Hugh J. Morris

Investigation of the viscous heating artefact arising from the use of thermocouples in a focused ultrasound field

Accurate temperature measurements in therapeutic ultrasound fields are necessary for understanding damage mechanisms, verification of thermal modelling and calibration of non-invasive clinical thermometry. However, artefactual heating, primarily due to viscous forces which result from motion relative to the surrounding tissue, occurs when metal thermocouples are used in an ultrasound field. The magnitude and time dependence of this artefact has been characterized by comparison with novel thin-film thermocouples (TFTs) at 1-2 cm focal depths in fresh degassed ex vivo bovine liver. High-intensity focused ultrasound exposures (1.7 MHz; free-field spatial-peak temporal-average intensities 40-600 W cm(-2)) were used. Subtraction of the TFT data from that obtained for other thermocouples yielded the time dependence of the viscous heating artefact. This was found to be intensity independent up to 600 W cm(-2) (below the threshold for cavitation and lesion formation) and remained significant at radial distances out to the first side lobe in the focal plane. The contribution of viscous heating to cooling was also found to be significant for at least 5 s after the end of insonation. The ratio of viscous artefact to absorptive heating after 5 s was: 1.76 +/- 0.07 for a fine-wire, 0.45 +/- 0.07 and 1.93 +/- 0.07 for two different sheathed-wires and 0.24 +/- 0.07 for a needle thermocouple.

Correlation Between Biomechanical Responses of Posterior Sclera and IOP Elevations During Micro Intraocular Volume Change

PURPOSE This study tested the hypothesis that intraocular pressure (IOP) elevations, induced by controlled increase of intraocular volume, are correlated with the biomechanical responses of the posterior sclera. METHODS Porcine globes were tested within 48 hours postmortem. The first group of globes (n = 11) was infused with 15 μL of phosphate-buffered saline at three different rates to investigate rate-dependent IOP elevations. The second group (n = 16) was first infused at the fast rate and then underwent inflation tests to investigate the relationship between IOP elevations (ΔIOP) and scleral strains. The strains in the superotemporal region of the posterior sclera were measured by ultrasound speckle tracking. Linear regression was used to examine the association between ΔIOP due to micro-volumetric infusion and the scleral strains at a specific inflation pressure. RESULTS The average ΔIOP was 14.9 ± 4.3 mm Hg for the infusion of 15 μL in 1 second. The ΔIOP was greater for the faster infusion rates but highly correlated across different rates (P < 0.001). A significant negative association was found between the ΔIOP and the tangential strains in both the circumferential (R(2) = 0.54, P = 0.003) and meridian (R(2) = 0.53, P = 0.002) directions in the posterior sclera. CONCLUSIONS This study showed a substantial increase in IOP, with a large intersubject variance during micro-volumetric change. A stiffer response of the sclera was associated with larger IOP spikes, providing experimental evidence linking corneoscleral biomechanics to IOP fluctuation. In vivo measurement of corneoscleral biomechanics may help better predict the dynamic profile of IOP.

Biaxial mechanical testing of posterior sclera using high-resolution ultrasound speckle tracking for strain measurements.

This study aimed to characterize the mechanical responses of the sclera, the white outer coat of the eye, under equal-biaxial loading with unrestricted shear. An ultrasound speckle tracking technique was used to measure tissue deformation through sample thickness, expanding the capabilities of surface strain techniques. Eight porcine scleral samples were tested within 72 h postmortem. High resolution ultrasound scans of scleral cross-sections along the two loading axes were acquired at 25 consecutive biaxial load levels. An additional repeat of the biaxial loading cycle was performed to measure a third normal strain emulating a strain gage rosette for calculating the in-plane shear. The repeatability of the strain measurements during identical biaxial ramps was evaluated. A correlation-based ultrasound speckle tracking algorithm was used to compute the displacement field and determine the distributive strains in the sample cross-sections. A Fung type constitutive model including a shear term was used to determine the material constants of each individual specimen by fitting the model parameters to the experimental stress-strain data. A non-linear stress-strain response was observed in all samples. The meridian direction had significantly larger strains than that of the circumferential direction during equal-biaxial loadings (Ps<0.05). The stiffness along the two directions was also significantly different (P=0.02) but highly correlated (R(2)=0.8). These results showed that the mechanical properties of the porcine sclera were nonlinear and anisotropic under biaxial loading. This work has also demonstrated the feasibility of using ultrasound speckle tracking for strain measurements during mechanical testing.

Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation.

Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs.

Corneoscleral stiffening increases IOP spike magnitudes during rapid microvolumetric change in the eye

Abstract Factors governing the steady‐state IOP have been extensively studied; however, the dynamic aspects of IOP are less understood. Clinical studies have suggested that intraocular pressure (IOP) fluctuation may be associated with glaucoma risk. This study aims to investigate how stiffening of corneoscleral biomechanical properties affects IOP spikes induced by rapid microvolumetric change. Porcine eyes (n = 25 in total) were subjected to volumetric infusions before and after external treatment of a circular area (11 mm diameter) in either the central cornea or posterior sclera. The treated area in the control group was immersed in phosphate‐buffered saline (PBS) for 40 min, while the treated area of the chemical crosslinking group was immersed in 4% glutaraldehyde/PBS for 40 min. A subset of the sham‐treated eyes was also subjected to volumetric infusions at a raised steady‐state IOP. The magnitude of IOP spikes increased after localized chemical crosslinking of either the cornea (27.5% increase, p < 0.001) or the sclera (14.3% increase, p < 0.001) with corneal crosslinking having a stronger effect than scleral crosslinking (p = 0.018). We also observed that raising the steady‐state IOP from 15 to 25 mmHg resulted in marked increase in IOP spike magnitudes by 63.9% (p < 0.001). These results suggested that an increased corneoscleral stiffness could significantly increase IOP spike magnitudes at the same volumetric change. Corneal stiffness appeared to have a strong impact on the IOP spike magnitude and may play a major role in regulating rapid volume‐pressure dynamics. An increase in steady‐state IOP also resulted in larger IOP fluctuations due to the increased “apparent” stiffness of the ocular shell, suggesting a potential interaction between the magnitude of IOP and its fluctuations. Corneoscleral properties may represent additional pathways for understanding and managing glaucoma risk and warrant future investigation. HighlightsStiffening a local area of either the cornea or the sclera resulted in increased magnitude of IOP spikes.Corneal stiffening of the same area has a larger impact on IOP spikes than scleral stiffening.The magnitude of steady‐state IOP significantly impacts the magnitude of IOP spikes.

Three-Dimensional Strains in Human Posterior Sclera Using Ultrasound Speckle Tracking

Intraocular pressure (IOP) induced strains in the peripapillary sclera may play a role in glaucoma progression. Using inflation testing and ultrasound speckle tracking, the 3D strains in the peripapillary sclera were measured in nine human donor globes. Our results showed that the peripapillary sclera experienced through-thickness compression and meridional stretch during inflation, while minimal circumferential dilation was observed when IOP was increased from 10 to 19 mmHg. The maximum shear was primarily oriented in the through-thickness, meridional cross sections and had a magnitude slightly larger than the first principal strain. The tissue volume had minimal overall change, confirming near-incompressibility of the sclera. Substantial strain heterogeneity was present in the peripapillary region, with local high strain areas likely corresponding to structural heterogeneity caused by traversing blood vessels. These 3D strain characteristics provide new insights into the biomechanical responses of the peripapillary sclera during physiological increases of IOP. Future studies are needed to confirm these findings and investigate the role of these biomechanical characteristics in ocular diseases.

Finite element modeling of the viscoelastic responses of the eye during microvolumetric changes

A linear viscoelastic finite element model was built to investigate factors that influenced the intraocular pressure (IOP) elevations due to micro-volumetric changes in the eye at three different rates. The viscoelastic properties of the cornea and the sclera, including the instantaneous modulus, equilibrium modulus, and relaxation time constants, parametrically varied to examine their effects on IOP elevations at different rates of volumetric changes. The simulated responses were in good agreement with the previously reported experimental results obtained from porcine globes, showing the general trend of higher IOP elevations at faster rates. The simulations showed that all viscoelastic properties influenced the profile of the dynamic IOP due to volumetric changes, and the relative significance of a specific parameter was highly dependent on the rate of change.

Directionality of individual cone photoreceptors in the parafoveal region.

The pointing direction of cone photoreceptors can be inferred from the Stiles-Crawford Effect of the First Kind (SCE-I) measurement. Healthy retinas have tightly packed cones with a SCE-I function peak either centered in the pupil or with a slight nasal bias. Various retinal pathologies can change the profile of the SCE-I function implying that the arrangement or the light capturing properties of the cone photoreceptors are affected. Measuring the SCE-I may reveal early signs of photoreceptor change before actual cell apoptosis occurs. In vivo retinal imaging with adaptive optics (AO) was used to measure the pointing direction of individual cones at eight retinal locations in four control human subjects. Retinal images were acquired by translating an aperture in the light delivery arm through 19 different locations across a subjects entrance pupil. Angular tuning properties of individual cones were calculated by fitting a Gaussian to the reflected intensity profile of each cone projected onto the pupil. Results were compared to those from an accepted psychophysical SCE-I measurement technique. The maximal difference in cone directionality of an ensemble of cones, ρ¯, between the major and minor axes of the Gaussian fit was 0.05 versus 0.29mm(-2) in one subject. All four subjects were found to have a mean nasal bias of 0.81mm with a standard deviation of ±0.30mm in the peak position at all retinal locations with mean ρ¯ value decreasing by 23% with increasing retinal eccentricity. Results show that cones in the parafoveal region converge towards the center of the pupillary aperture, confirming the anterior pointing alignment hypothesis.

Temperature Measurement in ex‐vivo Bovine Liver using Fine‐Wire and Thin‐Film Thermocouples

Temperatures due to ultrasonic exposures of ex vivo tissues are usually measured using fine‐wire thermocouples. These have also been used for thermometry in vivo and the results have been compared with those from other techniques such as magnetic resonance thermography. In this work, the use of both fine‐wire and thin‐film thermocouples in highly focused therapeutic ultrasound beams has been investigated. The phenomenon of viscous heating has been studied and an analytical method of quantifying the viscous heating artefact seen with fine‐wire thermocouples has been developed; no viscous heating was seen with thin‐film thermocouples. Using temperature rise versus time measured with these two types of thermocouple, the acoustic absorption coefficient of ex vivo bovine liver has been determined, and is found to be in good agreement with published values.

Rapid measurement of individual cone photoreceptor pointing using focus diversity.

A novel method is presented to rapidly measure the pointing direction of individual human cone photoreceptors using adaptive-optics (AO) retinal imaging. For a fixed entrance pupil position, the focal plane is rapidly modulated to image the guided light in various axial planes. For cones with different pointing directions, this focus diversity will cause a shift in their apparent position, allowing for their relative pointing to be determined. For four normal human subjects, retinal images were acquired, registered, and the positions of individual cones tracked throughout the dataset. Variation in cone tilt was 0.02 radians, agreeing with other objective measurements on the same subjects at the same retinal locations.