Gary Cook

King's College London | KCL · Division of Imaging Sciences and Biomedical Engineering

Purpose Interpretability is essential for reliable convolutional neural network (CNN) image classifiers in radiological applications. We describe a weakly supervised segmentation model that learns to delineate the target object, trained with only image-level labels (“image contains object” or “image does not contain object”), presenting a different...

Simple Summary This clinical study explored the use of the positron emission tomography radiotracer, [¹⁸F]FSPG, for cancer imaging. [¹⁸F]FSPG measures a process involved in antioxidant production, which is important for cancer prognosis. We compared the distribution of this imaging agent in subjects with head and neck squamous cell cancer (HNSCC) a...

Background Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. Aim The aim of this study was to investigate the association of fluorine-...

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...

Objective Bone loss in people with HIV (PWH) is poorly understood. Switching tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has yielded bone mineral density (BMD) increases. PETRAM (NCT#:03405012) investigated whether BMD and bone turnover changes correlate. Design Open-label, randomized controlled trial. Setting Single-site,...

Simple Summary The expression of the cysteine–glutamate cotransporter, system xc⁻, is increased in cancer cells across many cancer types. Imaging system xc⁻ provides new insights into tumour behaviour. The radiotracer (4S)-4-(3-[¹⁸F]Fluoropropyl)-L-glutamic acid (¹⁸F-FSPG) is specifically transported by system xc⁻, allowing for a non-invasive metho...

Purpose Interpretability is essential for reliable convolutional neural network (CNN) image classifiers in radiological applications. We describe a weakly supervised segmentation model that learns to delineate the target object, trained with only image-level labels (“image contains object” or “image does not contain object”), presenting a different...

Rheumatoid arthritis (RA) is an autoimmune disease that causes joint pain, stiffness, and erosion. Power Doppler ultrasound and MRI are imaging modalities used in detecting and monitoring the disease, but they have limitations. ⁹⁹mTc-maraciclatide gamma camera imaging is a novel technique that can detect joint inflammation at all sites in a single...

Background Radium-223 is a bone-seeking, alpha-emitting radionuclide used to treat men with bone metastases from castration resistant prostate cancer (mCRPC). Sclerotic bone lesions are non-evaluable by RECIST. There is a need for imaging response biomarkers. Methods We did a phase II randomised trial to assess disease response to radium-223. Men...

Cancer is a highly heterogeneous condition best visualised in positron emission tomography. Due to this heterogeneity, a general-purpose cancer detection model can be built using unsupervised learning anomaly detection models. While prior work in this field has showcased the efficacy of abnormality detection methods (e.g. Transformer-based), these...

We review the rationale, methodology, and clinical utility of quantitative [ ¹⁸ F] sodium fluoride ([ ¹⁸ F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (K i , also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. W...

Objectives: To investigate whether baseline 18F-sodium fluoride (NaF) and 18F-choline PET activity is associated with metastatic castration-resistant prostate cancer (mCRPC) global and individual bone metastases' DWI MR imaging response to radium-223 treatment. Methods: Thirty-six bone-only mCRPC patients were prospectively recruited from three...

Background Immune checkpoint inhibitors, including those against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), are routinely used to treat non-small cell lung cancer (NSCLC). PD-L1 is a validated prognostic and predictive immunohistochemical biomarker of anti-PD-1/PD-L1 therapy but displays temporospatial heterogeneity of expression...

Abstract Background Myocardial programmed death-ligand 1 (PD-L1) expression is implicated in immune checkpoint inhibitor (ICI)-associated myocarditis. Measurement of myocardial PD-L1 expression may have potential use as a mechanistic and predictive biomarker. The aim of this study was to determine non-invasive assessment of myocardial PD-L1 express...

Introduction: Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or out...

Cancer is a highly heterogeneous condition that can occur almost anywhere in the human body. [¹⁸F]fluorodeoxyglucose Positron Emission Tomography (¹⁸F-FDG PET) is a imaging modality commonly used to detect cancer due to its high sensitivity and clear visualisation of the pattern of metabolic activity. Nonetheless, as cancer is...

Cancer is a highly heterogeneous condition that can occur almost anywhere in the human body. 18F-fluorodeoxyglucose is an imaging modality commonly used to detect cancer due to its high sensitivity and clear visualisation of the pattern of metabolic activity. Nonetheless, as cancer is highly heterogeneous, it is challenging to train general-purpose...

Bloodstream infection or sepsis is a common cause of mortality globally. Staphylococcus aureus (S. aureus) is of particular concern, through its ability to seed metastatic infections in almost any organ after entering the bloodstream (S. aureus bacteraemia), often without localising signs. A positive blood culture for S. aureus bacteria should lead...

(1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011–2020 in South-East-London cancer centres. Clinicopathological c...

Objectives Radiomic models present an avenue to improve oesophageal adenocarcinoma assessment through quantitative medical image analysis. However, model selection is complicated by the abundance of available predictors and the uncertainty of their relevance and reproducibility. This analysis reviews recent research to facilitate precedent-based mo...

Studies of skeletal metabolism using measurements of bone metabolic flux (Ki) obtained with [18F] sodium fluoride ([18F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating...

Lutetium-177-prostate-specific membrane-617 (177Lu-PSMA-617) is an effective therapy for metastatic castration resistant prostate cancer (mCRPC) with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion to liver ratio of > 1 on 68Ga-PSMA-11 positron emission tomography (PET) scans. We ai...

Background: Internationally, there is a lack of data on the clinicopathological characteristics and outcomes of Black patients with NSCLC. Grouping of minority ethnic patients, such as ‘BAME,’ in advanced NSCLC is misleading. It is established that Asian ethnicity is associated with higher rates of targetable driver mutations and improved survival...

Cancers can have highly heterogeneous uptake patterns best visualised in positron emission tomography. These patterns are essential to detect, diagnose, stage and predict the evolution of cancer. Due to this heterogeneity, a general-purpose cancer detection model can be built using unsupervised learning anomaly detection models; these models learn...

Objective Immune checkpoint inhibitors have revolutionized the care of cancer patients and involve blockade of the PD-L1 receptor. Myocardial PD-L1 expression has been implicated in mice models in myocarditis and autoimmune dilated cardiomyopathy. PD-L1 myocardial expression may have a potential role in immune checkpoint inhibitor myocarditis. We a...

Introduction Pegargiminase (ADI-PEG 20I) degrades arginine in patients with argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). Imaging with proliferation biomarker 3'-deoxy-3'-fluorothymidine (18F FLT) PET-CT was performed in a phase 1 study of pegargiminase with pemetrexed a...

Immunotherapy has transformed the treatment landscape of many cancers, with durable responses in disease previously associated with a poor prognosis. Patient selection remains a challenge, with predictive biomarkers an urgent unmet clinical need. Current predictive biomarkers, including programmed death-ligand 1 (PD-L1) (measured with immunohistoch...

Objective: In clinical positron emission tomography (PET) imaging, quantification of radiotracer uptake in tumours is often performed using semi-quantitative measurements such as the standardised uptake value (SUV). For small objects, the accuracy of SUV estimates is limited by the noise properties of PET images and the partial volume effect. Ther...

Objective: To systematically review the prospective literature on the role of 68Ga and 18F PSMA PET/CT and PET/MRI as a tool for functional imaging in prostate cancer biochemical recurrence (BCR), particularly with respect to detection efficacy and impact on management. Methods: We performed a systematic literature search using PubMed in July 20...

Objectives To evaluate interval changes in heterogeneity on diffusion-weighted apparent diffusion coefficient (ADC) maps and T1-weighted post-gadolinium (T1w post gad) MRI in head and neck carcinoma (HNSCC), with and without chemo-radiotherapy (CRT) response. Methods This prospective observational cohort study included 24 participants (20 men, age...

Bone metastases are a common site of spread in advanced breast cancer and responsible for morbidity and high health care costs. Imaging contributes to staging and response assessment of the skeleton and has been instrumental in guiding patient management for several decades. Historically this has been with radiographs, computed tomography and bone...

Objectives To describe the findings of incidental asymptomatic COVID-19 infection on FDG PET-CT using a case-control design. Methods Incidental pulmonary findings suspicious of asymptomatic COVID-19 infection on FDG PET-CT were classified as a confirmed (positive RT-PCR test) or suspected case (no/negative RT-PCR test). Control cases were identifi...

Background: 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) may improve cancer staging by combining sensitive cancer detection with high-contrast resolution and detail. We compared the diagnostic performance of 18F-FDG PET/MRI to 18F-fluorodeoxyglucose positron emission tomography/computed tomograph...

This report describes the significance of the kinetic parameters (k-values) obtained from the analysis of dynamic positron emission tomography (PET) scans using the Hawkins model describing the pharmacokinetics of sodium fluoride ([18F]NaF) to understand bone physiology. Dynamic [18F]NaF PET scans may be useful as an imaging biomarker in early phas...

Background: Evaluation of gene interaction models in cancer genomics is challenging, as the true distribution is uncertain. Previous analyses have benchmarked models using synthetic data or databases of experimentally verified interactions - approaches which are susceptible to misrepresentation and incompleteness, respectively. The objectives of t...

Purpose: Pre-operative nodal staging is important for planning treatment in cervical cancer (CC) and endometrial cancer (EC) but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-Fluoro-deoxy-glucose-(FDG)-PET/CT and diffusion-weighted-MRI (DW-MRI) with conventional morphological MRI. Experimental desig...

Background A significant proportion of the radiation dose from a PET-CT examination is dependent on the CT protocol, which should be optimised for clinical purposes. Matching protocols on different scanners within an imaging centre is important for the consistency of image quality and dose. This paper describes our experience translating low-dose C...

Background and objectives: Nuclear medicine contributes greatly to the clinical management of patients and experimental medicine. This report aims to (1) outline the current landscape of nuclear medicine research in the UK, including current facilities and recent or ongoing clinical studies and (2) provide information about the available pathways...

Purpose To assess the applicability of the Fluorine-18 performance specifications defined by EANM Research Ltd (EARL), in Gallium-68 multi-centre PET-CT trials using conventional (ordered subset expectation maximisation, OSEM) and advanced iterative reconstructions which include the systems’ point spread function (PSF) and a Bayesian penalised like...

The ability of functional imaging to detect and monitor metastatic disease in the skeleton, with advantages over conventional imaging such as bone scintigraphy or computed tomography (CT), has led to positron emission tomography (PET), particularly with the tracer ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), to be adopted into clinical practice. ¹⁸F-sodium fl...

Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Fo...

Activating epidermal growth factor receptor gene mutations (EGFRm) are relatively common in non-small cell lung cancer (NSCLC) and are predictive of superior outcomes with EGFR tyrosine kinase inhibitors (TKIs). Eventually, acquired genetic or phenotypic resistance overcomes EGFR TKI therapy. Heterogeneity of acquired anti-EGFR resistance mechanism...

Objectives To evaluate the ability of post-chemo-radiotherapy (CRT) diffusion-weighted-MRI apparent diffusion coefficient (ADC mean ) and ¹⁸ F-FDG PET maximum standardized uptake value (SUV max ) to predict disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC), and to determine whether this ability is influenced by human papi...

The level of expression of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) is a predictive biomarker for cancer immunotherapy, however, its detection remains challenging due to tumour heterogeneity and the influence from the binding of therapeutic agents. We recently developed [99mTc]-NM-01 as a companion diagnostic imaging agent f...

Background Posttreatment diffusion–weighted magnetic resonance imaging (DW‐MRI) and 18F‐fluorodeoxygluocose (¹⁸F‐FDG) positron emission tomography (PET) with computed tomography (PET/CT) have potential prognostic value following chemo‐radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Correlations between these PET/CT (standardiz...

Correlation of metabolic parameters of FDG-PET/CT with immune PD-L1 tumour proportion score in early resected non-small cell lung cancer.

Objectives To perform a systematic review of design and reporting of imaging studies applying convolutional neural network models for radiological cancer diagnosis. Methods A comprehensive search of PUBMED, EMBASE, MEDLINE and SCOPUS was performed for published studies applying convolutional neural network models to radiological cancer diagnosis f...

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason...

Head and neck paragangliomas (HNPGLs) are rare tumors with ~30% genetic mutations, mainly in succinate dehydrogenase (SDHx) genes. The utility of FDG PET‐CT in HNPGLs is questioned by recent developments in novel radiotracers. We therefore performed a retrospective study in a single tertiary referral center to address the utility of FDG PET/CT in H...

Background 20% of breast cancers have over-expression of the human epidermal growth factor receptor-2 (HER2), which is an adverse prognostic factor and used to guide therapy selection. At present HER2 expression can only be determined using biopsy material which is then analysed using immunohistochemistry or fluorescence in situ hybridisation. GE-2...

Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Convolutional neural networks (CNNs) have achieved state-of-the-art results in image-to-image translation for brain applications. However, synthesising who...

Purpose Checkpoint inhibition therapy using monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is now standard management of non-small cell lung cancer (NSCLC). PD-L1 expression is a validated and approved prognostic and predictive biomarker for anti-PD-1/PD-L1 therapy. Technetium-99 m [99mTc]-labelled anti-P...

Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Especially for brain applications, convolutional neural networks (CNNs) have proven to be a valuable tool in this image translation task, achieving state-o...

Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Especially for brain applications, convolutional neural networks (CNNs) have proven to be a valuable tool in this image translation task, achieving state-o...

The use of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) has increased over the past few decades. Thus, accurate evaluation of post-SBRT treatment response is essential to avoid over-treatment of responders as well as missing the opportunity to salvage non-responders. There are some intricate imaging differences after live...

PURPOSE Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent...

Radiomics describes the extraction of multiple features from medical images, including molecular imaging modalities, that with bioinformatic approaches, provide additional clinically relevant information that may be invisible to the human eye. This information may complement standard radiological interpretation with data that may better characteriz...

Background Power Doppler ultrasound (PDUS) is superior to clinical examination in detecting synovitis in patients with rheumatoid arthritis (RA). Although dynamic and cheap it is impractical to scan large numbers of joints in routine clinical settings. MRI, whilst sensitive for synovitis, is expensive and routine use is limited to targeted joints....

Bone scintigraphy is used as a common screening test for suspected bone metastases because of its high sensitivity, availability, low cost and ability to scan the entire skeleton. Historical data and clinical experience has established bone scintigraphy as the reference standard in the search for skeletal metastatic disease, and many indications ha...

Prostate cancer (CaP) is the commonest malignancy to affect men in the UK. Extraprostatic disease detection at staging and in the setting of biochemical recurrence (BCR) is essential in determining treatment strategy. Conventional imaging including computed tomography (CT) and bone scintigraphy (BS) are limited in their ability to detect sites of l...

Introduction: The recent rise of checkpoint inhibitor therapy, predominantly programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies as a standard care of treatment in non-small cell lung cancer (NSCLC) amplifies the importance of a diagnostic tool for the assessment of PD-L1 expression. A nuclear medicine scan that is non-invas...

Bone metastases are common, especially in more prevalent malignancies such as breast and prostate cancer. They cause significant morbidity and draw on healthcare resources. Molecular and hybrid imaging techniques, including single photon emission computed tomography with computed tomography (SPECT/CT), positron emission tomography / CT and whole-bo...

Aim 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is valuable in the management of patients with oesophageal cancer, but a role in gastric cancer staging is debated. Our aim was to review the role of FDG PET-CT in a large gastric cancer cohort in a tertiary UK centre. Methods We retrospectively reviewed data f...

Background Power Doppler ultrasound (PDUS) is superior to clinical examination in detecting synovitis in patients with rheumatoid arthritis (RA). Although dynamic and cheap it is impractical to scan large numbers of joints in routine clinical settings. MRI, whilst sensitive for synovitis, is expensive and routine use is limited to targeted joints....

Radiolabeled bisphosphonates were developed in the 1970s for scintigraphic functional imaging of the skeleton in benign and malignant disease. Tracers such as 99mTc-methylene diphosphonate, that map focal or global changes in mineralization in the skeleton qualitatively and quantitatively, have been the backbone of nuclear medicine imaging for deca...

Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were der...

Purpose To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of ⁶⁸Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). Methods...

Radiomics is a rapidly evolving field of research concerned with the extraction and quantification of patterns - the so-called radiomic features - within medical images. Radiomic features capture tissue and lesion characteristics such as heterogeneity and shape, and may, alone or in combination with demographic, histological, genomic or proteomic d...

Purpose: Early and accurate localisation of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, XXX, aimed to evaluate the impact of 18F-fluciclovine on management of men with BCR of prostate cancer. Methods: Men with a first episode of BCR following curative-intent pri...

Staphylococcus aureus bacteraemia (SAB) continues to affect ∼25 000 patients in the UK per year with a high crude mortality of 30% at 90 days. Prompt source control improves outcomes in sepsis and SAB and is included in sepsis guidelines. A recent clinical trial of adjunctive antibiotic treatment in SAB found that the majority of recurrences of SAB...

Cancer evades immune detection and destruction via upregulation of immune checkpoint molecules, such as programmed death-1 (PD-1). Signalling from these molecules can be inhibited by antibodies targeting them or their ligands (e.g. PD-L1). Durable responses have been demonstrated, for example, in subsets of patients with melanoma or non-small cell...

While molecular imaging with positron emission tomography or single-photon emission computed tomography already reports on tumour molecular mechanisms on a macroscopic scale, there is increasing evidence that there are multiple additional features within medical images that can further improve tumour characterization, treatment prediction and progn...

Background Cancer evades immune detection and destruction via upregulation of immune checkpoint molecules, such as programmed death-1 (PD-1). Signalling from these molecules can be inhibited by antibodies targeting them or their ligands (e.g. PD-L1). Durable responses have been demonstrated, for example, in subsets of patients with melanoma or non-...

Background: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET)...

Aim: The aim was to validate promising radiomic features (RFs)1 on 18F-flourodeoxyglucose positron emission tomography/computed tomography-scans (18F-FDG PET/CT) of non-small cell lung cancer (NSCLC) patients undergoing definitive chemo-radiotherapy. Methods: 18F-FDG PET/CT scans performed for radiotherapy (RT) planning were retrieved. Auto-segm...

Objective The recent increase in publications on radiomic analysis as means to produce diagnostic and predictive biomarkers in head and neck cancers (HNCC) reveal complicated and often conflicting results. The objective of this paper is to systematically review the published data, and evaluate the current level of evidence accumulated that would de...