Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging.

BACKGROUND: Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. METHODS: Twenty-eight patients (mean age, 57 +/- 11 years; mean ejection fraction, 26 +/- 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. RESULTS: After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 +/- 12 before therapy versus 61 +/- 11 after therapy; P <.01) and peak exercise (144 +/- 20 before therapy versus 127 +/- 17 after therapy; P <.01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 +/- 36 watts versus 146.1 +/- 33 watts; P <.05) and exercise time tended to be higher (9.1 +/- 1.7 minutes versus 11.4 +/- 2.8 minutes; P =.06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (-54 mL) and left ventricular end-systolic volume (-62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 +/- 7 versus 36.2 +/- 9%; P <.05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P <.05). CONCLUSION: One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function.

Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics

Raman spectroscopy combined with chemometrics has recently become a widespread technique for the analysis of pharmaceutical solid forms. The application presented in this paper is the investigation of counterfeit medicines. This increasingly serious issue involves networks that are an integral part of industrialized organized crime. Efficient analytical tools are consequently required to fight against it. Quick and reliable authentication means are needed to allow the deployment of measures from the company and the authorities. For this purpose a method in two steps has been implemented here. The first step enables the identification of pharmaceutical tablets and capsules and the detection of their counterfeits. A nonlinear classification method, the Support Vector Machines (SVM), is computed together with a correlation with the database and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect product. If a counterfeit is detected, the second step allows its chemical profiling among former counterfeits in a forensic intelligence perspective. For this second step a classification based on Principal Component Analysis (PCA) and correlation distance measurements is applied to the Raman spectra of the counterfeits.

Investigation of resins suitable for the preparation of biological sample for 3-D electron microscopy.

In the last two decades, the third-dimension has become a focus of attention in electron microscopy to better understand the interactions within subcellular compartments. Initially, transmission electron tomography (TEM tomography) was introduced to image the cell volume in semi-thin sections (∼500nm). With the introduction of the focused ion beam scanning electron microscope, a new tool, FIB-SEM tomography, became available to image much larger volumes. During TEM tomography and FIB-SEM tomography, the resin section is exposed to a high electron/ion dose such that the stability of the resin embedded biological sample becomes an important issue. The shrinkage of a resin section in each dimension, especially in depth, is a well-known phenomenon. To ensure the dimensional integrity of the final volume of the cell, it is important to assess the properties of the different resins and determine the formulation which has the best stability in the electron/ion beam. Here, eight different resin formulations were examined. The effects of radiation damage were evaluated after different times of TEM irradiation. To get additional information on mass-loss and the physical properties of the resins (stiffness and adhesion), the topography of the irradiated areas was analysed with atomic force microscopy (AFM). Further, the behaviour of the resins was analysed after ion milling of the surface of the sample with different ion currents. In conclusion, two resin formulations, Hard Plus and the mixture of Durcupan/Epon, emerged that were considerably less affected and reasonably stable in the electron/ion beam and thus suitable for the 3-D investigation of biological samples.

Prediction of hemodynamic severity of coarctation by magnetic resonance imaging.

A published formula containing minimal aortic cross-sectional area and the flow deceleration pattern in the descending aorta obtained by cardiovascular magnetic resonance predicts significant coarctation of the aorta (CoA). However, the existing formula is complicated to use in clinical practice and has not been externally validated. Consequently, its clinical utility has been limited. The aim of this study was to derive a simple and clinically practical algorithm to predict severe CoA from data obtained by cardiovascular magnetic resonance. Seventy-nine consecutive patients who underwent cardiovascular magnetic resonance and cardiac catheterization for the evaluation of native or recurrent CoA at Children's Hospital Boston (n = 30) and the University of California, San Francisco (n = 49), were retrospectively reviewed. The published formula derived from data obtained at Children's Hospital Boston was first validated from data obtained at the University of California, San Francisco. Next, pooled data from the 2 institutions were analyzed, and a refined model was created using logistic regression methods. Finally, recursive partitioning was used to develop a clinically practical prediction tree to predict transcatheter systolic pressure gradient ≥ 20 mm Hg. Severe CoA was present in 48 patients (61%). Indexed minimal aortic cross-sectional area and heart rate-corrected flow deceleration time in the descending aorta were independent predictors of CoA gradient ≥ 20 mm Hg (p <0.01 for both). A prediction tree combining these variables reached a sensitivity and specificity of 90% and 76%, respectively. In conclusion, the presented prediction tree on the basis of cutoff values is easy to use and may help guide the management of patients investigated for CoA.

Fast Bias Field Correction for 9.4 Tesla Magnetic Resonance Imaging

In this paper the problem of intensity inhomogeneity athigh magnetic field on magnetic resonance images isaddressed. Specifically, rat brain images at 9.4Tacquired with a surface coil are bias corrected. Wepropose a low- pass frequency model that takes intoaccount not only background-object contours but alsoother important contours inside the image. Twopre-processing filters are proposed: first, to create avolume of interest without contours, and second, toextrapolate the image values of such masked area to thewhole image. Results are assessed quantitatively andvisually in comparison to standard low pass filterapproach, and they show as expected better accuracy inenhancing image intensity.

Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy.

BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

Qualitative grading of severity of lumbar spinal stenosis based on the morphology of the dural sac on magnetic resonance images.

STUDY DESIGN.: Retrospective radiologic study on a prospective patient cohort. OBJECTIVE.: To devise a qualitative grading of lumbar spinal stenosis (LSS), study its reliability and clinical relevance. SUMMARY OF BACKGROUND DATA.: Radiologic stenosis is assessed commonly by measuring dural sac cross-sectional area (DSCA). Great variation is observed though in surfaces recorded between symptomatic and asymptomatic individuals. METHODS.: We describe a 7-grade classification based on the morphology of the dural sac as observed on T2 axial magnetic resonance images based on the rootlet/cerebrospinal fluid ratio. Grades A and B show cerebrospinal fluid presence while grades C and D show none at all. The grading was applied to magnetic resonance images of 95 subjects divided in 3 groups as follows: 37 symptomatic LSS surgically treated patients; 31 symptomatic LSS conservatively treated patients (average follow-up, 2.5 and 3.1 years); and 27 low back pain (LBP) sufferers. DSCA was also digitally measured. We studied intra- and interobserver reliability, distribution of grades, relation between morphologic grading and DSCA, as well relation between grades, DSCA, and Oswestry Disability Index. RESULTS.: Average intra- and interobserver agreement was substantial and moderate, respectively (k = 0.65 and 0.44), whereas they were substantial for physicians working in the study originating unit. Surgical patients had the smallest DSCA. A larger proportion of C and D grades was observed in the surgical group. Surface measurementsresulted in overdiagnosis of stenosis in 35 patients and under diagnosis in 12. No relation could be found between stenosis grade or DSCA and baseline Oswestry Disability Index or surgical result. C and D grade patients were more likely to fail conservative treatment, whereas grades A and B were less likely to warrant surgery. CONCLUSION.: The grading defines stenosis in different subjects than surface measurements alone. Since it mainly considers impingement of neural tissue it might be a more appropriate clinical and research tool as well as carrying a prognostic value.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial).

ABSTRACT: BACKGROUND: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. METHODS: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Automated segmentation of multiple red blood cells with digital holographic microscopy.

We present a method to automatically segment red blood cells (RBCs) visualized by digital holographic microscopy (DHM), which is based on the marker-controlled watershed algorithm. Quantitative phase images of RBCs can be obtained by using off-axis DHM along to provide some important information about each RBC, including size, shape, volume, hemoglobin content, etc. The most important process of segmentation based on marker-controlled watershed is to perform an accurate localization of internal and external markers. Here, we first obtain the binary image via Otsu algorithm. Then, we apply morphological operations to the binary image to get the internal markers. We then apply the distance transform algorithm combined with the watershed algorithm to generate external markers based on internal markers. Finally, combining the internal and external markers, we modify the original gradient image and apply the watershed algorithm. By appropriately identifying the internal and external markers, the problems of oversegmentation and undersegmentation are avoided. Furthermore, the internal and external parts of the RBCs phase image can also be segmented by using the marker-controlled watershed combined with our method, which can identify the internal and external markers appropriately. Our experimental results show that the proposed method achieves good performance in terms of segmenting RBCs and could thus be helpful when combined with an automated classification of RBCs.

Assessing dystrophies and other muscle diseases at the nanometer scale by atomic force microscopy.

AIM: Atomic force microscopy nanoindentation of myofibers was used to assess and quantitatively diagnose muscular dystrophies from human patients. MATERIALS & METHODS: Myofibers were probed from fresh or frozen muscle biopsies from human dystrophic patients and healthy volunteers, as well as mice models, and Young's modulus stiffness values were determined. RESULTS: Fibers displaying abnormally low mechanical stability were detected in biopsies from patients affected by 11 distinct muscle diseases, and Young's modulus values were commensurate to the severity of the disease. Abnormal myofiber resistance was also observed from consulting patients whose muscle condition could not be detected or unambiguously diagnosed otherwise. DISCUSSION & CONCLUSION: This study provides a proof-of-concept that atomic force microscopy yields a quantitative read-out of human muscle function from clinical biopsies, and that it may thereby complement current muscular dystrophy diagnosis.

Quasi real-time Raman studies on the growth of Cu-In-S thin films

In this work annealing and growth of CuInS2 thin films is investigated with quasireal-time in situ Raman spectroscopy. During the annealing a shift of the Raman A1 mode towards lower wave numbers with increasing temperature is observed. A linear temperature dependence of the phonon branch of ¿2 cm¿1/100 K is evaluated. The investigation of the growth process (sulfurization of metallic precursors) with high surface sensitivity reveals the occurrence of phases which are not detected with bulk sensitive methods. This allows a detailed insight in the formation of the CuInS2 phases. Independent from stoichiometry and doping of the starting precursors the CuAu ordering of CuInS2 initially forms as the dominating ordering. The transformation of the CuAu ordering into the chalcopyrite one is, in contrast, strongly dependent on the precursor composition and requires high temperatures.

Diradicals acting through diamagnetic phenylene vinylene bridges: Raman spectroscopy as a probe to characterize spin delocalization

We present a complete Raman spectroscopic study in two structurally well-defined diradical species of different lengths incorporating oligo p-phenylene vinylene bridges between two polychlorinated triphenylmethyl radical units, a disposition that allows sizeable conjugation between the two radicals through and with the bridge. The spectroscopic data are interpreted and supported by quantum chemical calculations. We focus the attention on the Raman frequency changes, interpretable in terms of: (i) bridge length (conjugation length); (ii) bridge conformational structure; and (iii) electronic coupling between the terminal radical units with the bridge and through the bridge, which could delineate through-bond spin polarization, or spin delocalization. These items are addressed by using the"oligomer approach" in conjunction with pressure and temperature dependent Raman spectroscopic data. In summary, we have attempted to translate the well-known strategy to study the electron (charge) structure of π−conjugated molecules by Raman spectroscopy to the case of electron (spin) interactions via the spin delocalization mechanism.

Characterization of board impurities with a Raman device

Erilaisia epäpuhtauksia kulkeutuu paperinvalmistusprosessiin ja monenlaisia saostumia muodostuu paperinvalmistuksen prosesseissa. Epäpuhtaudet voivat aiheuttaa prosessiongelmia sekä alentaa tuotteen laatua. Epäpuhtauksien alkuperän ja koostumuksen selvittäminen edellyttää usein erilaisten analyysimenetelmien käyttöä. Epäpuhtauksien luokittelu on useasti välttämätöntä ennen tarkempaa kemiallista analyysia. Paperinvalmistuksen epäpuhtauksien kvalitatiiviseen luokitteluun on yleisimmin käytetty mikroskopian, IR-spektroskopian ja analyyttisen pyrolyysin menetelmiä. Raman spektroskopia on harvinaisempi menetelmä paperiteollisuuden tutkimuksessa. Raman instrumenttien kehittyminen on ollut voimakasta viimeisen vuosikymmenen aikana. Raman spektroskopia onkin osoittanut mandollisuutensa polymeerien, lääketeollisuuden ja polttoaineteollisuuden tutkimuksissa. Tässä työssä tutkittiin erään elintarvikepakkauskartongin epäpuhtauksia Raman spektroskoopilla. Työn tavoitteena oli selvittää Raman analyysin käyttökelpoisuutta kartongin epäpuhtauksien online-luokittelussa. Tutkimukset suoritettiin Spectracoden RP-1 Raman instrumentilla. Tutkimukset osoittivat, että näytteen fluoresenssi ja näytteen hajoaminen asettavat rajoituksia epäpuhtauksien Raman analyysille. Epäpuhtauksien online-tunnistaminen toimii käytettäessä suuria lasertehoja ja säteilytysaikoja. Näytteiden laserherkkyys ja fluoresenssi rajoittavat kuitenkin suurien laiteparametrien käyttöä. Laiteparametrien pienentäminen johti mittauksien signaali-kohina suhteen alenemiseen, mikä puolestaan aiheutti online-tunnistuksen toimimattomuuden.