Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders

Currently, there is no method to assess lymphatic function in persons with acquired
(developed following surgery or trauma) lymphedema, hereditary lymphedema or other
lympho-vascular disorders. The causes of these disorders, and the means to distinguish
between them, is not available from existing diagnostics. A method to monitor lymphatic
function could assist in the development of new therapies, the prediction of a patient's
susceptibility to develop these disorders, and the evaluation of patient's conditions or
responses to therapy and treatment. In this Phase I/II trial, we inject Indocyanine Green
(ICG) off-label as a lymph contrast agent and use a custom designed fluorescence imager to
conduct near-infrared fluorescence imaging to dynamically follow lymphatic trafficking in
subjects. Blood is also collected for DNA analysis. The resulting images are analyzed, and
the phenotypes observed in both normal and diseased subjects are used to correlate to
mutations of specific genes reported to be associated with lymphatic development.

Inclusion Criteria for Participation in NIRFLI with ICG (Group 1):

1. Negative urine pregnancy test within 36 hours prior to study drug administration, if
female of childbearing potential.

2. Females must complete the Female Enrollment Form. Those subjects of childbearing
potential must agree to use one of the medically accepted methods of contraception
listed on the form for a period of one month following the study. Female subjects of
non-childbearing potential, defined as physiologically incapable of becoming pregnant,
must meet the criteria listed on the Female Enrollment form, but are not restricted to
the use of contraception following study participation.

3. Subjects must be able to lie on their backs for periods of 10 minutes at at time for
up to a total of 60 minutes.

4. Children must be able to remain reasonably still for the time required for imaging.

5. Subjects with lymphatic dysfunction must be diagnosed with lymphedema, lipedema, or
vascular malformation/anomaly that suggests a lymphatic component.

Exclusion Criteria for Participation in NIRFLI with ICG (Group 1):

1. Persons with mobililty issues that could make participating too difficult

2. Women who are pregnant or breast-feeding

3. Persons who are allergic to iodine

4. Persons who weigh in excess of 400 lbs

5. If the subject is a female of child-bearing potential, she must agree to use a
contraceptive for one month after study participation.

6. Persons who do not meet inclusion criteria.

Inclusion Criteria for Participation in Genetic Analysis Only (Group 2):

1. The subject has a family member with lymphatic dysfunction.

2. The subject is willing to have blood drawn or saliva collected for DNA analysis

Exclusion Criteria for Participation in Genetic Analysis Only (Group 2):

1) The subject has experienced a medical problem from a prior blood draw