Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 × 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology.

[1]  A. A. Leão,et al.  SPREADING DEPRESSION OF ACTIVITY IN THE CEREBRAL CORTEX , 1944 .

[2]  J. Goodman Some effects of target-induced scintillation on optical radar performance , 1965 .

[3]  M. Stern,et al.  In vivo evaluation of microcirculation by coherent light scattering , 1975, Nature.

[4]  T. Hougen,et al.  Insulin effects on monovalent cation transport and Na-K-ATPase activity. , 1978, The American journal of physiology.

[5]  L. Sokoloff,et al.  Measurement of local cerebral blood flow with iodo [14C] antipyrine. , 1978, The American journal of physiology.

[6]  R. Nossal,et al.  Model for laser Doppler measurements of blood flow in tissue. , 1981, Applied optics.

[7]  J. Briers,et al.  Flow visualization by means of single-exposure speckle photography , 1981 .

[8]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[9]  W D Heiss,et al.  Functional recovery of cortical neurons as related to degree and duration of ischemia , 1983, Annals of neurology.

[10]  M. Lauritzen On the Possible Relation of Spreading Cortical Depression to Classical Migraine , 1985, Cephalalgia : an international journal of headache.

[11]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[12]  M. Lauritzen,et al.  Cerebral blood flow in migraine and cortical spreading depression. , 1987, Acta neurologica Scandinavica. Supplementum.

[13]  M. Lauritzen,et al.  Regional cerebral blood flow during cortical spreading depression in rat brain: increased reactive hyperperfusion in low‐flow states , 1987, Acta neurologica Scandinavica.

[14]  U. Dirnagl,et al.  Continuous Measurement of Cerebral Cortical Blood Flow by Laser—Doppler Flowmetry in a Rat Stroke Model , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  W D Heiss,et al.  Experimental Evidence of Ischemic Thresholds and Functional Recovery , 1992, Stroke.

[16]  N C Huang,et al.  The evolution of acute stroke recorded by multimodal magnetic resonance imaging. , 1993, Magnetic resonance imaging.

[17]  R D Frostig,et al.  Characterization of functional organization within rat barrel cortex using intrinsic signal optical imaging through a thinned skull. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Mies,et al.  Correlation between peri-infarct DC shifts and ischaemic neuronal damage in rat. , 1993, Neuroreport.

[19]  W. Heiss,et al.  Dynamic Penumbra Demonstrated by Sequential Multitracer PET after Middle Cerebral Artery Occlusion in Cats , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  K. Hossmann Viability thresholds and the penumbra of focal ischemia , 1994, Annals of neurology.

[21]  B Ruth,et al.  Measuring the steady-state value and the dynamics of the skin blood flow using the non-contact laser speckle method. , 1994, Medical engineering & physics.

[22]  M. Lauritzen,et al.  Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex. , 1995, Neuroreport.

[23]  M D Ginsberg,et al.  Induction of Spreading Depression in the Ischemic Hemisphere following Experimental Middle Cerebral Artery Occlusion: Effect on Infarct Morphology , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  J D Briers,et al.  Laser speckle contrast analysis (LASCA): a nonscanning, full-field technique for monitoring capillary blood flow. , 1996, Journal of biomedical optics.

[25]  J. David Briers,et al.  Laser Doppler and time-varying speckle: a reconciliation , 1996 .

[26]  A. Grinvald,et al.  Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[27]  H. Bolay,et al.  Mechanisms of motor dysfunction after transient MCA occlusion: persistent transmission failure in cortical synapses is a major determinant. , 1998, Stroke.

[28]  John A. Detre,et al.  Laser Doppler Imaging of Activation-Flow Coupling in the Rat Somatosensory Cortex , 1999, NeuroImage.

[29]  M D Ginsberg,et al.  The acute ischemic penumbra: topography, life span, and therapeutic response. , 1999, Acta neurochirurgica. Supplement.

[30]  David L. Thomas,et al.  Measuring Cerebral Blood Flow Using Magnetic Resonance Imaging Techniques , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  W D Heiss,et al.  Ischemic Penumbra: Evidence From Functional Imaging in Man , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  P. Enblad,et al.  A metabolic threshold of irreversible ischemia demonstrated by PET in a middle cerebral artery occlusion–reperfusion primate model* , 2000, Acta neurologica Scandinavica.

[33]  O W Witte,et al.  Functional Differentiation of Multiple Perilesional Zones after Focal Cerebral Ischemia , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  M. Shirakashi,et al.  Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry. , 2000, American journal of ophthalmology.