Cavitation in soft matter

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field

Femtosecond infrared intrastromal ablation and backscattering-mode adaptive-optics multiphoton microscopy in chicken corneas

The performance of femtosecond (fs) laser intrastromal ablation was evaluated with backscattering-mode adaptive-optics multiphoton microscopy in ex vivo chicken corneas. The pulse energy of the fs source used for ablation was set to generate two different ablation patterns within the corneal stroma at a certain depth. Intrastromal patterns were imaged with a custom adaptive-optics multiphoton microscope to determine the accuracy of the procedure and verify the outcomes. This study demonstrates the potential of using fs pulses as surgical and monitoring techniques to systematically investigate intratissue ablation. Further refinement of the experimental system by combining both functions into a single fs laser system would be the basis to establish new techniques capable of monitoring corneal surgery without labeling in real-time. Since the backscattering configuration has also been optimized, future in vivo implementations would also be of interest in clinical environments involving corneal ablation procedures

Thérapies ultrasonores cardiaques guidées par élastographie et échographie ultrarapides

Atrial fibrillation (AF) affects 2-3% of the European and North-American population, whereas ventricular tachyarrhythmia (VT) is related to an important risk of sudden death. AF and VT originate from dysfunctional electrical activity in cardiac tissues. Minimally-invasive approaches such as Radio-Frequency Catheter Ablation (RFCA) have revolutionized the treatment of these diseases; however the success rate of RFCA is currently limited by the lack of monitoring techniques to precisely control the extent of thermally ablated tissue.The aim of this thesis is to propose novel ultrasound-based approaches for minimally invasive cardiac ablation under guidance of ultrasound imaging. For this, first, we validated the accuracy and clinical viability of Shear-Wave Elastography (SWE) as a real-time quantitative imaging modality for thermal ablation monitoring in vivo. Second we implemented SWE on an intracardiac transducer and validated the feasibility of evaluating thermal ablation in vitro and in vivo on beating hearts of a large animal model. Third, a dual-mode intracardiac transducer was developed to perform both ultrasound therapy and imaging with the same elements, on the same device. SWE-controlled High-Intensity-Focused-Ultrasound thermal lesions were successfully performed in vivo in the atria and the ventricles of a large animal model. At last, SWE was implemented on a transesophageal ultrasound imaging and therapy device and the feasibility of transesophageal approach was demonstrated in vitro and in vivo. These novel approaches may lead to new clinical devices for a safer and controlled treatment of a wide variety of cardiac arrhythmias and diseases.La fibrillation atriale affecte 2-3% des européens et nord-américains, les tachycardies ventriculaires sont liées à un risque important de mort subite. Les approches minimalement invasives comme l’Ablation par Cathéter Radiofréquence (RFCA) ont révolutionné le traitement de ces maladies, mais le taux de réussite de la RFCA est limité par le manque de techniques d’imagerie pour contrôler cette ablation thermique.Le but de cette thèse est de proposer de nouvelles approches ultrasonores pour des traitements cardiaques minimalement invasifs guidés par échographie.Pour cela nous avons d’abord validé la précision et la viabilité clinique de l’Élastographie par Ondes de Cisaillement (SWE) en tant que modalité d’imagerie quantitative et temps réel pour l’ablation thermique in vivo. Ensuite nous avons implémenté la SWE sur un transducteur intracardiaque et validé la faisabilité d’évaluer l’ablation thermique in vitro et in vivo sur cœur battant de gros animal. Puis nous avons développé un transducteur intracardiaque dual-mode pour effectuer l’ablation et l’imagerie ultrasonores avec les mêmes éléments, sur le même dispositif. Les lésions thermiques induites par Ultrasons Focalisés de Haute Intensité (HIFU) et contrôlées par la SWE ont été réalisées avec succès in vivo dans les oreillettes et les ventricules chez le gros animal. Finalement la SWE a été implémentée sur un dispositif d’imagerie et thérapie ultrasonores transœsophagien et la faisabilité de cette approche a été démontrée in vitro et in vivo. Ces approches originales pourraient conduire à de nouveaux dispositifs cliniques pour des traitements plus sûrs et contrôlés d’un large éventail d’arythmies et maladies cardiaques

Modifying Ultrasound Waveform Parameters to Control, Influence, or Disrupt Cells

Ultrasound can be focused into deep tissues with millimeter precision to perform non-invasive ablative therapy for diseases such as cancer. In most cases, this ablation uses high intensity ultrasound to deposit non-selective thermal or mechanical energy at the ultrasound focus, damaging both healthy bystander tissue and cancer cells. Here we describe an alternative low intensity pulsed ultrasound approach known as “oncotripsy” that leverages the distinct mechanical properties of neoplastic cells to achieve inherent cancer selectivity. We show that when applied at a specific frequency and pulse duration, focused ultrasound selectively disrupts a panel of breast, colon, and leukemia cancer cell models in suspension without significantly damaging healthy immune or red blood cells. Mechanistic experiments reveal that the formation of acoustic standing waves and the emergence of cell-seeded cavitation lead to cytoskeletal disruption, expression of apoptotic markers, and cell death. The inherent selectivity of this low intensity pulsed ultrasound approach offers a potentially safer and thus more broadly applicable alternative to non-selective high intensity ultrasound ablation. In this dissertation, I describe the oncotripsy theory in its initial formulation, the experimental validation and investigation of testable predictions from that theory, and the refinement of said theory with new experimental evidence. Throughout, I describe how careful modifications to the ultrasound waveform directly can significantly impact how the ultrasound bio-effects control, influence, or disrupt cells in a selective and controlled manner.</p

Integrated butt-coupled membrane laser for Indium Phosphide on Silicon platform

In this work we present the design and technology development for an integrated butt-coupled membrane laser in the IMOS (Indium Phosphide Membrane On Silicon) platform . Laser is expected to have a small footprint (less than 50 µm 2 ), 1 mA threshold current and a direct modulation frequency of 10 GHz

Carbon nanotube mode-locked fiber lasers: recent progress and perspectives

Carbon nanotubes (CNTs) possess remarkable nonlinear optical properties; a particular application is to function as a mode locker used in ultrafast fiber lasers to produce ultrashort optical pulses. Various types of CNT saturable absorbers (SAs) and ultrafast fiber lasers have been demonstrated. In this review, typical fabrication process and development of CNT SAs are discussed and we highlight the recent investigation and progress of state-of-the-art ultrafast fiber lasers covering GHz, bidirectional ultrafast fiber lasers, vectorial mode fiber lasers, comb systems, and mode-locking dynamics. Our perspectives of ultrafast fiber lasers based on CNT SAs are given finally

Towards a solution of the closure problem for convective atmospheric boundary-layer turbulence

We consider the closure problem for turbulence in the dry convective atmospheric boundary layer (CBL). Transport in the CBL is carried by small scale eddies near the surface and large plumes in the well mixed middle part up to the inversion that separates the CBL from the stably stratified air above. An analytically tractable model based on a multivariate Delta-PDF approach is developed. It is an extension of the model of Gryanik and Hartmann [1] (GH02) that additionally includes a term for background turbulence. Thus an exact solution is derived and all higher order moments (HOMs) are explained by second order moments, correlation coefficients and the skewness. The solution provides a proof of the extended universality hypothesis of GH02 which is the refinement of the Millionshchikov hypothesis (quasi- normality of FOM). This refined hypothesis states that CBL turbulence can be considered as result of a linear interpolation between the Gaussian and the very skewed turbulence regimes. Although the extended universality hypothesis was confirmed by results of field measurements, LES and DNS simulations (see e.g. [2-4]), several questions remained unexplained. These are now answered by the new model including the reasons of the universality of the functional form of the HOMs, the significant scatter of the values of the coefficients and the source of the magic of the linear interpolation. Finally, the closures 61 predicted by the model are tested against measurements and LES data. Some of the other issues of CBL turbulence, e.g. familiar kurtosis-skewness relationships and relation of area coverage parameters of plumes (so called filling factors) with HOM will be discussed also

Imaging Feedback for Pulsed Cavitational Ultrasound Therapy: Histotripsy.

Histotripsy is a cavitational ultrasound therapy which mechanically fractionates soft tissue into subcellular debris using high intensity short ultrasound pulses. Histotripsy can be an effective tool for many clinical applications where non-invasive tissue removal is desired, including tumor therapy. For non-invasive tissue ablation therapy like histotripsy, image based feedback information allowing for accurate targeting, optimization of the on-going process, and prediction of the treatment efficacy in real time is the key to successful treatments. The overall goal of this research is to develop image based feedback methods that can accurately predict the clinical outcomes during and after histotripsy treatments. To achieve this goal, the research was conducted in two stages. In the first stage, new treatment strategies were investigated to produce homogeneous tissue fractionation. This ensures that feedback metrics obtained with any tissue characterization method are representative of the whole lesion instead of a misleading average of fully homogenized and non-homogenized zones. Specifically, two treatment strategies were developed. A focal zone sharpening technique, which limited the spatial extent of cavitation by preconditioning the cavitation nuclei in the surrounding area, was developed to create highly confined lesions with minimum scattered damage in the lesion boundaries. A cavitation memory removal strategy, which allowed for random distribution of cavitation in response to each therapy pulse, was developed to produce homogeneously fractionated lesions with a dramatically reduced therapy dose. In the second stage, three ultrasound image based methods were investigated to provide quantitative feedback information regarding the degree of tissue damage. These methods included ultrasound backscatter intensity analysis, ultrasound shear wave elasticity imaging, and characterization of shear wave propagation patterns. Strong correlations existed between the quantitative metrics derived from these methods and the degree of tissue fractionation as examined with histology, demonstrating the feasibility of using these metrics as quantitative feedback for histotripsy treatments. In conclusion, this research demonstrates that histotripsy can be a highly controllable tissue ablation therapy via precise control of cavitation. Significant potential exists for histotripsy to be developed into an image-guided modality for noninvasive ultrasound tissue ablation therapy.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/89658/1/tzuyin_1.pd

Comparing Gaussian and Bessel-Gauss beams for translating ultrafast laser ablation towards soft tissue surgery

The goal of this research was to further improve existing ultrafast laser surgery techniques. To do so, different beam shapes (Bessel-Gauss and Gaussian) were compared for performing ultrashort picosecond pulsed surgery on various soft biological tissues, with the goal of minimising collateral thermal damage. Initially, theoretical modelling was performed using OpticStudio to test axicons of various conical angles. A 20° axicon was selected, but unfortunately early tests on murine intestinal tissue indicated a lack of sufficient intensity to achieve plasma-mediated ablation of the tissue with the 6ps input pulses of 85 µJ energy. Subsequently, a reimaged setup was designed in OpticStudio to demagnify the beam by a factor of 1.4x. The ability of this demagnified Bessel-Gauss beam to perform plasma-mediated ablation of murine intestinal tissue was confirmed through histological analysis. Another setup was also designed to produce a Gaussian beam of equivalent spot size. These beams were then tested on porcine intestinal tissue using lower pulse repetition rates of 1, 2 and 3 kHz, with optimal ablation and thermal damage margins of less than 20 µm (confirmed through histological analysis) being achieved with the Bessel-Gauss beam for spatial pulse overlaps of 70%, while for the Gaussian beam the prominence of cavitation bubble formation at both 2 and 3 kHz inhibited the respective ablation processes at this same spatial pulse overlap. As the numbers of passes were increased, the Bessel-Gauss beam also showed a trend of increased ablation depths. This was attributed to its large depth of focus of over 1 mm, compared to the theoretical 48 µm depth of focus for the Gaussian beam. After characterisation of fixated, non-ablated porcine intestine sample surfaces to quantify the inhomogeneity, another set of ablation trials was performed at higher pulse repetition rates (5, 10 and 20 kHz) to test more clinically viable processes. For the Bessel-Gauss beam, spatial pulse overlaps of up to around 50% at 5, 10 and 20 kHz offered excellent thermal confinement (with damage margins of < 30 µm, < 50 µm and < 25 µm respectively) and shape control, but at 70% and greater pulse overlaps the ablated feature became hard to control despite good thermal confinement (< 40 µm). The Gaussian beam, while having the advantage of achieving plasma formation at lower input pulse energies, was again found to be more prone to undesirable cavitation effects. Cavitation bubbles were observed in the histology images for spatial pulse overlaps as low as 15% for 5 kHz and 30% for both 10 and 20 kHz. From the histology images it is clear to see that these effects became more pronounced as the pulse repetition rate was increased. Conversely, the more consistent spot size of the Bessel-Gauss beam across its longer focal depth resulted in a higher tolerance to cavitation bubble formation. This was also demonstrated by high-speed videos of the beams being scanned across porcine skin samples. This could be significant as it may allow for higher ablation rates. In addition, it could ease the design constraint of the maximum speed at which the beam can be scanned at the distal end of an endoscopic device. Despite this, both beams were able to achieve distinct ablation with high thermal confinement for certain parameters. This work further highlights fibre-delivered ultrashort laser pulses as a promising alternative to existing endoscopic tumour resection techniques, which carry a higher risk of bowel perforation.James Watt Scholarshi