ORIGINAL ARTICLE
Resistance Index in Mediastinal Lymph Nodes
A Feasibility Study
Felix J. F. Herth, MD,* Kazuhiro Yasufuku, MD,† Ralf Eberhardt, MD,* Hans Hoffmann, MD,‡
Mark Krasnik, MD,§ and Armin Ernst, MD*储
Objective: The purpose of this study was to determine the range of
Doppler ultrasonographic measurements of the resistance index in
presumed normal mediastinal lymph node arteries.
Methods: Consecutive patients referred for bronchoscopy for vari-
ous indications and normal CT findings in the mediastinum were
included. The resistance index (RI) in mediastinal lymph node
arteries was examined with Color Doppler ultrasonography. The
peak systolic velocity (PSV) and the end-diastolic velocity were
measured, which allowed for calculation of the resistance indices in
different lymph node stations and in each lymph node artery.
Results: Eighty-nine patients (32 female; 57 male; mean age, 42.2
years) were examined, and of these, 50 patients (24 female; 36 male;
mean age, 44.7 years) had measurable RIs. PSV and ESV were
measured in all visible nodes (n ⫽ 196) and an interpretable value
was obtained in 127 nodes (2.5 nodes per patient.). The median PSV
was 15.6 cm/s (range, 8.9 –23.2 cm/s, SD ⫾ 2.6, 25–75% percentile
13.8 –17.5), and the median end-diastolic velocity was 5.8 cm/s
(range, 3.6 –11.4 cm/s, SD 1.15 cm/s, 25–75% percentile 5.1– 6.3).
The median RI values for arteries were 0.63 (range, 0.52– 0.75, SD
0.04, 25–75% percentile 0.6 – 0.64) respectively. The Doppler mea-
surements lasted on average 4.3 minutes and no complications were
seen.
Conclusion: Color Doppler ultrasonography allows for quantifica-
tion of velocities like PSV and ESV in mediastinal lymph node
arteries, which in turn allow calculation of a resistance index.
Knowledge of the resistance index’s normal range (which describes
the resistance of the blood flow within the lumen of the lymph node
*Department of Pneumology and Critical Care Medicine, Thoraxklinik,
University of Heidelberg, Germany; †Department of Thoracic Surgery,
Chiba University, Chiba, Japan; ‡Department of Thoracic Surgery,
Thoraxklinik, University of Heidelberg, Germany; §Department of Tho-
racic Surgery, University of Gentofte, Copenhagen, Denmark; and 储In-
terventional Pulmonology, Beth Israel Deaconess Medical Center, Har-
vard Medical School, Boston.
Disclosure: Olympus Corporation has provided unrestricted educational grants
to the author’s institutions for CME related activities. None of the authors
have a direct financial conflict of interest related to the content of the
manuscript.
Address for correspondence: Prof. Felix J. F. Herth, MD, FCCP, Chair,
Department of Pneumology and Critical Care Medicine, Thoraxklinik
Heidelberg, University of Heidelberg, Amalienstr. 5, D-69126 Heidel-
berg, Germany. E-mail: Felix.Herth@thoraxklinik-heidelberg.de
Copyright © 2008 by the International Association for the Study of Lung
Cancer
ISSN: 1556-0864/08/0304-0348
348
artery) may be a useful adjunct to the ultrasonic assessment of the
mediastinum.
Key Words: Endobronchial ultrasound, Lymph node, Resistance
index, Bronchoscopy, Cancer.
(J Thorac Oncol. 2008;3: 348 –350)
G rayscale endobronchial ultrasound is an established tech-
nique for the evaluation of the mediastinum.1–5 The
visual appearance (except for their size) of lymph nodes on
endobronchial ultrasound usually has no impact on the dif-
ferential diagnosis. The information obtained is currently
only used for measurements and procedure guidance, such as
transbronchial needle aspiration.
A series of articles published during the past decade
indicate the potential of Doppler sonography for improving
the assessment of renal and liver abnormalities.6 –9 Changes in
intrarenal arterial waveforms were shown to be associated
with urinary obstruction, several types of intrinsic renal
disorders, and renal vascular disease.10 The Doppler resis-
tance index (RI) [RI ⫽ ([peak systolic velocity ⫺ end
diastolic velocity]/peak systolic velocity)] has been proposed
as a useful parameter for quantifying the alterations in renal
blood flow that may occur with renal disease.
The purpose of this study was to document the values
of the resistance indices of the lymph node arteries in a
radiographically normal mediastinum. To our knowledge,
this is the first description of the technique performed via
bronchoscopy.
PATIENTS AND METHODS
The protocol of this study was approved by the local
Institutional Review Board. All patients provided written
informed consent.
Between January 2007 and June 2007, consecutive
patients with an indication for bronchoscopy were screened
for the study. Included were patients referred for diagnostic
bronchoscopy with suspicion for nonmalignant diseases and a
normal CT-scan of the mediastinum (no lymph nodes larger
than 10 mm).
CT Scans
A chest radiograph and a multisclice CT scan of the
chest with and without contrast enhancement were performed
in all patients.
Journal of Thoracic Oncology • Volume 3, Number 4, April 2008
Journal of Thoracic Oncology • Volume 3, Number 4, April 2008
On-site CT examinations were performed with a Sie-
mens helical scanner (Erlangen, Germany), using a single
breath hold technique. Off-site CT scans were evaluated by
the same radiologists and were included if their quality was
similar to the on-site CT studies. If the quality of an off-site
CT was inadequate, an on-site CT was performed. Lymph
nodes were considered enlarged if the short-axis diameter
was more than 1 cm.
Bronchoscopy
Standard, conventional flexible bronchoscopy (model
BF-1T180 bronchoscope; Olympus, Tokyo, Japan) was first
performed to examine the tracheobronchial tree, followed by
endobronchial ultrasound examination using a dedicated ul-
trasound bronchoscope (model XBF-UC160F; Olympus).
Bronchoscopy procedures were performed with patients ei-
ther under local anesthesia and sedation (midazolam) or
under general anesthesia.
The flexible ultrasonic bronchoscope was connected to
the Aloka Ultrasound processor (Prosound alpha5, Tokyo,
Japan). The procedure was performed as described be-
fore.11,12 The lymph nodes in the mediastinum were screened
by the ultrasound technique. In case of a visible node, the
localization was described according to the Mountain-
Dressler classification.13 Lymph node sizes were measured in
the grayscale mode. Afterward, the Color Doppler mode was
activated, and intralymph node arteries were searched for and
examined, whenever possible.
Doppler Indices Measured
When a typical arterial signal (Figure 1) was identified
in a node, the measurements were obtained. Only vessels
assessable with a Doppler angle between 45° and 60° were
measured. Angle correction was performed and two param-
eters were obtained in the arteries. First, the peak systolic
FIGURE 1. Endobronchial ultrasound image and a correlat-
ing measurement of the resistance index. The conventional
ultrasound image is displayed in the left half of the image.
The sample volume is bordered by green markers. The right
half of the image shows the wave signal obtained by pulse
wave Doppler. The maximum and minimum flow is marked
and the values are determined. They can be seen displayed
in the box in the left lower corner.
Copyright © 2008 by the International Association for the Study of Lung Cancer
Resistance Index in Mediastinal Lymph Nodes
flow velocity was measured, followed by the end-diastolic
flow velocity. Values were obtained with the following set-
tings: a probe frequency of 7.5 MHz, a scanning magnifica-
tion of 40 mm maximum depth, a color Doppler scale of 0.6,
the PRF limit was set at “off,” noise reduction was “off,” the
color polarity was normal and the focus flow “auto.” Second,
the artery RI value was calculated from the Doppler trace
using the following equation: ([peak systolic velocity ⫺ end
diastolic velocity]/peak systolic velocity).14
Statistical Analysis
Resistance indices, peak systolic velocity (PSV), and
end-diastolic velocity of the arteries are expressed as medians
with ranges. Differences in the sonographic indexes and
measurements obtained above among the groups using the
SPSS program (version 10.1, Statistical Package for the
Social Sciences). The Wilcoxon and Whitney U test were
used for analysis.
RESULTS
The study population consisted of 89 patients (32 fe-
male; 57 male; mean age, 42.2 years). In 39 patients (8
female, 21 male), we were not able to visualize an arterial
signal in the lymph nodes. Measurement of the resistance
index in an arterial lymph node vessel was possible in 50
patients (24 female; 36 male; mean age, 44.7 years). The
indications for bronchoscopy was chronic cough in 32 (36%),
undiagnosed interstitial infiltrates in 42 (47%) (those suspi-
cious for sarcoidosis were excluded), hemoptysis in 10
(11%), and in five patients (6%) suspicion of foreign body
aspiration.
We were able to visualize lymph nodes in 50 patients
(24 female; 36 male; mean age, 44.7 years: 19 chronic cough,
24 IPF, 4 hemoptysis, 3 foreign body).
In all visible nodes, the measurement was performed (n ⫽
196) and a value was obtained in 127 nodes (2.54/pts.). All
measurable lymph nodes were located in positions 7 (n ⫽ 42),
4R (n ⫽ 43), or 4L (n ⫽ 42). We were also able to detect nodes
in position 2R (n ⫽ 44) and position 2L (n ⫽ 25), but in none
of these we were able to get a useful Color Doppler signal.
The mean lymph node size was 5.2 mm (range, 4 – 8
mm, SD 0.8), the mean Doppler procedure lasted 4.3 minutes
(range, 2.9 –9.6 minutes).
The median PSV was 15.6 cm/s (range, 8.9 –23.2 cm/s,
SD⫾ 2.6, 25–75% percentile 13.8 –17.5), and the median
end-diastolic velocity was 5.8 cm/s (range, 3.6 –11.4 cm/s,
SD⫾ 1.15 cm/s, 25–75% percentile, 5.1– 6.3). The median RI
values for arteries were 0.63 (range, 0.52– 0.75, SD⫾ 0.04,
25–75% percentile, 0.6 – 0.64), respectively. There were no
statistical differences within the lymph node stations (Table 1).
DISCUSSION
In this trial, we could show that a resistance index
measurement is possible in mediastinal lymph nodes using an
endobronchial ultrasound system.
To our knowledge, Spectral Doppler analysis of arteries
supplying the mediastinal lymph nodes has not yet been
described.
349
Herth et al.
TABLE 1. Measurements Obtained in Different Mediastinal
Lymph Node Stations
Overall LN 7 LN 4R LN 4L
N 127 42 43 42
Size (mm) 5.3 5.8 5.2 5.2
PSV (cm/s) 15.6 15.0 15.7 15.9
EDV (cm/s) 5.8 5.6 5.9 5.9
RI 0.63 0.62 0.62 0.39
PSV, peak systolic velocity; EDV, end diastolic velocity; RI, resistance index.
Most studies published on the potential use of Doppler
sonography describe the evaluation of renal and liver dis-
eases. Several studies have shown that a normal mean renal
RI is approximately 0.60. The largest series to date (58
patients) reported a mean (⫾SD) RI of 0.60 ⫾ 0.01 for
subjects without pre-existing renal disease.15 Prior studies
also reported normal mean RI values of 0.64 ⫾ 0.05,16 and
0.58 ⫾ 0.05.17
Similar levels of Doppler-derived indexes are described
for the liver18,19 and the spermatic cord arteries.20 This may
obviously not apply, because these are different tissues;
nevertheless, the similar results are encouraging. In general,
most sonographers now consider 0.70 to be the upper thresh-
old of the normal RI in adults.
In the present study, the mean RI obtained from medi-
astinal lymph nodes was comparable to other organs. The fact
that RI correlated with different diseases may indicate that an
increase in vascular resistance may proceed in parallel with
the change in the architecture of abnormal lymph nodes.
LIMITATIONS
The main limitation of our study is that reliable Doppler
measurements were limited to specific lymph node stations,
namely 4R, 4L, and 7 and that in 44% of cases no interpret-
able signal could be obtained. This limitation reflects the
difficulty even for the experienced sonographer in obtaining
reproducible and accurate measurements of these vessels in
other lymph node stations and it might be a consequence that
the position of the nodes in the more cervical trachea to the
bronchial wall does not allow a sufficient Doppler angle.
Another limitation was that lymph node histopatho-
logic examination was not performed in our patients. The
underlying pulmonary diseases were diagnosed using the
clinical records or transbronchial lung biopsies.
CONCLUSION
Knowledge of the mean values for the RI, PSV, and
ESV of vessels within the arterial vessels of mediastinal
lymph nodes could be useful in the assessment of suspected
mediastinal lymph node abnormalities. This pilot study con-
firms that the RI can in fact be measured in mediastinal lymph
350
Journal of Thoracic Oncology • Volume 3, Number 4, April 2008
nodes. Additional studies will need to be performed in normal
and abnormal lymph nodes to assess if a useful clinical
difference can be established.
P Value
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Copyright © 2008 by the International Association for the Study of Lung Cancer