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1. IMAGING OF NON SMALL
CELL LUNG CARCINOMA
NSCLC:
FROM MORPHOLOGY TO
FUNCTIONAL IMAGING
Dr. Yeung Wing Hang, Calvin
Specialist in Radiology
Hong Kong Baptist Hospital
30. DUAL ENERGY CT
(DECT) IMAGING
• material differentiation, identification and
quantification
• iodinated attenuation maps
• monochromatic images
• virtual unenhanced images
31. DUAL ENERGY CT
(DECT) IMAGING
• clear advantages in tumor detection,
lesion characterization, and evaluation of
response to therapy
32. DUAL ENERGY CT
(DECT) IMAGING
• in the detection of oncology-related
disorders (e.g., pulmonary embolism and
bowel ischemia) and comorbidities (e.g.,
renal stones and gout)
33. DUAL ENERGY CT
(DECT) IMAGING
• application of two distinct energy settings
• to differentiate materials with different
molecular compositions on the basis of their
attenuation profiles
• result in a transition from attenuation based
imaging to material-specific or spectral
imaging
35. DECT IMAGING IN NSCLC
•
iodine maps for assessment of the relative
vascularity of pulmonary nodules
• tissue enhancement can be accurately
assessed on iodine maps
36. DECT IMAGING IN NSCLC
•
on virtual unenhanced images, a reduction
in the size of calcifications compared with
that in actual unenhanced datasets
• there is a risk of overlooking small
calcified lesions
37. DECT IMAGING IN NSCLC
• To the differentiation of calcification from
enhancing tissue in solitary pulmonary
nodules is made with a single contrastenhanced CT acquisition and virtual
nonenhanced image reconstruction
38. DECT IMAGING IN NSCLC
• DECT
could
serve
as
a
valuable
func3onal
imaging
test
for
pa3ents
with
NSCLC
as
iodine
related
a>enua3on
correlates
with
SUV
of
FDG
PET-‐CT
(Schmid-‐Bindert
G
et
al,
Eur
Radiol
2012)
45. DECT EVALUATION OF
RESPONSE TO THERAPY
•
accurately assess the intratumoral
amount of iodinated contrast medium to
represent the perfusion and
vascularization of lesion
• the iodine map is more robust parameter
than attenuation (not influenced by
intratumoral hemorrhage)
46. DISORDERS RELATED TO
ONCOLOGIC THERAPY
•
pulmonary thromboembolism
• bowel ischemia
• comorbidities in oncologic patients:
renal stones and gout
53. Diffusion weighted image
of NSCLC
• DWI is sensitive to the random (Brownian)
motion of water molecules. In biologic tissue,
the presence of impeding barriers (e.g., cell
membranes, fibers, and macromolecules)
interferes with the free displacement
(diffusion) of water
• The signal intensity in DWI depends on the
separation and permeability of these impeding
boundaries
54. Relationship between change in tissue cellularity
and water mobility
Free Diffusion: Increase in extracellular
space and membrane permeability
allow greater water mobility
(eg water/ necrosis/ benign lesions)
Result: High ADC value
ADC: Apparent Diffusion Coefficient
)
Restricted Diffusion: highly cellular
environment, water diffusion is
restricted because of reduced
extracellular space and impermeability
of cell membrane.
(eg. Solid tumour/ malignancy)
Result: Low ADC value
55. DIFFUSION WEIGHTED
IMAGE (DWI)
• differentiation between benign and
malignant tumour
• decreased Brownian motion of water in
malignant tumour (increase cellularity)
• non-contrast, no ionizing radiation, fast
56. DIFFUSION WEIGHTED
IMAGE (DWI)
• ADC has been correlated with important
histologic properties, including the tumor
proliferation index, tumor grade, the
presence of necrosis, and tumor cell
apoptosis
• ADC is highly reproducible
58. DIFFUSION WEIGHTED
IMAGE (DWI)
False-positive findings:
• artifacts from image ghosting, poor fat
suppression, or susceptibility effects. The
clue to artifacts is that they may appear as
recapitulation of structures seen elsewhere
on the image or appear at boundaries
between fat and water interfaces
59. DIFFUSION WEIGHTED
IMAGE (DWI)
•
normal lymph nodes
• tiny foci (typically 1–2 mm) of impeded
diffusion are sometimes detected that
are difficult to correlate with
structures, ? small venules
60. DIFFUSION WEIGHTED
IMAGE (DWI)
False-negative findings:
• normal structures can exhibit impeded
water diffusion, e.g. salivary glands,
lymph nodes, spleen, spinal cord,
ovaries, testes, red marrow, endometrial
lining, bowel wall, peripheral nerves, and
neural ganglia
• some of the well differentiated
adenocarcinoma
61.
62. Diffusion weighted image
of NSCLC
• Pathologic processes that alter the physical
nature of the restricting barriers in biologic
tissue affect the diffusivity of the water
molecules, which can be visualized and
quantified using DWI
• A known clinical application is diagnosis of
acute ischaemic stroke
63. Diffusion weighted image
of NSCLC
• Important technologic advances, including
echoplanar imaging, high-gradient amplitudes,
multichannel coils, and parallel imaging, have
extended the applications of DWI outside the
brain
• Limitation of DWI in the thorax has been
overcome by the demonstrated feasibility of
DWI under free breathing (the concept of
diffusion-weighted whole-body imaging with
background body signal suppression)
64. Diffusion weighted image
of NSCLC
• Diffusion in biologic tissue is quantified
by means of an apparent diffusion
coefficient (ADC)
• At least 2 images with 2 different bvalues have to be acquired to calculate
an ADC
65. Diffusion weighted image
of NSCLC
• Lesion–to–spinal cord ratio (LSR) was
introduced, which is a semiquantitative
measure that represents the ratio of
lesion signal intensity to spinal cord
signal intensity
• LSR takes into account both diffusion
and T2 relaxation time, does not suffer
from image misregistration
66. Diffusion weighted image
of NSCLC
• Kanauchi et al. : nodules with low signal
intensity on DWI, comparable to or even
lower than that of the spinal cord (i.e.,
LSR ≥ 1), were classified as positive on
DWI. Otherwise, they were considered
negative on DWI
• The SUVmax of DWI-positive patients
(10.33 ± 4.93) was significantly higher (P
< 0.001) than that of DWI-negative
patients (3.10 ± 4.21)
70. 55/F NSCLC STAGE 4
21/10/2009
ADC:
1.01
x
103mm2/s
5/11/2009
ADC:
1.24
x
103mm2/s
23/11/2009
ADC:
2.15
x
103mm2/s
71. DIFFUSION WEIGHTED
IMAGE (DWI)
• Diffusion-weighted MR imaging might be
useful for monitoring the early response
to and the prognosis after chemotherapy
of NSCLC
• Patients with advanced NSCLC might be
able to avoid the cost of and cytotoxic
damage from ineffective drugs and might
be able to switch anticancer drugs early
if drugs were deemed ineffective on the
basis of early ADC change
(Yabuuchi
et
al)
72. 55/F Hx of CA lung, post lobectomy
3/6/2011
11/5/2012
3/6/2011
11/5/2012
73. Functional MR Imaging without Contrast
MR Whole Body Diffusion
Normal
40/M treated NPC with
Lung Liver & Bone Mets
66/M
Lymphoma
74. TUMOURS
•
independence from growth signals
• insensitivity to growth-inhibitory signals
• evasion of apoptosis
• development of a limitless potential for
replication
• development of sustained
angiogenesis
• tissue invasion and metastasis
75. CT/PET
Improve on the ability of the state of art
CT to:
• detect tumour
• define the extent of tumour
• measure response to treatment
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86. CT/PET
• FDG is not a target-specific PET tracer
• studies have shown that an SUV of 2.5 as the
cutoff value will detect malignancy at sensitivity of
97% and specificity of 78%.
87. CT/PET
• a considerable reduction in SUV was
associated with a pathologic response and
proved to be a better predictor of long-term
survival than anatomy-based criteria in
patients with NSCLC who underwent
neoadjuvant therapy, followed by complete
resection
88. CT/PET
• a decrease in SUV >20% after one cycle of
chemotherapy was associated with a longer
time to progression and a longer median
overall survival time in stage IIIB or IV NSCLC
• significantly
longer
median
survival
3me
was
found
in
pa3ents
with
complete
metabolic
response
than
in
pa3ents
with
incomplete
metabolic
response
in
stage
IIIA-‐N2
disease
89. CT/PET
• a larger decrease in SUV was observed in
responding patients than in nonresponders on
CT imaging
• volumetric PET parameters could provide
meaningful information about patient
prognosis
• PERCIST (Positron Emission Tomography
Response Criteria in Solid Tumors)
90. CT/PET
• FDG is not a target-specific PET tracer
• emerging new PET radiotracers may offer a clear
opportunity to improve the study of many biologic
features
• Fluoride-18-fluorothymidine (FLT) is used for the
noninvasive measurement of tumor proliferation
• Cu(II)-diacetyl-bis(N4)-methylthiosemi- carbazone
(Cu-ATSM) for hypoxia
91. CT/PET
• 18F-FLT uptake is specific for malignant lesions
and that there was a significant correlation
between 18F-FLT uptake and proliferative activity
• 18F-FLT PET imaging may have a potential role
in the evaluation of response assessment in lung
cancer, particularly when the treatment approach
includes inhibitors of proliferative activity such as
cyclin-dependent kinase inhibitors
92. MR/PET
Advantages over PET/ CT:
• the superior soft tissue contrast of MRI
allows better anatomical visualization of
soft tissue structures and bone marrow
than CT.
• simultaneous image acquisition enables
temporal co-registration of dynamic PET
data acquisition and morphologic/
functional MR data. MR perfusion, fMRI,
DWI
93. MR/PET
Advantages over PET/ CT:
• some studies comparing whole-body MR
with PET/CT have shown potential
advantages of MR particularly regarding
the early detection of brain-, liver- and
bone marrow metastases
• in fully integrated systems, MRI could also
be used to provide a gating signal in
addition to imaging
94. MR/PET
• PET/MR demonstrated higher sensitivity
than PET/CT for all pulmonary nodules at
61.6 % and 70.3 %
• PET/MR delivered greater sensitivity than
PET/CT in the detection of FDG-avid
nodules at 94.4 % and 95.6 %
• sensitivity for small non-FDG-avid nodules
was lower with PET/MR imaging than with
PET/CT
(Hersh Chandarana et al)
95. MR/PET
•
Contraindications of MR scan, eg. most
types of cardiac pacemakers and
implanted defibrillators as well as certain
metallic implants
96. NEW DRUGS
• target the EGFR pathway in NSCLC, smallmolecule inhibitors of the tyrosine kinase
domain of EGFR were developed (erlotinib
and gefitinib)
• activating EGFR mutations were discovered
in cancer cells from patients with NSCLC
who responded to the targeted therapy with
gefitinib and erlotinib
97. NEW DRUGS
• EGFR mutations in lung adenoCA are seen
in approximately in 15% of patients in the
United States and in 30% to 50% of
patients in Asia
• clinical features are known to be
associated with both EGFR mutations and
response to gefitinib and erlotinib, including
nonsmoker status, Asian ethnicity, and
female gender
98. NEW DRUGS
•
morphological assessment, RECIST uses
unidimensional measurements of the sum
of the longest lesion diameters
• many targeted agents are cytostatic and
therefore tumor shrinkage may not be seen
99. NEW DRUGS
•
functional imaging techniques, such as
perfusion CT, dynamic susceptibility
contrast MR imaging, dynamic contrastenhanced (DCE) MR imaging, or
diffusion-weighted MR imaging, provide
information on tissue phenotype or
behavior
100. NEW DRUGS
Comparison of Cytotoxic Therapy versus
NODs
• Tumoral effect: Cytotoxic Vs cytostatic
• Criteria for tumor response: Tumor
shrinkage Vs Tumor stabilization or
shrinkage
• Imaging techniques for response evaluation:
Anatomic (size and appearance) Vs
functional or molecular imaging
101. NEW DRUGS
Comparison of Cytotoxic Therapy versus
NODs
• Time of response evaluation: Late (2 mo)
Vs Early (2–6 wk)
• Toxic effects of drugs Usually nonspecific:
multisystemic involvement Vs Less toxic:
target-specific toxic effects
104. MOLECLAR IMAGING
• Molecular
imaging
is
expected
to
have
a
major
impact
on
the
early
diagnosis
of
diseases
and
disease
monitoring
in
the
next
decade
• Nuclear
imaging
techniques
have
been
the
mainstay
of
molecular
imaging
in
the
clinical
arena
• Con3nued
development
of
molecularly
targeted
contrast
agents
for
nonnuclear
imaging
techniques
such
as
MR,
CT
and
US
106. CONCLUSION
Along with molecular metabolic mechanisms
of tumor cells that increasingly come to light,
rapid development of functional and
molecular imaging has taken place in recent
years. By directly visualizing and measuring
the biological process in vivo, functional and
molecular imaging enables early assessment
of response to anticancer treatment for
NSCLC patient
