1. Can CT Perfusion Evaluate Cerebral Hemodynamic Change in Chronic Occlusive Cerebrovascular Diseases? - Comparison with Diamox-enhanced SPECT -
M. Hirata MD , Y. Sugawara MD , K. Kikuchi MD , H. Miki MD , T. Mochizuki MD , K. Murase PhD , S. Yamauchi RN 抄録
CTにおける脳灌流画像(CTP)では脳血流量(CBF)、脳血液量(CBV)、平均通過
時間(MTT)の複数のパラメータが得られることが特徴である。慢性閉塞性脳血管障害
において、各パラメータの変化が血行再建術の適応決定、効果判定に利用可能かどう
かを検討する。【方法】対象は慢性期の脳主幹動脈高度狭窄症例。責任血管領域に関
心領域を設定し、治療前のCTPにおけるCBF、CBV、MTTとXe-SPECT(133Xe REST+DIAMOX
)におけるCBF、血管反応性(CPR)との関連を評価した。また、治療症例では治療前後
でのそれぞれの変化を比較検討した。【結果】CTPのパラメータのうちMTTが最も鋭敏
にXe-SPECTにおけるCPR低下領域を反映しており、CTPにおけるMTTの延長とXe-SPECT
におけるCPRの低下に関連が認められた。特にCPRが高度に低下した部位においてMTT
の延長は高度であった。治療前後のXe-SPECTにおいてCBFには有意な改善は認められ
なかったがCPRには有意な改善が認められた。また、MTTにおいても同様に改善が認め
られた。【結論】脳灌流低下領域の評価においてCTPのパラメータのうちMTTが最も鋭
敏であり、慢性閉塞性脳血管障害においてMTTは治療の適応決定、効果判定に有用で
ある可能性が示唆された。

2. INTRODUCTION
Cerebral perfusion parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) are important for the determination of medical treatment plan and/or prognostic prediction of patients with cerebrovascular diseases (CVDs) (1, 2). Although the utilities of CT perfusion in acute stroke have been reported by many investigators (3-6), the role of quantitative CT perfusion parameters in patients with chronic occlusive CVD has not been elucidated enough (7) .
Prior studies from our group and others have shown that CBF and cerebral perfusion reserve (CPR) measurements using Diamox enhancement and SPECT are useful to evaluate hemodynamic status in chronic occlusive CVDs (8, 9).
In this exhibit, we will present the quantitative results of CT perfusion parameters in chronic occlusive CVDs and compare these with the data of Diamox-SPECT. Finally, we will discuss about the advantages and limitations in each of perfusion imaging modalities.
Cerebral perfusion parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) are important for the determination of medical treatment plan and/or prognostic prediction of patients with cerebrovascular diseases (CVDs). Although the utilities of CT perfusion in acute stroke have been reported by many investigators, the role of quantitative CT perfusion parameters in patients with chronic occlusive CVD has not been elucidated enough.
Prior studies from our group and others have shown that CBF and cerebral perfusion reserve (CPR) measurements using Diamox enhancement and SPECT are useful to evaluate hemodynamic status in chronic occlusive CVDs.
In this exhibit, we will present the quantitative results of CT perfusion parameters in chronic occlusive CVDs and compared these with the data of Diamox-SPECT. Finally, we will discuss about the advantages and limitations in each of perfusion imaging modalities.

3. Learning Objectives:
Describe the comparative results for quantitative values of CBF, CBV and MTT measured by CT perfusion in comparison with Diamox-enhanced SPECT.
Clarify the utilities and limitations in CT perfusion parameters in management of patients with chronic occlusive cerebrovascular diseases.
1. Describe the comparative results for quantitative values of CBF, CBV and MTT measured by CT perfusion in comparison with Diamox-enhanced SPECT. 2. Clarify the utilities and limitations in CT perfusion parameters in management of patients with chronic occlusive cerebrovascular diseases.

4. Cerebral Perfusion Reserve
BACKGROUND
Xe-133 SPECT in patients with chronic CVDs
We previously reported that cerebral perfusion reserve (CPR) significantly increased, but cerebral blood flow increased little immediately after PTA and /or stenting. Therefore, measurement of CPR is useful for evaluating therapeutic effects and for follow-up after PTA and stenting.
Cerebral Blood Flow
Cerebral Perfusion Reserve
我々はXe-133 SPECT を用いた慢性閉塞性脳血管障害患者における治療前後の検討でCBFには有意な改善が認められないがCPRにおいては有意な改善を認められ、CPRの評価が治療の効果判定と経過観察に有用であることを報告しました。
We previously reported that cerebral perfusion reserve significantly increased, but cerebral blood flow increased little immediately after PTA and stenting.
PTA and/or stenting
Increased little immediately after PTA and stenting. No significant changes on follow-up
Significantly increased immediately after treatment. Therapeutic effects continue on follow-up
Sugawara, et al. (SNM 2000) Hirata , et al. (SNM 2003)

5. BACKGROUND MR perfusion in patients with chronic CVDs
The MTT values in the territories of severely decreased CPR were significantly higher than those in the territories of moderately decreased or normal CPR
Severe CPR impairment can be estimated with MTT (8).
一方、菊池らはMRIを用いたPerfusion studyにおいて高度にperfusion reserve が低下した症例ではMTTに有意な延長が認められたと報告しています。
Cerebral perfusion reserve impairment can be evaluated with mean transit time measured using dynamic susceptibility contrast-enhanced MR imaging. The mean transit time values in the territories of severely decreased perfusion reserve were significantly higher than those in the territories of moderately decreased or normal perfusion reserve
Perfusion reserve
Severely decreased
CPR ≦ 0%
Moderately decreased
0% < CPR ≦ 15%
Normal
CPR > 15 %

6. BACKGROUND Pre PTA Post PTA CBF CBV MTT MR Perfusion 133Xe-SPECT
An example case: 73/M, PTA for Lt. MCA stenosis
Pre PTA
CBF
CBV
MTT
REST
DIAMOX 42
(27%)
Post PTA
MR Perfusion
133Xe-SPECT
CT Perfusion 30
1.6
5.4 32
5.1 29
REST
133Xe-SPECT
DIAMOX
Decrease of CPR
Improvement of CPR 26 23
(-13%)
MR Perfusion
これは左中大脳動脈の狭窄にてPTAを施行された症例です。治療前後でMRI Perfusion画像上Lt MCA領域にMTT延長が認められます。
治療後ではこの延長は軽減し左右差が目立たなくなっています。同時期に撮像したCT Perfusion画像でも若干の左右差のみでMR Perfusionと同様の所見を呈しています。
CBF
Increase of MTT
Normalization of MTT
CBV
MTT

7. Can CT Perfusion Evaluate Cerebral Hemodynamic Change in Chronic Occlusive Cerebrovascular Diseases?
Comparison of CBF, CBV and MTT measured by CT perfusion with CPR measured by Diamox-enhanced SPECT
CT perfusion
Diamox-enhanced 133Xe SPECT
Cerebral Blood Flow (CBF) ?
Cerebral Blood Volume (CBV)
現時点で慢性疾患に対するCTP応用の報告は少なくCBF、CBV、MTTの3パラメータの臨床的な意味合いについて十分な検討がなされていません。
そこで、慢性閉塞性脳血管障害の病態把握にCT perfusionの各parameterが利用可能かどうか、Diamox負荷 133Xe SPECTと比較検討しましたので報告します。To evaluate the usefulness of CT perfusion for chronic occlusive cerebrovascular disease
Cerebral Perfusion Reserve (CPR)
relation
Mean Transit Time (MTT)

8. METHODS CT perfusion protocol
CT Scanner: Light Speed QX/i (GE) or Ultra (GE)
Dynamic Scan:
Contrast medium: 300 mgI/ml, total ml
3-4 ml/s with power injector
Cine mode (5mm x 4i, 1 sec/rot)
5 sec delay for 60 sec
Data Analysis: Advantage Workstation 4.2 with CT perfusion 3
Xe-133 SPECT protocol
Xe-133 gas (1850 MBq) inhalation (Kanno-Lassen method)
Dynamic SPECT (20 s/scan x 16, Hitachi SPECT 2000H-40)
At rest and after Diamox® (1g)
SUBJECTS
6 male patients with chronic occlusive CVDs (Mean age = 63.3 ± 9.3 years)
方法です。
CTPおよびXe-133 SPECT の当院での撮像プロトコールです。
CTPは4chないし16chのMDCTを用いてボーラスで30-40 mlの造影剤を3-4 ml/sで注入し5㎜スライス4断面について検討しています。Function mapの作成にはGEのAdvantage Workstation 4.2 のCT perfusion 3を用いました。
Xe-133 SPECT はKanno-Lassen 法を用いrest とDiamox負荷後について撮像しています。
Rt. MCA stenosis: 2
Lt. MCA stenosis: 2
Rt.ICA and MCA stenosis with Lt. ICA occlusion: 1
Rt.ICA occlusion : 1

9. CBF(Diamox) - CBF(Rest)
METHODS
Regions of interest were placed in the MCA territories. The values of CBF, CBV and MTT measured by CT perfusion were compared with CPR values obtained from Diamox-enhanced 133Xe-SPECT.
CT perfusion
133Xe-SPECT
MTT
CBV
CBF
対象はMCAないしICAの慢性脳主幹動脈狭窄症例6症例です。
各症例について図のごとくCTPで得られた3つの function mapとそれと同レベルのXe-133 SPECT 上のMCA領域に赤で示した様にROIを設定しその領域の平均CBF、CBV、MTTとCPRとの関係を比較検討しました。
(すなわち、一症例について左右の2ROIで6症例12ROIについて検討しています。)
CPRについてはスライドの式にて算出しています。
Mean value in MCA territory
Mean CPR in MCA territory
CBF(Diamox) - CBF(Rest)
CPR = ×100 (%)
CBF(Rest)

10. Results -Relation between CPR and CTP parameters-
CBF
(mL/100g/min)
r = 0.58
CPR
CBV
(mL/100 g)
r = -0.34
Positive correlation was found between CBF and CPR.
Negative correlation was found between CBV and CPR.
Negative correlation was found between MTT and CPR.
The strongest correlation was found in MTT
-20 20 40 60
(%)
-20 20 40 60
(%)
CPR
MTT
(sec)
r = -0.63
Positive correlation was found between CBF and CPR.
Negative correlation was found between CBV and CPR.
Negative correlation was found between MTT and CPR.
The strongest correlation was found in MTT
結果です。
CTPの各パラメータとCPRとの関係を表しています。CBFとCPRに正の相関傾向、CBVおよびMTTとCPRとの間には負の相関傾向が認められました。相関係数はMR Perfusionでの検討と同様MTTで最も高く-0.63でした。
positive correlation was found between CBF and CPR. Negative was found between CBV and CPR
-20 20 40 60
(%)

11. Case 1: 57/M, Rt. MCA Occlusion
CT Perfusion
133Xe-SPECT
REST 19 29
DIAMOX
CBF
133Xe-SPECT 36 41
2.0
1.7
CBF ↓
CPR ↓
画像を供覧します。
これはRt MCA occlusionの症例です。CT上は明らかな梗塞巣を指摘できませんが、
SPECTにてRt MCA領域にCBFの軽度低下があり、CPRは著明に低下しています。
CT PerfusionではCBFの低下、CBVの上昇、MTTの延長が認められました。Function map上もCPRの低下部位とほぼ一致しています。特にMTT画像でわかりやすいです。
REST
CBV
No abnormal findings
32 (-10%) 52
(27%)
10.4
5.5
CBF ↓
CBV ↑
MTT ↑ ↑
DIAMOX
MTT

12. Case 1. 57/M, Rt. MCA Occlusion
The MTT values in the territories of severely decreased CPR were higher than those in the territories of moderately decreased or normal CPR
25%
40%
23%
38%
44%
37%
-24%
-26% 0%
CT Perfusion
133Xe-SPECT 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12
CBF
CBV
MTT
CPR
この症例について図のごとく12個のROIをとってそれぞれのROIについてCPRとの相関をグラフにしています。この症例ではROI毎にみてもMTTとの逆相関傾向が認められ相関係数は-0.74でした。
(mL/100g/min)
CBF
(mL/100 g)
CBV
(sec)
MTT
r= 0.24
r= -0.47
r= -0.74
CPR
CPR
CPR

13. Summary 1 Every CT perfusion parameters correlate with CPR.
MTT is the most sensitive to reflect severely decreased CPR in chronic occlusive CVDs.
MTT values was the most sensitive parameter to represent the territories of severely decreased CPR in chronic occlusive CVDs.
以上まとめますと、慢性閉塞性脳血管障害において、CTPのパラメータの内、MTTが最も鋭敏にCPRの変化を反映する傾向があり、CPRが高度に低下した部位において、MTTの延長も高度でした。
enhancement and SPECT are useful to evaluate hemodynamic status
, the MTT values was most sensitive
In the
The MTT values in the territories of severely decreased CPR were significantly higher than those in the territories of moderately decreased or normal CPR
CPR impairment can be evaluated with mean transit time (8).
The MTT values was most sensitive

14. What is the limitation in CT perfusion in management of patients with chronic occlusive cerebrovascular diseases?

15. Assessment of the therapeutic effects -Two example cases
STA-MCA anastomasis for Rt. ICA occlusion
CASE 2
CEA for Rt. ICA Stenosis
以下、今回検討した症例の内、治療前後で評価が出来た２症例について画像を供覧します。
Assessment of the effect of treatment
2 example cases effect of treatment
An example case of

16. 66/M, STA-MCA anastomasis for Rt. ICA occlusion
CASE.1
66/M, STA-MCA anastomasis for Rt. ICA occlusion
Pre STA-MCA
Post STA-MCA
133Xe-SPECT
CT Perfusion
133Xe-SPECT
CT Perfusion 27 35 30 39 30 35
CBF 28 36
CBF
REST
3.4
2.9
REST
3.2
2.2
CBV
CBV
30 (0%)
44 (26%)
29 (4%)
39 (6%)
一例目は
Rt ICA occlusionの症例です。STA-MCA前後の画像を提示しています。
治療前にSPECT上、右のMCA領域にCBFとCPRの低下が認められます。 CT Perfusionでも対側に比して右のMCA領域にCBFの低下、CBVの上昇、MTTの延長が認められました。
治療後のSPECTにても右のMCA領域のCBFとCPRに明らかな改善は認められませんでした。CTPでも大きな変化は認められません。
6.2
4.6
6.8
4.9
DIAMOX
DIAMOX
MTT
MTT
On CT perfusion
CBF values were decreased.
CBV and MTT values were increased.
On 133Xe-SPECT
CBF and CPR were decreased in Rt. MCA territory.
On 133Xe-SPECT and CT perfusion
No remarkable change was found.

17. CBV MTT CBF OEF CMRO2 133Xe-SPECT CT Perfusion CBF↓ CPR↓ CBV↑ MTT↑
Decrease of Perfusion Reserve
Infarction
Misery Perfusion
Normal
CBV
MTT
CBF
OEF
CMRO2
CASE.1
On 133Xe-SPECT, both CBF and CPR were decreased in Rt. MCA territory. This area could be categorized to "misery perfusion" in which CBF is reduced and the oxygen extraction fraction (OEF) is increased to maintain the cerebral metabolic rate of oxygen (CMRO2) (10) .
CT perfusion represented decrease of CBF and increase of CBV and MTT.
133Xe-SPECT
CT Perfusion
CBF↓
CPR↓
CBV↑
MTT↑
一般に脳灌流圧低下時の脳循環動態は図のごとく変化すると言われています。
Case1はCBFとCPRがともに低下しており
灌流圧低下に対する脳血管拡張によるauto regulationでも代償しきれずMisery Perfusionに陥った症例と考えられます。
この病態では、MTTの延長をはじめとするCTPパラメータの変化をとらえることが出来ました。
一方Case2は病側のCBFの低下は認めず、CPRのみ低下しておりauto regulationにより脳血流量が比較的保たれている状態と考えられます。この状態では、CTPパラメータの変化は明らかではありませんでした。
すなわち、CBVとMTTの変化がとらえられておらず、限界が示唆されました。
in which the cerebral blood flow (CBF) is reduced and the oxygen extraction fraction (OEF) is increased to maintain the cerebral metabolic rate of oxygen (CMRO2) and CBV
and represents an inadequate blood supply relative to metabolic demand

18. 68/M, CEA for Rt. ICA Stenosis
CASE.2
68/M, CEA for Rt. ICA Stenosis
Pre CEA
Post CEA
133Xe-SPECT
CT Perfusion
133Xe-SPECT
CT Perfusion 40 40 43 48
CBF
CBF 42 44 45 45
REST
REST
2.1
2.1
2.1
2.3
CBV
CBV
43 (2%)
一方、 Rt. ICA Stenosisに対してCEAを行った症例です。
治療前でSPECT上、安静時には明らかな左右差は認めませんが、Diamox負荷にて右MCA領域にCPRの低下が認められます。しかしながら、CT PerfusionではCBF、CBV、MTTに明らかな左右差無く病変部位を特定困難です。
治療後のSPECTにてCBFの増加は認めないもののCPRに明らかな改善が認められました。CT PerfusionではCBF、CBV、MTTに明らかな変化を認めません。
51 (18%)
61 (37%)
57 (29%)
4.7
4.6
4.1
3.9
DIAMOX
MTT
DIAMOX
MTT
On CT perfusion
CBF, CBV and MTT were normal.
On 133Xe-SPECT
CPR was decreased in the Rt. MCA territory.
CBF was not decreased.
On 133Xe-SPECT
CPR increased after treatment.
No remarkable change was found on CBF.
On CT perfusion
No remarkable change was found on CBF, CBV and MTT.

19. CBV MTT CBF OEF CMRO2 133Xe-SPECT CT Perfusion CBF → CPR ↓ CBV → MTT →
Decrease of Perfusion Reserve
Infarction
Misery Perfusion
Normal
CBV
MTT
CBF
OEF
CMRO2
CASE.2
On 133Xe-SPECT, only CPR was decreased in Rt. MCA territory. In this case, CBF , OEF and CMRO2 were maintained by autoregulatory vasodilatation (i.e. increase of CBV) (10) .
However, all CT perfusion parameters were normal. This suggest that CT perfusion potentially has limitation in the detection of mild hemodynamic changes.
133Xe-SPECT
CT Perfusion
CBF →
CPR ↓
CBV →
MTT →
一般に脳灌流圧低下時の脳循環動態は図のごとく変化すると言われています。
Case1はCBFとCPRがともに低下しており
灌流圧低下に対する脳血管拡張によるauto regulationでも代償しきれずMisery Perfusionに陥った症例と考えられます。
この病態では、MTTの延長をはじめとするCTPパラメータの変化をとらえることが出来ました。
一方Case2は病側のCBFの低下は認めず、CPRのみ低下しておりauto regulationにより脳血流量が比較的保たれている状態と考えられます。この状態では、CTPパラメータの変化は明らかではありませんでした。
すなわち、CBVとMTTの変化がとらえられておらず、限界が示唆されました。

20. Summary 2 Severe ischemic change is detectable by CT perfusion
CT perfusion potentially has limitation in the detection of mild ischemic changes.
SPECTにてCBFとCPRが低下した高度の灌流圧低下症例ではCBFの低下、CBVの上昇、MTTの延長が認められた。
SPECTにてCBFが正常でCPRのみが低下している軽度の灌流圧低下症例ではCTPパラメータの変化が認められなかった
On 133Xe-SPECT, both CBF and CPR were decreased in Rt. MCA territory. This case should be categorized to "misery perfusion" in which CBF is reduced and the oxygen extraction fraction (OEF) is increased to maintain the cerebral metabolic rate of oxygen (CMRO2).
CT perfusion represented decrease of CBF and increase of CBV and MTT.
CT perfusion can detect misery perfusion. However CT perfusion potentially has limitation on detection of slight change of parameters.
On 133Xe-SPECT, only CPR were decreased in Rt. MCA territory. In this case, CBF , OEF and CMRO2 were maintained by autoregulatory vasodilatation (i.e. increase of CBV).
However, all CT perfusion parameters were normal. This suggest that

21. Conclusion
MTT is the most sensitive to reflect severely decreased CPR in chronic occlusive CVDs.
CT perfusion potentially has limitation in the detection of mild ischemic changes.
CTPのパラメータのうちMTTが最も鋭敏に 慢性閉塞性脳血管障害の脳循環予備能（CPR）の低下を反映する傾向があった。
軽度の脳灌流圧低下症例ではCTPのパラメータの変化は乏しく有用性に限界が示唆された。
CBF (Rest) = 41.7 ± 2.4 ml/100g/min
Mean - 2 s.d. = 36.8 ml/100g/min
CPR = 41.1± 7.7 %
Mean - 2 s.d. = 25.7 %

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