Biomechanical Modelling of Porcine Kidney.

In this study, the viscoelastic properties of porcine kidney in the upper, middle and lower poles were investigated using oscillatory shear tests. The viscoelastic properties were extracted in the form of the storage modulus and loss modulus in the frequency and time domain. Measurements were taken as a function of frequency from 0.1 Hz to 6.5 Hz at a shear strain amplitude of 0.01 and as function of strain amplitude from 0.001 to 0.1 at a frequency of 1 Hz. Measurements were also taken in the time domain in response to a step shear strain. Both the frequency and time domain data were fitted to a conventional Standard Linear Solid (SLS) model and a semi-fractional Kelvin-Voigt (SFKV) model with a comparable number of parameters. The SFKV model fitted the frequency and time domain data with a correlation coefficient of 0.99. Although the SLS model well fitted the time domain data and the storage modulus data in the frequency domain, it was not able to capture the variation in loss modulus with frequency with a correlation coefficient of 0.53. A five parameter Maxwell-Wiechert model was able to capture the frequency dependence in storage modulus and loss modulus better than the SLS model with a correlation of 0.85.

Agarose as a Tissue Mimic for the Porcine Heart, Kidney, and Liver: Measurements and a Springpot Model.

Agarose gels are often used as a tissue mimic. The goal of this work was to determine the appropriate agarose concentrations that result in mechanical properties that match three different porcine organs. Strain tests were carried out with an amplitude varying from 0.01% to 10% at a frequency of 1 Hz on a range of agarose concentrations and porcine organs. Frequency sweep tests were performed from 0.1 Hz to a maximum of 9.5 Hz at a shear strain amplitude of 0.1% for agarose and porcine organs. In agarose samples, the effect of pre-compression of the samples up to 10% axial strain was considered during frequency sweep tests. The experimental measurements from agarose samples were fit to a fractional order viscoelastic (springpot) model. The model was then used to predict stress relaxation in response to a step strain of 0.1%. The prediction was compared to experimental relaxation data, and the results agreed within 12%. The agarose concentrations (by mass) that gave the best fit were 0.25% for the liver, 0.3% for the kidney, and 0.4% for the heart. At a frequency of 0.1 Hz and a shear strain of 0.1%, the agarose concentrations that best matched the shear storage modulus of the porcine organs were 0.4% agarose for the heart, 0.3% agarose for the kidney, and 0.25% agarose for the liver.

Foam gratings as an alternative to customized acoustic lenses.

This article describes a method of manipulating acoustic fields using transmission through foam gratings. The approach is investigated with an analytical model, a numerical model simulating full wave ultrasound propagation through the gratings, and experimental measurements. A grating is demonstrated that mimics a conventional ultrasound lens, modulating the phase of transmitted ultrasound while maximizing the transmitted amplitude. The performance of a foam grating is compared to a lens made of polydimethylsiloxane or three-dimensional printed resin. Using two gratings, independent control of amplitude and phase is demonstrated, with increased insertion loss. The primary advantages of this technique over conventional lenses are very rapid manufacture (<30 min), high repeatability due to the simplicity of manufacture, and the ability to control the amplitude of the transmitted ultrasound. Potential applications include generation of complex ultrasound fields for patient specific treatments in ultrasound therapy.

Transcranial ultrasound stimulation to human middle temporal complex improves visual motion detection and modulates electrophysiological responses.

BACKGROUND: Transcranial ultrasound stimulation (TUS) holds promise as a novel technology for non-invasive neuromodulation, with greater spatial precision than other available methods and the ability to target deep brain structures. However, its safety and efficacy for behavioural and electrophysiological modulation remains controversial and it is not yet clear whether it can be used to manipulate the neural mechanisms supporting higher cognitive function in humans. Moreover, concerns have been raised about a potential TUS-induced auditory confound. OBJECTIVES: We aimed to investigate whether TUS can be used to modulate higher-order visual function in humans in an anatomically-specific way whilst controlling for auditory confounds. METHODS: We used participant-specific skull maps, functional localisation of brain targets, acoustic modelling and neuronavigation to guide TUS delivery to human visual motion processing cortex (hMT+) whilst participants performed a visual motion detection task. We compared the effects of hMT+ stimulation with sham and control site stimulation and examined EEG data for modulation of task-specific event-related potentials. An auditory mask was applied which prevented participants from distinguishing between stimulation and sham trials. RESULTS: Compared with sham and control site stimulation, TUS to hMT+ improved accuracy and reduced response times of visual motion detection. TUS also led to modulation of the task-specific event-related EEG potential. The amplitude of this modulation correlated with the performance benefit induced by TUS. No pathological changes were observed comparing structural MRI obtained before and after stimulation. CONCLUSIONS: The results demonstrate for the first time the precision, efficacy and safety of TUS for stimulation of higher-order cortex and cognitive function in humans whilst controlling for auditory confounds.

Dual-Array Passive Acoustic Mapping for Cavitation Imaging With Enhanced 2-D Resolution.

Passive acoustic mapping (PAM) techniques have been developed for the purposes of detecting, localizing, and quantifying cavitation activity during therapeutic ultrasound procedures. Implementation with conventional diagnostic ultrasound arrays has allowed planar mapping of bubble acoustic emissions to be overlaid with B-mode anatomical images, with a variety of beamforming approaches providing enhanced resolution at the cost of extended computation times. However, no passive signal processing techniques implemented to date have overcome the fundamental physical limitation of the conventional diagnostic array aperture that results in point spread functions with axial/lateral beamwidth ratios of nearly an order of magnitude. To mitigate this problem, the use of a pair of orthogonally oriented diagnostic arrays was recently proposed, with potential benefits arising from the substantially expanded range of observation angles. This article presents experiments and simulations intended to demonstrate the performance and limitations of the dual-array system concept. The key finding of this study is that source pair resolution of better than 1 mm is now possible in both dimensions of the imaging plane using a pair of 7.5-MHz center frequency conventional arrays at a distance of 7.6cm. With an eye toward accelerating computations for real-time applications, channel count reductions of up to a factor of eight induce negligible performance losses. Modest sensitivities to sound speed and relative array position uncertainties were identified, but if these can be kept on the order of 1% and 1 mm, respectively, then the proposed methods offer the potential for a step improvement in cavitation monitoring capability.

Effect of Acoustic Radiation Force on Displacement of Nanoparticles in Collagen Gels.

Penetration of nanoscale therapeutic agents into the extracellular matrix (ECM) of a tumor is a limiting factor for the sufficient delivery of drugs in tumors. Ultrasound (US) in combination with microbubbles causing cavitation is reported to improve delivery of nanoparticles (NPs) and drugs to tumors. Acoustic radiation force (ARF) could also enhance the penetration of NPs in tumor ECM. In this work, a collagen gel was used as a model for tumor ECM to study the effects of ARF on the penetration of NPs as well as the deformation of collagen gels applying different US parameters (varying pressure and duty cycle). The collagen gel was characterized, and the diffusion of water and NPs was measured. The penetration of NPs into the gel was measured by confocal laser scanning microscopy and numerical simulations were performed to determine the ARF and to estimate the penetration distance and extent of deformation. ARF had no effect on the penetration of NPs into the collagen gels for the US parameters and gel used, whereas a substantial deformation was observed. The width of the deformation on the collagen gel surface corresponded to the US beam. Comparing ARF caused by attenuation within the gel and Langevin pressure caused by reflection at the gel-water surface, ARF was the prevalent mechanism for the gel deformation. The experimental and theoretical results were consistent both with respect to the NP penetration and the gel deformation.

Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. OBJECTIVE: We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. METHODS: In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS. RESULTS: We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. CONCLUSION: Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.

Ultrasound Neuromodulation: A Review of Results, Mechanisms and Safety.

Ultrasonic neuromodulation is a rapidly growing field, in which low-intensity ultrasound (US) is delivered to nervous system tissue, resulting in transient modulation of neural activity. This review summarizes the findings in the central and peripheral nervous systems from mechanistic studies in cell culture to cognitive behavioral studies in humans. The mechanisms by which US mechanically interacts with neurons and could affect firing are presented. An in-depth safety assessment of current studies shows that parameters for the human studies fall within the safety envelope for US imaging. Challenges associated with accurately targeting US and monitoring the response are described. In conclusion, the literature supports the use of US as a safe, non-invasive brain stimulation modality with improved spatial localization and depth targeting compared with alternative methods. US neurostimulation has the potential to be used both as a scientific instrument to investigate brain function and as a therapeutic modality to modulate brain activity.

Lipid-mRNA Nanoparticle Designed to Enhance Intracellular Delivery Mediated by Shock Waves.

Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based therapies. Encapsulation of macromolecules in lipid nanoparticles (LNPs) can protect the therapeutic agent during transport through the body and facilitate the intracellular delivery via a fusion-based pathway. Furthermore, designing LNPs responsive to stimuli can make their delivery more localized, thus limiting the side effects. However, the principles and criteria for designing such nanoparticles remain unclear. We show that the thermodynamic state of the lipid membrane of the nanoparticle is a key design principle for acoustically responsive fusogenic nanoparticles. We have optimized a cationic LNP (designated LNPLH) with two different phase transitions near physiological conditions for delivering mRNA. A bicistronic mRNA encoding a single domain intracellular antibody fragment and green fluorescent protein (GFP) was introduced into a range of human cancer cell types using LNPLH, and the protein expression was measured via fluorescence corresponding to the GFP expression. The LNPLH/mRNA complex demonstrated low toxicity and high delivery, which was significantly enhanced when the transfection occurred in the presence of acoustic shock waves. The results suggest that the thermodynamic state of LNPs provides an important criterion for stimulus responsive fusogenic nanoparticles to deliver macrodrugs to the inside of cells.

Spatial filters suppress ripple artifacts in the computation of acoustic fields with the angular spectrum method.

The angular spectrum method (ASM) is an effective tool for propagating wave fields between parallel planes through decomposition of the field into a series of independent plane waves. One source of error is interference from mirror sources introduced through the inherent periodicity of the fast Fourier transform (FFT) used to implement this method numerically. Here, spatial filters attenuate waves propagating at large angles, which are sensitive to mirror sources. Simulations show that this suppresses the ripple artifact whilst preserving the accuracy of the ASM-computed fields. To achieve comparable performance without filtering requires up to a 13.5-fold increase in computation time.

HIFU-induced changes in optical scattering and absorption of tissue over nine orders of thermal dose.

The optical properties of tissue change during thermal ablation. Multi-modal methods such as acousto-optic (AO) and photo-acoustic (PA) imaging may provide a real-time, direct measure of lesion formation. Baseline changes in optical properties have been previously measured over limited ranges of thermal dose for tissues exposed to a temperature-controlled water bath, however, there is scant data for optical properties of lesions created by HIFU. In this work, the optical scattering and absorption coefficients from 400-1300 nm of excised chicken breast exposed to HIFU were measured using an integrating sphere spectrophotometric technique. HIFU-induced spatiotemporal temperature elevations were measured using an infrared camera and used to calculate the thermal dose delivered to a localized region of tissue. Results obtained over a range of thermal dose spanning 9 orders of magnitude show that the reduced scattering coefficient increases for HIFU exposures exceeding a threshold thermal dose of CEM43 = 600 ± 81 cumulative equivalent minutes. HIFU-induced thermal damage results in changes in scattering over all optical wavelengths, with a 2.5-fold increase for thermal lesions exceeding 70 °C. The tissue absorption coefficient was also found to increase for thermally lesioned tissue, however, the magnitude was strongly dependent on the optical wavelength and there was substantial sample-to-sample variability, such that the existence of a threshold thermal dose could not be determined. Therapeutic windows, where the optical penetration depth is expected to be greatest, were identified in the near infrared regime centered near 900 nm and 1100 nm. These data motivate further research to improve the real-time AO and PA sensing of lesion formation during HIFU therapy as an alternative to thermometry.

On measuring the acoustic state changes in lipid membranes using fluorescent probes.

Ultrasound is increasingly being used to modulate the properties of biological membranes for applications in drug delivery and neuromodulation. While various studies have investigated the mechanical aspects of the interaction such as acoustic absorption and membrane deformation, it is not clear how these effects transduce into biological functions, for example, changes in the permeability or the enzymatic activity of the membrane. A critical aspect of the activity of an enzyme is the thermal fluctuations of its solvation or hydration shell. Thermal fluctuations are also known to be directly related to membrane permeability. Here solvation shell changes of lipid membranes subject to an acoustic impulse were investigated using a fluorescence probe, Laurdan. Laurdan was embedded in multi-lamellar lipid vesicles in water, which were exposed to broadband pressure impulses of the order of 1 MPa peak amplitude and 10 µs pulse duration. An instrument was developed to monitor changes in the emission spectrum of the dye at two wavelengths with sub-microsecond temporal resolution. The experiments show that changes in the emission spectrum, and hence the fluctuations of the solvation shell, are related to the changes in the thermodynamic state of the membrane and correlated with the compression and rarefaction of the incident sound wave. The results suggest that acoustic fields affect the state of a lipid membrane and therefore can potentially modulate the kinetics of channels and enzymes embedded in the membrane.

Full Modeling of High-Intensity Focused Ultrasound and Thermal Heating in the Kidney Using Realistic Patient Models.

OBJECTIVE: High-intensity focused ultrasound (HIFU) therapy can be used for noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using a nonlinear acoustic and thermal simulations in three patients. METHODS: The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size, and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion, and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second order polynomial function. RESULTS: The ultrasound field intensity was found to drop on average 11.1 dB with refraction and 6.4 dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1 dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Perfusion did not have a large effect on heating during short sonication durations. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. CONCLUSION: The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. SIGNIFICANCE: A method is proposed by that patient specific pre-treatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.

3D multicellular model of shock wave-cell interaction.

Understanding the interaction between shock waves and tissue is critical for advancing the use of shock waves for medical applications, such as cancer therapy. This work aims to study shock wave-cell interaction in a more realistic environment, relevant to in vitro and in vivo studies, by using 3D computational models of healthy and cancerous cells. The results indicate that for a single cell embedded in an extracellular environment, the cellular geometry does not influence significantly the membrane strain but does influence the von Mises stress. On the contrary, the presence of neighbouring cells has a strong effect on the cell response, by increasing fourfold both quantities. The membrane strain response of a cell converges with more than three neighbouring cell layers, indicating that a cluster of four layers of cells is sufficient to model the membrane strain in a large domain of tissue. However, a full 3D tissue model is needed if the stress evaluation is of main interest. A tumour mimicking multicellular spheroid model is also proposed to study mutual interaction between healthy and cancer cells and shows that cancer cells can be specifically targeted in an early stage tumour-mimicking environment. STATEMENT OF SIGNIFICANCE: This work presents 3D computational models of shock-wave/cell interaction in a biophysically realistic environment using real cell morphology in tissue-mimicking phantoms and multicellular spheroids. Results show that cell morphology does not strongly influence the membrane strain but influences the von Mises stress. While the presence of neighbouring cells significantly increases the cell response, four cell layers are enough to capture the membrane strain change in tissue. However, a full tissue model is necessary if accurate stress analysis is needed. The work also shows that cancer cells can be specifically targeted in early stage tumour mimicking environment. This work is a step towards realistic modelling of shock-wave/cell interactions in tissues and provides insight on the use of 3D models for different scenarios.

Response of Single Cells to Shock Waves and Numerically Optimized Waveforms for Cancer Therapy.

Shock waves are used clinically for breaking kidney stones and treating musculoskeletal indications. The mechanisms by which shock waves interact with tissue are still not well understood. Here, ultra-high-speed imaging was used to visualize the deformation of individual cells embedded in a tissue-mimicking phantom when subject to shock-wave exposure from a clinical source. Three kidney epithelial cell lines were considered to represent normal healthy (human renal epithelial), cancer (CAKI-2), and virus-transformed (HK-2) cells. The experimental results showed that during the compressive phase of the shock waves, there was a small (<2%) decrease in the projected cell area, but during the tensile phase, there was a relatively large (∼10%) increase in the projected cell area. The experimental observations were captured by a numerical model with a constitutive material framework consisting of an equation of state for the volumetric response and hyper-viscoelasticity for the deviatoric response. To model the volumetric cell response, it was necessary to change from a higher bulk modulus during the compression to a lower bulk modulus during the tensile shock loading. It was discovered that cancer cells showed a smaller deformation but faster response to the shock-wave tensile phase compared to their noncancerous counterparts. Cell viability experiments, however, showed that cancer cells suffered more damage than other cell types. These data suggest that the cell response to shock waves is specific to the type of cell and waveforms that could be tailored to an application. For example, the model predicts that a shock wave with a tensile stress of 4.59 MPa would increase cell membrane permeability for cancer cells with minimal impact on normal cells.

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model.

The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.

Full Modeling of High-Intensity Focused Ultrasound and Thermal Heating in the Kidney Using Realistic Patient Models.

OBJECTIVE: High-intensity focused ultrasound (HIFU) therapy can be used for noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have been variable. In this study, the efficacy of renal HIFU therapy was studied using nonlinear acoustic and thermal simulations in three patients. METHODS: The acoustic simulations were conducted with and without refraction in order to investigate its effect on the shape, size, and pressure distribution at the focus. The values for the attenuation, sound speed, perfusion, and thermal conductivity of the kidney were varied over the reported ranges to determine the effect of variability on heating. Furthermore, the phase aberration was studied in order to quantify the underlying phase shifts using a second-order polynomial function. RESULTS: The ultrasound field intensity was found to drop on average 11.1 dB with refraction and 6.4 dB without refraction. Reflection at tissue interfaces was found to result in a loss less than 0.1 dB. Focal point splitting due to refraction significantly reduced the heating efficacy. Of all the tissue parameters, perfusion was found to affect the heating the most. Small changes in temperature were seen with varying attenuation and thermal conductivity, but no visible changes were present with sound speed variations. The aberration study revealed an underlying trend in the spatial distribution of the phase shifts. CONCLUSION: The results show that the efficacy of HIFU therapy in the kidney could be improved with aberration correction. SIGNIFICANCE: A method is proposed by which patient specific pretreatment calculations could be used to overcome the aberration and therefore make ultrasound treatment possible.

Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates.

The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as "mechanical catalysts" to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.

CT Texture Analysis of Ex Vivo Renal Stones Predicts Ease of Fragmentation with Shockwave Lithotripsy.

INTRODUCTION: Understanding the factors affecting success of extracorporeal shockwave lithotripsy (SWL) would improve informed decision-making on the most appropriate treatment modality for an individual patient. Although stone size and skin-to-stone distance do correlate with fragmentation efficacy, it has been shown that stone composition and architecture, as reflected by structural heterogeneity on CT, are also important factors. This study aims to determine if CT texture analysis (CTTA), a novel, nondestructive, and objective tool that generates statistical metrics reflecting stone heterogeneity, could have utility in predicting likelihood of SWL success. MATERIALS AND METHODS: Seven spontaneously passed, intact renal tract stones, were scanned ex vivo using standard CT KUB and micro-CT. The stones were then fragmented in vitro using a clinical lithotripter, after which, chemical composition analysis was performed. CTTA was used to generate a number of metrics that were correlated to the number of shocks needed to fragment the stone. RESULTS: CTTA metrics reflected stone characteristics and composition, and predicted ease of SWL fragmentation. The strongest correlation with number of shocks required to fragment the stone was mean Hounsfield unit (HU) density (r = 0.806, p = 0.028) and a CTTA metric measuring the entropy of the pixel distribution of the stone image (r = 0.804, p = 0.039). Using multiple linear regression analysis, the best model showed that CTTA metrics of entropy and kurtosis could predict 92% of the outcome of number of shocks needed to fragment the stone. This was superior to using stone volume or density. CONCLUSIONS: CTTA metrics entropy and kurtosis have been shown in this experimental ex vivo setting to strongly predict fragmentation by SWL. This warrants further investigation in a larger clinical study for the contribution of CT textural metrics as a measure of stone heterogeneity, along with other known clinical factors, to predict likelihood of SWL success.