Field strength dependence of R<sub>1</sub> and R relaxivities of human whole blood to prohance, vasovist, and deoxyhemoglobin

Blockley, Nicholas P.; Jiang, Lijun; Gardener, Alexander G.; Ludman, Catherine N.; Francis, Susan T.; Gowland, Penny A.

doi:10.1002/mrm.21792

Cited by 135 publications

(169 citation statements)

References 23 publications

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“…Baseline R 2 * values for the human tumours were lower than those found in the xenografts because of the magnetic field strength dependence of R 2 * relaxivities (Blockley et al, 2008), and also showed less heterogeneity (R 2 * ¼ 7.1 -29.2 s À1 ). The susceptibility-weighted BOLD technique proved to be highly repeatable in human prostate cancer with a wCV of 4.7%.…”

Section: Human Testingmentioning

confidence: 72%

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Alonzi

Padhani

Maxwell³

et al. 2009

Br J Cancer

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Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R 2 * pixel maps were produced for each tumour and at each time point and changes in R 2 * induced by carbogen were determined. There was a mean reduction in R 2 * of 6.4% (P ¼ 0.003) for DU145 xenografts and 5.8% (P ¼ 0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R 2 * during carbogen inhalation with a mean reduction of 21.6% (P ¼ 0.0005). Decreases in prostate tumour R 2 * in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients. British Journal of Cancer (2009) The relationship of radiosensitivity to varying oxygenation and the detrimental effects of hypoxia in human tumours was first shown over 50 years ago (Gray et al, 1953;Tomlinson and Gray, 1955). Since then, it has been established that hypoxia is an important factor in radiotherapy treatment failure and has been associated in clinical studies with poor local tumour control and relapse in many cancer sites (Nordsmark et al, 1996;Fyles et al, 1998;Brizel et al, 1999;Movsas et al, 2002;Hoskin et al, 2003).Eppendorf microelectrode measurements have been used to invasively characterise the range and heterogeneity of oxygen partial pressures in the prostate and show that hypoxic regions exist in human prostate carcinoma (Movsas et al, 1999;Parker et al, 2004). The outcome of radical radiotherapy for prostate cancer is influenced by the presence of hypoxia. A study that prospectively analysed 57 patients with localised disease showed that hypoxic tumours had a significantly worse biochemical relapse-free survival at 2 years (31 vs 92%, Po0.0001; Movsas et al, 2002). Oxygenation status is therefore an additional prognostic factor beyond the classic prognostic factors (age, clinical stage, Gleason score and prostate-specific antigen) that predicts radiation treatment failure in prostate cancer. A modelling study based on these clinical data predicts an oxygen enhancement ratio for prostate cancer of 1.4 (95% confidence interval of 1.2-1.8) that is consistent with the in vitro OER measurements of human tumour cell lines under chronic hypoxia conditions (Wang et al, 2006). These data taken together suggest that hypoxia is likely to be a valid therapeutic target in prostate cancer.The ...

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Section: Human Testingmentioning

confidence: 72%

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Alonzi

Padhani

Maxwell³

et al. 2009

Br J Cancer

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“…Despite the fact that HCT is recognised as an important scaling factor for AIF (12), very few studies have investigated its impact on T 1 and T 2 Ã as a function of contrast agent concentration (15,28). The effect of HCT on blood T 1 values has been shown to be linear (33,34), whereas the effect of HCT on blood T 2 and T 2 Ã values has generally been investigated as a function of blood oxygenation (28,35,36). For the first time, the effect of HCT on blood-doped gadodiamide R 2 Ã values was evaluated for a range of HCTs.…”

Section: Discussionmentioning

confidence: 98%

Assessment of the effect of haematocrit‐dependent arterial input functions on the accuracy of pharmacokinetic parameters in dynamic contrast‐enhanced MRI

et al. 2011

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The detection and prognosis of prostate cancer in its early stages are critically important. It is therefore essential to improve the existing dynamic contrast-enhanced MRI (DCE MRI) techniques commonly used for the assessment of the tumour vascular environment. The goal of this study was to describe a method for the estimation of the arterial input function (AIF) in DCE MRI by measuring R(2) * values in the femoral artery of patients with early-stage prostate cancer. The calculation of contrast agent concentrations was based on calibration curves determined in whole blood samples for a range of normal haematocrit (HCT) values (HCT = 0.35-0.525). Individual AIFs corrected for HCT were compared with individual AIFs calibrated with a mean whole blood [R(2)*-Gd-DTPA-BMA] [Gd-DTPA-BMA, gadolinium diethylenetriaminepentaacetate-bis(methylamide) (gadodiamide)] curve at an assumed HCT = 0.44, as well as a population AIF at an assumed HCT = 0.45. The area under the curve of the first-pass bolus ranged between 0.6 min mM at HCT = 0.53 and 1.3 min mM at HCT = 0.39. Significant differences in magnitude at peak contrast agent concentrations (HCT = 0.36, [Gd-DTPA-BMA](max) = 9 ± 0.4 mM; HCT = 0.46, [Gd-DTPA-BMA](max) = 4.0 ± 0.2 mM) were found. Using model-based simulations, the accuracy of the kinetic parameters estimated using individual AIFs corrected for HCT demonstrated that, for the use of individual calibration curves with HCT values differing by more than 10%, K(trans) and k(ep) values were largely underestimated (up to 60% difference for K(trans)). Moreover, blood volume estimates were severely underestimated. Estimates of kinetic parameters in early-stage prostate cancer patients demonstrated that the efflux rate constant (k(ep)) was influenced significantly by the definition of AIF. Regardless of whether an individually calibrated AIF or a population AIF (average of all individually calibrated AIFs) was used, pixel-by-pixel mapping of k(ep) and v(b) in the prostate gland appeared to be more sensitive than with the usual biexponential approach.

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“…In this respect, these results provide evidence against the assumption that the specific nature of the contrast agent might be responsible for the conflicting results. Although Vasovist is based on gadolinium rather than on iron oxide particles as used for most animal studies, it temporarily binds to the blood albumin and also acts as a blood-pool contrast agent (Blockley et al, 2008;Majos et al, 2009;Morton et al, 2006). To which degree interspecies differences and/or influences from anesthesia have a role cannot be answered at this stage.…”

Section: Discussionmentioning

confidence: 99%

Basal Cerebral Blood Volume during the Poststimulation Undershoot in BOLD MRI of the Human Brain

Dechent

Schütze

Helms

et al. 2010

J Cereb Blood Flow Metab

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One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1-weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7%±0.4%), but no change relative to baseline in the poststimulation phase (0.2% ± 0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism.

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Field strength dependence of R₁ and R relaxivities of human whole blood to prohance, vasovist, and deoxyhemoglobin

Cited by 135 publications

References 23 publications

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Assessment of the effect of haematocrit‐dependent arterial input functions on the accuracy of pharmacokinetic parameters in dynamic contrast‐enhanced MRI

Basal Cerebral Blood Volume during the Poststimulation Undershoot in BOLD MRI of the Human Brain

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Field strength dependence of R1 and R relaxivities of human whole blood to prohance, vasovist, and deoxyhemoglobin

Cited by 135 publications

References 23 publications

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Assessment of the effect of haematocrit‐dependent arterial input functions on the accuracy of pharmacokinetic parameters in dynamic contrast‐enhanced MRI

Basal Cerebral Blood Volume during the Poststimulation Undershoot in BOLD MRI of the Human Brain

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Field strength dependence of R₁ and R relaxivities of human whole blood to prohance, vasovist, and deoxyhemoglobin