Synopsis
Educational Lecture to discuss on the clinical usefulness of combined use of PET and physiological imaging with MRI. Focus is set on chronic occlusive cerebrovascular diseases and malignant brain tumor.Introduction
With the advent of PET/MR imaging, it has
become vital to interpret the multiple physiological parameters that can be
obtained by PET and physiological MR imaging. The presenter has long been using
both of these imaging modalities for the treatment of occlusive cerebrovascular
disease and malignant brain tumor. In this lecture, correlation of multiple
PET/MR parameters among these disease will be demonstrated mainly by using
presenter’s clinical data together with literature review. Clinical
significance of these parameters will also be discussed.
Physiological parameters of cerebrovascular occlusive disease measured
with PET and MRI.
In order to estimate natural risk
and to determine the optimal treatment of occlusive cerebrovascular disease, it
is vital to clarify the degree of hemodynamic compromise in each patient.
Patients at high risk of ischemic stroke generally exhibit abnormally high
oxygen extraction fraction (OEF) and elevated cerebral blood volume, a
combination of states described as misery perfusion or Grade 2 hemodynamic
stress (Grubb
et al. 1998, Derdeyn et al. 2002). The concurrent measurement of
cerebral blood flow, metabolism, and blood volume by positron emission
tomography (PET) serves as the optimal method for evaluating hemodynamics in
patients. PET is usually unavailable in daily clinical practice, however, and
it provides only poor information on the structural integrity of hypo-perfused
tissue.
Perfusion-weighted magnetic
resonance imaging (PWI) provides various parameters on cerebral hemodynamics
non-invasively and in less time than PET. In the past, we conducted a study to compare the parameters obtained with DSC-MRI and
PET in moyamoya patients (Tanaka et al. 2006). In this paper, we demonstrate that mean transit time (MTT) and cerebral
blood volume (CBV) that was measured with DSC-MRI are reliable parameter to
estimate Grade 2
hemodynamic stress. By using DSC-MRI for the treatment of moyamoya disease,
we showed that DSC-MRI can be used with the same reliability as more invasive
measure such as PET or acetazolamide challenge test to determine the surgical
indication and to foresee the surgical result (Nariai et al. 1994, Ishii et al. 2014).
Recently, we have completed another comparative study in moyamoya disease
to compare the reliability of cerebral blood flow (CBF) value obtained with
ASL-MRI (Hara et al. submitted). In this, we compared the parameters among ASL-MRI, PET and DSC-MRI. Once we obtain CBF map using 2 post-labeling delays
(PLDs) (shorter ASL: sASL = 1525 ms, delayed ASL: dASL = 2525 ms), sASL-CBF
values had a moderate correlation with the PET-CBF values (r = 0.46) and the
correlation was greater (r = 0.50) in areas with MTT delay (delay of MTT in
comparison to control lesion (cerebellum) ) ≤1.5 s, while sASL
underestimated the PET-CBF in regions with MTT delay>1.5 s. The dASL-CBF
overestimated the PET-CBF regardless of MTT delay. (Figure 1)
More interesting finding was obtained by comparing
ASL-CBF using two different PLD with DSC-MRI measured time parameters. Ratio of
dASL-CBF to sASL-CBF (dASL-CBF/sASL-CBF) was significantly correlated with the time
parameters measured by DSC-MRI (Tmax, TTP, and MTT (r = 0.68, 0.55, 0.53, respectively)).
(Figure 2)
Although further trial is necessary to find optimum
combination of PLD, this result may lead to the development of new imaging
strategy to measure perfusion delay non-invasively using multiple PLD in
ASL-MRI. As MTT reflect the reciprocal of cerebral perfusion pressure (Powers et al. 1984), this strategy may be a sensitive imaging method
to evaluate impaired perfusion pressure in totally non-invasive manner.
Physiological parameters of malignant brain tumor measured with PET and
MRI.
It has now been well recognized
that morphological imaging is not enough to characterize the pathophysiology of
malignant brain tumor for the purpose of intensive treatment of them. Instead,
imaging of tumor biomarker using physiological imaging of PET and MRI (Waldman
et al. 2009).
The reasons why physiological
imaging is inevitable in malignant brain tumor treatment are summarized into two
points;1)glioma invades
into brain parenchyma without disruption of blood brain barrier (BBB) and,
therefore, area harboring tumor cells cannot be identified neither with
Gd-enhanced T1 images nor FLAIR images by MRI. 2) morphological imaging never
be able to distinguish between the active malignant tumor and the treatment induced
necrosis.
PET imaging using amino acid
probes, such as
11C methionine, is now recognized as useful tool to
solve these two problems (Nariai
et al. 2005). We reported that , with use of 11C
methionine PET, surgical removal of glioma based on PET guided navigation and gamma
knife treatment against recurrent metastatic brain tumor by differentiating
tumor and necrotic tissue led to the prolongation of patients’ survival after the
treatment (Tanaka
et al. 2009, Momose et al. 2014).
As these indicate, use of PET amino
acid imaging has high potential to improve the treatment of malignant brain
tumor. PET tumor imaging other than fluoro-deoxy-glucose, however, is now in the
stage of clinical trial, and accessibility is highly limited. Therefore, establishment
of physiological imaging with MRI (or X-ray CT) is awaited for practical
clinical use.
Our comparative study between
11C
methionine PET and dynamic CT perfusion (Nambu et al.
2003) revealed that the tumor uptake of
11C methionine and
dynamic CT measured tumor blood volume changes concordantly after gamma-knife
treatment against malignant glioma, but increased permeability of tumor vessel
that was induced by high dose irradiation did not caused increased uptake of
methionine (Figure 3). Figure 4-A indicated the non-correspondence between PET
measured methionine uptake and permeability of tumor vessels. Instead, in
Figure 4-B, we demonstrated that significant correlation between tumor blood
volume and methionine uptake.
This result can be applied for
physiological imaging with MRI. Presumably among various physiological tumor
parameters, those indicating tumor vessel density may be usable parameters to imitate
PET tumor imaging. As indicated in Figure 5, recurrent glioblastoma in the are
without Gd enhancement could be detected by
11C methionine PET imaging
and ASL-MRI. Biological status of of treatment induced tumor effect can be
imaged by
11C methionine PET and vessel density parameters depicted
by DSC-MRI and ASL-MRI (Figure 6).
Result
of both the ASL and the DSC study, however, could be influenced by permeability
of tumor vessels (Tanaka et al. 2011).
Contribution of permeability change on ASL and DSC measured parameters must be
examined as we denied the contribution of permeability change on the uptake of
11C
methionine using CT perfusion (Figure 3 and 4). To do this, we started clinical
study using DCE-MRI to examine tumor vessel permeability together with ASL,
DSC, and
11C methionine. Preliminary result may be introduced in the
lecture.
Conclusions
For the intensive treatment of cerebrovascular
occlusive disease and malignant brain tumor, PET can provide valuable
parameters that are supported by many clinical research evidence. Application
of such research result for routine clinical setting, development of physiological
MR study that can provide alternative parameters supported by comparative study
must be necessary . By now, we presented the reliability of DSC-MRI measured
MTT as alternative to PET-measured OEF, and the reliability of ASL or DSC MRI
based tumor vessel parameters as alternative to
11C methionine PET.
Further study to compare PET and physiological MRI parameters may lead to the establishment
of another good alternative for routine clinical use.
Acknowledgements
This study was partially supported by research grant from SENSHI Medical Research Foundation.References
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