Optimal reconstruction algorithms for high-resolution positron emission tomography

Lammertsma, A.A. [Promotor]Boellaard, R. [Copromotor

Reproducible Analysis of Rat Brain PET Studies Using an Additional [(18)F]NaF Scan and an MR-Based ROI Template

Background. An important step in the analysis of positron emission tomography (PET) studies of the brain is the definition of regions of interest (ROI). Image coregistration, ROI analysis, and quantification of brain PET data in small animals can be observer dependent. The purpose of this study was to investigate the feasibility of ROI analysis based on a standard MR template and an additional [(18)F]NaF scan. Methods. [(18)F]NaF scans of 10 Wistar rats were coregistered with a standard MR template by 3 observers and derived transformation matrices were applied to corresponding [(11)C]AF150(S) images. Uptake measures were derived for several brain regions delineated using the MR template. Overall agreement between the 3 observers was assessed by interclass correlation coefficients (ICC) of uptake data. In addition, [(11)C]AF150(S) ROI data were compared with ex vivo biodistribution data. Results. For all brain regions, ICC analysis showed excellent agreement between observers. Reproducibility, estimated by calculation of standard deviation of the between-observer differences, was demonstrated by an average of 17% expressed as coefficient of variation. Uptake of [(11)C]AF150(S) derived from ROI analysis closely matched ex vivo biodistribution data. Conclusions. The proposed method provides a reproducible and tracer-independent method for ROI analysis of rat brain PET data

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

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

Explainable artificial intelligence (XAI) in radiology and nuclear medicine: a literature review

Rational: Deep learning (DL) has demonstrated a remarkable performance in diagnostic imaging for various diseases and modalities and therefore has a high potential to be used as a clinical tool. However, current practice shows low deployment of these algorithms in clinical practice, because DL algorithms lack transparency and trust due to their underlying black-box mechanism. For successful employment, explainable artificial intelligence (XAI) could be introduced to close the gap between the medical professionals and the DL algorithms. In this literature review, XAI methods available for magnetic resonance (MR), computed tomography (CT), and positron emission tomography (PET) imaging are discussed and future suggestions are made.Methods: PubMed, and Clarivate Analytics/Web of Science Core Collection were screened. Articles were considered eligible for inclusion if XAI was used (and well described) to describe the behavior of a DL model used in MR, CT and PET imaging.Results: A total of 75 articles were included of which 54 and 17 articles described post and ad hoc XAI methods, respectively, and 4 articles described both XAI methods. Major variations in performance is seen between the methods. Overall, post hoc XAI lacks the ability to provide class-discriminative and target-specific explanation. Ad hoc XAI seems to tackle this because of its intrinsic ability to explain. However, quality control of the XAI methods is rarely applied and therefore systematic comparison between the methods is difficult.Conclusion: There is currently no clear consensus on how XAI should be deployed in order to close the gap between medical professionals and DL algorithms for clinical implementation. We advocate for systematic technical and clinical quality assessment of XAI methods. Also, to ensure end-to-end unbiased and safe integration of XAI in clinical workflow, (anatomical) data minimization and quality control methods should be included

Dynamic rubidium-82 PET/CT as a novel tool for quantifying hemodynamic differences in renal blood flow using a one-tissue compartment model

Purpose: Assessing renal perfusion in-vivo is challenging and quantitativeinformation regarding renal hemodynamics is hardly incorporated in medicaldecision-making while abnormal renal hemodynamics might play a crucial rolein the onset and progression of renal disease. Combining physiological stimuliwith rubidium-82 positron emission tomography/computed tomography (82 RbPET/CT) offers opportunities to test the kidney perfusion under various condi-tions. The aim of this study is: (1) to investigate the application of a one-tissuecompartment model for measuring renal hemodynamics with dynamic 82 RbPET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitiveto detect differences in renal hemodynamics in stress conditions compared toresting state.Methods: A one-tissue compartment model for the kidney was applied to car-diac 82 Rb PET/CT scans that were obtained for ischemia detection as part ofclinical care. Retrospective data, collected from 17 patients undergoing dynamicmyocardial 82 Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospectivedata, collected from 10 patients (five impaired kidney functions and five controls)undergoing dynamic myocardial 82 Rb PET/CT imaging, were used to evaluateimage-derived input functions (IDIFs), PET-based VOIs of the kidney, extractionfractions, and whether dynamic 82 Rb PET/CT can measure renal hemodynam-ics differences using the renal blood flow (RBF) values in rest and after exposureto adenosine pharmacological stress.Results: The delivery rate (K1 ) values showed no significant (p = 0.14) differ-ence between the mean standard deviation (SD) K1 values using one CT-basedVOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32),1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF inrest and RBF in pharmacological stress for the controls were overall significantlylower compared to the impaired kidney function group for both PET-based delin-eation methods (region growing and iso-contouring), with the smallest medianinterquartile range (IQR) of 0.40(0.28–0.66) and 0.96(0.62–1.15), respectively(p </p

Stimulation of the beta-2-adrenergic receptor with salbutamol activates human brown adipose tissue

While brown adipose tissue (BAT) is activated by the beta-3-adrenergic receptor (ADRB3) in rodents, in human brown adipocytes, the ADRB2 is dominantly present and responsible for noradrenergic activation. Therefore, we performed a randomized double-blinded crossover trial in young lean men to compare the effects of single intravenous bolus of the ADRB2 agonist salbutamol without and with the ADRB1/2 antago-nist propranolol on glucose uptake by BAT, assessed by dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan (i.e., primary outcome). Salbutamol, compared with salbutamol with propranolol, increases glucose uptake by BAT, without affecting the glucose uptake by skeletal muscle and white adipose tissue. The salbutamol-induced glucose uptake by BAT positively asso-ciates with the increase in energy expenditure. Notably, participants with high salbutamol-induced glucose uptake by BAT have lower body fat mass, waist-hip ratio, and serum LDL-cholesterol concentration. In conclusion, specific ADRB2 agonism activates human BAT, which warrants investigation of ADRB2 activation in long-term studies (EudraCT: 2020-004059-34).NWO091506191007

Prognostic value of quantitative [F-18]FDG-PET features in patients with metastases from soft tissue sarcoma

Background: Prognostic biomarkers are pivotal for adequate treatment decision making. The objective of this study was to determine the added prognostic value of quantitative [F-18]FDG-PET features in patients with metastases from soft tissue sarcoma (STS). Methods: Patients with metastases from STS, detected by (re)staging [F-18]FDG-PET/CT at Leiden University Medical Centre, were retrospectively included. Clinical and histopathological patient characteristics and [F-18]FDG-PET features (SUVmax, SUVpeak, SUVmean, total lesion glycolysis, and metabolic tumor volume) were analyzed as prognostic factors for overall survival using a Cox proportional hazards model and Kaplan-Meier methods. Results: A total of 31 patients were included. SUVmax and SUVpeak were significantly predictive for overall survival (OS) in a univariate analysis (p = 0.004 and p = 0.006, respectively). Hazard ratios (HRs) were 1.16 per unit increase for SUVmax and 1.20 per unit for SUVpeak. SUVmax and SUVpeak remained significant predictors for overall survival after correction for the two strongest predictive clinical characteristics (number of lesions and performance status) in a multivariate analysis (p = 0.02 for both). Median SUVmax and SUVpeak were 5.7 and 4.9 g/mL, respectively. The estimated mean overall survival in patients with SUVmax > 5.7 g/mL was 14 months; otherwise, it was 39 months (p 4.9 g/mL, the estimated mean overall survival was 18 months; otherwise, it was 33 months (p = 0.04). Conclusions: In this study, SUVmax and SUVpeak were independent prognostic factors for overall survival in patients with metastases from STS. These results warrant further investigation of metabolic imaging with [F-18]FDG-PET/CT in patients with metastatic STS.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Harmonisation of PET/CT contrast recovery performance for brain studies

Purpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed.Methods Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based "digital" systems) were used to acquire 30-min PET scans of a Hoffman 3D Brain phantom filled with similar to 33 kBq.mL(-1) [F-18]FDG. Scan data were reconstructed using various reconstruction settings. The images were rigidly coregistered to a template (voxel size 1.17 x 1.17 x 2.00 mm(3)) onto which several volumes of interest (VOIs) were defined. Recovery coefficients (RC) and grey matter to white matter ratios (GMWMr) were derived for eroded (denoted in the text by subscript e) and non-eroded grey (GM) and white (WM) matter VOIs as well as a mid-phantom cold spot (VOIcold) and VOIs from the Hammers atlas. In addition, left-right hemisphere differences and voxel-by-voxel differences compared to a reference image were assessed.Results Systematic differences were observed for reconstructions with and without point-spread-function modelling (PSFON and PSFOFF, respectively). Normalising to image-derived activity, upper and lower limits ensuring image comparability were as follows: for PSFON, RCGMe = [0.97-1.01] and GMWMr(e) = [3.51-3.91] for eroded VOI and RCGM = [0.78-0.83] and GMWMr = [1.77-2.06] for non-eroded VOI, and for PSFOFF, RCGMe = [0.92-0.99] and GMWMr(e) = [3.14-3.68] for eroded VOI and RCGM = [0.75-0.81] and GMWMr = [1.72-1.95] for non-eroded VOI.Conclusions To achieve inter-scanner comparability, we propose selecting reconstruction settings based on RCGMe and GMWMr(e) as specified in "Results". These proposed standards should be tested prospectively to validate and/or refine the harmonisation criteria.Neuro Imaging Researc

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study

Abstract: Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). Methods: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). Results: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). Conclusion: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT

⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy:A Feasibility Study

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.</p