Quantitative Contrast-Enhanced Magnetic Resonance Lymphangiography of the Upper Limbs in Breast Cancer Related Lymphedema: An Exploratory Study

Abstract

Background: Contrast-Enhanced Magnetic Resonance Lymphangiography (CE-MRL) presents some limitations: (i) it does not quantify lymphatic functionality; and (ii) enhancement of vascular structures may confound image interpretation. Furthermore, although CE-MRL is well described in the published literature for the lower limbs, there is a paucity of data with regards to its use in the upper limbs. In this proof-of-principle study, we propose a new protocol to perform CE-MRL in the upper limbs of patients with breast cancer-related lymphedema (BCRL) which addresses these limitations.Methods and Results: CE-MRL was performed using a previously published (morphological) protocol and the proposed protocol (quantitative) on both the ipsilateral (abnormal) and contralateral (normal) arms of patients with BCRL. The quantitative protocol employs contrast agent (CA) intradermal injections at a lower concentration to prevent T2*-related signal decay. Both protocols provided high-resolution three-dimensional images of upper limb lymphatic vessels. CA uptake curves were utilized to distinguish between lymphatic vessels and vascular structures. The quantitative protocol minimized venous enhancement and avoided spurious delays in lymphatic enhancement due to short T2* values, enabling correct CA uptake characterization. The quantitative protocol was therefore employed to measure the lymphatic fluid velocity, which demonstrated functional differences between abnormal and normal arms. The velocity values were in agreement with previously reported lymphoscintigraphy and near infra-red lymphangiography measurements.Conclusions: This work demonstrated the feasibility of CE-MRL of the upper limbs in patients with BRCL, introducing an advanced imaging and analysis protocol suitable for anatomical and functional study of the lymphatic system.

Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema

“…Reduced lymphatic processing capacity is also consistent with clinical symptoms of lymphedema that occur in advanced stages of lipedema. The relationship between lymphatic function and tissue sodium storage remains to be evaluated in vivo, although these studies may be possible with the emergence of lymphatic imaging modalities including indocyanine green near-infrared imaging 26 , 27 and magnetic resonance lymphangiography 28 – 30 . Noninvasive lymphangiography approaches 28 , 29 which exploit contrast derived from the long magnetic resonance relaxation times of lymphatic fluid relative to other tissues, may have particular relevance in this field as they can be performed in ten minutes or less and without exogenous contrast agents, thereby making them ideal candidates for surveillance imaging or evaluating therapy responses.…”

Systematic Review of Magnetic Resonance Lymphangiography From a Technical Perspective

“…Acquiring separate venographic images, with or without contrast, may improve visual conspicuity of veins or be used as subtraction masks for MRL data. Image registration may be necessary to reduce potentially confounding subtraction artifacts, however 8,64 . Noncontrast venograms were produced using balanced steady‐state free precession (bSSFP) by Mazzei et al 27 .…”

“…GBCA is most commonly administered undiluted in CE studies; however, as described previously, Borri et al . propose injections heavily diluted with saline such that each milliliter of injected solution contained 0.02 mL of contract agent, 0.1 mL of anesthetic and 0.88 mL saline 8 . Krishnamurthy et al .…”

Baseline Lymphatic Dysfunction Amplifies the Negative Effects of Lymphatic Injury

“…There is ongoing research seeking to identify the ideal test for lymphatic function in patients, but lymphoscintigraphy and ICG lymphangiography, similar to that performed in mice in this study, have been shown to be effective means of objective and noninvasive detection of early lymphatic disease (37). Magnetic resonance lymphangiography is also a promising diagnostic option, but is not yet widely available (38, 39). Ultimately, patients who are found to have pre-operative lymphatic dysfunction may then undergo therapeutic measures to increase lymphatic functional reserve prior to surgery and/or be considered for prophylactic options to prevent secondary lymphedema entirely.…”