Marco Borri1, Maria A. Schmidt1, Julie C. Hughes1, Erica D. Scurr1, Kristiana D. Gordon2,3, Peter S. Mortimer2,3, Dow-Mu Koh1, and Martin O. Leach1
1CR-UK Cancer Imaging Centre, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom, 2Cardiac and Vascular Sciences, St. George’s, University of London, London, United Kingdom, 3Skin Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom
Synopsis
The pathophysiology of breast cancer related lymphoedema (BCRL)
is not well understood, one of the main limiting factors being a lack of information
on lymphatic collecting vessels. We have recently proposed a novel
contrast-enhanced magnetic resonance lymphangiography protocol which allows the
identification of lymphatics via the use of associated contrast uptake curves. In this work we have quantified differences between affected and
unaffected arms in a cohort of patients with unilateral BCRL. Our analysis did
not detect significant differences in vessel counts between the two sides within
different sections of the forearm. However, there was a statistically
significant difference in vessel diameter between the two arms; lymphatics within the affected arms presented with a larger diameter.Introduction
Breast
cancer related lymphoedema of the arm (BCRL) is a peripheral swelling which
results from impaired lymphatic drainage after breast cancer treatment [1]. The
pathophysiology of BCRL is not well understood, one of the main limiting factors
being a lack of anatomical and functional information on both superficial
(epi-fascial) and deep (sub-fascial) lymphatic collecting vessels. We have
recently proposed a novel contrast-enhanced magnetic resonance lymphangiography
(CE-MRL) protocol which minimizes venous enhancement and allows the
identification of upper limb lymphatics via the use of associated contrast
uptake curves [2]. In this work we quantify differences between affected and
unaffected arms in a cohort of patients with unilateral BCRL.
Materials and Methods
Both
arms of 10 BCRL patients (table in
Figure 1) were imaged at 1.5 T (MAGNETOM Aera, Siemens
AG, Erlangen, Germany) on separate visits. A high resolution 3D T1W
fast-spoiled gradient-echo pulse sequence was employed (TE/TR=2.77/6.14 ms,
flip angle=12°, voxel size=1x1x1 mm, spectrally selective fat suppression, FOV=300
mm in the superior/inferior direction, acquisition time=66 s). Contrast was
administered with a 1 ml total volume intradermal injection to each of the four
inter-digital spaces (0.02 ml of gadoteridol, 0.1 ml of 1% lidocaine and 0.88
ml of saline, with resulting [Gd]=0.01 M) [2]. The forearm was imaged with 15 dynamic
acquisitions, in order to follow the passage of the contrast. In this analysis
we evaluate the presence of lymphatic collecting vessels in the final image volume,
subtracted from the first reference frame. The forearm (wrist to elbow) of each
patient was divided into 3 sections of equal length (distal, medial, proximal)
and the number of vessel segments in each section was counted, in order to characterize
vessel density and contrast progression along the arm. The total number of
vessels within the forearm, the number of long vessels crossing more than one
section, and the presence of deep lymphatic vessels were also recorded. Paired
sets of vessel counts were compared (affected versus unaffected arms) using a two-tailed
Wilcoxon signed-rank test (p<0.05). Vessel size was estimated by processing maximum
intensity projection (MIP) images to obtain the Frangi’s vesselness measure [3].
The scale (σ) of the Frangi’s filter, which provides an estimate of the vessel radius,
was extracted for all visible vessels along the entire length of the vessel. Cumulative
distributions of vessel size measurements from all images were compared (affected
versus unaffected arms, two-tailed Mann-Whitney test, p<0.05).
Results
Vessels
exhibiting persistent contrast uptake were identified as lymphatics, by
inspection of MIP images which retained for every voxel the correspondent
uptake curve (
Figure 2). In 9 patients the images revealed the presence of lymphatic
collecting vessels in both arms, whilst in one patient the unaffected arm
showed no contrast uptake. Lymphatic vessels were visualized at different
depths in the arm, but primarily within the epi-fascial compartment. In total,
a similar number of vessels were detected in the affected and unaffected arms
(43 and 46, respectively) and a comparable number of long vessels were present
(22 and 18, respectively). Vessel size histograms indicate that lymphatics in the
affected arm have larger diameter: the associated density function (
Figure 3) peaks
at 1.8 mm, while it is skewed towards 1 mm for the unaffected arms. Furthermore,
the two vessel diameter distributions were significantly different
(p<0.0001). The median number of vessel segments in each forearm was higher
in the unaffected arms within the distal and medial sections, and in total
(
Figure 4). However, differences in vessel counts between affected and unaffected
arms did not reach statistical significance according to the Wilcoxon signed-rank
test. Besides enhancing vessels, additional patterns seen in the affected arm
included: a) diffuse enhancement associated with contrast leakage, and b) characteristic
dermal backflow (
Figure 5).
Discussion and Conclusions
A
higher number of lymphatics vessels enhancing or further progression of
contrast along the arm could indicate improved ability to transport lymphatic
fluid. However, our analysis did not detect significant differences in vessel
counts between affected and unaffected sides within different sections of the forearm.
Nevertheless, there was a statistically significant difference between the two
distributions of vessel diameters. Lymphatic vessels within the affected arms
presented with a larger diameter. This might be an effect of increased
permeability of the vessel walls, which leads to leakage of contrast around the
vessel. Alternatively, vessels dilate if intraluminal pressure rises, as a
consequence of either downstream obstruction or increased lymph flow. In future
work we will quantify changes of vessel diameter with time and evaluate flow
through analysis of the uptake curves [2], in order to clarify the mechanisms
involved.
Acknowledgements
Cancer Research UK (CR-UK) and the Engineering and Physical Sciences
Research Council (EPSRC) support to the Cancer Imaging Centre at the Royal
Marsden NHS Foundation Trust and Institute of Cancer Research, in association with
the Medical Research Council (MRC) and Department of Health (England) (grants
C1060/A10334, C1090/A16464); NHS funding to the National Institute for Health
Research (NIHR) Biomedical Research Centre and the Clinical Research Facility
in Imaging. MB is funded by a Healthcare Science Doctoral Research Fellowship
(HCS-D13-04-002) from the NIHR and Health Education England (HEE). MOL is an
NIHR Senior Investigator. The views expressed are those of the author(s) and
not necessarily those of the NHS, the NIHR or the Department of Health.References
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