Caleb Roberts

The University of Manchester, Manchester, England, United Kingdom

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Publications (21)92.8 Total impact

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    ABSTRACT: Objectives Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and Methods COPD patients (n = 40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9 μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV1 was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies. Conclusions In COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.
    European Journal of Radiology 11/2014; · 2.16 Impact Factor
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    ABSTRACT: Background 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis. Methods Patients with advanced solid tumours received GSAO in a dose-escalation trial according to a standard ‘3 + 3’ design that was guided by toxicity and, for the final dose escalation, by arsenic PK data. Results A total of 34 patients were treated with GSAO across 9 dose levels (1.3–44.0 mg/m2). Treatment was well tolerated with few adverse events. An additional three patients were enrolled at the 12.4 mg/m2 dose level following a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m2 dose level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal atrial fibrillation). Conclusions The MTD of GSAO was 22.0 mg/m2/day. There was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of an anti-vascular effect of GSAO.
    Cancer Chemotherapy and Pharmacology 10/2013; · 2.57 Impact Factor
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    ABSTRACT: About 100 early-phase clinical trials and investigator-led studies of targeted antivascular therapies--both anti-angiogenic and vascular-targeting agents--have reported data derived from T1-weighted dynamic contrast-enhanced (DCE)-MRI. However, the role of DCE-MRI for decision making during the drug-development process remains controversial. Despite well-documented guidelines on image acquisition and analysis, several key questions concerning the role of this technique in early-phase trial design remain unanswered. This Review describes studies of single-agent antivascular therapies, in which DCE-MRI parameters are incorporated as pharmacodynamic biomarkers. We discuss whether these parameters, such as volume transfer constant (K(trans)), are reproducible and reliable biomarkers of both drug efficacy and proof of concept, and whether they assist in dose selection and drug scheduling for subsequent phase II trials. Emerging evidence indicates that multiparametric analysis of DCE-MRI data offers greater insight into the mechanism of drug action than studies measuring a single parameter, such as K(trans). We also provide an overview of current data and appraise the future directions of this technique in oncology trials. Finally, major hurdles in imaging biomarker development, validation and qualification that hinder a wide application of DCE-MRI techniques in clinical trials are addressed.
    Nature Reviews Clinical Oncology 02/2012; 9(3):167-77. · 15.03 Impact Factor
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    ABSTRACT: A major potential confound in axial 3D dynamic contrast-enhanced magnetic resonance imaging studies is the blood inflow effect; therefore, the choice of slice location for arterial input function measurement within the imaging volume must be considered carefully. The objective of this study was to use computer simulations, flow phantom, and in vivo studies to describe and understand the effect of blood inflow on the measurement of the arterial input function. All experiments were done at 1.5 T using a typical 3D dynamic contrast-enhanced magnetic resonance imaging sequence, and arterial input functions were extracted for each slice in the imaging volume. We simulated a set of arterial input functions based on the same imaging parameters and accounted for blood inflow and radiofrequency field inhomogeneities. Measured arterial input functions along the vessel length from both in vivo and the flow phantom agreed with simulated arterial input functions and show large overestimations in the arterial input function in the first 30 mm of the vessel, whereas arterial input functions measured more centrally achieve accurate contrast agent concentrations. Use of inflow-affected arterial input functions in tracer kinetic modeling shows potential errors of up to 80% in tissue microvascular parameters. These errors emphasize the importance of careful placement of the arterial input function definition location to avoid the effects of blood inflow.
    Magnetic Resonance in Medicine 10/2010; 65(1):108-19. · 3.40 Impact Factor
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    ABSTRACT: Little is known concerning the onset, duration, and magnitude of direct therapeutic effects of anti-vascular endothelial growth factor (VEGF) therapies. Such knowledge would help guide the rational development of targeted therapeutics from bench to bedside and optimize use of imaging technologies that quantify tumor function in early-phase clinical trials. Preclinical studies were done using ex vivo microcomputed tomography and in vivo ultrasound imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by quantitative magnetic resonance imaging in 10 patients with metastatic colorectal cancer treated with bevacizumab. Microcomputed tomography experiments showed reduction in perfused vessels within 24 to 48 h of G6-31 drug administration (P <or= 0.005). Ultrasound imaging confirmed reduced tumor blood volume within the same time frame (P = 0.048). Consistent with the preclinical results, reductions in enhancing fraction and fractional plasma volume were detected in patient colorectal cancer metastases within 48 h after a single dose of bevacizumab that persisted throughout one cycle of therapy. These effects were followed by resolution of edema (P = 0.0023) and tumor shrinkage in 9 of 26 tumors at day 12. These data suggest that VEGF-specific inhibition induces rapid structural and functional effects with downstream significant antitumor activity within one cycle of therapy. This finding has important implications for the design of early-phase clinical trials that incorporate physiologic imaging. The study shows how animal data help interpret clinical imaging data, an important step toward the validation of image biomarkers of tumor structure and function.
    Clinical Cancer Research 11/2009; 15(21):6674-82. · 8.19 Impact Factor
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    ABSTRACT: Dynamic contrast-enhanced MRI is becoming a standard tool for imaging-based trials of anti-vascular/angiogenic agents in cancer. So far, however, biomarkers derived from DCE-MRI parameter maps have largely neglected the fact that the maps have spatial structure and instead focussed on distributional summary statistics. Such statistics-e.g., biomarkers based on median values-neglect the spatial arrangement of parameters, which may carry important diagnostic and prognostic information. This article describes two types of heterogeneity biomarker that are sensitive to both parameter values and their spatial arrangement. Methods based on Rényi fractal dimensions and geometrical properties are developed, both of which attempt to describe the complexity of DCE-MRI parameter maps. Experiments using simulated data show that the proposed biomarkers are sensitive to changes that distribution-based summary statistics cannot detect and demonstrate that heterogeneity biomarkers could be applied in the drug trial setting. An experiment using 23 DCE-MRI parameter maps of gliomas-a class of tumour that is graded on the basis of heterogeneity-shows that the proposed heterogeneity biomarkers are able to differentiate between low- and high-grade tumours.
    Magnetic Resonance in Medicine 06/2009; 62(2):488-99. · 3.40 Impact Factor
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    ABSTRACT: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R(1)). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R(1) while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced DeltaR(1). DeltaR(1) showed significant increases of 0.021 to 0.058 s(-1) in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the DeltaR(1) curve (consistent with minimal increase in oxygen concentration). These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.
    International journal of radiation oncology, biology, physics 04/2009; 75(4):1209-15. · 4.59 Impact Factor
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    ABSTRACT: Magnetic resonance imaging has shown promise for evaluating tissue oxygenation. In this study differences in the tissue longitudinal relaxation rate (R(1)) and effective transverse relaxation rate (R(*)(2)), induced by inhalation of pure oxygen and carbogen, were evaluated in 10 healthy subjects. Significant reductions in R(1) were demonstrated following both oxygen and carbogen inhalation in the spleen (both P < 0.001), liver (P = 0.002 air vs. oxygen; P = 0.001 air vs. carbogen), skeletal muscle (both P < 0.001), and renal cortex (P = 0.005 air vs. oxygen; P = 0.008 air vs. carbogen). No significant change in R(*)(2) occurred following pure oxygen in any organ. However, a significant increase in R(*)(2) was observed in the spleen (P < 0.001), liver (P = 0.001), skeletal muscle (P = 0.026), and renal cortex (P = 0.001) following carbogen inhalation, an opposite effect to that observed in many studies of tumor pathophysiology. Changes in R(1) and R(*)(2) were independent of the gas administration order in the spleen and skeletal muscle. These findings suggest that the R(1) and R(*)(2) responses to hyperoxic gases are independent biomarkers of oxygen physiology.
    Magnetic Resonance in Medicine 12/2008; 61(1):75-83. · 3.40 Impact Factor
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    ABSTRACT: To prospectively use dynamic contrast material-enhanced magnetic resonance (MR) imaging and a tracer kinetic model to compare parotid gland microvascular characteristics in patients who have Sjögren syndrome (SS) with those in healthy volunteers. The local research ethics committee approved the study, and written informed consent was obtained from all participants. Twenty-one patients (19 women, two men; age range, 31-73 years) with a diagnosis of SS and 11 healthy volunteers (10 women, one man; age range, 41-68 years) underwent three-dimensional T1-weighted dynamic contrast-enhanced MR imaging of the parotid gland at 1.5 T. A voxel-wise tracer kinetic model and a model-free analysis were applied to the dynamic MR data. Parameter medians and standard deviations were computed to summarize gland microvascular characteristics and gland heterogeneity, respectively. Differences were investigated by using multivariate analysis of variance, t, or U tests. Further investigation was performed by using linear discriminant and receiver operating characteristic analyses. Compared with the healthy volunteers, the patients with SS had highly significant elevations (P < .001) in the model-free parameter initial area under the curve and in tracer kinetic model parameters, including transcapillary contrast agent transfer constant (P < .001) and extracellular extravascular volume (P < .001). Gland heterogeneity was significantly greater (P < .001) in the patients with SS. Parameter medians and standard deviations enabled excellent differentiation (areas under receiver operating characteristic curve, 0.96 and 1.00, respectively) between the patients with SS and the healthy volunteers. Dynamic contrast-enhanced MR imaging has the potential to be used in clinical settings to quantify microvascular function in SS and to differentiate between patients with and those without SS.
    Radiology 04/2008; 246(3):845-53. · 6.21 Impact Factor
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    ABSTRACT: Dynamic contrast-enhanced MRI (DCE-MRI) time series data are subject to unavoidable physiological motion during acquisition (e.g., due to breathing) and this motion causes significant errors when fitting tracer kinetic models to the data, particularly with voxel-by-voxel fitting approaches. Motion correction is problematic, as contrast enhancement introduces new features into postcontrast images and conventional registration similarity measures cannot fully account for the increased image information content. A methodology is presented for tracer kinetic model-driven registration that addresses these problems by explicitly including a model of contrast enhancement in the registration process. The iterative registration procedure is focused on a tumor volume of interest (VOI), employing a three-dimensional (3D) translational transformation that follows only tumor motion. The implementation accurately removes motion corruption in a DCE-MRI software phantom and it is able to reduce model fitting errors and improve localization in 3D parameter maps in patient data sets that were selected for significant motion problems. Sufficient improvement was observed in the modeling results to salvage clinical trial DCE-MRI data sets that would otherwise have to be rejected due to motion corruption.
    Magnetic Resonance in Medicine 12/2007; 58(5):1010-9. · 3.40 Impact Factor
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    ABSTRACT: To define a simple radiologic biomarker of prognosis in patients with advanced epithelial ovarian carcinoma on first-line chemotherapy. Twenty-seven patients receiving platinum-based chemotherapy with >2 cm residual disease [International Federation of Gynecology and Obstetrics (FIGO) stages IIIC or IV] after surgery were identified. The proportion of enhancing tumor tissue--the enhancing fraction--was calculated on pre-chemotherapy computed tomography scans at four Hounsfield unit (HU) thresholds and assessed for correlation with CA125 response, Response Evaluation Criteria in Solid Tumors (RECIST) radiologic response, and time to progression. Discriminative power was assessed by leave-one-out discriminant analysis. Pre-chemotherapy residual tumor volume did not correlate with clinical outcome. Pre-chemotherapy enhancing fraction at all thresholds significantly correlated with CA125 response (P < 0.001, rho = 0.553 for 50 HU; P < 0.001, rho = 0.565 for 60 HU; P < 0.001, rho = 0.553 for 70 HU; P = 0.001, rho = 0.516 for 80 HU). Significant correlations were also shown for radiologic response at all thresholds. Enhancing fraction predicted CA125 response with 81.9% to 86.4% specificity and Response Evaluation Criteria in Solid Tumors response with 74.9% to 76.8% specificity at 95% sensitivity (dependent on threshold). Enhancing fraction correlated with time to progression at the 60 HU (P = 0.045, rho = 0.336) and 70 HU (P = 0.042; rho = 0.340) thresholds. Pre-chemotherapy enhancing fraction is a simple quantitative radiologic measure. Further evaluation in larger trials is required to confirm the potential of enhancing fraction as a predictive factor, particularly for patients who may benefit from the addition of antiangiogenic therapy.
    Clinical Cancer Research 11/2007; 13(20):6130-5. · 8.19 Impact Factor
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    ABSTRACT: Molecular oxygen has been previously shown to shorten longitudinal relaxation time (T1) in the spleen and renal cortex, but not in the liver or fat. In this study, the magnitude and temporal evolution of this effect were investigated. Medical air, oxygen, and carbogen (95% oxygen/5% CO2) were administered sequentially in 16 healthy volunteers. T1 maps were acquired using spoiled gradient echo sequences (TR=3.5 ms, TE=0.9 ms, alpha=2 degrees/8 degrees/17 degrees) with six acquisitions on air, 12 on oxygen, 12 on carbogen, and six to 12 back on air. Mean T1 values and change in relaxation rate were compared between each phase of gas inhalation in the liver, spleen, skeletal muscle, renal cortex, and fat by one-way analysis of variance. Oxygen-induced T1-shortening occurred in the liver in fasted subjects (P<0.001) but not in non-fasted subjects (P=0.244). T1-shortening in spleen and renal cortex (both P<0.001) were greater than previously reported. Carbogen induced conflicting responses in different organs, suggesting a complex relationship with organ vasculature. Shortening of tissue T1 by oxygen is more pronounced and more complex than previously recognized. The effect may be useful as a biomarker of arterial flow and oxygen delivery to vascular beds.
    Magnetic Resonance in Medicine 10/2007; 58(3):490-6. · 3.40 Impact Factor
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    ABSTRACT: A fully human monoclonal antibody to anti-alpha(v) integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was infused on days 0, 28, 35, and 42, and clinical assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and [(18)F]-2-fluorodeoxyglucose positron emission tomography (FDG-PET) were done. Patients achieving stable disease or better were eligible for extended dosing every 3 weeks for up to 12 months. Among the 24 enrolled patients, CNTO 95 was associated with one episode of grade III and four episodes of grade II infusion-related fever (all responded to acetaminophen). Of the six patients who received extended dosing, one patient (10.0 mg/kg), with cutaneous angiosarcoma, had a 9-month partial response. Pre- and post-treatment lesion biopsies confirmed tumor cell alpha(v) integrin expression, as well as CNTO 95 penetration of the tumor and localization to tumor cells in association with reduced bcl-2 expression. A lesion in one patient (10.0 mg/kg) with stable ovarian carcinosarcoma was no longer detectable by FDG-PET by day 49. Exposure to CNTO 95 seemed to increase in a greater-than-dose-proportional manner; dose-dependent mean half-life ranged from 0.26 to 6.7 days. CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.
    Clinical Cancer Research 04/2007; 13(7):2128-35. · 8.19 Impact Factor
  • Medical Image Computing and Computer-Assisted Intervention - MICCAI 2007, 10th International Conference, Brisbane, Australia, October 29 - November 2, 2007, Proceedings, Part II; 01/2007
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    ABSTRACT: Rapid T(1)-weighted 3D spoiled gradient-echo (GRE) data sets were acquired in the abdomen of 23 cancer patients during a total of 113 separate visits to allow dynamic contrast-enhanced MRI (DCE-MRI) analysis of tumor microvasculature. The arterial input function (AIF) was measured in each patient at each visit using an automated AIF extraction method following a standardized bolus administration of gadodiamide. The AIFs for each patient were combined to obtain a mean AIF that is representative for any individual. The functional form of this general AIF may be useful for studies in which AIF measurements are not possible. Improvements in the reproducibility of DCE-MRI model parameters (K(trans), v(e), and v(p)) were observed when this new, high-temporal-resolution population AIF was used, indicating the potential for increased sensitivity to therapy-induced change.
    Magnetic Resonance in Medicine 12/2006; 56(5):993-1000. · 3.40 Impact Factor
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    ABSTRACT: Accurate sampling of the arterial input function (AIF) in low-temporal-resolution quantitative dynamic contrast-enhanced MRI (DCE-MRI) studies is crucial for accurate and reproducible parameter estimation. However, when conventional AIFs are sampled at low temporal resolution, they introduce an unpredictable degree of error. An alternative double contrast agent (CA) bolus injection protocol designed to compensate for temporal mis-sampling of the AIF and tissue uptake curve was simulated in addition to a commonly used single CA bolus injection protocol. A range of tissue uptake curves for each AIF form were generated using a distributed parameter model, and Monte Carlo simulation studies were performed over a range of offset times (to mimic temporal mis-sampling), temporal resolutions and SNR in order to compare the performance of both AIF forms in compartmental modeling. Insufficient data sampling of the single bolus AIF at temporal resolutions in excess of 9 s leads to large errors, which can be reduced by employing an additional, appropriately administered, second CA bolus injection.
    Magnetic Resonance in Medicine 10/2006; 56(3):611-9. · 3.40 Impact Factor
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    ABSTRACT: The quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data is subject to model fitting errors caused by motion during the time-series data acquisition. However, the time-varying features that occur as a result of contrast enhancement can confound motion correction techniques based on conventional registration similarity measures. We have therefore developed a heuristic, locally controlled tracer kinetic model-driven registration procedure, in which the model accounts for contrast enhancement, and applied it to the registration of abdominal DCE-MRI data at high temporal resolution. Using severely motion-corrupted data sets that had been excluded from analysis in a clinical trial of an antiangiogenic agent, we compared the results obtained when using different models to drive the tracer kinetic model-driven registration with those obtained when using a conventional registration against the time series mean image volume. Using tracer kinetic model-driven registration, it was possible to improve model fitting by reducing the sum of squared errors but the improvement was only realized when using a model that adequately described the features of the time series data. The registration against the time series mean significantly distorted the time series data, as did tracer kinetic model-driven registration using a simpler model of contrast enhancement. When an appropriate model is used, tracer kinetic model-driven registration influences motion-corrupted model fit parameter estimates and provides significant improvements in localization in three-dimensional parameter maps. This has positive implications for the use of quantitative DCE-MRI for example in clinical trials of antiangiogenic or antivascular agents.
    Academic Radiology 10/2006; 13(9):1112-23. · 2.08 Impact Factor
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    ABSTRACT: To evaluate and compare the reproducibility of the preferred phenomenological parameter IAUC60 (initial area under the time-concentration curve [IAUC] defined over the first 60 seconds postenhancement) with the preferred modeling parameter (K(trans)), as derived using two simple models, in abdominal and cerebral data collected in typical Phase I clinical trial conditions. Dynamic contrast enhanced MRI (DCE-MRI) time series were acquired at two imaging centers from a group of patients with abdominal tumors and a group with gliomas. At both imaging centers, precontrast T1 was calculated using a variable flip angle three-dimensional spoiled gradient echo acquisition that was used to quantify tissue contrast agent concentration, allowing voxelwise definition of summary DCE-MRI parameters. A comparison of reproducibility showed that there was no statistically significant difference in reproducibility between IAUC60 and K(trans), although there was a trend towards better reproducibility for K(trans) (P = 0.0782). The 95% confidence intervals (CIs) for individual changes showed that for IAUC60 and K(trans), changes in excess of 47% and 31%, respectively, are outside the range of normal variability. Although modeling is more complex and more computationally intensive than an IAUC parameterization, our data suggest this approach to be preferable to a model-free approach since it provides greater physiological insight without a reduction in statistical power for Phase I/II clinical drug trials.
    Journal of Magnetic Resonance Imaging 05/2006; 23(4):554-63. · 2.79 Impact Factor
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    ABSTRACT: Motion during time-series data acquisition causes model-fitting errors in quantitative dynamic contrast-enhanced (DCE) MRI studies. Motion correction techniques using conventional registration cost functions may produce biased results because they were not designed to deal with the time-varying information content due to contrast enhancement. We present a locally-controlled, 3D translational registration process driven by tracer kinetic modeling that successfully registers abdominal DCE-MRI data at high temporal resolution and compare this method to a similar approach based on registration to the time series mean image in data from 8 patients. When the registration is driven by an appropriate model, we find significant improvements in model-fitting. Also, model-driven registration influences parameter estimates and reduces repeat study variability in measurements of blood volume.
    Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 02/2005; 8(Pt 1):91-8.
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    ABSTRACT: To use contrast material-enhanced magnetic resonance (MR) imaging and a distributed-parameter tracer kinetics model for prospectively evaluating the vascular characteristics of prostate cancer. Twenty-two patients between 57 and 76 years of age (mean age, 67 years) with histologically proved adenocarcinoma of the prostate were examined by using three-dimensional dynamic contrast-enhanced T1-weighted MR imaging at 1.5 T. The local research ethics committee approved this study, and written consent was obtained from all patients. Data from regions of interest drawn in tumor, normal-appearing peripheral zone tissue, and muscle were analyzed to provide estimates of perfusion, blood volume, interstitial volume, and microvascular permeability-surface area product. These estimates were compared by using the nonparametric Wilcoxon signed rank test. Mean blood flow was significantly (P < .001) higher in 22 prostate tumors than in 20 contralateral peripheral zones (66 vs 32 mL/100 mL/min). Similarly, the interstitial distribution volume in tumors was enlarged compared with the interstitial distribution volume in normal peripheral zones (42 vs 27 mL/100 mL). Blood volume and microvascular permeability-surface area product values in tumors (1.0 mL/100 mL and 22 mL/100 mL/min, respectively) were similar to estimated values in peripheral zone tissue (1.5 mL/100 mL and 21 mL/100 mL/min, respectively). These findings show considerable promise for isolating vascular characteristics of prostate cancer.
    Radiology 01/2005; 233(3):709-15. · 6.21 Impact Factor

Publication Stats

874 Citations
92.80 Total Impact Points


  • 2004–2013
    • The University of Manchester
      • • Imaging, Genomics and Proteomics Research Group
      • • Centre for Imaging Sciences
      Manchester, England, United Kingdom
  • 2007
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom