Cross section of a mouse bearing a subcutaneous tumor. As can be seen, the tumor to background ra... more Cross section of a mouse bearing a subcutaneous tumor. As can be seen, the tumor to background ratio is high, and after 2Â h, the blood pool is under the detection limit, visible in the cross section of the heart. The figure additionally shows the high in vivo resolution that allowed the analysis of all the areas with different amounts of radiopeptide uptake levels. (TIF 165 kb)
99St Scientific Assembly and Annual Meeting of the Radiological Society of North America Rsna 2013 1 6 December 2013 Chicago Il Usa, 2013
PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, respons... more PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, response monitoring and outcome prediction. Many quantification techniques have been described, however in clinical practice these methods are scarcely used. The aim of this study is to evaluate the performance of the described methods and to identify the bottlenecks for the implementation in clinical practice. METHOD AND MATERIALS: We searched OVID, EMBASE, and Cochrane CENTRAL up to 24 March 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (FandT). RESULTS:From 6908 potentially relevant publications, 183 studies were included. The number of studies has been increasing steadily since 2009. Generally, 60 % studies use NSM,49% use SGLM, 11 % use FA, and 28% use FandT. Differential diagnosis, grading or outcome prediction was the goal in 86% studies, 36% studies were based on MRI, and 88% studies were conducted retrospectively. Tumours in the breast and brain together cover 49% of the studies. No relation was found between the discriminative power and the quantification methods used, or between the discriminative power and the imaging modality. The reported AUC ranged from 0.5 to 1 with a median of 0.89. A negative correlation was found between the AUC and the number of features estimated per tumour, which is presumably caused by overfitting in small datasets. In only 53.4% of the classification studies, the use of cross-validation was reported. None of the publications report the use of an external validation set to test their findings. Retrospective analyses were conducted in 60% of the studies without a clear description of the inclusion criteria. Only 12% of the studies had a prospective study design. Almost none of the papers evaluated the incremental value of the heterogeneity biomarker on top of clinical established markers. CONCLUSION:To enable the translation of imaging biomarkers from the research stage to clinical practice, research should focus more on prospective studies, use external datasets for validation, and focus on the added value of the proposed heterogeneity biomarker on top of the clinical established markers. CLINICAL RELEVANCE/APPLICATION:Heterogeneity has the potential of a valuable biomarker.
Angiogenesis is a very important process for tumor growth and proliferation. Given its high tempo... more Angiogenesis is a very important process for tumor growth and proliferation. Given its high temporal and spatial resolution, magnetic resonance (MR) imaging is well suited for use in the assessment of angiogenesis. MR angiography can be used clinically and experimentally for identification of tumor feeding and draining vessels, for tumor characterization, and for treatment planning. The morphologic structure of tumor vessels can be investigated in relation to tumor vessel permeability with use of specific contrast agents. To gain insight into tumor angiogenesis in vivo, the authors compared images obtained with digital photography, high-resolution MR angiography, and intravital microscopy through a dorsal skin-fold window in a rodent model. The close correlation between images obtained with these various modalities, with regard to the depiction of the developing tumor vasculature, indicates that noninvasive quantification of angiogenesis may be possible with MR imaging. Future directions in tumor imaging may include so-called four-dimensional MR angiography, in which high-resolution three-dimensional MR angiography is combined with dynamic contrast-enhanced MR imaging.
Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyper... more Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyperthermia treatment planning. Hyperthermia treatment planning is based on tissue segmentation for 3D patient model generation. We present here an automatic atlas-based segmentation algorithm for the organs at risk from CT images of the head and neck. To overcome the large anatomical variability, atlas registration and intensity-based classification were combined. A cost function composed of an intensity energy term, a spatial prior energy term based on the atlas registration and a regularization term is globally minimized using graph cut. The method was evaluated by measuring Dice similarity coefficient, mean and Hausdorff surface distances with respect to manual delineation. Overall a high correspondence was found with Dice similarity coefficient higher than 0.86 and a mean distance lower than the voxel resolution.
As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptid... more As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation. High-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq (111)In(DOTA-(βAla)2-JMV594) (25 pmol). Im...
Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine... more Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu-TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. ...
3rd IEEE International Symposium on Biomedical Imaging: Macro to Nano, 2006., 2006
Experimental evidence exists that especially the heterogeneity in contrast enhancement as evaluat... more Experimental evidence exists that especially the heterogeneity in contrast enhancement as evaluated by dynamic contrast enhanced MRI (DCE-MRI) is a predictive feature for treatment outcome in a variety of tumor types. In this study it is investigated whether texture descriptors derived from DCE-MRI based heuristic feature maps are suitable to quantify the heterogeneity in contrast uptake. An automated analysis method
In the last decade, the fractal dimension has become a popular parameter to characterize image te... more In the last decade, the fractal dimension has become a popular parameter to characterize image textures. Also in radiographs, various procedures have been used to estimate the fractal dimension. However, certain characteristics of the radiographic process, e.g., noise and blurring, interfere with the straightforward application of these estimation methods. In this study, the influence of quantum noise and image blur on several estimation methods was quantified by simulating the effect of quantum noise and the effect of modulation transfer functions, corresponding with different screen-film combinations, on computer generated fractal images. The results are extrapolated to explain the effect of film-grain noise on fractal dimension estimation. The effect of noise is that, irrespective of the noise source, the fractal dimension is overestimated, especially for lower fractal dimensions. On the other hand, blurring results in an underestimation of the dimensions. The effect of blurring is dependent on the estimation method used; the dimension estimates by the power spectrum method are lowered with a constant value, whereas the underestimation by the methods working in the spatial domain is dependent on the given dimension. The influence of the MTF and noise on fractal dimension estimation seriously limits the comparability of fractal dimensions estimated from radiographs which differ in noise content or MTF. Only when the power spectrum method is used, it is possible to correct for the influence of different MTFs of screen-film combinations. It is concluded that only when using the same object-focus distance, the same exposure conditions, the same digitizer at the same resolution, can fractal dimensions as estimated in radiographs be reliably compared.
Tissue structures, represented by textures in radiographs, can be quantified using texture analys... more Tissue structures, represented by textures in radiographs, can be quantified using texture analysis methods. Different texture analysis methods have been used to discriminate between different aspects of various diseases in primarily x rays of chest, bone, and breasts. However, most of these methods have not specifically been developed for use on radiographs. Certain characteristics of the radiographic process, e.g., noise and blurring, influence the visible texture. In order for a texture analysis method to be able to discriminate between different underlying textures, it should not be too sensitive for such processes as image noise and blur. In this study, we investigated the sensitivity of four different texture analysis methods for image noise and blur. First, a baseline measurement was performed of the discriminative performance of the Spatial Gray-Level Dependence method, the Fourier Power Spectrum, the Fractal Dimension, and the Morphological Gradient Method on images, which were not affected by radiographic noise and blur. Two types of images were used: fractal and Brodatz. Whereas the Brodatz images represent very different textures, the differences between the fractal images are more gradual. We assume that the behavior of the different texture analysis methods on the fractal images is representative for their performance on radiologic textures. On these types of images we simulated the effect of four different noise levels and the effect of two different modulation transfer functions, corresponding with different screenfilm combinations. The influence on the discriminative performance of the four texture analysis methods was evaluated. The influence of noise on the discriminative performance is, as expected, dependent on the image type used; the discrimination of more gradually different images, such as the fractal images, is already lowered for relatively low noise levels. In contrast, when the images are more different, only high noise levels decrease the discriminative performance. The discriminative power of the Morphological Gradient Method is least affected by image blur. We conclude that the discriminative performance of the Morphological Gradient Method is superior to that of other methods in circumstances which mimic the conditions prevailing in radiographs.
Magnetic Resonance Materials in Physics, Biology and Medicine, 2004
The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for qu... more The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF-alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K(PS) and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.
Experimental evidence supports an association between heterogeneity in tumor perfusion and respon... more Experimental evidence supports an association between heterogeneity in tumor perfusion and response to chemotherapy/radiotherapy, disease progression and malignancy. Therefore, changes in tumor perfusion may be used to assess early effects of tumor treatment. However, evaluating changes in tumor perfusion during treatment is complicated by extensive changes in tumor type, size, shape and appearance. Therefore, this study assesses the regional heterogeneity of tumors by dynamic contrast-enhanced MRI (DCE-MRI) and evaluates changes in response to isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan. Data were acquired in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175 (a soft-tissue sarcoma) were implanted in eight brown Norway rats. MRI of five drug-treated and three sham-treated rats was performed at baseline and 1 h after ILP intervention. Properly co-registered baseline and follow-up DCE-MRI were used to estimate the volume transfer constant (K(trans) ) pharmacokinetic maps. The regional heterogeneity was estimated in 16 tumor sectors and presented in cumulative map-volume histograms. On average, ILP-treated tumors showed a decrease in regional heterogeneity on the histograms. This study shows that heterogenic changes in regional tumor perfusion, estimated using DCE-MRI pharmacokinetic maps, can be measured and used to assess the short-term effects of a potentially curative treatment on the tumor microvasculature in an experimental soft-tissue sarcoma model.
Proceedings - International Symposium on Biomedical Imaging, 2012
Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyper... more Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyperthermia treatment planning. Hyperthermia treatment planning is based on tissue segmentation for 3D patient model generation. We present here an automatic atlas-based segmentation algorithm for the organs at risk from CT images of the head and neck. To overcome the large anatomical variability, atlas registration and intensity-based classification were combined. A cost function composed of an intensity energy term, a spatial prior energy term based on the atlas registration and a regularization term is globally minimized using graph cut. The method was evaluated by measuring Dice similarity coefficient, mean and Hausdorff surface distances with respect to manual delineation. Overall a high correspondence was found with Dice similarity coefficient higher than 0.86 and a mean distance lower than the voxel resolution.
Cross section of a mouse bearing a subcutaneous tumor. As can be seen, the tumor to background ra... more Cross section of a mouse bearing a subcutaneous tumor. As can be seen, the tumor to background ratio is high, and after 2Â h, the blood pool is under the detection limit, visible in the cross section of the heart. The figure additionally shows the high in vivo resolution that allowed the analysis of all the areas with different amounts of radiopeptide uptake levels. (TIF 165 kb)
99St Scientific Assembly and Annual Meeting of the Radiological Society of North America Rsna 2013 1 6 December 2013 Chicago Il Usa, 2013
PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, respons... more PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, response monitoring and outcome prediction. Many quantification techniques have been described, however in clinical practice these methods are scarcely used. The aim of this study is to evaluate the performance of the described methods and to identify the bottlenecks for the implementation in clinical practice. METHOD AND MATERIALS: We searched OVID, EMBASE, and Cochrane CENTRAL up to 24 March 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (FandT). RESULTS:From 6908 potentially relevant publications, 183 studies were included. The number of studies has been increasing steadily since 2009. Generally, 60 % studies use NSM,49% use SGLM, 11 % use FA, and 28% use FandT. Differential diagnosis, grading or outcome prediction was the goal in 86% studies, 36% studies were based on MRI, and 88% studies were conducted retrospectively. Tumours in the breast and brain together cover 49% of the studies. No relation was found between the discriminative power and the quantification methods used, or between the discriminative power and the imaging modality. The reported AUC ranged from 0.5 to 1 with a median of 0.89. A negative correlation was found between the AUC and the number of features estimated per tumour, which is presumably caused by overfitting in small datasets. In only 53.4% of the classification studies, the use of cross-validation was reported. None of the publications report the use of an external validation set to test their findings. Retrospective analyses were conducted in 60% of the studies without a clear description of the inclusion criteria. Only 12% of the studies had a prospective study design. Almost none of the papers evaluated the incremental value of the heterogeneity biomarker on top of clinical established markers. CONCLUSION:To enable the translation of imaging biomarkers from the research stage to clinical practice, research should focus more on prospective studies, use external datasets for validation, and focus on the added value of the proposed heterogeneity biomarker on top of the clinical established markers. CLINICAL RELEVANCE/APPLICATION:Heterogeneity has the potential of a valuable biomarker.
Angiogenesis is a very important process for tumor growth and proliferation. Given its high tempo... more Angiogenesis is a very important process for tumor growth and proliferation. Given its high temporal and spatial resolution, magnetic resonance (MR) imaging is well suited for use in the assessment of angiogenesis. MR angiography can be used clinically and experimentally for identification of tumor feeding and draining vessels, for tumor characterization, and for treatment planning. The morphologic structure of tumor vessels can be investigated in relation to tumor vessel permeability with use of specific contrast agents. To gain insight into tumor angiogenesis in vivo, the authors compared images obtained with digital photography, high-resolution MR angiography, and intravital microscopy through a dorsal skin-fold window in a rodent model. The close correlation between images obtained with these various modalities, with regard to the depiction of the developing tumor vasculature, indicates that noninvasive quantification of angiogenesis may be possible with MR imaging. Future directions in tumor imaging may include so-called four-dimensional MR angiography, in which high-resolution three-dimensional MR angiography is combined with dynamic contrast-enhanced MR imaging.
Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyper... more Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyperthermia treatment planning. Hyperthermia treatment planning is based on tissue segmentation for 3D patient model generation. We present here an automatic atlas-based segmentation algorithm for the organs at risk from CT images of the head and neck. To overcome the large anatomical variability, atlas registration and intensity-based classification were combined. A cost function composed of an intensity energy term, a spatial prior energy term based on the atlas registration and a regularization term is globally minimized using graph cut. The method was evaluated by measuring Dice similarity coefficient, mean and Hausdorff surface distances with respect to manual delineation. Overall a high correspondence was found with Dice similarity coefficient higher than 0.86 and a mean distance lower than the voxel resolution.
As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptid... more As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation. High-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq (111)In(DOTA-(βAla)2-JMV594) (25 pmol). Im...
Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine... more Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu-TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. ...
3rd IEEE International Symposium on Biomedical Imaging: Macro to Nano, 2006., 2006
Experimental evidence exists that especially the heterogeneity in contrast enhancement as evaluat... more Experimental evidence exists that especially the heterogeneity in contrast enhancement as evaluated by dynamic contrast enhanced MRI (DCE-MRI) is a predictive feature for treatment outcome in a variety of tumor types. In this study it is investigated whether texture descriptors derived from DCE-MRI based heuristic feature maps are suitable to quantify the heterogeneity in contrast uptake. An automated analysis method
In the last decade, the fractal dimension has become a popular parameter to characterize image te... more In the last decade, the fractal dimension has become a popular parameter to characterize image textures. Also in radiographs, various procedures have been used to estimate the fractal dimension. However, certain characteristics of the radiographic process, e.g., noise and blurring, interfere with the straightforward application of these estimation methods. In this study, the influence of quantum noise and image blur on several estimation methods was quantified by simulating the effect of quantum noise and the effect of modulation transfer functions, corresponding with different screen-film combinations, on computer generated fractal images. The results are extrapolated to explain the effect of film-grain noise on fractal dimension estimation. The effect of noise is that, irrespective of the noise source, the fractal dimension is overestimated, especially for lower fractal dimensions. On the other hand, blurring results in an underestimation of the dimensions. The effect of blurring is dependent on the estimation method used; the dimension estimates by the power spectrum method are lowered with a constant value, whereas the underestimation by the methods working in the spatial domain is dependent on the given dimension. The influence of the MTF and noise on fractal dimension estimation seriously limits the comparability of fractal dimensions estimated from radiographs which differ in noise content or MTF. Only when the power spectrum method is used, it is possible to correct for the influence of different MTFs of screen-film combinations. It is concluded that only when using the same object-focus distance, the same exposure conditions, the same digitizer at the same resolution, can fractal dimensions as estimated in radiographs be reliably compared.
Tissue structures, represented by textures in radiographs, can be quantified using texture analys... more Tissue structures, represented by textures in radiographs, can be quantified using texture analysis methods. Different texture analysis methods have been used to discriminate between different aspects of various diseases in primarily x rays of chest, bone, and breasts. However, most of these methods have not specifically been developed for use on radiographs. Certain characteristics of the radiographic process, e.g., noise and blurring, influence the visible texture. In order for a texture analysis method to be able to discriminate between different underlying textures, it should not be too sensitive for such processes as image noise and blur. In this study, we investigated the sensitivity of four different texture analysis methods for image noise and blur. First, a baseline measurement was performed of the discriminative performance of the Spatial Gray-Level Dependence method, the Fourier Power Spectrum, the Fractal Dimension, and the Morphological Gradient Method on images, which were not affected by radiographic noise and blur. Two types of images were used: fractal and Brodatz. Whereas the Brodatz images represent very different textures, the differences between the fractal images are more gradual. We assume that the behavior of the different texture analysis methods on the fractal images is representative for their performance on radiologic textures. On these types of images we simulated the effect of four different noise levels and the effect of two different modulation transfer functions, corresponding with different screenfilm combinations. The influence on the discriminative performance of the four texture analysis methods was evaluated. The influence of noise on the discriminative performance is, as expected, dependent on the image type used; the discrimination of more gradually different images, such as the fractal images, is already lowered for relatively low noise levels. In contrast, when the images are more different, only high noise levels decrease the discriminative performance. The discriminative power of the Morphological Gradient Method is least affected by image blur. We conclude that the discriminative performance of the Morphological Gradient Method is superior to that of other methods in circumstances which mimic the conditions prevailing in radiographs.
Magnetic Resonance Materials in Physics, Biology and Medicine, 2004
The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for qu... more The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF-alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K(PS) and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.
Experimental evidence supports an association between heterogeneity in tumor perfusion and respon... more Experimental evidence supports an association between heterogeneity in tumor perfusion and response to chemotherapy/radiotherapy, disease progression and malignancy. Therefore, changes in tumor perfusion may be used to assess early effects of tumor treatment. However, evaluating changes in tumor perfusion during treatment is complicated by extensive changes in tumor type, size, shape and appearance. Therefore, this study assesses the regional heterogeneity of tumors by dynamic contrast-enhanced MRI (DCE-MRI) and evaluates changes in response to isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan. Data were acquired in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175 (a soft-tissue sarcoma) were implanted in eight brown Norway rats. MRI of five drug-treated and three sham-treated rats was performed at baseline and 1 h after ILP intervention. Properly co-registered baseline and follow-up DCE-MRI were used to estimate the volume transfer constant (K(trans) ) pharmacokinetic maps. The regional heterogeneity was estimated in 16 tumor sectors and presented in cumulative map-volume histograms. On average, ILP-treated tumors showed a decrease in regional heterogeneity on the histograms. This study shows that heterogenic changes in regional tumor perfusion, estimated using DCE-MRI pharmacokinetic maps, can be measured and used to assess the short-term effects of a potentially curative treatment on the tumor microvasculature in an experimental soft-tissue sarcoma model.
Proceedings - International Symposium on Biomedical Imaging, 2012
Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyper... more Outcome optimization of hyperthermia tumor treatment in the head and neck requires accurate hyperthermia treatment planning. Hyperthermia treatment planning is based on tissue segmentation for 3D patient model generation. We present here an automatic atlas-based segmentation algorithm for the organs at risk from CT images of the head and neck. To overcome the large anatomical variability, atlas registration and intensity-based classification were combined. A cost function composed of an intensity energy term, a spatial prior energy term based on the atlas registration and a regularization term is globally minimized using graph cut. The method was evaluated by measuring Dice similarity coefficient, mean and Hausdorff surface distances with respect to manual delineation. Overall a high correspondence was found with Dice similarity coefficient higher than 0.86 and a mean distance lower than the voxel resolution.
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Papers by J. Veenland