High-Resolution Lymphatic Mapping of the Upper Extremities with MRI

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Project Summary Lymphedema is a condition in which the clearance of lymph is compromised, resulting in edema and swelling of limbs, with potentially devastating impact on quality of life and medical costs. The most common cause of lymphedema in the US is from cancer-related surgery. Lymphedema is progressive and has no cure. It is not known why some patients develop lymphedema while others do not. Studies of cadavers have shown that the lymphatic anatomy can vary across individuals, and it is believed that these variations may increase the risk for certain individuals to develop lymphedema. If this is true, steps may be taken to prevent lymphedema from developing, for example with a bypass at the time of surgery. However, there is no practical way to obtain a complete lymphatic anatomical map within an extremity in vivo. Current imaging techniques are limited by penetration depth, low resolution, invasiveness, and partial coverage. The challenge is to map lymphatic channels, with diameters of 0.4-0.8 mm, and to trace them from all regions of an extremity back to draining lymph nodes. This proposal focuses on the development of a novel high resolution magnetic resonance (MR) lymphography technique (hrMRL) for lymphatic mapping of the upper extremities in living people. hrMRL will be a combination of a fast spin echo sequence with tailored variable flip angles, background subtraction, and acceleration via undersampling with compressed sensing and deep learning. The first aim will be to construct and optimize each of these components in an iterative fashion using phantoms, followed by testing on 10 healthy subjects, with the goal of obtaining maps of the lymphatic channels of an entire extremity within a target time of 20 minutes, suitable for clinical adoption. In the second aim, hrMRL will first be used to obtain full lymphatic anatomic maps of the upper extremity of 35 healthy volunteers who previously underwent indocyanine green (ICG) lymphography, which will serve as a gold-standard reference. hrMRL will then be validated aginst ICG by comparing both maps and determining their degree of agreement. hrMRL is also expected to resolve additional lymphatic channels undetected by ICG, allowing us the opportunity to create more comprehensive maps and to characterize new pathways, in particular the deep lymphatic channels. If successful, hrMRL would be immediately impactful in the clinical setting, where it could guide measures to avoid onset of lymphedema, shifting the lymphedema management algorithm from one of supportive and corrective therapies to one of prevention, with the goal of reducing the incidence of this debilitating and costly disease.