Three-dimensional patient-specific dosimetry in radioimmunotherapy with 90Y-ibritumomab-tiuxetan.

Aim of the present article was to perform three-dimensional (3D) single photon emission tomography-based dosimetry in radioimmunotherapy (RIT) with (90)Y-ibritumomab-tiuxetan. A custom MATLAB-based code was used to elaborate 3D images and to compare average 3D doses to lesions and to organs at risk (OARs) with those obtained with planar (2D) dosimetry. Our 3D dosimetry procedure was validated through preliminary phantom studies using a body phantom consisting of a lung insert and six spheres with various sizes. In phantom study, the accuracy of dose determination of our imaging protocol decreased when the object volume decreased below 5 mL, approximately. The poorest results were obtained for the 2.58 mL and 1.30 mL spheres where the dose error evaluated on corrected images with regard to the theoretical dose value was -12.97% and -18.69%, respectively. Our 3D dosimetry protocol was subsequently applied on four patients before RIT with (90)Y-ibritumomab-tiuxetan for a total of 5 lesions and 4 OARs (2 livers, 2 spleens). In patient study, without the implementation of volume recovery technique, tumor absorbed doses calculated with the voxel-based approach were systematically lower than those calculated with the planar protocol, with average underestimation of -39% (range from -13.1% to -62.7%). After volume recovery, dose differences reduce significantly, with average deviation of -14.2% (range from -38.7.4% to +3.4%, 1 overestimation, 4 underestimations). Organ dosimetry in one case overestimated, in the other underestimated the dose delivered to liver and spleen. However, both for 2D and 3D approach, absorbed doses to organs per unit administered activity are comparable with most recent literature findings.

Impact of navigator timing on free-breathing submillimeter 3D coronary magnetic resonance angiography.

The purpose of this study was to investigate the impact of navigator timing on image quality in navigator-gated and real-time motion-corrected, free-breathing, three-dimensional (3D) coronary MR angiography (MRA) with submillimeter spatial image resolution. Both phantom and in vivo investigations were performed. 3D coronary MRA with real-time navigator technology was applied using variable navigator time delays (time delay between the navigator and imaging sequences) and varying spatial resolutions. Quantitative objective and subjective image quality parameters were assessed. For high-resolution imaging, reduced image quality was found as a function of increasing navigator time delay. Lower spatial resolution coronary MRA showed only minor sensitivity to navigator timing. These findings were consistent among volunteers and phantom experiments. In conclusion, for submillimeter navigator-gated and real-time motion-corrected 3D coronary MRA, shortening the time delay between the navigator and the imaging portion of the sequence becomes increasingly important for improved spatial resolution.

Spread spectrum magnetic resonance imaging.

We propose a novel compressed sensing technique to accelerate the magnetic resonance imaging (MRI) acquisition process. The method, coined spread spectrum MRI or simply s(2)MRI, consists of premodulating the signal of interest by a linear chirp before random k-space under-sampling, and then reconstructing the signal with nonlinear algorithms that promote sparsity. The effectiveness of the procedure is theoretically underpinned by the optimization of the coherence between the sparsity and sensing bases. The proposed technique is thoroughly studied by means of numerical simulations, as well as phantom and in vivo experiments on a 7T scanner. Our results suggest that s(2)MRI performs better than state-of-the-art variable density k-space under-sampling approaches.

Fetal dose reduction in head and neck radiotherapy of a pregnant woman.

BACKGROUND AND PURPOSE: A pregnant woman was referred for post-operative radiotherapy of a malignant schwannoma in the head and neck region. A best-treatment plan was devised in order to minimize the fetal dose. MATERIAL AND METHODS: The fetal dose resulting from radiological examinations was determined according to international protocols, that resulting from radiotherapy was calculated according to Recommendation 36 of the American Association of Physicists in Medicine (AAPM) Task Group. Pre-treatment dosimetry was performed with an anthropomorphic phantom. Several alternative treatment plans were evaluated. The use of a multileaf collimator (MLC) and a virtual wedge (VW) was compared to cerrobend blocks (CB) and physical wedge (PW). In-vivo dosimetry was performed using a vaginal probe containing thermoluminescent dosimeters (TLD). RESULTS: The total fetal dose resulting from diagnostic and radiotherapy procedures was estimated to be 36 mGy. The technique based on MLC and VW was elected for patient treatment. Measurements for this configuration resulted in afetal dose reduction of 82%. The shielding of the patient's abdomen further reduced the fetal dose by 42%. CONCLUSION: The use of VW and MLC for the treatment of a pregnant woman is highly recommended. Each case should be individually studied with pre-treatment and in-vivo dosimetry.

Azithromycin versus Sulfadiazine and Pyrimethamine for non-vision-threatening toxoplasmic retinochoroiditis: a pilot study.

BACKGROUND: The purpose of this pilot study is to compare the efficacy and tolerance of azithromycin alone as opposed to standard treatment with sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. MATERIAL/METHODS: We conducted a prospective, randomized, institutional clinical study comparing azithromycin to sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. Nineteen out of 75 patients fulfilled inclusion criteria and were randomized into 2 treatment regimens. Nine patients were treated with sulfadiazine and pyrimethamine and 10 patients with azithromycin at a dose of 500 mg qd. Main outcome measures assessed were time to sharpening of lesion borders, time to lesion scarring, time to disease inactivity, and treatment tolerance. RESULTS: Azithromycin monotherapy achieved lesion scarring and disease inactivity in all but 1 patient. Although no statistically significant difference was found between the 2 patient groups as regards main outcome measures for treatment efficacy, all median times to endpoints (days) were longer for the azithromycin group - time to sharpening of lesion borders on clinical evaluation (25.5 vs. 24) and masked evaluation of photographs (30.5 vs. 24), time to lesion scarring on clinical evaluation (73 vs. 47) and masked evaluation of photographs (71.5 vs. 36) and time to disease inactivity (73 vs. 49). Treatment tolerance was significantly better for the azithromycin group (p=0.0005). ConcluSIONS: Azithromycin monotherapy at a dose of 500 mg per day was shown to be effective and well-tolerated for the treatment of active, non-vision-threatening toxoplasmic retinochoroiditis. Duration of treatment was clinically longer for the azithromycin group.

Comparison of organ doses and image quality between CT and flat panel XperCT scans in wrist and inner ear examinations.

The aim of this study was to evaluate and compare organ doses delivered to patients in wrist and petrous bone examinations using a multislice spiral computed tomography (CT) and a C-arm cone-beam CT equipped with a flat-panel detector (XperCT). For this purpose, doses to the target organ, i.e. wrist or petrous bone, together with those to the most radiosensitive nearby organs, i.e. thyroid and eye lens, were measured and compared. Furthermore, image quality was compared for both imaging systems and different acquisition modes using a Catphan phantom. Results show that both systems guarantee adequate accuracy for diagnostic purposes for wrist and petrous bone examinations. Compared with the CT scanner, the XperCT system slightly reduces the dose to target organs and shortens the overall duration of the wrist examination. In addition, using the XperCT enables a reduction of the dose to the eye lens during head scans (skull base and ear examinations).

Limitations of stimulated echo acquisition mode (STEAM) techniques in cardiac applications.

Stimulated echoes are widely used for imaging functional tissue parameters such as diffusion coefficient, perfusion, and flow rates. They are potentially interesting for the assessment of various cardiac functions. However, severe limitations of the stimulated echo acquisition mode occur, which are related to the special dynamic properties of the beating heart and flowing blood. To the well-known signal decay due to longitudinal relaxation and through-plane motion between the preparation and the read-out period of the stimulated echoes, additional signal loss is often observed. As the prepared magnetization is fixed with respect to the tissue, this signal loss is caused by the tissue deformation during the cardiac cycle, which leads to a modification of the modulation frequency of the magnetization. These effects are theoretically derived and corroborated by phantom and in vivo experiments.

Contribution to the geology of Southern Turkey: new insights from the Mersin mélanges and from the Lycian and Antalya nappes

Abstract The study of fossil Tethyan continental margins implies the consideration of the oceanic domains to which they were connected. The advent of plate tectonics confirmed the importance of the detection of accretion-related mélanges. Ophiolitic mélanges are derived from both an upper ophiolitic obducting plate and a lower oceanic plate. Besides ophiolitic elements, the mélanges may incorporate parts of a magmatic arc and dismembered fragments of a passive continental margin. As the lower plate usually totally disappears during the obduction process, it can only be reconstructed from its elements found in the mélanges. Because of their key location at active margin boundaries, preserved accretion-related mélanges provide strong constraints on the geological evolution of former oceanic domains and their adjacent margins. The identification of Palaeotethyan remnants as accretionary series or reworked during the Late Triassic Eo-Cimmerian event, as well as the recognition of HugluPindos marginal sequences in southern Turkey and in the external Hellenides represent the main achievements of this work, making possible to establish new palaeogeographical correlations. The Mersin mélanges (Turkey), together with the Antalya and Mamonia (Cyprus) domains, are characterized by a series of exotic units found now south of the main Taurus range and compose the South-Taurides Exotic Units. The Mersin mélanges are subdivided in a Triassic and a Late Cretaceous unit. These units consist of the remnants of three major Tethyan oceans, the Palaeotethys, the Neotethys and the Huglu-Pindos. The definition and inventory of the Upper Antalya Nappes (Turkey) are still a matter of controversies and often conflicting interpretations. The recognition of Campanian radiolarians on top of the Kerner Gorge unit directly overlain by the Ordovician Seydi§ehir Fm. of the Tahtah Dag Nappe outlines a tectonic contact and demonstrates that the Upper Antalya Nappes system is composed of three different nappes, the Kerner Gorge, Bakirli and the Tahtah Dag nappes. Additionally, a limestone block in a doubtful tectonic position at the base of the Upper Antalya Nappes yielded for the first time two middle Viséan associations of foraminifers and problematic algae. The Tavas Nappe in the Lycian Nappes (Turkey) is classically divided into the Karadag, Teke Dere, Köycegiz and Haticeana units. As for the Mersin mélanges, the Tavas Nappe is highly composite and includes dismembered units belonging to the Palaeotethyan, Neotethyan and HugluPindos realms. The Karadag unit consists of a Gondwana-type platform succession ranging from the Late Devonian to the Late Triassic. It belongs to the Cimmerian Taurus terrane and was part of the northern passive margin of the Neotethys. The Teke Dere unit is composed of different parts of the Palaeotethyan succession including Late Carboniferous OIB-type basalts, Carboniferous MORB-type basalts, an Early Carboniferous siliciclastic series and a Middle Permian arc sequence. The microfauna and microflora identified in different horizons within the Teke Dere unit share strong biogeographical affinities with the northern Palaeotethyan borders. Kubergandian limestones in primary contact above the Early Carboniferous siliciclastics yielded a rich and diverse microfauna and microflora also identified in reworked cobbles within the Late Triassic Gevne Fm. of the Aladag unit (Turkey). The sedimentological evolution of the Köycegiz and Haticeana series is in many points similar to classical Pindos sequences. These series originated in the Huglu-Pindos Ocean along the northern passive margin of the Anatolian (Turkish transect) and Sitia-Pindos (Greek transect) terranes. Conglomerates at the base of the Lentas Unit in southern Crete (Greece) yielded a microfauna and microflora presenting also strong affinities with the northern borders of the Palaeotethys. This type of reworked sediments at the base of Pindos-like series would suggest a derivation from the Palaeotethyan active margin. -Résumé (French abstract) L'étude des marges continentales fossiles de l'espace téthysien implique d'étudier les domaines océaniques qui y étaient rattachés. Les progrès de la tectonique des plaques ont confirmé l'importance de la reconnaissance des mélanges d'accrétion. Les mélanges ophiolitiques dérivent d'une plaque supérieure ophiolitique qui obducte, et d'une plaque inférieure océanique. En plus d'éléments ophiolitiques, les mélanges peuvent aussi incorporer des parties d'un arc magmatique, ou des fragments d'une marge continentale passive. Comme la plaque inférieure disparaît généralement complètement durant le processus d'obduction, elle ne peut être reconstruite qu'au travers de ses éléments trouvés dans les mélanges. A cause de leur situation aux limites de marges actives, les mélanges d'accrétion bien préservés permettent de contraindre l'évolution géologique d'anciens océans et de leurs marges. L'identification de vestiges de la Paléotéthys en série d'accrétion ou remaniés lors de l'orogenèse éo-cimmérienne au Trias supérieur, ainsi que l'observation de séquences marginales de Huglu-Pinde en Turquie du sud et dans les Hellénides externes représentent les principaux résultats de ce travail, permettant d'établir de nouvelles corrélations paléogéographiques. Les mélanges de Mersin (Turquie), avec les domaines d'Antalya et de Mamonia (Chypre), sont caractérisés par des unités exotiques se trouvant au sud de la chaîne taurique, et forment les Unités Exotiques Sud-Tauriques. Les mélanges de Mersin sont subdivisés en une unité triasique, et une autre du Crétacé supérieur. Ces unités comprennent les reliques de trois principaux océans téthysiens, la Paléotéthys, la Néotéthys et Huglu-Pinde. L'inventaire et la définition des nappes supérieures d'Antalya (Turquie) sont encore matière à controverse et donne lieu à des interprétations conflictuelles. La découverte de radiolaires campaniens au sommet de l'unité de la Gorge de Kemer, directement recouverts par la formation ordovicienne de Seydisehir de la nappe du Tahtali Dag met en évidence un contact tectonique et démontre que les nappes supérieures sont composées de trois différentes nappes, celle de la Gorge de Kemer, celle du Bakirli et celle Tahtali Dag. De plus, un bloc de calcaire dont la position tectonique demeure incertaine à la base des nappes supérieures a fourni pour la première fois deux associations viséennes de foraminifères et d'algues problématiques. La nappe de Tavas dans les nappes lyciennes (Turquie) est séparée en unités du Karadag, du Teke Dere, de Köycegiz et d'Haticeana. Comme pour les mélanges de Mersin, la nappe de Tavas est composite et inclut des unités appartenant à la Paléotéthys, à la Néotéthys et à Huglu-Pinde. L'unité du Karadag est une plateforme carbonatée de type Gondwana se développant du Dévonien supérieur au Trias supérieur. Elle appartient au domaine cimmérien du Taurus et formait la marge nord de la Néotéthys. L'unité du Teke Dere est composée de différentes écailles paléotéthysiennes et inclut des basaltes d'île océanique du Carbonifère supérieur, des basaltes de ride océanique du Carbonifère, une série siliciclastique du Carbonifère supérieur et un arc du Permien moyen. Les microfaunes et -flores trouvées à différents niveaux de la série du Teke Dere partagent de fortes affinités paléogéographiques avec les marges nord de la Paléotéthys. Des calcaires du Kubergandien en contact primaire au-dessus de la série siliciclastique a donné de riches microfaunes et -flores, également identifiées dans des galets remaniés dans la formation de Gevne du Trias supérieur de l'Aladag. L'évolution sédimentologique des séries de Köycegiz et d'Haticeana sont très similaires aux séries classiques du Pinde. Ces séquences prennent leur racine dans l'océan de Huglu-Pinde, le long de la marge passive nord anatolienne (profil turc) et de la marge de Sitia-Pinde (profil grec). Des conglomérats à la base de l'unité de Lentas au sud de la Crète (Grèce) ont donné des microfaunes et flores partageant également de fortes similitudes avec les bordures nord de la Paléotéthys. Le type de sédiments remaniés à la base d'unités de type Pinde suggère une dérivation depuis la marge active de la Paléotéthys. -Résumé grand public (non-specialized abstract) Au début du 20ème siècle, Alfred Wegener bouleverse les croyances géologiques de l'époque et publie plusieurs articles sur la dérive ou la translation des continents. En utilisant des arguments géographiques (similarités des lignes de côte), paléontologiques (faunes et flores similaires) et climatiques (dépôts tropicaux et glaciaires), Wegener explique qu'il y a plusieurs millions d'années, les terres émergées actuelles ne devaient former qu'un seul et grand continent. La fin du 20ème siècle verra l'avènement de la théorie de la tectonique des plaques suite à la reconnaissance du cycle de Wilson, des rides médio-océaniques, des anomalies magnétiques dans les océans et des sutures océaniques qui représentent les reliques d'océans disparus. Le Cycle de Wilson se caractérise par une suite d'évènements géologiques majeurs pouvant se résumer de la manière suivante : (1) séparation d'un craton continental en deux parties, créant une limite de plaque divergente. C'est ce que l'on appelle un rift; (2) développement et croissance d'un océan entre ces deux blocs. Des roches magmatiques remontent à la surface de la terre et forment une chaîne de montagne sous-marine que l'on appelle ride médio-océanique ou dorsale. L'océan continue de se développer, et des sédiments se déposent à sa surface formant la suite ophiolitique ou trinité de Steinmann; (3) après une phase d'expansion plus ou moins longue, les conditions imposées aux limites des plaques à la surface de la terre changent, et l'océan se met à se refermer par disparition progressive (subduction) de sa croûte océanique sous une croûte continentale par exemple. Ceci crée une nouvelle limite de plaque, convergente cette fois; (4) la subduction de la plaque océanique sous la plaque continentale provoque une remontée de magma formant des chaînes volcaniques à la surface de la Terre ; (5) une fois que la plaque océanique a complètement disparu, les deux blocs préalablement séparés par l'océan font collision, formant ainsi une chaîne de montagne. Les chaînes de montagnes sont de manière générale formées par un empilement plus ou moins complexe de nappes. C'est au coeur de certaines de ces nappes que se trouvent les vestiges de l'océan disparu. Un des objectifs de ce travail était la recherche de ces vestiges dans le domaine téthysien de la Méditerranée orientale. Pour ce faire, nous avons parcourus une grande partie du sud de la Turquie, nous sommes allés à Chypre, dans le Sultanat d'Oman, en Iran, en Crète, et nous avons visités quelques îles grecques du Dodécanèse. La région de la Méditerranée orientale est une zone qui a été tectoniquement très active, et qui continue de l'être de nos jours par des phénomènes de subduction (ex. les volcans de Santorin), et par des mouvements coulissants entre des plaques continentales (ex. la faille nord-anatolienne) qui donnent régulièrement lieu à des tremblements de terre. Pour le géologue, la complexité de ces zones d'étude réside dans le fait que les chaînes de montagne actuelles ne contiennent en général pas seulement les restes d'un océan, mais bien de plusieurs bassins océaniques qui se sont succédés dans l'espace et dans le temps. Les nappes qui se trouvent au sud de la Turquie et dans le Dodécanèse forment un important jalon dans la chaîne alpine qui s'étend depuis les Alpes jusque dans l'Himalaya. L'idée d'un continuum au coeur de ce système se basait principalement sur l'âge des océans et sur la reconnaissance de similarités dans l'évolution des séries sédimentaires. La localisation des vestiges de la Paléotéthys ainsi que l'identification des séries sédimentaires ayant appartenu à l'océan de HugluPinde repris sous forme de nappes en Turquie et en Grèce sont cruciales pour permettre de bonnes corrélations locales et régionales. La reconnaissance, la compréhension et l'interprétation de ces séries sédimentaires permettront d'élaborer un modèle d'évolution géodynamique régional, s'appuyant sur des faits de terrains indiscutables, et prenant en compte les contraintes globales que ce genre d'exercice implique.

Solving ambiguities in contig assembly of Idiomarina loihiensis L2TR chromosome by in silico analyses.

Nucleotide composition analyses of bacterial genomes such as cumulative GC skew highlight the atypical, strongly asymmetric architecture of the recently published chromosome of Idiomarina loihiensis L2TR, suggesting that an inversion of a 600-kb chromosomal segment occurred. The presence of 3.4-kb inverted repeated sequences at the borders of the putative rearrangement supports this hypothesis. Reverting in silico this segment restores (1) a symmetric chromosome architecture; (2) the co-orientation of transcription of all rRNA operons with DNA replication; and (3) a better conservation of gene order between this chromosome and other gamma-proteobacterial ones. Finally, long-range PCRs encompassing the ends of the 600-kb segment reveal the existence of the reverted configuration but not of the published one. This demonstrates how cumulative nucleotide-skew analyses can validate genome assemblies.

Direct Fourier Tomographic Reconstruction Image-To-Image Filter

We present an open-source ITK implementation of a directFourier method for tomographic reconstruction, applicableto parallel-beam x-ray images. Direct Fourierreconstruction makes use of the central-slice theorem tobuild a polar 2D Fourier space from the 1D transformedprojections of the scanned object, that is resampled intoa Cartesian grid. Inverse 2D Fourier transform eventuallyyields the reconstructed image. Additionally, we providea complex wrapper to the BSplineInterpolateImageFunctionto overcome ITKâeuro?s current lack for image interpolatorsdealing with complex data types. A sample application ispresented and extensively illustrated on the Shepp-Loganhead phantom. We show that appropriate input zeropaddingand 2D-DFT oversampling rates together with radial cubicb-spline interpolation improve 2D-DFT interpolationquality and are efficient remedies to reducereconstruction artifacts.

Three-dimensional magnetic resonance myocardial motion tracking from a single image plane.

Three-dimensional imaging for the quantification of myocardial motion is a key step in the evaluation of cardiac disease. A tagged magnetic resonance imaging method that automatically tracks myocardial displacement in three dimensions is presented. Unlike other techniques, this method tracks both in-plane and through-plane motion from a single image plane without affecting the duration of image acquisition. A small z-encoding gradient is subsequently added to the refocusing lobe of the slice-selection gradient pulse in a slice following CSPAMM acquisition. An opposite polarity z-encoding gradient is added to the orthogonal tag direction. The additional z-gradients encode the instantaneous through plane position of the slice. The vertical and horizontal tags are used to resolve in-plane motion, while the added z-gradients is used to resolve through-plane motion. Postprocessing automatically decodes the acquired data and tracks the three-dimensional displacement of every material point within the image plane for each cine frame. Experiments include both a phantom and in vivo human validation. These studies demonstrate that the simultaneous extraction of both in-plane and through-plane displacements and pathlines from tagged images is achievable. This capability should open up new avenues for the automatic quantification of cardiac motion and strain for scientific and clinical purposes.

Pain assessment in PICU and NICU: Have we got it right?

Pain assessment in critically ill infants and nonverbal children remains a challenge for health professionals. Despite the numerous pain observational measures that have been developed or adapted for infants and children with impaired communication, pain prevalence in paediatric and neonatal intensive care unit remains too high. As pain assessment has been recognised as a pre-requisite for appropriate pain management, much effort was put in the validation or the adaptation of pain measures with little emphasis on implementation of these instruments into practice. Only a few studies demonstrated the benefit of using standardised protocols for the management of pain to guide practice with variable effects. When standardised protocols are undeniably useful in practice, they do not replace health professionals' clinical reasoning necessary to care for individuals. The diversity of the PICU population makes that pain scores need to be interpreted within its clinical context. This session will present pain assessment as a complex transaction that describes structured clinical reasoning from expert nurses that goes beyond the "silver" standard of hetero-evaluation of pain in non-communicative children. Besides pain scores, several patients and nurses factors play a major role in making decisions about analgesia and/or sedation. Patient's clinical instability, change in patient's clinical status, source for observed agitated behaviour, patient's known reactions to analgesia and sedation and anticipation of risks are factors that should be taken into account when implementing pain assessment and management guidelines in PICU and NICU.

An Efficient Segmentation Method for Ultrasound Images based on a Semi-supervised Approach and Patch-based Features

Segmenting ultrasound images is a challenging problemwhere standard unsupervised segmentation methods such asthe well-known Chan-Vese method fail. We propose in thispaper an efficient segmentation method for this class ofimages. Our proposed algorithm is based on asemi-supervised approach (user labels) and the use ofimage patches as data features. We also consider thePearson distance between patches, which has been shown tobe robust w.r.t speckle noise present in ultrasoundimages. Our results on phantom and clinical data show avery high similarity agreement with the ground truthprovided by a medical expert.

Simulations of action of DNA topoisomerases to investigate boundaries and shapes of spaces of knots.

The configuration space available to randomly cyclized polymers is divided into subspaces accessible to individual knot types. A phantom chain utilized in numerical simulations of polymers can explore all subspaces, whereas a real closed chain forming a figure-of-eight knot, for example, is confined to a subspace corresponding to this knot type only. One can conceptually compare the assembly of configuration spaces of various knot types to a complex foam where individual cells delimit the configuration space available to a given knot type. Neighboring cells in the foam harbor knots that can be converted into each other by just one intersegmental passage. Such a segment-segment passage occurring at the level of knotted configurations corresponds to a passage through the interface between neighboring cells in the foamy knot space. Using a DNA topoisomerase-inspired simulation approach we characterize here the effective interface area between neighboring knot spaces as well as the surface-to-volume ratio of individual knot spaces. These results provide a reference system required for better understanding mechanisms of action of various DNA topoisomerases.

Global tractography with embedded anatomical priors for quantitative connectivity analysis.

Tractography algorithms provide us with the ability to non-invasively reconstruct fiber pathways in the white matter (WM) by exploiting the directional information described with diffusion magnetic resonance. These methods could be divided into two major classes, local and global. Local methods reconstruct each fiber tract iteratively by considering only directional information at the voxel level and its neighborhood. Global methods, on the other hand, reconstruct all the fiber tracts of the whole brain simultaneously by solving a global energy minimization problem. The latter have shown improvements compared to previous techniques but these algorithms still suffer from an important shortcoming that is crucial in the context of brain connectivity analyses. As no anatomical priors are usually considered during the reconstruction process, the recovered fiber tracts are not guaranteed to connect cortical regions and, as a matter of fact, most of them stop prematurely in the WM; this violates important properties of neural connections, which are known to originate in the gray matter (GM) and develop in the WM. Hence, this shortcoming poses serious limitations for the use of these techniques for the assessment of the structural connectivity between brain regions and, de facto, it can potentially bias any subsequent analysis. Moreover, the estimated tracts are not quantitative, every fiber contributes with the same weight toward the predicted diffusion signal. In this work, we propose a novel approach for global tractography that is specifically designed for connectivity analysis applications which: (i) explicitly enforces anatomical priors of the tracts in the optimization and (ii) considers the effective contribution of each of them, i.e., volume, to the acquired diffusion magnetic resonance imaging (MRI) image. We evaluated our approach on both a realistic diffusion MRI phantom and in vivo data, and also compared its performance to existing tractography algorithms.