High-resolution ultrasound imaging of micro-bubble cavitation using separate emission / reception transducers

微泡或空化剂的使用使研究领域得到了广泛而迅速的扩展，它们的好处在局部药物输送应用和超声图像增强方面得到了反复证明。在这两种情况下，微泡的振荡被利用，但它们的影响可能会根据超声频率和强度而变化。在低超声强度下，微气泡以稳定运动振荡，也称为稳定空化，对入射超声场产生线性反射和谐波响应。相反，在更高的超声强度下，惯性空化以微泡的快速生长和崩溃为特征，因此具有扩展的带宽。由于高强度超声会对组织造成不可逆的热损伤，因此应防止惯性空化，从而控制局部强度。为此目的，需要在目标地区建立一个能够集中和监测当地强度的双重系统。现有的双系统基于经典波束形成算法和专用超声探头的使用，用于空化和成像，并选择中心频率来诱导稳定的空化。然而，由于现有超声探头的带宽有限，谐波成像往往局限于二次谐波。其他基于治疗和成像换能器分离的技术已在文献中提出用于低强度和高强度聚焦超声。这些组件允许发射和接收分离，但繁琐且分辨率有限，因此不适合在访问窗口最多限制为1平方厘米的复杂位点内进行药物递送或成像（例如脊髓或颞骨窗口）。此外，在受限区域的情况下，周围器官（骨骼、界面）会引起超声波的反射、折射和扩散，从而影响聚焦和成像性能。基于这些观察结果，为了在复杂位点的情况下更好地利用造影剂进行聚焦和成像，应该解决两个挑战：1)设计和制造专用紧凑型换能器；2)在有限数据带宽下适应空化状态跟踪的成像算法。因此，该研究项目由2名博士和1名MASc学生并行进行，其目标是：1)提出基于独立发射/接收和空间复合的新型紧凑型换能器设计；2)适应现有的紧凑型治疗换能器组件的微加工技术；3)开发基于高分辨率相关的成像技术，用于复杂介质中的造影剂成像。使用数值模拟和体外模拟将考虑不同的应用，例如：脊髓，椎骨处的多重反射损害成像和聚焦，以及基于造影剂的经颅应用，其中通过头骨传输引起的相位和振幅畸变将被考虑。临床和临床前研究人员将在商业超声原型平台（Verasonics Vantage）上实现实时实施，并将在进一步的项目中使用。

The use of microbubbles or cavitation agents has enabled a wide and rapidly expanding field of research, with their benefits being repeatedly demonstrated, both in localized drug delivery applications and ultrasound image enhancement. In both cases, the oscillations of microbubbles are exploited but their effects may vary depending on the ultrasound frequency and intensity. At low ultrasound intensities, the microbubbles oscillate in a stable motion, also known as stable cavitation, inducing linear reflection and harmonic response to an incident ultrasound field. In contrast, at higher ultrasound intensities, inertial cavitation characterized by rapid growth and collapse of the microbubbles occur, and is thus characterized by an extended bandwidth. Since high intensity ultrasound can cause irreversible thermal damage to tissue, inertial cavitation should be prevented, and the local intensity thus controlled. For this purpose, a dual system capable of focusing and monitoring the local intensity is required at the targeted area.Existing dual systems are based on the use of classical beamforming algorithms and dedicated ultrasound probe used for both cavitation and imaging with a central frequency selected to induce stable cavitation. However, due to the limited bandwidth of existing ultrasound probes, the harmonic imaging is often limited to the second harmonic. Other technologies based on the separation of therapeutic and imaging transducers have been proposed in the literature for low- and high-intensity focused ultrasound. Those assemblies allow separation of emission and reception but are cumbersome and limited in resolution, and thus not adapted to drug delivery or imaging within complex loci where the access window is limited to 1 cm2 at best (spinal cord or temporal bone window for instance). Moreover, in the case of constrained areas, surroundings organs (bones, interfaces) induce reflections, refraction and diffusion of ultrasound waves that may influence the focusing and imaging performance. Based on these observations, two challenges should be addressed in order to better exploit contrast agents in the case of complex loci for both focalization and imaging: 1) the design and manufacturing of dedicated compact transducers and 2) the adaptation of imaging algorithms for cavitation regime tracking with a limited data bandwidth. This research project is thus organized following three distinct thrusts, conducted in parallel by 2 PhD and 1 MASc students, that aim 1) to propose novel compact transducer design based on separate emission / reception and spatial compounding, 2) to adapt existing micro-machining techniques for compact theranostic transducer assemblies and 3) to develop high-resolution correlation-based imaging techniques for contrast agent imaging in complex media. Different applications will be considered using numerical simulations and in-vitro phantoms such as: spinal cord for which multiple reflections at the vertebra impair the imaging and focusing, and contrast agent-based transcranial applications for which the phase and amplitude aberrations induced by the transmission through the skull will be considered. Real-time implementation for clinical and pre-clinical researchers on a commercial ultrasound prototyping platform (Verasonics Vantage) will be achieved for use in a further project.