Ronald Boellaard

Amsterdam UMC · Radiology and Nuclear Medicine

Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...

Background Neuroinflammation plays a key role in Alzheimer’s disease (AD) pathophysiology. However, whether neuroinflammation has a prognostic effect on disease progression is largely unknown. Therefore, we aim to investigate the role of neuroinflammation as measured using PET on longitudinal cognition and survival. Method We included 29 amyloid‐p...

Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...

Purpose The aim of this study was to validate simplified methods for quantifying [⁶⁸Ga]Ga-FAPI-46 uptake against full pharmacokinetic modeling. Methods Ten patients with pancreatobiliary cancer underwent a 90-min dynamic PET/CT scan using a long axial field of view system. Arterial blood samples were used to establish calibrated plasma-input funct...

Purpose [ ¹⁸ F]NaF PET has become an increasingly important tool in clinical practice toward understanding and evaluating diseases and conditions in which bone metabolism is disrupted. Full kinetic analysis using nonlinear regression (NLR) with a two-tissue compartment model to determine the net rate of influx ( K i ) of [ ¹⁸ F]NaF is considered th...

Background: Bleomycin is an oncolytic and antibiotic agent used to treat various human cancers because of its antitumor activity. Unfortunately, up to 46% of the patients treated with bleomycin develop drug-induced interstitial lung disease (DIILD) and potentially life-threatening interstitial pulmonary fibrosis. Tools and biomarkers for predicting...

MYCN-amplified RB1 wild-type (MYCNampRB1+/+) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCNampRB1+/+ from the most prevalent RB1-/- retinoblastoma using pretreatment MR...

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of...

Introduction The novel positron emission tomography (PET) imaging tracer, [¹⁸F]F-AraG, targets activated T-cells, offering a potential means to improve our understanding of immune-oncological processes. The aim of this study was to determine the optimal pharmacokinetic model to quantify tumour lesion [¹⁸F]F-AraG uptake in patients with non-small ce...

The aim of this study was to validate a previously developed deep learning model in 5 independent clinical trials. The predictive performance of this model was compared with the international prognostic index (IPI) and 2 models incorporating radiomic PET/CT features (clinical PET and PET models). Methods: In total, 1,132 diffuse large B-cell lympho...

Methods to shorten [18F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [18F]FDG Patlak i...

Purpose To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial...

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark dataset allowing TMTV to be tested and applied as a reproducible biomarker. Methods: Sixty baseline 18F-FDG PET/CT scans were id...

Background Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome. Methods In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasib...

Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. ¹⁸ F-fluoride uptake in newly formed bone can be evaluated using [ ¹⁸ F]NaF (i.e., sodiumfluoride) PET/CT, ide...

Objective: It is unclear how self-reported severe fatigue and difficulty concentrating after SARS-CoV-2 infection relate to objective neuropsychological functioning. The study aimed to compare neuropsychological functioning between individuals with and without these persistent subjective complaints. Method: Individuals with and without persistent...

Background Spondyloarthritis (SpA) belongs to chronic inflammatory rheumatic diseases and primarily affects the axial skeleton. [¹⁸F]Fluoride PET/CT is an imaging approach that detects osteoblastic activity, and shows promise for early diagnosis and treatment assessment of SpA [1,2]. Visual assessment of [¹⁸F]Fluoride PET is time-consuming and subj...

3576 Background: The use of anti-Epidermal Growth Factor Receptor monoclonal antibody therapy (anti-EGFR mAb) for patients with metastatic colorectal cancer (mCRC) is ongoing subject of research. Initially, absence of mutations in KRASand NRAS oncogenes was identified as biomarker for response, however, not all patients benefitted. Molecular imagin...

Purpose Long axial field-of-view (LAFOV) PET/CT systems enable PET/CT scans with reduced injected activities because of improved sensitivity. With this study, we aimed to examine the foetal radiation dose from an ¹⁸ F-FDG PET/CT scan on a LAFOV PET/CT system with reduced injected activity. Methods Two pregnant women were retrospectively included a...

Immune-based treatment approaches are successfully used for the treatment of patients with cancer. While such therapies can be highly effective, many patients fail to benefit. To provide optimal therapy choices and to predict treatment responses, reliable biomarkers for the assessment of immune features in patients with cancer are of significant im...

Purpose This prospective study evaluates the biodistribution of ¹⁸ F-FLT PET in patients with advanced melanoma before and after treatment with BRAF/MEK inhibitors. Patients and Methods Eighteen BRAF-positive unresectable stage IIIc or IV melanoma patients referred for ¹⁸ F-FLT PET/CT before (BL) and during (D14) BRAF/MEK inhibition were included....

INTRODUCTION To support clinical trial designs focused on early interventions, our study determined reliable early amyloid‐β (Aβ) accumulation based on Centiloids (CL) in pre‐dementia populations. METHODS A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD‐PNHS) and Insi...

Introduction The novel positron emission tomography (PET) imaging tracer, [¹⁸F]F-AraG, targets activated T-cells, offering a potential means to improve our understanding of immune-oncological processes. The aim of this study was to determine the optimal pharmacokinetic model to quantify tumour lesion [¹⁸F]F-AraG uptake in patients with non-small ce...

This study investigated whether radiomic features extracted from pretreatment [18F]FDG PET could improve the prediction of both histopathologic tumor response and survival in patients with locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by surgery compared with conventional PET parameters and histopatholo...

Background Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings. Methods Eight [¹⁸...

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epile...

Background Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the ⁸⁹Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific i...

Background PET scans using zirconium-89 labelled monoclonal antibodies (⁸⁹Zr-mAbs), known as ⁸⁹Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of ⁸⁹Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best de...

Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of...

Background Different tau‐PET patterns have been observed in Alzheimer’s disease (AD) which may be associated with demographic factors, copathology and resilience. We and others previously found that not all Aβ‐positive AD patients are tau‐PET positive. It is currently not known whether tau pathology develops in these groups over time. Therefore, we...

Background Longitudinal amyloid‐PET‐based imaging endpoints are often included in clinical trials, where they provide critical evidence of treatment efficacy. We assessed the longitudinal variability of the Centiloid (CL) scale and its ability to predict early amyloid accumulation. Method Longitudinal amyloid‐PET with ¹⁸ F‐flutemetamol and ¹⁸ F‐fl...

Background Tau tangles are one of the pathological hallmarks of Alzheimer’s disease (AD) and can be quantified using PET. It remains unclear which molecular processes are related to tau aggregation. Protein levels in CSF can be used to study such underlying processes. This study aims to identify biological processes related to tau‐PET using unbiase...

Background Longitudinal amyloid‐PET‐based imaging endpoints are often included in clinical trials, where they provide critical evidence of treatment efficacy. We assessed the longitudinal variability of the Centiloid (CL) scale and its ability to predict early amyloid accumulation. Method Longitudinal amyloid‐PET with 18F‐flutemetamol and 18F‐flor...

Purpose The aims of this study were to investigate whether (early) PERCIST response monitoring with ¹⁸ F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct co...

Background: Accurate detection of patients at high risk of treatment failure following frontline immunochemotherapy in diffuse large B-cell lymphoma (DLBCL) is of paramount importance as these patients might benefit from early treatment escalation. Recently, we introduced the IMPI prognostic model based on metabolic tumor volume (MTV), age and stag...

Simple Summary The uptake on a ⁸⁹Zr-immuno-PET scan is not just the result of the binding of a radiolabeled antibody with its target (i.e., target engagement) but also includes background factors such as non-specific binding (for example, catabolism of antibodies inside endothelial cells). In this study, we wanted to isolate target engagement. We u...

Purpose Standardised uptake values (SUV) are commonly used to quantify ¹⁸F-FDG lesion uptake. However, SUVs may suffer from several uncertainties and errors. Long-axial field-of-view (LAFOV) PET/CT systems might enable image-based quality control (QC) by deriving ¹⁸F-FDG activity and weight from total body (TB) ¹⁸F-FDG PET images. In this study, we...

BACKGROUND Local treatment of diffuse glioma is currently guided by standard MRI sequences. Yet, the combination of apparent diffusion coefficient (ADC) and O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET PET) (ADC/FET) detects qualitatively assessed histopathological tumor presence more accurately than standard MRI imaging. It...

Introduction Radiomics extracted from prostate-specific membrane antigen (PSMA)-PET modeled with machine learning (ML) may be used for prediction of disease risk. However, validation of previously proposed approaches is lacking. We aimed to optimize and validate ML models based on ¹⁸F-DCFPyL-PET radiomics for the prediction of lymph-node involvemen...

Background Image harmonization has been proposed to minimize heterogeneity in brain PET scans acquired in multi-center studies. However, standard validated methods and software tools are lacking. Here, we assessed the performance of a framework for the harmonization of brain PET scans in a multi-center European clinical trial. Method Hoffman 3D br...

Background Dynamic PET imaging studies provide accurate estimates of specific binding, but also measure the relative tracer delivery (R 1 ), which is a proxy for relative cerebral blood flow (rCBF). Recently, studies suggested that R 1 obtained from different tracers could be used interchangeably and is irrespective of target tissue. However, the s...

The development of artificial intelligence (AI) within nuclear imaging involves several ethically fraught components at different stages of the machine learning pipeline, including during data collection, model training and validation, and clinical use. Drawing on the traditional principles of medical and research ethics, and highlighting the need...

Background Convolutional neural networks (CNNs), applied to baseline [¹⁸F]-FDG PET/CT maximum intensity projections (MIPs), show potential for treatment outcome prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to investigate the robustness of CNN predictions to different image reconstruction protocols. Baseline [¹⁸F]FDG...

Investigating prognostic factors in relapsed or primary refractory classical Hodgkin lymphoma (R/R cHL) patients is essential to optimize risk-adapted treatment strategies. We built a prognostic model using baseline quantitative 18F-FDG PET radiomics features and clinical characteristics to predict progression free survival (PFS) in R/R cHL patient...

BACKGROUND Diffuse glioma local treatment is currently guided by standard MRI sequences. Yet, the combination of apparent diffusion coefficient (ADC) and O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET PET) (ADC/FET) detects histopathological qualitative assessed tumor presence more accurately than standard imaging. It is unkno...

Preamble The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates c...

The deployment of artificial intelligence (AI) has the potential to make nuclear medicine and medical imaging faster, cheaper, and both more effective and more accessible. This is possible, however, only if clinicians and patients feel that these AI medical devices (AIMDs) are trustworthy. Highlighting the need to ensure health justice by fairly di...

Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time-to...

Introduction P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer’s...

The purpose of this study was to quantify any differences between the SUVs of 89Zr immuno-PET scans obtained using a PET/CT system with a long axial field of view (LAFOV; Biograph Vision Quadra) compared to a PET/CT system with a short axial field of view (SAFOV; Biograph Vision) and to evaluate how LAFOV PET scan duration affects image noise and S...

Background Behavioural symptoms and frontotemporal hypometabolism overlap between behavioural variant of frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), hampering diagnostic distinction. Voxel-wise comparisons of brain metabolism might identify specific frontotemporal-(hypo)metabolic regions between bvFTD and PPD. We invest...

Introduction: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation,...

Background Convolutional Neural Networks (CNN), applied to baseline [¹⁸F]-FDG PET/CT maximum intensity projections (MIPs) show potential for treatment outcome prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to investigate the robustness of CNN predictions to different image reconstruction protocols, such as the Europea...

Kidney hypoxia has been proposed as key pathophysiological mechanism in the development of chronic kidney disease, potentially stemming from a mismatch between oxygen delivery and oxygen consumption. SGLT2i are kidney protective drugs that initially lower glomerular filtration rate (GFR). Accordingly, we hypothesized that SGLT2i lower kidney oxygen...

Background Several studies validated R 1 as a marker for relative cerebral blood flow (rCBF). However, the similarities or differences of R 1 estimates obtained from different PET tracers has never been investigated. Aim The aim of the current study was head‐to‐head comparison of R 1 estimates, derived from dynamic [ ¹⁸ F]florbetapir and [ ¹⁸ F]fl...

Background Carotid occlusive disease (COD) is a risk factor for cognitive decline. One of the proposed underlying mechanisms is that cerebral hypoperfusion may result in accelerated accumulation of amyloid‐β in the brain. We hypothesized that patients with longstanding, unilateral COD have an asymmetrical burden of cerebral amyloid‐β, with more amy...

Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic...

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 unde...

Aim: To build and externally validate an [18F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Two multicentre datasets of patients with operable HNSCC treated with preoperative afatinib who underwent a baseline and evaluation [18F]FDG PET/CT scan were included (EORTC: n...

Cognitive impairment occurs in 40-65% of persons with multiple sclerosis and may be related to alterations in glutamatergic and GABAergic neurotransmission. Therefore, the aim of this study was to determine how glutamatergic and GABAergic changes relate to cognitive functioning in multiple sclerosis in-vivo. Sixty persons with multiple sclerosis (m...

Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response asses...

Background Image harmonization has been proposed to minimize heterogeneity in brain PET scans acquired in multi-center studies. However, standard validated methods and software tools are lacking. Here, we assessed the performance of a framework for the harmonization of brain PET scans in a multi-center European clinical trial. Method Hoffman 3D br...

The objective of this study was to externally validate the clinicalPET model developed in the HOVON-84 trial and to compare the model performance of our clinicalPET model to the international prognostic index (IPI). In total, 1195 Diffuse large B-cell lymphoma patients were included. 887 patients from 6 studies were used as external validation data...

Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time...

Purpose Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For ⁸⁹Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems...

Purpose The aim of this study was to develop a convolutional neural network (CNN) for the automatic detection and segmentation of gliomas using [¹⁸F]fluoroethyl-L-tyrosine ([¹⁸F]FET) PET. Methods Ninety-three patients (84 in-house/7 external) who underwent a 20–40-min static [¹⁸F]FET PET scan were retrospectively included. Lesions and background r...