Comprehensive Characterization of Breast Tissue Using Multi-modal MRI

摘要 磁共振弥散加权成像（DWI）以其独特的组织探测能力，已成为临床MRI的支柱 性能远远超出了传统的MRI可以实现其毫米分辨率。大多数DWI应用 依赖于与组织细胞相关的表观扩散系数（ADC）1，2。但 组织的综合性质不能通过单一测量充分地揭示3。最近 出版物指出，这些隐藏的属性可以使用b值“谱”的特定部分来探测。 在DWI 4中。例如，具有低b值的体素内非相干运动模型5 -7可以表征微运动。 无造影剂的血管分布，有可能补充动态对比增强MRI （DCE-MRI）高b值非高斯模型9 -24可以探测微结构，如连续- 时间随机游走模型17，19，21，25，26，它可以反映组织微观结构的异质性，从而能够研究 微观结构超越了细胞和血管。认识到乳房组织的复杂性， 成像界对将先进的DWI纳入其乳腺MRI表现出越来越大的兴趣 议定书27.然而，由于两个主要的原因，高级DWI对乳房的扩展尚未完全实现28，29 挑战首先，商业单次激发回波平面成像（ss-EPI）易于图像失真，这是不可能的。 由于偏离中心设置，乳房中的疼痛加剧30 -37。第二，多个MRI的综合方法- 还没有建立用于乳房组织表征的基于度量的方法38、39。该项目的主要目标是 开发两种成像工具，以实现乳房组织的全面表征：（1）一种新的、失真的- 弹性和时间效率高的DWI采集技术，以及（2）集成的多模态MRI分析框架。 我们的首要目标是将多高b值DWI的进步带到乳房。 假设乳腺肿瘤可以通过表征组织细胞结构、血管分布， 和不均匀性;这些属性可以通过利用一组DWI来全面探索 来自b值的整个谱的参数以及DCE-MRI度量。具体目标是： 1.为了开发一种新型的、抗失真的、时间效率高的脉冲序列，用于乳腺DWI的Steer-PROP， SPREAD -将启用具有从0到3000 s/mm 2的全频谱b值的DWI。 2.建立用于表征组织细胞结构、血管分布和异质性的基于MRI的指标;以及 开发一个集成的多模态MRI分析框架-MANUAL-乳腺。 3.证明SPREAD和MATERIAL在预测以下反应方面的潜在应用： 新辅助化疗（NAC）在乳腺癌中的应用。 该项目将提供新颖的工具，使DWI采集具有完整的b值谱和DWI 用于评估乳腺癌的恶性程度和评价治疗反应的分析。成功完成 将作为一个先进的扩散加权成像扩展到乳腺成像的原型。

ABSTRACT Diffusion-weighted MRI (DWI) has become a pillar of clinical MRI with its uniqueness to probe tissue properties well beyond the conventional MRI can achieve with its millimetric resolution. Most DWI applications rely on apparent diffusion coefficient (ADC) which has been associated with tissue cellularity1,2. However, the comprehensive properties of tissue cannot be adequately revealed by a single measurement3. Recent publications indicated these hidden properties can be probed using specific portions of the b-value “spectrum” in DWI4. For example, intravoxel incoherent motion model5–7 with low-b-values can characterize micro- vascularity without contrast agent, presenting a potential for complementing dynamic contrast-enhanced MRI (DCE-MRI)8. High-b-value non-Gaussian models9–24 can probe microstructures as in the case with continuous- time random walk model17,19,21,25,26 which can reflect tissue micro-structural heterogeneity, thus enable studying microstructures beyond cellularity and vascularity. Recognizing the complexity of the breast tissue, the breast imaging community has shown an increasing interest in incorporating advanced DWI into their breast MRI protocols27. However, expansion of advanced DWI to the breast has not been fully achieved28,29 due to two major challenges. Firstly, commercial single-shot echo-planar imaging (ss-EPI) is prone to image distortion, which is exacerbated in the breast due to off-center setting30–37. Secondly, an integrated approach with multiple MRI- based metrics has not been established for breast tissue characterization38,39. The main goal of this project is to develop two imaging tools to enable a comprehensive characterization of breast tissue: (1) a novel, distortion- resilient, and time-efficient DWI acquisition technique, and (2) an integrated multi-modal MRI analysis framework. Our overarching motivation is to bring the advancements in multi-high-b-value DWI to the breast. The hypothesis is that breast neoplasm can be evaluated by characterizing tissue cellularity, vascularity, and heterogeneity collectively; and these properties can be comprehensively probed by utilizing a set of DWI parameters from the entire spectrum of b-values together with DCE-MRI metrics. The specific aims are: 1. To develop a novel, distortion-resilient, and time-efficient pulse sequence, Steer-PROP for breast DWI – SPREAD – that will enable DWI with a full spectrum of b-values from 0 to 3000 s/mm2. 2. To establish MRI-based metrics for characterizing tissue cellularity, vascularity, and heterogeneity; and to develop an integrated multi-modal MRI analysis framework – TERMINAL – for the breast. 3. To demonstrate a potential application of SPREAD and TERMINAL in the context of predicting response to neoadjuvant chemotherapy (NAC) in breast cancer. This project will provide novel tools to enable DWI acquisition with a full b-value spectrum and DWI analysis for assessing malignancy and evaluating treatment response in breast cancer. Successful completion of the project will serve as a prototype for the expansion of advanced DWI into breast imaging.