In vivo measurement of tissue oxygenation by time-resolved luminescence spectroscopy: advantageous properties of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate.

Measuring tissue oxygenation in vivo is of interest in fundamental biological as well as medical applications. One minimally invasive approach to assess the oxygen partial pressure in tissue (pO2) is to measure the oxygen-dependent luminescence lifetime of molecular probes. The relation between tissue pO2 and the probes' luminescence lifetime is governed by the Stern-Volmer equation. Unfortunately, virtually all oxygen-sensitive probes based on this principle induce some degree of phototoxicity. For that reason, we studied the oxygen sensitivity and phototoxicity of dichlorotris(1, 10-phenanthroline)-ruthenium(II) hydrate [Ru(Phen)] using a dedicated optical fiber-based, time-resolved spectrometer in the chicken embryo chorioallantoic membrane. We demonstrated that, after intravenous injection, Ru(Phen)'s luminescence lifetime presents an easily detectable pO2 dependence at a low drug dose (1 mg∕kg) and low fluence (120 mJ∕cm2 at 470 nm). The phototoxic threshold was found to be at 10 J∕cm2 with the same wavelength and drug dose, i.e., about two orders of magnitude larger than the fluence necessary to perform a pO2 measurement. Finally, an illustrative application of this pO2 measurement approach in a hypoxic tumor environment is presented.

Simultaneous cell morphometry and refractive index measurement with dual-wavelength digital holographic microscopy and dye-enhanced dispersion of perfusion medium.

Digital holographic microscopy (DHM) allows optical-path-difference (OPD) measurements with nanometric accuracy. OPD induced by transparent cells depends on both the refractive index (RI) of cells and their morphology. This Letter presents a dual-wavelength DHM that allows us to separately measure both the RI and the cellular thickness by exploiting an enhanced dispersion of the perfusion medium achieved by the utilization of an extracellular dye. The two wavelengths are chosen in the vicinity of the absorption peak of the dye, where the absorption is accompanied by a significant variation of the RI as a function of the wavelength.

Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients.

The purpose of this study was to determine the prognostic accuracy of perfusion computed tomography (CT), performed at the time of emergency room admission, in acute stroke patients. Accuracy was determined by comparison of perfusion CT with delayed magnetic resonance (MR) and by monitoring the evolution of each patient's clinical condition. Twenty-two acute stroke patients underwent perfusion CT covering four contiguous 10mm slices on admission, as well as delayed MR, performed after a median interval of 3 days after emergency room admission. Eight were treated with thrombolytic agents. Infarct size on the admission perfusion CT was compared with that on the delayed diffusion-weighted (DWI)-MR, chosen as the gold standard. Delayed magnetic resonance angiography and perfusion-weighted MR were used to detect recanalization. A potential recuperation ratio, defined as PRR = penumbra size/(penumbra size + infarct size) on the admission perfusion CT, was compared with the evolution in each patient's clinical condition, defined by the National Institutes of Health Stroke Scale (NIHSS). In the 8 cases with arterial recanalization, the size of the cerebral infarct on the delayed DWI-MR was larger than or equal to that of the infarct on the admission perfusion CT, but smaller than or equal to that of the ischemic lesion on the admission perfusion CT; and the observed improvement in the NIHSS correlated with the PRR (correlation coefficient = 0.833). In the 14 cases with persistent arterial occlusion, infarct size on the delayed DWI-MR correlated with ischemic lesion size on the admission perfusion CT (r = 0.958). In all 22 patients, the admission NIHSS correlated with the size of the ischemic area on the admission perfusion CT (r = 0.627). Based on these findings, we conclude that perfusion CT allows the accurate prediction of the final infarct size and the evaluation of clinical prognosis for acute stroke patients at the time of emergency evaluation. It may also provide information about the extent of the penumbra. Perfusion CT could therefore be a valuable tool in the early management of acute stroke patients.

Quantitative Measurement of Brain Perfusion with Intravoxel Incoherent Motion MR Imaging.

Purpose: To evaluate the sensitivity of the perfusion parameters derived from Intravoxel Incoherent Motion (IVIM) MR imaging to hypercapnia-induced vasodilatation and hyperoxygenation-induced vasoconstriction in the human brain. Materials and Methods: This study was approved by the local ethics committee and informed consent was obtained from all participants. Images were acquired with a standard pulsed-gradient spin-echo sequence (Stejskal-Tanner) in a clinical 3-T system by using 16 b values ranging from 0 to 900 sec/mm(2). Seven healthy volunteers were examined while they inhaled four different gas mixtures known to modify brain perfusion (pure oxygen, ambient air, 5% CO(2) in ambient air, and 8% CO(2) in ambient air). Diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and blood flow-related parameter (fD*) maps were calculated on the basis of the IVIM biexponential model, and the parametric maps were compared among the four different gas mixtures. Paired, one-tailed Student t tests were performed to assess for statistically significant differences. Results: Signal decay curves were biexponential in the brain parenchyma of all volunteers. When compared with inhaled ambient air, the IVIM perfusion parameters D*, f, and fD* increased as the concentration of inhaled CO(2) was increased (for the entire brain, P = .01 for f, D*, and fD* for CO(2) 5%; P = .02 for f, and P = .01 for D* and fD* for CO(2) 8%), and a trend toward a reduction was observed when participants inhaled pure oxygen (although P > .05). D remained globally stable. Conclusion: The IVIM perfusion parameters were reactive to hyperoxygenation-induced vasoconstriction and hypercapnia-induced vasodilatation. Accordingly, IVIM imaging was found to be a valid and promising method to quantify brain perfusion in humans. © RSNA, 2012.

Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations

AIM: To discuss the use of new ultrasonic techniques that make it possible to visualize elastic (carotid) and muscular (radial) capacitance arteries non-invasively. RESULTS OF DATA REVIEW: Measurements of carotid wall thickness and the detection of atheromas are related to arterial pressure, to other risk factors and to the risk of subsequent complications. The use of high-frequency ultrasound (7.5-10 MHz), measurements of far wall thicknesses in areas free of atheromas at end-diastole (by ECG gating or pressure waveform recording) and descriptions of the size and characteristics of atherosclerotic plaques allow a non-invasive assessment of vascular hypertrophy and atherosclerosis in hypertensive patients. CONCLUSIONS: Careful attention to methodologic and physiologic factors is needed to provide accurate information about the anatomy of the dynamically pulsating arterial tree.

Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.

BACKGROUND: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort. METHODS: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model. RESULTS: Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency. CONCLUSION: There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.

Nonclassical measurement error with applications to labor and development issues

Zero correlation between measurement error and model error has been assumed in existing panel data models dealing specifically with measurement error. We extend this literature and propose a simple model where one regressor is mismeasured, allowing the measurement error to correlate with model error. Zero correlation between measurement error and model error is a special case in our model where correlated measurement error equals zero. We ask two research questions. First, we wonder if the correlated measurement error can be identified in the context of panel data. Second, we wonder if classical instrumental variables in panel data need to be adjusted when correlation between measurement error and model error cannot be ignored. Under some regularity conditions the answer is yes to both questions. We then propose a two-step estimation corresponding to the two questions. The first step estimates correlated measurement error from a reverse regression; and the second step estimates usual coefficients of interest using adjusted instruments.

Ambulatory measurement of ankle kinetics for clinical applications.

This study aimed to design and validate the measurement of ankle kinetics (force, moment, and power) during consecutive gait cycles and in the field using an ambulatory system. An ambulatory system consisting of plantar pressure insole and inertial sensors (3D gyroscopes and 3D accelerometers) on foot and shank was used. To test this system, 12 patients and 10 healthy elderly subjects wore shoes embedding this system and walked many times across a gait lab including a force-plate surrounded by seven cameras considered as the reference system. Then, the participants walked two 50-meter trials where only the ambulatory system was used. Ankle force components and sagittal moment of ankle measured by ambulatory system showed correlation coefficient (R) and normalized RMS error (NRMSE) of more than 0.94 and less than 13% in comparison with the references system for both patients and healthy subjects. Transverse moment of ankle and ankle power showed R>0.85 and NRMSE<23%. These parameters also showed high repeatability (CMC>0.7). In contrast, the ankle coronal moment of ankle demonstrated high error and lower repeatability. Except for ankle coronal moment, the kinetic features obtained by the ambulatory system could distinguish the patients with ankle osteoarthritis from healthy subjects when measured in 50-meter trials. The proposed ambulatory system can be easily accessible in most clinics and could assess main ankle kinetics quantities with acceptable error and repeatability for clinical evaluations. This system is therefore suggested for field measurement in clinical applications.

Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting.

Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (Elite? XL, Ascensia? Contour? and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance.

Usefulness of postmortem biochemistry in forensic pathology: illustrative case reports.

The aim of this work is to present some practical, postmortem biochemistry applications to illustrate the usefulness of this discipline and reassert the importance of carrying out biochemical investigations as an integral part of the autopsy process. Five case reports are presented pertaining to diabetic ketoacidosis in an adult who was not known to suffer from diabetes and in presence of multiple psychotropic substances; fatal flecainide intoxication in a poor metabolizer also presenting an impaired renal function; diabetic ketoacidosis showing severe postmortem changes; primary aldosteronism presented with intracranial hemorrhage and hypothermia showing severe postmortem changes. The cases herein presented can be considered representative examples of the importance of postmortem biochemistry investigations, which may provide significant information useful in determining the cause of death in routine forensic casework or contribute to understanding the pathophysiological mechanisms involved in the death process.

Adaptive Privacy Management System Design For Context-Aware Mobile Devices

While mobile technologies can provide great personalized services for mobile users, they also threaten their privacy. Such personalization-privacy paradox are particularly salient for context aware technology based mobile applications where user's behaviors, movement and habits can be associated with a consumer's personal identity. In this thesis, I studied the privacy issues in the mobile context, particularly focus on an adaptive privacy management system design for context-aware mobile devices, and explore the role of personalization and control over user's personal data. This allowed me to make multiple contributions, both theoretical and practical. In the theoretical world, I propose and prototype an adaptive Single-Sign On solution that use user's context information to protect user's private information for smartphone. To validate this solution, I first proved that user's context is a unique user identifier and context awareness technology can increase user's perceived ease of use of the system and service provider's authentication security. I then followed a design science research paradigm and implemented this solution into a mobile application called "Privacy Manager". I evaluated the utility by several focus group interviews, and overall the proposed solution fulfilled the expected function and users expressed their intentions to use this application. To better understand the personalization-privacy paradox, I built on the theoretical foundations of privacy calculus and technology acceptance model to conceptualize the theory of users' mobile privacy management. I also examined the role of personalization and control ability on my model and how these two elements interact with privacy calculus and mobile technology model. In the practical realm, this thesis contributes to the understanding of the tradeoff between the benefit of personalized services and user's privacy concerns it may cause. By pointing out new opportunities to rethink how user's context information can protect private data, it also suggests new elements for privacy related business models.

Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.