Small dense LDL cholesterol in human subjects with different chronic inflammatory diseases.

BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.

A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery.

We report a dual-band normalization technique for in vivo quantification of the metabolic biomarker, protoporphyrin IX (PpIX), during brain tumor resection procedures. The accuracy of the approach was optimized in tissue simulating phantoms with varying absorption and scattering properties, validated with fluorimetric assessments on ex vivo brain tissue, and tested on human data acquired in vivo during fluorescence-guided surgery of brain tumors. The results demonstrate that the dual-band normalization technique allows PpIX concentrations to be accurately quantified by correction with reflectance data recorded and integrated within only two narrow wavelength intervals. The simplicity of the method lends itself to the enticing prospect that the method could be applicable to wide-field applications in quantitative fluorescence imaging and dosimetry in photodynamic therapy.

Multiresolution MR elastography using nonlinear inversion.

PURPOSE: Nonlinear inversion (NLI) in MR elastography requires discretization of the displacement field for a finite element (FE) solution of the "forward problem", and discretization of the unknown mechanical property field for the iterative solution of the "inverse problem". The resolution requirements for these two discretizations are different: the forward problem requires sufficient resolution of the displacement FE mesh to ensure convergence, whereas lowering the mechanical property resolution in the inverse problem stabilizes the mechanical property estimates in the presence of measurement noise. Previous NLI implementations use the same FE mesh to support the displacement and property fields, requiring a trade-off between the competing resolution requirements. METHODS: This work implements and evaluates multiresolution FE meshes for NLI elastography, allowing independent discretizations of the displacements and each mechanical property parameter to be estimated. The displacement resolution can then be selected to ensure mesh convergence, and the resolution of the property meshes can be independently manipulated to control the stability of the inversion. RESULTS: Phantom experiments indicate that eight nodes per wavelength (NPW) are sufficient for accurate mechanical property recovery, whereas mechanical property estimation from 50 Hz in vivo brain data stabilizes once the displacement resolution reaches 1.7 mm (approximately 19 NPW). Viscoelastic mechanical property estimates of in vivo brain tissue show that subsampling the loss modulus while holding the storage modulus resolution constant does not substantially alter the storage modulus images. Controlling the ratio of the number of measurements to unknown mechanical properties by subsampling the mechanical property distributions (relative to the data resolution) improves the repeatability of the property estimates, at a cost of modestly decreased spatial resolution. CONCLUSIONS: Multiresolution NLI elastography provides a more flexible framework for mechanical property estimation compared to previous single mesh implementations.

Whole-brain MR-registered cryo-imaging of a porcine-human glioma model to compare contrast agent biodistributions.

As rapidly accelerating technology, fluorescence guided surgery (FGS) has the potential to place molecular information directly into the surgeon's field of view by imaging administered fluorescent contrast agents in real time, circumnavigating pre-operative MR registration challenges with brain deformation. The most successful implementation of FGS is 5-ALA-PpIX guided glioma resection which has been linked to improved patient outcomes. While FGS may offer direct in-field guidance, fluorescent contrast agent distributions are not as familiar to the surgical community as Gd-MRI uptake, and may provide discordant information from previous Gd-MRI guidance. Thus, a method to assess and validate consistency between fluorescence-labeled tumor regions and Gd-enhanced tumor regions could aid in understanding the correlation between optical agent fluorescence and Gd-enhancement. Herein, we present an approach for comparing whole-brain fluorescence biodistributions with Gd-enhancement patterns on a voxel-by-voxel basis using co-registered fluorescent cryo-volumes and Gd-MRI volumes. In this initial study, a porcine-human glioma xenograft model was administered 5-ALA-PpIX, imaged with MRI, and euthanized 22 hours following 5-ALA administration. Following euthanization, the extracted brain was imaged with the cryo-macrotome system. After image processing steps and non-rigid, point-based registration, the fluorescence cryo-volume and Gd-MRI volume were compared for similarity metrics including: image similarity, tumor shape similarity, and classification similarity. This study serves as a proof-of-principle in validating our screening approach for quantitatively comparing 3D biodistributions between optical agents and Gd-based agents.

Subzone based magnetic resonance elastography using a Rayleigh damped material model.

PURPOSE: Recently, the attenuating behavior of soft tissue has been addressed in magnetic resonance elastography by the inclusion of a damping mechanism in the methods used to reconstruct the resulting mechanical property image. To date, this mechanism has been based on a viscoelastic model for material behavior. Rayleigh, or proportional, damping provides a more generalized model for elastic energy attenuation that uses two parameters to characterize contributions proportional to elastic and inertial forces. In the case of time-harmonic vibration, these two parameters lead to both the elastic modulus and the density being complex valued (as opposed to the case of pure viscoelasticity, where only the elastic modulus is complex valued). METHODS: This article presents a description of Rayleigh damping in the time-harmonic case, discussing the differences between this model and the viscoelastic damping models. In addition, the results from a subzone based Rayleigh damped elastography study of gelatin and tofu phantoms are discussed, along with preliminary results from in vivo breast data. RESULTS: Both the phantom and the tissue studies presented here indicate a change in the Rayleigh damping structure, described as Rayleigh composition, between different material types, with tofu and healthy tissue showing lower Rayleigh composition values than gelatin or cancerous tissue. CONCLUSIONS: It is possible that Rayleigh damping elastography and the concomitant Rayleigh composition images provide a mechanism for differentiating tissue structure in addition to measuring elastic stiffness and attenuation. Such information could be valuable in the use of Rayleigh damped magnetic resonance elastography as a diagnostic imaging tool.

Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging.

PURPOSE: The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen/ carbogen, air/carbogen, and air/oxygen) was investigated. METHODS: Subjects breathed combinations of gases which were modulated in time. MR-guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air/air control to determine the hemodynamic changes compared to the baseline physiology. RESULTS: This study demonstrated that a gas stimulus consisting of alternating oxygen/carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air/oxygen or air/carbogen modulated breathing protocols. CONCLUSIONS: MR-guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements.

Considerations for NIR-I and short-wave infrared (SWIR) fluorescence imaging within a clinical operating room.

Short-wave infrared (SWIR/NIR-II) fluorescence imaging has received increased attention for use in fluorescence-guided surgery (FGS) due to the potential for higher resolution imaging of subsurface structures and reduced autofluorescence compared to conventional NIR-I imaging. As with any fluorescence imaging modality introduced in the operating room, an appropriate accounting of contaminating background signal from other light sources in the operating room is an important step. Herein, we report the background signals in the SWIR and NIR-I emitted from commonly-used equipment in the OR, such as ambient and operating lights, LCD screens and surgical guidance systems. These results can guide implementation of protocols to reduce background signal.

Sensitivity study and optimization of a 3D electric impedance tomography prostate probe.

In current clinical practice, the primary diagnostic method for testing for prostate cancer is ultrasound-guided biopsy. In this paper, we consider using a sonolucent array of electrodes, printed on a thin Kapton layer and positioned on the imaging window of a transrectal ultrasound probe, as a method for providing coregistered electrical and ultrasound imaging of the prostate. As the electrical properties of malignant tissues have been shown to differ significantly from benign tissues, the estimation of the electrical properties is expected to be helpful in distinguishing certain beginning pathologies from cancer and in improving the detection rate that current biopsy methods provide. One of the main difficulties in estimating electrical properties of tissues with this electrode configuration is the rapid decay of the sensitivity with distance from the sensing array. In order to partially overcome this difficulty, we propose to use prior information from the ultrasound (US). Specifically we intend to delineate the boundaries of the prostate from the US, to subdivide the organ into a small number of voxels and to estimate the conductivity as constant on each of these subvolumes. We use a 3D forward model based on the finite element method for studying the sensitivity of a simulated segmented prostate for three different electrode array designs. The three designs present different electrode areas and inter-electrode gaps. Larger electrodes are desirable as they present a better contact, but we show that as they result in smaller inter-electrode gaps, shunting currents can be significant and the sensitivity is reduced. Because our clinical measurement system employs a single current source, we consider tetrapolar measurement patterns for evaluating these electrode configurations. Optimal measurement patterns are well defined for adaptive systems, where multiple currents are injected at the same time. For the electrode array designs we consider, which are three dimensional, there are no established systematic methods for forming sets of linearly independent tetrapolar measurement patterns. We develop a novel method for automatically computing a full set of independent tetrapolar measurement patterns that maximizes the sensitivity in a region of interest (ROI). We use these patterns in the forward modeling and sensitivity studies. In addition to the electrode arrays on the probe, we study the use of a further configuration, where a distal electrode is positioned on the exterior of the body and used for current injection.

Distribution of Ixodes ricinus ticks and prevalence of tick-borne encephalitis virus among questing ticks in the Arctic Circle region of northern Norway.

This study investigated the geographical distribution of Ixodes ricinus and prevalence of the tick-borne encephalitis virus (TBEV) in northern Norway. Flagging for questing I. ricinus ticks was performed in areas ranging from Vikna in Nord-Trøndelag County, located 190km south of the Arctic Circle (66.3°N), to Steigen in Nordland County, located 155km north of the Arctic Circle. We found that ticks were abundant in both Vikna (64.5°N) and Brønnøy (65.1°N). Only a few ticks were found at locations ∼66°N, and no ticks were found at several locations up to 67.5°N. Real-time PCR (RT-PCR) analyses of the collected ticks (nymphs and adults) for the presence of TBEV revealed a low prevalence (0.1%) of TBEV among the nymphs collected in Vikna, while a prevalence of 0% to 3% was found among nymphs collected at five locations in Brønnøy. Adult ticks collected in Vikna and Brønnøy had higher rates of TBEV infection (8.6% and 0%-9.0%, respectively) than the nymphs. No evidence of TBEV was found in the few ticks collected further north of Brønnøy. This is the first report of TBEV being detected at locations up to 65.1°N. It remains to be verified whether viable populations of I. ricinus exist at locations north of 66°N. Future studies are warranted to increase our knowledge concerning tick distribution, tick abundance, and tick-borne pathogens in northern Norway.

Chemotherapy-induced nausea, vomiting, and fatigue--the role of individual differences related to sensory perception and autonomic reactivity.

BACKGROUND: In spite of antiemetics, postchemotherapy side effects continue to be common and may affect compliance to cancer treatment. Among the known factors associated with increased symptom severity are: younger age, treatment toxicity, expected severity, and distress, but little is still known about the role of other factors. The aim of our study was to investigate the role of individual differences related to sensory perception for posttreatment side effects. METHODS: Hundred and twenty-five women receiving adjuvant chemotherapy for breast cancer completed measures of absorption, autonomic perception, somatosensory amplification, trait anxiety, and expected severity at baseline. Pretreatment distress and posttreatment nausea, vomiting, and fatigue were assessed at the 1st, 4th, 6th and last cycles of chemotherapy. RESULTS: While univariate analyses showed several factors to be associated with side effects, only absorption and pretreatment distress remained independent predictors of nausea and fatigue when controlling for the remaining factors. Posttreatment vomiting was only predicted by expected severity of vomiting. CONCLUSION: Chemotherapy-induced side effects are related to increased autonomic nervous system activity, and absorption has been associated with increased autonomic nervous system reactivity to stress. The results suggest that individuals with high absorption may be at greater risk for developing side effects. Improved precision in identifying patients at risk of experiencing more severe side effects after cancer treatment will increase the ability to target treatments aimed at reducing these side effects.

Hyperspectral data processing improves PpIX contrast during fluorescence guided surgery of human brain tumors.

Fluorescence guided surgery (FGS) using aminolevulinic-acid (ALA) induced protoporphyrin IX (PpIX) provides intraoperative visual contrast between normal and malignant tissue during resection of high grade gliomas. However, maps of the PpIX biodistribution within the surgical field based on either visual perception or the raw fluorescence emissions can be masked by background signals or distorted by variations in tissue optical properties. This study evaluates the impact of algorithmic processing of hyperspectral imaging acquisitions on the sensitivity and contrast of PpIX maps. Measurements in tissue-simulating phantoms showed that (I) spectral fitting enhanced PpIX sensitivity compared with visible or integrated fluorescence, (II) confidence-filtering automatically determined the lower limit of detection based on the strength of the PpIX spectral signature in the collected emission spectrum (0.014-0.041 µg/ml in phantoms), and (III) optical-property corrected PpIX estimates were more highly correlated with independent probe measurements (r = 0.98) than with spectral fitting alone (r = 0.91) or integrated fluorescence (r = 0.82). Application to in vivo case examples from clinical neurosurgeries revealed changes to the localization and contrast of PpIX maps, making concentrations accessible that were not visually apparent. Adoption of these methods has the potential to maintain sensitive and accurate visualization of PpIX contrast over the course of surgery.

Viscoelastic power law parameters of in vivo human brain estimated by MR elastography.

The noninvasive imaging technique of magnetic resonance elastography (MRE) was used to estimate the power law behavior of the viscoelastic properties of the human brain in vivo. The mechanical properties for four volunteers are investigated using shear waves induced over a frequency range of 10-50Hz to produce a displacement field measured by magnetic resonance motion-encoding gradients. The average storage modulus (µR) reconstructed with non-linear inversion (NLI) increased from approximately 0.95 to 2.58kPa over the 10-50Hz span; the average loss modulus (µI) also increased from 0.29 to 1.25kPa over the range. These increases were modeled by independent power law (PL) relations for µR and µI returning whole brain, group mean exponent values of 0.88 and 1.07 respectively. Investigation of these exponents also showed distinctly different behavior in the region of the cerebral falx compared to other brain structures.

Suitability of poroelastic and viscoelastic mechanical models for high and low frequency MR elastography.

PURPOSE: Descriptions of the structure of brain tissue as a porous cellular matrix support application of a poroelastic (PE) mechanical model which includes both solid and fluid phases. However, the majority of brain magnetic resonance elastography (MRE) studies use a single phase viscoelastic (VE) model to describe brain tissue behavior, in part due to availability of relatively simple direct inversion strategies for mechanical property estimation. A notable exception is low frequency intrinsic actuation MRE, where PE mechanical properties are imaged with a nonlinear inversion algorithm. METHODS: This paper investigates the effect of model choice at each end of the spectrum of in vivo human brain actuation frequencies. Repeat MRE examinations of the brains of healthy volunteers were used to compare image quality and repeatability for each inversion model for both 50 Hz externally produced motion and ≈1 Hz intrinsic motions. Additionally, realistic simulated MRE data were generated with both VE and PE finite element solvers to investigate the effect of inappropriate model choice for ideal VE and PE materials. RESULTS: In vivo, MRE data revealed that VE inversions appear more representative of anatomical structure and quantitatively repeatable for 50 Hz induced motions, whereas PE inversion produces better results at 1 Hz. Reasonable VE approximations of PE materials can be derived by equating the equivalent wave velocities for the two models, provided that the timescale of fluid equilibration is not similar to the period of actuation. An approximation of the equilibration time for human brain reveals that this condition is violated at 1 Hz but not at 50 Hz. Additionally, simulation experiments when using the "wrong" model for the inversion demonstrated reasonable shear modulus reconstructions at 50 Hz, whereas cross-model inversions at 1 Hz were poor quality. Attenuation parameters were sensitive to changes in the forward model at both frequencies, however, no spatial information was recovered because the mechanisms of VE and PE attenuation are different. CONCLUSIONS: VE inversions are simpler with fewer unknown properties and may be sufficient to capture the mechanical behavior of PE brain tissue at higher actuation frequencies. However, accurate modeling of the fluid phase is required to produce useful mechanical property images at the lower frequencies of intrinsic brain motions.

Comparative theoretical performance for two types of regional hyperthermia systems.

Regional hyperthermia systems have drawn attention because of their potential for depositing power noninvasively in deep-seated tumors. Two such systems that have received clinical attention because of their ability to deposit significant amounts of power in tissue are magnetic induction devices and annular phased array applicators. In this paper, theoretical calculations for the specific absorption rate (SAR) and the resulting temperature distributions for these systems are compared. The finite element method is used in the formulation of both the electromagnetic and thermal boundary value problems. Six detailed patient models based on CT-scan data from the pelvic, visceral, and thoracic regions are generated to simulate a variety of tumor locations. In general, the annular phased array deposited more power within the tumor and produced better temperature distributions than the magnetic induction device. However, the ratio of the maximum power absorbed by the tumor to the maximum power absorbed in normal tissue does not appear to be high enough for either device to heat significant portions of perfused tumors to therapeutic temperatures under a wide range of physiological conditions. The results contained herein should aid the physician in comparative treatment planning with existing regional hyperthermia systems.

Optimization of the absorbed power distribution for an annular phased array hyperthermia system.

One of the systems under investigation for producing hyperthermia noninvasively for treating deep-seated tumors is the annular phased array. This device consists of two rings of eight electromagnetic apertures that are placed concentrically about the long axis of the patient and radiate energy toward the center. Previous theoretical and clinical studies have concentrated primarily on systems where the amplitude and phase of the signal applied to each aperture were the same, and these studies have shown that the system is capable of depositing power deep within the patient. Nevertheless, in many situations the system was not capable of producing desirable temperature distributions in the tumor and normal tissue. In this paper we report on a 2-dimensional theoretical investigation where an optimization routine was used to select the amplitude and phases of each of eight apertures. The optimization procedure and resulting calculations were based on CT scans of patients with tumors. The electrical and thermal properties of the different organs and tissues were taken into account. The optimization routine tried to achieve uniform absorbed power in the tumor region with zero absorbed power outside. Using the optimized amplitudes and phases, the SAR (specific absorption rate, W/kg) was calculated for the array. The results show that in general the optimization procedure was successful in that the power deposited within the tumor volume was increased with less power deposited into normal tissue when compared to the equal amplitude and phase case. This SAR data was then used as the input to a program based on the bioheat transfer equation, which calculated the temperature distribution in the patient model for an assumed set of blood perfusion rates. Depending on the location, size of the tumor, and blood perfusion rates, the improvement in the percentage of the tumor brought to therapeutic temperature varied from 0% to as much as 80%.

Theoretical temperature profiles for concentric coil induction heating devices in a two-dimensional, axi-asymmetric, inhomogeneous patient model.

In this paper we report on theoretical calculations for the temperature distributions produced by an rf magnetic induction device that is placed concentrically about the long axis of the patient. A two-dimensional, axi-asymmetric, inhomogeneous patient model was used in conjunction with a numerical moment method for calculating the electric fields in the tissues of the model and a numerical finite element method for calculating the resulting temperature distributions. The electric fields and the absorbed power per unit volume of tissue were calculated for both a thorax and viscera model, each of which included a tumor volume. The absorbed power values were input into the bioheat transfer equation and the temperature distributions were calculated for a wide range of blood flow rates. Based on the steady-state and transient results, our computer simulations predict poor therapeutic temperature profiles for tumors embedded deeply in the thorax and viscera. This heating technique appears to produce significant therapeutic volumes in superficial tumors located not greater than 7 cm in depth. These theoretical calculations should aid the clinician in the evaluation of induction heating devices for their effectiveness in heating deep-seated and superficial tumors.

Comparison of imaging geometries for diffuse optical tomography of tissue.

Images produced in six different geometries with diffuse optical tomography simulations of tissue have been compared using a finite element-based algorithm with iterative refinement provided by the Newton-Raphson approach. The source-detector arrangements studied include (i) fan-beam tomography, (ii) full reflectance and transmittance tomography, as well as (iii) sub-surface imaging, where each of these three were examined in a circular and a flat slab geometry. The algorithm can provide quantitatively accurate results for all of the tomographic geometries investigated under certain circumstances. For example, quantitatively accurate results occur with sub-surface imaging only when the object to be imaged is fully contained within the diffuse projections. In general the diffuse projections must sample all regions around the target to be characterized in order for the algorithm to recover quantitatively accurate results. Not only is it important to sample the whole space, but maximal angular sampling is required for optimal image reconstruction. Geometries which do not maximize the possible sampling angles cause more noise artifact in the reconstructed images. Preliminary simulations using a mesh of the human brain confirm that optimal images are produced from circularly symmetric source-detector distributions, but that quantitatively accurate images can be reconstructed even with a sub-surface imaging, although spatial resolution is modest.

Instrumentation and design of a frequency-domain diffuse optical tomography imager for breast cancer detection.

The instrument development and design of a prototype frequency-domain optical imaging device for breast cancer detection is described in detail. This device employs radio-frequency intensity modulated near-infrared light to image quantitatively both the scattering and absorption coefficients of tissue. The functioning components of the system include a laser diode and a photomultiplier tube, which are multiplexed automatically through 32 large core fiber optic bundles using high precision linear translation stages. Image reconstruction is based on a finite element solution of the diffusion equation. This tool for solving the forward problem of photon migration is coupled to an iterative optical property estimation algorithm, which uses a Levenberg-Marquardt routine with total variation minimization. The result of this development is an automated frequency-domain optical imager for computed tomography which produces quantitatively accurate images of the test phantoms used to date. This paper is a description and characterization of an automated frequency-domain computed tomography scanner, which is more quantitative than earlier systems used in diaphanography because of the combination of intensity modulated signal detection and iterative image reconstruction.

Prolonging myocardial preservation with a modified University of Wisconsin solution containing 2,3-butanedione monoxime and calcium.

The University of Wisconsin solution is an effective preservative for cold storage of the cardiac allograft. In an earlier study we showed that addition of calcium and 2,3-butanedione monoxime, a reversible inhibitor of myocardial contracture, further improved preservation of the rabbit heart. In this study we investigated the following: (1) the effects of different concentrations of 2,3-butanedione monoxime and calcium on function of the preserved rabbit heart, (2) how heart preservation is affected when 2,3-butanedione monoxime and calcium are added to the St. Thomas' Hospital and Stanford solutions, and (3) how 2,3-butanedione monoxime and calcium, at optimal concentrations in University of Wisconsin solution, affect hearts preserved up to 48 hours. Rabbit hearts were flushed with preservative and stored at 4 degrees C for 24, 30, 40, or 48 hours. Myocardial function was assessed during 60 minutes of isolated reperfusion, and myocardial adenine nucleotide content was measured after completion of reperfusion. Three concentrations of 2,3-butanedione monoxime (15, 30, and 60 mmol/L) in the University of Wisconsin solution were studied in hearts preserved for 30 hours. Storage with 2,3-butanedione monoxime at 30 mmol/L resulted in significantly better left ventricular developed pressure (p < 0.01), left ventricular end-diastolic volume (p < 0.01), rate of left ventricular pressure rise (p < 0.01), coronary flow (p < 0.05), rate-pressure product (p < 0.001), and adenine nucleotide regeneration (p < 0.05) than with 60 mmol/L, although function was not significantly different when the osmolarity of the solutions was equalized. There was significant reduction in end-diastolic volume (p < 0.05) and adenine nucleotide recovery (p < 0.01) when 2,3-butanedione monoxime was lowered to 15 mmol/L. Decreasing the calcium concentration from 1.0 to 0.1 mmol/L also had a deleterious effect on myocardial function (p < 0.05). The addition of 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium to the St. Thomas' or Stanford solutions improved preservation of the heart when compared with the unmodified solutions, but to a lesser degree than with the modified University of Wisconsin solution. After 24 to 48 hours of storage in University of Wisconsin solution containing 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium, there was substantial improvement in developed pressure (p < 0.001), end-diastolic volume (p < 0.05), and rate pressure product (p < 0.001), although there was little effect on heart rate and coronary flow, when compared with the unmodified University of Wisconsin solution.(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo electrical impedance spectroscopic monitoring of the progression of radiation-induced tissue injury.

This study evaluates the potential of electrical impedance spectroscopy (EIS) as a noninvasive technique for tracking the progression of radiation-induced damage in normal muscle tissue. Male Sprague-Dawley rats were irradiated locally to the gastrocnemius and biceps femoris muscle. Single doses were administered using a procedure that spares skin and bone. Complex impedance spectral measurements (taken at 50 frequency points between 1 kHz and 1 MHz) were made at monthly intervals using recessed disk electrodes applied to the skin. A histological scoring scheme was developed for evaluation of injury. A strong dose-dependent progression of injury evident in both spectral measurements and histological scoring has been observed. Latent time also appears to be dependent on dose with changes induced by 70 Gy evident by 2 months, changes induced by 90 Gy observed by 1 month, and dramatic changes found within 3 weeks at 150 Gy. Injury was morphologically comparable to the type of damage that occurs in response to small, fractionated doses, but on a much shorter time scale. Increased spectral shift was a consistent indicator of the extent of tissue injury at the time of measurement. The use of a large single dose resulted in an excellent model in terms of inducing a significant progression in tissue injury over a short post-treatment follow-up period in the muscle mass while also providing a consistent location for in vivo electrical impedance measurements. The results show that EIS can follow radiation-induced tissue change, suggesting that EIS has the potential to monitor the types of injury observed in late radiation damage of muscle tissue noninvasively.