Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography

Abstract

Background: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema.

Hypothesis: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema.

Study type: Prospective cross-sectional study.

Subjects: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14).

Field strength/sequence: 3T MR lymphangiography (nontracer 3D turbo-spin-echo).

Assessment: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features.

Statistical tests: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05.

Results: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84).

Data conclusion: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema.

Evidence level: 1 TECHNICAL EFFICACY: Stage 1.

Keywords: lipedema; lipoedema; lymphangiography; lymphedema; obesity.

Figure 1.. Lower-extremity clinical features of lipedema and lymphedema.

a) Lipedema presents with skin and subcutaneous abnormalities including skin dimpling in stage 2 (yellow arrow) and ankle cuffing from adipose deposition in type 3 sparing the feet (white arrow). b) Easy-bruising commonly accompanies lipedema (arrow). c) Secondary leg lymphedema due to cancer therapies often presents with asymmetrical swelling of the limbs and may only involve one limb (arrow). d) Dorsal foot swelling is characteristic of primary or secondary lymphedema (arrow).

Figure 2.. Imaging protocol to evaluate MR lymphangiography of the lower extremities.

a) Example MRI is displayed in a whole-body manner in a patient with lipedema with lymphedema (age=44 years, BMI=27.1 kg/m², lipedema stage 2 and lymphedema stage 2). Chemical-shift-encoded fat-weighted MRI is displayed for anatomical reference. b) MR lymphangiography was acquired in this participant in the pelvis, thigh, knee, and calf regions. Acquisitions are rendered stacked as a maximum-intensity-projection (green box). Hyperintensities in the subcutaneous tissue (arrow) and inguinal lymph node territories (circle) are observed, consistent with lymphatic anatomy and the patient’s symptomatology of bilateral lymphedema. MR lymphangiography was acquired at the level of the calf (blue box) for all participants. c) Transverse and d) coronal source images were viewed in orthogonal planes to evaluate image features (case example given: extravascular focal, vascular dilated).

Figure 3.. Representative MR lymphangiography features in subcutaneous adipose tissue (SAT) in participants with BMI<30 kg/m².

Lower-extremity T₁-weighted images show the SAT region (green overlay). Adjacent images are MR lymphangiography axial-source and coronal-MIP (maximum intensity projection) images. Cases are presented with annotated extravascular (open arrowheads) and vascular (arrows) signal patterns on MR lymphangiography for participants: a) female control (40 y/o, BMI=29.2 kg/m², calf-circumference=41 cm), b) lipedema (23 y/o, 22.7 kg/m², calf-circumference=40 cm, lipedema stage 1), c) lipedema with lymphedema (46 y/o, 24.9 kg/m², calf-circumference=43 cm, lipedema stage 2, lymphedema stage 1), and d) cancer treatment-related lymphedema (60 y/o, 24.8 kg/m², calf-circumference=37 cm, lymphedema stage 3). The participant with cancer-related lymphedema displays on T₁-weighted imaging thick skin (asterisk) and band-like soft tissue (closed arrowhead) within the SAT.

Figure 4.. Representative MR lymphangiography features in the subcutaneous adipose tissue (SAT) in participants with BMI>30 kg/m².

Lower-extremity T₁-weighted images show the SAT region (green overlay). Adjacent images are MR lymphangiography axial-source and coronal-MIP (maximum intensity projection) images. Cases are presented with annotated extravascular (open arrowheads) and vascular (arrows) signal patterns on MR lymphangiography for participants: a) female control (61 y/o, BMI=31.4 kg/m², calf-circumference=41 cm), b) lipedema (34 y/o, BMI=34.1 kg/m², calf-circumference=49 cm, lipedema stage 2), c) lipedema with lymphedema (48 y/o, BMI=36.3 kg/m², calf-circumference=42 cm, lipedema stage 3, lymphedema stage 2), and d) cancer treatment-related lymphedema (age=64 years, BMI=39.5 kg/m², calf circumference=46 cm, lymphedema stage 3). The participant with cancer-related lymphedema displays on T₁-weighted imaging thick skin (asterisk) and band-like soft tissue (closed arrowhead) within the SAT.

Figure 5.

Subcutaneous hyperintense signal patterns were scored on MR lymphangiography in study groups for a) extravascular (focal, diffuse, or not apparent) and b) vascular (linear, dilated, or not apparent) image features. The frequency (%) of image features present within each group is represented by the length of colorbars, and the sum of frequencies equals 100% in each group because all cases were scored. Notably, all image features had similar frequency between lipedema cohorts (i.e. with or without lymphedema). Image features were significantly associated with study group (Fisher’s exact test, *two-sided p<0.05 defined as the level of statistical significance).