Download Qualitative assessment: Comparing Imaging features of primary

Multimodality Imaging, Qualitative Assessment
Qualitative assessment: Comparing Imaging features of primary brain tumors utilizing MRI
perfusion and Methionine-Positron Emission Tomography with respect to histopathological
diagnosis.
Nathan T. Mortensen, D.O., Arash Kardan, M.D., Victor Heh, Ph.D.
Kettering Health Network/Grandview Medical Center
Introduction
Magnetic Resonance Imaging (MRI) perfusion has been
increasingly utilized as a tool for brain tumor characterization.
MRI perfusion can be a valuable imaging modality in that it
adds a physiologic element to traditional Magnetic Resonance
(MR), which is an exquisite diagnostic tool for assessment of
anatomical abnormalities. Methionine-Positron Emission
Tomography (Met-PET) is a very valuable imaging modality for
the evaluation of brain tumors given its preferential uptake in
neoplastic tissue, and relative lack of uptake in normal
background brain parenchyma. Studies have shown that these
imaging modalities have value. Many studies investigating
these imaging methods involve quantitative calculations.
Objective
Can we make qualitative assessments of primary brain tumors
utilizing of Methionine PET and MR perfusion?
To further elucidate imaging features of primary brain tumors
utilizing these imaging modalities.
Methods
This is a retrospective study. Patient charts were reviewed
from from July 1, 2012 – July 30, 2015. Approval was obtained
from the IRB, Kettering Health Network. Following IRB
approval, a list of 81 patients was provided from the Oncology
Outcomes department, Kettering Health Network, Dayton,
Ohio. The list contained patients with histologically proven
primary brain tumors.
Inclusion criteria
Patient age ranged from 18-89 years. Patients must have had
a primary brain tumor, and the patient must have had imaging
of the tumor with both a Methionine-PET and MRI perfusion
prior to biopsy or surgical intervention of the tumor. All
images reviewed for the study were the first set of MR with
perfusion, and Met-PET images pertinent to the patient’s
diagnosis in their imaging timeline.
Exclusion criteria:
Metastatic disease was not included in the study. The patient
must have had both an MRI with perfusion, and a Met-PET. If
the patient had an MR perfusion but no Met-PET, or vice
versa, the study was not included. Post surgical images
involving the lesion were not included.
Discussion
Figure 1: Glioblastoma Multiforme (WHO Grade IV)
FLAIR, T1C+, 11-C-Methionine PET co-registered to MR, and MR perfusion K2 permeability and Cerebral Blood Volume (CBV) images. There is features of increased FLAIR signal,
and peripherally enhancing lesion post contrast administration, with suggestion of central necrosis. 11-C-Met-PET shows hypermetabolic uptake relative to contralateral presumed
normal brain. MR perfusion shows concomitant increased permeability on K2 in the region of hypermatabolic activity, particularly at the area of peripheral enhancement which
suggests blood brain barrier disruption. There is no definite increased CBV relative to contralateral cortex, but it does appear equal to background regional to the lesion.
Methods (continued)
Image interpretation:
All images were reviewed and interpreted by Nathan
Mortensen, D.O. (PGY-4, third year radiology resident). The
reader was blinded to the histological diagnosis during all
image interpretation. Met-PET images were reviewed, along
with anatomical MRI images, with emphasis on FLAIR, T1
post-contrast (T1C+), and then MRI perfusion images with
emphasis on K2 permeability and cerebral blood volume
(CBV). All Met-PET studies were co-registered to the most
recent MR. A qualitative assessment of the Met-PET study
was made with any focal hypermetabolic areas being given a
score of +1 on visual inspection. Any Isometabolic areas were
given a score of 0, and any hypometabolic areas were given a
score of -1 on visual inspection. The reference for the MetPET studies would be presumed normal contralateral brain,
particularly with respect to the specific lobe or lobes of the
brain involved by tumor and how it related to the
contralateral lobe. For the MR perfusion, K2 permeability and
cerebral blood volume (CBV) maps were assessed. In a similar
fashion to the Met-PET images, qualitative analysis was made
by visual inspection comparing presumed normal
contralateral brain on the permeability and CBV maps. Again,
numerical values were given based on background perfusion.
If the tumor showed high permeability (K2) or cerebral blood
volume (CBV), it was given a score of +1 respectively. If it
appeared homogeneous to background permeability it was
scored as 0, and if it showed decreased permeability it was
scored as a -1. Tumor sizes were measured in the maximum
cross sectional diameter. Once imaging features were
documented, they were compared to their respective
histology.
Figure 2. Glioblastoma Multiforme (WHO Grade IV)
FLAIR, T1 C+, Co-registered MR with Methionine PET, MR perfusion K2 and CBV maps. Flair hyperintense, heterogenously enhancing, Met-PET hypermetabolic lesion demonstrates
increased K2 permeability at the lesion and accompanying increased CBV.
Figure 3: Anaplastic Astrocytoma (WHO Grade III)
FLAIR hyperintense signal at the periphery, T1C+ hypointense, non-enhancing left temporal lobe lesion. Met-PET co-registered to MR demonstrates hypermetabolic activity in
the anterior periphery of the lesion relative to contralateral presumed normal brain. MR permeability appears low to background as does CBV.
Figure 3: Oligoastrocytoma (WHO Grade II)
FLAIR hyperintense, T1 hypointense, T1C+ hypointense non-enhancing right frontal lobe lesion. Met-PET co-registered to MR shows hypermetabolic activity in the lesion relative
to presumed normal contralateral parenchyma. MR perfusion shows background on K2 permeability map, and evidence of low CBV.
Limitations:
Patient sample size is too small to conduct valid statistics. This is
a retrospective study. The images were interpreted
qualitatively, which in and of itself can pose limitations, such as
inter-observer variability. Furthermore, images were
interpreted by a radiology resident. The strength of the study
may have been improved with image interpretation carried out
by those who have fellowship training in neuroradiology and
nuclear medicine. Imaging parameters may have fluctuated
over the time interval of the study as well, given the lack of a
prospective model. In addition, the study is limited by its very
small sample size. However, it is difficult to find substantial
population sizes for such specialized imaging.
References:
Results
All 9 brain tumors showed hypermetabolic activity on MetPET at the tumor site relative to presumed normal
contralateral brain. All grade IV astrocytomas, 4/4 (100%)
showed increased K2 permeability relative to presumed
normal contralateral brain, and 3/4 (75%) of grade IV
astrocytomas showed increased cerebral blood volume with
respect to the contralateral parenchyma. There was 1
anaplastic astrocytoma, WHO grade III neoplasm, which
demonstrated low permeability and volume on K2 and CBV
respectively, but it was hypermetabolic on Met-PET. The four
remaining tumors are WHO grade II, and 3/4 (75%)
demonstrated background K2 permeability, while one
oligoastrocytoma appeared to show lower permeability with
respect to contralateral and background parenchyma. 2/2
oligoastrocytoma’s (100%) demonstrated lower CBV than
contralateral or background brain.
The Met-PET proved very valuable in the detection of tumor. All
tumors that fit the inclusion criteria showed hypermetabolic
activity at the lesion site relative to presumed normal
contralateral brain. However, out of the 9 tumors imaged, there
were 4 different histologies. Thus, Met-PET did not differentiate
histology or grade of tumor. However, the additional
information gained from the perfusion studies helped
differentiate high grade from low grade tumors. For example, all
four of the grade 4 astrocytoma’s demonstrated increased
permeability on K2, and 3 out of these 4 tumors showed
increased cerebral blood volume, suggesting both leaky
capillaries and increased vascularity respectively. The
suggestion of leaky capillaries on the K2 map coincides with the
fact that all four grade IV tumors demonstrated increased
enhancement on post-contrast imaging, which implies
breakdown of the blood brain barrier. There was one grade IV
tumor that showed background CBV, and demonstrated
peripheral enhancement. There were no low grade tumors
(WHO grade II) that showed increased permeability on K2. This
further supports existing research that shows an increase in
permeability is often associated with a high grade tumor, and is
likely related to abnormal leakiness of capillaries. This study
shows that with the use of multimodality imaging combining
Methionine PET and MR perfusion, one can detect high
metabolic activity in brain tumors and subsequently make more
qualitative assessments about brain tumor grade with the
addition of MR perfusion. This study points to high grade
tumors demonstrating increased k2 permeability and CBV, while
low grade show no increase in K2 or CBV. These are features
which have been demonstrated in other papers, and this data
further supports an expanding field in advanced neuroimaging,
where information gained from PET and MRI perfusion can help
better diagnose and stage patients. More studies which
investigate these imaging modalities in a prospective manner
may be helpful to further establish the strength of the data, and
better define with what degree of certainty we can differentiate
high grade from low grade neoplasm with imaging alone, which
may help with staging of patients as well as neurosurgical
planning. The results are compelling, and may be similar in a
larger sample size.
Figure 4: Oligodendroglioma (WHO Grade II)
FLAIR hyperintense, T1C+ hypointense non-enhancing right side lesion overlapping lobes. Met-PET is hypermetabolic relative to contralateral brain. MR perfusion shows
background permeability throughout, without evidence of focal increased permeability. The CBV map was interpreted as background in the study, but may be on the border of
increased. However, there are similar patchy increased areas in the cortex seen on the CBV map, particularly near the left periventricular white matter. It was felt that this area
did not stand out enough to be called increased.
Patient
Size (cm)
FLAIR
Size (cm)
T1
precontrast
Size (cm)
T1 C+
Postcontrast
MR
enhancement
K2
Permeability
Cerebral
Blood
Volume
CBV
11-Met
PET
Pathology
WHO
Grade
1
3.9x3.6
3.2x3.6
3.1x2.5
Peripheral
( +1 )
(0)
( +1)
Glioblastoma
IV
2
4.9x7.3
4.8x3.5
5.2x3.8
Peripheral
( +1 )
( +1)
( +1 )
Glioblastoma
IV
3
4.1x3.7
4.2x3.0
4.1x3.2
Heterogeneous
( +1 )
( +1 )
( +1)
Glioblastoma
IV
4
7.5x5.3
2.1x1.4
1.7x2.3
Heterogeneous
( +1 )
( +1 )
( +1 )
Glioblastoma
IV
5
4.3x7.2
3.5x5.0
3.5x5.0
Minimal
peripheral
( -1 )
( -1 )
( +1 )
Anaplastic
Astrocytoma
III
6
2.4x5.7
4.3x1.8
4.3x1.8
None apparent
(0)
( -1 )
( +1 )
Oligoastrocytoma
II
7
8.3x5.6
8.3x4.7
8.3x4.7
None apparent
( -1 )
(-1)
( +1 )
Oligoastrocytoma
II
8
6.1x3.5
5.3x3.4
5.3x3.4
None apparent
(0)
(0)
( +1 )
Oligodendroglioma
II
9
2.9x3.0
2.8x3.9
2.8x3.9
Minimal
(0)
(0)
( +1 )
Oligodendroglioma
II
Met-PET: Hypermetabolic = +1, isomeatolic = 0, Hypometabolic = -1
MR K2 permeability: increased = +1, background = 0, decreased = -1
MR Cerebral Blood Volume (CBV): increased = +1, background = 0, decreased = -1
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