Imaging Ischemic Tissue at Risk of Infarction during Stroke

Rocco, Richard J. Di; Kuczynski, Bruce L.; Pirro, John P.; Bauer, A.; Linder, Karen E.; Ramalingam, Kondareddiar; Cyr, John E.; Chan, Yee Wai; Raju, Natarajan; Narra, Ramakrishna; Nowotnik, David P.; Nunn, Adrian D.

doi:10.1038/jcbfm.1993.96

Cited by 37 publications

(14 citation statements)

References 20 publications

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“…These results imply that BMS-181321 only localized in areas of severe hypoxia, but not in areas of moderate hypoxia nor in irreversibly damaged tissue. In experiments on cats, BMS-181321 retention was detected by SPECT after 3 hours of MCAO 24 and was further confirmed on ex vivo autoradiograms. Interestingly, early SPECT imaging (immediately postinjection), but not late imaging, appeared to closely approximate CBF.…”

Section: Experimental Stroke Studiesmentioning

confidence: 59%

“…26 One hour after permanent middle cerebral artery occlusion (pMCAO) in rats, the relative uptake of 99m Tc-BMS-181321 in the most affected region was 6.4Ϯ2.2, corresponding to a mean 92% reduction of rCBF. 24 However, comparison of uptake ratios to rCBF on a pixel-by-pixel basis along the edge of this region revealed a gradual increase of uptake from around 50 mL/100g/min (corresponding to the penumbra threshold in that model) and a rapid rise at lower rCBF levels near the infarction threshold ( Figure 2). Importantly, when the tracer was administered 24 hours after pMCAO, no retention was seen in the area of infarction.…”

Section: Experimental Stroke Studiesmentioning

confidence: 86%

“…However, IAZA was injected 2 hours after pMCAO, by which time the entire penumbra perhaps manifested high DWI signal. This later time of administration than in the BMS-181321 study 24 probably accounts for the different behavior of the tracers at very low blood flows, ie, in the BMS study the core still demonstrated maintained cellular machinery for hypoxia tracer binding, whereas viability was probably lost in the IAZA study. 28 Finally, both the BMS and the IAZA studies seem to concur that hypoxia tracers do not show trapping in mildly hypoperfused tissues (ie, the oligemia), although close inspection of the data in Figures 3 and 4 of the IAZA article 28 suggests a mild but definite gradual tracer retention for perfusion values above the penumbra threshold.…”

Section: Takasawa Et Al Hypoxia Imaging In Ischemic Strokementioning

confidence: 89%

“…SPECT hypoxia ligands would therefore be desirable. Iodinated derivatives labeled with 123 I, such as IAZA, 27,28,[57][58][59] and perhaps also 99m Tc-BMS-181321, 24,35 appear promising. On the other hand, the increasingly wider availability of PET in general hospitals for oncology diagnosis may have unexpected implications for hypoxia imaging in stroke.…”

Section: Discussionmentioning

confidence: 99%

“…This heterogeneity precludes any normalization, and hence combined analysis, across studies, and consequently a descriptive approach will be adopted here (see supplemental Table I for details). With only 2 exceptions, 23,24 all of these studies have used ex vivo autoradiography. In gerbils, 17 3 H-misonidazole was shown to have good brain penetration and binding to hypoxic-ischemic tissue in correlation to stroke severity.…”

Section: Experimental Stroke Studiesmentioning

confidence: 99%

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Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic Stroke

Takasawa

Moustafa

Baron

2008

Stroke

107

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Background and Purpose-Nitroimidazole imaging is a promising contender for noninvasive in vivo mapping of brain hypoxia after stroke. However, there is a dearth of knowledge about the behavior of these compounds in the various pathophysiologic situations encountered in ischemic stroke. In this article we report the findings from a systematic review of the literature on the use of the nitroimidazoles to map hypoxia after stroke. Summary of Review-We describe the characteristics of nitroimidazoles as imaging tracers, their pharmacology, and results of both animal and clinical studies during and after focal cerebral ischemia. Findings in brain tumors are also presented to the extent that they enlighten results in stroke. Early results from application of kinetic modeling for quantitative measurement of tracer binding are briefly discussed. Conclusions-Based on this literature review, nitroimidazole hypoxia imaging agents are of considerable interest in stroke because they appear, both in animal models and in humans, to specifically detect the severely hypoxic viable tissue, but not the reperfused nor the necrotic tissue. To fully realize this potential in stroke, however, formal validation by concurrent measurement of tissue oxygen tension, together with development of novel ligands with faster distribution kinetics, faster clearance from normal tissue, and well-defined trapping mechanisms, are important goals for future investigations.

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Section: Experimental Stroke Studiesmentioning

confidence: 59%

Section: Experimental Stroke Studiesmentioning

confidence: 86%

Section: Takasawa Et Al Hypoxia Imaging In Ischemic Strokementioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Stroke Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic Stroke

Takasawa

Moustafa

Baron

2008

Stroke

107

View full text Add to dashboard Cite

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The relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow and hypoxia in an animal stroke model

et al. 1999

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This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc‐hexamethylpropylene amine oxime) and cerebral hypoxia (125I‐iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 ± 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps. Magn Reson Med 41:706–714, 1999. © 1999 Wiley‐Liss, Inc.

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