Identifying hypoxic tissue after acute ischemic stroke using PET and
            <sup>18</sup>
            F-fluoromisonidazole

Read, Stephen; Hirano, Teruyuki; Abbott, David F.; Sachinidis, John; Tochon-Danguy, Henri; Chan, Jasmine; Egan, Gary F.; Scott, Andrew M.; Bladin, Christopher; McKay, W J; Donnan, Geoffrey A

doi:10.1212/wnl.51.6.1617

Cited by 119 publications

(82 citation statements)

References 7 publications

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“…These results were confirmed in a larger study by Read et al in 1998 [37] : in 9 cases, FMISO-trapping was detected 6.25-42.5 h after stroke onset, but was absent in later examinations. Tissue with increased FMISO uptake was usually present in the periphery of the infarct identified on the co-registered late CT, but extended into normal tissue adjacent to the infarct in a few cases.…”

Section: Detection Of Hypoxic Tissuesupporting

confidence: 74%

PET imaging in ischemic cerebrovascular disease: current status and future directions

Heiss

2014

Neurosci. Bull.

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Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the fl ow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the fi nal infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinfl ammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.

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Section: Detection Of Hypoxic Tissuesupporting

confidence: 74%

PET imaging in ischemic cerebrovascular disease: current status and future directions

Heiss

2014

Neurosci. Bull.

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“…This zone of high activity had disappeared when imaging was performed during the chronic phase, indicating that the hypoxic tissue had either infarcted or recovered. This pattern and time course was confirmed in a larger study (60). 18 F-fluoromisonidazole trapping detected 6.25-42.5 h after stroke onset was distributed over the periphery of the infarct and extended into normal tissue.…”

Section: Noninvasive Imaging Of the Penumbrasupporting

confidence: 54%

Radionuclide Imaging in Ischemic Stroke

Heiss

2014

J Nucl Med

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) the physiologic and metabolic variables relevant for brain function and the radionuclides and methods to measure these variables in cerebrovascular disease, especially ischemic stroke; (2) the radionuclide methods to determine the thresholds of flow and metabolism relevant for preservation of function and morphology and the obtained values in their relevance to prognosis and potential treatment; and (3) the applications of radionuclide imaging for identifying pathophysiologic changes responsible for extension of ischemic lesions, for defining the hemodynamic reserve in vascular disease, for detecting remote effects outside the primary lesions, and for locating compensatory activation in disturbed functional networks.Financial Disclosure: Dr. Heiss is supported by the Wolf-Dieter Heiss Foundation within the Max Planck Society. The author of this article has indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through November 2017.Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the...

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“…5,6 Positron emission tomography (PET) using 15 O identifies areas of misery perfusion in a patient with acute ischemic stroke. 7,8 18 F-fluoromisonidazole (FMISO) is a PET marker of hypoxic but viable tissue that exists in an acute ischemic area in the human brain, [9][10][11][12] and areas with uptake of the tracer reportedly are metabolically compromised tissue at risk of infarction after acute ischemic stroke. 9,10,12 The mechanism of selective retention of 2-nitroimidazoles, including FMISO, in hypoxic tissue is not clearly understood but may involve nitroreductases.…”

mentioning

confidence: 99%

Hypoxic Viable Tissue in Human Chronic Cerebral Ischemia Because of Unilateral Major Cerebral Artery Steno-Occlusive Disease

Saura

Ogasawara

Beppu

et al. 2015

Stroke

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Background and Purpose— Positron emission tomography (PET) with radiolabeled 2-nitroimidazoles directly detects hypoxic but viable tissue present in an acute ischemic area in the human brain. This study using PET with 1-(2- 18 F-fluoro-1-[hydroxymethyl]ethoxy) methyl-2-nitroimidazole ( 18 F-FRP170) aimed to determine whether tissue with an abnormally elevated uptake of 18 F-FRP170 exists in human chronic cerebral ischemia because of unilateral atherosclerotic major cerebral artery steno-occlusive disease. Methods— 18 F-FRP170 PET was performed, and cerebral blood flow and metabolism were assessed using 15 O-gas PET in 20 healthy subjects and 52 patients. A region of interest (ROI) was automatically placed in 3 segments of the middle cerebral artery territory in both cerebral hemispheres with a 3-dimensional stereotaxic ROI template using SPM2, and each PET value was determined in each ROI. The ratio of values in the affected versus contralateral hemispheres was calculated for the 18 F-FRP170 PET image. Results— A significant correlation was observed between oxygen extraction fraction and 18 F-FRP170 ratios ( ρ =0.509; P <0.0001) in a total of 156 ROIs in 52 patients. The specificity and positive-predictive value for a combination of an elevated oxygen extraction fraction and a moderately reduced cerebral oxygen metabolism for detection of an abnormally elevated 18 F-FRP170 ratio (19 ROIs: 12%) were significantly greater than those for the individual categories (elevated oxygen extraction fraction, moderately reduced cerebral oxygen metabolism, or reduced cerebral blood flow). Conclusions— Tissues with abnormally elevated uptake of 18 F-FRP170 exist in human chronic cerebral ischemia characterized by a combination of misery perfusion and moderately reduced oxygen metabolism because of unilateral atherosclerotic major cerebral artery steno-occlusive disease.

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Identifying hypoxic tissue after acute ischemic stroke using PET and ¹⁸ F-fluoromisonidazole

Abstract: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).

Cited by 119 publications

References 7 publications

PET imaging in ischemic cerebrovascular disease: current status and future directions

PET imaging in ischemic cerebrovascular disease: current status and future directions

Radionuclide Imaging in Ischemic Stroke

Hypoxic Viable Tissue in Human Chronic Cerebral Ischemia Because of Unilateral Major Cerebral Artery Steno-Occlusive Disease

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Identifying hypoxic tissue after acute ischemic stroke using PET and 18 F-fluoromisonidazole

Abstract: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).

Cited by 119 publications

References 7 publications

PET imaging in ischemic cerebrovascular disease: current status and future directions

PET imaging in ischemic cerebrovascular disease: current status and future directions

Radionuclide Imaging in Ischemic Stroke

Hypoxic Viable Tissue in Human Chronic Cerebral Ischemia Because of Unilateral Major Cerebral Artery Steno-Occlusive Disease

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Identifying hypoxic tissue after acute ischemic stroke using PET and ¹⁸ F-fluoromisonidazole