Transcript seeing the same landscape with new eyes: imaging

eEdE-81
SEEING THE SAME
LANDSCAPE WITH NEW EYES:
IMAGING GLIAL NEOPLASMS
IN THE ERA OF NEWER
IMAGING MODALITIES
TANVIR RIZVI, MBBS, MD, DM ; SUGOTO MUKHERJEE, MBBS, MD
University of Virginia Health System
DISCLOSURES
 The authors have no financial or nonfinancial
relationships to disclose
OUTLINE
 Review advances in MR imaging for Glial Neoplasms
 Diffusion-weighted imaging (DWI) and Diffusion
Tensor Imaging (DTI) role in grading glial neoplasms
and preoperative planning
 Perfusion-weighted imaging (PWI) role
 Proton MR Spectroscopy (MRS) role in
characterization and differentiating from entities like
pseudo-progression
 Functional BOLD MRI (fMRI) in preoperative
planning employing different paradigms
 Intraoperative MRI (IoMRI) role during surgery
ADVANCED IMAGING: INTRODUCTION
 MR imaging has emerged as the modality of choice to
evaluate intracranial tumors and continues to have everexpanding and multifaceted role.
 Conventional sequences provide immense amount of
data including location, signal intensities and
enhancement characteristics of mass lesions.
 Newer imaging modalities can yield further refinement of
differential diagnosis or treatment plan.
 Improve preoperative assessment, expand surgical
approaches, aid in radiation treatment planning and help
in evaluating therapeutic options.
 Advanced techniques generate physiologic data and
information on chemical composition.
DIFFUSION-WEIGHTED IMAGING
 Echo-planar technique maps rate at which extracellular
water molecules diffuse through tissue. Mobility of water
molecules determined by both cellularity of environment
and thermal agitation.
 Fluid (csf)- No impedance to flow of water molecules: No
diffusion restriction.
 Brain tissue rates of diffusion slower.
 Pathologic processes further restrict diffusion thereby
reducing apparent diffusion coefficient (ADC). ADC
inversely proportional to cellular density due to limitation
of water movement in interstitial spaces [1].
DIFFUSION-WEIGHTED IMAGING
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ADC value of high-grade gliomas lower than low-grade gliomas [2] (darker on ADC maps).
DWI, ADC maps and contrast enhanced T1W axial images of lower to higher grade glial
neoplasms are shown.
DIFFUSION TENSOR IMAGING
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Displacement vs. tract disruption from tumor, surgery
Peritumoral invasion index of tumor invasiveness. Conventional imaging
overlap of edema and tumor cells.
DTI measures direction and magnitude of water diffusion based on data
obtained from 6 or more gradient directions as opposed to 3 directions in
DWI.
Anisotropy or directionally dependent water diffusion due to myelin sheath
restricting water movement across WM tracts.
Fractional anisotropy (FA) is mathematical index derived from DTI data that
implies microstructural integrity of brain tissue.
Fiber tracking techniques can reveal relationship between glioma and
adjacent WM tracts [3].
Low grade gliomas deviate rather than destruct or infiltrate adjacent WM.
Knowing WM tracts from functional cortex helps surgical planning, reduces
surgery time and minimizes need for intraoperative cortical stimulation.
DIFFUSION TENSOR IMAGING
DTI, post-contrast axial T1 and FLAIR images in a grade IV GBM of left medial temporal
lobe with extension to superior cerebral peduncle show disruption of corticospinal tracts on
left (arrow) with intact CST on right. By convention anterior-posterior tracts are labelled
green; cranio-caudal blue and right-left red.
Post-contrast axial T1 pre and post surgery in a right temporal GBM. Axial and coronal DTI
show disruption of corticospinal tract on right side post-surgery.
DIFFUSION TENSOR IMAGING
A
B
Axial T2 and post-contrast axial T1 images (A) show a left thalamic grade 1 pilocytic astrocytoma.
There is significant reduction in tumor size post-radiation on T2W and post-contrast axial T1
images (B). DTI shows no significant disruption and mild displacement of corticospinal tract and
uncinate fasciculus.
PERFUSION MRI
 3 types: Dynamic Susceptibility contrast (DSC) perfusion, dynamic
contrast material-enhanced perfusion and arterial spin labelling
(ASL).
 DSC perfusion most widely used currently. Negative enhancement
technique using T2 and T2* effects of contrast material. High
gadolinium concentration causes T2 shortening in adjacent tissues.
Degree of dephasing and resultant signal change during bolus
gadolinium injection can be measured and plotted as a time-signal
intensity curve with area under the curve proportional to cerebral
blood volume (CBV) [4]. Relative CBV measurements (rCBV)
obtained. Adversely affected by hemorrhagic and post-surgical
changes.
 Dynamic-contrast enhanced T1-weighted perfusion imaging with
calculation of K trans value (Contrast transfer coefficient) provides
better assessment of permeability between intra and extravascular
spaces and vessel leakiness.
PERFUSION MRI
 Strong correlation between grade of astrocytoma and
relative CBV measurements. Worsened tumor graderCBV increases.
 Oligodendroglioma even low grade tend to have
significantly elevated rCBV. Likely due to extensive
angiogenesis and dense capillary networks.
 Lymphoma lower relative CBV compared to GBM. Also
lymphomas may show increased signal relative to
baseline in recovery phase due to contrast material
leakage within interstitial space.
PERFUSION MRI
 33/M presents with complex partial seizures in 7/2011.
Grade III Oligoastrocytoma. Resection 9/6/2011.
Completed external beam Radiotherapy and Temodar.
12/29/2011
8/18/2015
4/26/2012
Biopsy 8/2015 GBM
7/10/2015
11/6/2014
Treatment Avastin + CCNU
Avastin + Vorinostat
3/19/2015
PERFUSION MRI 10.29.2015
Axial FLAIR and Post-contrast Axial
T1W images show significant increase
in recurrent tumor burden in left parietal
lobe with additional foci in left frontal
and left parietal periventricular locations.
Perfusion MRI shows significant
increase in rCBV, which is seen as a dip
in the curve on left side related to T2
shortening from gadolinium compared to
normal curve on right side.
PERFUSION MRI: PSEUDOPROGRESSION & RADIATION NECROSIS
 In 20-40% patients with CNS neoplasms undergoing RT and adjuvant
chemotherapy, size of enhancing lesion and associated T2 prolongation
temporarily increases, known as pseudoprogression.
 Can simulate tumor progression and treatment failure[5] resulting in
inappropriate discontinuation of effective therapy.
 More often in those with concurrent RT + Chemotherapy typically 6-12
weeks after treatment.
 Represents local inflammatory response and increased vascular
permeability[6].
 Clinically asymptomatic and associated with increased survival.
 Decrease rCBV within enhancing lesion on perfusion MRI.
 Areas of enhancement, T2 prolongation and significant edema mimicking
recurrence in radiation necrosis. Edema and mass effect disproportionate
to size of enhancing lesion.
 Hypoperfusion with reduced rCBV on Perfusion MRI. Recurrent glioma/
mets: Increased rCBV.
PROTON MR SPECTROSCOPY
 Analysis of different metabolites within the
brain.
 Initial diagnosis of brain tumors, directing
biopsy, grading and treatment assessment.
 Single or multivoxel.
 Major metabolites:
 NAA (2.02)- Normal neuronal marker
 Choline (3.2)- Cell membrane marker
 Creatine (3.0): energy marker
 Lactate (1.33): Metabolic acidosis
 Lipids (0.9): Tissue breakdown and cell
death.
PROTON MR SPECTROSCOPY
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Most CNS tumors: Elevated choline-creatine
and choline-NAA ratios (>2.2 separates high
from low grade) [2].
Increased cellularity (Elevated choline),
significant decrease normal neurons
(reduced NAA) and hypermetabolism
(moderate decrease Creatine) [7].
Lipid-lactate peaks not present in normal
brain. Present in areas of necrosis with
anaerobic glycolysis.
Primary CNS lymphoma: Elevated Cho-Cr
and Cho-NA ratios. Lactate-lipid peaks in
upto 90%.
Pitfall: Acute demyelinating plaque: Elevated
Cho-Cr and reduced NAA-Cr ratio mimic
tumor. Conventional imaging to differentiate.
High grade neoplasm elevated lipid; Low
grade neoplasm and gliomatosis: High MI
peak.
Pseudoprogression: Decreased metabolites
and increased lactate-lipid doublet.
8 year old male with brainstem glioma
shows T2 hyperintense pontine lesion
with raised choline and reduced NAA
on MR Spectroscopy
PSEUDOPROGRESSION
5.28.15
5.28.15
8.20.15
5.30.15 Postop
10.30.15
51/M MGMT hypermethylation negative GBM s/p resection with RT & concurrent
Temodar completed 7.31.15
PSEUDOPROGRESSION
Perfusion MRI shows decreased rCBV and PET-CT shows hypometabolism in
enhancing lesion seen around surgical cavity in left frontal lobe. MR Spectroscopy
shows low choline and NAA with lipid lactate doublet at 1.3 ppm.
FUNCTIONAL MRI
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The extent of resection, a major factor affecting long-term survival in brain
tumor patients can largely be determined by proximity of the lesion to the
eloquent brain regions prior to resection [1].
Outlining of eloquent brain regions prior to resection: Combination of fMRI
and DTI.
Functional MR imaging based on blood oxygen-level dependent (BOLD)
contrast effect and neurovascular coupling.
When certain cognitive task is being performed, activation of certain brain
regions and networks of brain regions increases, which leads to related
increase in cerebral blood flow.
This increase (neurovascular coupling) results in relative excess of
oxyhemoglobin in the regional vascular bed.
Echo-planar T2* gradient-echo sequences sensitive to changes in
hemoglobin oxygenation states with greater concentration of diamagnetic
oxyhemoglobin compared to paramagnetic deoxyhemoglobin resulting in
increased relative MR signal.
FUNCTIONAL MRI
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Changes of MR signal secondarily reflect regional cerebral neuronal activity
[8].
Signal changes small: Repeated measurements needed. Block imaging
paradigms used.
Alternating periods of active task (sensorimotor, language or vision) and a
control task (rest) performed over a 4-6 minute span. Tasks and control
periods statistically compared on a voxel-by-voxel basis to identify taskrelated signal changes.
Post-processing including motion correction, filtering and anatomic
coregistration to optimize exam quality.
Processing programs more widely available as integrated component of
clinical scanners, workstation and neuronavigation software packages.
“Resting state” or “functional connectivity” MR do not require active task[9].
Can assess multiple cognitive domains with single sequence. Useful in
children, sedated patient s or those with deficits who cannot perform task. In
domain of research.
FUNCTIONAL MRI: MOTOR PARADIGMS
 COMPLEX FINGER TAPPING
 SIMPLE FINGER TAPPING
 FOOT MOVEMENT- ANKLE
FLEXION/SIDE TO SIDE
 TONGUE MOVEMENT
 LIP PUCKERING
 PASSIVE HAND/FOOT STIMULATION
FUNCTIONAL MRI: MOTOR PARADIGMS
COMPLEX FINGER TAPPING
SIMPLE FINGER TAPPING
FUNCTIONAL MRI: MOTOR PARADIGM
LIP MOVEMENT
FOOT FLEXION
FUNCTIONAL MRI: SPEECH PARADIGM
 Verbal fluency
 Word generation
 Verb Generation
 Naming
 Sentence Completion
 Passive listening
 Comprehension

Language dominance:
 R HANDED – 95% LHD
 L HANDED - 70% LHD,
 AMBIDEXTROUS – 85%
LHD

Broca’s Area:
 Inferior frontal Gyrus- BA
44,45
 Pars opercularis and
triangularis
 Constant

Wernicke’s Area:
 Less well defined.
 Classic WA- Parts of
angular, supramarginal
superior and middle
temporal gyri and
planum temporale
FUNCTIONAL MRI: SPEECH PARADIGM

WORD GENERATION:
 Try to think of words
beginning with provided
letter.
 Activity predominantly in
Broca’s Area.

NAMING PARADIGM:
 What do you write with: A.
Pencil B. Car C. Paper
D. Pillow
 Activity in Broca’s and
Wernicke’s Area
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VERB GENERATION:
 If you see: clothes cards
 Think:
wash play
horse
ride
FUNCTIONAL MRI: SPEECH PARADIGM
 LATERALITY: SENTENCE COMPLETION PARADIGM
 Higher grade tumors: Lower sensitivity and specificity compared
to lower grade tumors due to cerebrovascular changes within
and adjacent to higher grade neoplasms.
 Multiple language paradigms essential to enhance sensitivity and
fully capture language networks.
FUNCTIONAL MRI: VISUAL MOTOR PARADIGM
 Visual flashes (Colored green): Keep eye on flashes.
 Motor (Colored red): When see word tap, repeatedly tap fingers on
keyboard.
SUMMARY OF fMRI PARADIGMS
INTRAOPERATIVE MRI
 Blend of MR imaging performed in an operative suite.
 Allows precise navigation and resection of intracranial lesions.
 First operating theater with MRI in Brigham and Women’s hospital in
1994.
 65-92% cases where neurosurgeons thought achieved gross total
resection, ioMRI showed more tumor that could be resected [10].
 3 types:
 Original open system with stationary magnet and stationary
patient. Limitation of ease of access, instruments and
monitoring equipment.
 Stationary magnet/movable patient (can use other modalities
like PET and binary fluoroscopy).
 Movable magnet/stationary patient.
 Clearly designated 5G line: Zone IV. MRI safe or MR conditional
instruments.
INTRAOPERATIVE MRI
A
B
C
D
Intraoperative magnetic resonance imaging (MRI) suite shows patient gantry in the operative suite (A).
The magnetic bore is brought in from its resting “bay” for scanning (B). The movable magnet is ready to
scan the stationary patient (C,D) during surgery and once that is done is sent back to its “bay”. Note the
yellow colored area refers to the 5-G line where only the MR safe devices can be used.
INTRAOPERATIVE MRI
Axial 3D T1 post-contrast and
T2 Space images (top row)
show a left mesial temporal
heterogeneously enhancing
mass lesion, which was
resected. Intraoperative MRI
(lower row) shows gross total
resection
POST-SURGICAL ROLE OF DWI
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Immediate post surgical: Areas of restricted diffusion may be seen from surgical
resection or ischemia may be seen around surgical cavity. At follow-up, these areas
enhance and mimic tumor recurrence. Compare new areas of enhancement with areas
of restricted diffusion at immediate postoperative imaging. If match: Enhancement
most likely reactive changes or subacute ischemia rather than recurrence.
New or enlarging area of restricted diffusion and signal abnormality in postoperative
margin that previously showed no diffusion restriction: Likely tumor recurrence.
Pre and
postoperative
images show
diffusion
restriction in
left posterior
temporal lobe
related to
venous
ischemia from
Vein of Labbe
sacrifice
during removal
of left temporal
GBM.
LET US REVIEW WHAT YOU HAVE LEARNT
 As the glial tumor grade increases, ADC value
a) Increases
b) Decreases
c) Remains unchanged.
d) is unpredictable.
LET US REVIEW WHAT YOU HAVE LEARNT
 As the glial tumor grade increases, ADC value
a) Increases
b) Decreases
c) Remains unchanged.
d) is unpredictable.
LET US REVIEW WHAT YOU HAVE LEARNT
 What happens to rCBV in pseudoprogression
a) Depends upon amount of enhancement
b) Increases
c) Depends upon FLAIR signal
d) Decreases
LET US REVIEW WHAT YOU HAVE LEARNT
 What happens to rCBV in pseudoprogression
a) Depends upon amount of enhancement
b) Increases
c) Depends upon FLAIR signal
d) Decreases
LET US REVIEW WHAT YOU HAVE LEARNT
 Which metabolite is most frequently raised in malignant
CNS tumors
a) NAA
b) Creatinine
c) Choline
d) Alanine
LET US REVIEW WHAT YOU HAVE LEARNT
 Which metabolite is most frequently raised in malignant
CNS tumors
a) NAA
b) Creatinine
c) Choline
d) Alanine
LET US REVIEW WHAT YOU HAVE LEARNT
 Which of the following statements is correct regarding
language mapping ?
a) Wernicke’s area is much better defined.
b) Broca’s area is less clearly defined.
c) Multiple language paradigms enhance sensitivity
and specificity of language lateralization.
d) Language lateralization is more accurate in higher
grade neoplasms compared to lower grade ones.
LET US REVIEW WHAT YOU HAVE LEARNT
 Which of the following statements is correct regarding
language mapping?
a) Wernicke’s area is much better defined.
b) Broca’s area is less clearly defined.
c) Multiple language paradigms enhance sensitivity
and specificity of language lateralization.
d) Language lateralization is more accurate in higher
grade neoplasms compared to lower grade ones.
LET US REVIEW WHAT YOU HAVE LEARNT
 Which line is important for safety reasons in intraoperative
MRI
a) 0.5G
b) 1.5G
c) 5G
d) 10G
LET US REVIEW WHAT YOU HAVE LEARNT
 Which line is important for safety reasons in intraoperative
MRI
a) 0.5G
b) 1.5G
c) 5G
d) 10G
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