Evolution des lésions ischémiques aiguës en IRM de diffusion

Within the first 24 hours after IV-rtPA, diffusion-weighted ischemic lesions can reverse, remain stable or grow. The aim of this thesis is to study these reversal and growth phenomena, to better understand their pathophysiology and to gain insight into the prognostic value of diffusion lesion volume. Diffusion lesion reversal was reported in animals and humans after arterial recanalization. In our sample of 155 patients, we studied this phenomenon with MRI performed before and 24 hours after thrombolysis using a voxel-based approach. First, we demonstrated that 24 hours diffusion reversal was frequent and sustained on a late MRI (median 54h) for over two-thirds of the voxels. Second, sustained reversal was associated with 24hr neurological improvement (OR=1.15, IC95%[ 1.03-1.27], P=0.008 per 1mL). Animal studies have suggested that white matter is more resistant to ischemia than gray matter. In humans, we confirmed that diffusion lesion reversal was more frequent in white matter than in gray matter and disclosed that white matter voxels were more prone to reverse than gray matter voxels. The amount of white matter in the initial diffusion lesion may therefore be a significant determinant of reversibility. Large diffusion lesion volume is associated with poor outcome. However, revascularization therapy can prevent infarct growth or even promote lesion reversal. It is still unclear whether these treatments are beneficial in patients with large diffusion volumes (≥70mL). In our series including 267 patients with middle cerebral artery stroke treated with thrombolysis, 54 patients had a ≥70mL diffusion volume, of which 12(22%) had a 3 month favorable outcome. Odds-ratio of recanalization for favorable outcome in the ≥70mL group was 4.87 [1.15-20.73], P=0.03 supporting a benefit of recanalization in this subgroup. Diffusion lesions growth is usually located within the ischemic penumbra. We hypothesized that if it occurred beyond its boundaries, it would translate into neurological deterioration. Unexplained early neurological deterioration is frequent (70% of early neurological deteriorations, 7% in our series of 309 thrombolysed patients) and its causes are not well-known (no symptomatic intra cerebral hemorrhage, malignant edema or post-stroke seizure). We confirmed our hypothesis in these patients with diffusion growth beyond the penumbra. This growth occurred in 9 of the 10 studied patients (7-137mL; > 10mL in 8 patients) and it was significantly larger than in the 30 controls with early neurological deterioration (P=0.047). Moreover its topography matched the neurological items that deteriorated. All together, these results contribute to a better understanding of acute ischemic lesions using diffusion-weighted imaging and may offer perspectives to adapt individual patient care.Après traitement d’un AIC par thrombolyse, les lésions ischémiques en diffusion peuvent être réversibles, stables et/ou progresser. Cette thèse a pour objectif d’étudier en IRM ces phénomènes de réversibilité et de progression, de mieux comprendre leur physiopathologie, et d’appréhender le rôle pronostic du volume des lésions en diffusion. La réversibilité en diffusion a été rapportée après recanalisation artérielle, chez l’animal et chez l’homme. Dans notre cohorte de 155 patients, nous avons étudié ce phénomène par une analyse voxel à voxel sur des IRM avant et 24h après thrombolyse. Nous avons montré que la réversibilité des anomalies en diffusion à 24h était fréquente et surtout persistait sur une IRM plus tardive (médiane 54h) pour plus de 70% des voxels [58.0-85.9], suggérant que ce phénomène n’était pas transitoire. De plus, seule la réversibilité permanente était associée à une amélioration neurologique à 24h (OR=1.15, CI95%[ 1.03-1.27], P=0.008 par mL). La substance blanche a été décrite comme plus résistante à l’ischémie sur des modèles murins. Chez l’homme, nous avons confirmé la prédominance en substance blanche des phénomènes de réversibilité, avec une probabilité de régression plus importante pour un voxel de substance blanche que pour un voxel de substance grise. Ces résultats pourraient aider à identifier avant décision thérapeutique les lésions potentiellement réversibles, c'est-à-dire celles prédominant en substance blanche. Même s’il existe une association entre le volume de lésion en diffusion avant traitement et le pronostic fonctionnel à 3 mois, la réversibilité des lésions pourrait remettre en cause les seuils de volume au-delà desquels une revascularisation pourrait être futile. En effet, en limitant la progression des anomalies en diffusion et en favorisant leur régression, la revascularisation pourrait aussi avoir un impact sur le pronostic fonctionnel des patients avec un large volume lésionnel (≥70mL). Dans une population de 267 patients avec un infarctus de l’artère cérébrale moyenne traités par thrombolyse, 54 avaient un volume en diffusion ≥70mL, dont 12(22%) avaient un pronostic fonctionnel favorable à 3 mois. L’odds-ratio de la recanalisation pour le pronostic fonctionnel favorable dans le groupe ≥70mL était de 4.87 [1.15-20.73], P=0.03 en faveur d’un impact positif de la recanalisation même dans ce groupe. En l’absence de reperfusion, les anomalies en diffusion progressent au sein de la pénombre ischémique. Selon le modèle « core/pénombre », cette progression lésionnelle ne doit pas s’accompagner d’une aggravation neurologique. Nous avons formulé l’hypothèse que si elle survenait au-delà de la pénombre (dans des zones asymptomatiques), elle s’accompagnerait d’une détérioration neurologique. La détérioration neurologique précoce non expliquée (absence de transformation hémorragique, d’œdème malin ou d’autre cause identifiable) est observée chez 7% de nos 309 patients thrombolysés. Nous avons validé l’hypothèse initiale d’une progression des anomalies en diffusion au-delà de la pénombre chez ces patients. Par une analyse voxel à voxel, elle était présente chez 9 cas/10 (7-137mL; > 10mL chez 8 cas), et son volume était significativement supérieur à celui des 30 contrôles sans détérioration précoce (P=0.047). De plus, sa topographie était congruente avec les fonctions neurologiques qui s’étaient détériorées. L’ensemble de ces résultats participe à une meilleure compréhension de l’évolution des lésions ischémiques aiguës en IRM de diffusion et offre des perspectives pour adapter la prise en charge individuelle afin d’améliorer le pronostic fonctionnel

Conventional liquid-based techniques versus Cytyc Thinprep(® )processing of urinary samples: a qualitative approach

BACKGROUND: The aim of our study was to objectively compare Cytyc Thinprep(® )and other methods of obtaining thin layer cytologic preparations (cytocentrifugation, direct smearing and Millipore(® )filtration) in urine cytopathology. METHODS: Thinprep slides were compared to direct smears in 79 cases. Cytocentrifugation carried out with the Thermo Shandon Cytospin(® )4 was compared to Thinprep in 106 cases, and comparison with Millipore filtration followed by blotting was obtained in 22 cases. Quality was assessed by scoring cellularity, fixation, red blood cells, leukocytes and nuclear abnormalities. RESULTS: The data show that 1) smearing allows good overall results to be obtained, 2) Cytocentrifugation with reusable TPX(® )chambers should be avoided, 3) Cytocentrifugation using disposable chambers (Cytofunnels(® )or Megafunnel(® )chambers) gives excellent results equalling or surpassing Thinprep and 4) Millipore filtration should be avoided, owing to its poor global quality. Despite differences in quality, the techniques studied have no impact on the diagnostic accuracy as evaluated by the rate of abnormalities. CONCLUSION: We conclude that conventional methods such as cytocentrifugation remain the most appropriate ones for current treatment of urinary samples. Cytyc Thinprep processing, owing to its cost, could be used essentially for cytology-based molecular studies

Opposite-side flavour tagging of B mesons at the LHCb experiment

The calibration and performance of the oppositeside flavour tagging algorithms used for the measurements of time-dependent asymmetries at the LHCb experiment are described. The algorithms have been developed using simulated events and optimized and calibrated with B + →J/ψK +, B0 →J/ψK ∗0 and B0 →D ∗− μ + νμ decay modes with 0.37 fb−1 of data collected in pp collisions at √ s = 7 TeV during the 2011 physics run. The oppositeside tagging power is determined in the B + → J/ψK + channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty is statistical and the second is systematic

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays

Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of prime importance in probing new physics. Here 7421 +/- 105 signal events from the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A time-dependent fit to the data yields a value of phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201

Measurement of the CP-violating phase phi_s in the decay Bs->J/psi phi

We present a measurement of the time-dependent CP-violating asymmetry in B_s -> J/psi phi decays, using data collected with the LHCb detector at the LHC. The decay time distribution of B_s -> J/psi phi is characterized by the decay widths Gamma_H and Gamma_L of the heavy and light mass eigenstates of the B_s-B_s-bar system and by a CP-violating phase phi_s. In a sample of about 8500 B_s -> J/psi phi events isolated from 0.37 fb^-1 of pp collisions at sqrt(s)=7 TeV we measure phi_s = 0.15 +/- 0.18 (stat) +/- 0.06 (syst) rad. We also find an average B_s decay width Gamma_s == (Gamma_L + Gamma_H)/2 = 0.657 +/- 0.009 (stat) +/- 0.008 (syst) ps^-1 and a decay width difference Delta Gamma_s == Gamma_L - Gamma_H} = 0.123 +/- 0.029 (stat) +/- 0.011 (syst) ps^-1. Our measurement is insensitive to the transformation (phi_s,DeltaGamma_s --> pi - phi_s, - Delta Gamma_s.Comment: 9 pages, 3 figure

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08 ^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical, the second systematic and the third is associated to the ratio of fragmentation fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/- 0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table

Absolute luminosity measurements with the LHCb detector at the LHC

Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. Using data taken in 2010, LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In addition to the classic "van der Meer scan" method a novel technique has been developed which makes use of direct imaging of the individual beams using beam-gas and beam-beam interactions. This beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. The results of the two methods have comparable precision and are in good agreement. Combining the two methods, an overall precision of 3.5% in the absolute luminosity determination is reached. The techniques used to transport the absolute luminosity calibration to the full 2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6, 9 and 10 and corresponding explanation in the tex

Measurements of the branching fractions of the decays B°s → D∓s K± and B°s → D¯sπ+

The decay mode B°s → D∓s K± allows for one of the theoretically cleanest measurements of the CKM angle γ through the study of time-dependent CP violation. This paper reports a measurement of its branching fraction relative to the Cabibbo-favoured mode B°s → D¯sπ+ based on a data sample corresponding to 0.37 fb¯¹ of proton-proton collisions at √s = 7TeV collected in 2011 with the LHCb detector. In addition, the ratio of B meson production fractions fs/fd, determined from semileptonic decays, together with the known branching fraction of the control channel B°s → D¯sπ+ is used to perform an absolute measurement of the branching fractions: B(B°s → D¯sπ+) = (2.95 ± 0.05 ± 0.17 -0.22 +0.18) × 10¯³ ; B(B°s → D∓s K±) = (1.90 ± 0.12 ± 0.13 -0.14 +0.12) × 10¯4 ; where the first uncertainty is statistical, the second the experimental systematic uncertainty, and the third the uncertainty due to f s/f

Search for CP violation in D+→K−K+π+D^{+} \to K^{-}K^{+}\pi^{+} decays

A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \to K^- K^+\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.