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Biomedical subjects

S Denslow

Publications and source records attributed to S Denslow.

At least 19 recordsLinked to original sources

A TMS coil positioning/holding system for MR image-guided TMS interleaved with fMRI.

OBJECTIVE: Transcranial magnetic stimulation (TMS) can be interleaved with fMRI to visualize regional brain activity in response to direct, non-invasive, cortical stimulation, making it a promising tool for studying brain function. A major practical difficulty is accurately positioning the TMS coil within the MRI scanner for stimulating a particular area of brain cortex. The objective of this work was to design and build a self-contained hardware/software system for MR-guided TMS coil positioning in interleaved TMS/fMRI studies. METHODS: A compact, manually operated, articulated TMS coil positioner/holder with 6 calibrated degrees of freedom was developed for use inside a cylindrical RF head coil, along with a software package for transforming between MR image coordinates, MR scanner space coordinates, and positioner/holder settings. RESULTS: Phantom calibration studies gave an accuracy for positioning within setups of dx=+/-1.9 mm, dy=+/-1.4 mm, dz=+/-0.8 mm and a precision for multiple setups of dx=+/-0.8 mm, dy=+/-0.1 mm, dz=+/-0.1 mm. CONCLUSIONS: This self-contained, integrated MR-guided TMS system for interleaved TMS/fMRI studies provides fast, accurate location of motor cortex stimulation sites traditionally located functionally, and a means of consistent, anatomy-based TMS coil positioning for stimulation of brain areas without overt response.

Calibration↗

Vagus nerve stimulation therapy: a research update.

Over the past 5 years, and especially within the last year, there has been a rapid expansion of vagus nerve stimulation (VNS)-related preclinical research, as well as clinical studies in indications other than epilepsy. The research advances in understanding VNS are occurring in the midst of a blossoming of other forms of therapeutic brain stimulation, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). In general, improved understanding of the neurobiological effects of VNS therapy as a function of the different use parameters (frequency, intensity, pulse width, duration, dose) is beginning to guide clinical use and help determine which diseases, in addition to epilepsy, VNS might treat.

Anxiety↗

Feasibility of vagus nerve stimulation-synchronized blood oxygenation level-dependent functional MRI.

RATIONALE AND OBJECTIVES: Left cervical vagus nerve stimulation (VNS) by use of an implanted neurocybernetic prosthesis (NCP) system is effective in treating epilepsy, with open data suggesting effectiveness in depression, yet the mechanisms of action are unknown. Our objective was to develop a methodology for performing VNS-synchronized functional magnetic resonance imaging (VNS-fMRI) and then to demonstrate its feasibility for studying VNS effects. METHODS: In nine patients implanted for treatment of intractable depression, a Macintosh computer was used to detect the signal from the implanted VNS stimulator and then to synchronize fMRI image acquisition with its regular firing. RESULTS: With our VNS-fMRI methodology, the blood oxygenation level-dependent response to VNS was shown in brain regions regulated by the vagus nerve: orbitofrontal and parieto-occipital cortex bilaterally, left temporal cortex, the hypothalamus, and the left amygdala. CONCLUSIONS: Vagus nerve stimulation pulses from an NCP system can be detected externally to determine its firing pattern, thus allowing VNS-fMRI studies of VNS-induced brain activity.

Adult↗

A new framework for echocardiographic assessment of left ventricular mechanics: sensitivity to heart failure.

A recent report describes an approach to ventricular mechanics that employs mean end-systolic fiber stress and an exact mathematical strain index based on wall thickness referenced to myocardial mass. We used echocardiography and mean arterial pressures to determine the strain index and wall stress in (1) normal hearts from patients and swine, (2) swine with pacing-induced congestive heart failure, and (3) patients with dilated cardiomyopathy. Pigs were also studied under afterload variation with phenylephrine. Paired values of stress and strain index from control hearts (both swine and human) were tightly clustered. Values from animals and patients with congestive heart failure deviated from this cluster. Excellent separation (sensitivity 83%, specificity 94%) was displayed between control and paced pigs, despite confounding effects of varying afterload. We conclude that these variables display little change over a large range of normal cardiac mass, but deviate from this range during heart failure.

Adolescent↗

Constraints on cardiac hypertrophy imposed by myocardial viscosity.

Laplace's law constrains how thin the ventricular wall may be without experiencing excessive stress. The present study investigated constraints, imposed by myocardial viscosity (resistance to internal rearrangement), on how thick the wall may be. The ventricle was modeled as a contracting, spherical shell. The analysis demonstrated that viscosity generates stress and energy dissipation with inverse fourth- and eighth-power dependence, respectively, on distance from the cavity center. This result derives from the combination of squared dependence of viscous forces on shearing velocity gradients and the greater shear rearrangement required for inner layers of a contracting sphere. These predictions are based solely on geometry and fundamentals of viscosity and are independent of material properties, cytoskeletal structure, and internal structural forces. Calculated values of energy and force required to overcome viscosity were clearly large enough to affect the extent of thickening of the left ventricle. It is concluded that load-independent viscous resistance to contraction is an important factor in cardiac mechanics, especially of the thickened ventricles of concentric hypertrophy.

Cardiomegaly↗

Wall thickness referenced to myocardial volume: a new noninvasive framework for cardiac mechanics.

Dimensional variables measured for study of left ventricular mechanics are subject to errors arising from difficulty in determining zero-stress dimensions for use as a reference. Based on a method validated for measurements within individuals, we have devised an approach that facilitates comparison between individuals while minimizing random scatter. We define an exact mathematical index of strain, ln(h(0)/h), using wall thickness (h) referenced to extrapolated wall thickness at zero-luminal volume (h(0)). Noninvasive data from rabbits, pigs, and humans all yielded highly similar myocardial stress, ln(h(0)/h), and work values. The stress-ln(h(0)/h) relationship during afterload variation was constant among individual pigs with a twofold variation in ventricular mass. Stress-ln(h(0)/h) data from our analysis displayed lower scatter than either pressure-volume data normalized to myocardial mass or stress-ln(h(0)/h) data referenced to end-diastolic dimensions. A Frank-Starling-like curve with high correlation (r(2) = 0.96) was constructed from single points from different pigs, suggesting a low level of size and intersubject scatter. This method offers high precision for noninvasive characterization of ventricular and myocardial mechanics and for comparisons between subjects and between species.

Animals↗

Right ventricular volumes revisited: a simple model and simple formula for echocardiographic determination.

Our objective was to establish a crescentic model of the right ventricle as the basis of a reported 2/3 (Area)(Length) empirical formula for volume. This formula has been investigated by others without cognizance of its connection to a clear geometric model. The particular model, an ellipsoidal shell or difference of ellipsoids, has been investigated by several groups by using different volume formulas. Accordingly, we obtained echocardiographic images in 2 orthogonal planes from 7 patients and 4 volunteers. Specified area and length measurements from these images were used to calculate right ventricular volumes. These volumes were compared with values determined through multislice, magnetic resonance imaging with summation of lumen areas, a widely accepted standard. Obtained high correlations compared favorably with those of previous investigators who used equivalent but less well understood methods. We conclude that the ellipsoidal shell model of the right ventricle provides a simple area-length formula for the determination of lumen volume with echocardiography.

Adolescent↗

Right ventricular volume estimation using an ellipsoidal shell model and single-plane magnetic resonance imaging.

RATIONALE AND OBJECTIVES: To investigate whether accurate right ventricular volumes could be obtained using an ellipsoidal shell model with magnetic resonance (MR) image measurements from a single imaging plane. METHODS: An initial retrospective patient study included 10 patients with congenital cardiac defects who had undergone same-day or next-day radiographic contrast ventriculography. An expanded study included MR scans of a total of 29 patients with congenital cardiac defects. Magnetic resonance scans of 10 healthy volunteers were also included in part of the study. Right ventricular volumes were calculated from (1) model-based calculations using single-plane cine MR imaging, and (2) multislice calculations based on contrast angiography. RESULTS: Regression of angiography-based volumes against MR-based volumes showed high correlation (r = 0.97, see = 12.5 mL) and slope near unity. Regression of right against left stroke volumes, both calculated from MR data, showed excellent correlation (r = 0.90, see = 11.6 ml) and slope near unity. CONCLUSIONS: The ellipsoidal shell model can be used to reliably estimate right ventricular volume using single-plane MR images.

Adolescent↗

Relationship between PVA and myocardial oxygen consumption can be derived from thermodynamics.

The pressure-volume area (PVA) has been shown to be an excellent, linear index of myocardial oxygen consumption. The thermodynamic basis for this result, however, has not been elucidated. The present study was undertaken to determine what information could be gained from analyzing the cardiac pressure-volume (P-V) cycle as an approximation to some "ideal" thermodynamic cycle operating under the constraints imposed by cardiovascular anatomy and physiology. The myocardium was approximated as a linear, chemically driven elastance in accordance with the time-varying elastance model. Analysis provided descriptions of a Carnot cycle for myocardium and a suboptimal ideal cycle, including isovolumic phases. Further analysis of the ideal cycle indicated that the end-systolic P-V relationship (ESPVR) is an approximation to the adiabatic P-V trajectory that primarily determines total energy consumption. Analysis also indicated possible explanations of current results that seem to be at odds with the time-varying elastance model. These results suggest that thermodynamic cycle analysis may provide a useful analytic tool for investigation of the cardiac cycle.

Animals↗

Right ventricular volume estimation with an ellipsoidal shell model and two-plane magnetic resonance imaging.

In patients with congenital and other heart disease, measurement of right ventricular (RV) volumes would be as useful as left ventricular (LV) volume measurement has been for diseases of the LV. Model-based techniques have had limited success. Simpson's rule (multislice) techniques require lengthy data collection and reduction. We investigated a technique for volume estimation with a new but simple geometric model. A retrospective patient study compared RV volumes from model-based calculations with dual-plane cine magnetic resonance (MR) imaging and multislice calculations with biplane cineangiography. Linear regression showed high correlation (r = 0.98, standard error of the estimate = 11.8 ml) between the two techniques, with a slope near unity. Comparison of calculated right and left stroke volumes also showed an excellent correlation (r = 0.93, standard error of the estimate = 10.4 ml) and a slope near unity. It is concluded that the ellipsoidal shell model can be used to estimate RV volume reliably and practically with dual-plane MR imaging.

Adolescent↗

Desktop publishing and medical imaging: paper as hardcopy medium for digital images.

Desktop-publishing software and hardware has progressed to the point that many widely used word-processing programs are capable of printing high-quality digital images with many shades of gray from black to white. Accordingly, it should be relatively easy to print digital medical images on paper for reports, instructional materials, and in research notes. Components were assembled that were necessary for extracting image data from medical imaging devices and converting the data to a form usable by word-processing software. A system incorporating these components was implemented in a medical setting and has been operating for 18 months. The use of this system by medical staff has been monitored.

Computer Graphics↗

An ellipsoidal shell model for volume estimation of the right ventricle from magnetic resonance images.

RATIONALE AND OBJECTIVES: I developed a volume estimation technique for the crescentic volume of the right ventricle (RV) of the heart. A geometric model was desired to avoid the lengthy data collection and reduction required by Simpson's rule. METHODS: An ellipsoidal shell model was developed that requires only simple mathematics and that resembles the RV shape. RV cast volumes were obtained by water displacement and Simpson's rule and model-based calculations using magnetic resonance (MR) imaging. RESULTS: Model-based estimates correlated well with water displacement volumes (r = 0.924), with a slope not significantly different from unity. Simpson's rule results showed a higher correlation (r = 0.994), but it required longer acquisition and processing. Geometric irregularity in the RV shape required no modification in mathematics. CONCLUSION: The model provides reliable RV volume estimates from two MR image planes. The mathematics provides a simple approach to a relatively complex, crescentic shape. Short times for data acquisition and analysis suggest the potential for time savings during routine clinical measurements.

Animals↗

Cloning and nucleotide sequence of the Vibrio proteolyticus aminopeptidase gene.

The gene encoding the Vibrio proteolyticus aminopeptidase was cloned and sequenced and its amino acid sequence was deduced. The gene encodes a 54 kDa protein, larger than the previously reported size of 30 kDa for the purified aminopeptidase. Sequence alignments revealed a 43-45% homology with two other Vibrio sp. extracellular proteinases.

Amino Acid Sequence↗

Myocardial stiffness derived from end-systolic wall stress and logarithm of reciprocal of wall thickness. Contractility index independent of ventricular size.

The slope of the end-systolic pressure-volume relation (ESPVR) is useful in assessing acute changes in contractile state. However, a limitation of ESPVR is that its slope decreases progressively as ventricular size increases without this change necessarily indicating a change in contractile state. In this respect, an index of contractile function that is independent of ventricular size would have an obvious advantage. The exponential constant (k) of the end-systolic relation between wall stress (sigma) and the natural logarithm of the reciprocal of wall thickness [ln(1/H)], sigma = Cekln(1/H), corresponds to the stiffness constant of the myocardium (kSM), a contractile index that should be independent of ventricular size and geometry. To examine the size independence of kSM, we studied left ventricular kSM during beta-blockade (to stabilize inotropic state) in 25 normal dogs with greatly differing ventricular sizes whose end-diastolic volumes ranged from 14 to 82 ml. The kSM was nearly constant (3.6 +/- 0.4) over this wide range of end-diastolic volumes and thus was independent of end-diastolic volume. Conversely, ESPVR, also obtained during beta-blockade, was closely and negatively correlated to end-diastolic volume (r = 0.92). To test the ability of kSM to measure changes in contractile state, we altered contractile state pharmacologically. The kSM increased from 3.7 +/- 0.5 to 4.8 +/- 0.8 (p less than 0.01) with infusion of dobutamine (after reversal of beta-blockade) and decreased to 3.1 +/- 0.3 (p less than 0.05) with inhalation of isoflurane, a negative inotrope, during beta-blockade (p less than 0.05). We conclude that kSM is independent of ventricular size and is sensitive to changes in inotropic state. As such, it should be useful as an index of contractile function.

Animals↗

Abnormal subendocardial blood flow in pressure overload hypertrophy is associated with pacing-induced subendocardial dysfunction.

To detect the functional significance of subendocardial hypoperfusion in the pressure-overloaded left ventricle, we studied subendocardial and subepicardial function and subendocardial and subepicardial blood flow simultaneously in seven dogs with left ventricular hypertrophy (left ventricle/body weight ratio, 7.2 g/kg) produced by chronic aortic banding. Seven normal dogs served as controls. Subendocardial and subepicardial segment lengths were measured by ultrasonic dimension gauges, and myocardial blood flow was measured with radioactive microspheres. Atrial pacing (180-200 beats/min for 5 minutes) was used to produce a chronotropic stress. In dogs with left ventricular hypertrophy, the subendocardial blood flow failed to increase during pacing compared with the baseline state (1.21 +/- 0.17 vs. 1.22 +/- 0.17 ml/min/g). Subendocardial shortening fraction deteriorated with pacing stress (before pacing, 30.6 +/- 3.9%; after pacing, 24.2 +/- 3.7%; p less than 0.001). In controls, subendocardial blood flow increased from 1.32 +/- 0.19 to 1.80 +/- 0.19 ml/min/g during pacing, and shortening fraction was preserved (before pacing, 25.5 +/- 3.9%; after pacing, 25.9 +/- 3.3%). Subepicardial blood flow in dogs with hypertrophy increased from 1.54 +/- 0.24 to 2.32 +/- 0.34 ml/min/g, and subepicardial shortening fraction was maintained (before pacing, 10.4 +/- 1.0%; after pacing, 10.5 +/- 1.2%) as it was in controls (subepicardial blood flow, from 1.27 +/- 0.18 to 2.12 +/- 0.17 ml/min/g; shortening fraction, from 16.6 +/- 2.5% to 15.5 +/- 2.2%). We conclude that, with pacing stress in pressure-overload hypertrophy, subendocardial blood flow failed to increase. This abnormality corresponded with a deterioration in subendocardial contractile function.

Analysis of Variance↗

Collagen synthesis in the developing chick heart.

We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.

Animals↗