【APT 白皮书】Philips 3D APT (3)

2021
09/07

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CTMR技术园蒋强盛
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How does APT-weighted imaging yield a new contrast mechanism that can help clinicians with glioma grading and differentiate treatment effect from tumor progression?

APT 加权成像是如何产生一个新的对比机制来帮助临床医师进行胶质瘤的分级,以及区分治疗效应与肿瘤进展的?


APTw imaging is sensitive to the concentration of amide protons contained in proteins and peptides, which are known to be elevated in high grade gliomas and in recurring tumors.

APT 加权成像对于蛋白质与多肽中的酰胺质子浓度十分敏感,并且我们知道,在高级别胶质瘤与复发肿瘤中,酰胺质子浓度升高。


What are the principles behind APT-weighted imaging?
APT 加权成像的原理是什么?
W hile conventional MRI relies on the behavior of water protons in tissue, APTw imaging uses the signal of amide protons (NH groups) contained in proteins and peptides. Protein/peptide levels are known to be particularly elevated in aggressive, highly proliferative tumor tissues and to be strongly correlated with the tumor grade, which is assessed on pathological features and defined by the World Health Organization (WHO grade). As a form of Chemical Exchange Saturation Transfer (CEST) imaging, APTw MRI exploits the fact that amide protons in small proteins/peptides constantly exchange with water protons in close spatial proximity(Please refer to Figure 1 for a schematic illustration). 
常规磁共振成像依赖于组织中水质子的表现,而 APT 加权成像利用蛋白质与多肽中的酰胺质子 (-NH信号来成像。众所周知,在侵袭性、高度增殖的肿瘤组织中蛋白质/多肽水平将升高,并且跟肿瘤级别密切相关。肿瘤级别通过病理特点进行评估,并且由国际卫生组织进行分级(WHO grade)。作为化学交换饱和转移(CEST)成像的一种,APTw 成像利用了蛋白质/多肽中的酰胺质子与附近的水分子中的氢质子处于不断地交换当中这一特点(请参考图 1 示意图)。

Figure 1: Illustration of the bio-physical principles of Amide Proton Transfer weighted (APTw) MRI based on chemical exchange. Protons (H) bound to proteins and peptides are saturated with a long, frequency-specific RF pulse. These saturated protons exchange with protons part of diffusing water (H2O), resulting in a signal reduction of the water signal which correlates with the local concentration of proteins and peptides.

图 1:图解 APTw MRI 生理物理原理,APTw 基于化学交换。对与蛋白质和多肽结合的氢质子使用一持续时间长、特定频率的射频脉冲进行饱和,这些被饱和的质子与邻近的水分子中的氢质子进行交换,将导致自由水信号降低,降低的程度与局部蛋白质和多肽的浓度相关。


Because the amide protons have a different resonance frequency than the water protons, it is possible to selectively saturate the amide signal using radiofrequency (RF) irradiation tuned at a frequency of +3.5 ppm from the water resonance. When a water molecule is in close proximity to the amide group, the protons may exchange and carry over the nuclear spin saturation. In particular, the saturation is then found in the water signal that can be subsequently imaged by conventional means. When the saturation of the amide protons is maintained for about two seconds by continuous RF or pulsed RF, the final water saturation level is amplified due to accumulation of multiple proton saturation-exchange events. In addition, the resulting water saturation level is strongly correlated to the concentration of proteins/peptides in the tissue (in the cytoplasm of the tumor cells). This is observed via a drop of the total water signal in the respective imaging voxel.

由于酰胺质子与自由水质子的共振频率不同,那么可以实现使用比自由水共振频率高 3.5ppm 的射频脉冲选择性地对酰胺质子进行饱和。当有一个水分子与酰胺基靠得很近的时候,这个水分子中的氢质子就可能与酰胺质子进行化学交换,那么就把饱和的氢质子转移到水分子中了。尤其是,这一饱和效应进而可以在水信号中探测到,那么就可以使用常规的成像方法进行成像。当使用连续式或脉冲式脉冲对酰胺质子进行持续饱和达大约两秒时,由于质子饱和交换的不断累积,最终使得水质子被饱和的程度被扩大。除此之外,最终水质子被饱和的程度与组织中蛋白质/多肽(在肿瘤细胞的细胞质中)的浓度密切相关。这一饱和程度通过每一个成像体素中的水信号的下降程度来显示。

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关键词:
成像,饱和,酰胺,质子

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