An acoustic wavelet technology for delivering smart imaging probes to the brain

博士项目的目标：创建一种声子波技术，通过血脑屏障传递成像探针。合成新的和现有的单模和双模成像探针。使用核磁共振和荧光实验成像交付的成像探针。项目描述/背景：分子成像探针具有改变神经成像的潜力。虽然CT和常规MRI提供了大脑的结构和解剖信息，但分子探针可以识别特定于疾病及其阶段的过程。这可以让医生更早、更准确地对疾病进行分类，并将其与最佳治疗方案(即个性化药物)相匹配。一些重要的需求尚未得到满足，包括在手术切除胶质母细胞瘤后定位隐藏的癌细胞；及早识别阿尔茨海默病，以便启动正确的治疗。然而，由于血脑屏障，分子成像探针无法进入大脑，因此仍然不切实际。因此，目前，分子成像靶点仅限于血管内靶点，例如内皮细胞上的受体，这些靶点不太可能成为疾病的直接指标。我们希望将分子成像探针的范围扩大到所有血管外靶点--神经元、小胶质细胞和细胞外空间的疾病过程(例如，阿尔茨海默病中的ABeta斑块)。崔的实验室已经开发出一种声子波技术，可以通过血脑屏障输送药物。声波是一种短的、低压的超声波脉冲。与此同时，朗教授的实验室专门制造分子成像探针。在这个博士项目中，我们希望将小波技术与这些成像探针结合起来，创建一个使用MRI或其他成像模式对特定疾病过程进行成像的平台。为了能够通过小波传递使用分子成像探针，它必须不损害血脑屏障和脑组织。我们开发了一种用于血脑屏障开放的声学小波序列(图1)。在最近出版的《放射学》(2019)中，我们展示了以下内容：药物向实质的扩散传递进入细胞的传递短时间内血脑屏障通透性改变(&lt；20分钟)大小选择性的血脑屏障通透性改变

Aim of the PhD Project:Create an acoustic wavelet technology that delivers imaging probes across the blood-brain barrier.Synthesise new and existing single- and dual-modality imaging probes.Image the delivered imaging probes using MRI and fluorescence experiments.Project Description / Background:Molecular imaging probes have the potential to transform neuroimaging. Whereas CT and conventional MRI provide structural and anatomic information of the brain, molecular probes can identify processes that are specific to a disease and its stage. This could allow doctors to classify the disease earlier and more accurately, and match it with the best therapeutic option (i.e., personalised medicine). Some important unmet needs include locating hidden cancer cells after surgical removal of a glioblastoma tumour; and identifying Alzheimer's disease early so that the correct treatments can be initiated.However, molecular imaging probes cannot enter the brain, because of the blood-brain barrier, and thus remain impractical. Thus, at the moment, molecular imaging targets are constrained to intravascular targets, such as receptors on endothelial cells, which are unlikely to be direct indicators of the disease. We would like to widen the scope of molecular imaging probes to all extravascular targets - neurons, microglial cells, and disease processes in the extracellular space (e.g., ABeta plaques in Alzheimer's disease).Dr. Choi's lab has developed an acoustic wavelet technology that can deliver drugs across the blood-brain barrier. Acoustic wavelets are short, low-pressure ultrasound pulses. Meanwhile, Prof. Long's lab specialises in creating molecular imaging probes. In this PhD project, we would like to combine the wavelet technology with these imaging probes to create a platform for imaging specific disease processes using MRI or other imaging modalities.To enable the use of molecular imaging probes by wavelet delivery, it must not damage the blood-brain barrier and brain tissue. We have developed an acoustic wavelet sequence for blood-brain barrier opening (Fig. 1). In a recent publication Radiology (2019), we have shown the following:Diffuse delivery of drugs to parenchymaDelivery into cellsShort duration BBB permeability change (< 20 min)Size-selective BBB permeability change