Linear response range characterization and in vivo application of laser speckle imaging of blood flow dynamics.

Noninvasive blood flow imaging can provide critical information on the state of biological tissue and the efficacy of approaches to treat disease. With laser speckle imaging (LSI), relative changes in blood flow are typically reported, with the assumption that the measured values are on a linear scale. A linear relationship between the measured and actual flow rate values has been suggested. The actual flow rate range, over which this linear relationship is valid, is unknown. Herein we report the linear response range and velocity dynamic range (VDR) of our LSI instrument at two relevant camera integration times. For integration times of 1 and 10 ms, the best case VDR was 80 and 60 dB, respectively, and the worst case VDR was 20 and 50 dB. The best case VDR values were similar to those reported in the literature for optical Doppler tomography. We also demonstrate the potential of LSI for monitoring blood flow dynamics in the rodent dorsal skinfold chamber model. These findings imply that LSI can provide accurate wide-field maps of microvascular blood flow rate dynamics and highlight heterogeneities in flow response to the application of exogenous agents.

[1]  Bernard Choi,et al.  Optical clearing of in vivo human skin: Implications for light‐based diagnostic imaging and therapeutics , 2004, Lasers in surgery and medicine.

[2]  M. Dewhirst,et al.  Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development. , 2005, Journal of biomedical optics.

[3]  T. W. Ridler,et al.  Picture thresholding using an iterative selection method. , 1978 .

[4]  J. Cracowski,et al.  Local hyperhemia to heating is impaired in secondary Raynaud's phenomenon , 2005, Arthritis research & therapy.

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

[6]  Xiao-Xin Li,et al.  Fundus and histopathological study of radial optic neurotomy in the normal miniature pig eye. , 2005, Archives of ophthalmology.

[7]  Siavash Yazdanfar,et al.  Phase-referenced Doppler optical coherence tomography in scattering media. , 2005, Optics letters.

[8]  Shaoqun Zeng,et al.  Hyperosmotic chemical agent's effect on in vivo cerebral blood flow revealed by laser speckle. , 2004, Applied optics.

[9]  Dai Fukumura,et al.  Dissecting tumour pathophysiology using intravital microscopy , 2002, Nature Reviews Cancer.

[10]  J. Nelson,et al.  Characterization of fluid flow velocity by optical Doppler tomography. , 1995, Optics letters.

[11]  J D Briers,et al.  Capillary Blood Flow Monitoring Using Laser Speckle Contrast Analysis (LASCA). , 1999, Journal of biomedical optics.

[12]  Zhongping Chen,et al.  Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media. , 1997, Optics letters.

[13]  J. Barton,et al.  Flow measurement without phase information in optical coherence tomography images. , 2005, Optics express.

[14]  Bernard Choi,et al.  Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens , 2006, Lasers in surgery and medicine.

[15]  Anna Devor,et al.  Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging. , 2005, Applied optics.

[16]  W. Ferrell,et al.  Pathophysiology of vascular dysfunction in a rat model of chronic joint inflammation , 2004, The Journal of physiology.

[17]  R. D. Ferguson,et al.  Wide-field retinal hemodynamic imaging with the tracking scanning laser ophthalmoscope. , 2004, Optics express.

[18]  M. Dewhirst,et al.  Intravital Fluorescence Facilitates Measurement of Multiple Physiologic Functions and Gene Expression in Tumors of Live Animals , 2003, Disease markers.

[19]  Christoph Abels,et al.  Selective photothermolysis of blood vessels following flashlamp-pumped pulsed dye laser irradiation: in vivo results and mathematical modelling are in agreement. , 2005, The Journal of investigative dermatology.

[20]  J. Goodman Statistical Optics , 1985 .

[21]  Julius Pekar,et al.  High speed, wide velocity dynamic range Doppler optical coherence tomography (Part I): System design, signal processing, and performance. , 2003, Optics express.

[22]  M. Moskowitz,et al.  Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  Q. Luo,et al.  Modified laser speckle imaging method with improved spatial resolution. , 2003, Journal of biomedical optics.

[24]  M. Dewhirst,et al.  Targeting tumor microvessels using doxorubicin encapsulated in a novel thermosensitive liposome. , 2004, Molecular cancer therapeutics.

[25]  S. Yun,et al.  Phase-resolved optical frequency domain imaging. , 2005, Optics express.

[26]  J Izatt,et al.  Investigating pulsed dye laser-blood vessel interaction with color Doppler optical coherence tomography. , 1998, Optics express.

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

[28]  Charles E. Riva,et al.  Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina , 2005, Progress in Retinal and Eye Research.

[29]  P. Cabrales,et al.  Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution. , 2005, American journal of physiology. Heart and circulatory physiology.

[30]  Zhihua Ding,et al.  Phase-resolved functional optical coherence tomography: simultaneous imaging of in situ tissue structure, blood flow velocity, standard deviation, birefringence, and Stokes vectors in human skin. , 2002, Optics letters.

[31]  Gracie Vargas,et al.  Morphological Changes in Blood Vessels Produced by Hyperosmotic Agents and Measured by Optical Coherence Tomography¶ , 2003, Photochemistry and photobiology.

[32]  Dai Fukumura,et al.  Peritumor Lymphatics Induced by Vascular Endothelial Growth Factor-C Exhibit Abnormal Function , 2004, Cancer Research.

[33]  Arthur W Toga,et al.  Spatiotemporal Evolution of Functional Hemodynamic Changes and Their Relationship to Neuronal Activity , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  Victor X D Yang,et al.  Interstitial Doppler optical coherence tomography. , 2005, Optics letters.

[35]  Anders M. Dale,et al.  Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex , 2005, NeuroImage.

[36]  Bernard Choi,et al.  Laser speckle imaging for monitoring blood flow dynamics in the in vivo rodent dorsal skin fold model. , 2004, Microvascular research.

[37]  W. Goto,et al.  Effects of adenosine on optic nerve head circulation in rabbits. , 2004, Experimental eye research.

[38]  Kevin R. Forrester,et al.  A laser speckle imaging technique for measuring tissue perfusion , 2004, IEEE Transactions on Biomedical Engineering.