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Biomedical subjects

R S Balaban

Publications and source records attributed to R S Balaban.

At least 37 records · Page 2Linked to original sources

Myocardial velocity gradient imaging by phase contrast MRI with application to regional function in myocardial ischemia.

Velocity-encoded phase contrast magnetic resonance imaging (MRI) has the potential to quantify regional myocardial contractile function with a sensitivity to motion comparable to implanted ultrasonic crystals. An MRI sequence and post-processing algorithm were developed to measure myocardial velocity gradients on a 1.5 T MRI scanner. These methods were validated on a rotating phantom and applied to dogs before (n = 11) and during prolonged coronary occlusion (n = 5). In phantom validation studies, the average absolute error corresponded to motion equivalent to 0.03 +/- 0.04 mm (mean +/- SD) during the repetition time of the experiment. Rigid body corrections during post-processing significantly simplified the interpretation of myocardial velocity vectors. In vivo, rigid body motion contributes substantially to the recorded myocardial velocities in systole and diastole and can give the false impression of regional wall motion abnormalities. After rigid body correction, normal systolic and diastolic velocity vectors in short-axis views of the left ventricle were primarily directed toward the center of the left ventricle. Transmural radial strain rate was 2.0 +/- 0.6 sec-1 during systole and -3.6 +/- 1.1 sec-1 during early diastole in normal canine hearts. Ischemic myocardium was easily discriminated from normal left ventricle by velocity-encoded phase contrast MRI both qualitatively and quantitatively (P < 0.01 in systole and P < 0.05 in early diastole). Although the myocardial velocity images have a spatial resolution on the order of a millimeter, the velocity encoding describes the mechanical consequences of focal myocardial ischemia with sensitivity to submillimeter displacement of the pixels. The three-dimensional nature of velocity-encoded MRI is particularly well suited to the study of the complex motion of the heart in vivo.

Animals↗

DENSE: displacement encoding with stimulated echoes in cardiac functional MRI.

Displacement encoding with stimulated echoes (DENSE) was developed for high-resolution myocardial displacement mapping. Pixel phase is modulated by myocardial displacement and data spatial resolution is limited only by pixel size. 2D displacement vector maps were generated for the systolic action in canines with 0.94 x 1.9 mm nominal in-plane resolution and 2.3 mm/pi displacement encoding. A radial strain of 0.208 was measured across the free left ventricular wall over 105 ms during systole. DENSE displacement maps require small first-order gradient moments for encoding. DENSE magnitude images exhibit black-blood contrast which allows for better myocardial definition and reduced motion-related artifacts.

Animals↗

High-resolution strain analysis of the human heart with fast-DENSE.

Single breath-hold displacement data from the human heart were acquired with fast-DENSE (fast displacement encoding with stimulated echoes) during systolic contraction at 2.5 x 2.5 mm in-plane resolution. Encoding strengths of 0.86-1.60 mm/pi were utilized in order to extend the dynamic range of the phase measurements and minimize effects of physiologic and instrument noise. The noise level in strain measurements for both contraction and dilation corresponded to a strain value of 2.8%. In the human heart, strain analysis has sufficient resolution to reveal transmural variation across the left ventricular wall. Data processing required minimal user intervention and provided a rapid quantitative feedback. The intrinsic temporal integration of fast-DENSE achieves high accuracy at the expense of temporal resolution.

Heart↗

Comparison of 3D BOLD functional MRI with spiral acquisition at 1.5 and 4.0 T.

In order to investigate the merit of high field strength for BOLD-contrast-based functional magnetic resonance imaging (fMRI) studies, multishot gradient-echo fMRI experiments during motor cortex activation were performed on 1.5- and 4.0-T scanners with equivalent hardware, on the same volunteers. In these studies, artifactual vascular enhancement related to inflow effects was minimized, and large brain areas were covered by using a 3D scan technique. Temporal signal stability was optimized by using spiral readout gradients. The sensitivity for detection of activated regions was assessed by measuring the number of "activated voxels" and their average t score in predefined regions of interest. When comparing fMRI experiments with the same total scan time, performed on six subjects, and with acquisition parameters optimized for each field strength separately, the 4.0-T scanner proved to give superior results, with a 70% greater number of activated voxels and a 20% higher average t score for the activated voxels.

Humans↗

Impairment of myocardial calcium homeostasis by antibodies against the adenine nucleotide translocator.

The adenine nucleotide translocator (ANT) is an autoantigen in myocarditis and dilated cardiomyopathy. Carrier-specific antibodies impair myocardial energy metabolism and heart function. They cross-react with a myolemmal calcium channel and alter calcium fluxes in isolated myocytes. To test whether antibodies against the ANT can alter calcium homeostasis in intact hearts, guinea pigs were immunized with the carrier protein and their isolated hearts loaded with the intracellular calcium indicator INDO-1. The diastolic and systolic ratios of fluorescence signals at 410 nm and 510 nm (emission wavelengths of the calcium-bound and calcium-free indicator), 'd-s410/510', were measured by excitation at 364 nm. This index of the transient calcium concentration associated with the contraction cycle correlated with the external heart work (EHW) in non-immunized controls. EHW of immunized animals was lower (76 +/- 62 vs 153 +/- 47 mJ/g/min in controls, p < 0.005) and the amplitude of d-s410/510 was elevated (27.6 +/- 4.1% of the average ratio of the whole heart cycle vs 21.7 +/- 1.2% in controls, p < 0.005) and essentially independent of EHW. Isoproterenol stimulation increased EHW in all hearts but d-s410/510 was hightened in control hearts, only. Thus, a disorder between cytosolic calcium transients and work was recorded in hearts from guinea pigs immunized with the ANT. It may contribute to an immunopathic mechanism of heart failure subsequent to myocarditis.

Animals↗

Real-time cardiac MRI using DSP's.

A real-time cardiac magnetic resonance imaging (MRI) system has been implemented using digital signal processing (DSP) technology. The system enables real-time acquisition, processing, and display of ungated cardiac movies at moderate video rates of 20 images/s. A custom graphical user interface (GUI) provides interactive control of data acquisition parameters and image display functions. Images can be compressed into moving-picture experts group (MPEG) movies, but are displayed on the console without compression during the scan. Compared to existing real-time MRI systems, implementation with DSP's allows rapid parallel computations, fast data transfers, and greater system flexibility, including the ability to scale to multiple channels, at the expense of somewhat higher component cost.

Artifacts↗

Myocardial oxygenation in vivo: optical spectroscopy of cytoplasmic myoglobin and mitochondrial cytochromes.

The oxygenation state of myoglobin and the redox state of cytochrome c provide information on the PO(2) in the cytosol and mitochondria, respectively. An optical "window" from approximately 540 to 585 nm was found in the pig heart in vivo that permitted the monitoring of myoglobin and cytochrome c without interference from Hb oxygenation or blood volume. Scanning reflectance spectroscopy was performed on the surgically exposed left ventricle of pigs. Difference spectra between control and a total left anterior descending coronary artery occlusion revealed maxima and minima in this spectral region consistent with myoglobin deoxygenation and cytochrome c and b reduction. Comparison of in vivo data with in vitro fractions of the heart, including Hb-free tissue whole heart and homogenates, mitochondria, myoglobin, and pig red blood cells, reveals minimal contributions of Hb in vivo. This conclusion was confirmed by expanding the blood volume of the myocardium and increasing mean Hb O(2) saturation with an intracoronary infusion of adenosine (20 microgram. kg(-1). min(-1)), which had no significant effect on the 540- to 585-nm region. These results also suggested that myoglobin O(2) saturation was not blood flow limited under these conditions in vivo. Work jump studies with phenylephrine also failed to change cytochrome c redox state or myoglobin oxygenation. Computer simulations using recent physical data are consistent with the notion that myoglobin O(2) saturation is >92% under basal conditions and does not change significantly with moderate workloads. These studies show that reflectance spectroscopy can assess myocardial oxygenation in vivo. Myoglobin O(2) saturation is very high and is not labile to moderate changes in cardiac workload in the open-chest pig model. These findings indicate that myoglobin does not contribute significantly to O(2) transport via facilitated diffusion under these conditions.

Animals↗

Visible-light photon migration through myocardium in vivo.

Empirical data between 510 and 590 nm of diffuse reflected light from the pig heart in vivo have shown that myoglobin and cytochrome c absorption peaks with little apparent contribution of red blood cell (RBC) Hb. Monte Carlo simulations of photon migration in tissue were performed to compare the effects of myoglobin and cytochromes with those of blood Hb on photon pathlengths and diffuse reflectance of visible wavelengths (450-600 nm) from the pig heart in vivo. Wavelength dependence of the input parameters, including the transport-corrected scattering coefficients (1.1-1.2 mm(-1)) and the absorption coefficients of blood-free solubilized heart tissue (0.43-1.47 mm(-1)), as well as the absorption coefficients of Hb, were determined by an integrating sphere method and standard spectrophotometry, respectively. The Monte Carlo simulations indicate that in the 510- to 590-nm range the mean path length within the myocardium for diffusely reflected light varies from 1.4 to 1.2 mm, whereas their mean penetration depth within the epicardium is only 330-400 micrometer for blood-free heart tissue. Analysis shows that the blood Hb absorption extrema are only observable between 510 and 590 nm when RBC concentration in tissue is >0.5%. Blood within vessels much larger than capillaries does not contribute significantly to the spectral features, because virtually all light in this spectral range is absorbed during transit through large vessels (>100 micrometer). This analysis suggests that diffuse reflected light in the 510- to 590-nm region will show spectral features uniquely associated with myoglobin and cytochrome c oxygenation states within 400 micrometer of the surface of the heart in situ as long as the capillary RBC concentration remains <0.5%.

Absorption↗

Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle.

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867-874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo (n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and (31)P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 microM or decrease the free energy of ATP hydrolysis to -55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 micromol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions (P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

Adenosine Diphosphate↗

Detection of proton chemical exchange between metabolites and water in biological tissues.

Metabolites in proton chemical exchange with water were detected via the water proton signal using saturation transfer techniques in model systems and biological tissues. The metabolites were selectively saturated and the resulting decrease in the much larger water proton pool was used to monitor the metabolite. This indirect detection scheme can result in a several orders of magnitude increase in sensitivity for metabolites over direct detection methods. A control irradiation scheme was devised to compensate for macromolecular/water magnetization transfer. Using this approach, significant chemical exchange regions at approximately 1 and 2.5 ppm were detected in kidney medulla. Using a difference imaging technique between a control irradiation above (-1.74 ppm) and below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney was calculated. These data revealed a linear gradient of chemical exchange increasing from the cortex to the medulla. Studies on medullary acid extracts and urine revealed that the exchange observed in the kidney was predominantly with low molecular weight metabolites. Urea (1 ppm) was identified as contributing to the kidney/urine chemical exchange; however, other unidentified metabolites may also contribute to this effect. These studies demonstrate that tissue metabolites can be detected and imaged via the water protons using the signal amplification properties of saturation transfer in the presence of water/macromolecule magnetization transfer.

Acids↗

Hall effect imaging.

This paper presents a new imaging method based on the classical Hall effect (HE), which describes the origin of a detectable voltage from a conductive object moving in a magnetic field. HE images are formed using ultrasound imaging techniques in a magnetic field. These images reflect the electrical properties of the sample. To demonstrate the feasibility of this method, images of plastic and biological samples are collected. The contrast mechanism and signal-to-noise issues are discussed. Since electrical parameters vary widely among tissue types and pathological states, HE imaging may be a useful tool for biological research and medical diagnosis.

Adipose Tissue↗

Correction for inner filter effects in turbid samples: fluorescence assays of mitochondrial NADH.

Fluorescent determinations of NADH in porcine heart mitochondria were subject to significant errors caused by alterations in inner filter effects during numerous metabolic perturbations. These inner filter effects were primarily associated with changes in mitochondrial volume and accompanying light scattering. The observed effects were detected in a standard commercial fluorometer with emission orthogonal to the excitation light path and, to a lesser extent, in a light path geometry detecting only the surface fluorescence. A method was developed to detect and correct for inner filter effects on mitochondrial NADH fluorescence measurements that were independent of the optical path geometry using an internal fluorescent standard and linear least-squares spectral analysis. A simple linear correction with the inner fluorescence reference was found to adequately correct for inner filter effects. This approach may be useful for other fluorescence probes in isolated mitochondria or other light-scattering media.

Adenosine Diphosphate↗

Ultrasonic imaging of the electroacoustic effect in macromolecular gels.

The electroacoustic effect occurs in electrolytes and colloidal suspensions. It describes the phenomenon in which a voltage applied to the sample produces an acoustic signal or vice versa. The basic mechanism is that charged particles in the sample have various mobilities due to different masses and viscosities. Under an external voltage they respond differently to the electrical force. This results in an overall acoustic vibration. The electroacoustic effect has been the basis for many measurement tools of solutions and other materials. In this note a method to image macromolecular gel samples using the electroacoustic effect at ultrasound frequencies is presented. Radiofrequency electrical excitation produces ultrasonic signal due to spatial changes in the electroacoustic some amplitude of the sample, which is used to construct an image similar to ultrasonography. This method is demonstrated in agar gel and egg-white protein phantoms. The image contrast mechanism is also discussed.

Gels↗

The potential for Hall effect breast imaging.

Hall effect imaging is a noninvasive imaging method that combines ultrasound with a strong magnetic field to investigate the electrical properties of tissue. Although technical development is at an early stage, its value for detecting or characterizing pathologies in the breast and other organs is promising. In vitro studies in the past showed that tissue electrical properties are closely related to its physiology and morphology. Hall effect imaging may become a new tool to study these electrical properties in the body and potentially provide unique diagnostic information.

Journal Article↗

The intrinsic signal-to-noise ratio in human cardiac imaging at 1.5, 3, and 4 T.

Cardiac imaging is inherently demanding on the signal-to-noise performance of the MR scanner and may benefit from high field strengths. However, the complex behavior of the radiofrequency field in the human body at high frequencies makes model-based analyses difficult. This study aims to obtain reliable comparisons of the signal-to-noise profile in the human chest in vivo at 1.5, 3, and 4 T. By using an RF-field-mapping method, it is shown that the intrinsic signal-to-noise increases with the field strength up to 4 T with a less than linear relation. The RF field profile is markedly distorted at 4 T, and the onset of this distortion is dependent on the body size. The high power deposition and the consequences of the RF field distortion are discussed.

Algorithms↗

Simulation of B1 field distribution and intrinsic signal-to-noise in cardiac MRI as a function of static magnetic field.

Two issues that pertain to the optimal static magnetic field for cardiac MRI were addressed: intrinsic signal-to-noise ratio (ISNR) and radiofrequency power deposition. From 1.5 to 9.5 T, proton Larmor frequencies of 63 to 400 MHz, numerical simulations were performed of the RF fields from a surface coil and a body coil loaded by a heterogeneous, three-dimensional, symmetric model of the human chest. The RF field distribution, the power required to produce the RF field, and the ISNR at the center of the heart were computed. The model was validated by comparison with experimental data up to 4 T. The RF field distortion was quantified and found to increase linearly up to 6 T due mostly to dielectric resonance modes. Body coil simulations beyond 6 T showed the onset of higher-order modes at the center of the heart. A range of expected RF power requirements was constructed as a function of field up to 9.5 T for surface coils and up to 6.8 T for body coils. Over this range of static field, ISNR for a constant coil geometry was bracketed by an upper limit that was slightly greater than linear with field and a lower limit that was slightly less than linear with field. The RF power and ISNR showed a strong dependence on chest thickness at 1.5 and 4.0 T. Additionally, independent of chest thickness, the model predicts a lower limit of a factor of 5 increase in RF power as the static field is increased from 1.5 to 4 T. Implications for imaging with other nuclei are discussed. Methods for checking the self-consistency of electrodynamic simulations are presented.

Algorithms↗

Assessing contrast on MR images.

Magnetic resonance imaging pulse sequences are frequently judged by their ability to facilitate discrimination between pathologic and normal tissue. Objective analysis is usually based on signal intensity measurements. However, the literature shows disagreement as to how this analysis should be performed. The ability to visually differentiate two objects on the basis of signal intensity depends on the contrast-to-noise ratio (CNR). This parameter, however, can be calculated only by measuring the intensity of photons reaching the eye from two distinct objects and, hence, is display dependent. The signal difference-to-noise ratio (SDNR) is a display-independent parameter that reflects the contrast-generating ability of a pulse sequence. When comparing two imaging sequences, the SDNR is proportional to the CNR, assuming the images being compared are displayed so that corresponding regions have the same intensity (i.e., photon fluxes). Because the SDNR is display independent, it should be the preferred parameter for assessing the contrast-generating ability of a pulse sequence. The value and limitations of these parameters are discussed.

Humans↗

Maximum oxidative phosphorylation capacity of the mammalian heart.

It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P(i)-driven heart mitochondrial respiratory rate (MV(O2 mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha1 alpha3 (cytochrome oxidase; Cyt a) content. To extrapolate this rate to the intact heart, the Cyt a content of the myocardium (nmol Cyt a/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P(i)-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O2 x min(-1) x nmol Cyt a(-1) in the dog and pig, respectively. The Cyt a content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt a/g wet wt, respectively. With these values, the MV(O2 mito) was calculated to be 29.5 (dog) and 24.3 (pig) micromol O2 x min(-1) x g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart.

Adenosine Diphosphate↗