• Tidak ada hasil yang ditemukan

F. Experimental Protocols

VIII. Problems and Perspectives

This book covers the methods for functional brain imaging. Assuming that all neuroimaging approaches are available and one could freely choose one’s instrument, where is the role of near-infrared spectroscopy and imaging? Table 2 gives an overview of advantages and dis- advantages of NIR methods and indicates most likely appli- cations of the method.

The most significant disadvantages are the relatively poor spatial resolution (on the order of centimeters) and the limited depth penetration (probably mostly confined to the cortex). The most important advantages are the biochemical specificity of the signals and the flexibility of the approach.

Table 2

Advantage Disadvantage Research application Potential clinical application

Good temporal resolution Poor spatial resolution Neurovascular coupling (linearity, Assessment of disturbed neurovascular individual determination of coupling in neurological disorders coupling index? etc.)

Biochemically defined Poor depth penetration Functional imaging in babies, Monitoring of cerebral oxygenation in

measurement parameters children comatose patients in intensive care unit

Assessment of intra vascular Susceptibility to artifacts Functional imaging in “natural” Monitoring of tissue at risk during surgery and intracellular metabolic situation (walking, standing, etc.) or after stroke (ischemic penumbra) events and neuronal activity

High flexibility (bedside Add-on information to f MRI and Detection of hematoma (epidural, subdural)

examination) PET studies (Cyt-Ox, fast signals)

Extremely good sensitivity to Molecular imaging in the mouse Molecular imaging in neurological disorders

small concentrations brain

Furthermore, the ability to detect extremely small substance concentrations should give the perspective of an alternative to PET. In rodent studies, cross-sectional optical CT for detection of fluorescent tracers (Ntziachristos and Weissleder, 2001) is feasible; in humans, it is questionable whether information about the entire brain can be obtained;

however, the cortex should also be accessible to molecular studies.

References

Bartocci, M., Winberg, J., Ruggiero, C., Bergqvist, L. L., Serra, G., and Lagercrantz, H. (2000). Activation of olfactory cortex in newborn infants after odor stimulation: A functional near-infrared spectroscopy study. Pediatr. Res. 48, 18–23.

Benaron, D. A., Hintz, S. R., Villringer, A., Boas, D., Kleinschmidt, A., Frahm, J., Hirth, C., Obrig, H., van, H. J., Kermit, E. L., Cheong, W. F., and Stevenson, D. K. (2000). Noninvasive functional imaging of human brain using light. J. Cereb. Blood Flow Metab. 20, 469–477.

Bremer, C., Tung, C. H., and Weissleder, R. (2001). In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat. Med. 7, 743–748.

Buchheim, K., Schuchmann, S., Siegmund, H., Gabriel, H. J., Heinemann, U., and Meierkord, H. (1999). Intrinsic optical signal measurements reveal characteristic features during different forms of spontaneous neu- ronal hyperactivity associated with ECS shrinkage in vitro. Eur. J.

Neurosci. 11, 1877–1882.

Cannestra, A. F., Black, K. L., Martin, N. A., Cloughesy, T., Burton, J. S., Rubinstein, E., Woods, R. P., and Toga, A. W. (1998). Topographical and temporal specificity of human intraoperative optical intrinsic signals.

NeuroReport 9, 2557–2563.

Cheung, C., Culver, J. P., Takahashi, K., Greenberg, J. H., and Yodh, A. G.

(2001). In vivo cerebrovascular measurement combining diffuse near- infrared absorption and correlation spectroscopies. Phys. Med. Biol. 46, 2053–2065.

Colier, W. N., Quaresima, V., Wenzel, R., van der Sluijs, M. C., Oeseburg, B., Ferrari, M., and Villringer, A. (2001). Simultaneous near-infrared spec- troscopy monitoring of left and right occipital areas reveals contra-lateral hemodynamic changes upon hemi-field paradigm. Vision Res. 41, 97–102.

Cope, M., and Delpy, D. T. (1988). System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra- red transillumination. Med. Biol. Eng. Comput. 26, 289–294.

Dirnagl, U., Kaplan, B., Jacewicz, M., and Pulsinelli, W. (1989).

Continuous measurement of cerebral cortical blood flow by laser- Doppler flowmetry in a rat stroke model. J. Cereb. Blood Flow Metab.

9, 589–596.

Dirnagl, U., Villringer, A., Gebhardt, R., Haberl, R. L., Schmiedek, P., and Einhaupl, K. M. (1991). Three-dimensional reconstruction of the rat brain cortical microcirculation in vivo. J. Cereb. Blood Flow Metab. 11, 353–360.

Dreier, J. P., Ebert, N., Priller, J., Megow, D., Lindauer, U., Klee, R., Reuter, U., Imai, Y., Einhaupl, K. M., Victorov, I., and Dirnagl, U.

(2000). Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: A model for delayed ischemic neurological deficits after subarachnoid hemorrhage?

J. Neurosurg. 93, 658–666.

Drexler, W., Morgner, U., Ghanta, R. K., Kartner, F. X., Schuman, J. S., and Fujimoto, J. G. (2001). Ultrahigh-resolution ophthalmic optical coher- ence tomography. Nat. Med. 7, 502–507.

Duncan, A., Meek, J. H., Clemence, M., Elwell, C. E., Tyszczuk, L., Cope, M., and Delpy, D. T. (1995). Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys. Med. Biol. 40, 295–304.

Firbank, M., Okada E., and Deply, D. T. (1998). A theoretical study of the signal contribution of regions of the adult head to near-infrared spec- troscopy studies of visual evoked responses. Neuroimage 8, 69–78.

Fox, P. T., Raichle, M. E., Mintun, M. A., and Dence, C. (1988).

Nonoxidative glucose consumption during focal physiologic neural activity. Science 241, 462–464.

Franceschini, M. A., Moesta, K. T., Fantini, S., Gaida, G., Gratton, E., Jess, H., Mantulin, W. W., Seeber, M., Schlag, P. M., and Kaschke, M. (1997).

Frequency-domain techniques enhance optical mammography: Initial clinical results. Proc. Natl. Acad. Sci. USA 94, 6468–6473.

Fransson, P., Kruger, G., Merboldt, K. D., and Frahm, J. (1998). Temporal characteristics of oxygenation-sensitive MRI responses to visual activa- tion in humans. Magn. Reson. Med. 39, 912–919.

Frostig, R. D., Lieke, E. E., Ts’o, D. Y., and Grinvald, A. (1990). Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc. Natl. Acad. Sci. USA 87, 6082–6086.

Gopinath, S. P., Robertson, C. S., Contant, C. F., Narayan, R. K., Grossman, R. G., and Chance, B. (1995). Early detection of delayed traumatic intracranial hematomas using near-infrared spectroscopy. J. Neurosurg.

83, 438–444.

Gratton, G., Corballis, P. M., Cho, E., Fabiani, M., and Hood, D. C. (1995).

Shades of gray matter: Noninvasive optical images of human brain responses during visual stimulation. Psychophysiology 32, 505–509.

Gratton, G., and Fabiani, M. (2001). The event-related optical signal: A new tool for studying brain function. Int. J. Psychophysiol. 42, 15–27.

Gratton, G., Goodman-Wood, M. R., and Fabiani, M. (2001). Comparison of neuronal and hemodynamic measures of the brain response to visual stimulation: An optical imaging study. Hum. Brain Mapp. 13, 13–25.

Grinvald, A. (1992). Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception. Brain Topogr. 5, 71–75.

Haberl, R. L., Heizer, M. L., and Ellis, E. F. (1989). Laser-Doppler assess- ment of brain microcirculation: Effect of local alterations. Am. J.

Physiol. 256, H1255–H1260.

Haglund, M. M., Ojemann, G. A., and Blasdel, G. G. (1993). Optical imaging of bipolar cortical stimulation. J. Neurosurg. 78, 785–793.

Haller, M., Mironov, S. L., and Richter, D. W. (2001). Intrinsic optical signals in respiratory brain stem regions of mice: Neurotransmitters, neuromodulators, and metabolic stress. J. Neurophysiol. 86, 412–421.

Harms, G. S., Cognet, L., Lommerse, P. H., Blab, G. A., Kahr, H., Gamsjager, R., Spaink, H. P., Soldatov, N. M., Romanin, C., and Schmidt, T. (2001). Single-molecule imaging of L-type Ca(2+) channels in live cells. Biophys. J. 81, 2639–2646.

Heeger, D. J., Huk, A. C., Geisler, W. S., and Albrecht, D. G. (2000). Spikes versus BOLD: What does neuroimaging tell us about neuronal activity?

Nat. Neurosci. 3, 631–633.

Heekeren, H. R., Kohl, M., Obrig, H., Wenzel, R., von Pannwitz, W., Matcher, S. J., Dirnagl, U., Cooper, C. E., and Villringer, A. (1999).

Noninvasive assessment of changes in cytochrome-c oxidase oxidation in human subjects during visual stimulation. J. Cereb. Blood Flow Metab. 19, 592–603.

Hemelt, M. W., and Kang, K. A. (1999). Determination of a biological absorber depth utilizing multiple source-detector separations and multi- ple frequency values of near-infrared time-resolved spectroscopy.

Biotechnol. Prog. 15, 622–629.

Hill, D. K., and Keynes, R. D. (1949). J. Physiol. 108, 278–281.

Hillman, E. M., Hebden, J. C., Schweiger, M., Dehghani, H., Schmidt, F.

E., Delpy, D. T., and Arridge, S. R. (2001). Time resolved optical tomog- raphy of the human forearm. Phys. Med. Biol. 46, 1117–1130.

Hintz, S. R., Benaron, D. A., Siegel, A. M., Zourabian, A., Stevenson, D.

K., and Boas, D. A. (2001). Bedside functional imaging of the prema- ture infant brain during passive motor activation. J. Perinat. Med. 29, 335–343.

Hintz, S. R., Cheong, W. F., van, H. J., Stevenson, D. K., and Benaron, D.

A. (1999). Bedside imaging of intracranial hemorrhage in the neonate using light: Comparison with ultrasound, computed tomography, and magnetic resonance imaging. Pediatr. Res. 45, 54–59.

Hock, C., Muller-Spahn, F., Schuh-Hofer, S., Hofmann, M., Dirnagl, U., and Villringer, A. (1995). Age dependency of changes in cerebral hemo- globin oxygenation during brain activation: A near-infrared spec- troscopy study. J. Cereb. Blood Flow Metab. 15, 1103–1108.

Hock, C., Villringer, K., Muller-Spahn, F., Hofmann, M., Schuh-Hofer, S., Heekeren, H., Wenzel, R., Dirnagl, U., and Villringer, A. (1996). Near infrared spectroscopy in the diagnosis of Alzheimer’s disease. Ann. N. Y.

Acad. Sci. 777, 22–29.

Hock, C., Villringer, K., Muller-Spahn, F., Wenzel, R., Heekeren, H., Schuh-Hofer, S., Hofmann, M., Minoshima, S., Schwaiger, M., Dirnagl, U., and Villringer, A. (1997). Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer’s disease monitored by means of near-infrared spectroscopy (NIRS)—Correlation with simultaneous rCBF–PET measure- ments. Brain Res. 755, 293–303.

Holthoff, K., and Witte, O. W. (1996). Intrinsic optical signals in rat neo- cortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space. J. Neurosci. 16, 2740–2749.

Hoshi, Y., Oda, I., Wada, Y., Ito, Y., Yutaka, Y., Oda, M., Ohta, K., Yamada, Y., and Mamoru, T. (2000). Visuospatial imagery is a fruitful strategy for the digit span backward task: A study with near-infrared optical tomog- raphy. Brain Res. Cognit. Brain Res 9, 339–342.

Hoshi, Y., and Tamura, M. (1993). Dynamic multichannel near-infrared optical imaging of human brain activity. J. Appl. Physiol. 75, 1842–1846.

Igawa, M., Atsumi, Y., Takahashi, K., Shiotsuka, S., Hirasawa, H., Yamamoto, R., Maki, A., Yamashita, Y., and Koizumi, H. (2001).

Activation of visual cortex in REM sleep measured by 24-channel NIRS imaging. Psychiatry Clin. Neurosci. 55, 187–188.

Isobe, K., Kusaka, T., Nagano, K., Okubo, K., Yasuda, S., Kondo, M., Itoh, S., and Onishi, S. (2001). Functional imaging of the brain in sedated newborn infants using near infrared topography during passive knee movement. Neurosci. Lett. 299, 221–224.

Kato, T., Kamei, A., Takashima, S., and Ozaki, T. (1993). Human visual cortical function during photic stimulation monitoring by means of near- infrared spectroscopy. J. Cereb. Blood Flow Metab. 13, 516–520.

Kirkpatrick, P. J., Lam, J., Al-Rawi, P., Smielewski, P., and Czosnyka, M.

(1998). Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J. Neurosurg. 89, 389–394.

Kleinfeld, D., Mitra, P. P., Helmchen, F., and Denk, W. (1998). Fluctuations and stimulus-induced changes in blood flow observed in individual cap- illaries in layers 2 through 4 of rat neocortex. Proc. Natl. Acad. Sci. USA 95, 15741–15746.

Kleinschmidt, A., Obrig, H., Requardt, M., Merboldt, K. D., Dirnagl, U., Villringer, A., and Frahm, J. (1996). Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy. J. Cereb. Blood Flow Metab. 16, 817–826.

Kohl, M., Lindauer, U., Dirnagl, U., and Villringer, A. (1998a). Separation of changes in light scattering and chromophore concentrations during cortical spreading depression in rats. Opt. Lett. 23, 555–557.

Kohl, M., Nolte, C., Heekeren, H. R., Horst, S., Scholz, U., Obrig, H., and Villringer, A. (1998b). Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals. Phys.

Med. Biol. 43, 1771–1782.

Lindauer, U., Royl, G., Leithner, C., Kuhl, M., Gold, L., Gethmann, J., Kohl-Bareis, M., Villringer, A., and Dirnagl, U. (2001). No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. NeuroImage 13, 988–1001.

Lockwood, A. H., LaManna, J. C., Snyder, S., and Rosenthal, M. (1984).

Effects of acetazolamide and electrical stimulation on cerebral oxidative

metabolism as indicated by the cytochrome oxidase redox state. Brain Res. 308, 9–14.

Mackert, B. M., Wubbeler, G., Leistner, S., Trahms, L., and Curio, G.

(2001). Non-invasive single-trial monitoring of human movement- related brain activation based on DC-magnetoencephalography.

NeuroReport 12, 1689–1692.

MacVicar, B. A., and Hochman, D. (1991). Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J. Neurosci. 11, 1458–1469.

Malonek, D., and Grinvald, A. (1996). Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy:

Implications for functional brain mapping. Science 272, 551–554.

Matcher, S. J., and Cooper, C. E. (1994). Absolute quantification of deoxy- haemoglobin concentration in tissue near infrared spectroscopy. Phys.

Med. Biol. 39, 1295–1312.

Mathiesen, C., Caesar, K., Akgoren, N., and Lauritzen, M. (1998).

Modification of activity-dependent increases of cerebral blood flow by excitatory synaptic activity and spikes in rat cerebellar cortex. J.

Physiol. 512, 555–566.

Mayhew, J., Johnston, D., Martindale, J., Jones, M., Berwick, J., and Zheng, Y. (2001). Increased oxygen consumption following activation of brain: Theoretical footnotes using spectroscopic data from barrel cortex. NeuroImage 13, 975–987.

Meek, J. H., Elwell, C. E., Khan, M. J., Romaya, J., Wyatt, J. S., Delpy, D.

T., and Zeki, S. (1995). Regional changes in cerebral haemodynamics as a result of a visual stimulus measured by near infrared spectroscopy.

Proc. R. Soc. London (Biol.) 261, 351–356.

Menon, R. S., Ogawa, S., Hu, X., Strupp, J. P., Anderson, P., and Ugurbil, K. (1995). BOLD based functional MRI at 4 tesla includes a capillary bed contribution: Echo-planar imaging correlates with previous optical imaging using intrinsic signals. Magn. Reson. Med. 33, 453–459.

Miyai, I., Tanabe, H. C., Sase, I., Eda, H., Oda, I., Konishi, I., Tsunazawa, Y., Suzuki, T., Yanagida, T., and Kubota, K. (2001). Cortical mapping of gait in humans: A near-infrared spectroscopic topography study.

NeuroImage 14, 1186–1192.

Nollert, G., Mohnle, P., Tassaniprell, P., and Reichart, B. (1995).

Determinants of cerebral oxygenation during cardiac surgery.

Circulation 92, 327–333.

Nollert, G., Shin, Nagashima, M., and Shum-Tim, D. (1997). Cerebral oxy- genation during cardiopulmonary bypass in children. J. Thoracic Cardiovasc. Surg. 114, 871–873.

Nomura, Y., and Tamura, M. (1991). Quantitative analysis of the hemoglo- bin oxygenation state of rat brain in vivo by picosecond time-resolved spectrophotometry. J. Biochem. Tokyo 109, 455–461.

Ntziachristos, V., and Weissleder, R. (2001). Experimental three-dimen- sional fluorescence reconstruction of diffuse media by use of a normal- ized Born approximation. Opt. Lett. 26, 893–895.

Obrig, H., Israel, H., Kohl-Bareis, M., Uludag K., Wenzel, R., Müller, B., and Villringer, A. (2002). Habituation of the visually evoked potential (VEP) and its vascular response: Implications for neurovascular cou- pling in the healthy adult. Neuroimage, in press.

Obrig, H., Hirth, C., Junge-Hulsing, J. G., Doge, C., Wolf, T., Dirnagl, U., and Villringer, A. (1996). Cerebral oxygenation changes in response to motor stimulation. J. Appl. Physiol. 81, 1174–1183.

Onoe, H., Watanabe, Y., Tamura, M., and Hayaishi, O. (1991). REM sleep-associated hemoglobin oxygenation in the monkey forebrain studied using near-infrared spectrophotometry. Neurosci. Lett. 129, 209–213.

Paus, T., Marrett, S., Worsley, K. J., and Evans, A. C. (1995). Extraretinal modulation of cerebral blood flow in the human visual cortex:

Implications for saccadic suppression. J. Neurophysiol. 74, 2179–2183.

Quaresima, V., Sacco, S., Totaro, R., and Ferrari, M. (2000). Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near infrared spectroscopy approaches. J. Biomed. Opt. 5, 201–205.

Rector, D. M., Poe, G. R., Kristensen, M. P., and Harper, R. M. (1997).

Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation. J. Neurophysiol. 78, 1707–1713.

Rector, D. M., Rogers, R. F., Schwaber, J. S., Harper, R. M., and George, J.

S. (2001). Scattered-light imaging in vivo tracks fast and slow processes of neurophysiological activation. NeuroImage 14, 977–994.

Rees, G., Friston, K., and Koch, C. (2000). A direct quantitative relation- ship between the functional properties of human and macaque V5. Nat.

Neurosci. 3, 716–723.

Röther, J. Knab, R., Hamzei, F., Fiehler, J. R., Buchel, C., and Weiller, C.

(2002). Negative dip in BOLD fMRI is caused by blood flow—oxygen consumption uncoupling in humans. Neuroimage 15, 98–102.

Rumsey, W. L., Vanderkooi, J. M., and Wilson, D. F. (1988). Imaging of phosphorescence: A novel method for measuring oxygen distribution in perfused tissue. Science 241, 1649–1651.

Sakamoto, T., Jonas, R. A., Stock, U. A., Hatsuoka, S., Cope, M., Springett, R. J., and Nollert, G. (2001). Utility and limitations of near-infrared spectroscopy during cardiopulmonary bypass in a piglet model. Pediatr.

Res. 49, 770–776.

Sakatani, K., Xie, Y., Lichty, W., Li, S., and Zuo, H. (1998). Language-acti- vated cerebral blood oxygenation and hemodynamic changes of the left prefrontal cortex in poststroke aphasic patients: A near-infrared spec- troscopy study. Stroke 29, 1299–1304.

Salzberg, B. M., and Obaid, A. L. (1988). Optical studies of the secretory event at vertebrate nerve terminals. J. Exp. Biol. 139, 195–231.

Schmitz, B., Bock, C., Hoehn-Berlage, M., Kerskens, C. M., Bottiger, B.

W., and Hossmann, K. A. (1998). Recovery of the rodent brain after cardiac arrest: A functional MRI study. Magn. Reson. Med. 39, 783–788.

Steinbrink, J., Kohl, M., Obrig, H., Curio, G., Syre, F., Thomas, F., Wabnitz, H., Rinneberg, H., and Villringer, A. (2000). Somatosensory evoked fast optical intensity changes detected non-invasively in the adult human head. Neurosci. Lett. 291, 105–108.

Steinbrink, J., Wabnitz, H., Obrig, H., Villringer, A., and Rinneberg, H.

(2001). Determining changes in NIR absorption using a layered model of the human head. Phys. Med. Biol. 46, 879–896.

Steinhoff, B. J., Herrendorf, G., and Kurth, C. (1996). Ictal near infrared spectroscopy in temporal lobe epilepsy: A pilot study. Seizure 5, 97–101.

Stepnoski, R. A., LaPorta, A., Raccuia-Behling, F., Blonder, G. E., Slusher, R. E., and Kleinfeld, D. (1991). Noninvasive detection of changes in

membrane potential in cultured neurons by light scattering. Proc. Natl.

Acad. Sci. USA 88, 9382–9386.

Toronov, V., Webb, A., Choi, J. H., Wolf, M., Michalos, A., Gratton, E., and Hueber, D. (2001). Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic reso- nance imaging. Med. Phys. 28, 521–527.

Uludag, K., Kohl, M., Steinbrink, J., Obrig, H., and Villringer, A. (2001).

Crosstalk in the Lambert–Beer calculation for near-infrared wavelengths estimated by Monte Carlo simulations. J. Biomed. Opt., 7, 51–59.

Villringer, A., and Chance, B. (1997). Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci. 20, 435–442.

Villringer, A., Haberl, R. L., Dirnagl, U., Anneser, F., Verst, M., and Einhaupl, K. M. (1989). Confocal laser microscopy to study microcir- culation on the rat brain surface in vivo. Brain Res. 504, 159–160.

Villringer, A., Planck, J., Hock, C., Schleinkofer, L., and Dirnagl, U.

(1993). Near infrared spectroscopy (NIRS): A new tool to study hemo- dynamic changes during activation of brain function in human adults.

Neurosci. Lett. 154, 101–104.

Villringer, A., Planck, J., Stodieck, S., Bötzel, K., Schleinkofer, L., and Dirnagl, U. (1994). Noninvasive assessment of cerebral hemodynamics and tissue oxygenation during activation of brain cell function in human adults using near infrared spectroscopy. Adv. Exp. Med. Biol. 345, 559–565.

von Pannwitz, W., Obrig, H., Heekeren, H., Müller, A., Kohl, M., Wolf, T., Wenzel, R., Dirnagl, U., and Villringer, A. (1998). Clinical approaches in near-infrared spectroscopy. In “Transcranial Cerebral Oximetry” (G.

Litscher and G. Schwarz, eds.), pp. 166–183. Pabst Science, Berlin.

Watanabe, E., Maki, A., Kawaguchi, F., Takashiro, K., Yamashita, Y., Koizumi, H., and Mayanagi, Y. (1998). Non-invasive assessment of lan- guage dominance with near-infrared spectroscopic mapping. Neurosci.

Lett. 256, 49–52.

Wenzel, R., Wobst, P., Heekeren, H. H., Kwong, K. K., Brandt, S. A., Kohl, M., Obrig, H., Dirnagl, U., and Villringer, A. (2000). Saccadic suppres- sion induces focal hypooxygenation in the occipital cortex. J. Cereb.

Blood Flow Metab. 20, 1103–1110.

Wobst, P., Wenzel, R., Kohl, M., Obrig, H., and Villringer, A. (2001).

Linear aspects of changes in deoxygenated hemoglobin concentration and cytochrome oxidase oxidation during brain activation. NeuroImage 13, 520–530.

7

Dynamic Measurements

of Local Cerebral Blood Flow:

Examples from Rodent Whisker Barrel Cortex

Thomas A. Woolsey, Ling Wei, and Joseph P. Erinjeri

Departments of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri 63110

I. Why Measure Local Cerebral