R01 Variable Anatomy & Function

BACKGROUND: The lateral upper arm (LUA) pathway is a route of superficial lymphatic drainage that bypasses the axilla by draining to the deltopectoral, clavicular, and cervical lymph nodes. Despite the fact that anatomic variations of the LUA pathway have been implicated in breast cancer-related lymphedema (BCRL) risk after axillary lymph node dissection (ALND), the incidence of the LUA pathway variations in the healthy population has never been reported.

METHODS: Healthy female volunteers underwent bilateral lymphatic mapping of the upper extremities with indocyanine green (ICG) lymphography. ICG was injected in six standard sites in the hand/wrist and upper arm. Major anatomic variations of the LUA pathway were recorded including bundle phenotype (long, short, or absent), proximal visualization sites, and forearm pathway continuation to the long bundle phenotype.

RESULTS: 90 arms of 45 volunteers were included. The LUA pathway was present in 99% of arms and a long-versus-short bundle phenotype was observed in 71% versus 28% of arms. When the long bundle was present, it was formed by continuity with the forearm posterior radial channel alone (47%), posterior ulnar channel alone (34%), or both channels (19%). The LUA pathway was traced proximally to the deltopectoral groove in 89% of arms and to the axilla in 11% of arms.

CONCLUSIONS: We observed similar proportions of arms with long and short bundle phenotypes in comparison to our previous report of the LUA pathway in breast cancer patients with nodal disease. Defining the incidence of the LUA pathway with its variations in the general population is important as variations in this pathway may have implications for an individual's risk of developing BCRL.

BACKGROUND: The lateral upper arm lymphatic pathway is theorized as a route of superficial lymphatic drainage protective against breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). This study describes lymph nodes draining the lateral upper arm pathway.

METHODS: Healthy female volunteers underwent bilateral ICG lymphography and nuclear lymphoscintigraphy. Nuclear tracer was injected over the cephalic vein in the upper arm. Lymph nodes with tracer uptake were recorded as deltopectoral, Station 1 (Axillary Levels I or II and Interpectoral), or Station 2 (Axillary Level III, Infraclavicular, Supraclavicular Levels IV or Vb, and Cervical Level Va).

RESULTS: 72 arms of 36 volunteers were included. Functional drainage to deltopectoral lymph nodes was observed in 38% (27/72) of arms. Drainage to Station 1, Station 2, and neither station was observed in 96% (69/72), 36% (26/72), and 3% (2/72) of arms, respectively. No differences were observed between arms with or without deltopectoral lymph nodes draining to Station 1 lymph nodes (93% vs 98%, p = 0.286) or neither station (4% vs 2%, p = 0.711), respectively. A significant difference was observed between arms with or without deltopectoral lymph nodes draining to Station 2 lymph nodes (52% vs 27%, p = 0.031).

CONCLUSIONS: Deltopectoral lymph node drainage is significantly correlated with Station 2 lymph node drainage. As Station 2 lymph nodes are preserved in an ALND, the presence of deltopectoral lymph node drainage represents an important potential protective biomarker for BCRL development.

BACKGROUND: Superficial to deep system rerouting of lymph protects against breast cancer-related lymphedema (BCRL). Humeral lymph nodes are a marker for deep lymphatic drainage. Epitrochlear lymph nodes are a site of superficial to deep collateralization based on cadaveric dissections. Functional connectivity between epitrochlear and humeral lymph nodes remains unexamined with in vivo imaging. We utilized lymphoscintigraphy to document epitrochlear and humeral lymph node drainage in healthy volunteers.

METHODS: Healthy female volunteers received four intradermal hand/wrist injections of 99-Tcm sulfur colloid to each upper extremity and were imaged with SPECT/CT at 2 h. Two nuclear medicine physicians independently reviewed the SPECT/CT scans to document lymph nodes with tracer uptake. A Chi-square test was performed to assess the correlation between functional epitrochlear and humeral lymph node drainage.

RESULTS: A total of 72 arms of 36 volunteers were included. Drainage to epitrochlear and humeral lymph nodes was observed in 57% (41/72) and 51% (37/72) of arms, respectively. Drainage to both epitrochlear and humeral lymph nodes was observed in 40% (29/72) of arms. Epitrochlear and humeral lymph node drainage were absent in 32% (27/72) of arms. The proportion of arms with humeral lymph node drainage was significantly greater in arms with (71%, 29/41) versus without (26%, 8/31) epitrochlear lymph node drainage [χ2 = 14.262 (1), p < 0.001].

CONCLUSIONS: Epitrochlear and humeral lymph node drainage are significantly correlated, suggesting a superficial to deep pathway may function at baseline in 40% of arms. The absence of epitrochlear and humeral lymph node drainage may represent a biomarker for BCRL risk.

Despite significant strides in lymphatic system imaging, the timely diagnosis of lymphatic disorders remains elusive. One main cause for this is the absence of standardized, quantitative methods for real-time analysis of lymphatic contractility. Here, we address this unmet need by combining near-infrared lymphangiography imaging with an innovative analytical workflow. We combined data acquisition, signal processing, and statistical analysis to integrate traditional peak and-valley with advanced wavelet time-frequency analyses. Decision theory was used to evaluate the primary drivers of attributable variance in lymphangiography measurements to generate a strategy for optimizing the number of repeat measurements needed per subject to increase measurement reliability. This approach not only offers detailed insights into lymphatic pumping behaviors across species, sex and age, but also significantly boosts the reliability of these measurements by incorporating multiple regions of interest and evaluating the lymphatic system under various gravitational loads. By addressing the critical need for improved imaging and quantification methods, our study offers a new standard approach for the imaging and analysis of lymphatic function that can improve our understanding, diagnosis, and treatment of lymphatic diseases. The results highlight the importance of comprehensive data acquisition strategies to fully capture the dynamic behavior of the lymphatic system.

OBJECTIVE: We evaluated whether superficial lymphatic anatomy and functional lymph node drainage are symmetric between the right and left upper extremities of healthy female volunteers, and if handedness is associated with symmetry of superficial lymphatic anatomy.

BACKGROUND: Symmetry of lymphatic anatomy has been assumed historically. This assumption of individual anatomic symmetry is being utilized clinically and in research without validation.

METHODS: 36 normal female volunteers underwent bilateral indocyanine green (ICG) lymphography and lymphoscintigraphy of the upper extremities. Eight collecting vessel pathways of each upper extremity were mapped on ICG lymphography. 13 lymph node groups were visualized on lymphoscintigraphy. Symmetry of lymphatic anatomy and functional drainage were established by comparing the right and left extremities of each participant. Hand dominance was assessed by hand grip strength on a hand dynamometer.

RESULTS: Among the 36 participants, 10 (28%) showed symmetry of all eight upper extremity lymphatic pathways with ICG. However, only 1 (3%) participant demonstrated complete symmetry amongst the 13 lymph node groups. Total symmetry of lymphatic channels was observed on ICG in seven (39%) participants with hand dominance and three (17%) participants without hand dominance (X2 = 2.215, P = 0.137).

CONCLUSION: Lymphatic anatomy and functional drainage of the upper extremities are not consistently symmetric. Functional nodal drainage as demonstrated by lymphoscintigraphy shows less symmetry than anatomic studies of lymphatic channels using ICG. Symmetric lymphatic anatomy does not appear to correlate with hand dominance. These findings challenge the prevailing assumption of left-right lymphatic symmetry.