Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
Department of Neurosciences, Laboratory for Muscle Diseases and Neuropathies, KU Leuven, Leuven Brain Institute (LBI), Leuven, Belgium.
J Cachexia Sarcopenia Muscle. 2023 Jun;14(3):1468-1481. doi: 10.1002/jcsm.13234. Epub 2023 Apr 20.
Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown.
We included 27 adult patients with LGMDR12 and 27 age-matched and sex-matched healthy controls and acquired 6-point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale.
In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r = 0.85, P < 0.001) and vastus lateralis (r = 0.68, P = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo-distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P < 0.001), and different patterns of fat replacement within each of the muscles.
We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.
尽管磁共振成像（MRI）中质子密度脂肪分数（PDFF）的测量被广泛用于跟踪肌肉疾病的进展，但仍不清楚这些发现与肢带型肌营养不良症 12 型（LGMD12）患者肌肉活检中的组织病理学变化有何关系。此外，尽管已知 LGMD12 导致的肌肉受累与其他肌营养不良症不同，但这些肌肉内脂肪替代的空间分布尚不清楚。
我们纳入了 27 名成年 LGMD12 患者和 27 名年龄和性别匹配的健康对照者，并采集了大腿的 6 点 Dixon 图像和全身的 T1 和短 tau 反转恢复（STIR）MR 图像。在 16 名患者和 15 名对照者中，我们分别对股二头肌、股外侧肌和股直肌进行了 3 次肌肉活检，这些肌肉在 LGMD12 中分别受到严重、中度和轻度影响。我们将 PDFF 与相应肌肉活检中的脂肪百分比以及罗切斯特组织病理学分级量表进行了相关性分析。
在患者中，我们证明了 MRI 上的 PDFF 与股二头肌（r=0.85，P<0.001）和股外侧肌（r=0.68，P=0.005）活检脂肪百分比之间具有很强的相关性。我们还发现 PDFF 与罗切斯特组织病理学分级量表之间的相关性也相似。在 5 名肌肉活检有炎症改变的患者中，有 3 名患者的 MRI 相应肌肉出现了 STIR 高信号。通过对 18 个从起点到止点的大腿肌肉进行 MRI 上的 PDFF 建模，我们观察到 LGMD12 患者所有大腿肌肉的远近分布均存在明显不均匀的脂肪替代（P<0.001），并且每个肌肉内的脂肪替代模式也不同。
我们证明了 MRI 上的脂肪分数与病变肌肉活检中的脂肪百分比之间具有很强的相关性，并验证了 Dixon 脂肪分数成像作为 LGMD12 的一种疗效评估手段。影像学上大腿肌肉内不均匀的脂肪替代强调了只分析肌肉样本而不是整个肌肉的风险，这对临床试验具有重要意义。
