SUVfdg: a standard-uptake-value (SUV) body habitus normalizer specific to fluorodeoxyglucose (FDG) in humans

In PET, several different Standard Uptake Value (SUV) metrics have been proposed utilizing different normalizers in an attempt to take into consideration the patient to patient differences in radionuclide uptake due to differences in body habitus (body weight, surface area, lean body mass). These normalizers are to some extent aribitrary in that they are selected from the list of proposed body habitus metrics, none of which necessarily describes well the distribution volume into which a given radionuclide labeled compound distributes with the body. 

In this work we propose a new body habitus normalizer, SUVfdg, that is specific to the tracer 18F-FDG and which like previously proposed SUV normalizers is a simple function of a patient's height and weight. Derivation of this metric assumed that absolute normal-liver FDG uptake rate is not itself a function of body habitus (i.e. is not correlated with height, weight, etc). The SUVfdg metric was tested in an independent cohort and shown to have little to no correlation with body habitus measures in normal liver, spleen and blood. When applied to normal brain uptake, it was shown to vary as a function of patient age.

Methods
After exclusions for type and extent of cancer and timing of the scan, a cohort of 481 patients was selected for analysis of 18F-FDG uptake into “normal” tissues (presumed to be unaffected by their disease). Among these, 65 patients had only brain concentrations measured and the remaining 416 were randomly divided into an 86-patient test set and a 330-patient training set. Within the test set, normal liver, spleen and blood measures were made. In the training set, only normal liver concentrations were measured. Using data from the training set, a simple polynomial function of height and weight was selected (following a subjective procedure) to predict each patient’s mean liver percent injected dose per milliliter. This function, when used to normalize measured %ID/ml concentrations, defines a new SUV metric (SUVfdg) which we compared to SUV metrics normalized by body weight (SUVbw), lean-body mass (SUVlbm) and body surface-area (SUVbsa) in a five-fold cross-validation. SUVfdg was also tested on the independent holdout sets utilizing the measurements of normal liver, blood, spleen and brain.

在正电子发射断层扫描（PET）中，已有多项研究提出了不同的标准化摄取值（Standard Uptake Value，SUV）指标，这些指标采用不同的归一化因子，旨在抵消因身体体型（体质量、体表面积、去脂体重）差异导致的患者间放射性核素摄取差异。这类归一化因子在一定程度上具有任意性，因为它们仅从已提出的身体体型相关指标中选取，而没有任何一种指标能够精准描述放射性核素标记化合物在体内的分布容积。

本研究提出一种针对示踪剂18F-氟代脱氧葡萄糖（18F-FDG）的新型身体体型归一化因子SUVfdg，与此前提出的SUV归一化因子类似，该指标仅与患者身高和体质量呈简单函数关系。该指标的推导基于一个假设：正常肝脏的FDG绝对摄取速率本身不受身体体型影响（即与身高、体质量等参数无相关性）。SUVfdg指标在独立队列中进行了验证，结果显示其在正常肝脏、脾脏及血液中几乎与身体体型指标无相关性；而将其应用于正常脑组织摄取时，则表现出随患者年龄变化的特征。

研究方法
在根据癌症类型、病变范围及扫描时间完成入排筛选后，本研究纳入481例患者，用于分析“正常”组织（推测不受肿瘤病变影响）的18F-FDG摄取情况。其中65例患者仅检测了脑组织的FDG摄取浓度，剩余416例患者被随机分为86例的测试集与330例的训练集。测试集采集了正常肝脏、脾脏及血液的摄取数据，训练集仅采集了正常肝脏的浓度数据。基于训练集数据，本研究通过主观筛选流程选取了一个关于身高与体质量的简单多项式函数，用于预测每位患者的肝脏组织每毫升注射剂量百分比均值。将该函数用于归一化实测的%ID/ml浓度后，即可得到新型SUV指标SUVfdg；本研究通过五折交叉验证，将SUVfdg与以体质量归一化的SUV（SUVbw）、去脂体重（lean body mass）归一化的SUV（SUVlbm）及体表面积（body surface area）归一化的SUV（SUVbsa）进行了对比。此外，本研究还利用独立预留集的正常肝脏、血液、脾脏及脑组织的摄取数据对SUVfdg进行了验证。