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      Optimal Brain 99mTc–Ethyl Cysteinate Dimer SPECT Imaging and Analysis to Detect Misery Perfusion on 15O PET Imaging in Patients With Chronic Occlusive Disease of Unilateral Major Cerebral Artery

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          Abstract

          Purpose

          Misery perfusion is defined as marginally sufficient cerebral blood supply relative to cerebral metabolic demand. The aim of the present study was to determine the optimal brain 99mTc–ethyl cysteinate dimer (ECD) SPECT imaging and analysis to detect misery perfusion on 15O PET imaging in patients with chronic occlusive disease of unilateral internal carotid or middle cerebral artery (MCA).

          Methods

          For 97 patients, cerebral blood flow, cerebral metabolic rate of oxygen, and oxygen extraction fraction were measured using 15O PET; 99mTc-ECD SPECT was performed using dynamic scanning with a scan duration of 10 minutes each for 50 minutes after tracer administration. A region of interest was placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres in all standardized images using a 3-dimensional stereotaxic region-of-interest template and affected-to-contralateral asymmetry ratio in the MCA territory (AR MCA) and contralateral-to-affected asymmetry ratio in the cerebellar hemisphere (AR cbl) were calculated.

          Results

          The AR MCA or AR cbl on 99mTc-ECD SPECT with a scan time of 20 to 30 minutes after tracer administration (AR MCA20–30 or AR cbl20–30) was correlated with AR MCA on PET cerebral blood flow ( r = 0.654) or AR MCA on PET cerebral metabolic rate of oxygen ( r = 0.576), respectively, more strongly than with other scan times. The area under the receiver operating characteristic curve for detecting abnormally elevated AR MCA on PET oxygen extraction fraction was significantly greater for AR cbl20–30/AR MCA20–30 (0.947) than for AR MCA20–30 alone (0.780) (difference between areas, 0.167; P = 0.0001) on 99mTc-ECD SPECT.

          Conclusions

          Combination of asymmetries in the cerebellar and cerebral hemispheres on 99mTc-ECD SPECT in a scan time of 20 to 30 minutes after tracer administration optimally detects misery perfusion in unilateral internal carotid artery or MCA occlusive disease.

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          Most cited references28

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          Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values.

          A method is described for quantifying regional cerebral blood flow (rCBF), oxygen extraction (rOER), and oxygen utilization (rCMRO2) in man non-invasively, using inhaled 15O-labeled CO2 and O2 and positron emission tomography. The theoretical considerations and practical aspects are described. The results of rCBF, rCMRO2, and rOER for gray and white matter in normal volunteers are presented. The significance and limitations of the results are discussed. The method appears suitable for the study of human cerebral aerobic metabolism and blood flow under differing physiological conditions and in a wide variety of neurological disorders.
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            Is misery perfusion still a predictor of stroke in symptomatic major cerebral artery disease?

            Studies in the 1990s demonstrated that misery perfusion is a predictor of subsequent stroke in medically treated patients with symptomatic major cerebral artery disease. A recent randomized controlled trial demonstrated no benefit of bypass surgery for such patients. In this light, outcome in patients with misery perfusion has regained interest. The purpose of this study was to determine whether misery perfusion is still a predictor of subsequent stroke despite recent improvements in medical treatment for secondary prevention of stroke, and if so, whether the predictive value of misery perfusion has changed in recent years. We prospectively studied 165 non-disabled patients with symptomatic atherosclerotic internal carotid artery or middle cerebral artery occlusive diseases who underwent positron emission tomography from 1999 to 2008. Misery perfusion was defined as decreased cerebral blood flow, increased oxygen extraction fraction and decreased ratio of cerebral blood flow to blood volume in the hemisphere supplied by the diseased artery. All patients were followed up for 2 years until stroke recurrence or death. Bypass surgery was performed in 19 of 35 patients with and 16 of 130 patients without misery perfusion. The 2-year incidence of ipsilateral ischaemic stroke was six and four patients with and without misery perfusion, including two and one after surgery, respectively (P < 0.002). Total strokes occurred in nine patients with misery perfusion and 12 patients without (P < 0.01). The relative risk conferred by misery perfusion in whole sample was 6.3 (95% confidence interval 1.7-22.4, P < 0.005) for ipsilateral ischaemic stroke and 3.5 (95% confidence interval 1.4-8.9, P < 0.01) for all strokes, while the respective values in medically treated patients were 12.6 (95% confidence interval 2.7-57.8, P < 0.005) and 4.7 (95% confidence interval 1.3-16.3, P < 0.02). The all-stroke incidence in patients entering the study from 2004 to 2008 (4/72) was significantly lower than in those entering from 1999 to 2003 (17/93; P < 0.02), although the prevalence of misery perfusion or bypass surgery did not differ. Between these periods, patients without misery perfusion demonstrated a decrease in stroke rate (from 16.2% to 0%), but patients with misery perfusion did not (26.3 and 25.0%). In symptomatic major cerebral artery disease, misery perfusion remains a predictor of subsequent stroke, although the recurrence rate was lower than the previous study. In patients without misery perfusion, the risk of stroke was reduced over time. Thus, identification and stricter management of patients with misery perfusion are essential to further improve prognosis.
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              Reversal of focal "misery-perfusion syndrome" by extra-intracranial arterial bypass in hemodynamic cerebral ischemia. A case study with 15O positron emission tomography.

              Tomographic images of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) using the 15O continuous inhalation technique, and positron emission tomography, were obtained from a patient with cerebral ischemia distal to an occluded left internal carotid artery. There was a focal mismatch between CBF and oxygen metabolism in the brain supplied by the middle cerebral artery where CBF was decreased and OEF increased ("misery-perfusion syndrome" as opposed to "luxury-perfusion syndrome"). These abnormalities were most marked in the parieto-occipital watershed area. After left superficial temporal to middle cerebral artery anastomosis, the clinical attacks ceased and a repeat study did not demonstrate the previous CBF and OEF abnormalities. This suggests that this pattern of abnormalities indicates potential viable tissue. The concept of "misery-perfusion" may be of some importance in the pathophysiological mechanisms of hemodynamic cerebral ischemia and serve as a rational basis for revascularization procedures.
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                Author and article information

                Journal
                Clin Nucl Med
                Clin Nucl Med
                RLU
                Clinical Nuclear Medicine
                Lippincott Williams & Wilkins
                0363-9762
                1536-0229
                July 2017
                08 May 2017
                : 42
                : 7
                : 499-505
                Affiliations
                From the Department of Neurosurgery and Cyclotron Research Center, Iwate Medical University, Morioka, Japan.
                Author notes
                Correspondence to: Kuniaki Ogasawara, MD, Department of Neurosurgery, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505 Japan. E-mail: kuogasa@ 123456iwate-med.ac.jp .
                Article
                RLU50883 00001
                10.1097/RLU.0000000000001670
                5464751
                28481786
                c1c2369b-354c-4d8a-9360-02b55089837a
                Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 9 September 2016
                : 27 February 2017
                Page count
                Pages: 0
                Categories
                Original Articles
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                99mtc-ecd,crossed cerebellar hypoperfusion,misery perfusion,spect

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