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Thesis ; Online: Applications of 4D-MRI in proton therapy

Boye, Dirk

2016

Keywords	NMR-MIKROSKOPIE ; NMR-ABBILDUNDSVERFAHREN ; PROTONENRADIOTHERAPIE (RADIOTHERAPIE) ; PROTON RADIOTHERAPY (RADIOTHERAPY) ; NMR MICROSCOPY ; NMR IMAGING ; info:eu-repo/classification/ddc/610 ; Medical sciences ; medicine
Language	English
Publisher	ETH Zürich
Publishing country	ch
Document type	Thesis ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Developmental biology of fibroblasts and neoplastic disease.

Brouty-Boyé, D

Progress in molecular and subcellular biology

2006 Volume 40, Page(s) 55–77

MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Developmental Biology ; Epithelium/growth & development ; Fibroblasts/pathology ; Humans ; Neoplasms/pathology
Language	English
Publishing date	2006-11-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	0079-6484
ISSN	0079-6484
DOI	10.1007/3-540-27671-8_3
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Article: Effects of contour propagation and background corrections in different MRI flow software packages.

Boye, D / Springer, O / Wassmer, F / Scheidegger, S / Remonda, L / Berberat, J

Acta radiologica open

2015 Volume 4, Issue 6, Page(s) 2058460115589124

Abstract: Background: Velocity-encoded magnetic resonance imaging (VENC-MRI) is a commonly used technique in cardiac examinations. This technique utilizes the phase shift properties of protons moving along a magnetic field gradient. VENC-MRI offers a unique way ... ...

Abstract	Background: Velocity-encoded magnetic resonance imaging (VENC-MRI) is a commonly used technique in cardiac examinations. This technique utilizes the phase shift properties of protons moving along a magnetic field gradient. VENC-MRI offers a unique way of measuring the severity of valve regurgitation by directly quantifying the regurgitation flow volume. Purpose: To compare flow analysis results of different software programs and to assess the effect of background correction in sample patient cases. Material and methods: A phantom was built out of Polymethyl methacrylate (PMMA) which provides tubes of different diameters. These tubes can be connected to an external water circuit to generate a water flow inside the tubes. Expected absolute flow quantities inside the tubes were determined from preset tube- and flow-parameters. Different flow conditions were measured with a VENC-MRI sequence and the images evaluated using different software packages. In a second step six randomly selected patients showing different degrees of aortic insufficiency were evaluated in clinical terms. Results: The contour propagation algorithms used in the software packages performed differently even on static phantom geometry. In terms of clinical evaluation the software packages performed similarly. Enabling background correction or leaving out manual correction of propagated contours changed results for severity of aortic insufficiency. Conclusion: Turning on background correction and manual correction of propagated contours in MRI flow volume measurements is strongly recommended.
Language	English
Publishing date	2015-06-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2818429-4
ISSN	2058-4601
ISSN	2058-4601
DOI	10.1177/2058460115589124
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Article ; Online: Deformable motion reconstruction for scanned proton beam therapy using on-line x-ray imaging.

Zhang, Ye / Knopf, A / Tanner, C / Boye, D / Lomax, A J

Physics in medicine and biology

2013 Volume 58, Issue 24, Page(s) 8621–8645

Abstract: Organ motion is a major problem for any dynamic radiotherapy delivery technique, and is particularly so for spot scanned proton therapy. On the other hand, the use of narrow, magnetically deflected proton pencil beams is potentially an ideal delivery ... ...

Abstract	Organ motion is a major problem for any dynamic radiotherapy delivery technique, and is particularly so for spot scanned proton therapy. On the other hand, the use of narrow, magnetically deflected proton pencil beams is potentially an ideal delivery technique for tracking tumour motion on-line. At PSI, our new Gantry is equipped with a Beams Eye View (BEV) imaging system which will be able to acquire 2D x-ray images in fluoroscopy mode during treatment delivery. However, besides precisely tracking motion from BEVs, it is also essential to obtain information on the 3D motion vector throughout the whole region of interest, and any sparsely acquired surrogate motion is generally not sufficient to describe the deformable behaviour of the whole volume in three dimensions. In this study, we propose a method by which 3D deformable motions can be estimated from surrogate motions obtained using this monoscopic imaging system. The method assumes that example motions over a number of breathing cycles can be acquired before treatment for each patient using 4DMRI. In this study, for each of 11 different subjects, 100 continuous breathing cycles have been extracted from extended 4DMRI studies in the liver and then subject specific motion models have been built using principle component analysis (PCA). To simulate treatment conditions, a different set of 30 continuous breathing cycles from the same subjects have then been used to generate a set of simulated 4DCT data sets (so-called 4DCT(MRI) data sets), from which time-resolved digitally reconstructed radiographs (DRRs) were calculated using the BEV geometry for three treatment fields respectively. From these DRRs, surrogate motions from fiducial markers or the diaphragm have been used as a predictor to estimate 3D motions in the liver region for each subject. The prediction results have been directly compared to the 'ground truth' motions extracted from the same 30 breath cycles of the originating 4DMRI data set. Averaged over all 11 subjects, and for three field directions, for 99% of predicted positions, median (max) error magnitudes of better than 2.63(5.67) mm can be achieved when fiducial markers was chosen as predictor. Furthermore, three single fields, 4D dose calculations have been performed as a verification tool to evaluate the prediction performance of such a model in the context of scanned proton beam therapy. These show a high similarity between plans considering either PCA predicted motion or ground truth motion, where absolute dose differences of more than 5% (V(dosediff = 5%)) occur for the worst field scenarios in only 3.61% (median) or 15.13% (max) of dose calculation points in the irradiated volume. The magnitude of these dose differences were insignificantly dependent on whether surrogate motions were tracked by monoscopic or stereoscopic imaging systems, or whether fiducial markers or diaphragm were chosen as surrogate. This study has demonstrated that on-line deformable motion reconstruction from sparse surrogate motions is feasible, even when using only a monoscopic imaging system. In addition, it has also been found that diaphragm motion can be considered as a good predictor for respiratory deformable liver motion prediction, implying that fiducial markers might not be compulsory if used in conjunction with a patient specific PCA based model.
MeSH term(s)	Feasibility Studies ; Fluoroscopy ; Image Processing, Computer-Assisted/methods ; Movement ; Principal Component Analysis ; Proton Therapy/methods ; Radiotherapy Dosage ; Respiration
Language	English
Publishing date	2013-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/0031-9155/58/24/8621
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Article ; Online: Mapping motion from 4D-MRI to 3D-CT for use in 4D dose calculations: a technical feasibility study.

Boye, Dirk / Lomax, Tony / Knopf, Antje

Medical physics

2013 Volume 40, Issue 6, Page(s) 61702

Abstract: Purpose: Target sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of being a "snap-shot" of the motion during acquisition ... ...

Abstract	Purpose: Target sites affected by organ motion require a time resolved (4D) dose calculation. Typical 4D dose calculations use 4D-CT as a basis. Unfortunately, 4D-CT images have the disadvantage of being a "snap-shot" of the motion during acquisition and of assuming regularity of breathing. In addition, 4D-CT acquisitions involve a substantial additional dose burden to the patient making many, repeated 4D-CT acquisitions undesirable. Here the authors test the feasibility of an alternative approach to generate patient specific 4D-CT data sets. Methods: In this approach motion information is extracted from 4D-MRI. Simulated 4D-CT data sets [which the authors call 4D-CT(MRI)] are created by warping extracted deformation fields to a static 3D-CT data set. The employment of 4D-MRI sequences for this has the advantage that no assumptions on breathing regularity are made, irregularities in breathing can be studied and, if necessary, many repeat imaging studies (and consequently simulated 4D-CT data sets) can be performed on patients and/or volunteers. The accuracy of 4D-CT(MRI)s has been validated by 4D proton dose calculations. Our 4D dose algorithm takes into account displacements as well as deformations on the originating 4D-CT/4D-CT(MRI) by calculating the dose of each pencil beam based on an individual time stamp of when that pencil beam is applied. According to corresponding displacement and density-variation-maps the position and the water equivalent range of the dose grid points is adjusted at each time instance. Results: 4D dose distributions, using 4D-CT(MRI) data sets as input were compared to results based on a reference conventional 4D-CT data set capturing similar motion characteristics. Almost identical 4D dose distributions could be achieved, even though scanned proton beams are very sensitive to small differences in the patient geometry. In addition, 4D dose calculations have been performed on the same patient, but using 4D-CT(MRI) data sets based on variable breathing patterns to show the effect of possible irregular breathing on active scanned proton therapy. Using a 4D-CT(MRI), including motion irregularities, resulted in significantly different proton dose distributions. Conclusions: The authors have demonstrated that motion information from 4D-MRI can be used to generate realistic 4D-CT data sets on the basis of a single static 3D-CT data set. 4D-CT(MRI) presents a novel approach to test the robustness of treatment plans in the circumstance of patient motion.
MeSH term(s)	Artifacts ; Feasibility Studies ; Humans ; Image Enhancement/methods ; Imaging, Three-Dimensional/methods ; Magnetic Resonance Imaging/methods ; Motion ; Multimodal Imaging/methods ; Radiometry/methods ; Radiotherapy, Image-Guided/methods ; Reproducibility of Results ; Respiratory Mechanics ; Respiratory-Gated Imaging Techniques/methods ; Sensitivity and Specificity ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2013-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1118/1.4801914
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Article ; Online: Respiratory liver motion estimation and its effect on scanned proton beam therapy.

Zhang, Ye / Boye, D / Tanner, C / Lomax, A J / Knopf, A

Physics in medicine and biology

2012 Volume 57, Issue 7, Page(s) 1779–1795

Abstract: Proton therapy with active scanning beam delivery has significant advantages compared to conventional radiotherapy. However, so far only static targets have been treated in this way, since moving targets potentially lead to interplay effects. For 4D ... ...

Abstract	Proton therapy with active scanning beam delivery has significant advantages compared to conventional radiotherapy. However, so far only static targets have been treated in this way, since moving targets potentially lead to interplay effects. For 4D treatment planning, information on the target motion is needed to calculate time-resolved dose distributions. In this study, respiratory liver motion has been extracted from 4D CT data using two deformable image registration algorithms. In moderately moving patient cases (mean motion range around 6 mm), the registration error was no more than 3 mm, while it reached 7 mm for larger motions (range around 13 mm). The obtained deformation fields have then been used to calculate different time-resolved 4D treatment plans. Averaged over both motion estimations, interplay effects can increase the D₅-D₉₅ value for the clinical target volume (CTV) from 8.8% in a static plan to 23.4% when motion is considered. It has also been found that the different deformable registration algorithms can provide different motion estimations despite performing similarly for the selected landmarks, which in turn can lead to differing 4D dose distributions. Especially for single-field treatments where no motion mitigation is used, a maximum (mean) dose difference (averaged over three cases) of 32.8% (2.9%) can be observed. However, this registration ambiguity-induced uncertainty can be reduced if rescanning is applied or if the treatment plan consists of multiple fields, where the maximum (mean) difference can decrease to 15.2% (0.57%). Our results indicate the necessity to interpret 4D dose distributions for scanned proton therapy with some caution or with error bars to reflect the uncertainties resulting from the motion estimation. On the other hand, rescanning has been found to be an appropriate motion mitigation technique and, furthermore, has been shown to be a robust approach to also deal with these motion estimation uncertainties.
MeSH term(s)	Algorithms ; Dose Fractionation ; Four-Dimensional Computed Tomography ; Humans ; Liver/diagnostic imaging ; Liver/physiopathology ; Liver/radiation effects ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/physiopathology ; Liver Neoplasms/radiotherapy ; Movement ; Protons/therapeutic use ; Radiotherapy Planning, Computer-Assisted/methods ; Respiration
Chemical Substances	Protons
Language	English
Publishing date	2012-04-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/0031-9155/57/7/1779
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Article: Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen.

Briard, D / Azzarone, B / Brouty-Boyé, D

Clinical and experimental immunology

2005 Volume 140, Issue 2, Page(s) 265–273

Abstract: Summary The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts ... ...

Abstract	Summary The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34(+) blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a(+)CD38(+)CD68(+)CD86(+) HLA-DR(+)CD14(-)CD80(-) dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a(+) cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.
MeSH term(s)	Antigens, CD1/analysis ; Antigens, CD34/blood ; Cell Adhesion/immunology ; Cell Communication/immunology ; Cell Differentiation/immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/immunology ; Fibroblasts/immunology ; Flow Cytometry ; Humans ; Immunophenotyping ; Interleukin-15/immunology ; Killer Cells, Natural/immunology ; Lymphocyte Activation/immunology ; Macrophage Colony-Stimulating Factor/immunology ; Spleen/immunology ; Stromal Cells/immunology
Chemical Substances	Antigens, CD1 ; Antigens, CD34 ; CD1a antigen ; Interleukin-15 ; Macrophage Colony-Stimulating Factor (81627-83-0)
Language	English
Publishing date	2005-03-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1111/j.1365-2249.2005.02792.x
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Article: Review on 4D models for organ motion compensation.

Tanner, Christine / Boye, Dirk / Samei, Golnoosh / Szekely, Gabor

Critical reviews in biomedical engineering

2012 Volume 40, Issue 2, Page(s) 135–154

Abstract: Minimal invasive tumor therapies are getting ever more sophisticated with novel treatment approaches and new devices allowing for improved targeting precision. Applying these effectively requires precise localization of the structures of interest. Vital ... ...

Abstract	Minimal invasive tumor therapies are getting ever more sophisticated with novel treatment approaches and new devices allowing for improved targeting precision. Applying these effectively requires precise localization of the structures of interest. Vital processes, such as respiration and heartbeat, induce organ motion, which cannot be neglected during therapy. This review focuses on 4D organ models to compensate for respiratory motion during therapy. An overview is given on the effects of motion on the therapeutical outcome, methods required to capture and quantify respiratory motion, range of reported tumor motion, types of surrogates used when tumors are not directly observable, and methods for temporal prediction of surrogate motion. Organ motion models, which predict the location of structures of interest from surrogates measured during therapy, are discussed in detail.
MeSH term(s)	Algorithms ; Four-Dimensional Computed Tomography/methods ; Heart/physiology ; Humans ; Models, Anatomic ; Motion ; Neoplasms/therapy ; Phantoms, Imaging ; Principal Component Analysis ; Radiotherapy Planning, Computer-Assisted/methods ; Respiration ; Respiratory-Gated Imaging Techniques/methods
Language	English
Publishing date	2012-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1411103-2
ISSN	0278-940X
ISSN	0278-940X
DOI	10.1615/critrevbiomedeng.v40.i2.40
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Article: Discrimination of fibroblast subtypes by multivariate analysis of gene expression.

Spanakis, E / Brouty-Boyé, D

International journal of cancer

1997 Volume 71, Issue 3, Page(s) 402–409

Abstract: Fibroblasts and myofibroblasts from normal, fibrotic or tumoral breast tissues present multiple quantitative differences in gene expression even when grown in isolation. We were therefore prompted to investigate whether one could recognize various ... ...

Abstract	Fibroblasts and myofibroblasts from normal, fibrotic or tumoral breast tissues present multiple quantitative differences in gene expression even when grown in isolation. We were therefore prompted to investigate whether one could recognize various subtypes by their constitutive-gene expression profile. Quantitative autoradiographic data for 34 constitutively expressed transcripts were submitted to multivariate analysis of variance, followed by discriminant analysis and single linkage cluster analysis. Models assuming up to 8 putative fibroblast subtypes (among fibroblasts or myofibroblasts from breast skin, normal mammary stroma, tumor-adjacent "normal" stroma, post-radiation fibrosis lesions and benign or malignant tumors) and an epithelial-cell group used as an internal control resulted in 100% correct classification. Myofibroblasts from various origins clustered close to, although distinctly apart from, their corresponding alpha-smooth-muscle-actin-negative counterparts. Malignant tumor fibroblasts were phenotypically more distant from normal cells compared with other pathological types. Our results support the hypothesis of co-adaptive transformation of stromal and epithelial tissues during breast tumoral development and suggest that different types of fibroblasts give rise to different types of myofibroblasts. Discriminant analysis of quantitative molecular variation may be considered for the development of a powerful artificial-intelligence method for cell typing and should be particularly useful when no reliable discrete molecular markers are available.
MeSH term(s)	Breast/cytology ; Breast/metabolism ; Breast/radiation effects ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Breast Neoplasms/radiotherapy ; Discriminant Analysis ; Enzymes/biosynthesis ; Enzymes/genetics ; Female ; Fibroblasts/classification ; Fibroblasts/cytology ; Fibroblasts/pathology ; Fibrosis ; Gene Expression ; Growth Substances/biosynthesis ; Growth Substances/genetics ; Humans ; Interleukins/biosynthesis ; Interleukins/genetics ; Multivariate Analysis ; Nuclear Proteins/biosynthesis ; Nuclear Proteins/genetics ; Phenotype ; Protein Kinases/biosynthesis ; Protein Kinases/genetics ; Skin/cytology ; Skin/metabolism ; Skin/pathology
Chemical Substances	Enzymes ; Growth Substances ; Interleukins ; Nuclear Proteins ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	1997-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/(sici)1097-0215(19970502)71:3<402::aid-ijc17>3.0.co;2-h
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Article ; Online: Adequate margin definition for scanned particle therapy in the incidence of intrafractional motion.

Knopf, Antje-Christin / Boye, Dirk / Lomax, Antony / Mori, Shininchiro

Physics in medicine and biology

2013 Volume 58, Issue 17, Page(s) 6079–6094

Abstract: Advanced 4D dose calculations (4DDCs) for scanned particle therapy show that in the incidence of motion, it is insufficient to use target contours defined on one reference CT phase. ICRU Report 62 (ICRU 1999 ICRU Report 62 (Bethesda, MD: ICRU)) advises ... ...

Abstract	Advanced 4D dose calculations (4DDCs) for scanned particle therapy show that in the incidence of motion, it is insufficient to use target contours defined on one reference CT phase. ICRU Report 62 (ICRU 1999 ICRU Report 62 (Bethesda, MD: ICRU)) advises that variations in size, shape and position of CTVs relative to anatomic reference points have to be considered for internal target volumes (ITVs). In addition to geometrical margin adaption, changes of water equivalent path length have to be considered for particle therapy. Different ITV concepts have been applied to six representative patients (liver and lung indications) based on 4DCT. Geometrical ITVs (gITV) were calculated by combining deformed CTVs over all motion phases. To take into account path length changes, range adapted ITVs (raITV) were established as the union of range adapted CTVs in all phases. For gated delivery, gat_gITVs and gat_raITVs were calculated. Extensive 4DDCs have been performed for two exemplary patients to illustrate that neither re-scanning nor gating can sufficiently compensate for motion effects if no appropriate margins are employed and to evaluate the effectiveness of gITVs and raITVs. CTVs significantly differ from gITVs and raITVs in size (up to a factor 2 in volume). But also raITVs and gITVs differ significantly in size and are spatially displaced, particularly for lung patients. raITVs show a strong field dependence in shape. All volumes are reduced in size when gating is applied and considered during margin adaption. 4D dose distributions show big improvements when gITV or raITV are used compared to CTVs. However, the use of either gITVs or raITVs do not result in significant differences. If raITVs are used, slightly better target coverage is gained at the cost of more healthy tissue exposure. Our results emphasize that adapted target volumes have to be used for scanned particle therapy in the presence of motion. However, even though gITVs and raITVs differ significantly in shape and size, this difference does not necessarily translate into significant differences in the resultant 4D dose distributions.
MeSH term(s)	Algorithms ; Dose Fractionation ; Four-Dimensional Computed Tomography ; Humans ; Image Processing, Computer-Assisted ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/radiotherapy ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/radiotherapy ; Movement ; Photons/therapeutic use ; Proton Therapy ; Radiotherapy Dosage ; Radiotherapy, Image-Guided/methods
Language	English
Publishing date	2013-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/0031-9155/58/17/6079
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