Lymphatic imaging, lymphedema beyond the first world, and the future of lymphedema research

Discussed with Dr. Melissa Aldrich, Ph.D.

Dr. Aldrich is an assistant professor at The University of Texas Health Science Center at Houston. Her interests lie in investigating immune factors that influence lymphatic dysfunction and in translating lymphatic imaging technology to the clinic.

Dr. Aldrich has investigated the effects of inflammation on lymphatic function in mice and found that cytokines act as systemic mediators of lymphatic pumping. This study was the first to show that the effects of cytokines on lymphatic function are systemic and define a role for inflammation in some lymphatic diseases.

“Faculty Profile.” Dr. Melissa Aldrich Ph.D. – Faculty – IMM – UTHealth, https://www.uth.edu/imm/faculty/profile?id=85ea8c30-5b79-4787-baf2-7c526078f44a.

In a conversation over the phone, Dr. Aldrich and I discussed revolutionary lymphatic imaging technology, the effects of lymphedema in developing countries, and the future of lymphedema research.

Lymphatic imaging

Near-infrared fluorescence lymphatic imaging

Medicare and medicaid were thinking about dropping coverage for pneumatic compression therapy (PCT), claiming they didn’t have adequate proof that it worked. Thus, Dr. Aldrich took part in a study in which near-infrared fluorescence lymphatic imaging (NIRFLI) was used to visualize lymphatic anatomy and function before, during, and after PCT. Optically transparent PCT garments (specifically made for the study) allowed visualization of lymph movement during single PCT treatment sessions. Visualization revealed significant extravascular/lymphatic vascular movement of intradermally injected dye in all subjects. In other words, NIRFLI shows where lymph is backing up in a limb in real time; this is something that similar machinery is not able to show. One 16-year-old girl in the early stages of lymphedema had, in fact, recently gone through a lymphoscintigraphy (a special type of nuclear medicine imaging). However, the lymphoscintigraphy hadn’t given doctors a clear result for what her condition was, because in the early stages of lymphedema, only one’s little lymphatic vessels, rather than one’s deep vessels, are affected, which the lymphoscintigraphy cannot capture clearly. The girl later went through NIRFLI, which successfully showed how her lymph was moving. The girl actually became the star of Dr. Aldrich’s study; she was younger and healthier than other subjects, so you could clearly see the results of NIRFLI when studying her affected legs. Thanks to her, people are still going to receive insurance coverage for their PCT after Dr. Aldrich and her team were able to show that yes, PCT can truly move lymph and yes, the numbers are statistically significant.

… people are still going to receive insurance coverage for their PCT after Dr. Aldrich and her team were able to show that yes, PCT can truly move lymph and yes, the numbers are statistically significant.

Aldrich, Melissa B., et al. “Effect of Pneumatic Compression Therapy on Lymph Movement in Lymphedema-Affected Extremities, as Assessed by near-Infrared Fluorescence Lymphatic Imaging.” Journal of Innovative Optical Health Sciences, https://www.worldscientific.com/doi/abs/10.1142/S1793545816500498.

Imaging after cancer treatment

Dr. Aldrich works at a hospital with an MD concerned about lymphedema. Said MD was tired of seeing cancer patients walk out of treatment with lymphedema, wondering Can I do something to change this?
Dr. Aldrich images women before and after breast cancer surgery and during radiation therapy using an imaging machine her colleagues invented and patented. This machine can see through skin to one’s lymphatic vessels to decipher whether or not the vessels are pumping. Whilst other machines can see vessels, they cannot see them moving.
If Dr. Aldrich discovers early lymphedema in a patient’s imaging, the hospital nurse will write an order for physical therapy for lymphedema in addition to cancer treatment physical therapy. Some patients go through with the additional physical therapy, while others don’t. One patient who developed early lymphedema and saw the fuzzy backflow of lymph in her imaging began using compression garments and went back to her exercise routine. Several months later, her lymphedema was completely gone. Thus, if you catch the lymph early after cancer treatment, you may be able to treat it.
Dr. Aldrich has found that chemotherapy itself can slow down lymphatic pumping unless the patient exercises, which produces a hormone that preserves smooth muscles cells, which push lymph along. If lymph is not pushed along, it remains stagnant and starts building up layers of fat.

Upcoming projects

Referral Network

Dr. Aldrich recently received an email from a young lady living in a rural area of Texas. She recently developed lymphedema and was not getting any treatment; she couldn’t wear any shoes, because her feet were too swollen. All Dr. Aldrich could do was tell the young lady that she could look for a lymphedema therapist if her medical insurance would cover it. However, most insurance policies won’t cover bandages. (According to Dr. Aldrich, this should change soon.)

Dr. Aldrich felt terrible, because this young lady simply wasn’t getting care she needed; she hardly even knew what she was dealing with. Fortunately, Dr. Aldrich began working with LE&RN in their effort to develop an online referral service. There are a lot of people that develop lymphedema and figure it out, but they don’t know where to go to find a good therapist, surgeon, etc.

There are a lot of people that develop lymphedema and figure it out, but they don’t know where to go to find a good therapist, surgeon, etc.

The LE&RN office gets many calls from people trying to figure out where to go, so they’re attempting to put together a network and central site with referral information for reputable “centers of excellence” (i.e. establishments of expertise in regard to lymphedema) based on the user’s location. Dr. Aldrich is on the committee for this project as a PhD researcher. She has created different classes of centers of excellence so that users will be referred to the proper establishment based on what they need: a diagnosis, surgery, complete decongestive therapy, etc. Each center of excellence will be required to closely collaborate with other centers of excellence so that patients have access to every aspect of treatment. For example, a surgical center that mainly deals with patients after cancer treatment can get their “boy scout badge” for being a center of excellence specifically as a good surgical center, but they are required to have their own referral system to those who do complete decongestive therapy in case a patient is seeking further guidance after surgery.

Lymphedema in developing countries

There are three types (or as Dr. Aldrich says, “flavors”) of secondary lymphedema: lymphedema after cancer, lymphedema caused by mosquito bites (lymphatic filariasis, considered globally as a neglected tropical disease), and lymphedema caused by inflammatory soil. Although lymphedema after cancer is a growing issue in the developed world, cases of lymphedema, caused by mosquito bites and inflammatory soil, are even more prevalent and highly unrecognized in the developing world.
Lymphatic filariasis is spread by infected mosquitoes. Their bites deposit a parasite that travels to the lymph system, sometimes resulting in swelling of the legs, arms, and genitalia. This condition often clusters in families and is most prevalent in Haiti, Ethiopia, and parts of India. In the small villages of these third world countries, local witch doctors will say that those with lymphedema are actually inflicted by a demon and thus should be denied taxis or support, even though they have huge, swollen legs and can’t walk. Volunteers have gone to Haiti with bandages to set up makeshift clinics in an effort to teach people how to manage their lymphedema, but the volunteers have quickly run out of bandages after being swamped; there are simply too many people to treat. However, those were first examined at the clinic were treated successfully; they learned how to self-massage and put compression garments on, even if they had to use duct tape and banana leaves as bandages, and soon were able to move efficiently.

Lymphatic filariasis
Photo: World Health Organization

Additionally, a million and a half people in Ethiopia are affected by the third type of secondary lymphedema. These people walk without shoes on, the immune cells in their feet coming into contact with minerals in the inflammatory soil beneath them. Some experience an inflammatory reaction and develop lymphedema, which looks just like every other type of lymphedema.
Thus, Dr. Aldrich has a hypothesis that, with the exception of primary lymphedema, each type of lymphedema has something very similar in its downstream cause (immune based/inflammatory-based).

The future

There’s a lot that the medical community doesn’t know about lymphatics, but there’s a lot that they’re learning. 12 years ago, Dr. Aldrich didn’t know what lymphedema was; people just didn’t talk about it. But Dr. Aldrich believes that in less than 10 years, the word (about lymphedema) will get out, especially with the internet. People are working on stuff and trying; it’s encouraging. 10 years ago, you couldn’t say that.

There’s a lot that the medical community doesn’t know about lymphatics, but there’s a lot that they’re learning… People are working on stuff and trying; it’s encouraging. 10 years ago, you couldn’t say that.

One day, you’re not gonna have to fight or feel so alone. People are gonna be more accommodating and understanding, and you’re going to have access to better care. Therapists are looking to optimize treatment, researchers are looking for better treatment, and the most exciting thing is that more money is being funded to this research. There will be more research done, better answers for why lymphedema is the way it is, more support groups, and hopefully, a cure.
Dr. Aldrich says that even CRISPR is promising in lymphedema research. By the time I, Savannah Paetzel, am approaching middle age, researchers are either going to have a total cure or something that’s such a great treatment that lymphedema will have minimal impact on my life. For now, the best I have is compression and PCT.
As for the future for Dr. Aldrich, she would love to take lymphatic imaging overseas and get it into more hospitals. This has proven to be necessary; a man at a particular hospital had one leg larger than the other. He felt socially ostracized and couldn’t hang out with people his age or be mobile. Physicians saw that he had something going on with his veins, but they didn’t know about the lymphatics behind his issue. Dr. Aldrich took her lymphatic imaging to the man and found that he actually had lymphedema, the cause of his swelling. Doctors were then able to take care of some of his lymphatic vessels and stop the leaking.