Imaging and Screening for Lymphoedema
By Mr Alex Ramsden, Consultant Plastic and Reconstructive Surgeon at the Oxford University Hospitals
This article is taken from the Winter 2014 issue of LymphLine, the LSN’s quarterly newsletter available to all LSN members. For details of how to become a member, click here.
Introduction
Lymphoedema is tissue swelling due to a failure of lymphatic drainage. The diagnosis is often made by doctors of various types based on the history and examination of the patient with tissue swelling (oedema). However, there are many causes of oedema, particularly of the lower limb, so making the diagnosis can sometimes be difficult from history and examination alone. There are two main types of lymphoedema, primary and secondary. Investigations in primary lymphoedema aim to confirm a diagnosis and exclude other reasons for oedema. Other tests that may be used are genetic screening and blood tests but these are not discussed here. The diagnosis of secondary lymphoedema is easier to make from the patient’s history and here investigations are directed towards confirming the diagnosis but also to grade the extent of lymphoedema. Investigations can provide the patient with an indication of future disease progression and can also form the basis for individualised treatment programs. Recent developments in the surgical treatment of lymphoedema have led to the need to help identify groups of patients that would benefit most. New investigations can decide if surgery would be beneficial and guide a highly targeted surgical approach.
Lymphoedema is a relatively neglected condition by the medical research establishment. Probably because it is nonfatal and commonly considered difficult to treat, there has been little progress with the development of investigations until recently. As surgical treatments become available there is a new and growing demand amongst surgeons for better and more accurate investigations.
An ideal investigation for lymphoedema would be cheap, safe and reliable. It would provide accurate diagnosis, guide treatment options and be suitable for all patients. It would demonstrate both the lymphatic anatomy and give an indication of functional capacity. This ideal investigation currently doesn’t exist but this review will consider common investigations and when they might be used.
The main problem all investigative techniques face is the small size of the ultra fine network of lymphatics they are attempting to visualise. Many commonly used forms of simple imaging such as computed tomography (CT), magnetic resonance imaging (MRI) or ultrasound (US) can’t see the fine lymphatic system as most vessels are measured in millimeters. This size is beyond the current resolution of these systems without enhancement techniques.
There are two main types of investigation. One type injects a special marker substance into the lymphatic system. The specific properties of this marker allow it to be seen by the imaging technique, highlighting the lymphatic system specifically, allowing it to build up a functional and anatomical picture of the lymphatic system. The second type images an area of the body using non-specific means but can visualise anatomical structures, which may be the cause of or be affected by lymphoedema.
Lymphoscintigraphy
This technique has been in use for over 60 years and involves injection of a radioactive tracer into the foot or hand. The tracer is the correct size to be taken up into the lymphatic system and moves slowly along the lymphatic channels. The radioactive material produces gamma radiation, which can then be detected using a gamma camera in a radiology department. A picture is built up of where the radiotracer has moved in the body of the patient. By taking pictures at different time intervals, following injection, a quantitative assessment of function can be made. Images are often taken 30 minutes, 1 and 2 hours after the injection and give an indication of how slowly the radiotracer moves through the body. The camera is very sensitive and the dose of radiation is low. The black and white images produced are interpreted by a radiologist, but don’t provide accurate anatomical information as they have low resolution. Radiation passes completely through the body and so even deep lymphatic channels can be visualised. They can be difficult to interpret and unreliable. This technique can diagnose lymphoedema and give an indication of the function of the lymphatic system. It is considered the gold standard for investigation of primary lymphoedema.
Indocyanine Green (ICG) Lymphography
Introduced in 2007, ICG lymphography involves a fluorescent marker rather than one that is radioactive. The injected dye will fluoresce in infra-red light and a special video camera is used to make images from the light given out by the dye. Indocyanine Green dye has been used in many fields of medicine such as neurosurgery for around 50 years. A tiny dose is injected into the skin of the hand or foot. It is absorbed into the lymphatics and moves up the limb with the lymphatic fluid. The dye can then easily be visualised by the infra-red camera and the lymphatics mapped. It doesn’t require a radiologist to interpret the images or expensive gamma cameras and so is cheaper than lymphoscintigraphy. Indeed, the images can be displayed in clinic on a laptop computer so that both the doctor and patient can see the images giving the patient a real idea of the nature and extent of any lymphoedema.
Live imaging allows the patient to see the effect of lymphatic massage as the dye can be seen being pushed along intact lymphatics and accessory channels.
The rate of movement of the dye up the limb can also be measured giving an indication of lymphatic transport speed. A practical advantage of this technique is that it can be used in an outpatient clinic or theatre with simple portable equipment. Surgeons can mark the lymphatic channels on the skin and plan surgical intervention accurately in discussion with the patient.
Unfortunately, the infra-red light only penetrates a couple of centimeters into the body and so deeper lymphatics such as those in the abdomen cannot be visualised. ICG lymphography is an important step forward in the investigation of lymphoedema.
Magnetic Resonance Lymphography
Magnetic Resonance Imaging (MRI) is a routine investigation from orthopaedics to neurology. Recent demands for improved anatomical accuracy from lymphatic surgeons has prompted research into the role of MRI for lymphoedema. Plain MRI doesn’t currently have the resolution to see lymphatic vessels but can differentiate between lymphoedema and lipoedema due to the different appearance of subcutaneous fat. It is very good at imaging lymph nodes and their anatomy. To image the lymphatic vessels, MRI needs to be enhanced with contrast agents that are taken up by the lymphatics and show up clearly on MRI scanning. This process allows 3D images to be produced that demonstrate the lymphatic anatomy throughout the limb and trunk. Resolution is significantly better than lymphoscintigraphy and there is no radiation dose. However, this investigation is only performed in very specialist centres, requires an experienced radiologist to interpret the images and is expensive. These limitations may be overcome if it can be proven to add significant and useful information. Computed Tomography (CT) scanning with contrast media is a similar process. These scans have an advantage of giving accurate information on other structures that may cause lymphatic obstruction such as tumours. Currently MRI and CT imaging techniques are at the early phase of development but show promising advantages that may be realised in the next decade.
Ultrasound (US)
Commonly used as a complementary investigation for lymphoedema, ultrasound can exclude venous disorders that can cause limb swelling such as deep venous thrombosis. It doesn’t have the resolution to image lymphatic vessels but can show oedema, lymph nodes and fibrosis in the subcutaneous tissue.
Screening for lymphoedema
Evidence suggests that early treatment of lymphoedema slows disease progression and gives better outcomes. It is known that between 20 and 40% of patients undergoing axillary procedures for breast cancer are at risk of developing lymphoedema, and the figure may be higher for other cancers. Early diagnosis in these high-risk groups is important. Recent reports from Japan show that ICG lymphography can diagnose lymphoedema at a very early stage before patients develop significant clinical signs. Early identification of the earliest signs of lymphoedema would allow surgical intervention before significant limb swelling and before garments are required. By closely monitoring high-risk groups and treating at the earliest possible opportunity the chronic changes of lymphoedema may be avoided. Surgical intervention at this stage promises to be easier and with greater chance of preventing the disease. Reliance on compression garment use may be reduced or avoided altogether.
‘Recent reports from Japan show that ICG lymphography can diagnose lymphoedema at a very early stage before patients develop significant clinical signs.’
Summary
Imaging in lymphoedema aims to confirm the diagnosis and plan treatment. Lymphoscintigraphy remains a gold standard investigation in the diagnosis of lymphoedema. ICG lymphography is low risk, accurate in making a diagnosis and excellent for surgical planning. MRI and CT scanning are specialist and developing areas that may add important information in future. Simple screening tests allow early diagnosis and intervention aimed at preventing disease progression.
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