ORIGINAL RESEARCH • THORACIC IMAGING

Contrast-enhanced Interstitial Transpedal MR

Lymphangiography for Thoracic Chylous Effusions
Claus C. Pieper, MD • Andreas Feisst, MD • Hans H. Schild, MD
From the Department of Radiology, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. Received July 18, 2019; revision requested September 17; revision
received January 2, 2020; accepted January 13. Address correspondence to C.C.P. (e-mail: claus.christian.pieper@ukbonn.de).

Conflicts of interest are listed at the end of this article.

See also the editorial by Maki and Itkin in this issue.

Radiology 2020; 295:458–466 • https://doi.org/10.1148/radiol.2020191593 • Content codes:

Background: Abnormalities of the central lymphatic system (CLS) are increasingly treated by interventional radiology approaches.
Planning of these procedures, however, is challenging because of the lack of clinical imaging tools.

Purpose: To evaluate the clinical usefulness of contrast agent2enhanced interstitial transpedal MR lymphangiography in the prein-
terventional workup of lymphatic interventions in patients with thoracic chylous effusions.

Materials and Methods: Patients with chylous effusions evaluated from January 2014 and December 2017 were included in this ret-
rospective analysis of transpedal MR lymphangiography. Indications were chylothorax (n = 19; 76%), cervical lymphatic fistula (n
= 2; 8%), and combined chylothorax and chylous ascites (n = 4; 16%). Patients underwent transpedal MR lymphangiography at
1.5 T with T1-weighted imaging after interstitial pedal of gadolinium-based contrast medium under local anesthesia. Contrast-
enhanced MRI was evaluated for technical success, depiction of pathologic abnormalities of the CLS, and access site for lymphatic
interventions (ie, clinically useful examination). Reader agreement for image quality and overall degree of visualization was as-
sessed with weighted k. Interrelations between overall image quality and degree of visualization of CLS structures were assessed by
Spearman r. Efficacy of transpedal MR lymphangiography was calculated by using radiographic lymphangiography as the reference
standard.

Results: Twenty-five patients (mean age, 54 years 6 18 [standard deviation]; 13 men) were evaluated. Eight percent (two of 25)
of examinations failed (lymphoma in one patient and technical failure in one patient). Contrast agent injection was well tolerated
without complications. Interrater agreement of image quality was excellent (k = 0.96). The degree of CLS visualization correlated
with overall image quality (r = 0.71; P , .001). Retroperitoneal lymphatics, cisterna chyli, and thoracic duct were viewed with an
accuracy of 23 of 25 (92%), 24 of 25 (96%), and 23 of 25 (92%), respectively. Anatomic variations, a lymphatic pathologic abnor-
mality, and interventional access routes were identified with an accuracy of 22 of 25 (88%), 23 of 25 (92%), and 24 of 25 (96%),
respectively. Overall, 23 of 25 (92%) transpedal MR lymphangiograms provided clinically useful information.

Conclusion: Transpedal interstitial MR lymphangiography was well tolerated by the patient and identified specific pathologic abnor-
malities causing thoracic chylous leakages before lymphatic intervention.
© RSNA, 2020

Online supplemental material is available for this article.

C hylous leakages from the central lymphatic system

(CLS; ie, cisterna chyli, thoracic duct, and direct tribu-
taries) (1) can occur after trauma or a surgical procedure,
or may develop spontaneously because of various medical
conditions (2,3). Minimally invasive lymph vessel embo-
lization has been established as an alternative treatment
option in patients with persistent leakage (2,4–7). For
adequate planning of these often complex interventional
procedures, preinterventional imaging of the CLS is help-
ful. However, adequate imaging of the lymphatic system
remains challenging. Different MRI-based lymphatic
imaging approaches have been developed (8,9) including
unenhanced MR lymphangiography and dynamic con-
trast-enhanced (DCE) MR lymphangiography. However,
both techniques have specific drawbacks: on unenhanced
MR lymphangiography it can be difficult to distinguish
lymphatic vessels from surrounding tissue with high T2
signal, especially in patients with large effusions. DCE
MR lymphangiography is a useful tool in evaluating CLS
anatomy, function, and lymphatic pathologic changes
This copy is for personal use only. To order printed copies, contact reprints@rsna.org
(9,10). However, this method is time consuming and
requires inguinal intranodal injection of a gadolinium-
based contrast-agent.
Transpedal MR lymphangiography uses pedal inter-
stitial injection of a standard MRI contrast agent and is
a technically simple alternative to DCE MR lymphangi-
ography (11). Our study aimed to evaluate the clinical
usefulness of interstitial transpedal MR lymphangiogra-
phy in the preinterventional workup for lymphatic inter-
ventions in patients with thoracic lymphatic pathologic
abnormalities.
Materials and Methods
Transpedal MR lymphangiography reported in this ar-
ticle were performed as part of our standard clinical pre-
interventional workup of patients with chylous effusions.
Patients were informed about the procedure in detail
including off-label contrast agent use and provided writ-
ten informed consent for the examination. Retrospective
analysis of data for research use was approved by the lo-

Abbreviations
CLS = central lymphatic system, DCE = dynamic contrast enhanced
Summary
In patients with thoracic chylous effusions, the anatomy of the
central lymphatic system and lymphatic abnormalities were reliably
viewed at interstitial transpedal MR lymphangiography.
Key Results
n Interstitial transpedal MR lymphangiography had a high technical
success rate (92%) by using a gadolinium-based contrast agent.
n The cisterna chyli and thoracic duct were identified with an accu-
racy of 96% and 92%, respectively.
n Lymphatic abnormalities and interventional access routes were
identified with an accuracy of 92% and 96%, respectively.
cal institutional review board with a waiver for further written
informed patient consent.
A previous study (11) documenting technical feasibility of in-
terstitial transpedal MR lymphangiography of the CLS included
five patients who were also included in our study.
Patient Selection
Transpedal MR lymphangiography is part of the standard
diagnostic workup for patients who have clinically proven
refractory lymphatic leakage and who were referred to the
Department of Radiology (University Hospital Bonn, Bonn,
Germany), a tertiary reference center for lymphatic patho-
logic abnormalities. MRI is performed unless patients present
with contraindications for MRI, have severe claustrophobia,
or do not agree to the examination. Clinical and procedural
data of all patients were recorded. We reviewed transpedal MR
lymphangiography examinations in consecutive patients with
isolated thoracic lymphatic leakages or combined thoracic and
abdominal leakages scheduled for lymphatic intervention be-
tween January 2014 and December 2017. The indications were
traumatic or iatrogenic chylothorax in eight patients (32%),
nontraumatic chylothorax in 11 patients (44%), postoperative
cervical lymphatic fistula in two patients (8%), and combined
chylothorax and chylous ascites in four patients (16%).
Transpedal MR Lymphangiography
All transpedal MR lymphangiography examinations were per-
formed by the same radiologist (C.C.P., a diagnostic and inter-
ventional radiologist with 8 years of experience) on a 1.5-T sys-
tem (Ingenia; Philips Healthcare, Best, the Netherlands) with
the patient in supine position and outstretched legs without
a leg wedge to allow for free lymph flow. Conscious sedation
was applied if necessary. No general anesthesia was performed.
A 16-channel phased-array coil was used to cover the torso
from neck to groin. Both feet were prepared for aseptic injection
and local anesthesia was performed with 0.2-mL mepivacain 1%
(Mecain; Actavis, Langenfeld, Germany) per interdigital space
by using a 27-gauge needle. Six milliliters of 1.0 mmol/mL
gadobutrol (Gadovist; Bayer Vital, Leverkusen, Germany) were
diluted with 0.9% saline solution to 8 mL to increase the volume
for injection, which resulted in a slight reduction of osmolality.
Radiology: Volume 295: Number 2—May 2020 n radiology.rsna.org
Pieper et al
Figure 1: Injection sites (arrows) in the foot for interdigital intradermal
gadolinium contrast agent application.
Before contrast agent administration, an axial breath-hold
three-dimensional T1-weighted multigradient-echo, re-
ferred to as mDIXON, sequence was performed (repetition
time msec/echo time msec, 5.4/1.8 and 4; acquisition time per
stack, 10 seconds) (12). Three separate stacks of slices were ac-
quired to cover the entire torso.
After noncontrast imaging, 1 mL of diluted contrast medium
per interdigital space was injected intradermally by inserting the
needle tangentially into the superficial dermis, avoiding pen-
etration into the subcutis on both feet (overall, 8 mL of diluted
contrast solution; 4 mL per foot) (Fig 1). After injection, pa-
tients moved their legs by walking or doing knee bends for 325
minutes with subsequent immediate performance of the three-
dimensional mDIXON sequence (except for the first patient, in
whom image acquisition was started 30 minutes after contrast
injection) (Table 1). Imaging was repeated at least 5 times at
intervals of 5 minutes to observe lymphatic flow on water-only
images until the contrast medium was washed out of the CLS
and renal contrast medium excretion was observed. If no con-
trast enhancement of the CLS was observed within 30 minutes
after injection, the examination was aborted.
Radiographic Lymphangiography
All patients underwent radiographic lymphangiography with
Lipiodol (Guerbet, France) (transpedal, two patients; and
transnodal, 23 patients) as described previously (2). Lymphatic
interventions were performed in the same session as radio-
graphic lymphangiography if indicated (3,4). Radiation expo-
sure at lymphangiography and intervention, and technical and
clinical success were documented.
Image Analysis and Definitions
Qualitative assessment of all transpedal MR lymphangiogra-
phy examinations was performed independently by two radi-
ologists (C.C.P. and A.F., a diagnostic radiologist with 6 years
of experience) who were blinded to clinical details and final
diagnosis. The interval between the readout sessions was 2
weeks. Disagreements were discussed in consensus for further
459
Interstitial Transpedal MR Lymphangiography for Thoracic Chylous Effusions
Table 1: Detailed Instructions for Transpedal MR Lymphangiography
Parameter Transpedal Injection* Positioning Leg Maneuvers
Time
0 min Supine None
10 min 1 mL per interdigital space Supine None
15 min Patient gets up and moves legs/
walking/knee bends
20 min Supine None
25 min Supine None
30 min Supine None
35 min Supine None
40 min Supine None
45 min Supine None
Note.—mDIXOM = axial breath-hold three-dimensional T1-weighted multigradient-echo sequence, T1w = T1 weighted.
* Transpedal injection was 6 mL of 1.0 mmol/mL gadobutrol diluted to 8 mL.
analyses. The examination was rated as technically successful
if CLS visualization was excellent to moderate or if lymphatic
pathologic abnormalities preventing contrast flow into the
CLS were identified.
Overall image quality was rated on a five-point scale (Fig
E1 [online]). Contrast-enhanced MR and radiographic lym-
phangiograms were evaluated regarding depiction of the rele-
vant CLS anatomy: retroperitoneal lymphatics, cisterna chyli,
thoracic duct, and anatomic variations. Overall visualization
of CLS anatomy was rated as excellent, moderate, poor, or
not visible.
Images were further assessed for the presence of a lymphatic
pathologic abnormality (eg, chylolymphatic leakage or reflux)
and an access route for lymphatic interventions. Chylolym-
phatic leakage was defined as pooling of contrast medium
outside of lymphatic channels, and reflux was defined as retro-
grade contrast medium flow within lymphatic structures.
The time between contrast agent injection and visualization
of the respective central lymphatic structures was recorded.
Venous contrast enhancement obscuring lymphatics and the
time interval from initial contrast enhancement of the CLS to
complete washout were assessed. Final diagnosis of a lymphatic
pathologic abnormality and the clinical usefulness of transpedal
MR lymphangiography for patient treatment were determined
in consensus by the radiologists performing the intervention
(C.C.P. and H.H.S., a diagnostic and interventional radiolo-
gist with over 40 years of experience), blinded to clinical course
of the patients. Adverse events associated with transpedal MR
lymphangiography were recorded if manifest.
Statistical Analysis
Statistical analyses were performed by using software (SPSS,
version 23.0; IBM, Armonk, NY). Descriptive statistics were
performed for patient characteristics, and imaging findings
were provided as mean 6 standard deviation for normally dis-
tributed continuous variables, median and range for skewed
continuous variables, or count for categorical variables. Inter-
rater agreement for image quality and overall degree of visu-
alization of the CLS was analyzed by using weighted k val-
460
Imaging Location MRI Pulse Sequences
Entire torso Noncontrast axial T1w
mDIXON
None
None
Entire torso Axial T1w mDIXON
Entire torso Axial T1w mDIXON
Entire torso Axial T1w mDIXON
Entire torso Axial T1w mDIXON
Entire torso Axial T1w mDIXON
Entire torso Axial T1w mDIXON
ues. k values were rated as follows: minor, less than 0.20; fair,
0.2120.40; moderate, 0.4120.60; good, 0.6120.80; and
almost perfect agreement, 0.8121.00 (13,14). Interrelations
between overall image quality and degree of visualization of
CLS structures were assessed by calculating Spearman correla-
tion coefficient. Efficacy of transpedal MR lymphangiography
for depiction of CLS structure, anatomic variations, lymphatic
pathologic abnormalities, and interventional access routes were
calculated by using the results of radiographic lymphangiogra-
phy as a reference standard. P values less than .05 were consid-
ered to indicate statistical significance.
Results
Patient Demographics
We evaluated 25 consecutive patients (mean age, 54 years 6
18 [standard deviation]; age range, 19285 years; 13 men). For
further patient characteristics see Table 2. A flowchart (Fig 2)
shows patients inclusions and exclusions.
Technical Success of Transpedal MR Lymphangiography
Examinations
Interdigital pedal contrast agent injection was well tolerated in
all patients without complications, with a mean follow-up time
of 3.8 years 6 1.0.
Overall, 23 of 25 transpedal MR lymphangiography exami-
nations (92%) were technically successful with visualization of
either the relevant CLS anatomy including anatomic variations
or depiction of a lymphatic pathologic abnormality. In the re-
maining two patients (Fig 3), transpedal MR lymphangiography
was unsuccessful because of severe bilateral lymphedema in a
patient with lymphoma and in a second patient because image
acquisition was started too late after contrast agent injection dur-
ing our early experience with transpedal MR lymphangiography.
Image Quality
Image quality was rated as excellent in seven patients (28%),
good in nine patients (36%), moderate in six patients (24%),
and poor in three patients (12%). Overall interrater agreement
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Table 2: Demographic and Clinical Variables of Patients
with Thoracic Chylous Effusions
Variable
No. of patients
Sex
Male
Female
Mean age (y)
Clinical indication for lymphatic intervention
Traumatic/iatrogenic chylothorax
Nontraumatic chylothorax
Cervical lymphatic fistula
Combined chylothorax/chylous ascites
Previous treatments
Medium chain triglyceride diet
Parenteral nutrition
Somatostatin/octreotide
Mean drainage volume prior to intervention
  (mL/day)
Note.—Unless otherwise indicated, data are number of patients and
data in parentheses are percentages. Mean data are 6 standard
deviation.
Figure 2: Study flowchart and exclusions.
of image quality was almost perfect with a weighted k coef-
ficient of 0.96. The most prevalent cause of poor image quality
was prominent motion artifacts (severe in three patients [12%]
and moderate in seven patients [28%]), especially because of
shortness of breath in patients with severe pleural effusions.
Contrast enhancement of the CLS was rated as excellent in 12
examinations (48%), moderate in 11 examinations (44%), and
not visible in two examinations (8%) (ie, technically unsuccess-
ful). In all technically successful transpedal MR lymphangiogra-
phy examinations (23 of 25; 92%), contrast enhancement was
observed within 15 minutes after the start of injection (within 5
minutes, first postcontrast image: 15 [60%]; within 5–10 min-
utes, eight [32%]; and within 10–15 minutes, two [8%]). After
first CLS visualization, the contrast agent was washed out after a
mean of 26.3 minutes 6 7.2.
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Pieper et al
CLS Visualization
Retroperitoneal lymphatics showed contrast enhancement on
23 of 25 (92%) transpedal MR lymphangiograms and 25 of 25
Value (100%) radiographic lymphangiograms (Fig 4). The cisterna
25 chyli and the thoracic duct were viewed on 20 of 25 (80%) and
21 of 25 (84%) MR lymphangiograms, respectively, and 21 of
13 (52) 25 (84%) and 23 of 25 (92%) radiographic lymphangiograms,
12 (48) respectively (Fig 5). Efficacy of transpedal MR lymphangiogra-
54 6 18 phy is summarized in Table 3.
At MR lymphangiography, the thoracic duct was viewed
8 (32) continuously in 14 of 25 patients (56%) and discontinuously
11 (44) in seven of 25 patients (28%). In three patients (12%), con-
2 (8) trast enhancement was excellent only below the leakage site
4 (16) (chylous ascites in one patient and leakage in the lower third of
the thoracic duct in two patients; Fig E1 [online]).
12 (48)
Overall interrater agreement concerning the degree of visu-
17 (68)
alization of CLS structures at MR lymphangiography was high
4 (16)
(weighted k coefficient, 0.828). Further analysis showed that
1252 6 785
overall degree of visualization of the CLS correlated with overall
image quality (r = 0.72; P , .001). However, in both techni-
cally unsuccessful examinations, lack of CLS visualization was
not attributable to poor image quality because image quality
was moderate in these instances. Slow venous enhancement was
manifest in all examinations but did not obscure the CLS.
Anatomic variations were depicted on 15 of 25 (60%)
transpedal MR lymphangiograms and on 18 of 25 (72%) ra-
diographic lymphangiograms: partial duplications of the tho-
racic duct in 11 and 13 patients (Fig E1 [online]), a network
of small lymphatics instead of a thoracic duct in two and three
patients, and a right-side thoracic duct terminating in the right
venous angle in two and two patients, respectively. A possible
access site for transabdominal lymphatic intervention (either
cisterna chyli or lower part of the thoracic duct) was identified
on 23 of 25 (92%) transpedal MR lymphangiograms and on
24 of 25 (96%) radiographic lymphangiograms.
A lymphatic pathologic abnormality was identified on 22
of 25 (88%) MR lymphangiograms and on 24 of 25 (96%)
radiographic lymphangiograms. Detection rates of lymphatic
pathologic abnormalities are summarized in Table 4. Typical
examples of lymphatic pathologic abnormalities are shown in
Figures 4–6.
Clinical Success
All technically successful transpedal MR lymphangiography
examinations (23 of 25; 92%) provided information that was
deemed to be clinically useful by the interventionalists in guid-
ing the subsequent lymphatic intervention. Eight of 25 (32%)
patients underwent radiographic lymphangiography without
further intervention and 17 of 25 (68%) patients underwent
additional transcatheter lymphatic embolization in the iden-
tified pathologic abnormality, all of which were technically
successful. Overall, 21 of 25 (84%) interventional radiologic
treatments were clinically successful with termination of the
leakage (six of eight [75%] after radiographic lymphangiogra-
phy and 15 of 17 [88%] after embolization). Median doses of
the diagnostic and interventional procedures are summarized
in Table 5.
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Interstitial Transpedal MR Lymphangiography for Thoracic Chylous Effusions

Figure 3: Technical failure. Axial images in a 79-year-old man with bilateral chylothorax and non-Hodgkin lymphoma.
The patient had severe bilateral lymphedema of both legs. (a, b) Axial T1-weighted contrast-enhanced transpedal
MR lymphangiography, (c, d) corresponding axial CT images after lipiodol injection, and (e, f) digital radiographic
lymphangiogram. At MR-lymphangiography there was no contrast enhancement of the central lymphatic system. On the
corresponding radiographic lymphangiographic and CT images after lipiodol injection, chylous reflux into mediastinal and
peribronchial lymphatics (arrows) and only faint venous runoff was identified as the cause of chylothorax.

Discussion water-soluble gadolinium-based contrast agent was well toler-

We evaluated whether transpedal MR lymphangiography
could be an alternative imaging technique to radiographic lym-
phangiography for evaluation of the central lymphatic system
(CLS) in patients with chylous effusions and/or chylous ascites.
We found that interstitial pedal contrast agent injection with a
ated and there were no procedural or delayed complications.
We observed a high rate (92%) of technical success with a close
correlation (r = 0.72; P , .001) between the degree of CLS
visualization and overall image quality. There was an 8% (two
of 25) examination failure rate (lymphoma in one patient and

462 radiology.rsna.org n Radiology: Volume 295: Number 2—May 2020


Figure 4: MR lymphangiography and corresponding digital radiographic lymphangiography.
Images in a 69-year-old woman with right-sided chylothorax after esophagectomy. (a) Axial T1-
weighted image and (b) coronal maximum intensity projection of a contrast-enhanced transpedal
MR lymphangiogram and (c) corresponding digital radiographic lymphangiogram. MR and ra-
diographic lymphangiography both showed retroperitoneal lymphatics and a localized lymphatic
leakage (arrows) into the right mediastinal pleural recess as the cause of chylothorax. After embo-
lization of the lymphatics at the leakage site, drainage via an indwelling pleural catheter stopped
within 1 day.
technical failure in one patient). Interrater agreement of image
quality was excellent (k = 0.96). The degree of CLS visualiza-
tion correlated with overall image quality (r = 0.71; P , .001).
Retroperitoneal lymphatics, cisterna chyli, and thoracic duct
were viewed with an accuracy of 23 of 25 (92%), 24 of 25
(96%), and 23 of 25 (92%), respectively. More importantly,
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Pieper et al
potentially treatment-influencing (15) anatomic
variations, lymphatic pathologic abnormalities,
and interventional access routes were identified
with an accuracy of 22 of 25 (88%), 23 of 25
(92%), and 24 of 25 (96%), respectively. Overall,
92% (23 of 25) of the transpedal MR lymphan-
giograms provided clinically useful information.
In future studies, this transpedal MR lymphan-
giography could be used for planning anatomically
modified interventional procedures, shorter inter-
ventions, and less radiation exposure for patients sus-
pected of having lymphatic pathologic abnormalities.
MR lymphangiography by using interstitial pedal
injection of a gadolinium-based contrast medium is
an established technique for evaluation of peripheral
lymphatics in patients with lymphedema or who are
suspected of having pelvic lymph node metastases
(16,17). Typically, only the peripheral lymphatics up
to the level of the pelvic lymph nodes are viewed at
standard transpedal MR lymphangiography even in
extremities without edema (18). Therefore, alterna-
tive contrast agents have been developed (dendrimer-
based gadolinium-labeled contrast medium [19],
lipophilic perfluorinated gadolinium chelates [20],
and gadofosveset premixed with human albumin
[21]) to allow for enhancement of the CLS. How-
ever, these contrast agents are not commercially avail-
able for clinical use.
Existing imaging approaches for the CLS are as-
sociated with certain disadvantages. Radiographic
lymphangiography is time consuming, invasive,
involves the use of medical radiation, and involves
the known risks of lipiodol (8). Especially because
of relatively high radiation doses for diagnostic ra-
diographic lymphangiography (20 mSv for thoracic
lymphatic leakage and 19 mSv for lymphatic flow
abnormalities in our study), its use should be lim-
ited to therapeutic procedures (22) after evaluation
of the lymphatic system by using nonionizing MR
lymphangiography. Lymphoscintigraphy is an estab-
lished technique in examining peripheral lymphatics,
but it does not provide sufficient anatomic resolution
for CLS evaluation (8). Unenhanced MR lymphan-
giography can depict central lymphatics, but it can
be difficult to distinguish them from surrounding
tissue, especially in cases of large effusions or medi-
astinal edema (8). DCE MR lymphangiography is a
recently introduced and promising approach (9,23)
with contrast agent injected directly into inguinal
lymph nodes. An advantage of transpedal MR lym-
phangiography over intranodal DCE MR lymphan-
giography is that it forgoes the need for sonography-guided lymph
node puncture outside of the MRI department and therefore the
risk of needle dislocation during transport into the imager. It is
therefore less time consuming and less invasive. However, because
successful transpedal MR lymphangiography examination re-
quires active leg movement by the patients, it cannot be performed
463
Interstitial Transpedal MR Lymphangiography for Thoracic Chylous Effusions

Figure 5: MR lymphangiography and corresponding digital radiographic lymphangiography. Images in a 53-year-old

man with combined bilateral chylothorax and chylous ascites after thrombosis of the left subclavian and brachiocephalic
vein. (a–c) Axial T1-weighted contrast-enhanced transpedal MR lymphangiograms and (d) corresponding digital radio-
graphic lymphangiogram. MR lymphangiography and radiographic lymphangiography both showed enhancement of a
normal thoracic duct (arrows). There was reflux from the terminal thoracic duct into mediastinal and peribronchial lymphatics
(arrowheads) and only faint venous runoff as the cause of chylothorax and chylous ascites. Mediastinal and peribronchial
lymphatics were embolized. Leakage stopped subsequently within 2 days.

Table 3: Efficacy of Transpedal MR Lymphangiography to View the Central Lymphatics in Patients with Thoracic Chylous Leaks

No. of Identified Structures No. of Identified

Parameter at Radiography Structures at MRI Sensitivity Specificity Accuracy
Transpedal MR lymphangiography
Visualization of retroperitoneal 25/25 23/25 23/25 (92) [0.87,1] NA 23/25 (92)
  lymphatics
Visualization of cisterna chyli 21/25 20/25 20/21 (95) [0.84,1] 4/4 (100) 24/25 (96)
Visualization of thoracic duct 23/25 21/25 21/23 (91) [0.86,1] 2/2 (100) 23/25 (92)
Visualization of access site 24/25 23/25 23/24 (96) [0.86,1] 1/1 (100) 24/25 (96)
Visualization of lymphatic 24/25 22/25 22/24 (92) [0.86,1] 1/1 (100) 23/25 (92)
  pathology
Visualization of anatomic variants 18/25 15/25 15/18 (83) [0.82,1] 7/7 (100) 22/25 (88)
Note.—Data are numerator/denominator; data in parentheses are percentages and data in brackets are 95% confidence intervals. Lipiodol
lymphangiography was used as the reference standard. NA = not applicable.

under general anesthesia. Furthermore, dynamic information on lymphatic flow abnormalities are anticipated (eg, in children after
lymph flow is limited compared with DCE MR lymphangiog- Fontan surgery), DCE MR lymphangiography is the preferred
raphy, in which the flow of the entire contrast medium can be examination. Unlike DCE MR lymphangiography, exact tim-
viewed (9). In patients who require anesthesia or when complex ing of image acquisition is necessary when performing transpedal

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 Pieper et al

Table 4: Lymphatic Pathologic Abnormalities Identified at Transpedal MR Lymphangiography and Digital Radiographic
Lymphangiography

Identified Lymphatic Pathologic Abnormality Radiographic Lymphangiography Transpedal MR Lymphangiography

Postsurgical lymphatic leakage 9/25 (36) 9/25 (36)
Chylous reflux 12/25 (48) 10/25 (40)
Leakage from lymphatic anomaly/malformation 3/25 (12) 3/25 (12)
No pathologic abnormality identified 1/25 (4) 3/25 (12)
Note.—Data are numerator/denominator; data in parentheses are percentages.

Figure 6: MR lymphangiography and corresponding digital radiographic lymphangiography. Images in a 51-year-old woman with recurrent spontaneous chylothorax.
(a–c) Axial T1-weighted contrast-enhanced transpedal MR lymphangiography, (d) sagittal reconstruction, and (e, f) corresponding digital radiographic lymphangio-
grams. MR lymphangiography shows normal lymphatic runoff via the cisterna chyli (black arrow) and the thoracic duct (white arrows) without depiction of a lymphatic
pathologic abnormality or anatomic variation. Radiographic lymphangiography also did not show a pathologic abnormality. Chylothorax did not recur after lymphangiog-
raphy (follow-up, 3 years).

Table 5: Radiation Dose in Radiographic Lymphangiography and Interventional Procedures

Median Dose Diagnostic Median Dose Interventional Procedure Total Median Dose
Parameter Lymphangiography (mSv) to Stop Chylous Leak (mSv) (mSv)
Thoracic lymphatic leak 20 (11.5–28.5) [9] 15 (10.5–19.5) [9] 34 (23–45) [9]
Pathologic abnormalities of lymphatic flow 19 (12–26) [16] 12 (2.5–21.5) [8] 23 (10–36) [16]
Note.—Data in parentheses are interquartile range and data in brackets are number of patients.

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Interstitial Transpedal MR Lymphangiography for Thoracic Chylous Effusions
MR lymphangiography because there is only a narrow window of
10250 minutes after injection when adequate enhancement can
be observed, starting within 5215 minutes after injection of the
contrast agent.
In peripheral MR lymphangiography, venous contamination
can obscure lymphatic vessels, making differentiation between
lymphatic and venous vessels difficult. To counteract venous
contrast enhancement, dual-agent relaxation contrast MR lym-
phangiography was recently introduced by using a venous infu-
sion of ferumoxytol to suppress any signal from the veins (24).
However, venous contamination was not a problem in any of
our patients. When water-only multiecho gradient-echo images
are obtained (12), no subtraction of enhanced and unenhanced
images is necessary, which allows for good distinction of central
lymphatics from surrounding tissue.
Transpedal MR lymphangiography can be performed with a
standard commercially available extracellular contrast agent with-
out complications in our study sample with a mean follow-up of
3.8 years 6 1.0. However, interstitial injection of gadobutrol is an
off-label use. Local infections or reactions to the contrast medium
are potential complications (25). Injection should be performed
intradermally, whereas intramuscular injections should be avoided
(25). Image quality in our study was primarily influenced by the
presence of motion artifacts from breathing. Large effusions re-
ducing functional lung volume should therefore be drained before
transpedal MR lymphangiography if possible.
Our study had limitations. First, it was limited by the small
size of the reported study sample because thoracic chylous effu-
sions are a relatively rare clinical problem, and about 70% of these
are self-limited (2). Second, we only included adult patients, be-
cause pediatric patients typically require general anesthesia. Be-
cause transpedal MR lymphangiography requires active muscle
movement of the patients, nodal DCE MR lymphangiography
is the examination technique of choice in pediatric cases.
In conclusion, interstitial transpedal MR lymphangiography
may be a valuable diagnostic tool in patients with thoracic chy-
lous leakages, providing information on the anatomy of the cen-
tral lymphatic system and the underlying lymphatic pathologic
abnormalities, and possible interventional access routes. Prospec-
tive comparative studies are warranted to determine the optimal
clinical applications for both transpedal MR lymphangiography
and dynamic contrast-enhanced MR lymphangiography.
Acknowledgment: We thank Jennifer Nadal, MSc (Institute for Medical Biom-
etry, Informatics and Epidemiology, University of Bonn) for her support regarding
statistical analysis.
Author contributions: Guarantors of integrity of entire study, C.C.P., H.H.S.;
study concepts/study design or data acquisition or data analysis/interpretation, all
authors; manuscript drafting or manuscript revision for important intellectual con-
tent, all authors; approval of final version of submitted manuscript, all authors;
agrees to ensure any questions related to the work are appropriately resolved, all au-
thors; literature research, all authors; clinical studies, all authors; statistical analysis,
C.C.P.; and manuscript editing, all authors
466
Disclosures of Conflicts of Interest: C.C.P. Activities related to the present ar-
ticle: disclosed no relevant relationships. Activities not related to the present article:
disclosed money paid to author for consultancy from Guerbet; money paid to au-
thor’s institution for grants/grants pending from Guerbet; money paid to author
for lectures from Philips Healthcare, Bayer Vital, and Guerbet. Other relationships:
disclosed no relevant relationships. A.F. disclosed no relevant relationships. H.H.S.
disclosed no relevant relationships.
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radiology.rsna.org n Radiology: Volume 295: Number 2—May 2020