Strong exciton-plasmon coupling in dye-doped film on a planar hyperbolic metamaterial.

We experimentally demonstrate the direct strong coupling between the S0→S1 absorption transition of rhodamine 6G (R6G) dye molecules and the surface plasmon polaritons of a hyperbolic metamaterial (HMM) substrate. The surface plasmon mode was excited by a guided mode of the R6G-doped polymer thin film on the HMM. The coupling strengths of the interactions between the surface plasmon and two molecular exciton modes are greater than the average linewidths of the individual modes indicating a strong coupling regime. This is the first, to the best of our knowledge, experimental demonstration of the direct strong coupling between the resonance mode supported by the HMM and the dye molecules on the HMM surface, not embedded in the HMM structure. The study may provide the foundation for the development of novel planar photonic or electronic devices.

Molecular packing-dependent exciton dynamics in functionalized anthradithiophene derivatives: From solutions to crystals.

Understanding the impact of inter-molecular orientation on the optical properties of organic semiconductors is important for designing next-generation organic (opto)electronic and photonic devices. However, fundamental aspects of how various features of molecular packing in crystalline systems determine the nature and dynamics of excitons have been a subject of debate. Toward this end, we present a systematic study of how various molecular crystal packing motifs affect the optical properties of a class of high-performance organic semiconductors: functionalized derivatives of fluorinated anthradithiophene. The absorptive and emissive species present in three such derivatives (exhibiting "brickwork," "twisted-columnar," and "sandwich-herringbone" motifs, controlled by the side group R) were analyzed both in solution and in single crystals, using various modalities of optical and photoluminescence spectroscopy, revealing the nature of these excited states. In solution, in the emission band, two states were identified: a Franck-Condon state present at all concentrations and an excimer that emerged at higher concentrations. In single crystal systems, together with ab initio calculations, it was found in the absorptive band that Frenkel and Charge Transfer (CT) excitons mixed due to nonvanishing CT integrals in all derivatives, but the amount of admixture and exciton delocalization depended on the packing, with the "sandwich-herringbone" packing motif least conducive to delocalization. Three emissive species in the crystal phase were also identified: Frenkel excitons, entangled triplet pairs 1(TT) (which are precursors to forming free triplet states via singlet fission), and self-trapped excitons (STEs, similar in origin to excimers present in concentrated solution). The "twisted-columnar" packing motif was most conducive to the formation of Frenkel excitons delocalized over 4-7 molecules depending on the temperature. These delocalized Frenkel states were dominant across the full temperature range (78 K-293 K), though at lower temperatures, the entangled triplet states and STEs were present. In the derivative with the "brickwork" packing, all three emissive species were observed across the full temperature range and, most notably, the 1(TT) state was present at room temperature. Finally, the derivative with the "sandwich-herringbone" packing exhibited localized Frenkel excitons and had a strong propensity for self-trapped exciton formation even at higher temperatures. In this derivative, no formation of the 1(TT) state was observed. The temperature-dependent dynamics of these emissive states are reported, as well as their origin in fundamental inter-molecular interactions.

Safety of strong, static magnetic fields.

Issues associated with the exposure of patients to strong, static magnetic fields during magnetic resonance imaging (MRI) are reviewed and discussed. The history of human exposure to magnetic fields is reviewed, and the contradictory nature of the literature regarding effects on human health is described. In the absence of ferromagnetic foreign bodies, there is no replicated scientific study showing a health hazard associated with magnetic field exposure and no evidence for hazards associated with cumulative exposure to these fields. The very high degree of patient safety in strong magnetic fields is attributed to the small value of the magnetic susceptibility of human tissues and to the lack of ferromagnetic components in these tissues. The wide range of susceptibility values between magnetic materials and human tissues is shown to lead to qualitatively differing behaviors of these materials when they are exposed to magnetic fields. Mathematical expressions are provided for the calculation of forces and torques.

Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins.

Regulation of epithelial Na(+) channel (ENaC) subunit levels by protein kinase C (PKC) was investigated in A6 cells. PKC activation altered ENaC subunit levels, differentially decreasing the levels of both beta and gamma, but not alphaENaC. Temporal regulation of beta and gammaENaC by PKC differed; gammaENaC decreased with a time constant of 3.7 +/- 1.0 h, whereas betaENaC decreased in 13.9 +/- 3. 0 h. Activation of PKC also resulted in a decrease in trans-epithelial Na(+) reabsorption for up to 48 h. PMA activation of PKC resulted in negative feedback inhibition of PKC protein levels beginning within 4 h. Both beta and gammaENaC levels, as well as transport tended toward pretreatment values after 48 h of PMA treatment. PKC inhibitors attenuated the effects of PMA on ENaC subunit levels and Na(+) transport. These results directly show for the first time that PKC differentially regulates ENaC subunit levels by decreasing the levels of beta and gamma but not alphaENaC protein. These results imply a PKC-dependent, long term decrease in Na(+) reabsorption.

In vivo pedicle screw placement: image-guided virtual vision.

Near-real-time frameless stereotaxy registering intraoperative anatomy to a preoperative three-dimensional computer model has been developed for use with in vivo pedicle screw placement. Eight patients underwent thoracolumbar and lumbar spine stabilization surgery using this new technology, and 32 pedicle screws were placed. Three additional patients had 12 pedicle screws removed during revision surgery, and they allowed the authors to estimate the accuracy of this navigational system. Accuracy was determined by comparing pedicle screw position on postoperative computed tomographs for the first eight patients and on preoperative computed tomographs for the latter three patients, with the intraoperative computer trajectory data gathered during operation. In the group of eight patients, all screws were intrapedicular. In evaluating all 11 patients, the overall accuracy was +/- 2 mm, but the greatest error of 5.4 mm was noted in the sagittal plane measurement. During the development phase of this technology, time constraints prolong surgery, but this may be addressed once the tool's accuracy has been confirmed and intraoperative radiographic confirmation becomes unnecessary. In vivo real-time frameless stereotaxy for pedicle screw placement offers promise for the future. Refinements are needed to improve accuracy and address time constraints.

Does gastroscopy induce myocardial ischemia in patients with coronary heart disease?

BACKGROUND AND STUDY AIMS: Gastroscopy has been reported to be dangerous for unstable patients with coronary heart disease (CHD). The aims of this study were to find out whether endoscopy is equally liable to cause myocardial ischemia in stable CHD patients, and whether this can be predicted prior to endoscopy, and to find out the frequency of abnormal findings in patients for whom a secondary prophylaxis with acetylsalicylic acid (ASA) is indicated. PATIENTS AND METHODS: Electrocardiograph recording using a Holter monitor was performed during gastroscopy in 71 patients with stable CHD, to check for silent ischemia. To predict potential ischemia during gastroscopy, the Holter monitoring ECG was applied prior to a treadmill test, and withdrawn after gastroscopy 16-22 hours later. RESULTS: During gastroscopy, 30 patients (42%) had silent ischemia, but only 1 patient (1%) became symptomatic. Ischemia was dependent on heart-rate (median heart rate with ischemia 124 beats/min, without 104 beats/min). Abnormal findings on gastroscopy were found in 53 patients (75%). They implied a potential bleeding risk in 30 patients (42%) and prevented the indication for ASA in 6 of them (8%). CONCLUSIONS: Gastroscopy is potentially a harmful procedure for CHD patients, but the incidence of ischemic periods may be reduced by conscious sedation and, if the patient is receiving beta-blocking agent therapy, by applying this medication prior to gastroscopy.

Very-high-field magnetic resonance imaging: instrumentation and safety issues.

Because of their advantage in terms of signal-to-noise ratio, high-field magnetic resonance imaging systems have become favored in the last few years for functional magnetic resonance imaging (fMRI) applications. In many ways the conceptual development of these high-field scanners has involved more-or-less straightforward extensions of practices at lower field strengths. However, in other ways specific engineering challenges have been encountered and largely overcome in the quest for scanners capable of realizing the advantages of high-field systems. An understanding of the technical trade-offs that can be made in terms of hardware performance is useful in deciding on the optimum system for a given fMRI application. In this article the technical issues surrounding high-field scanning are reviewed in the context of a typical brain mapping protocol. In addition there is a discussion of the safety issues related to the use of these systems.

Dimensions of quality of life and self-monitoring therapy with oral anticoagulants--still research or everyday practice?

In correlation with increased life expectancy of patients, quality of life (QOL) has become a factor of increasing interest by the patient himself and also of importance in health-care planning and recruitment of financial resources. In this context, self-monitoring of long-term anticoagulant treatment might be a strategy that could mean a step forward in health-related as well as general life satisfaction for patients participating in self-monitoring programs. Also, the new strategy of increased home-control of anticoagulant treatment illustrates the complexity of multiple factors that can lead to changes in the subjective feeling and objective aspects of QOL. Our intention in a pilot study was to probe the feasibility of QOL research and relevant factors of influence by retrospectively evaluating data from two groups of outpatients seen in a large treatment center. The high frequency (n = 8 in sample 2) of disturbed sleep as a simple screening indicator stresses the probable importance of undetected depression, which might require treatment and could confound research as to QOL. Instruments to measure QOL in oral anticoagulation self-monitoring should therefore be adapted to the heterogeneous structure of factors in the target population, and include psychological parameters, especially in regard to health-related locus of control and mood.

Rural attitudes, opinions, and drug use.

There are two primary purposes of this paper. The first is to summarize the results of a survey conducted in a rural area of Kentucky on attitudes and behaviors regarding substance use. The second purpose is to examine differences in drug attitudes and behaviors for higher and lower density rural areas. Participants for this study were contacted by telephone in March 1996. The sample was generated by random digit dialing for eight county telephone exchanges. The sample included 334 respondents from the eight counties who were grouped into respondents from higher density areas (n = 132) and lower density areas (n = 202). Results indicated that respondents from both higher density and lower density areas were similar on drug use and attitudes. However, lower density areas reported their county as a worse place to live and less safe than respondents from higher density areas. Respondents from lower density areas were also more likely to report there was more alcohol/drug use and more alcohol bootlegging in the past year, and that bootlegging alcohol is a serious problem in their county. Future research could include the examination of heterogeneity of rural areas using different indices.

Functional MRI of the lumbar spine in erect position in a superconducting open-configuration MR system: preliminary results.

The purpose of this study was to determine the feasibility of obtaining, and findings in, functional MRI of the lumbar spine in an erect position and with flexion and extension. Thirty subjects (including 5 volunteers) were imaged in a sitting position and while performing flexion and extension. The alternations in posterior disk margin, size of neural foramina, and central canal were evaluated. In addition, routine supine imaging was accomplished in 15 of these subjects. The foraminal size and posterior disk margins did not change appreciably from supine to upright position. With extension, there was an increased disk bulge in 27% of disks (40% of those with desiccation). Central canal size (50%) and foraminal size (27%) decreased with extension, especially at levels with disk desiccation. Images obtained with our open-configuration MR unit were diagnostically adequate, although of inferior quality compared with those obtained with a conventional unit. Our preliminary results show the feasibility of obtaining diagnostic images of the erect lumbar spine with flexion and extension. The results are in agreement with those obtained with cadaveric studies. The utility of this method in diagnostic imaging of patients with low back pain remains to be determined.

MR safety at high magnetic fields.

MR imaging requires the exposure of human patients to magnetic fields that are much more intense than ever occur naturally. Under most circumstances, however, these fields do not appear to pose a health or safety risk even at levels well above those currently in clinical use. This margin of safety results from the extreme weakness of the diamagnetic interaction between human tissues and magnetic fields. Ferromagnetic materials, however, present either as implants within the patient or inadvertently introduced into the scanner environment, pose significant risks and must be scrupulously avoided. At very high field strengths, there is evidence for mild sensory effects, such as vertigo and metallic tastes, which do not appear to be harmful.

Experience with MR-guided therapy.

The use of magnetic resonance imaging (MRI) for the real time guidance of surgical procedures is now undergoing clinical trials. Among the many procedures explored, open craniotomy neurosurgery appears to be among the most promising. Over 50 such cases have been done at the Brigham and Women's Hospital (BWH) in Boston. We review the technical approach used in these and related procedures. We consider the way in which imaging is used to augment and improve the procedures. As well, the implications of these protocols for remote diagnosis and telesurgery are explored. Finally, the implications of this experience for the insertion of new technology into medicine are discussed.

In vitro simulation. Early results of stereotaxy for pedicle screw placement.

STUDY DESIGN: Frameless stereotaxy with doppler ultrasound and three dimensional computer model registration is assessed in vitro for pedicle screw placement. OBJECTIVE: To identify feasibility of pedicle screw navigation and placement using this technology. SUMMARY OF BACKGROUND DATA: Inaccurate pedicle screw placement can lead to neurovascular injury or suboptimal fixation. Present techniques in pedicle screw placement involve only confirmation of hole orientation. METHOD: Forty-four pedicle screws were placed in lumbosacral models and cadaver specimens. Accuracy was assessed with a computed tomography scan and vertebral cross sectioning. RESULTS: All screws were intrapedicular. Accuracy of anterior cortical fixation was 1.5 mm, with a range of 2.5 mm. CONCLUSION: In vitro frameless stereotaxy is accurate for pedicle screw placement. This technology adds a component of navigation to pedicle screw placement.

The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds.

The concept of magnetic susceptibility is central to many current research and development activities in magnetic resonance imaging (MRI); for example, the development of MR-guided surgery has created a need for surgical instruments and other devices with susceptibility tailored to the MR environment; susceptibility effects can lead to position errors of up to several millimeters in MR-guided stereotactic surgery; and the variation of magnetic susceptibility on a microscopic scale within tissues contributes to MR contrast and is the basis of functional MRI. The magnetic aspects of MR compatibility are discussed in terms of two levels of acceptability: Materials with the first kind of magnetic field compatibility are such that magnetic forces and torques do not interfere significantly when the materials are used within the magnetic field of the scanner; materials with the second kind of magnetic field compatibility meet the more demanding requirement that they produce only negligible artifacts within the MR image and their effect on the positional accuracy of features within the image is negligible or can readily be corrected. Several materials exhibiting magnetic field compatibility of the second kind have been studied and a group of materials that produce essentially no image distortion, even when located directly within the imaging field of view, is identified. Because of demagnetizing effects, the shape and orientation, as well as the susceptibility, of objects within and adjacent to the imaging region is important in MRI. The quantitative use of susceptibility data is important to MRI, but the use of literature values for the susceptibility of materials is often difficult because of inconsistent traditions in the definitions and units used for magnetic parameters-particularly susceptibility. The uniform use of SI units for magnetic susceptibility and related quantities would help to achieve consistency and avoid confusion in MRI.

Imaging of brain iron by magnetic resonance: T2 relaxation at different field strengths.

Soon after the advent of magnetic resonance imaging (MRI) as a diagnostic modality in the 1980s, it was recognized that some of the contrast found in brain imaging correlated with patterns of iron deposition. The presence of non-heme iron had previously been established by pathological studies on post-mortem brains. The iron concentration is highest in specific nuclei of the basal ganglia and some associated structures. It is low at birth and increases with age until a relatively constant level is reached at an age of 20-30 years. There is evidence for further increases in very elderly persons. Although iron is ubiquitous in human tissues, only in a few situations is the concentration large enough to affect MRI. Because MRI has the ability to detect, in a noninvasive fashion, the naturally occurring iron in the basal ganglia and related nuclei, it may be used to study the physiology and pathology of these important structures. Magnetic resonance imaging has confirmed the results of earlier post mortem studies of the anatomical localization and age-dependence of brain iron. Initial steps have been toward the use of MRI to study disorders of thought, movement, and behavior that are believed to be related to brain iron. However, additional understanding is required of the physical details of the contrast mechanism, the physiology of the iron accumulation, and the significance of abnormal patterns of iron deposition. In this report, data are presented on the normal variation in MRI parameters and their dependence on magnetic field strength. The potential clinical and basic science applications are briefly reviewed. Information from widely differing fields is relevant to the study of the physical and pathological significance of brain iron, and for this reason, extensive, although not exhaustive, literature references are included.

Superconducting open-configuration MR imaging system for image-guided therapy.

PURPOSE: To develop a superconducting magnetic resonance (MR) imager that provides direct access to the patient and permits interactive MR-guided interventional procedures. MATERIALS AND METHODS: A 0.5-T superconducting magnet that allows a region of vertical access to the patient was designed and constructed. This magnet was integrated with newly designed shielded gradient coils, flexible surface coils, and nonmagnetic displays and with position-monitoring probes and device-tracking instrumentation. RESULTS: The magnet homogeneity was 12.3 ppm, and the gradient field was linear to within 1% over an imaging region 30 cm in diameter. The signal-to-noise ratio was 10% higher than in a comparable 0.5-T superconducting imager. Images were obtained in several anatomic regions with use of routine pulse sequences. Interactive image plane selection and near real-time imaging, with use of fast gradient-recalled echo sequences, were demonstrated at a rate of one image every 1.5 seconds. CONCLUSION: MR-guided interventional procedures can be performed with full patient access with use of an open-configuration, superconducting MR magnet with near real-time imaging and interactive image plane control.

Focused US system for MR imaging-guided tumor ablation.

PURPOSE: To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. MATERIALS AND METHODS: The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. RESULTS: The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. CONCLUSION: MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

The usefulness of a contrast agent and gradient-recalled acquisition in a steady-state imaging sequence for magnetic resonance imaging-guided noninvasive ultrasound surgery.

RATIONALE AND OBJECTIVES: The ability of magnetic resonance imaging to detect small temperature elevations from focused ultrasound surgery beams was studied. In addition, the value of a contrast agent in delineating the necrosed tissue volume was investigated. MATERIALS AND METHODS: Gradient-recalled acquisition in a steady state (GRASS) T1-weighted images were used to follow the temperature elevation and tissue changes during 2-minute sonications in the thigh muscles of 10 rabbits. The effects of the treatment on the vascular network was investigated by injecting a contrast agent bolus before or after the sonication. RESULTS: The signal intensity decreased during the sonication, and the reduction was directly proportional to the applied power and increase in temperature. The signal intensity returned gradually back to baseline after the ultrasound was turned off. Injection of the contrast agent increased the signal intensity in muscle, but not in the necrosed tissue. The dimensions of the delineated tissue volume were the same as measured from the T2-weighted fast-spin-echo images and postmortem tissue examination. CONCLUSIONS: These results indicate that magnetic resonance imaging can be used to detect temperature elevations that do not cause tissue damage and that contrast agent can be used to delineate the necrosed tissue volume.

MR temperature mapping of focused ultrasound surgery.

Deep lying soft tissue tumors may be treated by a nonincisional surgical procedure executed inside an MR imaging system using a thermal effect delivered by a focused ultrasound transducer. A prototype system is constructed to assess MRI thermal monitoring and the localization of the heat zone in muscle. The temperature distribution of the focal spot is imaged with MRI while mechanically moving the transducer with an hydraulic 3-axis positioner. Acoustic power is applied with a spherical shell transducer using 1- to 10-s duration pulses at frequencies of 1.5 MHz to selectively coagulate tissue at 60-70 degrees C. The procedure is monitored with a series of fast second gradient echo, T1-weighted, temperature sensitive MR sequences. Acquisitions are optimized for high temperature sensitive images that yield the thermal diffusivity, heat flow time constant and the focal spot size in muscle. MR temperature maps of muscle provide localization and dosimetry both in the focal region and near field.

Magnetic resonance-guided thermal surgery.

A demonstration of MR guided thermal surgery involved experiments with imaging of focused ultrasound in an MRI system, measurements of the thermal transients and a thermal analysis of the resulting images. Both the heat distribution and the creation of focused ultrasound lesions in gel phantoms, in vitro bovine muscle and in vivo rabbit muscle were monitored with magnetic resonance imaging. Thermal surgical procedures were modeled by an elongated gaussian heat source where heat flow is controlled by tissue thermal properties and tissue perfusion. Temperature profiles were measured with thermocouples or calculated from magnetic resonance imaging in agreement with the model. A 2-s T1-weighted gradient-refocused acquisition provided thermal profiles needed to localize the heat distribution produced by a 4-s focused ultrasound pulse. Thermal analysis of the images give an effective thermal diffusion coefficient of 0.0015 cm2/s in gel and 0.0033 cm2/s in muscle. The lesions were detected using a T2-weighted spin-echo or fast spin-echo pulse sequence in agreement with muscle tissue sections. Potential thermal surgery applications are in the prostate, liver, kidney, bladder, breast, eye and brain.