DataSheet1_Precision MRI phenotyping of muscle volume and quality at a population scale.docx

Introduction: Magnetic resonance imaging (MRI) enables direct measurements of muscle volume and quality, allowing for an in-depth understanding of their associations with anthropometric traits, and health conditions. However, it is unclear which muscle volume measurements: total muscle volume, regional measurements, measurements of muscle quality: intermuscular adipose tissue (IMAT) or proton density fat fraction (PDFF), are most informative and associate with relevant health conditions such as dynapenia and frailty.
Methods: We have measured image-derived phenotypes (IDPs) including total and regional muscle volumes and measures of muscle quality, derived from the neck-to-knee Dixon images in 44,520 UK Biobank participants. We further segmented paraspinal muscle from 2D quantitative MRI to quantify muscle PDFF and iron concentration. We defined dynapenia based on grip strength below sex-specific cut-off points and frailty based on five criteria (weight loss, exhaustion, grip strength, low physical activity and slow walking pace). We used logistic regression to investigate the association between muscle volume and quality measurements and dynapenia and frailty.
Results: Muscle volumes were significantly higher in male compared with female participants, even after correcting for height while, IMAT (corrected for muscle volume) and paraspinal muscle PDFF were significantly higher in female compared with male participants. From the overall cohort, 7.6% (N = 3,261) were identified with dynapenia, and 1.1% (N = 455) with frailty. Dynapenia and frailty were positively associated with age and negatively associated with physical activity levels. Additionally, reduced muscle volume and quality measurements were associated with both dynapenia and frailty. In dynapenia, muscle volume IDPs were most informative, particularly total muscle exhibiting odds ratios (OR) of 0.392, while for frailty, muscle quality was found to be most informative, in particular thigh IMAT volume indexed to height squared (OR = 1.396), both with p-values below the Bonferroni-corrected threshold (p<8.8×10−5).
Conclusion: Our fully automated method enables the quantification of muscle volumes and quality suitable for large population-based studies. For dynapenia, muscle volumes particularly those including greater body coverage such as total muscle are the most informative, whilst, for frailty, markers of muscle quality were the most informative IDPs. These results suggest that different measurements may have varying diagnostic values for different health conditions.

引言：磁共振成像（Magnetic resonance imaging, MRI）可直接获取肌肉体积与质量的测量数据，从而能够深入解析其与人体测量学特征及健康状态的关联。但目前尚不明确，在肌肉体积测量指标（包括整体肌肉体积、区域肌肉体积）以及肌肉质量测量指标（肌间脂肪组织（intermuscular adipose tissue, IMAT）、质子密度脂肪分数（proton density fat fraction, PDFF））中，哪些指标具有最优的信息价值，且能与肌力减退症、衰弱综合征等相关健康状态产生关联。
方法：本研究针对44520名英国生物样本库（UK Biobank）参与者的颈膝段Dixon成像数据，提取了包括整体及区域肌肉体积、肌肉质量指标在内的影像衍生表型（image-derived phenotypes, IDPs）。此外，我们通过二维定量磁共振成像对椎旁肌肉进行分割，以量化其PDFF及铁浓度。本研究基于性别特异性握力截断值定义肌力减退症，并依据五项标准（体重下降、疲乏、握力、低体力活动水平、步行速度缓慢）定义衰弱综合征。采用逻辑回归分析肌肉体积与质量指标与肌力减退症、衰弱综合征的关联。
结果：相较于女性参与者，男性的肌肉体积显著更高，即使在校正身高因素后仍如此；而校正肌肉体积后的IMAT及椎旁肌肉PDFF在女性群体中显著更高。整体队列中，7.6%（N=3261）的参与者被诊断为肌力减退症，1.1%（N=455）被诊断为衰弱综合征。肌力减退症与衰弱综合征均与年龄呈正相关，与体力活动水平呈负相关。此外，肌肉体积与质量指标的降低均与肌力减退症、衰弱综合征相关。在肌力减退症分析中，肌肉体积IDPs的信息价值最优，其中整体肌肉体积的比值比（odds ratios, OR）为0.392；而在衰弱综合征分析中，肌肉质量指标的信息价值最优，尤其是校正身高平方后的大腿IMAT体积（OR=1.396），二者的p值均低于邦费罗尼校正阈值（p<8.8×10⁻⁵）。
结论：本研究的全自动分析方法可实现肌肉体积与质量的量化，适用于大规模人群队列研究。对于肌力减退症，肌肉体积指标（尤其是覆盖范围更广的整体肌肉体积）具有最优的诊断价值；而对于衰弱综合征，肌肉质量标志物则是最优的影像衍生表型。上述结果表明，不同的肌肉测量指标对不同健康状态的诊断价值存在差异。