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ABSTRACT: The aim of this research was to determine whether the proportion of a tumour that enhances (enhancing fraction, EnF) and changes
in EnF with enhancement threshold differ between low and high grade glioma. Forty-four patients (45 gliomas comprising 16
grade II, 5 grade III and 24 grade IV) were studied. Imaging included pre- and post-contrast-enhanced T1-weighted sequences and T1-weighted DCE-MRI. Thresholded enhancement maps were generated for each tumour by using a range of values of the initial area
under the contrast concentration curve (IAUC). A plot of EnF versus threshold value was generated. We examined the relationship
between tumour grade and enhancement metrics including: EnF (threshold IAUC > 0mMols), EnF (threshold IAUC > 2.5mMols),
initial slope of the EnF/threshold curve (∂EnF), IAUC, and two previously described signal-intensity-based metrics. EnF, defined
as the proportion of tumour showing any enhancement (threshold IAUC > 0mMols), showed no difference between low and high
grade glioma. All other measures demonstrated significant differences between grade II and IV, and low (grade II) and high
grade (grades III/ IV) gliomas (p < 0.01). Two measures, ∂EnF and Pronin’s measure of enhancement, showed differences between grade III and IV (p < 0.05). No measure separated grade II from III. Metrics which describe the enhancing fraction and its variation with enhancement
threshold ∂EnF show considerably different behaviour in low and high grade tumours. These observations suggest that these
metrics may provide important biological information concerning tumour biology and therapeutic responses and encourage further
research to characterise and validate these novel biomarkers.
European Radiology 04/2012; 19(6):1489-1498. · 3.22 Impact Factor
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Chris J Rose, Samantha J Mills,
James P B O'Connor,
Giovanni A Buonaccorsi,
Caleb Roberts,
Yvonne Watson,
Susan Cheung,
Sha Zhao,
Brandon Whitcher,
Alan Jackson,
Geoffrey J M Parker
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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. · 2.96 Impact Factor
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James P B O'Connor,
Josephine H Naish,
Geoff J M Parker,
John C Waterton,
Yvonne Watson,
Gordon C Jayson,
Giovanni A Buonaccorsi,
Sue Cheung,
David L Buckley,
Deirdre M McGrath,
Catharine M L West,
Susan E Davidson,
Caleb Roberts, Samantha J Mills,
Claire L Mitchell,
Lynn Hope,
N Chan Ton,
Alan Jackson
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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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James P.B. O'Connor,
Josephine H. Naish,
Alan Jackson,
John C. Waterton,
Yvonne Watson,
Sue Cheung,
David L. Buckley,
Deirdre M. McGrath,
Giovanni A. Buonaccorsi, Samantha J. Mills,
Caleb Roberts,
Gordon C. Jayson,
Geoff J.M. Parker
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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 (R1) and effective transverse relaxation rate (R), induced by inhalation of pure oxygen and carbogen, were evaluated in 10 healthy subjects. Significant reductions in R1 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 occurred following pure oxygen in any organ. However, a significant increase in R 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 R1 and R were independent of the gas administration order in the spleen and skeletal muscle. These findings suggest that the R1 and R responses to hyperoxic gases are independent biomarkers of oxygen physiology. Magn Reson Med 61:75–83, 2009. © 2008 Wiley-Liss, Inc.
Magnetic Resonance in Medicine 12/2008; 61(1):75 - 83. · 2.96 Impact Factor
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James P B O'Connor,
Josephine H Naish,
Alan Jackson,
John C Waterton,
Yvonne Watson,
Sue Cheung,
David L Buckley,
Deirdre M McGrath,
Giovanni A Buonaccorsi, Samantha J Mills,
Caleb Roberts,
Gordon C Jayson,
Geoff J M Parker
[show abstract]
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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. · 2.96 Impact Factor
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James P B O'Connor,
Gordon C Jayson,
Alan Jackson,
Dana Ghiorghiu,
Bernadette M Carrington,
Chris J Rose, Samantha J Mills,
Ric Swindell,
Caleb Roberts,
Claire L Mitchell,
Geoffrey J M Parker
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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. · 7.74 Impact Factor
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ABSTRACT: The purpose of this study was to examine the relationship between contrast transfer coefficient [K(trans)] and grade in gliomas.
Median values of K(trans), CBV(T1), and of the 95th percentile (95%) of the distribution (K(trans) [95%] and CBV(T1) [95%]) were calculated in 39 patients with glioma. Group comparisons and post hoc pairwise comparisons were performed. The relationship between variables and grade used Spearman rho and canonical discriminant analysis. The separation of high- from low-grade tumors was separately assessed by using Mann-Whitney U tests and logistic regression. Receiver operator curve analysis was performed for high- and low-grade tumors and grade III and grade IV tumors.
There were significant differences between grades for all variables (P < .001). Pairwise comparisons demonstrated significant differences between grades II and III and II and IV for all variables except K(trans), which did not show significance in the grade II and III comparison, and between III and IV for CBV(T1) and CBV(T1) (95%; P < .01). All variables correlated with grade (P < .01). Discriminant analysis showed independent relation between both CBV(T1) and K(trans) (95%) and grade, and the canonical function produced a total correct classification of 74.4% of cases. Logistic regression analysis for low- versus high-grade tumors showed K(trans) (95%) and CBV(T1) to be independent factors (P < .01 and P < .05).
There are strong independent relationships between both CBV and K(trans) and histologic grade in gliomas. Both measurements show good discriminative power in distinguishing between low- and high-grade tumors with diagnostic sensitivity and specificity >90%.
American Journal of Neuroradiology 26(10):2455-65. · 2.93 Impact Factor
