Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

Robinson, Simon P.; Rijken, P.F.J.W.; Howe, Franklyn A.; McSheehy, Paul M.J.; Sanden, Boudewijn van der; Heerschap, Arend; Stubbs, Marion; Kogel, Albert J. van der; Griffiths, John R.

doi:10.1002/jmri.10274

Cited by 129 publications

(151 citation statements)

References 40 publications

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“…The reasons for even hypoxic tumours having limited and heterogeneous responses are complex, but undoubtedly include the fact that tumours may have adapted to widely different perfusion environments. It is to be noted that even when vessels are present, red blood cell transport through these vessels may not be effective (Robinson et al, 2003). Thus, hypoxic tumours with high blood volume (due to high microvessel density coupled with large vessels) will have raised baseline R 2 * values.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…However, good correlations between areas of intense neovascularization were not always obtained (8,22). In the present case, VSI and BV values represent weighted averages over these pixels.…”

Section: Discussionmentioning

confidence: 99%

“…The sections were incubated with an antibody against the basal lamina component collagen type IV to delineate functional and non perfused vasculature in tumors and their healthy contralateral part. Qualitative image analysis only was performed using a fluorescence microscope to examine the vasculature of the tumors on three sections per tumor (8). Haematoxylin and eosin stained sections were also made for histological examination.…”

Section: Histogram Segmentationmentioning

confidence: 99%

Histogram analysis of the microvasculature of intracerebral human and murine glioma xenografts

Just

2010

Magnetic Resonance in Med

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The purpose of this study is to examine the usefulness of histogram analysis combined with vessel size index (VSI) magnetic resonance imaging for the specific characterization of brain tumor microvasculature in a panel of six volume-matched glioma xenografts. Using a simple descriptive histogram analysis, significant differences of the mean tumoral VSI (P 5 0.0035 for 9L, P 5 0.008 for glioma mix, P 5 0.05 for C6), the 75th VSI percentile (P 5 0.003-0.075) as well as the 25th and median blood volume (BV) percentiles were found in murine gliomas compared to their contralateral healthy brain. Using a segmented histogram analysis, dilatation of already existing vessels in murine gliomas and development of new small caliber vessels in human glioblastomas were suggested. Most gliomas showed a higher proportion of pixels with BV below 1% (glioma mix [21% vs 1%], Glioblastoma 2 (GBM2) [9% vs 3.7%]) and a smaller proportion of pixels with BV in the range 1.7-6.3% (65 vs 90% for glioma mix, 80 vs 85% in GBM2) relative to their contralateral part. In glioblastomas, VSI and BV distributions were similar to normal brain distributions and in agreement with immunohistochemical findings. The histogram analysis of VSI and BV heterogeneity in experimental brain tumors allowed detection of microregional differences in gliomas from different origins. Magn Reson Med 65:778-789,

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“…Furthermore, VF showed no correlation with K Both blood oxygenation level-dependent (BOLD) (1) MRI and dynamic contrast enhanced (DCE) MRI have emerged as useful techniques for noninvasive imaging of tumor vasculature (2,3). BOLD-MRI has been used to study tumor vascular growth (4), hemodynamic changes in response to treatments (5-12), acute hypoxia (13), vessel maturation (14 -17), and functional status of the vascular bed (14,15,18,19). DCE-MRI also provides important information regarding tumor function and anatomy.…”

mentioning

confidence: 99%

“…BOLD-MRI has been used to study tumor vascular growth (4), hemodynamic changes in response to treatments (5)(6)(7)(8)(9)(10)(11)(12), acute hypoxia (13), vessel maturation (14 -17), and functional status of the vascular bed (14,15,18,19). DCE-MRI also provides important information regarding tumor function and anatomy.…”

mentioning

confidence: 99%

Determination of the maturity and functionality of tumor vasculature by MRI: Correlation between BOLD‐MRI and DCE‐MRI using P792 in experimental fibrosarcoma tumors

Baudelet

Cron

Gallez

2006

Magnetic Resonance in Med

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Using hypercapnia and carbogen as functional markers of vessel maturation and function, we compared blood oxygen leveldependent (BOLD) contrast with standard dynamic contrastenhanced (DCE)-MRI quantitative parameters in murine fibrosarcoma. Our results show that there was no correlation between vessel maturity and contrast-agent uptake rate (K Trans in ) or contrast agent efflux rate (k ep ). In addition, DCE-MRI provided higher estimates of the fraction of functional tumor compared to BOLD-MRI. The two putative markers of regional vascular density, i.e., the magnitude of BOLD signal change during carbogen challenge (VF) and the fractional plasma volume found by DCE-MRI (V p ), were only weakly correlated (r 2 ‫؍‬ 0.02-0.14). Furthermore, VF showed no correlation with K Both blood oxygenation level-dependent (BOLD) (1) MRI and dynamic contrast enhanced (DCE) MRI have emerged as useful techniques for noninvasive imaging of tumor vasculature (2,3). BOLD-MRI has been used to study tumor vascular growth (4), hemodynamic changes in response to treatments (5-12), acute hypoxia (13), vessel maturation (14 -17), and functional status of the vascular bed (14,15,18,19). DCE-MRI also provides important information regarding tumor function and anatomy. Parameters such as blood flow, capillary permeability, interstitial space, and blood volume can be determined by analyzing the kinetics of contrast-media uptake and wash-out (3,20,21).Assessment of vessel maturation and function with BOLD-or DCE-MRI is an approach whose utility for cancer investigations is well recognized. However, few studies have examined these two techniques simultaneously on the same subject. Thus, our understanding of mechanisms that may relate BOLD-and DCE-MRI remains relatively underdeveloped. Among the few investigators who have focused on this issue, Rijpkema et al. (22) compared BOLD-MRI (response to 98%O 2 /2%CO 2 gas) and DCE-MRI in meningioma patients. In their study, changes in T* 2 were found to correlate inversely with the wash-out rate of the Gd contrast agent. In two other papers, Peller et al. (23) and Jiang et al. (24) found no relationship between BOLD-and DCE-MRI. However, the latter two studies employed semiquantitative DCE-MRI analyses instead of pharmacokinetic modeling. Although the reported parameters (maximum rate of enhancement and peak enhancement) may be related to physiological parameters, their lack of clear physiological significance could make their interpretation difficult (25).In this study we compared BOLD-MRI measurement of vessel maturation (using hypercapnia, i.e., elevated levels of CO 2 ) and BOLD-MRI measurement of vessel functionality (using carbogen breathing, i.e., elevated levels of O 2 and CO 2 ) with DCE-MRI using standardized pharmacokinetic quantities (25).DCE-MRI measurement of uptake and wash-out of a contrast agent can help to characterize vasculature during the neoangiogenesis process (20). In this study we assessed how these parameters correlated with BOLD-MRI measurements of neovascular maturation and...

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Tumor vascular architecture and function evaluated by non‐invasive susceptibility MRI methods and immunohistochemistry

Cited by 129 publications

References 40 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

Histogram analysis of the microvasculature of intracerebral human and murine glioma xenografts

Determination of the maturity and functionality of tumor vasculature by MRI: Correlation between BOLD‐MRI and DCE‐MRI using P792 in experimental fibrosarcoma tumors

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