Quantification, improvement, and harmonization of small lesion detection with state-of-the-art PET.

In recent years, there have been multiple advances in positron emission tomography/computed tomography (PET/CT) that improve cancer imaging. The present generation of PET/CT scanners introduces new hardware, software, and acquisition methods. This review describes these new developments, which include time-of-flight (TOF), point-spread-function (PSF), maximum-a-posteriori (MAP) based reconstruction, smaller voxels, respiratory gating, metal artefact reduction, and administration of quadratic weight-dependent 18F-fluorodeoxyglucose (FDG) activity. Also, hardware developments such as continuous bed motion (CBM), (digital) solid-state photodetectors and combined PET and magnetic resonance (MR) systems are explained. These novel techniques have a significant impact on cancer imaging, as they result in better image quality, improved small lesion detectability, and more accurate quantification of radiopharmaceutical uptake. This influences cancer diagnosis and staging, as well as therapy response monitoring and radiotherapy planning. Finally, the possible impact of these developments on the European Association of Nuclear Medicine (EANM) guidelines and EANM Research Ltd. (EARL) accreditation for FDG-PET/CT tumor imaging is discussed.

Amplitude-based optimal respiratory gating in positron emission tomography in patients with primary lung cancer.

OBJECTIVES: Respiratory motion during PET imaging introduces quantitative and diagnostic inaccuracies, which may result in non-optimal patient management. This study investigated the effects of respiratory gating on image quantification using an amplitude-based optimal respiratory gating (ORG) algorithm. METHODS: Whole body FDG-PET/CT was performed in 66 lung cancer patients. The respiratory signal was obtained using a pressure sensor integrated in an elastic belt placed around the patient's thorax. ORG images were reconstructed with 50%, 35%, and 20% of acquired PET data (duty cycle). Lesions were grouped into anatomical locations. Differences in lesion volume between ORG and non-gated images, and mean FDG-uptake (SUVmean) were calculated. RESULTS: Lesions in the middle and lower lobes demonstrated a significant SUVmean increase for all duty cycles and volume decrease for duty cycles of 35% and 20%. Significant increase in SUVmean and decrease in volume for lesions in the upper lobes were observed for a 20% duty cycle. The SUVmean increase for central lesions was significant for all duty cycles, whereas a significant volume decrease was observed for a duty cycle of 20%. CONCLUSIONS: This study implies that ORG could influence clinical PET imaging with respect to response monitoring and radiotherapy planning. KEY POINTS: Quantifying lesion volume and uptake in PET is important for patient management. Respiratory motion artefacts introduce inaccuracies in quantification of PET images. Amplitude-based optimal respiratory gating maintains image quality through selection of duty cycle. The effect of respiratory gating on lesion quantification depends on anatomical location.

Single-institution clinical experience using robust intensity modulated proton therapy in chordoma and chondrosarcoma of the mobile spine and sacrum: Feasibility and need for plan adaptation.

BACKGROUND: Due to its specific physical characteristics, proton irradiation is especially suited for irradiation of chordomas and chondrosarcoma in the axial skeleton. Robust plan optimization renders the proton beam therapy more predictable upon individual setup errors. Reported experience with the planning and delivery of robustly optimized plans in chordoma and chondrosarcoma of the mobile spine and sacrum, is limited. In this study, we report on the clinical use of robustly optimized, intensity modulated proton beam therapy in these patients. METHODS: We retrospectively reviewed patient, treatment and acute toxicity data of all patients with chordoma and chondrosarcoma of the mobile spine and sacrum, treated between 1 April 2019 and 1 April 2020 at our institute. Anatomy changes during treatment were evaluated by weekly cone-beam CTs (CBCT), supplemented by scheduled control-CTs or ad-hoc control-CTs. Acute toxicity was scored weekly during treatment and at 3 months after therapy according to CTCAE 4.0. RESULTS: 17 chordoma and 3 chondrosarcoma patients were included. Coverage of the high dose clinical target volume was 99.8% (range 56.1-100%) in the nominal and 80.9% (range 14.3-99.6%) in the voxel-wise minimum dose distribution. Treatment plan adaptation was needed in 5 out of 22 (22.7%) plans. Reasons for plan adaptation were either reduced tumor coverage or increased dose to the OAR. CONCLUSIONS: Robustly optimized intensity modulated proton beam therapy for chordoma and chondrosarcoma of the mobile spine is feasible. Plan adaptations due to anatomical changes were required in approximately 23 percent of treatment courses.

Improving the Spatial Alignment in PET/CT Using Amplitude-Based Respiration-Gated PET and Patient-Specific Breathing-Instructed CT.

Appropriate attenuation correction is important for accurate quantification of SUVs in PET. Patient respiratory motion can introduce a spatial mismatch between respiration-gated PET and CT, reducing quantitative accuracy. In this study, the effect of a patient-specific breathing-instructed CT protocol on the spatial alignment between CT and amplitude-based optimal respiration-gated PET images was investigated. Methods: 18F-FDG PET/CT imaging was performed on 20 patients. In addition to the standard low-dose free-breathing CT, breath-hold CT was performed. The amplitude limits of the respiration-gated PET were used to instruct patients to hold their breath during CT acquisition at a similar amplitude level. Spatial mismatch was quantified using the position differences between the lung-liver transition in PET and CT images, the distance between PET and CT lesions' centroids, and the amount of overlap as indicated by the Jaccard similarity coefficient. Furthermore, the effect on attenuation correction was quantified by measuring SUVs, metabolic tumor volume, and total lesion glycolysis (TLG) of lung lesions. Results: All patients found the breathing instructions feasible; however, 4 patients had trouble complying with the instructions. In total, 18 patients were included. The average distance between the lung-liver transition between PET and CT was significantly reduced for breath-hold CT (1.7 ± 2.1 mm), compared with standard CT (5.6 ± 7.3 mm) (P = 0.049). Furthermore, the mean distance between the lesions' centroids on PET and CT was significantly smaller for breath-hold CT (3.6 ± 2.0 mm) than for standard CT (5.5 ± 6.5 mm) (P = 0.040). Quantification of lung lesion SUV was significantly affected, with a higher SUVmean when breath-hold CT (6.3 ± 3.9 g/cm3) was used for image reconstruction than for standard CT (6.1 ± 3.8 g/cm3) (P = 0.044). Though metabolic tumor volume was not significantly different, TLG reached statistical significance. Conclusion: Optimal respiration-gated PET in combination with patient-specific breathing-instructed CT results in an improved alignment between PET and CT images and shows an increased SUVmean and TLG. Even though the effects are small, a more accurate SUV and TLG determination is of importance for a more stable PET quantification, which is relevant for radiotherapy planning and therapy response monitoring.

Metal Artifact Reduction of CT Scans to Improve PET/CT.

In recent years, different metal artifact reduction methods have been developed for CT. These methods have only recently been introduced for PET/CT even though they could be beneficial for interpretation, segmentation, and quantification of the PET/CT images. In this study, phantom and patient scans were analyzed visually and quantitatively to measure the effect on PET images of iterative metal artifact reduction (iMAR) of CT data. Methods: The phantom consisted of 2 types of hip prostheses in a solution of 18F-FDG and water. 18F-FDG PET/CT scans of 14 patients with metal implants (either dental implants, hip prostheses, shoulder prostheses, or pedicle screws) and 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT scans of 7 patients with hip prostheses were scored by 2 experienced nuclear medicine physicians to analyze clinical relevance. For all patients, a lesion was located in the field of view of the metal implant. Phantom and patients were scanned in a PET/CT scanner. The standard low-dose CT scans were processed with the iMAR algorithm. The PET data were reconstructed using attenuation correction provided by both standard CT and iMAR-processed CT. Results: For the phantom scans, cold artifacts were visible on the PET image. There was a 30% deficit in 18F-FDG concentration, which was restored by iMAR processing, indicating that metal artifacts on CT images induce quantification errors in PET data. The iMAR algorithm was useful for most patients. When iMAR was used, the confidence in interpretation increased or stayed the same, with an average improvement of 28% ± 20% (scored on a scale of 0%-100% confidence). The SUV increase or decrease depended on the type of metal artifact. The mean difference in absolute values of SUVmean of the lesions was 3.5% ± 3.3%. Conclusion: The iMAR algorithm increases the confidence of the interpretation of the PET/CT scan and influences the SUV. The added value of iMAR depends on the indication for the PET/CT scan, location and size/type of the prosthesis, and location and extent of the disease.

The Impact of Optimal Respiratory Gating and Image Noise on Evaluation of Intratumor Heterogeneity on 18F-FDG PET Imaging of Lung Cancer.

Accurate measurement of intratumor heterogeneity using parameters of texture on PET images is essential for precise characterization of cancer lesions. In this study, we investigated the influence of respiratory motion and varying noise levels on quantification of textural parameters in patients with lung cancer. METHODS: We used an optimal-respiratory-gating algorithm on the list-mode data of 60 lung cancer patients who underwent 18F-FDG PET. The images were reconstructed using a duty cycle of 35% (percentage of the total acquired PET data). In addition, nongated images of varying statistical quality (using 35% and 100% of the PET data) were reconstructed to investigate the effects of image noise. Several global image-derived indices and textural parameters (entropy, high-intensity emphasis, zone percentage, and dissimilarity) that have been associated with patient outcome were calculated. The clinical impact of optimal respiratory gating and image noise on assessment of intratumor heterogeneity was evaluated using Cox regression models, with overall survival as the outcome measure. The threshold for statistical significance was adjusted for multiple comparisons using Bonferroni correction. RESULTS: In the lower lung lobes, respiratory motion significantly affected quantification of intratumor heterogeneity for all textural parameters (P < 0.007) except entropy (P > 0.007). The mean increase in entropy, dissimilarity, zone percentage, and high-intensity emphasis was 1.3% ± 1.5% (P = 0.02), 11.6% ± 11.8% (P = 0.006), 2.3% ± 2.2% (P = 0.002), and 16.8% ± 17.2% (P = 0.006), respectively. No significant differences were observed for lesions in the upper lung lobes (P > 0.007). Differences in the statistical quality of the PET images affected the textural parameters less than respiratory motion, with no significant difference observed. The median follow-up time was 35 mo (range, 7-39 mo). In multivariate analysis for overall survival, total lesion glycolysis and high-intensity emphasis were the two most relevant image-derived indices and were considered to be independent significant covariates for the model regardless of the image type considered. CONCLUSION: The tested textural parameters are robust in the presence of respiratory motion artifacts and varying levels of image noise.

Improving the Spatial Alignment in PET/CT Using Amplitude-Based Respiration-Gated PET and Respiration-Triggered CT.

UNLABELLED: Respiratory motion during PET can cause inaccuracies in the quantification of radiotracer uptake, which negatively affects PET-guided radiotherapy planning. Quantitative accuracy can be improved by respiratory gating. However, additional miscalculation of standardized uptake value (SUV) in PET images can be caused by inappropriate attenuation correction due to a spatial mismatch between gated PET and CT. In this study, the effect of respiration-triggered CT on the spatial match between CT and amplitude-based respiration-gated PET images is investigated. METHODS: (18)F-FDG PET/CT was performed in 38 patients. Images were acquired on 2 PET/CT scanners, one without and one with continuous bed motion during PET acquisition. The amplitude limits of the amplitude-based respiration-gated PET were used for the respiration-triggered sequential low-dose CT. Both standard (spiral) and triggered CT scans were used to reconstruct the PET data. Spatial mismatch was quantified using the position difference between the lung-liver boundary in PET and CT images, the distance between PET and CT lung lesions' centroids, and the amount of overlap of lesions indicated by the Jaccard similarity coefficient. Furthermore, the effect of attenuation correction was quantified by measuring SUVs in lung lesions. RESULTS: For triggered CT, the average distance between the lung-liver boundary in PET and CT was significantly reduced (4.5 ± 6.7 mm) when compared with standard CT (9.2 ± 8.1 mm) (P < 0.001). The mean distance between the lesions' centroids in PET and CT images was 6.3 ± 4.0 and 5.6 ± 4.2 mm (P = 0.424), for the standard and triggered CT, respectively. Similarly, the Jaccard similarity coefficient was 0.30 ± 0.21 and 0.32 ± 0.20 (P = 0.609) for standard and triggered CT, respectively. For 6 lesions, there was no overlap of PET and CT when the standard CT was used; compared with the triggered CT, these lesions showed (partial) overlap. The maximum and mean SUV increase of the PET/CT compared with the PET/triggered CT was 5.7% ± 11.2% (P < 0.001) and 6.1% ± 10.2% (P = 0.001), respectively. CONCLUSION: Amplitude-based respiration-gated PET in combination with respiration-triggered CT resulted in a significantly improved match in the area of the liver dome and a significantly higher SUV for lung lesions. However, lesions in the lungs did not show a consistent improvement in spatial match.

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.

UNLABELLED: Respiratory motion during PET has a significant effect on the quantification of radiotracer uptake in PET images. Even when respiratory motion is considered using PET gating techniques, inaccuracies in standardized uptake values can be caused by inappropriate attenuation correction due to a spatial mismatch between PET and CT. In this study, the effect of breath-hold CT imaging on the spatial match between CT and amplitude-based respiratory-gated PET images is investigated. METHODS: Whole-body (18)F-FDG PET/CT imaging was performed in 52 patients with 125 lung lesions. (18)F-FDG PET was performed using optimized, amplitude-based respiratory gating. For CT, 36 patients were randomly assigned to the free-breathing (FB) group and 16 to the rest-expiratory breath-hold (BH) group. Spatial mismatch between the PET and CT images was quantified by measuring the distance between the centroids of PET and CT lesions and calculating the Jaccard similarity coefficient (JSC). RESULTS: In the upper lobes, the average distance between the centroids of the PET and CT lesions was 4.7 ± 3.1 and 6.0 ± 3.0 mm for the FB and BH groups, respectively (P = 0.11). For the middle and lower lobes, the distances were 5.8 ± 4.3 and 5.1 ± 2.9 mm (P = 0.70), respectively, and for the central region 4.8 ± 4.6 and 5.6 ± 2.0 mm (P = 0.24), respectively. The JSC for the upper lobes was 0.28 ± 0.17 and 0.28 ± 0.19, for the FB and the BH group, respectively (P = 0.83). For the middle and lower lobes, the JSC was 0.22 ± 0.16 and 0.28 ± 0.18 (P = 0.20), respectively, and for the central region 0.39 ± 0.17 and 0.13 ± 0.04 (P = 0.04), respectively. CONCLUSION: Providing breathing instructions to the patients during the CT acquisition did not improve the spatial alignment between the respiratory-gated PET images and the CT images. The difficulty experienced in using this clinical protocol, such as patient compliance and operator dependence, emphasizes the need for other strategies.

Reduction of contrast medium volume in abdominal aorta CTA: multiphasic injection technique versus a test bolus volume.

OBJECTIVE: The purpose of this study is to reduce the administered contrast medium volume in abdominal CTA by using a test bolus injection, with the preservation of adequate quantitative and qualitative vessel enhancement. STUDY DESIGN: For this technical efficacy study 30 patients, who were referred for a CTA examination of the abdominal aorta, were included. Randomly 15 patients were assigned to undergo a multiphasic injection protocol and received 89 mL of contrast medium (Optiray 350) (protocol I). Fifteen patients were assigned to the test bolus injection protocol (protocol II), which implies injection of a 10 mL test bolus of Optiray 350 prior to performing CTA with a 40 mL of contrast medium. Quantitative assessment of vascular enhancement was performed by measuring the amount of Hounsfield Units in the aorta at 30 positions from the celiac trunk to the iliac arteries in both groups. Qualitative assessment was performed by three radiologists who scored the images at a 5-point scale. RESULTS: Quantitative assessment showed that there was no significant difference in vascular enhancement for patients between the two protocols, with mean attenuation values of 280.9 ± 50.84 HU and 258.60 ± 39.28 HU, respectively. The image quality of protocol I was rated 4.31 (range: 3.67/5.00) and of protocol II 4.11 (range: 2.67/5.00). These differences were not statistically significant. CONCLUSION: This study showed that by using a test bolus injection and the administration of 50 mL of contrast medium overall, CTA of the abdominal aorta can reliably be performed, with regard to quantitative and qualitative adequate vessel enhancement.

Reduced contrast medium in abdominal aorta CTA using a multiphasic injection technique.

PURPOSE: The purpose of this study was to determine if with a multiphasic injection technique the administered amount of contrast medium for abdominal computerized tomographic angiography (CTA) can be decreased, whilst improving CT image quality. MATERIALS AND METHODS: In 30 patients a multiphasic injection method was compared to the standard uniphasic contrast medium injection protocol. Fifteen patients underwent abdominal CTA with a standard uniphasic injection protocol (protocol I) receiving 100mL of a non-ionic radiopaque contrast agent (Ioversol). The second group of 15 patients underwent CTA with a multiphasic injection protocol (protocol II) receiving a total of 89 mL Ioversol. Vascular contrast enhancement and difference in enhancement uniformity were assessed quantitatively and image quality was assessed by three independent radiologists. RESULTS: Quantitative assessment of the vascular contrast enhancement showed that there was no significant difference in enhancement uniformity for patients between the protocols. The image quality was rated as being good to excellent in 81.8% and 88.0% of the scans, for protocol I and protocol II, respectively. However these differences were not statistically significant. CONCLUSION: By using a multiphasic injection technique with CTA of the abdominal aorta a reduction of 11 percent of contrast medium can be realized. Enhancement patterns are quantitatively as well as qualitatively comparable to the standard contrast medium injection protocol.