Robert Kirton

Generalized spatiotemporal myocardial strain analysis for DENSE and SPAMM imaging

Displacement encoding using stimulated echoes (DENSE) and spatial modulation of magnetization (SPAMM) are MRI techniques for quantifying myocardial displacement and strain. However, DENSE has not been compared against SPAMM in phantoms exhibiting nonhomogeneous strain, and interobserver variability has not been compared between DENSE and SPAMM. To perform these comparisons, there is a need for a generalized analysis framework for the evaluation of myocardial strain. A spatiotemporal mathematical model was used to represent myocardial geometry and motion. The model was warped to each frame using tissue displacement maps calculated from either automated phase unwrapping (DENSE) or nonrigid registration (SPAMM). Strain and motion were then calculated from the model using standard methods. DENSE and SPAMM results were compared in a deformable gel phantom exhibiting known nonhomogeneous strain, and interobserver errors were determined in 19 healthy human volunteers. Nonhomogeneous strain in the phantom was accurately quantified using both DENSE and SPAMM. In the healthy volunteers, DENSE produced better interobserver errors than SPAMM for radial strain (−0.009 ± 0.069 vs. 0.029 ± 0.152, respectively, bias ±95% confidence interval). In conclusion, generalized spatiotemporal modeling enables robust myocardial strain analysis for DENSE or SPAMM. Magn Reson Med, 2011.

A unique micromechanocalorimeter for simultaneous measurement of heat rate and force production of cardiac trabeculae carneae

To study cardiac muscle energetics quantitatively, it is of paramount importance to measure, simultaneously, mechanical and thermal performance. Ideally, this should be achieved under conditions that minimize the risk of tissue anoxia, especially under high rates of energy expenditure. In vitro, this consideration necessitates the use of preparations of small radial dimensions. To that end, we have constructed a unique micromechanocalorimeter, consisting of an open-ended flow-through microcalorimeter, a force transducer, and a pair of muscle-length actuators. The device enables the metabolic and mechanical performance of cardiac trabeculae carneae to be investigated for prolonged periods in a continuously replenished oxygen- and nutrient-rich environment.

Characterization of a flow-through microcalorimeter for measuring the heat production of cardiac trabeculae

The energy consumption of isolated cardiac trabeculae can be inferred from measurements of their heat production. Once excised from the heart, to remain viable, trabeculae require continuous superfusion with an oxygen- and nutrient-rich solution. Flow-through calorimeters enable trabeculae to be maintained in a stable and controlled environment for many hours at a time. In this paper we describe and characterize a flow-through microcalorimeter, with sensitivity in the 1μW range, for measuring the heat output of 10μg cardiac trabeculae. The device uses infrared-sensitive, thin-film thermopile sensors to provide a noncontact method for measuring temperature differences. The sensors are capable of resolving 5μK temperature differences within the superfusing fluid. The microcalorimeter has a sensitivity of 2.56V∕W at a flow rate of 1μl∕s, with a time constant of approximately 3.5 s. The sensitivity and time constant are strongly dependent upon the flow rate. Predictions of a finite-element model of the calori...

Energetics of stress production in isolated cardiac trabeculae from the rat

The heat liberated upon stress production in isolated cardiac muscle provides insights into the complex thermodynamic processes underlying mechanical contraction. To that end, we simultaneously measured the heat and stress (force per cross-sectional area) production of cardiac trabeculae from rats using a flow-through micromechanocalorimeter. In a flowing stream of O(2)-equilibrated Tyrode solution (∼22°C), the stress and heat production of actively contracting trabeculae were varied by 1) altering stimulus frequency (0.2-4 Hz) at optimal muscle length (L(o)), 2) reducing muscle length below L(o) at 0.2 and 2 Hz, and 3) changing extracellular Ca(2+) concentrations ([Ca(2+)](o); 1 and 2 mM). Linear regression lines were adequate to fit the active heat-stress data. The active heat-stress relationships were independent of stimulus frequency and muscle length but were dependent on [Ca(2+)](o), having greater intercepts at 2 mM [Ca(2+)](o) than at 1 mM [Ca(2+)](o) (3.5 and 2.0 kJ·m(-3)·twitch(-1), respectively). The slopes among the heat-stress relationships did not differ. At the highest experimental stimulus frequency, pronounced elevation of diastolic Ca(2+) resulted in incomplete twitch relaxation. The resulting increase of diastolic stress, which occurred with negligible metabolic energy expenditure, subsequently diminished due to the time-dependent loss of myofilament Ca(2+)-sensitivity.

Radius-dependent decline of performance in isolated cardiac muscle does not reflect inadequacy of diffusive oxygen supply

The study of cardiac energetics commonly involves the use of isolated muscle preparations (papillary muscles or trabeculae carneae). Their contractile performance has been observed to vary inversely with thickness. This inverse dependence has been attributed, almost without exception, to inadequate diffusion of oxygen into the centers of muscles of large diameter. It is thus commonly hypothesized that the radius-dependent diminution of performance reflects the development of an anoxic core. We tested this hypothesis theoretically by solving a modification of the diffusion equation, in which the rate of oxygen consumption is a sigmoidal function of the partial pressure of oxygen. The model demonstrates that sufficiently thick muscles, operating at sufficiently high rates of oxygen demand or sufficiently low ambient partial pressures of oxygen, will indeed show diminished energetic performance, whether indirectly indexed as stress (force per cross-sectional area) development or as the rate of heat production. However, such simulated behavior requires the adoption of extreme parameter values, often differing by an order of magnitude from their experimental equivalents. We thus conclude that the radius-dependent diminution of muscle performance in vitro cannot be attributed entirely to an insufficient supply of oxygen via diffusion.

Strain softening behaviour in nonviable rat right‐ventricular trabeculae, in the presence and the absence of butanedione monoxime

Strain softening is commonly reported during mechanical testing of passive whole hearts. It is typically manifested as a stiffer force–extension relationship in the first deformation cycle relative to subsequent cycles and is distinguished from viscoelasticity by a lack of recovery of stiffness, even after several hours of rest. The cause of this behaviour is presently unknown. In order to investigate its origins, we have subjected trabeculae to physiologically realistic extensions (5–15% of muscle length at 26°C and 0.5 mm Ca2+), while measuring passive force and dynamic stiffness. While we did not observe strain softening in viable trabeculae, we found that it was readily apparent in nonviable (electrically inexcitable) trabeculae undergoing the same extensions. This result was obtained in both the presence and absence of 2,3‐butanedione monoxime (BDM). Furthermore, BDM had no effect on the passive compliance of viable specimens, while its presence partly inhibited, but could not prevent, stiffening of nonviable specimens. Loss of viability was accompanied by a uniform increase of dynamic stiffness over all frequencies examined (0.2–100 Hz). The presence of strain softening during length extensions of nonviable tissue resulted in a comparable uniform decrease of dynamic stiffness. It is therefore concluded that strain softening is neither intrinsic to viable rat right ventricular trabeculae nor influenced by BDM but, rather, reflects irreversible damage of tissue in partial, or full, rigor.

Myocardial twitch duration and the dependence of oxygen consumption on pressure-volume area: experiments and modelling

•  The energy expenditure of the heart is linearly related to its work performance, as measured by its development of pressure–volume area. •  We have explored the basis of this phenomenon both experimentally (by measuring the heat production of isolated ventricular tissue undergoing cyclic contraction and relaxation) and theoretically (using mathematical modelling). •  We provide the first evidence that the heat production of isolated trabeculae undergoing fixed‐end contractions varies linearly with force–length area, and confirm that twitch duration increases progressively with muscle length. •  Mathematical modelling reveals that length‐dependent prolongation of the twitch reflects length‐ (or, equivalently, force‐) dependent binding of Ca2+ to troponin‐C, together with Ca2+‐dependent crossbridge cooperativity. •  Mathematical modelling further reveals that the apparent linear dependence of heat production on force–length area is remarkably robust against departures from the linearity of length‐dependent twitch duration.

Design and development of a novel intra-vaginal pressure sensor

Introduction and hypothesisThe influence of intra-abdominal pressure (IAP) on prolapse development is poorly understood. Nonetheless, chronic cough, high BMI, or heavy lifting predisposes women to pelvic organ prolapse (POP). This study aims to develop and test a novel, wireless intra-vaginal pressure sensor (IVPS) to quantify intra-abdominal pressure changes across a range of well-defined activities.MethodsThe IVPS shape was based on silicone moulds of the vagina and was designed to sit in the proximal vagina. It is thin, compliant and negligibly distorts the surrounding tissues. Repeatability was assessed in 14 volunteers performing three sets of activities (cycles). Each cycle consisted of 18 activities. The IVPS was removed and reinserted after completing either the first or second of the three-cycle exercise routine (order). Participants independently inserted and removed the device. A nested split-plot, factorial ANOVA determined the effect of order using mean IAP increase (mean) and peak-to-peak fluctuations in IAP (amplitude) as dependent variables. Descriptive analysis examined the relative change in IAP across the activities. Cronbach’s alpha ®) determined repeatability.ResultsAll women found the IVPS comfortable and easy to insert. There was excellent correlation between cycles across all variables, r > 0.935 (mean) and r > 0.964 (amplitude). The order was not statistically significant, demonstrating a highly repeatable measurement.ConclusionThis is the first device to measure IAP at high frequency with the freedom of a wireless system. The IVPS aims to provide information to advise women better on suitable pre- and post-operative activities.

A sensitive flow-through microcalorimeter for measuring the heat production of cardiac trabeculae

Measurement of the energy consumption of isolated cardiac muscle requires a flow-through microcalorimeter with sensitivity in the /spl mu/W range. In this paper we describe and characterize a sensitive flow-through microcalorimeter, designed and constructed for measuring the heat output of cardiac trabeculae. The device exploits a non-contact, temperature-sensing technique utilizing infra-red-sensitive, thin-film thermopile sensors. The microcalorimeter achieves a sensitivity of 1.8 - 1.9 V/W at a flow rate of 1 /spl mu/l/s, with a time constant of approximately 3.5 s. The typical power signal-to-noise ratio is better than 200. Predictions of a finite element model of the calorimeters characteristics compare favourably with measured data.

Inexpensive optical system for microarray ELISA

The use of antibody-based diagnostic testing has increased significantly over the past decade, giving rise to a wide range of diagnostic devices. At one end of the cost-range are rapid inexpensive point-of-care tests based on immunochromatographic strips which provide a qualitative positive or negative test outcome. On the other hand, quantitative tests generally require the use of dedicated and expensive laboratory instruments. There remains a need for diagnostic instruments and tests that can provide quantitative assessment of disease markers at low cost. This paper describes the development of a novel low cost optical device for reading colorimetric and fluorescent immunodiagnostic test results. This portable instrument uses a webcam to capture test results from a specially designed 16-well slide containing a miniaturized array of test spots. Arrays are illuminated with either LEDs or lasers, while transmitted or emitted light is captured through a long-pass filter, allowing two different types of optical measurement to be performed within the same device. This device was used to read results from an array of antibodies conjugated with either an enzymatic or fluorescent tag resulting in a colored or fluorescent readout.