Showing papers in "British Journal of Radiology in 2018"

Liver fat imaging—a clinical overview of ultrasound, CT, and MR imaging

Abstract: Hepatic steatosis is a frequently encountered imaging finding that may indicate chronic liver disease, the most common of which is non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease is implicated in the development of systemic diseases and its progressive phenotype, non-alcoholic steatohepatitis, leads to increased liver-specific morbidity and mortality. With the rising obesity epidemic and advent of novel therapeutics aimed at altering metabolism, there is a growing need to quantify and monitor liver steatosis. Imaging methods for assessing steatosis range from simple and qualitative to complex and highly accurate metrics. Ultrasound may be appropriate in some clinical instances as a screening modality to identify the presence of abnormal liver morphology. However, it lacks sufficient specificity and sensitivity to constitute a diagnostic modality for instigating and monitoring therapy. Newer ultrasound techniques such as quantitative ultrasound show promise in turning qualitative assessment of steatosis on conventional ultrasound into quantitative measurements. Conventional unenhanced CT is capable of detecting and quantifying moderate to severe steatosis but is inaccurate at diagnosing mild steatosis and involves the use of radiation. Newer CT techniques, like dual energy CT, show potential in expanding the role of CT in quantifying steatosis. MRI proton-density fat fraction is currently the most accurate and precise imaging biomarker to quantify liver steatosis. As such, proton-density fat fraction is the most appropriate noninvasive end point for steatosis reduction in clinical trials and therapy response assessment.

Automation in intensity modulated radiotherapy treatment planning-a review of recent innovations.

Abstract: Radiotherapy treatment planning of complex radiotherapy techniques, such as intensity modulated radiotherapy and volumetric modulated arc therapy, is a resource-intensive process requiring a high l...

Deep learning beyond cats and dogs: recent advances in diagnosing breast cancer with deep neural networks

Abstract: Deep learning has demonstrated tremendous revolutionary changes in the computing industry and its effects in radiology and imaging sciences have begun to dramatically change screening paradigms. Specifically, these advances have influenced the development of computer-aided detection and diagnosis (CAD) systems. These technologies have long been thought of as “second-opinion” tools for radiologists and clinicians. However, with significant improvements in deep neural networks, the diagnostic capabilities of learning algorithms are approaching levels of human expertise (radiologists, clinicians etc.), shifting the CAD paradigm from a “second opinion” tool to a more collaborative utility. This paper reviews recently developed CAD systems based on deep learning technologies for breast cancer diagnosis, explains their superiorities with respect to previously established systems, defines the methodologies behind the improved achievements including algorithmic developments, and describes remaining challenges in ...

Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application

Abstract: Currently, different radiometals are in use for imaging and therapy in nuclear medicine: 68Ga and 111In are examples of nuclides for positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, while 177Lu and 225Ac are used for β-- and α-radionuclide therapy. The application of diagnostic and therapeutic radionuclides of the same element (radioisotopes) would utilize chemically-identical radiopharmaceuticals for imaging and subsequent treatment, thereby enabling the radiotheranostic concept. There are two elements which are of particular interest in this regard: Scandium and Terbium. Scandium presents three radioisotopes for theranostic application. 43Sc (T1/2 = 3.9 h) and 44Sc (T1/2 = 4.0 h) can both be used for PET, while 47Sc (T1/2 = 3.35 d) is the therapeutic match-also suitable for SPECT. Currently, 44Sc is most advanced in terms of production, as well as with pre-clinical investigations, and has already been employed in proof-of-concept studies in patients. Even though the production of 43Sc may be more challenging, it would be advantageous due to the absence of high-energetic γ-ray emission. The development of 47Sc is still in its infancy, however, its therapeutic potential has been demonstrated preclinically. Terbium is unique in that it represents four medically-interesting radioisotopes. 155Tb (T1/2 = 5.32 d) and 152Tb (T1/2 = 17.5 h) can be used for SPECT and PET, respectively. Both radioisotopes were produced and tested preclinically. 152Tb has been the first Tb isotope that was tested (as 152Tb-DOTATOC) in a patient. Both radionuclides may be of interest for dosimetry purposes prior to the application of radiolanthanide therapy. The decay properties of 161Tb (T1/2 = 6.89 d) are similar to 177Lu, but the coemission of Auger electrons make it attractive for a combined β-/Auger electron therapy, which was shown to be effective in preclinical experiments. 149Tb (T1/2 = 4.1 h) has been proposed for targeted α-therapy with the possibility of PET imaging. In terms of production, 161Tb and 155Tb are most promising to be made available at the large quantities suitable for future clinical translation. This review article is dedicated to the production routes, the methods of separating the radioisotopes from the target material, preclinical investigations and clinical proof-of-concept studies of Sc and Tb radionuclides. The availability, challenges of production and first (pre)clinical application, as well as the potential of these novel radionuclides for future application in nuclear medicine, are discussed.

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.

Abstract: AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates This nanoparticle has been recently accepted in clinical trials in association with radiotherapy This review will summarize the principal preclinical results that have led to first in man administration No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys) Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…) The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Development and validation of a radiomic signature to predict HPV (p16) status from standard CT imaging: a multicenter study.

Abstract: Objectives:Human papillomavirus (HPV) positive oropharyngeal cancer (oropharyngeal squamous cell carcinoma, OPSCC) is biologically and clinically different from HPV negative OPSCC. Here, we evaluate the use of a radiomic approach to identify the HPV status of OPSCC.Methods:Four independent cohorts, totaling 778 OPSCC patients with HPV determined by p16 were collected. We randomly assigned 80% of all data for model training (N = 628) and 20% for validation (N = 150). On the pre-treatment CT images, 902 radiomic features were calculated from the gross tumor volume. Multivariable modeling was performed using least absolute shrinkage and selection operator. To assess the impact of CT artifacts in predicting HPV (p16), a model was developed on all training data (Mall) and on the artifact-free subset of training data (Mno art). Models were validated on all validation data (Vall), and the subgroups with (Vart) and without (Vno art) artifacts. Kaplan–Meier survival analysis was performed to compare HPV status bas...

Theranostic radiopharmaceuticals: established agents in current use.

Abstract: Although use of the term "theranostic" is relatively recent, the concept goes back to the earliest days of nuclear medicine, with the use of radioiodine for diagnosis and therapy of benign and malignant thyroid disease being arguably the most successful molecular radiotherapy in history. A diagnostic scan with 123I-, 124I-, or a low activity of 131I-iodide is followed by therapy with high activity 131I-iodide. Similarly, adrenergic tumours such as phaeochromocytoma and neuroblastoma can be imaged with 123I-metaiodobenzylguanidine and treated with 131I-metaiodobenzylguanidine. Bone scintigraphy can be used to select patients with painful bone metastases from prostate cancer who may benefit from treatment with beta- or alpha-particle emitting bone seeking agents, the most recent and successful of which is 223Ra radium chloride. Anti-CD20 monoclonal antibodies can be used to image and treat non-Hodgkins lymphoma, though this has not been as commercially successful as initially predicted. More recently established theranostics include somatostatin receptor targeting peptides for diagnosis and treatment of neuroendocrine tumours with agents such as 68Ga-DOTATATE and 177Lu-DOTATATE, respectively. Finally, agents which target prostate-specific membrane antigen are becoming increasingly widely available, despite the current lack of a commercial product. With the recent licensing of the somatostatin peptides and the rapid adoption of 68Ga- and 177Lu-labelled prostate-specific membrane antigen targeting agents, we have built upon the experience of radioiodine and are already seeing a great expansion in the availability of widely accepted theranostic radiopharmaceuticals.

SPECT/CT: an update on technological developments and clinical applications

Abstract: Functional nuclear medicine imaging with single-photon emission CT (SPECT) in combination with anatomical CT has been commercially available since the beginning of this century. The combination of the two modalities has improved both the sensitivity and specificity of many clinical applications and CT in conjunction with SPECT that allows for spatial overlay of the SPECT data on good anatomy images. Introduction of diagnostic CT units as part of the SPECT/CT system has also potentially allowed for a more cost-efficient use of the equipment. Most of the SPECT systems available are based on the well-known Anger camera principle with NaI(Tl) as a scintillation material, parallel-hole collimators and multiple photomultiplier tubes, which, from the centroid of the scintillation light, determine the position of an event. Recently, solid-state detectors using cadmium-zinc-telluride became available and clinical SPECT cameras employing multiple pinhole collimators have been developed and introduced in the market. However, even if new systems become available with better hardware, the SPECT reconstruction will still be affected by photon attenuation and scatter and collimator response. Compensation for these effects is needed even for qualitative studies to avoid artefacts leading to false positives. This review highlights the recent progress for both new SPECT cameras systems as well as for various data-processing and compensation methods.

Towards enhanced PET quantification in clinical oncology.

Abstract: Positron emission tomography (PET) has, since its inception, established itself as the imaging modality of choice for the in vivo quantitative assessment of molecular targets in a wide range of biochemical processes underlying tumour physiology. PET image quantification enables to ascertain a direct link between the time-varying activity concentration in organs/tissues and the fundamental parameters portraying the biological processes at the cellular level being assessed. However, the quantitative potential of PET may be affected by a number of factors related to physical effects, hardware and software system specifications, tracer kinetics, motion, scan protocol design and limitations in current image-derived PET metrics. Given the relatively large number of PET metrics reported in the literature, the selection of the best metric for fulfilling a specific task in a particular application is still a matter of debate. Quantitative PET has advanced elegantly during the last two decades and is now reaching the maturity required for clinical exploitation, particularly in oncology where it has the capability to open many avenues for clinical diagnosis, assessment of response to treatment and therapy planning. Therefore, the preservation and further enhancement of the quantitative features of PET imaging is crucial to ensure that the full clinical value of PET imaging modality is utilized in clinical oncology. Recent advancements in PET technology and methodology have paved the way for faster PET acquisitions of enhanced sensitivity to support the clinical translation of highly quantitative four-dimensional (4D) parametric imaging methods in clinical oncology. In this report, we provide an overview of recent advances and future trends in quantitative PET imaging in the context of clinical oncology. The pros/cons of the various image-derived PET metrics will be discussed and the promise of novel methodologies will be highlighted.

Innovations in image-guided preoperative breast lesion localization

Abstract: Screening mammography increases detection of non-palpable breast lesions requiring image-guided localization prior to surgery. Accurate preoperative localization is crucial for successful surgical outcomes. Wire-guided localization is currently the most widely used localization method for non-palpable breast lesions; however, this technique has multiple disadvantages including patient discomfort, possible wire transection and migration, suboptimal surgical incision placement due to wire location and limited scheduling flexibility decreasing operating room efficiency. As a result, promising new techniques including radioactive seed localization, non-radioactive radar localization and magnetic seed localization have been developed as alternatives. In this article, we provide an overview of these techniques and discuss their advantages, drawbacks and currently available outcome data.

UK quantitative WB-DWI technical workgroup: Consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer

Abstract: Objective:Application of whole body diffusion-weighted MRI (WB-DWI) for oncology are rapidly increasing within both research and routine clinical domains. However, WB-DWI as a quantitative imaging biomarker (QIB) has significantly slower adoption. To date, challenges relating to accuracy and reproducibility, essential criteria for a good QIB, have limited widespread clinical translation. In recognition, a UK workgroup was established in 2016 to provide technical consensus guidelines (to maximise accuracy and reproducibility of WB-MRI QIBs) and accelerate the clinical translation of quantitative WB-DWI applications for oncology.Methods:A panel of experts convened from cancer centres around the UK with subspecialty expertise in quantitative imaging and/or the use of WB-MRI with DWI. A formal consensus method was used to obtain consensus agreement regarding best practice. Questions were asked about the appropriateness or otherwise on scanner hardware and software, sequence optimisation, acquisition protocols...

Abbreviated breast MRI for screening women with dense breast: the EA1141 trial

Abstract: Early diagnosis improves survival of females with breast cancer. Mammographic screening improves early diagnosis of breast cancer. And yet, there appears to be room for improvement. Major shortcomings of mammographic screening are overdiagnosis of prognostically unimportant cancer, as well as underdiagnosis of cancers that are indeed relevant. Failure to detect biologically relevant breast cancer with mammographic screening is driven not only by host-related factors, i.e. breast tissue density, but also by tumour-related factors: Biologically relevant cancers may exhibit imaging features that render them indistinguishable from normal or benign breast tissue on mammography. These cancers will then progress to become the advanced-stage interval cancers observed in females undergoing mammographic screening. Since breast cancer continues to represent a major cause of cancer death in females, the search for improved breast cancer screening method continues. Abbreviated breast MRI has been proposed for this pur...

Respiratory motion correction for free-breathing 3D abdominal MRI using CNN-based image registration: a feasibility study.

Abstract: Objective:Free-breathing abdomen imaging requires non-rigid motion registration of unavoidable respiratory motion in three-dimensional undersampled data sets. In this work, we introduce an image registration method based on the convolutional neural network (CNN) to obtain motion-free abdominal images throughout the respiratory cycle.Methods:Abdominal data were acquired from 10 volunteers using a 1.5 T MRI system. The respiratory signal was extracted from the central-space spokes, and the acquired data were reordered in three bins according to the corresponding breathing signal. Retrospective image reconstruction of the three near-motion free respiratory phases was performed using non-Cartesian iterative SENSE reconstruction. Then, we trained a CNN to analyse the spatial transform among the different bins. This network could generate the displacement vector field and be applied to perform registration on unseen image pairs. To demonstrate the feasibility of this registration method, we compared the perform...

Fully automated segmentation and quantification of visceral and subcutaneous fat at abdominal CT: application to a longitudinal adult screening cohort.

Abstract: Objective:To investigate a fully automated CT-based adiposity tool, applying it to a longitudinal adult screening cohort.Methods:A validated automated adipose tissue segmentation algorithm was applied to non-contrast abdominal CT scans in 8852 consecutive asymptomatic adults (mean age, 57.1 years; 3926 M/4926 F) undergoing colonography screening. The tool was also applied to follow-up CT scans in a subset of 1584 individuals undergoing longitudinal surveillance (mean interval, 5.6 years). Visceral and subcutaneous adipose tissue (VAT and SAT) volumes were segmented at levels T12-L5. Primary adipose results are reported herein for the L1 level as mean cross-sectional area. CT-based adipose measurements at initial CT and change over time were analyzed.Results:Mean VAT values were significantly higher in males (205.8 ± 107.5 vs 108.1 ± 82.4 cm2; p < 0.001), whereas mean SAT values were significantly higher in females (171.3 ± 111.3 vs 124.3 ± 79.7 cm2; p < 0.001). The VAT/SAT ratio at L1 was three times high...

Differentiated thyroid cancer theranostics: radioiodine and beyond.

Abstract: The term theranostics is the combination of a diagnostic tool that helps to define the right therapeutic tool for specific disease. It signifies the "we know which sites require treatment (diagnostic scan) and confirm that those sites have been treated (post-therapy scan)" demonstrating the achievable tumor dose concept. This term was first used by John Funkhouser at the beginning of the 90s, at the same time the concept of personalized medicine appeared. In nuclear medicine, theranostics is easy to apply and understand because of an easy switch from diagnosis to therapy with the same vector. It helps in maximizing tumor dose and sparing normal tissue with high specific and rapid uptake in metastasis. The oldest application of this concept is radioactive iodine I-131 (RAI). The first treatment based on the theranostic concept was performed on thyroid cancer patients with RAI in 1946. From then on management of differentiated thyroid cancer (DTC) has evolved on the multimodality concept. We now use the term "our" patient instead of "my" patient to signify this. However, the initial surgical management followed by RAI as per the theranostics has remained the mainstay in achieving a cure in most of DTC patients. The normal thyroid cells metabolise iodine, the principle of which is utilized in imaging of the thyroid gland with isotopes of iodine. RAI treatment of DTC is based on the principle of sodium iodide symporter (NIS) expressing thyroid cells with DTC cells having the ability of trapping circulating RAI successfully helping in treatment of residual and metastatic disease. NIS is usually negative in poorly differentiated cells and is inversely proportional to Glucose transporter receptor Type 1 expression. Both positive and negative NIS are the key components of the theranostic approach in treatment of DTC. Presence or absence of NIS is documented by either whole body iodine scintigraphy (WBS) or 2-deoxy-2(18F) fludeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT). Currently, single photon emission CT and CT (SPECT-CT) has significantly improved the precision and sensitivity of whole body iodine scintigraphy with its capability of accurate localization of disease foci whether iodine avid or non-avid. This has helped in a more personalized approach in treatment. This review will give an overview of the role of NIS in the theranostic approach to management with RAI, its current status and also the molecular approach to treatment in RAI refractory disease.

Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer.

Abstract: Various kinds of image-guided techniques have been successfully applied in the last years for the treatment of tumours, as alternative to surgical resection. High intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image-guided technique that allows for achieving tissue destruction with the application of focused ultrasound at high intensity. This technique has been successfully applied for the treatment of a large variety of diseases, including oncological and non-oncological diseases. One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected “systemic” response to treatments designed to be “local”. In the present article the mechanisms of action of HIFU are described, and the main clinical applications of this technique are reported, with a particular focus on the immune-stimulation process that might originate from tumour ablations.

Overuse of CT and MRI in paediatric emergency departments

Abstract: The aim of this review is to survey CT and MRI overuse in the paediatric emergency department (ED) population. CT is one of the most important modalities employed in the ED. Not surprisingly, its high accuracy, rapid acquisition and availability have resulted in overuse. An obvious limitation of CT is ionizing radiation; in addition there are economic implications to overuse. Studies from the last two decades have shown increase in paediatric ED CT utilization in the first decade, reaching a plateau forming around 2008, followed by a decrease in the last decade. This decrease occurred in conjunction with campaigns raising awareness to the risks of radiation exposure. Although a trend of decrease in overuse have been observed, great variability has been shown across different facilities, as well as among physicians, with more pronounced overuse in non-teaching and non-children dedicated EDs. The leading types of paediatric ED CTs are head and abdominal scans. Decision rules, such as PECARN for head injury and the Alvarado score for abdominal pain, as well as using alternative imaging modalities, have been shown to reduce CT overuse in these two categories. MRI has the obvious benefit of avoiding radiation exposure, but the disadvantages of higher costs, less availability and less tolerability in younger children. Although anecdotally paediatric ED MRI usage has increased in recent years, only scarce reports have been published. In our opinion, there is need to conduct up-to-date studies covering paediatric CT and MRI overuse trends, usage variability and adherence to clinical protocols.

The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy.

Abstract: Altered by ionising radiation, the vascular network is considered as a prime target to limit normal tissue damage and improve tumour control in radiotherapy (RT). Irradiation damages and/or activates endothelial cells, which then participate in the recruitment of circulating cells, especially by overexpressing cell adhesion molecules, but also by other as yet unknown mechanisms. Radiation-induced lesions are associated with infiltration of immune-inflammatory cells from the blood and/or the lymph circulation. Damaged cells from the tissues and immune-inflammatory resident cells release factors that attract cells from the circulation, leading to the restoration of tissue balance by fighting against infection, elimination of damaged cells and healing of the injured area. In normal tissues that surround the tumours, the development of an immune-inflammatory reaction in response to radiation-induced tissue injury can turn out to be chronic and deleterious for the organ concerned, potentially leading to fibros...

Immune-related tumour response assessment criteria: a comprehensive review.

Abstract: Growing emphasis on precision medicine in oncology has led to increasing use of targeted therapies that encompass a spectrum of drug classes including angiogenesis inhibitors, immune modulators, signal transduction inhibitors, DNA damage modulators, hormonal agents etc. Immune therapeutic drugs constitute a unique group among the novel therapeutic agents that are transforming cancer treatment, and their use is rising. The imaging manifestations in patients on immune therapies appear to be distinct from those typically seen with conventional cytotoxic therapies. Patients on immune therapies may demonstrate a delayed response, transient tumour enlargement followed by shrinkage, stable size, or initial appearance of new lesions followed by stability or response. These newer patterns of response to treatment have rendered conventional criteria such as World Health Organization and response evaluation criteria in solid tumours suboptimal in monitoring changes in tumour burden. As a consequence, newer imaging response criteria such as immune-related response evaluation criteria in solid tumours and immune-related response criteria are being implemented in many trials to effectively monitor patients on immune therapies. In this review, we discuss the traditional and new imaging response criteria for evaluation of solid tumours, review the outcomes of various articles which compared traditional criteria with the new immune-related criteria and discuss pseudo-progression and immune-related adverse events.

A review on radiomics and the future of theranostics for patient selection in precision medicine

Abstract: The growing complexity and volume of clinical data and the associated decision-making processes in oncology promote the advent of precision medicine. Precision (or personalised) medicine describes preventive and/or treatment procedures that take individual patient variability into account when proscribing treatment, and has been hindered in the past by the strict requirements of accurate, robust, repeatable and preferably non-invasive biomarkers to stratify both the patient and the disease. In oncology, tumour subtypes are traditionally measured through repeated invasive biopsies, which are taxing for the patient and are cost and labour intensive. Quantitative analysis of routine clinical imaging provides an opportunity to capture tumour heterogeneity non-invasively, cost-effectively and on large scale. In current clinical practice radiological images are qualitatively analysed by expert radiologists whose interpretation is known to suffer from inter- and intra-operator variability. Radiomics, the high-throughput mining of image features from medical images, provides a quantitative and robust method to assess tumour heterogeneity, and radiomics-based signatures provide a powerful tool for precision medicine in cancer treatment. This study aims to provide an overview of the current state of radiomics as a precision medicine decision support tool. We first provide an overview of the requirements and challenges radiomics currently faces in being incorporated as a tool for precision medicine, followed by an outline of radiomics' current applications in the treatment of various types of cancer. We finish with a discussion of possible future advances that can further develop radiomics as a precision medicine tool.

Obesity, metabolic disease and the pancreas-Quantitative imaging of pancreatic fat.

Abstract: The association between pancreatic fat, obesity and metabolic disease is well-documented, and although a potentially exciting target for novel therapies, remains poorly understood. Non-invasive quantitative imaging-derived biomarkers can provide insights into pathophysiology and potentially provide robust trial endpoints for development of new treatments. In this review, we provide an overview of the pathophysiology of non-alcoholic fatty pancreas disease and associations with metabolic factors, obesity and diabetes. We then explore approaches to pancreatic fat quantification using ultrasound, CT and MRI, reviewing the strengths, limitations and current published evidence in the assessment of pancreatic fat. Finally, we explore the broader challenges of pancreatic fat quantification as we move toward translating these methods into the clinical setting.

HPV, hypoxia and radiation response in head and neck cancer.

Abstract: Over the last decades, the incidence of human papilloma virus (HPV) positive head and neck squamous-cell carcinoma (HNSCC) has significantly increased. Infection with high-risk HPV types drives tumourigenesis through expression of the oncoproteins E6 and E7. Currently, the primary treatment of HNSCC consists of radiotherapy, often combined with platinum-based chemotherapeutics. One of the common features of HNSCC is the occurrence of tumour hypoxia, which impairs the efficacy of radiotherapy and is a negative prognostic factor. Therefore, it is important to detect and quantify the severity of hypoxia, as well as develop strategies to specifically target hypoxic tumours. HPV-positive tumours are remarkably radiosensitive compared to HPV-negative tumours and consequently the HPV-positive patients have a better prognosis. This provides an opportunity to elucidate mechanisms of radiation sensitivity, which may reveal targets for improved therapy for HPV-negative head and neck cancers. In this review, we will discuss the differences between HPV-positive and HPV-negative head and neck tumours and methods of hypoxia detection and targeting in these disease types. Particular emphasis will be placed on the mechanisms by which HPV infection impacts radiosensitivity.

Development of clinical simultaneous SPECT/MRI

Abstract: There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.

Diagnostic accuracy of 18F-FDG PET/CT for detection of peritoneal carcinomatosis; a systematic review and meta-analysis.

Abstract: Objective:The current review aimed to investigate the performance of the diagnostic accuracy of 18F- fludeoxyglucose positron emission tomography/CT (PET/CT) in detecting peritoneal carcinomatosis (PC) through a systematic review and meta-analysis. Methods:The MEDLINE via PubMed and EMBASE from the earliest available date of indexing to 31 March 2017, were searched for studies evaluating the diagnostic performance of 18F-FDG PET/CT in detecting PC. We evaluated the pooled sensitivities and specificities across included studies, calculated positive and negative likelihood ratios (LR+ and LR−), and plotted summary receiver operating characteristic curves. Deek’s funnel plot asymmetry tests were used to assess the possible underlying publication bias. Results:The current meta-analysis demonstrated no significant publication bias (p = 0.21). Across 14 studies (671 patients), the overall sensitivity of 18F-FDG PET/CT was 0.87 [95% CI (0.77−0.93)] with heterogeneity (χ2 = 94.2, p = 0.00) and a pooled specificit...

Recent advances in theranostics and challenges for the future

Abstract: Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging. However, the retrospective uncontrolled data currently available are inadmissible for formal regulatory agency evaluation. The challenge is to engage with oncologists and urologists, and to collaborate with the pharmaceutical industry, to design and perform the controlled clinical trials required for regulatory approval, and eventual reimbursement for theranostic nuclear oncology procedures. Strategies to facil...

Molecular imaging of prostate cancer.

Abstract: Prostate cancer is a common malignancy with various treatments from surveillance, surgery, radiation and chemotherapy. The institution of appropriate, effective treatment relies in part on accurate imaging. Molecular imaging techniques offer an opportunity for increased timely detection of prostate cancer, its recurrence, as well as metastatic disease. Advancements within the field of molecular imaging have been complex with some agents targeting receptors and others acting as metabolic intermediaries. In this article, we provide an overview of the most clinically relevant radiotracers to date based on a combination of the five states model and the National Comprehensive Cancer Network Guidelines.

Obesity, body weight regulation and the brain: insights from fMRI

Abstract: Obesity constitutes a major global health threat Despite the success of bariatric surgery in delivering sustainable weight loss and improvement in obesity-related morbidity, effective non-surgical treatments are urgently needed, necessitating an increased understanding of body weight regulation Neuroimaging studies undertaken in people with healthy weight, overweight, obesity and following bariatric surgery have contributed to identifying the neurophysiological changes seen in obesity and help increase our understanding of the mechanisms driving the favourable eating behaviour changes and sustained weight loss engendered by bariatric surgery These studies have revealed a key interplay between peripheral metabolic signals, homeostatic and hedonic brain regions and genetics Findings from brain functional magnetic resonance imaging (fMRI) studies have consistently associated obesity with an increased motivational drive to eat, increased reward responses to food cues and impaired food-related self-control processes Interestingly, new data link these obesity-associated changes with structural and connectivity changes within the central nervous system Moreover, emerging data suggest that bariatric surgery leads to neuroplastic recovery A greater understanding of the interactions between peripheral signals of energy balance, the neural substrates that regulate eating behaviour, the environment and genetics will be key for the development of novel therapeutic strategies for obesity This review provides an overview of our current understanding of the pathoaetiology of obesity with a focus upon the role that fMRI studies have played in enhancing our understanding of the central regulation of eating behaviour and energy homeostasis

Non-occlusive mesenteric ischaemia: CT findings, clinical outcomes and assessment of the diameter of the superior mesenteric artery.

Abstract: Objective:Review of the experience of a tertiary care centre for almost 10 years in the CT diagnosis of non-occlusive mesenteric ischaemia (NOMI). Analysis of CT findings, correlation with clinical outcomes and evaluation of the usefulness of measuring the superior mesenteric artery (SMA) diameter for the diagnosis of NOMI.Methods:106 patients were diagnosed with NOMI in a biphasic CT examination from 2008 to 2017 in our hospital. Clinical outcomes and CT findings were reviewed. In 55 patients, the diameter of the SMA was compared with a previous CT scan where NOMI was not the diagnosis, and statistical analysis using paired t-test was performed.Results:81 patients (76%) had findings consistent with small bowel ischaemia and the ileum was the segment most commonly involved (47%). Lack of wall enhancement, pneumoperitoneum, pneumatosis intestinalis and portal venous gas were all considered signs of bowel necrosis and surgery was performed promptly. 70 patients had signs of vascular narrowing of the SMA bra...

Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen

Abstract: Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason’s score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99mTc and 111In or positron emitters like 68Ga and 18F for diagnosis as well as with their theranostic pairs such as 177Lu (β-emitter) or 225Ac (α-emitter) for therapy. This review summarizes the theranostic role of PSMA ligands for molecular imaging and targeted molecular radiotherapy, moving towards precision oncology.

An introduction to the clinical practice of theranostics in oncology.

Abstract: "Those who cannot remember the past are condemned to repeat it." George Santayana 1905 "If men could learn from history, what lessons it might teach us! But passion and party blind our eyes, and the light which experience gives is a lantern on the stern, which shines only on the waves behind us!" Samuel Taylor Coleridge 1835 The medical speciality of theranostic nuclear oncology has taken three-quarters of a century to move the stern light cast retrospectively by single-centre clinical reports, to the forepeak in the bow of our theranostic craft, where prospective randomised controlled multicentre clinical trials now illuminate the way forward. This recent reorientation of nuclear medicine clinical research practice to align with that of standard medical and radiation oncology protocols, reflects the paradigm shift toward individualised molecular oncology and precision medicine. Theranostics is the epitome of personalised medicine. The specific tumour biomarker is quantitatively imaged on positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. If it is clearly demonstrated that a tumoricidal radiation absorbed dose can be delivered, the theranostic beta or alpha-emitting radionuclide pair, coupled to the same targeted molecule, is then administered, to control advanced metastatic cancer in that individual patient. This prior selection of patients who may benefit from theranostic treatment is in direct contrast to the evolving oncological indirect treatments using immune-check point inhibitors, where there is an urgent need to define biomarkers which can reliably predict response, and thus avoid the high cost and toxicity of these agents in patients who are unlikely to benefit. The immune and molecular treatment approaches of oncology are a recent phenomenon and the efficacy and safety of immune-check point blockade and chimeric antigen receptor T-cell therapies are currently under evaluation in multicentre randomised controlled trials. Such objective evaluation is compromised by the inadequacy of conventional response evaluation criteria in solid tumour (RECIST) CT/MR anatomical/functional imaging to define tumour response, in both immune-oncology and theranostic nuclear oncology. This introduction to the clinical practice of theranostics explores ways in which nuclear physicians can learn from the lessons of history, and join with their medical, surgical and radiation oncology colleagues to establish a symbiotic collaboration to realise the potential of personalised molecular medicine to control advanced cancer and actually enhance quality of life whilst prolonging survival.