Quantitative measurement of blood flow volume in the major intracranial arteries by using 123i-iodoamphetamine SPECT.

ORIGINAL ARTICLE

Quantitative Measurement of Blood Flow Volume in the Major Intracranial Arteries by Using 123I-Iodoamphetamine SPECT Shigeki Yamada, PhD, MD,*Þþ Masaharu Kobayashi, M Eng,Þ Yoshihiko Watanabe, MD,þ Hidenori Miyake, PhD, MD,þ and Marie Oshima, PhDÞ

Purpose: The aim of this study was to establish the novel automatic method to quantify blood flow volumes of the major intracranial arteries by using SPECT. Methods: We created the vascular templates to cover the territory supplied by the major intracranial arteries. Each blood flow volume was calculated as the regional cerebral blood flow on SPECT using this template volume size of the template. In this study, we evaluated the volume flows in 22 cerebral hemispheres with normal perfusion and 28 hemispheres with severe stenosis in the internal cerebral artery (ICA) or middle cerebral artery (MCA) and that at acetazolamide test in 16 normal hemispheres and 20 hemispheres with stenosis. Results: The mean blood flow volumes of the ICA and MCA in the normal hemispheres increased to more than 40% after acetazolamide test (161Y228 mL/min for ICA and 111Y157 mL/min for MCA), although those in the hemispheres with stenosis increased to less than 35% (158Y192 mL/min for ICA and 107Y127 mL/min for MCA). The receiver operating characteristic analyses revealed that the simple difference between the blood flow volume at acetazolamide test and that at rest using the new MCA template was superior to detecting reduction of cerebrovascular reactivity (CVR), compared with the conventional percent CVR using the original template. Conclusions: Blood flow volumes of the intracranial arteries had been able to be quantified automatically on SPECT, and difference of CVR was available for predicting the blood demand-supply balance. Key Words: brain imaging, cerebral blood flow, cerebral blood flow measurement, cerebral hemodynamics, IMP SPECT (Clin Nucl Med 2014;39: 868Y873)

ith the improvements in the accuracy of the 123I-N-isopropyl-piodoamphetamine (123I-IMP) autoradiographic (ARG) technique of SPECT, quantitative measurements of regional cerebral blood flow (rCBF; mL/min per 100 g of brain tissue) and cerebrovascular reactivity (CVR; %) can also be used as predictors for subsequent ischemic stroke in patients with occlusion or stenosis of the major intracranial arteries.1Y4 Previous rCBF studies with 123I-IMP SPECT and 15O gas PET have demonstrated variability, reliability, and significant correlation between SPECT and PET evaluations of rCBF.3,5Y8 Furthermore, automatically set 3-dimensional region of interest (ROI) for the NEUROSTAT has been shown to improve the reproducibility of the SPECT and PET

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Received for publication January 21, 2014; revision accepted July 2, 2014. From the *Department of Neurosurgery and Stroke Center, Rakuwakai Otowa Hospital, Kyoto; †Interfaculty Initiative in Information Studies/Institute of Industrial Science, The University of Tokyo, Tokyo; and ‡Department of Neurosurgery, Hamamatsu Rosai Hospital, Shizuoka, Japan. Conflicts of interest and sources of funding: none declared. Reprints: Shigeki Yamada PhD, MD, Department of Neurosurgery and Stroke Center, Rakuwakai Otowa Hospital, Otowachinji-cho 2, Yamashina-ku, Kyoto City, Kyoto 607-8602, Japan. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0363-9762/14/3910Y0868

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examinations9Y12 and can help standardize these quantitative results.13 We previously reported the importance of the inflow and outflow boundary conditions for the patient-specific computational flowdynamic simulation models using the arterial circle of Willis.14 The realistic value of quantitative volume flow in the major intracranial arteries is the pivotal parameter as the outflow boundary condition for the patient-specific simulation studies. However, there has been no reliable method to quantify blood flow volumes in such narrow and complex intracranial arteries. The aim of this study is to establish the novel method to quantify blood flow volume in the major intracranial arteries by using the 123I-IMP SPECT study to convert the limited regions of automatically set ROIs into the maximum extended regions of the territories supplied by the major intracranial arteries.

PATIENTS AND METHODS Three-Dimensional ROI Template for Major Intracranial Artery on SPECT or PET To evaluate rCBF, we used the NEURO FLEXER software, which had been developed and provided free by the Nihon MediPhysics Co, Ltd, Tokyo, Japan, based on the NEUROSTAT (University of Washington, Seattle, Wash, http://www.rad.washington.edu/research/ Research/groups/nbl/neurostat-3d-ssp). The original presetting ROI templates in digital imaging and communications in medicine format contained the regions of cerebral hemispheres, basal ganglia, thalamus, cerebellar cortex, cerebellar vermis, and pons and the vascular territories supplied by the anterior, middle, and posterior cerebral arteries (anterior cerebral artery [ACA], middle cerebral artery [MCA], and posterior cerebral artery [PCA]).10 Because the original templates for the vascular territories were intended for rCBF measurement, these regions were focused in the gray matter and excluded the watershed boundary regions between ACA and MCA, those between MCA and PCA, and the regions close to the lateral ventricle (Fig. 1A). Therefore, we created the ROI templates for the vascular territories of the ACA, MCA, and PCA while referring to the arterial territories of the human cerebral hemispheres.15Y17 These territories included their border zones to cover all of the territories fundamentally perfused by each intracranial artery with the aim to calculate the blood flow volume of these intracranial arteries (Fig. 1B). The territories of the internal cerebral artery (ICA) and the vertebral artery (VA) were defined as the combination territories of the ACA and MCA, and the PCA and the ipsilateral regions of the cerebellum and the brainstem, respectively. The MCA territory was divided into 3 regions as follows: anterior MCA trunk (M2 ant), which supplied the anterior and superior parts of the Sylvian fissure; posterior MCA trunk (M2 post), which supplied the posterior and inferior parts of the Sylvian fissure; and the perforators of the main MCA trunk (M1 seg), which were mainly lateral lenticulostriate arteries (Fig. 1C and D). As a matter of convenience, the territory supplied by the anterior choroidal artery, which usually branched from the ICA at the distal side of the circle of Willis, was included in the territory of M1 seg because of the difficulty

Clinical Nuclear Medicine

& Volume 39, Number 10, October 2014

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.



Cerebral Blood Flow Volume by IMP SPECT

FIGURE 1. Images of the 3-dimensional automatically set ROI templates in the territories of the ACA, MCA, PCA (A and B) and detailed MCA territories (C and D). A and C, Original ROI templates for the measurement of rCBF (mL/min per 100 g). B and D, New ROI templates for the measurement of blood flow volume (mL/min). Each voxel can be detected by automatically set ROI. The background image is an MRI sample image. The upper row shows the axial section, the middle row shows the coronal section, and the lower row shows the sagittal section. Red color indicates the left ACA territory for A and B, and the left M2 anterior territory (M2 ant) for C and D. Green color indicates the left MCA territory for A and B, and the left M2 posterior territory (M2 post) for C and D. Blue color indicates the left PCA territory for A and B, the left basal ganglia for C, and the left M1 segmental territory (M1 seg) for D. The right-side templates were created by the mirror images of the left-side templates.

distinguishing the territory of the anterior choroidal artery supplying the basal ganglia, internal capsule, and so on, from the M1 seg.

Image Acquisition SPECT studies were performed with a Siemens E-Cam rotating F-camera (Siemens, Munich, Germany) with a parallel-hole collimator (64 64 matrix, 9 mm full width at half maximum). Data collection was started at the IV injection of 222 MBq 123I-IMP tracer (Nihon Medi-Physics Co, Ltd), and the duration of scanning was 28 minutes. Data were obtained from 90 projections with each sampling time being 20 to 30 seconds and were automatically reconstructed images by the QSPECT package.13 The rCBF is estimated by the IMPARG method, as described by Iida et al.5 Briefly, the 2-compartment model is used to describe the kinetics of IMP in the brain. The distribution volume of IMP, which was defined as the ratio of the influx rate to the efflux rate, was set in the fixed value of 35.0 mL/g for the whole brain. The density of human brain tissue is assumed 1.04 g/mL. The method used a standard arterial input calibrated by the radioactivity of a single arterial whole-blood sample 10 minutes after IV injection. If the patients required evaluation of the CVR, they underwent a dual-table ARG study, which included dual administrations of split-dose (111 MBq) 123 I-IMP tracer in a single SPECT session, according to the multicenter standardized protocol reported by Iida et al.13 At 10 minutes * 2014 Lippincott Williams & Wilkins

before the second IMP injection, 1000 mg of acetazolamide (Diamox) loading was performed.

Quantitative Measurement of Blood Flow Volume and CVR Evaluation Figure 2 shows the sample images automatically created by the NEURO FLEXER software using the original and new vascular templates in a representative patient with symptomatic severe left ICA stenosis. Each blood flow volume (mL/min) was calculated as the mean rCBF (mL/min per 100 g of brain tissue) in each vascular territory voxel volume (voxel number voxel size) 1.04 (density of a human brain tissue)/100. Cerebrovascular reactivity was evaluated by 2 methods. The first was the conventional method, percent CVR (%CVR), which was calculated as (rCBF or flow volume at acetazolamide test j rCBF or flow volume at rest)/rCBF or volume flow at rest 100 (%). The second was the difference of CVR (dCVR), which was simply calculated as rCBF or flow volume at acetazolamide test j rCBF or flow volume at rest. Hemispheres with CVR reduction were defined as less than 15% of the %CVR in the MCA territory or greater than 20% of the disparity of %CVR between ipsilateral and contralateral hemispheres, and others were categorized in preserved CVR, according to the previous reports.1,2,4 www.nuclearmed.com


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FIGURE 2. SPECT images from the representative case of symptomatic severe left ICA stenosis. IMP SPECT images at rest (A) and acetazolamide challenge test (C) using the original template for the measurement of rCBF (mL/min per 100 g). IMP SPECT images at rest (B) and acetazolamide challenge test (D) using the new template for the measurement of blood flow volume (mL/min). The white lines indicate the borders of the ROIs. The rCBF at rest in the left ICA territory was lower than in the right ICA territory. After acetazolamide challenge, the right ICA territory showed an obvious increase in rCBF, whereas the left ICA territory did not show an increase.

Study Population The study design, protocol, and data management were approved by the ethical committee for human research at our institute. Informed written consent concerning usage of imaging data for our research was obtained from all participants. The inclusion criterion for this study was that the SPECT examination was conducted before any revascularization procedures. Twenty-five patients (17 men, 8 women; mean age, 66.1 T 10.5 years) who underwent quantitative 123I-IMPARG SPECT for consideration of surgical indications for revascularization were prospectively participated in this study. Eight patients had severe stenosis at the origin of the ICA, 16 had severe stenosis or occlusion in the main trunk of the MCA (3 had bilateral stenoses in the main trunk of the MCA), and 1 had bilateral VA severe stenoses. Severe stenosis was defined as greater than 70% stenosis on digital subtraction angiography or 3-dimensional CT angiography. There were 7 SPECT examinations that were conducted only at rest and without acetazolamide test. Therefore, blood flow volumes at rest were evaluated in 28 hemispheres with severe stenosis or occlusion in the ICA or MCA and 22 hemispheres without any stenosis (defined as normal hemispheres) after acetazolamide test in 20 hemispheres with severe stenosis and 16 normal hemispheres.

Statistical Analysis Mean values and SDs for blood flow volume, %CVR, and dCVR in each major intracranial artery were calculated. All P values in the comparisons of the mean values between normal hemispheres and hemispheres with stenosis were less than 0.001 using the Wilcoxon rank sum test. Therefore, the mean values in the 2 groups of hemispheres were compared using the nonparametric Spearman rank 870

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correlation coefficients (Q) for more rigorous statistical evaluation. Furthermore, the %CVRs and dCVRs using the new MCA and ICA territories were compared with these using the original MCA and ICA templates in the receiver operating characteristic (ROC) analyses. The area under the ROC curve (AUC) was calculated for evaluating the optimal cutoff points to maximize the sum of sensitivity and specificity for detecting CVR reduction. All statistical analyses were performed using the R software (version 3.0.1; R Foundation for Statistical Computing, Vienna, Austria, http://www.R-project.org). Statistical significance was assumed at a P value of less than 0.05.

RESULTS Table 1 shows the mean values (SDs) for blood flow volumes in normal cerebral hemispheres and hemispheres with ICA or MCA stenosis. After acetazolamide test, the mean flow volumes of the ICA and MCA increased to 228 and 157 mL/min in the normal hemispheres, whereas in the hemispheres with stenosis, these showed a slight increase to 192 and 127 mL/min, and the correlations were statistically significant. At rest, however, there was no statistically significant correlation between the flow volumes and the hemispheres with stenosis. The mean blood flow volumes of the ACA, PCA, and VA at rest and acetazolamide test had no significant correlation with stenosis. As results, the mean dCVRs using the new ICA and MCA templates (mL/min) in the hemispheres with stenosis were approximately half of those in the normal hemispheres (Table 2). The mean dCVRs using the original ICA and MCA templates were greater than 10 mL/min per 100 g in the normal hemispheres and less than 0 mL/min per 100 g in the hemispheres with stenosis (Table 2). The mean %CVRs in the normal hemispheres using the new and original * 2014 Lippincott Williams & Wilkins




TABLE 1. Summary of Blood Flow Volume (mL/min) Normal Hemisphere, Mean (SD) At rest Number 22 ICA 161.0 (23.9) ACA 56.0 (8.4) MCA 110.6 (16.5) M2 ant 54.1 (7.9) M2 post 51.4 (8.5) M1 seg 13.3 (2.0) PCA 47.3 (8.5) VA 73.8 (12.1) At acetazolamide test Number 16 ICA 227.6 (43.0) ACA 77.9 (14.9) MCA 157.0 (29.7) M2 ant 76.8 (14.0) M2 post 72.9 (14.7) M1 seg 19.1 (3.6) PCA 67.7 (13.1) VA 102.1 (19.5)

Hemisphere With Stenosis, Mean (SD)

Q*

TABLE 3. %CVR in New Templates Compared With That in Original Templates Normal Hemisphere, Hemisphere With Mean (SD) Stenosis, Mean (SD)

P† Number

28 157.8 (28.3) 55.9 (9.4) 106.9 (20.0) 52.6 (10.0) 48.8 (9.4) 13.1 (2.9) 48.4 (8.8) 77.6 (14.0)

0.11 0.04 0.15 0.10 0.17 0.16 j0.04 j0.14

0.463 0.788 0.305 0.475 0.237 0.270 0.788 0.334

20 192.3 (26.8) 71.1 (11.9) 127.4 (19.8) 61.1 (10.1) 59.5 (9.3) 16.4 (3.5) 65.1 (10.8) 102.6 (17.3)

0.43 0.24 0.55 0.61 0.50 0.33 0.12 j0.02

0.009 0.164 G0.001 G0.001 0.002 0.049 0.492 0.901

Bold values mean statistically significant values ( p G 0.05). *Spearman rank correlation coefficient. †P value was calculated using Spearman rank correlation coefficient (Q).

templates for the ICA and MCA territories were greater than 40%, whereas these in the hemispheres with stenosis were less than 30% (Table 3). The Spearman rank correlation coefficients for the dCVR were substantially higher than those for %CVR. As results of CVR evaluation, 1 of 3 patients diagnosed with bilateral MCA severe stenoses had bilateral hemispheres with CVR reduction, 12 patients had a TABLE 2. dCVR in New Templates (mL/min) Compared With That in Original Templates (mL/min per 100 g) Normal Hemisphere, Hemisphere With Mean (SD) Stenosis, Mean (SD) Number


16

P†

0.54 0.57 0.59 0.59 0.55 0.27

G0.001 G0.001 G0.001 G0.001 G0.001 0.109

0.66 0.73 0.69 0.73 0.72

G0.001 G0.001 G0.001 G0.001 G0.001

0.47

0.004

*Spearman rank correlation coefficient. †P value was calculated using Spearman rank correlation coefficient (Q).

* 2014 Lippincott Williams & Wilkins

P†

16

20

40.4 (19.5) 41.9 (20.1) 41.6 (20.6) 42.1 (20.6) 45.4 (17.9) 37.2 (18.5)

22.3 (17.1) 19.9 (18.1) 16.9 (19.9) 22.0 (17.8) 24.8 (16.6) 27.4 (18.6)

0.46 0.005 0.51 0.001 0.54 G0.001 0.48 0.003 0.53 G0.001 0.24 0.164

43.7 (19.9) 42.8 (21.7) 40.7 (20.1) 46.3 (23.8) 45.9 (20.3)

27.0 (17.4) 17.2 (20.6) 15.5 (21.5) 17.5 (21.9) 25.5 (21.1)

0.42 0.010 0.53 G0.001 0.52 0.001 0.56 G0.001 0.48 0.003

45.1 (19.5)

35.0 (22.9)

0.23

0.179

*Spearman rank correlation coefficient. †P value was calculated using Spearman rank correlation coefficient (Q).

unilateral hemisphere with CVR reduction, and 5 had preserved CVR. The ROC curves illustrating the accuracy the dCVR and %CVR for detecting CVR reduction are shown in Figure 3 (MCA templates) and Figure 4 (ICA templates). The dCVRs using the new MCA and ICA templates were superior to detecting CVR reduction, compared with the dCVRs using the original MCA and ICA templates. The AUC for the dCVR using the new MCA template was the highest (0.90), and the optimal cutoff point, sensitivity, and specificity were 18.6 mL/min, 95.5%, and 71.4%, respectively (Fig. 3). The ROC curves for the %CVR using the new MCA and ICA templates were similar, and these AUCs were around 0.8. There were no any statistically significant differences of AUCs among %CVR or dCVR estimated using the new and original MCA and ICA templates.

DISCUSSION Q*

20

New template (blood flow volume, mL/min) ICA 64.9 (32.6) 32.6 (22.8) MCA 46.0 (22.8) 19.2 (16.6) M2 ant 22.4 (11.4) 7.8 (9.5) M2 post 21.4 (10.7) 9.8 (7.0) M1 seg 5.9 (2.4) 3.1 (2.0) ACA 21.0 (10.9) 14.6 (10.1) Original template (rCBF; mL/min per 100 g) ICA 14.7 (7.5) j3.4 (14.6) MCA 14.4 (8.2) j6.9 (15.3) M2 ant 13.5 (7.3) j6.7 (14.2) M2 post 15.9 (9.2) j7.8 (17.3) Basal 16.6 (7.7) j5.3 (15.5) ganglia ACA 15.1 (7.4) 0.0 (15.6)

New template, % ICA MCA M2 ant M2 post M1 seg ACA Original template, % ICA MCA M2 ant M2 post Basal ganglia ACA

Q*

We could quantitatively measure blood flow volumes of the ICA, VA, ACA, MCA, and PCA by using 123I-IMP SPECT with the automatically set 3-dimensional ROI templates for vascular territories. The past SPECT or PET data in digital imaging and communications in medicine format could also be used for the measurement of blood flow volumes simply to convert the original templates into the new vascular templates. Phase-contrast magnetic resonance angiography (PC-MRA) is accepted as a criterion standard for the quantification of blood flow volumes in the arteries proximal to the circle of Willis.18Y20 The reported mean volume flows of the ICA and basilar artery on PC-MRA are 97.6 to 367 mL/min and 63 to 192 mL/min, respectively, which fluctuate depending on arterial stenoses and variations in the anatomy of the circle of Willis.21Y25 Tanaka et al estimated that distribution of the relative flow rates of the ACA:MCA:PCA would be 1:3:1 from their results of PC-MRA for flow distributions in the ICA and VA on the variations in the circle of Willis.24 Zhao et al26 have reported successful flow measurements in the main trunk of the ACA (mean volume flows [SD], 83 [27] mL/min), MCA (148 [29] mL/min), and PCA (65 [14] mL/min) by PC-MRA and NOVA software using a complex partition algorithm.26 In the present study, SPECT at acetazolamide test in the normal hemispheres indicated that the mean volume flow (SD) of the ACA was 78 (15) mL/min, that of the MCA was www.nuclearmed.com


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FIGURE 3. ROC curves for detecting CVR reduction using the new and original MCA templates. The ROC graphs show specificity on the x-axis and sensitivity on the y-axis. The left graph shows dCVR, and the right shows %CVR. The solid lines indicate ROC curves using the new MCA templates, and the dashed lines indicate those using original MCA templates. The black marks indicate the optimal cutoff points of the maximum AUC. The optimal cutoff point for dCVR (specificity, sensitivity) was 18.6 mL/min (95.5%, 71.4%) using the new MCA template and 4.9 mL/min per 100 g (81.8%, 85.7%) using the original MCA template. That for %CVR (specificity, sensitivity) was 18.0% (90.9%, 64.3%) using the new MCA template and 26.0% (72.7%, 85.7%) using the original MCA template.

157 (30) mL/min, and that of the PCA was 68 (13) mL/min, which were very similar to the results reported by Zhao et al.26 Therefore, these blood flow volumes measured in this study are considered as probable values. However, direct measurement of blood flow volume in the ACA or MCA by using PC-MRA is generally and theoretically difficult because of narrow diameter, 3-dimensional orientation (bending and tortuosity), and relatively low flow of the target intracranial artery. Actually, we could not obtain the stable results of the blood flow volumes in the ACA and MCA on the PC-MRA examination. There is a possibility that the flow volume quantified on SPECT would be different from the actual flow volume, especially the flow volume of the

MCA in a severe ischemic case with severe stenosis or occlusion of the MCA main trunk. A part of the anatomical MCA territory demonstrated on our vascular template might be supplied from the ipsilateral ACA and PCA via cortical leptomeningeal anastomoses. Therefore, these flow volumes quantified on SPECT should be treated as intrinsic outflow volumes of the major intracranial arteries in the normal perfusion territories. Using our new templates, the dCVR method, which was simply calculated as flow volume at acetazolamide test j flow volume at rest, was available for detecting CVR reduction at the same level or more accurately than the conventional %CVR method. One of the potential disadvantages for the dCVR method might be

FIGURE 4. ROC curves for detecting CVR reduction using the new and original ICA templates. The solid lines indicate ROC curves using the new ICA templates, and the dashed lines indicate those using original ICA templates. The black marks indicate the optimal cutoff points of the maximum AUC. The optimal cutoff point for dCVR (specificity, sensitivity) was 41.0 mL/min (72.7%, 85.7%) using the new ICA template and 11.0 mL/min per 100 g (59.1%, 92.9%) using the original ICA template. That for %CVR (specificity, sensitivity) was 22.5% (77.3%, 78.6%) using the new ICA template and 26.5% (72.7%, 78.6%) using the original ICA template. 872

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influenced by the size of infarcted lesions because the measurement of blood flow volume uses automatically set ROIs templates for the vascular territories. In this study, the mean blood flow volumes of the major intracranial arteries in the hemispheres with stenosis at rest were almost the same values compared with those in the normal hemispheres because the hemispheres with stenosis did not have large infarcted lesions. From the viewpoint of clinical examination; however, inclusion of infarcted lesions may not affect the decision making for cerebral revascularization because of no blood demand or supply in the completely infarcted brain.

CONCLUSIONS Quantitative values of blood flow volumes and dCVR in the major intracranial arteries can be measured on 123I-IMP SPECT using the new automatically set ROIs templates for the vascular territories. These values might be available for predicting subsequent ischemic attack and planning therapeutic strategies in future simulation studies on computational fluid dynamics as distal outflow estimation. This novel technique will pave the way for a new use of nuclear medicine images. ACKNOWLEDGMENTS The authors thank the radiology staff of the Hamamatsu Rousai Hospital, Shizuoka, in particular, Yuuki Nonogawa, Shinichi Ozeki, Kazuo Moriya, Yasunori Morishita, Kuniaki Yamauchi, and Katsunori Kawazoe, for handling the SPECT scanners. The authors also thank Hidetoyo Nishida and Kazuhiro Nishikawa (Nihon Medi-Physics Co, Ltd, Tokyo, Japan) for their help using the NEURO FLEXER and Dr Satoshi Minoshima, Department of Radiology and Bioengineering, Washington University, Seattle, Wash, who created the NEUROSTAT software. Dr Yamada takes responsibility for the data management, accuracy of statistical analysis, conduct of the research, and drafting of the manuscript. Dr Kobayashi mainly contributed on fund handling and drafting of the manuscript. Drs Watanabe and Miyake mainly contributed on data collection and drafting of the manuscript. Dr Oshima mainly contributed on research conception, fund handling, supervision, and drafting of the manuscript. REFERENCES 1. Kuroda S, Kamiyama H, Abe H, et al. Acetazolamide test in detecting reduced cerebral perfusion reserve and predicting long-term prognosis in patients with internal carotid artery occlusion. Neurosurgery. 1993;32:912Y919. 2. Kuroda S, Houkin K, Kamiyama H, et al. Long-term prognosis of medically treated patients with internal carotid or middle cerebral artery occlusion: can acetazolamide test predict it? Stroke. 2001;32:2110Y2116. 3. Kuroda S, Shiga T, Ishikawa T, et al. Reduced blood flow and preserved vasoreactivity characterize oxygen hypometabolism due to incomplete infarction in occlusive carotid artery diseases. J Nucl Med. 2004;45:943Y949. 4. Ogasawara K, Ogawa A, Terasaki K, et al. Use of cerebrovascular reactivity in patients with symptomatic major cerebral artery occlusion to predict 5-year outcome: comparison of xenon-133 and iodine-123-IMP single-photon emission computed tomography. J Cereb Blood Flow Metab. 2002;22:1142Y1148. 5. Iida H, Itoh H, Nakazawa M, et al. Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT. J Nucl Med. 1994;35:2019Y2030. 6. Iida H, Akutsu T, Endo K, et al. A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography. J Cereb Blood Flow Metab. 1996;16:781Y793.



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Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation.

Dynamic SPECT measurement of absolute myocardial blood flow in a porcine model.

Quantitative Signature of Coronary Steal in a Patient with Occluded Coronary Arteries Supported by Collateral Circulation Using Dynamic SPECT.

Measurement of cerebral blood flow, cerebral blood volume, and cerebral capillary permeability in glioma-bearing rats.

[The regional blood flow in intracranial tumors: a comparison of HMPAO-SPECT with a newer magnetic resonance tomographic procedure].

Mathematical model representing blood flow in arteries.

3D-reconstruction of coronary arteries in view of flow measurement.

Measurement of pulmonary capillary blood flow in infants by plethysmography.

Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI.

Noninvasive MRI measurement of the absolute cerebral blood volume-cerebral blood flow relationship during visual stimulation in healthy humans.

Regional cerebral blood flow measurement using a scintillation camera.

Measurement of regional cerebral blood volume by computerized axial tomography.

Measurement of regional cerebral blood volume by emission tomography.

Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124iodine in patients with breast cancer.

The effect of morphine on regional cerebral blood flow measured by 99mTc-ECD SPECT in dogs.

Radioisotope blood volume measurement in hemodialysis patients.