Volume-targeted and whole-heart coronary magnetic resonance angiography using an intravascular contrast agent.

PURPOSE: To compare volume-targeted and whole-heart coronary magnetic resonance angiography (MRA) after the administration of an intravascular contrast agent. MATERIALS AND METHODS: Six healthy adult subjects underwent a navigator-gated and -corrected (NAV) free breathing volume-targeted cardiac-triggered inversion recovery (IR) 3D steady-state free precession (SSFP) coronary MRA sequence (t-CMRA) (spatial resolution = 1 x 1 x 3 mm(3)) and high spatial resolution IR 3D SSFP whole-heart coronary MRA (WH-CMRA) (spatial resolution = 1 x 1 x 2 mm(3)) after the administration of an intravascular contrast agent B-22956. Subjective and objective image quality parameters including maximal visible vessel length, vessel sharpness, and visibility of coronary side branches were evaluated for both t-CMRA and WH-CMRA. RESULTS: No significant differences (P = NS) in image quality were observed between contrast-enhanced t-CMRA and WH-CMRA. However, using an intravascular contrast agent, significantly longer vessel segments were measured on WH-CMRA vs. t-CMRA (right coronary artery [RCA] 13.5 +/- 0.7 cm vs. 12.5 +/- 0.2 cm; P < 0.05; and left circumflex coronary artery [LCX] 11.9 +/- 2.2 cm vs. 6.9 +/- 2.4 cm; P < 0.05). Significantly more side branches (13.3 +/- 1.2 vs. 8.7 +/- 1.2; P < 0.05) were visible for the left anterior descending coronary artery (LAD) on WH-CMRA vs. t-CMRA. Scanning time and navigator efficiency were similar for both techniques (t-CMRA: 6.05 min; 49% vs. WH-CMRA: 5.51 min; 54%, both P = NS). CONCLUSION: Both WH-CMRA and t-CMRA using SSFP are useful techniques for coronary MRA after the injection of an intravascular blood-pool agent. However, the vessel conspicuity for high spatial resolution WH-CMRA is not inferior to t-CMRA, while visible vessel length and the number of visible smaller-diameter vessels and side-branches are improved.

Flow-targeted inversion-prepared b-TFE coronary MR angiography: initial results in patients.

PURPOSE: Visualization of coronary blood flow in the right and left coronary system in volunteers and patients by means of a modified inversion-prepared bright-blood coronary magnetic resonance angiography (cMRA) sequence. MATERIALS AND METHODS: cMRA was performed in 14 healthy volunteers and 19 patients on a 1.5 Tesla MR system using a free-breathing 3D balanced turbo field echo (b-TFE) sequence with radial k-space sampling. For magnetization preparation a slab selective and a 2D selective inversion pulse were used for the right and left coronary system, respectively. cMRA images were evaluated in terms of clinically relevant stenoses (< 50 %) and compared to conventional catheter angiography. Signal was measured in the coronary arteries (coro), the aorta (ao) and in the epicardial fat (fat) to determine SNR and CNR. In addition, maximal visible vessel length, and vessel border definition were analyzed. RESULTS: The use of a selective inversion pre-pulse allowed direct visualization of the coronary blood flow in the right and left coronary system. The measured SNR and CNR, vessel length, and vessel sharpness in volunteers (SNR coro: 28.3 +/- 5.0; SNR ao: 37.6 +/- 8.4; CNR coro-fat: 25.3 +/- 4.5; LAD: 128.0 cm +/- 8.8; RCA: 74.6 cm +/- 12.4; Sharpness: 66.6 % +/- 4.8) were slightly increased compared to those in patients (SNR coro: 24.1 +/- 3.8; SNR ao: 33.8 +/- 11.4; CNR coro-fat: 19.9 +/- 3.3; LAD: 112.5 cm +/- 13.8; RCA: 69.6 cm +/- 16.6; Sharpness: 58.9 % +/- 7.9; n.s.). In the patient study the assessment of 42 coronary segments lead to correct identification of 10 clinically relevant stenoses. CONCLUSION: The modification of a previously published inversion-prepared cMRA sequence allowed direct visualization of the coronary blood flow in the right as well as in the left coronary system. In addition, this sequence proved to be highly sensitive regarding the assessment of clinically relevant stenotic lesions.

Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T.

BACKGROUND AND OBJECTIVES: The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). DESIGN: We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. RESULTS: T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P ≤ 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. CONCLUSIONS: There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura.

The impact of spatial resolution and respiratory motion on MR imaging of atherosclerotic plaque.

PURPOSE: To examine the impact of spatial resolution and respiratory motion on the ability to accurately measure atherosclerotic plaque burden and to visually identify atherosclerotic plaque composition. MATERIALS AND METHODS: Numerical simulations of the Bloch equations and vessel wall phantom studies were performed for different spatial resolutions by incrementally increasing the field of view. In addition, respiratory motion was simulated based on a measured physiologic breathing pattern. RESULTS: While a spatial resolution of > or = 6 pixels across the wall does not result in significant errors, a resolution of < or = 4 pixels across the wall leads to an overestimation of > 20%. Using a double-inversion T2-weighted turbo spin echo sequence, a resolution of 1 pixel across equally thick tissue layers (fibrous cap, lipid, smooth muscle) and a respiratory motion correction precision (gating window) of three times the thickness of the tissue layer allow for characterization of the different coronary wall components. CONCLUSIONS: We found that measurements in low-resolution black blood images tend to overestimate vessel wall area and underestimate lumen area.

Improved three-dimensional free-breathing coronary magnetic resonance angiography using gadocoletic acid (B-22956) for intravascular contrast enhancement.

PURPOSE: To evaluate gadocoletic acid (B-22956), a gadolinium-based paramagnetic blood pool agent, for contrast-enhanced coronary magnetic resonance angiography (MRA) in a Phase I clinical trial, and to compare the findings with those obtained using a standard noncontrast T2 preparation sequence. MATERIALS AND METHODS: The left coronary system was imaged in 12 healthy volunteers before B-22956 application and 5 (N = 11) and 45 (N = 7) minutes after application of 0.075 mmol/kg of body weight (BW) of B-22956. Additionally, imaging of the right coronary system was performed 23 minutes after B-22956 application (N = 6). A three-dimensional gradient echo sequence with T2 preparation (precontrast) or inversion recovery (IR) pulse (postcontrast) with real-time navigator correction was used. Assessment of the left and right coronary systems was performed qualitatively (a 4-point visual score for image quality) and quantitatively in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, visible vessel length, maximal luminal diameter, and the number of visible side branches. RESULTS: Significant (P < 0.01) increases in SNR (+42%) and CNR (+86%) were noted five minutes after B-22956 application, compared to precontrast T2 preparation values. A significant increase in CNR (+40%, P < 0.05) was also noted 45 minutes postcontrast. Vessels (left anterior descending artery (LAD), left coronary circumflex (LCx), and right coronary artery (RCA)) were also significantly (P < 0.05) sharper on postcontrast images. Significant increases in vessel length were noted for the LAD (P < 0.05) and LCx and RCA (both P < 0.01), while significantly more side branches were noted for the LAD and RCA (both P < 0.05) when compared to precontrast T2 preparation values. CONCLUSION: The use of the intravascular contrast agent B-22956 substantially improves both objective and subjective parameters of image quality on high-resolution three-dimensional coronary MRA. The increase in SNR, CNR, and vessel sharpness minimizes current limitations of coronary artery visualization with high-resolution coronary MRA.

Spatial visualization of DNA in solution.

An image analysis method is presented which allows for the reconstruction of the three-dimensional path of filamentous objects from two of their projections. Starting with stereo pairs, this method is used to trace the trajectory of DNA molecules embedded in vitreous ice and leads to a faithful representation of their three-dimensional shape in solution. This computer-aided reconstruction is superior to the subjective three-dimensional impression generated by observation of stereo pairs of micrographs because it enables one to look at the reconstructed molecules from any chosen direction and distance and allows quantitative analysis such as determination of distances, curvature, persistence length, and writhe of DNA molecules in solution.

The geometric structure of the brain fiber pathways.

The structure of the brain as a product of morphogenesis is difficult to reconcile with the observed complexity of cerebral connectivity. We therefore analyzed relationships of adjacency and crossing between cerebral fiber pathways in four nonhuman primate species and in humans by using diffusion magnetic resonance imaging. The cerebral fiber pathways formed a rectilinear three-dimensional grid continuous with the three principal axes of development. Cortico-cortical pathways formed parallel sheets of interwoven paths in the longitudinal and medio-lateral axes, in which major pathways were local condensations. Cross-species homology was strong and showed emergence of complex gyral connectivity by continuous elaboration of this grid structure. This architecture naturally supports functional spatio-temporal coherence, developmental path-finding, and incremental rewiring with correlated adaptation of structure and function in cerebral plasticity and evolution.

Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy

PURPOSE: To illustrate the evolution of brain perfusion-weighted magnetic resonance imaging (PWI-MRI) in severe neonatal hypoxic-ischemic (HI) encephalopathy, and its possible relation to further neurodevelopmental outcome. MATERIALS AND METHODS: Two term neonates with HI encephalopathy underwent an early and a late MRI, including PWI. They were followed until eight months of age. A total of three "normal controls" were also included. Perfusion maps were obtained, and relative cerebral blood flow (rCBF) and cerebral blood volume (rCBV) values were measured. RESULTS: Compared to normal neonates, a hyperperfusion (increased rCBF and rCBV) was present on early scans in the whole brain. On late scans, hyperperfusion persisted in cortical gray matter (normalization of rCBF and rCBV ratios in white matter and basal ganglia, but not in cortical gray matter). Diffusion-weighted imaging (DWI) was normalized, and extensive lesions became visible on T2-weighted images. Both patients displayed very abnormal outcome: Patient 2 with the more abnormal early and late hyperperfusion being the worst. CONCLUSION: PWI in HI encephalopathy did not have the same temporal evolution as DWI, and remained abnormal for more than one week after injury. This could be a marker of an ongoing mechanism underlying severe neonatal HI encephalopathy. Evolution of PWI might help to predict further neurodevelopmental outcome.

Baseline Results of an Acute Ischemic Stroke Registry Including Acute Multimodal Imaging (ASTRAL)

Background: The DEFUSE (n_74) and EPITHET (n_101) studies have in common that a baseline MRI was obtained prior to treatment (tPA in DEFUSE; tPA or placebo in EPITHET) in the 3-6 hour time-window. There were however important methodological differences between the studies. A standardized reanalysis of pooled data was undertaken to determine the effect of these differences on baseline characteristics and study outcomes. Methods: To standardize the studies 1) the DWI and PWI source images were reprocessed and segmented using automated image processing software (RAPID); 2) patients were categorized according to their baseline MRI profile as either Target Mismatch (PWITmax_6/DWI ratio_ 1.8 and an absolute mismatch _15mL), Malignant (DWI or PWITmax_10 lesion _ 100 mL), or No Mismatch. 3) favorable clinical response was defined as NIHSS score of 0-1 or a _8 points improvement on the NIHSSS at day 90. Results: Prior to standardization there was no difference in the proportion of Target Mismatch patients between EPITHET and DEFUSE (54% vs 49%, p_0.6), but the EPITHET study had more patients with the Malignant profile than DEFUSE (35% vs 9%, p_0.01) and fewer patients that had No Mismatch (11% vs 42%, p_0.01). These differences in baseline MRI profiles between EPITHET and DEFUSE were largely eliminated by standardized processing of PWI and DWI images with RAPID software (Target Mismatch 49% vs 48%; Malignant 15% vs 8%; No Mismatch 36% vs 25%; p_NS for all comparisons) Reperfusion was strongly associated with a favorable clinical response in mismatch patients (figure). This relationship was not affected by the standardization procedures (pooled odds ratio of 8.8 based on original data and 6.6 based on standardized data). Conclusion: Standardization of image analyses procedures in acute stroke is important as non-standardized techniques introduce significant variability in DWI and PWI imaging characteristics. Despite methodological differences, the DEFUSE and EPITHET studies show a consistent and robust association between reperfusion and favorable clinical response in Target Mismatch patients regardless of standardization. These data support an RCT of iv tPA in the 3-6 hour time-window for Target Mismatch patients identified using RAPID.

Occlusive arterial disease of abdominal aorta and lower extremities: comparison of helical CT angiography with transcatheter angiography.

The purpose of this study was to evaluate helical CT angiography in the assessment of occlusive arterial disease of abdominal aorta and the lower extremities. Sixteen patients underwent both transcatheter angiography and helical CT. Helical CT was inconclusive in 6.2% of segments whereas angiography was inconclusive in 5%. The overall sensitivity of helical CT was 91% and specificity 93%. Segmental analysis found a sensitivity of 43% in infrapopliteal arteries, and a specificity of 86%.

Micromeasurement of total and regional CO2 productions in the one-day-old chick embryo.

A conductometric micromethod combined with image analysis system has been developed allowing to determine the CO2 production within 'two-dimensional' tissues, i.e., flat and thin cell layers or epithelial sheets. The preparation was mounted into an airtight chamber separated in two compartments by a thin silicone membrane permeable to gases. The lower compartment contained the nutritive medium and the preparation. The upper compartment and a conductivity measuring capillary connected in series were perfused with a solution of Ba(OH)2. The CO2 produced by the tissue precipitated as BaCO3 and the resulting decrease of electrical conductivity was linearly related to the total CO2 production. In addition, the pattern of CO2 production was directly observable as the BaCO3 crystals formed upon the silicone membrane over the regions which produced CO2. The spatial distribution of the crystals was quantified by video image processing and the regional CO2 production evaluated with a spatial resolution of 100 microns. This new microtechnique was originally developed to study the CO2 production in the early chick blastoderm which is a disc 1-5 cells thick. At the stage of young neurula the CO2 production was found to be 235 +/- 37 nmol.h-1 (mean +/- SD; n = 10) per blastoderm and large variations of local CO2 production were detected from one region to another (from 0.6 to 6.5 nmol.h-1.mm-2). These results indicate a high metabolic and functional differentiation of cells within the blastoderm. The possible applications and improvements of such a microtechnique are discussed.

Multi-scale systems analysis of plant development : beyond cellular signaling and tissue morphodynamics

Les plantes sont essentielles pour les sociétés humaines. Notre alimentation quotidienne, les matériaux de constructions et les sources énergétiques dérivent de la biomasse végétale. En revanche, la compréhension des multiples aspects développementaux des plantes est encore peu exploitée et représente un sujet de recherche majeur pour la science. L'émergence des technologies à haut débit pour le séquençage de génome à grande échelle ou l'imagerie de haute résolution permet à présent de produire des quantités énormes d'information. L'analyse informatique est une façon d'intégrer ces données et de réduire la complexité apparente vers une échelle d'abstraction appropriée, dont la finalité est de fournir des perspectives de recherches ciblées. Ceci représente la raison première de cette thèse. En d'autres termes, nous appliquons des méthodes descriptives et prédictives combinées à des simulations numériques afin d'apporter des solutions originales à des problèmes relatifs à la morphogénèse à l'échelle de la cellule et de l'organe. Nous nous sommes fixés parmi les objectifs principaux de cette thèse d'élucider de quelle manière l'interaction croisée des phytohormones auxine et brassinosteroïdes (BRs) détermine la croissance de la cellule dans la racine du méristème apical d'Arabidopsis thaliana, l'organisme modèle de référence pour les études moléculaires en plantes. Pour reconstruire le réseau de signalement cellulaire, nous avons extrait de la littérature les informations pertinentes concernant les relations entre les protéines impliquées dans la transduction des signaux hormonaux. Le réseau a ensuite été modélisé en utilisant un formalisme logique et qualitatif pour pallier l'absence de données quantitatives. Tout d'abord, Les résultats ont permis de confirmer que l'auxine et les BRs agissent en synergie pour contrôler la croissance de la cellule, puis, d'expliquer des observations phénotypiques paradoxales et au final, de mettre à jour une interaction clef entre deux protéines dans la maintenance du méristème de la racine. Une étude ultérieure chez la plante modèle Brachypodium dystachion (Brachypo- dium) a révélé l'ajustement du réseau d'interaction croisée entre auxine et éthylène par rapport à Arabidopsis. Chez ce dernier, interférer avec la biosynthèse de l'auxine mène à la formation d'une racine courte. Néanmoins, nous avons isolé chez Brachypodium un mutant hypomorphique dans la biosynthèse de l'auxine qui affiche une racine plus longue. Nous avons alors conduit une analyse morphométrique qui a confirmé que des cellules plus anisotropique (plus fines et longues) sont à l'origine de ce phénotype racinaire. Des analyses plus approfondies ont démontré que la différence phénotypique entre Brachypodium et Arabidopsis s'explique par une inversion de la fonction régulatrice dans la relation entre le réseau de signalisation par l'éthylène et la biosynthèse de l'auxine. L'analyse morphométrique utilisée dans l'étude précédente exploite le pipeline de traitement d'image de notre méthode d'histologie quantitative. Pendant la croissance secondaire, la symétrie bilatérale de l'hypocotyle est remplacée par une symétrie radiale et une organisation concentrique des tissus constitutifs. Ces tissus sont initialement composés d'une douzaine de cellules mais peuvent aisément atteindre des dizaines de milliers dans les derniers stades du développement. Cette échelle dépasse largement le seuil d'investigation par les moyens dits 'traditionnels' comme l'imagerie directe de tissus en profondeur. L'étude de ce système pendant cette phase de développement ne peut se faire qu'en réalisant des coupes fines de l'organe, ce qui empêche une compréhension des phénomènes cellulaires dynamiques sous-jacents. Nous y avons remédié en proposant une stratégie originale nommée, histologie quantitative. De fait, nous avons extrait l'information contenue dans des images de très haute résolution de sections transverses d'hypocotyles en utilisant un pipeline d'analyse et de segmentation d'image à grande échelle. Nous l'avons ensuite combiné avec un algorithme de reconnaissance automatique des cellules. Cet outil nous a permis de réaliser une description quantitative de la progression de la croissance secondaire révélant des schémas développementales non-apparents avec une inspection visuelle classique. La formation de pôle de phloèmes en structure répétée et espacée entre eux d'une longueur constante illustre les bénéfices de notre approche. Par ailleurs, l'exploitation approfondie de ces résultats a montré un changement de croissance anisotropique des cellules du cambium et du phloème qui semble en phase avec l'expansion du xylème. Combinant des outils génétiques et de la modélisation biomécanique, nous avons démontré que seule la croissance plus rapide des tissus internes peut produire une réorientation de l'axe de croissance anisotropique des tissus périphériques. Cette prédiction a été confirmée par le calcul du ratio des taux de croissance du xylème et du phloème au cours de développement secondaire ; des ratios élevés sont effectivement observés et concomitant à l'établissement progressif et tangentiel du cambium. Ces résultats suggèrent un mécanisme d'auto-organisation établi par un gradient de division méristématique qui génèrent une distribution de contraintes mécaniques. Ceci réoriente la croissance anisotropique des tissus périphériques pour supporter la croissance secondaire. - Plants are essential for human society, because our daily food, construction materials and sustainable energy are derived from plant biomass. Yet, despite this importance, the multiple developmental aspects of plants are still poorly understood and represent a major challenge for science. With the emergence of high throughput devices for genome sequencing and high-resolution imaging, data has never been so easy to collect, generating huge amounts of information. Computational analysis is one way to integrate those data and to decrease the apparent complexity towards an appropriate scale of abstraction with the aim to eventually provide new answers and direct further research perspectives. This is the motivation behind this thesis work, i.e. the application of descriptive and predictive analytics combined with computational modeling to answer problems that revolve around morphogenesis at the subcellular and organ scale. One of the goals of this thesis is to elucidate how the auxin-brassinosteroid phytohormone interaction determines the cell growth in the root apical meristem of Arabidopsis thaliana (Arabidopsis), the plant model of reference for molecular studies. The pertinent information about signaling protein relationships was obtained through the literature to reconstruct the entire hormonal crosstalk. Due to a lack of quantitative information, we employed a qualitative modeling formalism. This work permitted to confirm the synergistic effect of the hormonal crosstalk on cell elongation, to explain some of our paradoxical mutant phenotypes and to predict a novel interaction between the BREVIS RADIX (BRX) protein and the transcription factor MONOPTEROS (MP),which turned out to be critical for the maintenance of the root meristem. On the same subcellular scale, another study in the monocot model Brachypodium dystachion (Brachypodium) revealed an alternative wiring of auxin-ethylene crosstalk as compared to Arabidopsis. In the latter, increasing interference with auxin biosynthesis results in progressively shorter roots. By contrast, a hypomorphic Brachypodium mutant isolated in this study in an enzyme of the auxin biosynthesis pathway displayed a dramatically longer seminal root. Our morphometric analysis confirmed that more anisotropic cells (thinner and longer) are principally responsible for the mutant root phenotype. Further characterization pointed towards an inverted regulatory logic in the relation between ethylene signaling and auxin biosynthesis in Brachypodium as compared to Arabidopsis, which explains the phenotypic discrepancy. Finally, the morphometric analysis of hypocotyl secondary growth that we applied in this study was performed with the image-processing pipeline of our quantitative histology method. During its secondary growth, the hypocotyl reorganizes its primary bilateral symmetry to a radial symmetry of highly specialized tissues comprising several thousand cells, starting with a few dozens. However, such a scale only permits observations in thin cross-sections, severely hampering a comprehensive analysis of the morphodynamics involved. Our quantitative histology strategy overcomes this limitation. We acquired hypocotyl cross-sections from tiled high-resolution images and extracted their information content using custom high-throughput image processing and segmentation. Coupled with an automated cell type recognition algorithm, it allows precise quantitative characterization of vascular development and reveals developmental patterns that were not evident from visual inspection, for example the steady interspace distance of the phloem poles. Further analyses indicated a change in growth anisotropy of cambial and phloem cells, which appeared in phase with the expansion of xylem. Combining genetic tools and computational modeling, we showed that the reorientation of growth anisotropy axis of peripheral tissue layers only occurs when the growth rate of central tissue is higher than the peripheral one. This was confirmed by the calculation of the ratio of the growth rate xylem to phloem throughout secondary growth. High ratios are indeed observed and concomitant with the homogenization of cambium anisotropy. These results suggest a self-organization mechanism, promoted by a gradient of division in the cambium that generates a pattern of mechanical constraints. This, in turn, reorients the growth anisotropy of peripheral tissues to sustain the secondary growth.

Computer-assisted two-dimensional preoperative planning for total hip arthroplasty: clinical evaluation.

The purpose of this study is to clinically validate a new two-dimensional preoperative planning software for cementless total hip arthroplasty (THA). Manual and two-dimensional computer-assisted planning were compared by an independent observer for each of the 30 patients with osteoarthritis who underwent THA. This study showed that there were no statistical differences between the results of both preoperative plans in terms of stem size and neck length (<1 size) and hip rotation center position (<5 mm). Two-dimensional computer-assisted preoperative planning provided successful results comparable to those using the manual procedure, thereby allowing the surgeon to simulate various stem designs easily.