Key words lymphatic - lymphography - thorax - MR imaging
Introduction
Intractable chylous effusions are associated with considerable morbidity and mortality
[1 ]
[2 ]. One of the main problems, especially in minimally invasive treatment of lymphatic
pathologies [2 ]
[3 ]
[4 ]
[5 ] is the lack of simple imaging techniques for the visualization of the central lymphatic
system (CLS; i. e., cisterna chyli (CCh), thoracic duct (TD) and direct tributaries)
[6 ].
There are certain disadvantages associated with existing CLS imaging approaches. Conventional
X-ray lymphangiography is technically challenging, invasive and time-consuming [7 ]. Lymphoscintigraphy has insufficient anatomical resolution for CLS evaluation [7 ]. On non-contrast MR-lymphangiography, central lymphatics can be evaluated, but it
can be difficult to distinguish lymphatics from surrounding tissue [7 ]
[8 ]. Dynamic contrast-enhanced MR-lymphangiography is a promising new approach [9 ]
[10 ]. However, it is time-consuming due to necessary sonographically guided lymph node
puncture outside the scanner room, and usually requires general anesthesia or at least
sedation.
To overcome these disadvantages, we sought to develop an MR imaging technique that
can provide information on CLS anatomy, without time-consuming intranodal contrast
application or general anesthesia. The aim of this study is to describe this new technique
for transpedal MR-lymphangiography (tMRL) with interstitial injection of a standard
gadolinium-based contrast agent and to assess its ability to visualize the CLS in
patients with chylous effusions.
Materials and Methods
We retrospectively reviewed our recent experiences (10/2015 – 04/16) with tMRL to
visualize the central lymphatics in seven patients referred to our institution for
the treatment of clinically proven therapy-resistant chylous effusions. Patient characteristics
and procedural information are given in case studies in the results section. Institutional
review board approval and the patients’ written informed consent for the procedure
and for data analysis were obtained.
MR imaging was performed by the same radiologist (C.C.P. with more than 5 years of
experience) on a 1.5 Tesla MR scanner (Ingenia, Philips Healthcare, Best, The Netherlands)
with the patient in a supine position. A leg wedge was not used to allow for free
lymph flow. Patients were neither sedated nor intubated. A 16-channel phased-array
coil was used to cover the entire torso. After preparation of both feet for aseptic
injection, local anesthesia was administered with 0.2 ml mepivacaine 1 % (Mecain,
Actavis, Langenfeld, Germany) per interdigital space using a 27-gauge needle. 6 ml
of 1.0 mmol/ml gadobutrol (Gadovist, Bayer Vital, Leverkusen, Germany) were diluted
with saline solution to 8 ml to increase the volume for injection.
An axial non-contrast breath-hold three-dimensional T1-weighted multi-gradient echo
(mDIXON) sequence was acquired [11 ] ([Table 1 ]). Three separate stacks of axial slices were sufficient to cover the entire torso.
Table 1
Imaging parameters.Tab. 1 Sequenzparameter.
Repetition time
Shortest
Echo time
1.8 ms and 4 ms
Flip angle
15°
k-space acquisition
Cartesian
Field of view
300 × 400 mm
Acquired voxel size
1 × 1.2 × 2.5 mm³
Reconstructed voxel size
1 × 1 × 1mm³
Parallel imaging factor
1.65
Acquisition time per stack
10 seconds
Thereafter, bilateral interstitial intradermal injection of 1 ml of the diluted contrast
medium per interdigital space was performed (overall 8 ml of 6.0 mmol gadobutrol which
is the recommended standard dose for intravenous application in patients with a bodyweight
of 60 kg). The patients were asked to move their legs for 3 – 5 minutes. The three-dimensional
mDIXON sequence was then repeated every 5 minutes to observe lymphatic flow until
washout and renal contrast medium excretion were observed. The time a patient remained
in the scanner was documented.
MR examinations were assessed qualitatively by two radiologists (C.C.P. and H.H.S.).
Visualization of the central lymphatics (excellent, moderate, poor, not visible),
delineation of their anatomy and the presence of chylolymphatic leakage or reflux
were evaluated. Leakage was defined as progressive pooling of contrast medium outside
of lymphatic structures, reflux as retrograde contrast medium flow within lymphatic
channels. Technical success was defined as excellent or moderate visualization of
the CLS (especially of the TD, as a CCh can be anatomically absent in up to 30 % of
cases [12 ]) or detection of pathology preventing contrast flow into the CLS. Venous contrast
contamination obscuring the lymphatics was assessed. Diagnosis of lymphatic pathology
and impact of tMRL on patient management were determined in consensus by both radiologists.
The time for visualization of different parts of the lymphatic system was recorded.
Any adverse events associated with tMRL were noted.
Results
Case studies
Patient 1
A 24-year-old patient presented with left-sided non-traumatic chylothorax. Thoracoscopic
surgery and parenteral nutrition had been unsuccessful with persisting leakage of
1000 ml/day. On tMRL the pelvic and retroperitoneal lymphatics, CCh and the lower
two-thirds of the TD appeared normal with segmental TD duplication in the lower thorax.
Abnormally dilated lymphatic ducts surrounded the left-sided termination of the TD
([Fig. 1 ]). Chylolymphatic leakage or reflux was not observed. A diagnosis of localized lymphatic
malformation as the cause of the chylothorax was established and confirmed by conventional
lymphangiography during the subsequent lymphatic intervention. After transabdominal
embolization of the malformation, drainage via the chest tube ceased immediately.
Fig. 1 Case study 1. a -c Axial tMRL images in a patient with extensive left-sided chylothorax with mediastinal
shift to the right. Examination showed normal thoracic lymphatic anatomy with duplication
of the thoracic duct in the lower thorax (inset magnification in c ) and dilated left-sided lymphatics surrounding the termination of the TD (arrows).
Due to the employed imaging technique, the thyroid gland appears hyperintense in a . This does not reflect contrast enhancement. d Posterior-anterior intra-interventional image after transabdominal embolization showing
the left periclavicular lymphatic malformation (arrows). The duplication of the TD
in the lower thorax is partially obscured by mild contrast medium leakage from the
puncture site.Abb. 1 Fallstudie 1. a -c Axiale tMRL-Bilder eines Patienten mit ausgedehntem linksseitigem Chylothorax mit
Mediastinalshift nach rechts. Die Untersuchung zeigt normale anatomische Verhältnisse
der thorakalen Lymphbahnen mit Duplikation des Ductus thoracicus im unteren Thoraxdrittel
(Vergrößerung in c ) sowie dilatierte Lymphgefäße im Bereich der Mündung des Ductus thoracicus im linken
Venenwinkel (Pfeile). Technisch bedingt kommt die Schilddrüse in a hyperintens zur Darstellung. Dies ist kein Ausdruck einer Kontrastmittelaufnahme.
d Intrainterventionelle posterior-anterior Aufnahme nach transabdomineller Embolisation
mit Nachweis der links periklavikulären lymphatischen Malformation (Pfeile). Die Duplikation
des Ductus thoracicus im unteren Thoraxdrittel ist partiell durch einen geringen Kontrastmittelaustritt
aus der Punktionsstelle überlagert.
Patient 2
A 54-year-old patient suffering from necrotizing pancreatitis with left subclavian
vein thrombosis developed bilateral chylothorax, chylopericardium and chylous ascites
that were refractory to conservative treatment. TD ligation, pleurectomy and irradiation
of the TD had been unsuccessful. Lymphoscintigraphy was reported to show normal tracer
flow without depiction of pathology.
On tMRL contrast medium flow was unobstructed. The CLS appeared normal with segmental
duplications of the TD in the mid and upper thorax. There was extensive chylolymphatic
reflux from the cervical part of the TD into dilated mediastinal, pericardial and
bronchial lymphatics ([Fig. 2 ]). Leakage was not identified. Reflux was confirmed by intranodal lymphangiography.
After TD embolization, drainage via bilateral chest tubes and an ascites drain ceased
within three days. The chylopericardium also decreased on follow-up imaging.
Fig. 2 Case study 2. Sagittal maximum intensity projection a and axial slices b , c of a tMRL examination in a patient with bilateral chylothorax, chylopericardium and
chylous ascites showing extensive chylolymphatic reflux from the cervical part of
the thoracic duct (arrows) into the mediastinal, bronchial, pulmonary and pericardial
lymphatics (arrow heads).Abb. 2 Fallstudie 2. Sagittale Maximum Intensity Projection a und axiale Schichten b , c der tMRL-Untersuchung eines Patienten mit bilateralem Chylothorax, Chyloperikard
und Chylaszites. Die Untersuchung zeigt einen ausgedehnten chylolymphatischen Reflux
ausgehend vom zervikalen Anteil des Ductus thoracicus (Pfeile) in mediastinale, bronchiale,
pulmonale und perikardiale Lymphbahnen (Pfeilspitzen).
Patient 3
A 78-year-old patient developed chylous ascites refractory to conservative treatment
after surgical abdominal aortic aneurysm repair. tMRL demonstrated normal pelvic lymphatics.
At the bifurcation of the aortic graft, contrast medium leaked into a small retroaortic
recess which communicated with the peritoneal cavity. Intranodal oily lymphangiography
was performed with continuation of parenteral nutrition. After one week the leakage
resolved and did not recur during follow-up of 15 months under full oral nutrition.
Patient 4
A 62-year-old patient developed a left-sided chylothorax after surgery for recurrent
pleural mesothelioma. Parenteral nutrition with somatostatin application and several
attempts of TD ligation and pleurodesis were unsuccessful. tMRL demonstrated unobstructed
lymph flow without reflux. Several tortuous lymphatic channels in the middle and upper
thorax coalesced into a single TD before its termination. Retrocardially the tortuous
lymphatic channels showed contrast leakage into the left pleural cavity ([Fig. 3 ]). Intranodal lymphangiography confirmed the diagnosis of postoperative leakage of
three lymphatic channels. Leakage ceased immediately after successful TD embolization.
Fig. 3 Case study 4. Multiplanar reconstruction a and axial slices b – d of tMRL demonstrates several tortuous lymphatic channels in the middle to upper thorax
(arrow) with postoperative chylous leakage (arrow heads) with left-sided chylothorax.
Singular thoracic duct before its termination (short arrows).Abb. 3 Fallstudie 4. Multiplanare Rekonstruktion a und axiale Bilder b – d einer tMRL mit mehreren geschlängelt verlaufenden Lymphbahnen im mittleren und oberen
Thoraxdrittel (Pfeile) und postoperativer chylöser Leckage (Pfeilspitzen) mit linksseitigem
Chylothorax. Singulärer Ductus thoracicus vor seiner Mündung im linken Venenwinkel
(kurze Pfeile).
Patient 5
A 58-year-old patient suffered from a right-sided chylothorax after esophagectomy
with gastric interposition for esophageal cancer. Chest tube drainage did not drop
below 1000 ml per day under total parenteral nutrition. tMRL was performed to assess
lymphatic anatomy which can be altered after gastric interposition surgery. The retroperitoneal
lymphatics, the CCh and the lower part of the TD appeared normal. Contrast medium
extravasation from a side branch of the TD was visible retrocardially ([Fig. 4 ]). Importantly tMRL demonstrated an additional retroaortic lymphatic channel receiving
lymph flow from the retroperitoneal lymphatics not draining into the CCh. This channel
drained into the TD immediately below the leakage. During embolization special care
was taken to occlude this channel and the leakage site itself to prevent further chylolymphatic
flow towards the leak. Leakage ceased immediately after intervention.
Fig. 4 Case study 5. Coronal reconstruction of a tMRL in a patient with a postoperative
chylothorax after esophagectomy demonstrates the cisterna chyli (arrows) and the lower
thoracic duct (short arrows) with contrast extravasation into the right pleural cavity
(arrow heads). Observe a retroaortic lymph channel draining into the thoracic duct
at the site of leakage (black arrow).Abb. 4 Fallstudie 5. Die koronare Rekonstruktion einer tMRL eines Patienten mit postoperativem
Chylothorax nach Ösophagektomie zeigt die Cisterna chyli (Pfeile), den unteren Anteil
des Ductus thoracicus (kurze Pfeile) und eine Kontrastmittelextravasation in die rechte
Pleurahöhle (Pfeilspitzen). Zusätzlich ist eine retroaortale Lymphbahn abgrenzbar,
die unmittelbar unterhalb der Leckagestelle in den Ductus thoracicus drainiert (schwarzer
Pfeil).
Patient 6
A 54-year-old patient presented with chylous ascites refractory to conservative treatment
after radical peritonectomy and hyperthermic intraperitoneal chemotherapy for peritoneal
metastases of colorectal cancer (1500 ml per day). tMRL showed prompt contrast enhancement
of the pelvic lymphatics while the retroperitoneal lymphatics showed only minimal
enhancement. The CLS and a leakage site could not be identified. Intranodal oily lymphangiography
initially demonstrated venous drainage of contrast medium due to inguinal lymphovenous
anastomoses. After additional pelvic lymph node punctures, contrast agent ascended
into the retroperitoneal lymphatics demonstrating diffuse leakage into the peritoneal
cavity. As in tMRL the CLS did not show any enhancement. Leakage ultimately resolved
under parenteral nutrition two weeks after lymphangiography.
Patient 7
A 72-year-old female patient with a history of lymphoma currently in partial remission
after radiochemotherapy presented with a right-sided chylothorax unresponsive to conservative
treatment. tMRL demonstrated unobstructed lymph flow without reflux. The CLS appeared
normal without leakage. There was residual lymphoma in the upper retroperitoneum surrounding
the CCh not showing contrast enhancement. Based on these findings, a lymphatic intervention
was not indicated. Continuation of conservative treatment ultimately was successful
without recurrence of the chylothorax.
Overall imaging results
Interstitial tMRL was technically successful in 6/7 patients with visualization of
the CLS rated as excellent in 5/7 and good in 1/7 patients. tMRL confirmed the location
of leakage in 3/7, demonstrated a lymphatic malformation in 1/7, reflux in 1/7 and
confirmed normal chylolymphatic flow in the central lymphatics in 1/7 patients. In
patient 6 neither CLS enhancement nor leakage was detectable.
In technically successful cases, contrast medium was detectable in the central lymphatics
on initial images acquired after contrast injection. Image acquisition was performed
for at least 20 min after contrast injection (at least 5 repetitions of the 3 D T1w-sequence).
The median time a patient was in the scanner for contrast-enhanced MRL (including
preparation, pre-injection T1-images, contrast injection and post-contrast T1-images)
was 48 min (range 37 – 61 min). Contrast medium washout was observed within 15 to
25 minutes after initial post-contrast images. Although contrast medium was also already
present within the renal pelvis on initial images, relevant venous contamination was
not observed.
tMRL findings were considered helpful in all technically successful cases, and considerably
influenced further treatment in four patients. In patient 2 suffering from chylothorax,
chylopericardium and chylous ascites, the decision to perform TD embolization despite
the presence of ascites was supported by tMRL findings of chylolymphatic reflux as
the primary pathology. In patient 3 intranodal lymphangiography was performed with
confidence that the leakage site can be reached with ethiodized oil, providing a possible
treatment option. Subsequent treatment was successful in this case. In patient 5 delineation
of an aberrant retroaortic lymphatic channel led to an alteration in the extent of
lymph vessel embolization to ensure successful treatment. In patient 7 tMRL findings
led to continuation of conservative therapy without attempted intervention.
All examinations were well tolerated without complications. Neither general anesthesia
nor conscious sedation was necessary.
Discussion
Contrast-enhanced MR-lymphangiography with interdigital interstitial injection of
a standard gadolinium-based contrast medium is an established technique for the evaluation
of peripheral lymphatics of the upper and lower extremities. It has recently been
used in the evaluation of peripheral edema as well as in an effort to improve the
detection of lymph node metastases in the pelvis [13 ]
[14 ]. However, pedal interstitial contrast injection was so far not deemed suitable for
visualization of the central lymphatics – especially in adults – as contrast medium
typically reaches only the pelvic lymphatics [10 ]
[15 ]. So far, contrast enhancement of the central lymphatics after interstitial contrast
injection has only been reported in one case of an infant with chylothorax [16 ]. In the past different contrast agents have been developed to overcome this limitation
(dendrimer-based gadolinium-labeled contrast medium [17 ]; lipophilic perfluorinated gadolinium chelates [18 ]). Although yielding good results in swine models, these contrast agents are not
available for clinical use. Another approach utilized interstitial application of
gadofosveset premixed with human albumin which led to CLS visualization in a swine
model [19 ]. This approach requires preparation of the contrast agent/albumin mixture and has
so far not been investigated in humans. Furthermore, gadofosveset is currently not
available for clinical use in Germany.
Alternatively, dynamic contrast-enhanced MR-lymphangiography (DCE-MRL) [9 ]
[10 ] that permits dynamic evaluation of lymphatic flow has shown promising results in
a variety of lymphatic pathologies. However, it requires general anesthesia (or at
least sedation) and time-consuming sonographically guided needle placement into inguinal
lymph nodes outside the scanner room, which is associated with a risk of accidental
needle dislodgment.
The results of our study demonstrate that tMRL with interstitial injection of a standard
contrast agent is feasible and can be employed to visualize the CLS. In contrast to
DCE-MRL, tMRT requires adequate timing of image acquisition in order to evaluate the
passage of the contrast agent. Initial experiences show that image acquisition should
start within a few minutes after contrast injection. In contrast to MRL of the lower
extremity, in which the patient lies still during the whole examination, asking the
patients to move their legs after contrast injection seems to be key to tMRL of the
central lymphatics. It remains unclear why patient 6 did not show enhancement of the
central lymphatics. A possible explanation may be the presence of diffuse retroperitoneal
leakage, but also bilateral inguinal lymphovenous shunts as identified on conventional
lymphangiography may have contributed to poor enhancement.
The most important advantage of tMRL is that it can be performed without general anesthesia
or sedation. Contrast injection can be performed inside the scanner room without the
need for time-consuming sonographically guided puncture. Using the water-only images
of the breath-hold mDIXON sequence [11 ] forgoes the need for image subtraction and allows for good distinction of central
lymphatics from surrounding tissue. A further advantage of our technique is the use
of a commercially available extracellular contrast agent. It is important to note,
however, that interstitial application is an off-label use. Infection and local reactions
to the contrast medium at the injection sites are possible complications [20 ], but were not observed in our experience. Intramuscular injections, however, should
be avoided [20 ].
This study is limited by its retrospective character with inherent methodological
problems and by its small sample size. However, in 6/7 patients tMRL findings were
confirmed by results of fluoroscopic intranodal lymphangiography. Dynamic information
on lymph flow evaluated by tMRL may be limited compared to DCE-MRL with which the
entire contrast medium passage can be observed.
In conclusion, this study demonstrates the feasibility of contrast-enhanced MR imaging
of the CLS by interstitial pedal injection of a standard extracellular contrast agent.
tMRL is a new imaging technique that allows for assessment of pathologic conditions
of central lymphatics that can be performed in clinical routine without general anesthesia.
Implications for patient care
Interstitial transpedal MR-lymphangiography allows for minimally invasive assessment
of central lymphatic anatomy and pathology in patients suffering from chylous effusions.
tMRL can be performed in clinical routine without general anesthesia or sedation.
It can be employed in the pre-interventional workup of lymphatic interventions, possibly
influencing the therapeutic strategy.
