Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Ceelen, Wim; Smeets, Peter; Backes, Walter H.; Damme, Nancy Van; Boterberg, Tom; Demetter, Pieter; Bouckenooghe, Isabel; Visschere, Marieke De; Peeters, Marc; Pattyn, Piet

doi:10.1016/j.ijrobp.2005.10.026

Cited by 51 publications

(50 citation statements)

References 34 publications

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“…Therefore they concluded that DCE-MRI does not simply reflect static histological vascular properties in patients with rectal cancer. Monitoring 11 rats before and after fractionated short-term radiotherapy (Ceelen et al, 2006) observed a significant reduction of K trans and v e , while in non irradiated muscle tissue no changes were observed. After RT, pO 2 levels were inversely related to both K trans and v e .N o fig.…”

Section: Dce-mri In Rectal Cancermentioning

confidence: 93%

“…A high temporal resolution can be difficult to obtain because the acquisition of a single volume could require several seconds as a large part of the whole abdomen is scanned. One approach to overcome this problem is to choose a single slice containing the tumor, so that the sampling interval can be maintained below a few seconds (Blomqvist et al, 1998;Ceelen et al, 2006;de Lussanet et al, 2005). However, this approach is not able to manage with the heterogeneity of the tumour ).…”

Section: Spatial and Temporal Resolutionmentioning

confidence: 99%

“…Previous considerations support a Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) approach that could gain a renewed role to MRI adding functional data to the morphological examination. DCE-MRI has been reported by many authors as a tool potentially able to permit an evaluation of pre-CRT effectiveness basing on the strict relationship between tumor growth and angiogenesis (Ceelen et al, 2006;de Lussanet et al, 2005;Kremser et al, 2007). DCE-MRI is gaining a large consensus as a technique for diagnosis, staging and assessment of therapy response for different types of tumours, due to its capability to detect highly active angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic Contrast Enhanced Magnetic Resonance Imaging in Rectal Cancer

Fusco¹,

Sansone²,

Petrillo³

et al. 2011

Rectal Cancer - A Multidisciplinary Approach to Management

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Section: Dce-mri In Rectal Cancermentioning

confidence: 93%

Section: Spatial and Temporal Resolutionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic Contrast Enhanced Magnetic Resonance Imaging in Rectal Cancer

Fusco¹,

Sansone²,

Petrillo³

et al. 2011

Rectal Cancer - A Multidisciplinary Approach to Management

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“…Experimentally, P792 has been used to study permeability effects of anti-angiogenesis therapy in a prostate cancer model (Pradel et al, 2003). We have previously demonstrated that P792 selectively enhances tumour tissue in this colorectal cancer model (Ceelen et al, 2006).…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…We previously used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (CA) to demonstrate a significantly decreased neovascular leakage after fractionated RT in a rat colorectal cancer model (Ceelen et al, 2006). Dynamic contrastenhanced magnetic resonance imaging allows noninvasive in vivo study of microvascular properties of a complete tumour, thereby taking into account the important spatial heterogeneity of solid tumours with zones of well perfused tissue, as well as hypoxic or necrotic areas (Hylton, 2006).…”

mentioning

confidence: 99%

Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

et al. 2007

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Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 Â 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO 2 measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 a (HIF-1a), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPOtreated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1a, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation. British Journal of Cancer (2007) Anaemia commonly occurs in colorectal cancer patients especially if they are treated with neoadjuvant radiotherapy (RT) or chemotherapy. Anaemia not only adversely affects the clinical condition of these patients, but also contributes to the development of tumour hypoxia, recognised as a major negative determinant of sensitivity to RT, chemoradiotherapy, and certain chemotherapeutic agents (Harrison and Blackwell, 2004;van Halteren et al, 2004).Recent clinical studies have shown that administration of recombinant human erythropoietin (rhEPO, epoetin alfa) increases haemoglobin levels and improves quality of life in patients with cancer-related anaemia (Littlewood et al, 2001). Over the last decade, it has become clear that the action or rhEPO extends into a wide range of cellular mechanisms involved in stem cell development, maintenance of cellular integrity, and physiological angiogenesis (Maiese et al, 2005). The demonstration of the erythropoietin (EPO) receptor in various neoplastic tissues and the observation in a recent clinical trial that mortality was higher in nonanaemic rhEPO-treated breast cancer patients highlighted the possible effects of rhEPO on tumour growth and angiogenesis (Leyland-Jones, 2003). Preclinical studies investigating the role of EPO and EPO -EPO receptor signalling on tumour growth and angiogenesis have yielded contradictory results. Yasuda et al (2003) noted the inhibition of angiogenesis and tumour cell survival in stomach and melanoma xenografts following blockade of EPO signalling. The results of Hardee et al (2005), however, suggested that a...

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In vitro setup to study permeability characteristics of contrast agents by MRI

Heilmann

Vautier

Robert

et al. 2009

Contrast Media & Molecular

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An experimental setup consisting of a hollow fiber module (HFM) was developed for the in vitro study of contrast agent (CA) permeability. Controllable flow and known fiber characteristics allowed permeability studies under well-defined conditions with CAs of different molecular weight (MW). In the MRI experiments performed at 4.7 T, the system was perfused at a constant flow rate (5 ml/min) with water and four CA of different MW: Gd-DOTA (MW=0.6 kDa), P846 (3.5 kDa), P792 (6.5 kDa) and P717 (50.5 kDa). R(1) time courses were measured with a saturation-recovery multi-gradient-echo snapshot sequence in the fiber-free HFM input and the fiber-filled center. Concentration time courses were calculated, and CA extravasation was analyzed with a pharmacokinetic model yielding exchange rate constant k(ie). Only Gd-DOTA (k(ie)=2.37+/-0.16 min(-1)) and P846 (k(ie)=0.58+/-0.17 min(-1)) showed quantifiable extravasation. P717 perfusion yielded an intra-capillary volume fraction of 15.6+/-2.7% compared with 12% estimated from the HFM manufacturer's specifications. In conclusion, the experimental setup allowed classification of in vitro permeability characteristics for CAs with different MW and therefore holds potential for systematic comparison of CAs currently under development.

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Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Cited by 51 publications

References 34 publications

Dynamic Contrast Enhanced Magnetic Resonance Imaging in Rectal Cancer

Dynamic Contrast Enhanced Magnetic Resonance Imaging in Rectal Cancer

Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

In vitro setup to study permeability characteristics of contrast agents by MRI

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