Patient-Specific Method of Generating Parametric Maps of Patlak K(i) without Blood Sampling or Metabolite Correction: A Feasibility Study.

Currently, kinetic analyses using dynamic positron emission tomography (PET) experience very limited use despite their potential for improving quantitative accuracy in several clinical and research applications. For targeted volume applications, such as radiation treatment planning, treatment monitoring, and cerebral metabolic studies, the key to implementation of these methods is the determination of an arterial input function, which can include time-consuming analysis of blood samples for metabolite correction. Targeted kinetic applications would become practical for the clinic if blood sampling and metabolite correction could be avoided. To this end, we developed a novel method (Patlak-P) of generating parametric maps that is identical to Patlak K(i) (within a global scalar multiple) but does not require the determination of the arterial input function or metabolite correction. In this initial study, we show that Patlak-P (a) mimics Patlak K(i) images in terms of visual assessment and target-to-background (TB) ratios of regions of elevated uptake, (b) has higher visual contrast and (generally) better image quality than SUV, and (c) may have an important role in improving radiotherapy planning, therapy monitoring, and neurometabolism studies

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.</p

Radiomics in [¹⁸F]FDG PET/CT:A leap in the dark?

Positron emission tomography (PET) imaging with the non-metabolisable glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), combined with low dose computed tomography (CT) for anatomical reference, is an important tool to detect and stage cancer or active inflammations. Visual interpretation of PET/CT images consists of (qualitative) assessment of radiotracer uptake in different tissues and their density. Furthermore, the location, size, shape, and relation with surrounding tissues of these lesions provide important clues on their nature. Yet, medical images contain much more information about tissue biology hidden in the myriad of voxels of both lesions and healthy tissue than can be assessed visually. Quantification of radiotracer uptake heterogeneity and other tissue characteristics is studied in the field of radiomics. Radiomics is a form of medical image processing that aims to find stable and clinically relevant image-derived biomarkers for lesion characterisation, prognostic stratification, and response prediction, thereby contributing to precision medicine. Radiomics consists of the conversion of (parts of) medical images into a high-dimensional set of quantitative features and the subsequent mining of this dataset for potential information useful for the quantification or monitoring of tumour or disease characteristics in clinical practice. This thesis contributed to a deeper understanding of the methodological aspects of handcrafted radiomics in [18F]FDG PET/CT, specifically in small datasets. However, most radiomic papers present proof-of-concept studies and clinical implementation is still far away. At some point in the future, radiomic biomarkers may be used in clinical practice, but at the moment we should acknowledge the limitations of the field and try to overcome these. Only then, we will be able to cross the translational gap towards clinical readiness. Future research should focus on standardisation of feature selection, model building, and ideally a tool that implements these aspects. In such a way, radiomics may redeem the promise of bringing forth imaging biomarkers that contribute to precision medicine.<br/

Dynamic Contrast Enhanced Computed Tomography Measurement of Perfusion in Hepatic Cancer

ABSTRACT In recent years, the incidence and mortality rate for hepatocellular carcinoma (HCC) have increased due to the emergence of hepatitis B, C and other diseases that cause cirrhosis. The progression from cirrhosis to HCC is characterized by abnormal vascularization and by a shift from a venous to an arterial blood supply. A knowledge of HCC vascularity which is manifested as alterations in liver blood flow may distinguish among different stages of liver disease and can be used to monitor response to treatment. Unfortunately, conventional diagnostic imaging techniques lack the ability to accurately quantify HCC vascularity. The purpose of this thesis was to validate and assess the diagnostic capabilities of dynamic contrast enhanced computed tomography (DCE-CT) and perfusion software designed to measure hepatic perfusion. Chapter 2 described a study designed to evaluate the accuracy and precision of hepatic perfusion measurement. The results showed a strong correlation between hepatic artery blood flow measurement with DCE-CT and radioactive microspheres under steady state in a rabbit model for HCC (VX2 carcinoma). Using repeated measurements and Monte Carlo simulations, DCE-CT perfusion measurements were found to be precise; with the highest precision in the tumor rim. In Chapter 3, we used fluorine-18 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and DCE-CT perfusion to determined an inverse correlation between glucose utilization and tumor blood flow; with an R of 0.727 (P \u3c 0.05). This suggests a limited supply of oxygen (possibly hypoxia) and that the tumor cells were surviving via anaerobic glycolysis. in In Chapter 4, hepatic perfusion data showed that thalidomide caused a reduction of tumor perfusion in the responder group during the first 8 days after therapy, P \u3c 0.05; while perfusion in the partial responder and control group remained unchanged, P \u3e 0.05. These changes were attributed to vascular remodeling and maturation resulting in a more functional network of endothelial tubes lined with pericytes. The results of this thesis demonstrate the accuracy and precision of DCE-CT hepatic perfusion measurements. It also showed that DCE-CT perfusion has the potential to enhance the functional imaging ability of hybrid PET/CT scanners and evaluate the efficacy of anti-angiogenesis therapy