New diagnostic modalities in the evaluation of lymphedema

Objective: Currently, lymphedema (LED) is typically diagnosed clinically on the basis of a patient's history and characteristic physical findings. Whereas the diagnosis of LED is sometimes confirmed by lymphoscintigraphy (LSG), the technique is limited in both its ability to identify disease and to guide therapy. Recent advancements provide opportunities for new imaging techniques not only to assist in the diagnosis of LED, based on anatomic changes, but also to assess contractile function and to guide therapeutic intervention. The purpose of this contribution was to review these imaging techniques. Methods: Literature for each technique is reviewed and discussed, and the evidence for each of these new diagnostic techniques was assessed on several criteria to determine if each could (1) establish whether disease is present, (2) determine the severity of the disease process, (3) define the pathophysiologic mechanism of the disease process, (4) demonstrate whether intervention is possible as well as what type, and (5) objectively grade the response to therapy. Results: LSG is currently the standard test to confirm LED. Duplex ultrasound (DUS) is a simple, readily available noninvasive test that can identify LED by specific tissue characteristics as well as the response to therapy. Magnetic resonance imaging and computed tomography scans similarly demonstrate the alterations in epidermal and subcutaneous tissue, but the latter can also detect obstructing neoplasms as a cause of secondary LED. Moreover, magnetic resonance lymphangiography details lymphatic vessels and nodes and their function. Newer fluorescence imaging techniques provide opportunities to image lymphatic anatomy and function. Visible microlymphangiography by fluorescein sodium is limited by tissue light absorption to imaging depths of 200 pm. Near-infrared fluorescence lymphatic imaging, a newer test using intradermal injection of indocyanine green, can penetrate several centimeters of tissue and can visualize the initial and conducting lymphatics, the lymph node basins, and the active function of lymphangions (the key module) in exquisite detail. Conclusions: The availability and the noninvasive nature of DUS should make this modality the first choice for establishing the diagnosis of LED based on tissue changes. Further studies comparing DUS with LSG, however, are needed. The costs of magnetic resonance imaging and computed tomography limit their adoption as a means to regularly assess the lymphatics. Whereas lymphatic truncal anatomy and transit times can be delineated by the older technique of LSG, near infrared fluorescence lymphatic imaging is rapid, highly sensitive, and repeatable and provides exquisite detail for lymphatic vessel anatomy and function of the lymphangions as well as the response to therapy.