Noncontrast Magnetic Resonance Lymphography in Secondary Lymphedema Due to Prostate Cancer

Michaela Cellina, Daniele Gibelli, Carlo Martinenghi, Massimo Soresina, Andrea Menozzi, Denisa Giardini, Giancarlo Oliva


Background: As survival from malignancies continues to improve, a greater emphasis is being placed on the quality of life after cancer treatments. Lymphedema (LE) represents a common and devastating sequela of neoplastic therapies, even if its incidence in patients submitted to lymphadenectomy for prostatic cancer is still poorly documented. The purpose of the current study was to analyze the imaging findings provided by noncontrast magnetic resonance (MR) lymphography in secondary lower limb LE related to prostate cancer therapies.

Methods and Results: Patients with diagnosed secondary LE related to prostatic cancer treatment who underwent noncontrast MR lymphography (NCMRL) between November 2019 and February 2020 were assessed. Image datasets were retrospectively reviewed for the severity of lymphedema and characteristics of the subcutaneous tissue, muscular compartment appearance, number of iliac and inguinal lymphatics, and number of locoregional lymph nodes. Ten patients with 17 affected lower extremities, nine right extremities, and eight left extremities were included in our analysis. Magnetic resonance imaging grading was classified as one in four extremities, two in five extremities, and three in eight lower extremities. Honeycomb pattern was observed in 15 extremities, without significant correlation with MR grading (p = 0.684); dermal thickening showed correlation with MR grading (p < 0.001), as well as reduction of muscular trophism (p = 0.021). We observed a significant correlation between the number of inguinal lymph nodes and recognizable inguinal lymphatics (p = 0.039).

Conclusion: NCMRL is able to provide useful information for the management of secondary lower limb LE caused by prostate cancer treatments.

Lymphat Res Biol. 2020 Dec 7

Noncontrast MR Lymphography in Secondary Lower Limb Lymphedema

Michaela Cellina, Carlo Martinenghi, Marta Panzeri, Massimo Soresina, Andrea Menozzi, Gibelli Daniele, Giancarlo Oliva


Background: Invasive imaging techniques have been applied for lymphedema (LE) assessment; noncontrast MR lymphography (NCMLR) has potential as an alternative, but its performance is not known in secondary lower limb LE.

Purpose: To assess the role of NCMRL for the classification and characterization of secondary lower limb LE.

Study type: Retrospective.

Population: Fifty adults with clinically diagnosed secondary LE.

Field strength/sequence: 1.5T, 3D T2 -weighted turbo spin-echo, 3D T2 -weighted turbo spin-echo short tau inversion recovery.

Assessment: Three radiologists assessed the following characteristics on NCMRL: honeycomb pattern, dermal thickening, muscular abnormalities, distal dilated lymphatics, inguinal lymph node number, appearance of iliac lymphatic trunks. An LE grading based on the MR images was assigned. The relationship between imaging findings and clinical staging was evaluated, as well as between dermal backflow at lymphoscintigraphy and MR staging, and between the limb swelling duration and peripheral lymphatics dilatation.

Statistical tests: Pearson's correlation test and Cramer's V coefficient were computed to measure the strength of association. The Mann-Whitney test was used to compare the limb swelling duration between patients with and without dilated distal vessels. Agreement among raters was assessed through Kendall's W coefficient of correlation.

Results: Clinical stage and the MR grading were correlated, with Cramer's V coefficient of 1 for reader 1 (P < 0.05), 0.846 for reader 2 (P < 0.05), and 0.912 (P < 0.05) for reader 3; agreement between interraters was very good (W = 0.0.75; P = 0.05). A honeycomb pattern (P < 0.05), dermal thickening (P < 0.001), muscular abnormalities (P < 0.05), iliac lymphatic trunks appearance (P < 0.05), distal dilated vessels (P < 0.05), and lymph nodes number (P < 0.05) were significantly correlated with LE clinical stage. Dermal backflow at lymphoscintigraphy was described in 10 (20%) patients and showed a significant correlation with the MR grading (P < 0.05).

Data conclusion: These preliminary results suggest that NCMRL may provide information useful for the staging and management of patients affected by secondary lower limb LE.

J Magn Reson Imaging. 2020 Aug 14

Non-contrast MR Lymphography of Lipedema of the Lower Extremities

Michaela Cellina, Daniele Gibelli, Massimo Soresina, Andrea Menozzi, Carlo Martinenghi, Marta Panzeri, Giancarlo Oliva

Aim: To assess imaging findings and characteristics of the lymphatic system in patients affected by lipedema and lipolymphedema of the lower extremities on Non-Contrast MR Lymphography (NCMRL).

Materials and methods: 44 lower extremities in 11 consecutive female patients affected by lipedema, and 11 patients with lipolymphedema were examined by NCMRL. MR imaging was performed on 1.5-T system MR equipment. The examination consisted of one 3D short-tau inversion recovery (STIR) and one heavily T2-weighted 3D-Turbo Spin Echo (TSE) sequence.

Results: All patients showed symmetrical enlargement of the lower extremities with increased subcutaneous fat tissue. The fat tissue was homogeneous, without any signs of edema in pure lipedema patients. In all the extremities with lipolymphedema, high signal intensity areas in the epifascial region could be detected on the 3D-TSE sequence (p < .001) with evidence of mild epifascial fluid collections (p < .001). No sign of honeycomb pattern fat appearance was observed. The appearance of the iliac lymphatic trunks was normal in both lipedema and lipolymphedema patients. Dilated peripheral lymphatics were observed in 2 patients affected by lipedema, indicating a subclinical status of lymphedema, and in 10 patients with lipolymphedema (p = .001). Signs of vascular stasis were observed in both groups, without statistically significant difference (p = .665).

Conclusion: NCMRL is a non-invasive imaging technique that is suitable for the evaluation of patients affected by lipedema and lipolymphedema, helping in the differential diagnosis.

Magn Reson Imaging. 2020 Jun 17;71:115-124

A proposal for a semiquantitative scoring system for lymphedema using Non-contrast Magnetic Resonance Lymphography (NMRL): Reproducibility among readers and correlation with clinical grading.

Franconeri A, Ballati F, Panzuto F, Raciti MV, Smedile A, Maggi A, Asteggiano C, Esposito M, Stoppa D, Lungarotti L, Bortolotto C, Giardini D, De Silvestri A, Calliada F.

To assess the ability and reproducibility of Non-contrast Magnetic Resonance Lymphography (NMRL) in detecting and quantify lymphedema, using a semiquantitative scoring system.


This is a monocentric retrospective study of 134 consecutive patients with a clinical diagnosis of limb lymphedema who performed a Non-contrast Magnetic Resonance Lymphography (NMRL) at our Institution between November 2014 and February 2017. Lymphedema was classified based both on clinical and radiologic evaluation. An NMRL total score was obtained for each limb's segment and compared to the clinical grade, used as reference standard. NMRL intra-observer, inter-observer variability and intraclass correlation were calculated. NMRL sensitivity, specificity, and accuracy in identifying lymphedema were provided. Based on score distribution an NMRL four-stage system was developed.


NMRL showed 92% sensitivity, 77% specificity and 82% accuracy in identifying lymphedema. An almost perfect agreement was obtained by expert operators, while substantial agreement was obtained by non-expert operators. Substantial agreement resulted also for the inter-observer variability (Cohen's Kappa K = 0.73, CI 95% [0.69-0.78]). The intra-class correlation showed an almost perfect relationship both by expert and non-expert operators. Excellent correlation between clinical grade and NMRL score and between clinical grade and NMRL stage were found for each segment.


NMRL is a confident and reproducible exam with high sensitivity, good specificity and high accuracy in lymphedema detection; the semiquantitative NMRL score resulted a reliable and reproducible tool able to quantify lymphedema severity.

Magn Reson Imaging. 2020 Feb 10;68:158-166

Secondary Lymphedema Following Radical Prostatectomy: Noncontrast Magnetic Resonance Lymphangiography Assessment and Vascularized Lymph Node Transfer.

Cellina M1, Martinenghi C2, Gibelli D3, Menozzi A4, Soresina M4, Boccanera D4, Giardini D5, Oliva G1.


Lymphedema (LE) is a progressive chronic disorder, frequently related to malignancies and their treatment in Western countries. It markedly affected patients' quality of life, and its management is challenging, mainly based on conservative therapy, as bandages and manual lymphatic drainage, with limited results.Recent advances in imaging technology and microsurgical techniques have changed the approach to this disorder, particularly the recent application of magnetic resonance for the study of LE and the increasingly widespread use of surgical interventions, such as vascularized lymph node transfer. As secondary LE due to radical prostatectomy and/or radiation treatment is a frequent cause of chronic disability in the male population, and few data are available in literature about which imaging technique can be applied to diagnose it and about the surgical modalities to treat this condition, we want to propose an overview on the lymphatic vessels anatomy and function, on the applications of noncontrast magnetic resonance lymphangiography and about the pieces of information this examination can provide, and on the technique of vascularized lymph node transfer and the rationale of this surgical procedure in secondary LE related to prostatic malignancy treatment.

Ann Plast Surg. 2020 Jan 3. doi: 10.1097/SAP.0000000000002149

Noncontrast Magnetic Resonance Lymphangiography in a Rare Case of Everolimus-Related Lymphedema.

Cellina M1, Oliva G1, Soresina M2, Menozzi A2, Boccanera D2, Gibelli D3


Everolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in solid-organ transplant recipients. Although mTOR inhibitors are usually well tolerated, their adverse effects have been reported: sirolimus treatment in transplant patients has been rarely reported to be associated with lymphedema of the skin and subcutaneous tissues, whereas the use of everolimus seemed to be less burdened by this type of adverse effect. We report the case of a 58-year-old man with a history of end-stage renal disease of unknown etiology who had undergone right renal transplantation 11 years before. After the transplant, the patient soon developed bilateral progressive swelling involving feet and legs. The symptoms of the left limb improved markedly after discontinuing everolimus. This condition has been classified as everolimus-induced lymphedema. The patient was referred to our department for the execution of a noncontrast magnetic resonance lymphangiography, that is, a noninvasive magnetic resonance imaging technique that has recently proposed for the study of lymphedema. Noncontrast magnetic resonance lymphangiography showed asymmetry between the lower extremities with signs of advanced lymphedema located in the right lower limb and dilated peripheral lymphatic vessels.Drug withdrawal is currently the only effective solution for treating this type of secondary lymphedema; however, with the prolonged use of the drug, lymphedema tends to persist even after mTOR inhibitor suspension, with only partial clinical improvement, as in this case.This case report describes the imaging characteristics of such condition at noncontrast magnetic resonance lymphangiography and discusses the rare adverse effects of everolimus. Immediate suspension of the drug is the only effective strategy to avoid the persistence of this disorder.

Ann Plast Surg. 2020 Jan;84(1):113-116.

Non-contrast Magnetic Resonance Lymphangiography: an emerging technique for the study of lymphedema.

Cellina M1, Oliva G2, Menozzi A3, Soresina M3, Martinenghi C4, Gibelli D5


Lymphedema (LE) is a chronic disabling disease, characterized by the accumulation of macromolecules and liquids in the interstitial space. Patients affected by LE should undergo appropriate imaging to confirm the diagnosis, to evaluate characteristics and the severity of LE and to allow for correct management and treatment plan. However, there is no consensus regarding the best imaging technique to study this disorder. We want to propose an overview of the studies published on Non-contrast Magnetic Resonance Lymphangiography, a relatively new technique for the diagnosis, assessment and management of lymphedema.

Clin Imaging. 2019 Jan - Feb;53:126-133. doi: 10.1016/j.clinimag.2018.10.006.

Volumetric analysis of Non-contrast Magnetic Resonance Lymphangiography in patients affected by lower extremities primary lymphedema.

Cellina M1, Gibelli D2, Floridi C3, Oliva G4



Since the response to conservative and surgical treatments in lymphedema is based only on clinical evaluation, we want to propose a new technique for the volume calculation of lower extremities affected by lymphedema.


Ten female patients affected by primary LE of the lower limbs (mean age 33 ± 5 years; age range 16-42) underwent NCMRL in September 2019. Acquisition protocol included a STIR sequence (FOV 460 × 504 mm; matrix 315 × 384 pixel; voxel size 1.1 × 1.1 × 1.0 mm; TR 3000 ms; TE 254 ms; TI 160 ms). Two readers independently performed a manual segmentation with ITK-SNAP open-source software to assess the volume of the lower limbs. The agreement for volumetric segmentation between the two operators was assessed through intraclass correlation coefficient (ICC).


Mean segmentation time was 5 ± 0.3 min. ICC demonstrated excellent intra-examiner agreements for both readers 1 (ICC = 0.9991, p < 0.0001) and 2 (ICC = 0.9989, p < 0.0001). Inter-reader agreement was excellent (ICC = 0.9991, p < 0.0001).


Manual segmentation with ITK-SNAP of NCMRL examinations in patients affected by primary lower limb LE represents a reproducible procedure for an objective evaluation of volumes, useful for follow-up.

Radiol Med. 2019 Dec 17. doi: 10.1007/s11547-019-01122-9.

Non-contrast magnetic resonance lymphography: technique, indications, interpretation. Linfografia RM senza m.d.c.: tecnica, indicazioni, interpretazione

M. Cellina, C. Rosti, D. Gibelli, A. Menozzi, M. Soresina, D. Boccanera, V. Di Candido, G. Oliva.

Il linfedema (LE) è tuttora un problema clinico impegnativo, causato dall’accumulo di macromolecole e liquidi nello spazio interstiziale, per malfunzionamento della circolazione linfatica, che determina per il paziente una condizione debilitante. Tradizionalmente il LE è stato trattato con terapie conservative, ma il recente avvento di nuove tecniche chirurgiche ha reso necessario l’utilizzo di tecniche di imaging per valutare il linfedema, stabilirne la severità, studiare l’aspetto dei vasi linfatici. Non c’è attualmente consenso sulla migliore tecnica di imaging per indagare il linfedema. La Linfografia RM senza mezzo di contrasto, basata su sequenze fortemente pesate in T2, potrebbe essere una valida alternativa per la diagnosi e la pianificazione del trattamento di LE. Vogliamo descrivere la tecnica della linfografia RM senza mezzo di contrasto e fornire una breve panoramica sulle sue indicazioni, in accordo con gli studi pubblicati in letteratura, le informazioni che possiamo ottenere da questa metodica, i suoi limiti e i suoi punti di forza.

Il Giornale Italiano di Radiologia Medica 2019 Marzo-Aprile;6(2):183-90.


"Linforisonanza e trapianto di linfonodi: nuove possibilità per il trattamento del linfedema”

M. Soresina, A. Menozzi, D. Giardini, M.Cellina, G. Oliva
68° Congresso Nazionale SICPRE 2019 (Società Italiana di Chirurgia Plastica Ricostruttiva ed Estetica

"Secondary Lymphedema in Oncologic Patients: What Can Non-Contrast Magnetic Resonance Lymphangiography (NCMRL) Tell Us?"

M. I. Cellina; M. A. Orsi, P. Mirani; C. Martinenghi, M. Soresina; A. Menozzi; et al. 

RSNA 2019 (Radiological Society of North America)

“Non-Contrast MR Lymphography (NCMRL): Acquisition protocol and interpretation of imaging findings"

M. Cellina, M. Soresina, A. Menozzi, D. Boccanera, M. A. Orsi, E. Belloni, F. Calliada, G. Oliva.
ECR 2019 (European Congress of Radiology)

"Non-Contrast MR Lymphography: This Is How We Do It!"

M. Cellina‚ M. A. Orsi‚ P. Mirani‚ D. Gibelli‚ G. Van Der Byl‚F. Leone‚ G. Oliva
RSNA 2018 (Radiological Society of North America)

"Linfografia RM senza mdc: tecnica, indicazioni, interpretazione"

M.Cellina, M. Orsi, P. Mirani, G. van der Byl, F. Leone, G. Oliva
Congresso Nazionale SIRM 2018