Generation of a NG2-EYFP mouse for studying the properties of NG2-expressing cells

A range of vectors were made in which the EYFP gene or the Cre gene were inserted in the start codon of the NG2 gene. The NG2-EYFP vectors were used to generate NG2-EYFP “knockin” mice by homologous recombination. The F1 generation showed lack of EYFP expression, due to NeoR cassette interference. Excision of the NeoR, by breeding the F1 generation to ELLA-Cre mice allowed proper expression of EYFP. NG2-EYFP heterozygous mice were characterized in detail for astrocytic, neurogenic and oligodendrocytic properties through antibody labeling. NG2-EYFP+ cells did not label for the astrocyte marker GFAP, but some cells did express S100 Beta. The cells did not label with any neuronal markers like Beta III tubulin, Neun, and double cortin, but many of the NG2-EYFP+ cells made intimate contacts to the neurons. These contacts are widespread throughout the grey and white matter of the brain. The NG2-EYFP+ cells did label for oligodendrocyte markers like PDGFα-R, NG2, Olig2, O4, and Sox 10. There were a few cells termed phantom cells that did label for NG2, but had no EYFP expression. This could have been caused by improper excision of the NeoR cassette in the F2 generation. The heterozygous mouse is a tool to allow the characterization of the in vivo properties of the NG2+ cells. Breeding of these mice to homozygosity yielded an NG2-knockout mouse, which was also subjected to initial characterization. The NG2-EYFP homozygous showed equivalent cell labeling results to the NG2-EYFP heterozygous mouse, but the phantom cells disappeared in the knockout. The results show that the NG2 cells are a heterogenous population that does not express astrocytic or neuronal markers. The homozygous mouse is an ideal tool to further dissect the properties of the cells, lacking NG2 in vivo.

Diffusionsgewichtete Helium-3 Magnetresonanztomographie zur Untersuchung der Lunge

Die diffusionsgewichtete Magnetresonanztomographie (MRT) mit dem hyperpolarisierten Edelgas-Isotop 3He ist ein neues Verfahren zur Untersuchung von Erkrankungen der Atem-wege und der Lunge. Die Diffusionsbewegung der 3He-Atome in den Luftwegen der Lunge wird durch deren Wände begrenzt, wobei diese Einschränkung sowohl von den Dimensionen der Atemwege als auch von den Messparametern abhängt. Man misst daher einen scheinbaren Diffusionskoeffizienten (Apparent Diffusion Coefficient, ADC) der kleiner ist als der Diffusionskoeffizient bei freier Diffusion. Der ADC gestattet somit eine qualitative Abschät-zung der Größe der Luftwege und deren krankhafte Veränderung, ohne eine direkte Abbil-dung der Luftwege selbst. Eine dreidimensionale Abbildung der räumlichen Verteilung von Lungenschädigungen wird dadurch möglich. Ziel der vorliegenden Arbeit war es, ein tieferes physikalisch fundiertes Verständnis der 3He-Diffusionsmessung zu ermöglichen und die Methode der diffusionsgewichteten 3He-MRT hin zur Erfassung des kompletten 3He-Diffusionstensors weiterzuentwickeln. Dazu wurde systematisch im Rahmen von Phantom- und tierexperimentellen Studien sowie Patientenmes-sungen untersucht, inwieweit unterschiedliche Einflussfaktoren das Ergebnis der ADC-Messung beeinflussen. So konnte beispielsweise nachgewiesen werden, dass residuale Luftströmungen am Ende der Einatmung keinen Einfluss auf den ADC-Wert haben. Durch Simulationsrechnungen konnte gezeigt werden, in welchem Maße sich die durch den Anregungspuls hervorgerufene Abnah-me der Polarisation des 3He-Gases auf den gemessenen ADC-Wert auswirkt. In einer Studie an lungengesunden Probanden und Patienten konnte die Wiederholbarkeit der ADC-Messung untersucht werden, aber auch der Einfluss von Gravitationseffekten. Diese Ergebnisse ermöglichen genauere Angaben über systematische und statistische Messfehler, sowie über Grenzwerte zwischen normalem und krankhaft verändertem Lungengewebe. Im Rahmen dieser Arbeit wurde die bestehende diffusionsgewichtete Bildgebung methodisch zur Erfassung des kompletten Diffusionstensors von 3He in der Lunge weiterentwickelt. Dies war wichtig, da entlang der Luftwege weitestgehend freie Diffusion vorherrscht, während senkrecht zu den Luftwegen die Diffusion eingeschränkt ist. Mit Hilfe von Simulationsrech-nungen wurde der kritische Einfluss von Rauschen in den MRT-Bildern auf die Qualität der Messergebnisse untersucht. Diese neue Methodik wurde zunächst an einem Phantom beste-hend aus einem Bündel aus Glaskapillaren, deren innerer Durchmesser mit dem des mensch-lichen Azinus übereinstimmt, validiert. Es ergab sich eine gute Übereinstimmung zwischen theoretischen Berechnungen und experimentellen Ergebnissen. In ersten Messungen am Menschen konnten so unterschiedliche Anisotropiewerte zwischen lungengesunden Proban-den und Patienten gefunden werden. Es zeigte sich eine Tendenz zu isotroper Diffusion bei Patienten mit einem Lungenemphysem. Zusammenfassend tragen die Ergebnisse der vorliegenden Arbeit zu einem besseren Ver-ständnis der ADC-Messmethode bei und helfen zukünftige Studien aufgrund des tieferen Verständnisses der die 3He Messung beeinflussenden Faktoren besser zu planen.

Über das Vermessen tubulärer Strukturen in der Computertomographie

Die chronisch obstruktive Lungenerkrankung (engl. chronic obstructive pulmonary disease, COPD) ist ein Überbegriff für Erkrankungen, die zu Husten, Auswurf und Dyspnoe (Atemnot) in Ruhe oder Belastung führen - zu diesen werden die chronische Bronchitis und das Lungenemphysem gezählt. Das Fortschreiten der COPD ist eng verknüpft mit der Zunahme des Volumens der Wände kleiner Luftwege (Bronchien). Die hochauflösende Computertomographie (CT) gilt bei der Untersuchung der Morphologie der Lunge als Goldstandard (beste und zuverlässigste Methode in der Diagnostik). Möchte man Bronchien, eine in Annäherung tubuläre Struktur, in CT-Bildern vermessen, so stellt die geringe Größe der Bronchien im Vergleich zum Auflösungsvermögen eines klinischen Computertomographen ein großes Problem dar. In dieser Arbeit wird gezeigt wie aus konventionellen Röntgenaufnahmen CT-Bilder berechnet werden, wo die mathematischen und physikalischen Fehlerquellen im Bildentstehungsprozess liegen und wie man ein CT-System mittels Interpretation als lineares verschiebungsinvariantes System (engl. linear shift invariant systems, LSI System) mathematisch greifbar macht. Basierend auf der linearen Systemtheorie werden Möglichkeiten zur Beschreibung des Auflösungsvermögens bildgebender Verfahren hergeleitet. Es wird gezeigt wie man den Tracheobronchialbaum aus einem CT-Datensatz stabil segmentiert und mittels eines topologieerhaltenden 3-dimensionalen Skelettierungsalgorithmus in eine Skelettdarstellung und anschließend in einen kreisfreien Graphen überführt. Basierend auf der linearen System Theorie wird eine neue, vielversprechende, integral-basierte Methodik (IBM) zum Vermessen kleiner Strukturen in CT-Bildern vorgestellt. Zum Validieren der IBM-Resultate wurden verschiedene Messungen an einem Phantom, bestehend aus 10 unterschiedlichen Silikon Schläuchen, durchgeführt. Mit Hilfe der Skelett- und Graphendarstellung ist ein Vermessen des kompletten segmentierten Tracheobronchialbaums im 3-dimensionalen Raum möglich. Für 8 zweifach gescannte Schweine konnte eine gute Reproduzierbarkeit der IBM-Resultate nachgewiesen werden. In einer weiteren, mit IBM durchgeführten Studie konnte gezeigt werden, dass die durchschnittliche prozentuale Bronchialwandstärke in CT-Datensätzen von 16 Rauchern signifikant höher ist, als in Datensätzen von 15 Nichtrauchern. IBM läßt sich möglicherweise auch für Wanddickenbestimmungen bei Problemstellungen aus anderen Arbeitsgebieten benutzen - kann zumindest als Ideengeber dienen. Ein Artikel mit der Beschreibung der entwickelten Methodik und der damit erzielten Studienergebnisse wurde zur Publikation im Journal IEEE Transactions on Medical Imaging angenommen.

Entwicklungen zur Absolutquantifizierung der Lungenperfusion mittels kontrastmittelverstärkter Magnetresonanztomographie

Die regionale Bestimmung der Durchblutung (Perfusion) ermöglicht differenzierte Aussagen über den Gesundheitszustand und die Funktionalität der Lunge. Durch neue Messverfahren ermöglicht die Magnetresonanztomographie (MRT) eine nicht-invasive und strahlungsfreie Untersuchung der Perfusion. Obwohl die Machbarkeit qualitativer MRT-Durchblutungsmessungen bereits gezeigt wurde, fehlt bisher eine validierte quantitative Methode. Ziel dieser Arbeit war eine Optimierung der bestehenden Messprotokolle und mathematischen Modelle zur Absolutquantifizierung der Lungenperfusion mit Magnetresonanztomographie. Weiterhin sollte die Methodik durch Vergleich mit einem etablierten Referenzverfahren validiert werden. Durch Simulationen und Phantommessungen konnten optimale MRT-Messparameter und ein standardisiertes Protokoll festgelegt werden. Des Weiteren wurde eine verallgemeinerte Bestimmung der Kontrastmittelkonzentration aus den gemessenen Signalintensitäten vorgestellt, diskutiert und durch Probandenmessungen validiert. Auf der Basis dieser Entwicklungen wurde die MRT-Durchblutungsmessung der Lunge tierexperimentell mit der Positronenemissionstomographie (PET) intraindividuell verglichen und validiert. Die Ergebnisse zeigten nur kleine Abweichungen und eine statistisch hochsignifikante, stark lineare Korrelation. Zusammenfassend war es durch die Entwicklungen der vorgestellten Arbeit möglich, die kontrastmittelgestützte MRT-Durchblutungsmessung der Lunge zu optimieren und erstmals zu validieren.

Measurement of the $B^0$ - $\bar{B}^0$ and $B^0_s$ - $\bar{B}^0_s$ production asymmetries in pp collisions at $\sqrt{s}=7$ TeV and $\sqrt{s}=8$ TeV with the LHCb experiment

The production rate of $b$ and $\bar{b}$ hadrons in $pp$ collisions are not expected to be strictly identical, due to imbalance between quarks and anti-quarks in the initial state. This phenomenon can be naively related to the fact that the $\bar{b}$ quark produced in the hard scattering might combine with a $u$ or $d$ valence quark from the colliding protons, whereas the same cannot happen for a $b$ quark. This thesis presents the analysis performed to determine the production asymmetries of $B^0$ and $B^0_s$. The analysis relies on data samples collected by the LHCb detector at the Large Hadron Collider (LHC) during the 2011 and 2012 data takings at two different values of the centre of mass energy $\sqrt{s}=7$ TeV and at $\sqrt{s}=8$ TeV, corresponding respectively to an integrated luminosity of 1 fb$^{-1}$ and of 2 fb$^{-1}$. The production asymmetry is one of the key ingredients to perform measurements of $CP$ violation in b-hadron decays at the LHC, since $CP$ asymmetries must be disentangled from other sources. The measurements of the production asymmetries are performed in bins of $p_\mathrm{T}$ and $\eta$ of the $B$-meson. The values of the production asymmetries, integrated in the ranges $4 < p_\mathrm{T} < 30$ GeV/c and $2.5<\eta<4.5$, are determined to be: \begin{equation} A_\mathrm{P}(\B^0)= (-1.00\pm0.48\pm0.29)\%,\nonumber \end{equation} \begin{equation} A_\mathrm{P}(\B^0_s)= (\phantom{-}1.09\pm2.61\pm0.61)\%,\nonumber \end{equation} where the first uncertainty is statistical and the second is systematic. The measurement of $A_\mathrm{P}(B^0)$ is performed using the full statistics collected by LHCb so far, corresponding to an integrated luminosity of 3 fb$^{-1}$, while the measurement of $A_\mathrm{P}(B^0_s)$ is realized with the first 1 fb$^{-1}$, leaving room for improvement. No clear evidence of dependences on the values of $p_\mathrm{T}$ and $\eta$ is observed. The results presented in this thesis are the most precise measurements available up to date.

Le tecniche di machine learning per il trattamento della sindrome dell'arto fantasma

Questo elaborato ha come scopo quello di analizzare ed esaminare una patologia oggetto di attiva ricerca scientifica, la sindrome dell’arto fantasma o phantom limb pain: tracciando la storia delle terapie più utilizzate per la sua attenuazione, si è giunti ad analizzarne lo stato dell’arte. Consapevoli che la sindrome dell’arto fantasma costituisce, oltre che un disturbo per chi la prova, uno strumento assai utile per l’analisi delle attività nervose del segmento corporeo superstite (moncone), si è svolta un’attività al centro Inail di Vigorso di Budrio finalizzata a rilevare segnali elettrici provenienti dai monconi superiori dei pazienti che hanno subito un’amputazione. Avendo preliminarmente trattato l’argomento “Machine learning” per raggiungere una maggiore consapevolezza delle potenzialità dell’apprendimento automatico, si sono analizzate la attività neuronali dei pazienti mentre questi muovevano il loro arto fantasma per riuscire a settare nuove tipologie di protesi mobili in base ai segnali ricevuti dal moncone.

Multicentre study for a robust protocol in single-voxel spectroscopy: quantification of MRS signals by time-domain fitting algorithms

Magnetic Resonance Spectroscopy (MRS) is an advanced clinical and research application which guarantees a specific biochemical and metabolic characterization of tissues by the detection and quantification of key metabolites for diagnosis and disease staging. The "Associazione Italiana di Fisica Medica (AIFM)" has promoted the activity of the "Interconfronto di spettroscopia in RM" working group. The purpose of the study is to compare and analyze results obtained by perfoming MRS on scanners of different manufacturing in order to compile a robust protocol for spectroscopic examinations in clinical routines. This thesis takes part into this project by using the GE Signa HDxt 1.5 T at the Pavillion no. 11 of the S.Orsola-Malpighi hospital in Bologna. The spectral analyses have been performed with the jMRUI package, which includes a wide range of preprocessing and quantification algorithms for signal analysis in the time domain. After the quality assurance on the scanner with standard and innovative methods, both spectra with and without suppression of the water peak have been acquired on the GE test phantom. The comparison of the ratios of the metabolite amplitudes over Creatine computed by the workstation software, which works on the frequencies, and jMRUI shows good agreement, suggesting that quantifications in both domains may lead to consistent results. The characterization of an in-house phantom provided by the working group has achieved its goal of assessing the solution content and the metabolite concentrations with good accuracy. The goodness of the experimental procedure and data analysis has been demonstrated by the correct estimation of the T2 of water, the observed biexponential relaxation curve of Creatine and the correct TE value at which the modulation by J coupling causes the Lactate doublet to be inverted in the spectrum. The work of this thesis has demonstrated that it is possible to perform measurements and establish protocols for data analysis, based on the physical principles of NMR, which are able to provide robust values for the spectral parameters of clinical use.

Performance analysis of reconstruction algorithms for breast microwave imaging

The problem of localizing a scatterer, which represents a tumor, in a homogeneous circular domain, which represents a breast, is addressed. A breast imaging method based on microwaves is considered. The microwave imaging involves to several techniques for detecting, localizing and characterizing tumors in breast tissues. In all such methods an electromagnetic inverse scattering problem exists. For the scattering detection method, an algorithm based on a linear procedure solution, inspired by MUltiple SIgnal Classification algorithm (MUSIC) and Time Reversal method (TR), is implemented. The algorithm returns a reconstructed image of the investigation domain in which it is detected the scatterer position. This image is called pseudospectrum. A preliminary performance analysis of the algorithm vying the working frequency is performed: the resolution and the signal-to-noise ratio of the pseudospectra are improved if a multi-frequency approach is considered. The Geometrical Mean-MUSIC algorithm (GM- MUSIC) is proposed as multi-frequency method. The performance of the GMMUSIC is tested in different real life computer simulations. The performed analysis shows that the algorithm detects the scatterer until the electrical parameters of the breast are known. This is an evident limit, since, in a real life situation, the anatomy of the breast is unknown. An improvement in GM-MUSIC is proposed: the Eye-GMMUSIC algorithm. Eye-GMMUSIC algorithm needs no a priori information on the electrical parameters of the breast. It is an optimizing algorithm based on the pattern search algorithm: it searches the breast parameters which minimize the Signal-to-Clutter Mean Ratio (SCMR) in the signal. Finally, the GM-MUSIC and the Eye-GMMUSIC algorithms are tested on a microwave breast cancer detection system consisting of an dipole antenna, a Vector Network Analyzer and a novel breast phantom built at University of Bologna. The reconstruction of the experimental data confirm the GM-MUSIC ability to localize a scatterer in a homogeneous medium.

Modelli compartimentali per l'analisi di segnali ottenuti tramite DCE MRI per studi di perfusione epatica

Il presente lavoro di tesi si inserisce all'interno di uno studio dal titolo: "Strategia di posizionamento multi-step come approccio pragmatico per ridurre il rischio di encefalopatia epatica post-TIPS (shunt trans-giugulare porto-sistemico intraepatico) in pazienti cirrotici con ascite refrattaria". Il progetto di tesi si è concentrato sull'analisi dei segnali ottenuti tramite DCE MRI, con lo scopo di implementare in ambiente MatLab due modelli differenti (Dual input - Mono compartment e Dual input - Dual compartment) che descrivono la cinetica del tracciante all'interno del sistema vascolare epatico e valutare l'efficacia dei parametri di perfusione associati nella descrizione delle variazioni in termini di microcircolazione introdotte dall'inserimento del TIPS. Inizialmente si sono voluti valutare, tramite simulazione, gli effetti in termini di amplificazione del rumore e stima dei parametri perfusionali dell'approssimazione lineare nella conversione da intensità di segnale MR a concentrazione di mezzo di contrasto. Successivamente, sempre attraverso simulazioni, per entrambi i modelli considerati è stato scelto uno schema di model-fitting e quindi testata l'affidabilità in termini di accuratezza e precisione delle stime dei parametri ottenute in funzione del livello di rumore associato alle curve di intensità di segnale. Parallelamente all'implementazione dei modelli per la stima di parametri di perfusione, sono stati realizzati dei phantom con l'obiettivo di simulare il parenchima epatico prima e dopo l'arrivo del mezzo di contrasto e poter testare la sequenza utilizzata durante l'acquisizione dei dati su paziente. Infine sono stati considerati gli esami di DCE MRI effettuati su un campione di nove pazienti pre e post-TIPS, utilizzando per l'analisi dei segnali entrambi i modelli implementati in fase di simulazione e successivamente valutando le variazioni nel valori associati ai parametri di perfusione introdotte dall'inserimento del TIPS.

Tomographic 3D reconstruction through linear inversion for breast microwave imaging

In the present thesis we address the problem of detecting and localizing a small spherical target with characteristic electrical properties inside a volume of cylindrical shape, representing female breast, with MWI. One of the main works of this project is to properly extend the existing linear inversion algorithm from planar slice to volume reconstruction; results obtained, under the same conditions and experimental setup are reported for the two different approaches. Preliminar comparison and performance analysis of the reconstruction algorithms is performed via numerical simulations in a software-created environment: a single dipole antenna is used for illuminating the virtual breast phantom from different positions and, for each position, the corresponding scattered field value is registered. Collected data are then exploited in order to reconstruct the investigation domain, along with the scatterer position, in the form of image called pseudospectrum. During this process the tumor is modeled as a dielectric sphere of small radius and, for electromagnetic scattering purposes, it's treated as a point-like source. To improve the performance of reconstruction technique, we repeat the acquisition for a number of frequencies in a given range: the different pseudospectra, reconstructed from single frequency data, are incoherently combined with MUltiple SIgnal Classification (MUSIC) method which returns an overall enhanced image. We exploit multi-frequency approach to test the performance of 3D linear inversion reconstruction algorithm while varying the source position inside the phantom and the height of antenna plane. Analysis results and reconstructed images are then reported. Finally, we perform 3D reconstruction from experimental data gathered with the acquisition system in the microwave laboratory at DIFA, University of Bologna for a recently developed breast-phantom prototype; obtained pseudospectrum and performance analysis for the real model are reported.

Determination of Pelvic Orientation from Ultrasound Images Using Patch-SSMs and a Hierarchical Speed of Sound Compensation Strategy

In the field of computer assisted orthopedic surgery (CAOS) the anterior pelvic plane (APP) is a common concept to determine the pelvic orientation by digitizing distinct pelvic landmarks. As percutaneous palpation is - especially for obese patients - known to be error-prone, B-mode ultrasound (US) imaging could provide an alternative means. Several concepts of using ultrasound imaging to determine the APP landmarks have been introduced. In this paper we present a novel technique, which uses local patch statistical shape models (SSMs) and a hierarchical speed of sound compensation strategy for an accurate determination of the APP. These patches are independently matched and instantiated with respect to associated point clouds derived from the acquired ultrasound images. Potential inaccuracies due to the assumption of a constant speed of sound are compensated by an extended reconstruction scheme. We validated our method with in-vitro studies using a plastic bone covered with a soft-tissue simulation phantom and with a preliminary cadaver trial.

Comparison of three optical tracking systems in a complex navigation scenario

Three-dimensional rotational X-ray imaging with the SIREMOBIL Iso-C3D (Siemens AG, Medical Solutions, Erlangen, Germany) has become a well-established intra-operative imaging modality. In combination with a tracking system, the Iso-C3D provides inherently registered image volumes ready for direct navigation. This is achieved by means of a pre-calibration procedure. The aim of this study was to investigate the influence of the tracking system used on the overall navigation accuracy of direct Iso-C3D navigation. Three models of tracking system were used in the study: Two Optotrak 3020s, a Polaris P4 and a Polaris Spectra system, with both Polaris systems being in the passive operation mode. The evaluation was carried out at two different sites using two Iso-C3D devices. To measure the navigation accuracy, a number of phantom experiments were conducted using an acrylic phantom equipped with titanium spheres. After scanning, a special pointer was used to pinpoint these markers. The difference between the digitized and navigated positions served as the accuracy measure. Up to 20 phantom scans were performed for each tracking system. The average accuracy measured was 0.86 mm and 0.96 mm for the two Optotrak 3020 systems, 1.15 mm for the Polaris P4, and 1.04 mm for the Polaris Spectra system. For the Polaris systems a higher maximal error was found, but all three systems yielded similar minimal errors. On average, all tracking systems used in this study could deliver similar navigation accuracy. The passive Polaris system showed ? as expected ? higher maximal errors; however, depending on the application constraints, this might be negligible.

Effect of beam hardening on arterial enhancement in thoracoabdominal CT angiography with increasing patient size: an in vitro and in vivo study

To assess the effect of beam hardening on arterial enhancement in thoracoabdominal computed tomographic (CT) angiography in various body sizes in a phantom and in a clinical study.

Copper filtration in pediatric digital X-ray imaging: its impact on image quality and dose

The effect of copper (Cu) filtration on image quality and dose in different digital X-ray systems was investigated. Two computed radiography systems and one digital radiography detector were used. Three different polymethylmethacrylate blocks simulated the pediatric body. The effect of Cu filters of 0.1, 0.2, and 0.3 mm thickness on the entrance surface dose (ESD) and the corresponding effective doses (EDs) were measured at tube voltages of 60, 66, and 73 kV. Image quality was evaluated in a contrast-detail phantom with an automated analyzer software. Cu filters of 0.1, 0.2, and 0.3 mm thickness decreased the ESD by 25-32%, 32-39%, and 40-44%, respectively, the ranges depending on the respective tube voltages. There was no consistent decline in image quality due to increasing Cu filtration. The estimated ED of anterior-posterior (AP) chest projections was reduced by up to 23%. No relevant reduction in the ED was noted in AP radiographs of the abdomen and pelvis or in posterior-anterior radiographs of the chest. Cu filtration reduces the ESD, but generally does not reduce the effective dose. Cu filters can help protect radiosensitive superficial organs, such as the mammary glands in AP chest projections.

Monte Carlo Dose Calculation on Deforming Anatomy

This article presents the implementation and validation of a dose calculation approach for deforming anatomical objects. Deformation is represented by deformation vector fields leading to deformed voxel grids representing the different deformation scenarios. Particle transport in the resulting deformed voxels is handled through the approximation of voxel surfaces by triangles in the geometry implementation of the Swiss Monte Carlo Plan framework. The focus lies on the validation methodology which uses computational phantoms representing the same physical object through regular and irregular voxel grids. These phantoms are chosen such that the new implementation for a deformed voxel grid can be compared directly with an established dose calculation algorithm for regular grids. Furthermore, separate validation of the aspects voxel geometry and the density changes resulting from deformation is achieved through suitable design of the validation phantom. We show that equivalent results are obtained with the proposed method and that no statistically significant errors are introduced through the implementation for irregular voxel geometries. This enables the use of the presented and validated implementation for further investigations of dose calculation on deforming anatomy.