Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma

PURPOSE Altered metabolic activity has been identified as a potential contributing factor to the neurodegeneration associated with primary open angle glaucoma (POAG). Consequently, we sought to determine whether there is a relationship between the loss of visual function in human glaucoma and resting blood perfusion within primary visual cortex (V1). METHODS Arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10 participants with POAG. Resting cerebral blood flow (CBF) was measured from dorsal and ventral V1. Behavioral measurements of visual function were obtained using standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF were compared to differences in visual function for the superior and inferior hemifield. RESULTS Differences in CBF between ventral and dorsal V1 were correlated with differences in visual function for the superior versus inferior visual field. A statistical bootstrapping analysis indicated that the observed correlations between fMRI responses and measurements of visual function for SAP (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all p<0.05). CONCLUSIONS Resting blood perfusion in human V1 is correlated with the loss of visual function in POAG. Altered CBF may be a contributing factor to glaucomatous optic neuropathy, or it may be an indication of post-retinal glaucomatous neurodegeneration caused by damage to the retinal ganglion cells.

[1]  F A Miles,et al.  Initiation of saccades during fixation or pursuit: evidence in humans for a single mechanism. , 1996, Journal of neurophysiology.

[2]  F. Medeiros,et al.  Relationship of SITA and full-threshold standard perimetry to frequency-doubling technology perimetry in glaucoma. , 2005, Investigative ophthalmology & visual science.

[3]  R. Buxton,et al.  Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II) , 1998 .

[4]  P. Sample,et al.  Short-wavelength automated perimetry. , 2003, Ophthalmology clinics of North America.

[5]  P. Kaufman,et al.  Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. , 2000, Archives of ophthalmology.

[6]  J. Yamagami,et al.  Visual Field Damage in Normal-tension Glaucoma Patients With or Without Ischemic Changes in Cerebral Magnetic Resonance Imaging , 2004, Japanese Journal of Ophthalmology.

[7]  T. Hirai,et al.  MR changes in the calcarine area resulting from retinal degeneration. , 1997, AJNR. American journal of neuroradiology.

[8]  J. Morrison,et al.  Magnocellular and parvocellular visual pathways are both affected in a macaque monkey model of glaucoma. , 1997, Australian and New Zealand journal of ophthalmology.

[9]  Gregory G. Brown,et al.  BOLD and Perfusion Response to Finger-Thumb Apposition after Acetazolamide Administration: Differential Relationship to Global Perfusion , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  E C Wong,et al.  Comparison of simultaneously measured perfusion and BOLD signal increases during brain activation with T1‐based tissue identification , 2000, Magnetic resonance in medicine.

[11]  J. Flammer,et al.  Autoregulation, a balancing act between supply and demand. , 2008, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[12]  M. Stern,et al.  Comparative study of brain magnetic resonance imaging findings in patients with low-tension glaucoma and control subjects. , 1997, Ophthalmology.

[13]  G. Aguirre,et al.  Experimental Design and the Relative Sensitivity of BOLD and Perfusion fMRI , 2002, NeuroImage.

[14]  T. Kansu,et al.  Visual Recovery Patterns in Children with Leber's Hereditary Optic Neuropathy , 2004, International Ophthalmology.

[15]  M. C. Leske,et al.  Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings , 2009, Current opinion in ophthalmology.

[16]  M. Kaiser-Kupfer,et al.  Association of visual field, cup-disc ratio, and magnetic resonance imaging of optic chiasm. , 1997, Archives of ophthalmology.

[17]  G. Bruce Pike,et al.  The effect of global cerebral vasodilation on focal activation hemodynamics , 2006, NeuroImage.

[18]  R S Harwerth,et al.  Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways. , 2000, Investigative ophthalmology & visual science.

[19]  Robert N Weinreb,et al.  Diagnostic accuracy of the Matrix 24-2 and original N-30 frequency-doubling technology tests compared with standard automated perimetry. , 2008, Investigative ophthalmology & visual science.

[20]  Mark S. Cohen,et al.  Simultaneous EEG and fMRI of the alpha rhythm , 2002, Neuroreport.

[21]  Ravi Thomas,et al.  Primary open angle glaucoma. , 1990, The National medical journal of India.

[22]  Robert N Weinreb,et al.  Retinotopic organization of primary visual cortex in glaucoma: a method for comparing cortical function with damage to the optic disk. , 2007, Investigative ophthalmology & visual science.

[23]  R. Weinreb,et al.  Comparison of high-pass resolution perimetry and standard automated perimetry in glaucoma. , 1995, American journal of ophthalmology.

[24]  J. Detre,et al.  Arterial spin labeling perfusion fMRI with very low task frequency , 2003, Magnetic resonance in medicine.

[25]  A. Dale,et al.  Functional analysis of primary visual cortex (V1) in humans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Flanders Conventional MRI and magnetisation transfer imaging of the brain and optic pathway in primary open-angle glaucoma , 2010 .

[27]  Christine C. Boucard,et al.  Changes in cortical grey matter density associated with long-standing retinal visual field defects , 2009, Brain : a journal of neurology.

[28]  J W Belliveau,et al.  Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. , 1995, Science.

[29]  Seong-Gi Kim Quantification of relative cerebral blood flow change by flow‐sensitive alternating inversion recovery (FAIR) technique: Application to functional mapping , 1995, Magnetic resonance in medicine.

[30]  M. Brodsky,et al.  Magnetic resonance imaging of the visual pathways in human albinos. , 1993, Journal of pediatric ophthalmology and strabismus.

[31]  Leopold Schmetterer,et al.  The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma. , 2011, Experimental eye research.

[32]  E. DeYoe,et al.  Functional magnetic resonance imaging (FMRI) of the human brain , 1994, Journal of Neuroscience Methods.

[33]  Thomas T. Liu,et al.  A signal processing model for arterial spin labeling functional MRI , 2005, NeuroImage.

[34]  K. Golnik,et al.  Magnetic resonance imaging in patients with low-tension glaucoma. , 1995, Archives of ophthalmology.

[35]  I. Narabayashi,et al.  Comparative study of cerebral blood flow in patients with normal-tension glaucoma and control subjects. , 2006, American journal of ophthalmology.

[36]  Robert O. Duncan,et al.  Cortical Magnification within Human Primary Visual Cortex Correlates with Acuity Thresholds , 2003, Neuron.

[37]  M. Sherwood,et al.  Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia. , 2004, Investigative ophthalmology & visual science.

[38]  A Ralph Henderson,et al.  The bootstrap: a technique for data-driven statistics. Using computer-intensive analyses to explore experimental data. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[39]  P. Kaufman,et al.  Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma , 2003, Progress in Retinal and Eye Research.

[40]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[41]  D. Gaasterland,et al.  Investigative Ophthalmology & Visual Science , 1978 .

[42]  Thomas T. Liu,et al.  Physiological noise reduction for arterial spin labeling functional MRI , 2006, NeuroImage.

[43]  D. Budenz,et al.  Ocular Perfusion Pressure and Glaucoma , 2011, International ophthalmology clinics.

[44]  T. Sugiyama,et al.  A pilot study for the effects of donepezil therapy on cerebral and optic nerve head blood flow, visual field defect in normal-tension glaucoma. , 2010, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[45]  P. Kaufman,et al.  Experimental glaucoma and cell size, density, and number in the primate lateral geniculate nucleus. , 2000, Investigative ophthalmology & visual science.

[46]  Vision Research , 1961, Nature.

[47]  R S Harwerth,et al.  Experimental glaucoma in primates: changes in cytochrome oxidase blobs in V1 cortex. , 2001, Investigative ophthalmology & visual science.

[48]  Irene Tracey,et al.  Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: Implications for clinical trial design , 2005, NeuroImage.

[49]  Abraham Z. Snyder,et al.  Assessing optic nerve pathology with diffusion MRI: from mouse to human , 2008, NMR in biomedicine.

[50]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Ryo Kawasaki,et al.  Vascular risk factors in glaucoma: a review , 2011, Clinical & experimental ophthalmology.

[52]  Adrian T. Lee,et al.  fMRI of human visual cortex , 1994, Nature.

[53]  Jeroen van der Grond,et al.  Occipital Proton Magnetic Resonance Spectroscopy (1H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects , 2007, PloS one.

[54]  Hongxia Ren,et al.  Functional, Perfusion and Diffusion MRI of acute Focal Ischemic Brain Injury , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[55]  Linda M Zangwill,et al.  Noninvasive measurement of the cerebral blood flow response in human lateral geniculate nucleus with arterial spin labeling fMRI , 2008, Human brain mapping.

[56]  J. Flanagan,et al.  Vascular Reactivity of Optic Nerve Head and Retinal Blood Vessels in Glaucoma—A Review , 2010, Microcirculation.

[57]  R. Weinreb Ocular blood flow in glaucoma. , 2009, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[58]  P. Kaufman,et al.  Atrophy of relay neurons in magno- and parvocellular layers in the lateral geniculate nucleus in experimental glaucoma. , 2001, Investigative ophthalmology & visual science.

[59]  Tim Hesterberg,et al.  Bootstrap Methods and Permutation Tests* 14.1 the Bootstrap Idea 14.2 First Steps in Using the Bootstrap 14.3 How Accurate Is a Bootstrap Distribution? 14.4 Bootstrap Confidence Intervals 14.5 Significance Testing Using Permutation Tests Introduction , 2004 .

[60]  N Fujita,et al.  Lateral geniculate nucleus: anatomic and functional identification by use of MR imaging. , 2001, AJNR. American journal of neuroradiology.

[61]  D H Brainard,et al.  The Psychophysics Toolbox. , 1997, Spatial vision.

[62]  Chris A. Johnson,et al.  Performance of efficient test procedures for frequency-doubling technology perimetry in normal and glaucomatous eyes. , 2002, Investigative ophthalmology & visual science.

[63]  A. Vingrys,et al.  The role of blood pressure in glaucoma , 2011, Clinical & experimental optometry.

[64]  K. Kashiwagi,et al.  Association of Magnetic Resonance Imaging of Anterior Optic Pathway with Glaucomatous Visual Field Damage and Optic Disc Cupping , 2004, Journal of glaucoma.

[65]  G. Crelier,et al.  Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Christopher Bowd,et al.  Retinotopic organization of primary visual cortex in glaucoma: Comparing fMRI measurements of cortical function with visual field loss , 2007, Progress in Retinal and Eye Research.

[67]  M. Bach,et al.  Retrobulbar optic nerve diameter measured by high-speed magnetic resonance imaging as a biomarker for axonal loss in glaucomatous optic atrophy. , 2009, Investigative ophthalmology & visual science.

[68]  G. Glover,et al.  Retinotopic organization in human visual cortex and the spatial precision of functional MRI. , 1997, Cerebral cortex.

[69]  Robert N Weinreb,et al.  Identifying glaucomatous vision loss with visual-function-specific perimetry in the diagnostic innovations in glaucoma study. , 2006, Investigative ophthalmology & visual science.

[70]  Timothy Q. Duong,et al.  Blood-flow magnetic resonance imaging of the retina , 2008, NeuroImage.

[71]  D G Pelli,et al.  The VideoToolbox software for visual psychophysics: transforming numbers into movies. , 1997, Spatial vision.

[72]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[73]  E. Wu,et al.  Proton magnetic resonance spectroscopy revealed choline reduction in the visual cortex in an experimental model of chronic glaucoma. , 2009, Experimental eye research.

[74]  A. Flanders,et al.  Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging , 2009 .