabolism. In preclinical research, dedicated scanners with high sensitivity and high spatio-temporal resolution are employed, designed to cope with the demanding technological requirements posed by the small heart size and very high heart rates of mice and rats. In this paper, a bimodal cardiac PET/CT imaging protocol for experimental mouse and/or rat models of cardiac diseases is described, from animal preparation and image acquisition and reconstruction to image processing and visualization.
In particular, the 18F-labeled fluorodeoxyglucose ([18F]FDG)-PET scan allows for the measurement and visualization of glucose metabolism in the different segments of the left ventricle (LV). Polar maps are convenient tools to display this information. The CT part consists of a time-resolved 3D reconstruction of the entire heart (4D-CT) using retrospective gating without electrocardiography (ECG) leads, allowing the morphofunctional evaluation of the LV and the subsequent quantification of the most important cardiac function parameters, such as ejection fraction (EF) and stroke volume (SV). Using an integrated PET/CT scanner, this protocol can be executed within the same anesthesia induction without the need to reposition the animal between different scanners. Hence, PET/CT can be seen as a comprehensive tool for the morphofunctional and metabolic evaluation of the heart in several small animal models of cardiac diseases.

Here, we present an experimental imaging protocol for the quantification of cardiac function and morphology using high-resolution positron emission tomography/computed tomography for small animals. Both mice and rats are considered, discussing the different requirements of computed tomography contrast agents for the two species.

Positron emission tomography (PET) and computed tomography (CT) are among the most employed diagnostic imaging techniques, and both serve in understanding ...

A Standardized Workflow for Hyperpolarized 129Xe MRI to Study Pulmonary Function

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129Xe as an MR contrast agent and as interest in 129Xe MRI increases among research and clinical institutions. Members of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation&#160;and delivery of individual 129Xe doses, and best practices for monitoring subject safety and 129Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129Xe flip angle and center frequency, and 129Xe MRI ventilation image analysis.

Author Spotlight: Standardization and Best Practices for Advancing Lung Imaging Using 129Xe MRI

Hyperpolarized 129Xe magnetic resonance imaging (MRI) is a method for studying regionally resolved aspects of pulmonary function. This work presents an end-to-end standardized workflow for hyperpolarized 129Xe MRI of lung ventilation, with specific attention to pulse sequence design, 129Xe dose preparation, scan workflow, and best practices for subject safety monitoring.

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is ...

Dynamic Lung Ventilation Assessment with 3D Phase Resolved Functional Lung MRI

Three-Dimensional Phase Resolved Functional Lung Magnetic Resonance Imaging

Pulmonary magnetic resonance imaging (MRI) offers a variety of radiation-free techniques tailored to assess regional lung ventilation or its surrogates. These techniques encompass direct measurements, exemplified by hyperpolarized gas MRI and fluorinated gas MRI, as well as indirect measurements facilitated by oxygen-enhanced MRI and proton-based Fourier decomposition (FD) MRI. In recent times, there has been substantial progress in the field of FD MRI, which involved improving spatial/temporal resolution, refining sequence design and postprocessing, and developing a comprehensive whole-lung approach.
The two-dimensional (2D) phase-resolved functional lung (PREFUL) MRI stands out as an FD-based approach developed for the comprehensive assessment of regional ventilation and perfusion dynamics, all within a single MR acquisition. Recently, a new advancement has been made with the development of 3D PREFUL to assess dynamic ventilation of the entire lung using 8 min exam with a self-gated sequence.
The 3D PREFUL acquisition involves employing a stack-of-stars spoiled-gradient-echo sequence with a golden angle increment. Following the compressed sensing image reconstruction of approximately 40 breathing phases, all the reconstructed respiratory-resolved images undergo registration onto a fixed breathing phase. Subsequently, the ventilation parameters are extracted from the registered images.
In a study cohort comprising healthy volunteers and patients with chronic obstructive pulmonary disease, the 3D PREFUL ventilation parameters demonstrated strong correlations with measurements obtained from pulmonary function tests. Additionally, the interscan repeatability of the 3D PREFUL technique was deemed to be acceptable, indicating its reliability for repeated assessments of the same individuals.
In summary, 3D PREFUL ventilation MRI provides a whole lung coverage and captures ventilation dynamics with enhanced spatial resolution compared to 2D PREFUL. 3D PREFUL technique offers a cost-effective alternative to hyperpolarized 129Xe MRI, making it an attractive option for patient-friendly evaluation of pulmonary ventilation.

Three-dimensional (3D) phase-resolved functional lung (PREFUL) is a functional magnetic resonance imaging (MRI) technique that allows for quantification of regional ventilation of the whole human lung volume, using tidal breathing and contrast-agent free acquisition for 8 min. Here, we present an MR protocol to collect and analyze 3D PREFUL imaging data.

Pulmonary magnetic resonance imaging (MRI) offers a variety of radiation-free techniques tailored to assess regional lung ventilation or its surrogates. ...

Advanced Lung Imaging for Disease Detection and Monitoring

Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components.
Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems.
PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns.
Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

Author Spotlight: Enhancing Diagnostic Strategies and Biomarker Development for Comprehensive Lung Function Analysis

Here, we describe the implementation of phase-resolved functional lung MRI as a contrast-agent-free proton MR technique for the assessment of pulmonary ventilation and perfusion dynamics. Validated and applicable across different field strengths and age groups, it could enhance clinical decision-making in the future by aiding in disease quantification and therapy monitoring.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time ...

Protocol for High-Resolution Lung Imaging Using 3T UTE MRI with Self-Gating

Pulmonary Structural MRI using Free-Breathing, Self-Gated Ultra-short Echo Time Imaging

High quality MRI of the lungs is challenged by low tissue density, fast MRI signal relaxation, and respiratory and cardiac motion. For these reasons, structural imaging of the lungs is performed almost exclusively using Computed Tomography (CT). However, CT imaging delivers ionizing radiation, and thus is less well suited for certain vulnerable populations (e.g., pediatrics) or for research applications. As an alternative, MRI using ultra-short echo times (UTE) is attracting interest. This technique can be performed during free-breathing over the course of a ~5-10 min scan. Respiratory motion information is encoded alongside images; this information can be used to "self-gate" images. Self-gating thus removes the requirement of advanced MRI pulse sequence programming or the use of respiratory bellows, which simplifies image acquisition. In this protocol, simple, robust, and computationally efficient acquisition and reconstruction methods for acquiring high quality UTE MRI of the lungs are presented. This protocol was developed for use on a 3T MRI scanner, but the same principles can be implemented at lower magnetic field strength. The protocol includes recommended parameter settings for 3D radial UTE image acquisition as well as directions for self-gated image reconstruction to generate images at distinct respiratory phases. Through the implementation of this protocol, users can generate high-resolution UTE images of the lungs with minimal to minimal-to-no motion artifacts. These images can be used to evaluate pulmonary structure, which can be implemented for research use in a variety of pulmonary conditions.

Author Spotlight: Optimized Lung MRI Protocol with Computationally Efficient Reconstruction Methods

A protocol is described for generating high-resolution structural images of the lungs using ultra-short-echo time (UTE) Magnetic Resonance Imaging (MRI). This protocol allows for images to be acquired using a simple MRI pulse sequence during free-breathing.

High quality MRI of the lungs is challenged by low tissue density, fast MRI signal relaxation, and respiratory and cardiac motion. For these reasons, ...

Acquisition and Semi-Automated Analysis of Respiratory Muscle Surface Electromyography

Evaluating respiratory drive presents challenges due to the obtrusiveness and impracticality of current methods like functional magnetic resonance imaging (fMRI). Electromyography (EMG) offers a surrogate measure of respiratory drive to the muscles, allowing the determination of both the magnitude and timing of muscle activation. The magnitude reflects the level of muscle activation, while the timing indicates the onset and offset of muscle activity relative to specific events, such as inspiratory flow and activation of other muscles. These metrics are critical for understanding respiratory coordination and control, especially under varying loads or in the presence of respiratory pathophysiology. This study outlines a protocol for acquiring and analyzing respiratory muscle EMG signals in healthy adults and patients with respiratory health conditions. Ethical approval was obtained for the studies, which included participant preparation, electrode placement, signal acquisition, preprocessing, and postprocessing. Key steps involve cleaning the skin, locating muscles via palpation and ultrasound, and applying electrodes to minimize electrocardiography (ECG) contamination. Data is acquired at a high sampling rate and gain, with synchronized ECG and respiratory flow recordings. Preprocessing includes filtering and transforming the EMG signal, while postprocessing involves calculating onset and offset differences relative to the inspiratory flow. Representative data from a healthy male participant performing incremental inspiratory threshold loading (ITL) illustrate the protocol's application. Results showed earlier activation and prolonged duration of extradiaphragmatic muscles under higher loads, correlating with increased EMG magnitude. This protocol facilitates a detailed assessment of respiratory muscle activation, providing insights into both normal and pathophysiologic motor control strategies.

Here, we describe a protocol to record and analyze respiratory electromyography (EMG) signals. It includes the anatomic references for placing the EMG electrodes over several respiratory muscles, removing electrocardiographic noise from the EMG signals, and acquiring the EMG root mean square (RMS) and onset timing of activity.

Evaluating respiratory drive presents challenges due to the obtrusiveness and impracticality of current methods like functional magnetic resonance imaging ...

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

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