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Stroke. 2004;35:351-353
doi: 10.1161/01.STR.0000115163.59487.FD
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(Stroke. 2004;35:351.)
© 2004 American Heart Association, Inc.

Advances in Stroke 2003

Neuroimaging

Steven Warach, MD, PhD Jean-Claude Baron, MD, FRCP, FMedSci

From the National Institute of Neurological Disorders and Stroke (S.W.) National Institutes of Health, Bethesda, MD; and the Department of Neurology (J.-C.B.), University of Cambridge, UK.

Correspondence to Dr. Steven Warach, National Institutes of Health, NINDS, 10 Center Drive, MSC 1063, Building 10, Rm B1D733, Bethesda, MD 20892-4129. E-mail warachs{at}ninds.nih.gov


Key Words: Advances in Stroke • magnetic resonance imaging • stroke • tomography, emission computed

This past year saw a continuing array of reports of MRI and, increasingly, CT approaches to predicting clinical outcomes and tissue infarction from acute anatomical, hemodynamic, and diffusion variables alone or in combination.1–10 Until definitive comparisons among predictive models are undertaken and one is validated on prospective, large, well-controlled samples as predictive of response to therapy, such predictive models—whether the simple perfusion>diffusion mismatch or sophisticated multiparametric models—will be of limited utility for routine clinical decision making. However, selection of patients with diffusion-perfusion patterns predictive of lesion growth has become a strategy in stroke trial design for enriching the sample of subjects most likely to demonstrate a treatment effect, analogous to the routine enrichment strategies of limiting range of age, severity, or stroke subtype. Toward that end, a novel diagnostic classification system was recently described for acute ischemic cerebrovascular syndrome (AICS) that defines the degree of diagnostic certainty by integrating neuroimaging and laboratory data with prior clinically based classification schemes to define 4 categories ranging from definite to not AICS.11 Clinical trials testing new treatments for acute ischemic stroke or secondary stroke prevention may benefit by limiting enrollment to patients with definite AICS whenever feasible.

Adding to the physiological variables measurable by MRI to determine tissue viability is a technique to determine oxygen extraction ratio and cerebral oxygen metabolism based on the sensitivity of susceptibility-weighted MRI (T2* effects) to blood oxygen saturation.12 This study of Lee and colleagues described results in 7 hyperacute stroke patients, demonstrated the feasibility of obtaining oxygen metabolic maps in conjunction with diffusion and perfusion MRI in the hyperacute period, and reported lower oxygen metabolic rates in ischemic brain that goes on to infarct than in regions that do not infarct. Further technical refinements and validation are required to make this a routine tool for acute stroke imaging, but these and metabolite imaging methods by MRI spectroscopy are able to study hyperacute stroke13,14 and are especially favored by the 3 Tesla and higher field strength clinical MRI scanners that are emerging into routine practice.

Mapping the penumbra and core with novel positron-emission tomography (PET) approaches is an area of considerable interest. Using the hypoxia marker 18F-labeled fluoromisonidazole (FMISO), Markus and colleagues validated a quantitative voxel-based 3-dimensional model of high FMISO uptake assumed to represent the penumbra (the "penumbragram") and showed that the evolution of the penumbra occurs from central to peripheral regions as observed in animal models, with the distribution predominately superior and mesial in the cortex.15 In 34 patients with large middle cerebral artery (MCA) stroke, Dohmen and colleagues compared the value of 11C-labeled flumazenil PET mapping of core and penumbra performed within 24 hours of onset, with intensive neuromonitoring including ICP, PtO2, lactate, pyruvate, and glutamate to predict the development of malignant brain swelling.16 Their data clearly show that PET was a better early predictor of malignant MCA infarction than neuromonitoring. Having imaging-based clinically applicable early reliable predictors of malignant MCA infarction would allow craniectomy to be performed within 24 hours to prevent secondary ischemia from increased intracranial pressure.

Studies of silent strokes diagnosed by imaging evidence of infarct without an associated clinical event have become of increasing interest as further evidence accumulates that silent strokes have important clinical implications. A preliminary estimate has indicated that silent ischemic infarcts diagnosed by MRI occur with an incidence as great as 10 times that of symptomatic stroke,17 although prospective longitudinal studies suggest the true incidence of silent strokes may be closer to a 5-fold increase.18 The latter study, the Rotterdam Scan Study, was a prospective serial MRI study of approximately 1000 patients from the general population, aged 60 to 90, without a history of stroke or dementia. Patients with silent brain infarcts and white matter lesions had a >3-fold increased risk of symptomatic stroke independent of other stroke risk factors, compared with those without infarcts on MRI in the general population,18 and patients with silent infarcts at baseline were twice as likely to develop dementia over the subsequent 4 years.19 The presence of silent brain infarcts on the baseline MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function.

New silent strokes diagnosed by diffusion-weighted MRI in the week following a clinical stroke have been found in a substantial proportion of patients.20 In 99 patients scanned within 6 hours of onset of their index clinical stroke, 34 had new distinct ischemic lesions on serial scans performed within the next week, whereas only 2 of those patients had clinically evident stroke. In 15 of these 34 patients, the new lesions were outside the vascular territory of initial symptomatic ischemia. Multiple acute lesions in different vascular territories on the <6-hour MRI were predictive of new lesions over the first week, suggesting state of increased ischemic risk over the first week, and subsequent studies have found that new silent ischemic lesions within the first week predicted further silent strokes over the next 3 months. In summary, silent strokes diagnosed by MRI are a risk for cognitive deficits, dementia, and subsequent strokes, both symptomatic and asymptomatic. Whether the presence of silent infarcts on MRI justifies the aggressive secondary stroke prevention therapy currently reserved for patients with symptomatic stroke will need to be tested in randomized controlled trials.

Imaging of the potentially vulnerable atheromatous carotid plaques has been approached from a variety of imaging modalities. Ultrasound, CT, and MRI have respective advantages and disadvantages for imaging degree of stenosis, intima-media thickness, calcifications, fibrous cap thickness, and lipid core. An inflamed carotid plaque associated with recent clinical events may be imaged with 18F-fluorodeoxyglucose PET,21 and mononuclear inflammatory cells in experimental plaque take up MRI-detectable ultra-small superparamagnetic iron oxide particles (SPIO) injected into the circulation.22 Multimodal MRI has shown the most promise in differentiating the calcifications, fibrous cap, and lipid core of the plaque, which have been related to clinical events, and has 80% to 90% accuracy in identifying histologically confirmed unstable fibrous caps.23 Histologically confirmed hemorrhagic components of the complicated carotid plaque has been identified as high-signal intensity on coronal, fat, suppressed T1-weighted MRI.24 This technique has been shown to distinguish symptomatic from asymptomatic carotid arteries, especially in cases of moderate stenosis.25 The future of clinical in vivo plaque imaging promises molecular probes and targeted contrast agents to further refine the risk of a plaque beyond the percent stenosis and plaque morphology.

The entry and movement of inflammatory cells26 or stem cells27,28 in the brain can potentially be tracked by labeling cells with contrast agents. Cells exogenously labeled with ultrasmall SPIO have been tracked throughout the brain in animal models with MRI. Although not yet studied in humans, this is likely to occur in the near future. In a model of experimental allergic encephalomyelitis, intravenous injection of SPIO particles were taken up by mobile macrophages and other organ-specific phagocytotic cells. Ultrasmall SPIO remain for several days in the lysosomes of macrophages, where they induce a prominent signal increase in T1 and a signal decrease in T2-weighted images.26 Labeling of mesenchymal stem cells and other mammalian cells has been achieved in vitro using commercially available transfection agents and FDA-approved dextran-coated SPIO, and may make this strategy amenable for clinical use.28 Using a similar type of approach to labeling, embryonic stem cells injected contralateral to a cerebral infarct were observed by high-resolution MRI over a 3-week period to migrate across the corpus callosum and accumulate at the boundary of the infarct.27 The techniques have implications for the study of endogenous inflammatory processes in stroke as well as for the assessment of stem cell therapeutic approaches. The next several years may see the development of other molecular imaging approaches with PET as well as MRI to investigate the evolving stroke pathobiology in vivo and guide the development of novel stroke therapies.

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Stroke Association.

Received December 10, 2003; accepted December 11, 2003.

References

  1. Butcher K, Parsons M, Baird T, Barber A, Donnan G, Desmond P, Tress B, Davis S. Perfusion thresholds in acute stroke thrombolysis. Stroke. 2003; 34: 2159–2164.[Abstract/Free Full Text]
  2. Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, Colman PG, Chambers BR, Davis SM. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003; 34: 2208–2214.[Abstract/Free Full Text]
  3. Na DG, Ryoo JW, Lee KH, Moon CH, Yi CA, Kim EY, Lee SJ, Yi BY, Kim JH, Byun HS. Multiphasic perfusion computed tomography in hyperacute ischemic stroke: comparison with diffusion and perfusion magnetic resonance imaging. J Comput Assist Tomogr. 2003; 27: 194–206.[CrossRef][Medline] [Order article via Infotrieve]
  4. Hunter GJ, Silvennoinen HM, Hamberg LM, Koroshetz WJ, Buonanno FS, Schwamm LH, Rordorf GA, Gonzalez RG. Whole-brain CT perfusion measurement of perfused cerebral blood volume in acute ischemic stroke: probability curve for regional infarction. Radiology. 2003; 227: 725–730.[Abstract/Free Full Text]
  5. Croquelois A, Wintermark M, Reichhart M, Meuli R, Bogousslavsky J. Aphasia in hyperacute stroke: language follows brain penumbra dynamics. Ann Neurol. 2003; 54: 321–329.[CrossRef][Medline] [Order article via Infotrieve]
  6. Shih LC, Saver JL, Alger JR, Starkman S, Leary MC, Vinuela F, Duckwiler G, Gobin YP, Jahan R, Villablanca JP, et al. Perfusion-weighted magnetic resonance imaging thresholds identifying core, irreversibly infarcted tissue. Stroke. 2003; 34: 1425–1430.[Abstract/Free Full Text]
  7. Thomalla GJ, Kucinski T, Schoder V, Fiehler J, Knab R, Zeumer H, Weiller C, Rother J. Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging. Stroke. 2003; 34: 1892–1899.[Abstract/Free Full Text]
  8. Singer OC, de Rochemont Rdu M, Foerch C, Stengel A, Lanfermann H, Sitzer M, Neumann-Haefelin T. Relation between relative cerebral blood flow, relative cerebral blood volume, and mean transit time in patients with acute ischemic stroke determined by perfusion-weighted MRI. J Cereb Blood Flow Metab. 2003; 23: 605–611.[CrossRef][Medline] [Order article via Infotrieve]
  9. Liu Y, Karonen JO, Vanninen RL, Nuutinen J, Perkio J, Vainio PA, Soimakallio S, Aronen HJ. Detecting the subregion proceeding to infarction in hypoperfused cerebral tissue: a study with diffusion and perfusion weighted MRI. Neuroradiology. 2003; 45: 345–351.[CrossRef][Medline] [Order article via Infotrieve]
  10. Nighoghossian N, Hermier M, Adeleine P, Derex L, Dugor JF, Philippeau F, Ylmaz H, Honnorat J, Dardel P, Berthezene Y, et al. Baseline magnetic resonance imaging parameters and stroke outcome in patients treated by intravenous tissue plasminogen activator. Stroke. 2003; 34: 458–463.[Abstract/Free Full Text]
  11. Kidwell CS, Warach S. Acute ischemic cerebrovascular syndrome: diagnostic criteria. Stroke. 2003; 34: 2995–2998.[Abstract/Free Full Text]
  12. Lee JM, Vo KD, An H, Celik A, Lee Y, Hsu CY, Lin W. Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients. Ann Neurol. 2003; 53: 227–232.[CrossRef][Medline] [Order article via Infotrieve]
  13. Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, Tress BM, Davis SM. Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002; 52: 20–28.[CrossRef][Medline] [Order article via Infotrieve]
  14. Nicoli F, Lefur Y, Denis B, Ranjeva JP, Confort-Gouny S, Cozzone PJ. Metabolic counterpart of decreased apparent diffusion coefficient during hyperacute ischemic stroke: a brain proton magnetic resonance spectroscopic imaging study. Stroke. 2003; 34: e82–e87.
  15. Markus R, Reutens DC, Kazui S, Read S, Wright P, Chambers BR, Sachinidis JI, Tochon-Danguy HJ, Donnan GA. Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke. Stroke. 2003; 34: 2646–2652.[Abstract/Free Full Text]
  16. Dohmen C, Bosche B, Graf R, Staub F, Kracht L, Sobesky J, Neveling M, Brinker G, Heiss WD. Prediction of malignant course in MCA infarction by PET and microdialysis. Stroke. 2003; 34: 2152–2158.[Abstract/Free Full Text]
  17. Leary MC, Saver JL. Annual incidence of first silent stroke in the United States: a preliminary estimate. Cerebrovasc Dis. 2003; 16: 280–285.[CrossRef][Medline] [Order article via Infotrieve]
  18. Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke. 2003; 34: 1126–1129.[Abstract/Free Full Text]
  19. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003; 348: 1215–1222.[Abstract/Free Full Text]
  20. Kang DW, Latour LL, Chalela JA, Dambrosia J, Warach S. Early ischemic lesion recurrence within a week after acute ischemic stroke. Ann Neurol. 2003; 54: 66–74.[CrossRef][Medline] [Order article via Infotrieve]
  21. Rudd JH, Warburton EA, Fryer TD, Jones HA, Clark JC, Antoun N, Johnstrom P, Davenport AP, Kirkpatrick PJ, Arch BN, et al. Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation. 2002; 105: 2708–2711.[Abstract/Free Full Text]
  22. Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, Frederik PM, Daemen MJ, van Engelshoven JM. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003; 107: 2453–2458.[Abstract/Free Full Text]
  23. Mitsumori LM, Hatsukami TS, Ferguson MS, Kerwin WS, Cai J, Yuan C. In vivo accuracy of multisequence MR imaging for identifying unstable fibrous caps in advanced human carotid plaques. J Magn Reson Imaging. 2003; 17: 410–420.[CrossRef][Medline] [Order article via Infotrieve]
  24. Moody AR, Murphy RE, Morgan PS, Martel AL, Delay GS, Allder S, MacSweeney ST, Tennant WG, Gladman J, Lowe J, Hunt BJ. Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia. Circulation. 2003; 107: 3047–3052.[Abstract/Free Full Text]
  25. Murphy RE, Moody AR, Morgan PS, Martel AL, Delay GS, Allder S, MacSweeney ST, Tennant WG, Gladman J, Lowe J, Hunt BJ. Prevalence of complicated carotid atheroma as detected by magnetic resonance direct thrombus imaging in patients with suspected carotid artery stenosis and previous acute cerebral ischemia. Circulation. 2003; 107: 3053–3058.[Abstract/Free Full Text]
  26. Rausch M, Hiestand P, Baumann D, Cannet C, Rudin M. MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE. Magn Reson Med. 2003; 50: 309–314.[CrossRef][Medline] [Order article via Infotrieve]
  27. Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK, et al. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci U S A. 2002; 99: 16267–16272.[Abstract/Free Full Text]
  28. Frank JA, Miller BR, Arbab AS, Zywicke HA, Jordan EK, Lewis BK, Bryant LH Jr, Bulte JW. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 2003; 228: 480–487.[Abstract/Free Full Text]



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