Research Interests: Radiology, Nonparametric Statistics, Adolescent, Positron Emission Tomography, Medicine, and 15 moreMolecular Imaging, Prospective studies, Humans, Female, Male, Multimodal imaging, Phenotype, Aged, Adult, Prognosis, Computerized tomography, Gynecological cancer, Cohort Studies, Neoplasm staging, and lung neoplasms
Research Interests:
In the 1930s, Otto Warburg reported that anaerobic metabolism of glucose is a fundamental property of all tumours, even in the presence of an adequate oxygen supply. He also demonstrated a relationship between the degree of anaerobic... more
In the 1930s, Otto Warburg reported that anaerobic metabolism of glucose is a fundamental property of all tumours, even in the presence of an adequate oxygen supply. He also demonstrated a relationship between the degree of anaerobic metabolism and tumour growth rate. Today, this phenomenon forms the basis of tumour imaging with fluorodeoxyglucose positron emission tomography (FDG-PET). More recently, Folkman has demonstrated that malignant growth and survival are also dependent on tumour vascularity which is increasingly evaluated in vivo using techniques such as contrast enhanced computed tomography or magnetic resonance imaging (MRI). Although it is reasonable to hypothesise that the metabolic requirements of tumours are mirrored by alterations in tumour haemodynamics, the relationship between tumour blood flow and metabolism is in fact complex. A well-developed tumour vascular supply is required to ensure a sufficient delivery of glucose and oxygen to support the metabolism essential for tumour growth. However, an inadequate vascularisation of tumour will result in hypoxia, a factor that is known to stimulate anaerobic metabolism of glucose. Thus, the balance between tumour blood flow and metabolism will be an important indicator of the biological status of a tumour and hence the tumour's likely progression and response to treatment. This article reviews the molecular biology of tumour vascularisation and metabolism, relating these processes to currently available imaging techniques while summarising the imaging studies that have compared tumour blood flow and metabolism. The potential for vascular metabolic imaging to assess tumour aggression and sub-classify treatment response is highlighted.
Research Interests:
Research Interests:
A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from... more
A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use.
Research Interests:
Research Interests:
Research Interests:
Increased angiogenic activity, which is inherent for both primary and metastatic malignant tumors, results in neovascularization and thus an elevated tumor blood volume, as well as hyperpermeability of the immature neovessels (1-5). This... more
Increased angiogenic activity, which is inherent for both primary and metastatic malignant tumors, results in neovascularization and thus an elevated tumor blood volume, as well as hyperpermeability of the immature neovessels (1-5). This particular aspect of tumor biology has been the basis for non-invasive imaging techniques targeting the quantification of blood volume and microvascular permeability. To date, most scientific emphasis has been placed on the development and validation of magnetic resonance (MR)-based techniques. As such, dynamic, contrast-enhanced magnetic MR imaging has proven its utility for the prediction of tumor malignancy and treatment monitoring in several animal models (6-9). More recently, a contrast-enhanced MR technique has been implemented in clinical studies of human gliomas (10,11). Estimates of microvascular permeability, PS, (rather than cerebral blood volume, CBV) have subsequently shown to be predictive of the pathological grade (10,11), and to correlate with the mitotic activity of a tumor (11). While, in principle, a useful tool, the application of MR is limited for example by prevalence and costs, as well as the presence of post-surgical artifacts and in some cases contraindications. An alternative non-invasive imaging tool is computed tomography (CT). We present two cases where dynamic contrast-enhanced CT was used inpatients with metastatic brain tumors. The purpose of this feasibility study was to assess whether this technique, as an alternative to MR, can be used to observe and kinetically analyze the contrast agent bolus to compute maps of CBV, cerebral blood flow (CBF) and PS in human brain tumors.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The rapid uptake of (68)Ga prostate-specific membrane antigen HBED-CC positron emission tomography (PSMA PET) imaging for prostate cancer staging has led to concerns regarding its specificity, with uptake in both malignant and... more
The rapid uptake of (68)Ga prostate-specific membrane antigen HBED-CC positron emission tomography (PSMA PET) imaging for prostate cancer staging has led to concerns regarding its specificity, with uptake in both malignant and nonmalignant tissues. We describe 3 separate malignancies identified on PSMA PET imaging. The misnomer "prostate-specific membrane antigen" is demonstrated by this case and highlights the importance of continued investigation of the potential role of PSMA PET in other malignancies.
Research Interests:
Computed tomography (CT) remains one of the mainstay techniques for anatomical evaluation of tumor growth and response to therapy, both in clinical practice and drug trials (see Chapter 3). Computed tomography measurements of perfusion... more
Computed tomography (CT) remains one of the mainstay techniques for anatomical evaluation of tumor growth and response to therapy, both in clinical practice and drug trials (see Chapter 3). Computed tomography measurements of perfusion can be added to a conventional CT examination to provide a functional response assessment within the same examination. This combined approach can overcome some of the
Research Interests:
Research Interests:
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and... more
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored…
Research Interests:
Research Interests:
Research Interests:
Research Interests:
ABSTRACT
Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical... more
Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenom...
Research Interests:
PURPOSE To assess the relationship between tumor size, tumor metabolism and tumor blood flow in non-small cell lung cancer by combining 18F FDG PET and dynamic contrast enhanced CT. METHOD AND MATERIALS 21 patients (12 male; 9 female;... more
PURPOSE To assess the relationship between tumor size, tumor metabolism and tumor blood flow in non-small cell lung cancer by combining 18F FDG PET and dynamic contrast enhanced CT. METHOD AND MATERIALS 21 patients (12 male; 9 female; mean-age 69.7 years, range 57-80years) with suspected operable non-small cell lung cancer underwent FDG-PET and dynamic contrast-enhanced CT using an integrated GE Healthcare (Waukesha, WI) 64 detector PET/CT. Dynamic CT comprised 4x10mm slices performed through the centre of the tumour (detector width 4cm). Analysis of the temporal changes in the tumour attenuation following injection of intravenous contrast material (50mls of iodine concentration 50mg/ml) yielded tumor perfusion and the Standardized Perfusion Value(SPV). The uptake of FDG was quantified using Standard Uptake Value (SUV) to assess tumor metabolism. Regression analysis was used to explore relationships between tumor metabolism and vascularity whilst the metabolic-flow difference (SUV-S...
PURPOSE Heterogeneity is an important determinant of the tumor microenvironment that can be assessed by CT Texture Analysis (CTTA) incorporated into Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose (FDG). This study... more
PURPOSE Heterogeneity is an important determinant of the tumor microenvironment that can be assessed by CT Texture Analysis (CTTA) incorporated into Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose (FDG). This study investigates the relationship between tumor heterogeneity and FDG uptake in colorectal cancer. METHOD AND MATERIALS Sixty colorectal cancer patients were prospectively recruited. FDG-PET/CT imaging data undertaken for staging before primary tumor resection was analysed. Histological data on KRAS mutation status was available in 33 patients. The maximum standardized uptake value (SUVmax) for the primary tumor was calculated from FDG accumulation. CTTA used Laplacian of Gaussian filtration to assess tumor heterogeneity at fine, medium and coarse scales with quantification as standard-deviation (SD), skewness and kurtosis. SUVmax and CTTA parameters were compared between KRAS mutated (n= 17) and wild-type (n=16) groups. RESULTS SUVmax could not reliably distin...
PURPOSE To describe a decision modeling approach for the identification of potential clinical applications for prognostic imaging biomarkers in oncology. METHOD AND MATERIALS An approach that uses decision modeling to identify potential... more
PURPOSE To describe a decision modeling approach for the identification of potential clinical applications for prognostic imaging biomarkers in oncology. METHOD AND MATERIALS An approach that uses decision modeling to identify potential applications for prognostic imaging biomarkers was defined. The approach requires cross-validated data indicating the hazard ratio and proportion of high risk patients identified by the imaging biomarker along with the 95% confidence intervals (CI). The biomarker also needs to be prognostic independent of tumor stage and other potential imaging biomarkers. Decision modeling is then used to assess potential health outcomes and costs from proposed biomarker deployments with Monte Carlo analysis quantifying the likelihood of realizing beneficial outcomes. The approach was used to assess potential applications of CT texture analysis (CTTA) for the personalization of chemotherapy for patients with advanced non-small cell lung cancer. RESULTS The cross-val...
ABSTRACT
This pilot study investigates whether heterogeneity in focal breast lesions and surrounding tissue assessed on mammography is potentially related to cancer invasion and hormone receptor status. Texture analysis (TA) assessed the... more
This pilot study investigates whether heterogeneity in focal breast lesions and surrounding tissue assessed on mammography is potentially related to cancer invasion and hormone receptor status. Texture analysis (TA) assessed the heterogeneity of focal lesions and their surrounding tissues in digitized mammograms from 11 patients randomly selected from an imaging archive [ductal carcinoma in situ (DCIS) only, n = 4; invasive carcinoma (IC) with DCIS, n = 3; IC only, n = 4]. TA utilized band-pass image filtration to highlight image features at different spatial frequencies (filter values: 1.0-2.5) from fine to coarse texture. The distribution of features in the derived images was quantified using uniformity. Significant differences in uniformity were observed between patient groups for all filter values. With medium scale filtration (filter value = 1.5) pure DCIS was more uniform (median = 0.281) than either DCIS with IC (median = 0.246, p = 0.0102) or IC (median = 0.249, p = 0.0021)....
Research Interests:
Purpose. To assess whether the differences in vascular-metabolic relationships between lymphoma masses and colorectal liver metastases predicted from previous histopathological studies can be demonstrated by dynamic contrast-enhanced CT... more
Purpose. To assess whether the differences in vascular-metabolic relationships between lymphoma masses and colorectal liver metastases predicted from previous histopathological studies can be demonstrated by dynamic contrast-enhanced CT (DCE-CT) combined with fluorodeoxyglucose positron emission tomography (FDG-PET). Methods. DCE-CT and FDG-PET studies were drawn from an imaging archive for patients with either lymphoma masses (n = 11) or hepatic metastases from colorectal cancer (CRM: n = 12). Tumour vascularity was assessed using DCE-CT measurements of perfusion. Tumour glucose metabolism was expressed as the mean FDG Standardised Uptake Value (SUV(FDG)). The relationship between metabolism and vascularity in each group was assessed from SUV(FDG) /perfusion ratios and Pearson correlation coefficients. Results. An SUV(FDG) threshold of 3.0 was used to designate lymphoma masses as active (AL, n = 6) or inactive lymphoma (IL, n = 5). Tumour perfusion was significantly higher in AL (0...
Research Interests:
Analysis of time-attenuation data has enabled CT to measure capillary permeability within the brain and kidney. As yet, such techniques have not been applied to nodal masses in patients with lymphoma. Tumour angiogenesis is known to... more
Analysis of time-attenuation data has enabled CT to measure capillary permeability within the brain and kidney. As yet, such techniques have not been applied to nodal masses in patients with lymphoma. Tumour angiogenesis is known to produce capillaries that exhibit increased permeability and CT measurements of permeability could therefore potentially provide a marker of tumour viability. This study aims to determine the feasibility and limitations of CT measurement of capillary permeability within lymphoma nodal masses. Six patients with biopsy proven lymphoma have been studied. Time-attenuation curves from the aorta and nodal mass were generated from a single-location dynamic sequence of images acquired over 3 min following an intravenous bolus of iopamidol. A nuclear medicine data processing technique, Patlak analysis, was used to calculate capillary permeability and blood volume within the nodal mass. Renal blood vessel permeability was also determined in four patients. Median ly...
Research Interests:
Research Interests:
The availability of rapid imaging with multidetector CT systems and commercial analysis software has made perfusion imaging with CT an everyday technique, not only for the brain but also for other body organs. Perfusion imaging is usually... more
The availability of rapid imaging with multidetector CT systems and commercial analysis software has made perfusion imaging with CT an everyday technique, not only for the brain but also for other body organs. Perfusion imaging is usually performed as an adjunct to a conventional CT examination and is therefore particularly appropriate when a conventional CT is part of routine clinical protocols. The derived values are reproducible and have been validated against a range of reference techniques. Within neuroradiology, perfusion CT has attracted interest in the assessment of acute stroke but can also be used to assess secondary injury in head trauma and as an adjunct to CT angiography to evaluate cerebral spasm in subarachnoid haemorrhage. Within oncology, perfusion CT provides an imaging correlate for tumour vascularity that can be used to discriminate benign and malignant lesions, as an indicator of tumour aggressiveness, to reveal occult tumour and improve the delineation of tumou...
Research Interests: Image Processing, Computed Tomography, Humans, Functional Assessment, Contrast-Enhanced Ultrasound, and 10 moreClinical Sciences, Single Photon Emission Computed Tomography, Blood Flow, Subarachnoid haemorrhage, X ray Computed Tomography, Cerebrovascular Disorders, Contrast Media, Brain Neoplasms, CT angiography, and Head Trauma
This study compares three techniques that evaluate hepatic haemodynamics for the detection of metastatic liver disease to determine the interrelationships between the techniques and to assess their equivalence. The three techniques... more
This study compares three techniques that evaluate hepatic haemodynamics for the detection of metastatic liver disease to determine the interrelationships between the techniques and to assess their equivalence. The three techniques studied were dedicated CT measurements of hepatic enhancement, CT measurements of perfusion and Doppler perfusion indices. 53 patients with proven malignancies of either breast or colon underwent a single location dynamic CT for measurement of hepatic perfusion and enhancement, whilst a subset of 12 patients underwent both CT perfusion and Doppler perfusion studies. Statistically significant correlations were found between CT arterial phase enhancement and CT arterial perfusion (r=0.612, p<0.001), and between both of these parameters and Doppler arterial flow (r=0.867, p<0.001 and r=0.842, p<0.001, respectively). Significant correlations were also found between both the ratio of CT arterial enhancement to peak enhancement and the CT arterial perf...
Research Interests:
Research Interests:
This study aimed to produce Patlak images of the kidney from dynamic CT data and to determine whether such images are substantially affected by fluid movement between renal tubular segments. Renal permeability was measured in 31 kidneys... more
This study aimed to produce Patlak images of the kidney from dynamic CT data and to determine whether such images are substantially affected by fluid movement between renal tubular segments. Renal permeability was measured in 31 kidneys by applying Patlak analysis to time-density data from kidney and aorta during dynamic CT. Permeability parameters were correlated against plasma urea. The renal region (cortex or medulla) with the greatest permeability was determined from parametric images generated using pixel by pixel analysis. The mean value for whole kidney permeability was 517.5 microliters min-1 ml-1. A correlation was found between whole kidney permeability and plasma urea (p < 0.01). Permeability values were highest in the renal medulla in 24 (77%) kidneys. The higher medullary values of permeability are artefactual, resulting from movement of fluid and contrast medium between cortex and medulla. Although Patlak images do not reflect true intrarenal permeability values, th...
Research Interests:
Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was... more
Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was to use the quantitative functional information and high spatial resolution of perfusion computed tomography to study neovascularization of hepatic metastases. Perfusion CT was performed in 13 patients with hepatic metastases from various primary tumours. Arterial perfusion was measured in the metastasis; both arterial and portal perfusion were measured in a small rim of liver tissue immediately adjacent to the metastasis. Perfusion measurements were correlated against survival of the patient in nine cases. Arterial perfusion was increased above normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26-3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range: 0.14-1.60 ml min-1 ml-1). Portal perfusion of ad...
Research Interests:
To assess changes in hepatic perfusion in patients with colorectal cancer with computed tomography (CT), diagnostic potential of CT perfusion measurements, and implications for design of contrast enhancement protocols. In 27 patients with... more
To assess changes in hepatic perfusion in patients with colorectal cancer with computed tomography (CT), diagnostic potential of CT perfusion measurements, and implications for design of contrast enhancement protocols. In 27 patients with colorectal cancer, arterial and portal perfusion were calculated from temporal changes in attenuation after intravenous administration of contrast material. Arterial perfusion greater than 0.25 mL/min/mL was seen in nine (82%) of the 11 patients with overt metastases versus six (38%) of the 16 patients with no overt metastases (P < .05). Portal perfusion of 0.25 mL/min/mL or less was found in five (46%) of the patients with overt metastases versus three (19%) of the patients with no overt metastases. Follow-up imaging showed progressive metastatic disease in three patients, all of whom had decreased portal perfusion. Increased arterial perfusion appears to be an indicator of liver metastases, whereas reduced portal perfusion may indicate progres...