Is There a Need for New Imaging Methods for Lymph Node Evaluation?

Transcutanous ultrasound (TUS) covers a number of established techniques for evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy 1 2 3 4. Likewise, in breast 5 6, mediastinal 7 8 9 and abdominal ultrasound 10 11 12 13 14 and staging procedures 15 16. Endoscopic ultrasound (EUS) techniques for lymph node evaluation have also been described extensively 16 17 18. Currently ultrasound examinations are mainly conventional B-mode (TUS, EUS) techniques 19. Applied criteria are common for all imaging methods including CT and MRI and depend on the assessment the size, shape and border of lymph nodes as well as visualization of central necrosis. Evidence for functional assessment of lymphadenopathy by positron emission tomography (PET) so far is useful in some diseases. It has to be taken into account that exclusion of malignant nodal infiltration is almost impossible since at least one third is found in lymph nodes with a size of less than 5(–10) mm 20 21 22 23 24 25 26 27 28 29 30 31 which are below the reliability for detection. In addition, suspicious lymphadenopathy may be caused by inflammatory diseases, including sarcoidosis, tuberculosis and many other diseases which reduce sensitivity. The value of modern ultrasound techniques for lymph node evaluation on evidence based principles has not been discussed widely so far. Recent advances include panoramic imaging 32 33, 3-dimensional (3 D) ultrasound 34 35 36, contrast enhanced ultrasound (CEUS) 37 38 39 40, 3D-CEUS 41, contrast-enhanced endoscopic ultrasound (CE-EUS) 42 43, Real-Time Elastography (RTE) 44 45 46 and other strain imaging techniques have improved the accuracy of ultrasound for the differential diagnosis of lymphadenopathy in daily routine. CEUS and CE-EUS with contrast specific imaging mode as well as elastography are new technique that have proven helpful to identify malignant areas within lymph nodes and are therefore are useful for the guidance of fine needle aspiration (FNA) 47. In addition, CEUS also becomes a promising tool for the assessment of treatment response for malignant lymph nodes and lymphomas as they could better show the change of vascularity 48. Normal lymph nodes have a single vascular pedicle at the hilum containing arteries and veins, regularly branching towards the periphery and ending in the sinuous capillaries of the nodal cortex, this typical vessel architecture does not significantly change in most inflammatory processes 49. Malignant lymphadenopathies in the early stage still display the original architecture, but vascularity may be increased due to local immune reaction. When the malignant process progresses, the original architecture becomes deformed due to bulky neoplastic colonization, necrosis or desmoplastic reaction, and original nodal vascular structure including hilar blood vessel would be distorted and destroyed. In addition, neoplastic infiltration of the cortex associated with production of angiogenetic factor by tumor cells and recruitment of capsular vessels leads to peripheral hypervascularity with tortuous and aberrant feeding vessels at the periphery and sinusoid neovascularity within the tumoral nests 3 49 50. CEUS with contrast special imaging mode, using second generation contrast agents such as SonoVue®, permits the use of the low MI required for the detailed visualization of the vascularity of LNs. It allows realtime analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necroses or deposits of neoplastic cells. CEUS and quantification (time intensity curve) softwares will be helpful for the differential diagnosis of benign and malignant LNs. Compared with benign nodes, malignant nodes often have higher maximum intensity and duration of enhancement. CEUS has even been tested for visualization of the lymphatic vessels and sentinel nodes 51 52. CE-EUS can be performed on both Doppler mode with high MI and contrast specific mode with low MI 53 54. CE-EUS might improve the detection of small intranodal vessels and thus it might be useful in characterization of LNs 43 55. Real-time elastography allows assessment and visualization of relative elasticity differences. It is a method for in-vivo characterisation of tissue hardness, e. g. of lymph nodes 47 56 57 58. Transcutaneous probes and longitudinal and radial echoendoscopes can be used for elastography 44 59 60 61 62 63. The area to be evaluated is defined by a ROI in a similar way to Colour Doppler Imaging 62 64. The necessary pressure can be applied by manipulating the probe, though very little additional pressure is required, as the forces from the pulsation of adjacent vessels are often sufficient 47 56. The ROI must be sufficiently large to contain the lesion and enough surrounding “normal” tissue for comparison; optimally containing equal amounts of each. New technical developments allow for averaging over several frames to calculate the mean histogram value which corresponds to overall elasticity within a selected area 65. Comparing two different areas within the ROI allows calculation of the strain ratio. Interobserver agreement proved to be good for general RTE impression and for strain ratio, but not for a defined scoring system 63. Currently the European Federation for Ultrasound in Medicine and Biology (EFSUMB) is preparing a set of recomendations for the use of elastography, inspired by those on CEUS previously published 15 66. EFSUMB has recently published recommendations on the use of dynamic contrast enhanced ultrasound (D-CEUS) 67. In conclusion, there is a need for new imaging techniques for better characterisation of lymph nodes in daily routine. Contrast enhanced ultrasound techniques and elastographic (strain) imaging are the tools to improve the diagnostic work up of lymphadenopathy. We challenge the interested reader to initiate prospective, interdisciplinary and multicentric studies to prose the use of the described new technologies for better diagnosis of benign and malignant lymph node diseases.