Innovations in diagnostics. Pathways Vol 8, No 2. Spring 2019.

Research Advances

Innovations in diagnostics

Early lymphedema detection and other benefits to diagnostic techniques

By Mike Bernas

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iagnostic techniques and tools for use for lymphedema are still far from complete and there are not many agreed upon standards. Although there are several common techniques with worldwide use, newer ideas continue to develop to improve the field.

First, let’s examine exactly what we mean by diagnostics for use in lymphedema. Is this looking just at confirmation of swelling? That certainly is a measurement utilized by many physicians, researchers, and payers (those who pay for the procedure) to document swelling as well as response to treatment. Can it be early detection of fluid build-up before swelling is apparent? This is attractive to medical professionals, researchers, and patients who want to know as soon as possible if swelling will occur (since we do know that earlier treatment is usually more successful). Should diagnostics be limited to identifying and documenting by imaging the underlying changes or impairments

to lymph fluid flow which leads to the development of swelling? Determining peripheral changes is certainly important for clear diagnosis from a medical (and insurance) point-of-view, but it does not always change treatment approaches and therefore may not be as important for the patient and therapist.

Volume measurements The most widely utilized method to measure the volume of a limb is using a tape measure1.

This is usually assessed at every 4 or 10 cm and then the values are entered into a mathematical formula to determine an approximate volume. A recent systematic review demonstrated that the interclass correlation coefficients (measure of consistency) in the upper limbs for both inter- and intra-rater were excellent (≥.98)2. The classic method for determining volume of the limb uses the Archimedes principle of water displacement. Although this method is used in some clinics, it has

Michael Bernas, MS is an Associate Professor and the Director of the Scholarly Pursuit and Thesis student research projects at the TCU and UNTHSC School of Medicine (Texas). His expertise is in imaging techniques of the lymphatic system, animal models of lymphedema and treatment, lymphatic and blood vascular growth factors, genetics of lymphedema, and diagnosis/evaluation of patients in the clinic.

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not gained wide use since it can be difficult for some patients to place their arm or legs into the device and cleaning the device does take some time. The third modality for volume measurement is the use of an optoelectronic limb volumeter (also called infrared perometry), which uses an array of lights and sensors to measure the limb.

These devices are expensive and not utilized by many treatment clinics worldwide.

The systematic review also found both of these techniques also have high interclass correlation coefficients2. Although not the standard utilized in all clinics, Armer et al. in a large study has recommended that a volume increase ≥10% be utilized for documenting lymphedema3 (See Editors Note page 4).

Can we measure tissue fluid increase before volume increase?

While documenting the swelling is very important for diagnosis, many patients, physicians, and therapists would like to get the earliest possible indication of potential Ly m p h e d e m a p a t h w a y s . c a 5

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Editor’s Note:

Challenging the definition Lymphedema has very often been defined as >10% limb volume increase in comparing affected (or lymphedematous) and unaffected limbs or in comparing pre-surgery limb volume to subsequent limb volume using water displacement, sequential circumference limb tape measurement, or infrared perometer.

Yet, more and more clinicians and researchers have noticed that even minimal 5% limb volume increase can lead to significantly poor quality of life and more lymphedema symptoms.

Importantly, lymphedema symptoms may indicate an early stage of lymphedema in which limb volume changes cannot be verified by currently used criteria of >10% limb volume increase. Timely intervention in early disease stage can prevent lymphedema from progressing into a chronic condition that no surgical or medical interventions at present can cure.

It is time to challenge the definition of lymphedema as >10% limb volume increase by taking into consideration of minimal limb volume increase and lymphedema symptoms.

Check lymphedemapathways.com for full explanation and references.

development of swelling. This means detecting early fluid buildup in a limb before actual swelling takes place (sometimes referred to as pre-clinical edema).

There are two main approaches for measuring tissue fluid. One measures discrete locations for tissue water content (tissue dielectric constant)4 and the other utilizes very low (undetectable) currents through the body to determine calculated values of extracellular fluid (bioimpedance spectroscopy or BIS)5. Although these techniques are being researched and their validity touted, many payers as you might expect are not convinced that lymphedema exists until there is documented swelling. This has not stopped clinics from utilizing these techniques 6 Ly m p h e d e m a p a t h w a y s . c a

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for early detection of potential future swelling.

Some studies have examined the correlation between BIS and limb volume ratio and showed significant correlation6 while others have used the BIS values to assess breast cancer patients before surgery and then follow up to 12 months post surgery to gauge the clinical benefit5.

Will these changes be useful for evaluation or early detection?

The above study by Ridner et al.6 suggests the possible clinical benefit of using BIS as a tool for screening and following at risk patients for the development of lymphedema where this technique might be the most useful. Recent advances in the technology have produced devices that patients simply stand on with hands and feet touching electrodes to quickly and efficiently obtain data. As the time needed to administer is minimal, perhaps devices such as these will become more frequent in physician’s offices to assess patients, providing that reimbursement issues can be resolved.

Advances in imaging The current gold standard for imaging is lymphoscintigraphy (LAS). In this nuclear medicine test, one small injection is performed in the hand and/ or foot and a tracer enters the lymphatic system. The tracer is subsequently transported through larger and larger lymphatic vessels including deep vessels to the neck where the thoracic duct (the largest lymphatic vessel in the body) enters

the bloodstream. This test is accepted medical practice and can be done anywhere where a nuclear medicine facility exists.

The image can document areas where the lymphatic system is not flowing (primarily due to obstruction in patients following cancer treatment) or in more complicated cases where lymph may leak into the abdomen or chest cavities7. LAS imaging documents changes in the lymphatic system that underlie the development of swelling.

A more recent imaging technique utilizes ICG fluorescent dye to depict the superficial lymphatic system as a reflection of underlying blockage. Although the use of this technique is currently restricted for imaging lymphedema patients as part of research studies, it is currently utilized by surgeons performing lymphaticovenous anastomoses (LVA) and lymph node transfers.

It does not have the ability to demonstrate the deep lymphatic system and its use is more reserved for superficial lymphatic imaging. Researchers Low Frequency are exploring new Current passes around cells detection systems as well as new dyes to improve this technique.

Ultrasound is utilized by some clinics and researchers to High Frequency Current passes through cells examine both the skin and subcutaneous tissues in patients with lymphedema. Although differences can be seen, specific values (and techniques) to define lymphedema have not yet been defined and work is continuing to strengthen these efforts.

The greatest use for ultrasound is for examining

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