Intravitreal ranibizumab for age-related macular degeneration - optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

PURPOSE:To determine whether the need for retreatment after an initial loading phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients.SETTING:Prospective mono-centre cohort study.METHODS:Prospective study with 42 patients with exudative age-related macular degeneration (AMD), treatment na?ve, giving informed consent. Loading dose of 3 monthly doses of ranibizumab (0,5mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on spectral domain optical coherence tomography (HD-OCT Cirrus Zeiss?, cube 512x126). The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, etc after each injection) in order to detect exudative recurrences early, and injection followed within 3 days in cases of subretinal fluid, or intraretinal cysts, or central thickness increase of >50?m. Intervals were calculated between injections and the following recurrence was calculated for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). RESULTS Visual acuity (VA) improved from a mean ETDRS letter score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2, +6.4 letters) at month 3 and increased further to 74.7 (SD 9.0, +13.1 letters from baseline) at month 12. The 15 patients who have completed the study by October 2010 showed maintenance of the VA improvement. Retinal thickness of the central foveal subfield improved from a mean value of 366?m(baseline) to 253?m(month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5) per 12 months of follow-up (after 3 loading doses), ranging from 0 to 12, with mean individual treatment-recurrence intervals ranging from 28 to >365 days (mean 58 days). Intraindividual variability of treatment-recurrence intervals, measured as SD of the individual intervals, was 7.1days as a mean value(range 1.7 ? 22.6 days) for the 33 patients with more than 1 injection during follow-up. SD was higher for longer intervals of an individual patient. It ranged within 20% of the mean intra-individual interval for 30 patients(91%) and within 15% for 21 patients(64%). The first interval was within 1 week of the mean intra-individual interval in 64% of patients and within 2 weeks in 89% of patients.CONCLUSIONS:The majority of AMD patients showed a relatively stable rhythm for PRN injections of intravitreal ranibizumab after initial loading phase, associated with excellent functional and anatomical results. The initial interval between last loading dose and first recurrence may have a predictive value for further need of treatment, therefore potentially facilitating follow-up and patient care.

Accurate and efficient simulation of multiphase flow in a heterogeneous reservoir by using error estimate and control in the multiscale finite-volume framework

The multiscale finite-volume (MSFV) method is designed to reduce the computational cost of elliptic and parabolic problems with highly heterogeneous anisotropic coefficients. The reduction is achieved by splitting the original global problem into a set of local problems (with approximate local boundary conditions) coupled by a coarse global problem. It has been shown recently that the numerical errors in MSFV results can be reduced systematically with an iterative procedure that provides a conservative velocity field after any iteration step. The iterative MSFV (i-MSFV) method can be obtained with an improved (smoothed) multiscale solution to enhance the localization conditions, with a Krylov subspace method [e.g., the generalized-minimal-residual (GMRES) algorithm] preconditioned by the MSFV system, or with a combination of both. In a multiphase-flow system, a balance between accuracy and computational efficiency should be achieved by finding a minimum number of i-MSFV iterations (on pressure), which is necessary to achieve the desired accuracy in the saturation solution. In this work, we extend the i-MSFV method to sequential implicit simulation of time-dependent problems. To control the error of the coupled saturation/pressure system, we analyze the transport error caused by an approximate velocity field. We then propose an error-control strategy on the basis of the residual of the pressure equation. At the beginning of simulation, the pressure solution is iterated until a specified accuracy is achieved. To minimize the number of iterations in a multiphase-flow problem, the solution at the previous timestep is used to improve the localization assumption at the current timestep. Additional iterations are used only when the residual becomes larger than a specified threshold value. Numerical results show that only a few iterations on average are necessary to improve the MSFV results significantly, even for very challenging problems. Therefore, the proposed adaptive strategy yields efficient and accurate simulation of multiphase flow in heterogeneous porous media.

Portal vein embolization: what do we know?

Portal vein embolization (PVE) has been developed to increase the size of the future remnant liver (FRL) left in place after major hepatectomy, thus reducing the risk of postoperative liver insufficiency. PVE consist in embolizing preoperatively portal branches of the segments that will be resected. Indication is based on preoperative measurements of the FRL by computed tomography and its ratio with either the theoretical liver volume or by direct measurement of the functional liver volume. After PVE, the volume and function of the FRL increases in 3 to 6 weeks, permitting extensive resections in patients otherwise contraindicated for liver resection. The PVE technique is variable from one center to another; however n-butyl-cyano-acrylate provides an interesting compromise between hypertrophy rate and procedure risk.

Angiofil-mediated visualization of the vascular system by microcomputed tomography: a feasibility study.

Visualization of the vascular systems of organs or of small animals is important for an assessment of basic physiological conditions, especially in studies that involve genetically manipulated mice. For a detailed morphological analysis of the vascular tree, it is necessary to demonstrate the system in its entirety. In this study, we present a new lipophilic contrast agent, Angiofil, for performing postmortem microangiography by using microcomputed tomography. The new contrast agent was tested in 10 wild-type mice. Imaging of the vascular system revealed vessels down to the caliber of capillaries, and the digital three-dimensional data obtained from the scans allowed for virtual cutting, amplification, and scaling without destroying the sample. By use of computer software, parameters such as vessel length and caliber could be quantified and remapped by color coding onto the surface of the vascular system. The liquid Angiofil is easy to handle and highly radio-opaque. Because of its lipophilic abilities, it is retained intravascularly, hence it facilitates virtual vessel segmentation, and yields an enduring signal which is advantageous during repetitive investigations, or if samples need to be transported from the site of preparation to the place of actual analysis, respectively. These characteristics make Angiofil a promising novel contrast agent; when combined with microcomputed tomography, it has the potential to turn into a powerful method for rapid vascular phenotyping.

Complications of Valve Lung Volume Reduction in a Case of Previous Pleurodesis.

Lung volume reduction with valves is increasingly used to treat selected patients with severe emphysema. The indications for this procedure have been previously described; however, its contraindications have not yet been conclusively established. This case highlights the potentially severe complications of endobronchial one-way valve placement in the setting of a previous pleurodesis.

Bi-planar 2D-to-3D registration in Fourier domain for stereoscopic X-ray motion tracking

In this paper we present a new method to track bonemovements in stereoscopic X-ray image series of the kneejoint. The method is based on two different X-ray imagesets: a rotational series of acquisitions of the stillsubject knee that will allow the tomographicreconstruction of the three-dimensional volume (model),and a stereoscopic image series of orthogonal projectionsas the subject performs movements. Tracking the movementsof bones throughout the stereoscopic image series meansto determine, for each frame, the best pose of everymoving element (bone) previously identified in the 3Dreconstructed model. The quality of a pose is reflectedin the similarity between its simulated projections andthe actual radiographs. We use direct Fourierreconstruction to approximate the three-dimensionalvolume of the knee joint. Then, to avoid the expensivecomputation of digitally rendered radiographs (DRR) forpose recovery, we reformulate the tracking problem in theFourier domain. Under the hypothesis of parallel X-raybeams, we use the central-slice-projection theorem toreplace the heavy 2D-to-3D registration of projections inthe signal domain by efficient slice-to-volumeregistration in the Fourier domain. Focusing onrotational movements, the translation-relevant phaseinformation can be discarded and we only consider scalarFourier amplitudes. The core of our motion trackingalgorithm can be implemented as a classical frame-wiseslice-to-volume registration task. Preliminary results onboth synthetic and real images confirm the validity ofour approach.

Postmortem pump-driven reperfusion of the vascular system of porcine lungs: towards a new model for surgical training.

PURPOSE: The objective of this experiment is to establish a continuous postmortem circulation in the vascular system of porcine lungs and to evaluate the pulmonary distribution of the perfusate. This research is performed in the bigger scope of a revascularization project of Thiel embalmed specimens. This technique enables teaching anatomy, practicing surgical procedures and doing research under lifelike circumstances. METHODS: After cannulation of the pulmonary trunk and the left atrium, the vascular system was flushed with paraffinum perliquidum (PP) through a heart-lung machine. A continuous circulation was then established using red PP, during which perfusion parameters were measured. The distribution of contrast-containing PP in the pulmonary circulation was visualized on computed tomography. Finally, the amount of leak from the vascular system was calculated. RESULTS: A reperfusion of the vascular system was initiated for 37 min. The flow rate ranged between 80 and 130 ml/min throughout the experiment with acceptable perfusion pressures (range: 37-78 mm Hg). Computed tomography imaging and 3D reconstruction revealed a diffuse vascular distribution of PP and a decreasing vascularization ratio in cranial direction. A self-limiting leak (i.e. 66.8% of the circulating volume) towards the tracheobronchial tree due to vessel rupture was also measured. CONCLUSIONS: PP enables circulation in an isolated porcine lung model with an acceptable pressure-flow relationship resulting in an excellent recruitment of the vascular system. Despite these promising results, rupture of vessel walls may cause leaks. Further exploration of the perfusion capacities of PP in other organs is necessary. Eventually, this could lead to the development of reperfused Thiel embalmed human bodies, which have several applications.

Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome.

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke.

16-OR: Investigation of Sharp Trauma and Gunshot Cases Using Post-mortem CT-Angiography

Investigation of violent death, especially cases of sharp trauma and gunshot, is an important part of medico-legal investigations. Beside the execution of a conventional autopsy, the performance of a post-mortem Multi-Detector Computed Tomography (MDCT)-scan has become a highly appreciated tool. In order to investigate also the vascular system, post-mortem CT-angiography has been introduced. The most studied and widespread technique is the Multi-phase post-mortem CT-angiography (MPMCTA). Its sensitivity to detect vascular lesions is even superior to conventional autopsy. The application of MPMCTA for cases of gunshot and sharp-trauma is therefore an obvious choice, as vascular lesions are common in such victims. In most cases of sharp trauma and in several cases of gunshots, death can be attributed to exsanguinations. MPMCTA is able to detect the exact source of bleeding and also to visualize trajectories, which are of most importance in these cases. The reconstructed images allow to clearly visualizing the trajectory in a way that is easily comprehensible for not medically trained legal professionals. The sensitivity of MPMCTA for soft tissue and organ lesions approximately matches the sensitivity of conventional autopsy. However, special care, experience and effective use of the imaging software is necessary for performing the reconstructions of the trajectory. Large volume consuming haemorrhages and shift of inner organs are sources of errors and misinterpretations. This presentation shall give an overview about the advantages and limitations of the use of MPMCTA for investigating cases of gunshot and sharp-trauma.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen.

Transaxial tomoscintigraphy (or single-photon emission computerised tomography) was used to detect secondary deposits of carcinoma in 17 patients who had been injected with iodine-131-labelled monoclonal antibodies against carcinoembryonic antigen. Of 17 tumor sites studied by tomoscintigraphy 16 were detected (sensitivity 94%); five sites had a volume smaller than 10 cm3. Tomoscintigraphy also detected three unknown tumour deposits later confirmed by surgery or radiology. In contrast, when 21 tumour sites in the same patients were studied by rectilinear scintigraphy, only nine tumour sites were detected (sensitivity 43%), of which eight had a volume larger than 50 cm3.

CT dose optimization when changing to CT multi-detector row technology

The purpose of this article was to review the strategies to control patient dose in adult and pediatric computed tomography (CT), taking into account the change of technology from single-detector row CT to multi-detector row CT. First the relationships between computed tomography dose index, dose length product, and effective dose in adult and pediatric CT are revised, along with the diagnostic reference level concept. Then the effect of image noise as a function of volume computed tomography dose index, reconstructed slice thickness, and the size of the patient are described. Finally, the potential of tube current modulation CT is discussed.