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Fig. 1: Schematic illustration of the LN anatomy
Cortex
Cortical sinus
Lymph capillary
Medullary sinus
Capsule
Vein Lymph vessel Artery
T. Fischer, G. Schäfer
Interdisciplinary US Centre, Institute of Radiology at CC6, Charitéplatz 1, 10117 Berlin
SMI – a new technique for the analysis
of the microvascular tree in reactive and
suspected malignant lymphadenopathy
in advanced stages of malignant melanoma
Introduction
High-resolution lymph node (LN) sonography in
patients with malignant melanoma is a routine
­diagnostic procedure in medical centres. Its aim ­
is the early detection of lymph node and subcuta-
neous metastases in relation to tumour stage.
LN sonography exhibits a high acceptance when
compared with other diagnostic techniques, with
good accessibility of the lymph node stations under
investigation (J Dtsch Dermatol Ges. 2013 Aug; 11
Suppl 6:1-116, 1-126. doi: 10.1111/ddg.12113_
suppl. Malignant melanoma S3-guideline “diagnosis,
therapy and follow-up of melanoma”). These
follow-up investigations not only result in the early
detection of a relapse, they also help to prolong
overall survival. In addition, during the same
session suspect lymph nodes can be biopsied
using FNAC (fine-needle aspiration cytology).
Confirmed metastases must be surgically removed
as soon as possible (Schäfer et al. Expert Rev
Anticancer Ther. 2007). While the neck, axilla
and groin are regarded as regions for investigation
that are ­particularly easily accessible, this strategy
can be applied to numerous LN changes other
than LN metastases. Sentinel biopsy for example
is a ­further important procedure after sonographic
­assessment of the relevant LN.
Sonographic criteria
Established sonographic criteria include LN
­dimensions in relation to the region of the
body and the so-called longitudinal/transverse
diameter ratio (= Solbiati index, >2), which
essentially describes the transformation from an
oval to a spherical shape. The blurred margins of
the LN, a potential capsular rupture, necrosis or
displacement/broadening of the anatomical struc-
tures of the hilum and the cortex can be recorded
using B-image sonography (Fig. 1, Table 1). The
peripheral tree-like branching of ­hilar vessels is
also regarded as an important ­diagnostic criterion.
Increased vascularisation in reactive lymphade-
nopathy with preserved vascular structure is
particularly characteristic. Cut-offs, displacement
of vessels into the margins or the increase in the
chaotic nature of the vascular­­pattern can be
differential diagnostic indicators of LN metastases.
However, due to the technical ­limitations of colour-
coded Doppler sonography (CCDS) and power
Doppler (PD), only the macrovascular architecture
is visualized. While these techniques can be used
to visualize normal larger hilar vessels, the analysis
of the microvessels remains difficult even in
contrast-enhanced ultrasound (CEUS) – which
Benign Mallgnant
Form elongated oval round to round-oval, spherical
Solbiati index
(longitudinal/transverse diameter)
> 2 < 2
Margins sharp partially blurred, partially sharp
Cortex narrow with low echogenicity absent or asymmetrically hypoechoic
Centre relatively homogeneous, high echogenicity inhomogeneous, hypoechoic
Hilum usually present on image absent/asymmetric
Table 1: Differentiation criteria for lymph nodes that have undergone inflammatory or metastatic change
Doppler signals
Conventional Doppler Imaging
Superb Microvascular Imaging (SMI)
intensity
velocity
intensity
velocity
intensity
velocity
moreover incurs additional costs. Analysis of the
vascular architecture is particularly complicated
in the case of small LNs (< 5mm) (Cui, XW et al.
Worl J Gastroenterol 2013). Superb Microvascular
Imaging (SMI), whose basic principles will be briefly
explained below, is a novel sonographic technique
to complement CEUS and elastography. Drawing
on an initial group of patients with malignant
melanoma, typical examples are described where
B-mode imaging, CCDS, PD and SMI, as well as
elasto­graphy were performed.
Superb Microvascular Imaging (SMI)
SMI is based on a powerful intelligent algorithm,
applying a similar concept to that used for
ultrasonic Doppler signals. SMI effectively
separates flow signals from overlaying tissue
motion artefacts, preserving even the subtlest
low-flow components with unmatched detail
and definition.
1. Doppler signals
Both blood flow and tissue motion (clutter) produce
ultrasonic Doppler signals. The strong clutter signals
overlap the low-velocity blood flow components.
2. Conventional Doppler imaging
Conventional Doppler imaging applies a wall filter
to remove clutter and motion artefacts, resulting
in a loss of low-flow components.
3. SMI
SMI does not primarily focus on Doppler shift or
the strength of a specific signal, but on its local
distribution across the region of interest. While
tissue motion occurs simultaneously across a
region, blood flow always occurs locally. High-
density ultrasound system architecture with
real-time application capability allows the system
to identify and remove global motion signals in real
time, while preserving subtle low-flow components.
Non-interventional study
To date, 10 patients have been included in an initial
non-interventional study. The SMI technique was
used in addition to the standard programme
involving B-image sonography, CCDS, PD and
FNAC on the Aplio 500 ultrasound system.
All patients had a confirmed Clark’s Level III-IV
melanoma and were treated as part of follow-up.
In 3 out of 10 cases, the primary diagnosis that
2	SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy
in advanced stages of malignant melanoma
B
C
A
D
E
had been made previously was changed based
on vascular detection using SMI and this change
was confirmed by FNAC and surgical excision.
In 7 out of 10 cases, the images of the finest
vascular networks generated with SMI were
subjectively superior to those generated by the
standard techniques, CCDS and PD. This applied
both to reactively enlarged LNs (Fig. 2 A – E) and to
metastases (Fig. 3). The vascular architecture of
superficial and small LNs, in particular, was easier
to assess using SMI (Fig. 4). Up to a penetration
depth of 2.5 cm and, in particular, in subcutaneous
locations, SMI exhibited clear advantages in
delineating the hilar vessels and the smallest of
peripheral branches. Surprisingly, SMI detected
microvessel in portions that had previously been
classified as avascular or necrotic, and a targeted
FNAC was immediately performed (Fig. 4).
A subcutaneous manifestation was found in
2 of the 10 patients in the region of the scar.
The assessment was initially difficult due to
postoperative seroma but detection of vessels
was particularly important in these cases in
order to be able to carry out a FNAC as quickly
as possible. The investigation was performed in
the frequency range of between 14 and 18 MHz,
depending on penetration depth. In the case of
suspected malignancy, elastography was carried
out on the suspect area of the affected LN. It
revealed a good correlation between the absence
of elasticity and the presence of bizarre vascular
patterns produced by the melanoma metastases
(Fig. 5). Furthermore, SMI was able to visualize
vessels that pass through the capsule; another
important detail for the assessment of potential
metastatic spread that conventional techniques
did not offer.
In summary, SMI, which can be used with or
without contrast agents, constitutes a novel and
promising technique for visualizing microcirculation.
In an initial non-interventional study, additional
information was found in 3 of 10 cases that had
not been detected previously using the conventional
techniques CCDS and PD. In particular, SMI
provided relevant information that allowed the
evaluation of small lesions, subcutaneous masses
and structures in the region of the scar.
Figure 2 A – E: Right axillary reactive lymphadenopathy (A). Unremarkable finding in FNAC. Illustration of the full vascular tree with its microarchitecture in SMI mode (B, C).
The large vessels close to the hilum are seen in CCDS (D) and power Doppler (E), the vascular tree is not free of artefacts and its detection is limited.
SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 3
	 in advanced stages of malignant melanoma
A
B
C
D
E
B
CA
Figure 3 A – E: Large right inguinal LN metastasis that has been histologically confirmed (A). The pathological vascular pattern and the vessels
passing through the LN capsule are visualized only by SMI (B). Power Doppler (C) and CCDS (D) only allow delineation of the macrovessels. In this
case, no change in the diagnosis was to be expected based on the clear situation. Of note, however, is the level of detail visible in the microvessels
and the fact that very fine vessels have broken through the capsule (E). The sensitive, artefact-free image produced by SMI of pathological vascular
networks is well documented in this figure.
Figure 4 A – C: 6 mm metastasis adjacent to the region of the scar on the right thigh. Vessels with branching in the margins are visualized by SMI,
while the lesion appears avascular in power Doppler. Metastasis confirmed with FNAC (C).
SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 4
	 in advanced stages of malignant melanoma
B
C
A
Figure 5 A – C: Correlation between SMI (A), colour Doppler (B) and elastography (C) for a large LN metastasis. SMI visualizes the finest tumour vascular networks.
SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 5
	 in advanced stages of malignant melanoma
ULTRASOUND CT MRI X-RAY SERVICES
www.toshiba-medical.eu
© Toshiba Medical Systems Corporation 2014 all rights reserved.
Design and specifications subject to change without notice.
02/2014 MWPUL0025EUC
Printed in Europe

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White paper "SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy in advanced stages of malignant melanoma."

  • 1. Fig. 1: Schematic illustration of the LN anatomy Cortex Cortical sinus Lymph capillary Medullary sinus Capsule Vein Lymph vessel Artery T. Fischer, G. Schäfer Interdisciplinary US Centre, Institute of Radiology at CC6, Charitéplatz 1, 10117 Berlin SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy in advanced stages of malignant melanoma Introduction High-resolution lymph node (LN) sonography in patients with malignant melanoma is a routine ­diagnostic procedure in medical centres. Its aim ­ is the early detection of lymph node and subcuta- neous metastases in relation to tumour stage. LN sonography exhibits a high acceptance when compared with other diagnostic techniques, with good accessibility of the lymph node stations under investigation (J Dtsch Dermatol Ges. 2013 Aug; 11 Suppl 6:1-116, 1-126. doi: 10.1111/ddg.12113_ suppl. Malignant melanoma S3-guideline “diagnosis, therapy and follow-up of melanoma”). These follow-up investigations not only result in the early detection of a relapse, they also help to prolong overall survival. In addition, during the same session suspect lymph nodes can be biopsied using FNAC (fine-needle aspiration cytology). Confirmed metastases must be surgically removed as soon as possible (Schäfer et al. Expert Rev Anticancer Ther. 2007). While the neck, axilla and groin are regarded as regions for investigation that are ­particularly easily accessible, this strategy can be applied to numerous LN changes other than LN metastases. Sentinel biopsy for example is a ­further important procedure after sonographic ­assessment of the relevant LN. Sonographic criteria Established sonographic criteria include LN ­dimensions in relation to the region of the body and the so-called longitudinal/transverse diameter ratio (= Solbiati index, >2), which essentially describes the transformation from an oval to a spherical shape. The blurred margins of the LN, a potential capsular rupture, necrosis or displacement/broadening of the anatomical struc- tures of the hilum and the cortex can be recorded using B-image sonography (Fig. 1, Table 1). The peripheral tree-like branching of ­hilar vessels is also regarded as an important ­diagnostic criterion. Increased vascularisation in reactive lymphade- nopathy with preserved vascular structure is particularly characteristic. Cut-offs, displacement of vessels into the margins or the increase in the chaotic nature of the vascular­­pattern can be differential diagnostic indicators of LN metastases. However, due to the technical ­limitations of colour- coded Doppler sonography (CCDS) and power Doppler (PD), only the macrovascular architecture is visualized. While these techniques can be used to visualize normal larger hilar vessels, the analysis of the microvessels remains difficult even in contrast-enhanced ultrasound (CEUS) – which
  • 2. Benign Mallgnant Form elongated oval round to round-oval, spherical Solbiati index (longitudinal/transverse diameter) > 2 < 2 Margins sharp partially blurred, partially sharp Cortex narrow with low echogenicity absent or asymmetrically hypoechoic Centre relatively homogeneous, high echogenicity inhomogeneous, hypoechoic Hilum usually present on image absent/asymmetric Table 1: Differentiation criteria for lymph nodes that have undergone inflammatory or metastatic change Doppler signals Conventional Doppler Imaging Superb Microvascular Imaging (SMI) intensity velocity intensity velocity intensity velocity moreover incurs additional costs. Analysis of the vascular architecture is particularly complicated in the case of small LNs (< 5mm) (Cui, XW et al. Worl J Gastroenterol 2013). Superb Microvascular Imaging (SMI), whose basic principles will be briefly explained below, is a novel sonographic technique to complement CEUS and elastography. Drawing on an initial group of patients with malignant melanoma, typical examples are described where B-mode imaging, CCDS, PD and SMI, as well as elasto­graphy were performed. Superb Microvascular Imaging (SMI) SMI is based on a powerful intelligent algorithm, applying a similar concept to that used for ultrasonic Doppler signals. SMI effectively separates flow signals from overlaying tissue motion artefacts, preserving even the subtlest low-flow components with unmatched detail and definition. 1. Doppler signals Both blood flow and tissue motion (clutter) produce ultrasonic Doppler signals. The strong clutter signals overlap the low-velocity blood flow components. 2. Conventional Doppler imaging Conventional Doppler imaging applies a wall filter to remove clutter and motion artefacts, resulting in a loss of low-flow components. 3. SMI SMI does not primarily focus on Doppler shift or the strength of a specific signal, but on its local distribution across the region of interest. While tissue motion occurs simultaneously across a region, blood flow always occurs locally. High- density ultrasound system architecture with real-time application capability allows the system to identify and remove global motion signals in real time, while preserving subtle low-flow components. Non-interventional study To date, 10 patients have been included in an initial non-interventional study. The SMI technique was used in addition to the standard programme involving B-image sonography, CCDS, PD and FNAC on the Aplio 500 ultrasound system. All patients had a confirmed Clark’s Level III-IV melanoma and were treated as part of follow-up. In 3 out of 10 cases, the primary diagnosis that 2 SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy in advanced stages of malignant melanoma
  • 3. B C A D E had been made previously was changed based on vascular detection using SMI and this change was confirmed by FNAC and surgical excision. In 7 out of 10 cases, the images of the finest vascular networks generated with SMI were subjectively superior to those generated by the standard techniques, CCDS and PD. This applied both to reactively enlarged LNs (Fig. 2 A – E) and to metastases (Fig. 3). The vascular architecture of superficial and small LNs, in particular, was easier to assess using SMI (Fig. 4). Up to a penetration depth of 2.5 cm and, in particular, in subcutaneous locations, SMI exhibited clear advantages in delineating the hilar vessels and the smallest of peripheral branches. Surprisingly, SMI detected microvessel in portions that had previously been classified as avascular or necrotic, and a targeted FNAC was immediately performed (Fig. 4). A subcutaneous manifestation was found in 2 of the 10 patients in the region of the scar. The assessment was initially difficult due to postoperative seroma but detection of vessels was particularly important in these cases in order to be able to carry out a FNAC as quickly as possible. The investigation was performed in the frequency range of between 14 and 18 MHz, depending on penetration depth. In the case of suspected malignancy, elastography was carried out on the suspect area of the affected LN. It revealed a good correlation between the absence of elasticity and the presence of bizarre vascular patterns produced by the melanoma metastases (Fig. 5). Furthermore, SMI was able to visualize vessels that pass through the capsule; another important detail for the assessment of potential metastatic spread that conventional techniques did not offer. In summary, SMI, which can be used with or without contrast agents, constitutes a novel and promising technique for visualizing microcirculation. In an initial non-interventional study, additional information was found in 3 of 10 cases that had not been detected previously using the conventional techniques CCDS and PD. In particular, SMI provided relevant information that allowed the evaluation of small lesions, subcutaneous masses and structures in the region of the scar. Figure 2 A – E: Right axillary reactive lymphadenopathy (A). Unremarkable finding in FNAC. Illustration of the full vascular tree with its microarchitecture in SMI mode (B, C). The large vessels close to the hilum are seen in CCDS (D) and power Doppler (E), the vascular tree is not free of artefacts and its detection is limited. SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 3 in advanced stages of malignant melanoma
  • 4. A B C D E B CA Figure 3 A – E: Large right inguinal LN metastasis that has been histologically confirmed (A). The pathological vascular pattern and the vessels passing through the LN capsule are visualized only by SMI (B). Power Doppler (C) and CCDS (D) only allow delineation of the macrovessels. In this case, no change in the diagnosis was to be expected based on the clear situation. Of note, however, is the level of detail visible in the microvessels and the fact that very fine vessels have broken through the capsule (E). The sensitive, artefact-free image produced by SMI of pathological vascular networks is well documented in this figure. Figure 4 A – C: 6 mm metastasis adjacent to the region of the scar on the right thigh. Vessels with branching in the margins are visualized by SMI, while the lesion appears avascular in power Doppler. Metastasis confirmed with FNAC (C). SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 4 in advanced stages of malignant melanoma
  • 5. B C A Figure 5 A – C: Correlation between SMI (A), colour Doppler (B) and elastography (C) for a large LN metastasis. SMI visualizes the finest tumour vascular networks. SMI – a new technique for the analysis of the microvascular tree in reactive and suspected malignant lymphadenopathy 5 in advanced stages of malignant melanoma
  • 6. ULTRASOUND CT MRI X-RAY SERVICES www.toshiba-medical.eu © Toshiba Medical Systems Corporation 2014 all rights reserved. Design and specifications subject to change without notice. 02/2014 MWPUL0025EUC Printed in Europe