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Cited by 49Optical Imaging and Spectroscopy TechniquesAdvanced Fluorescence Microscopy TechniquesCellular Mechanics and Interactions

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Microfiberoptic Measurement of Extracellular Space Volume in Brain and Tumor Slices Based on Fluorescent Dye Partitioning

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Zhang, Hua, Verkman, A.S.·2010·Biophysical Journal
DOI 10.1016/j.bpj.2010.06.023PMC PMC2920647
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Abstract

The fractional volume occupied by extracellular space in tissues, termed alpha, is an important parameter of tissue architecture that affects cellular functions and drug delivery. We report a technically simple fluorescent dye partitioning method to measure alpha in tissue slices based on microfiberoptic detection of dye fluorescence in tissue versus overlying solution. Microfiberoptic tip geometry and dyes were selected for alpha determination from fluorescence intensity ratios, without the need to correct for illumination profile, light scattering/absorption, or dye binding. The method was validated experimentally using cell-embedded gels of specified alpha-values and optical properties. In mouse brain slices, alpha was strongly location-dependent, ranging from 0.16 in thalamus to 0.22 in brainstem, and was sensitive to cell volume changes. Aquaporin-4 water channel gene deletion caused significant extracellular space expansion, with alpha = 0.181 +/- 0.002 in cortex in wild-type mice and 0.211 +/- 0.003 in Aquaporin-4 knockout mice. In slices of LLC1 cell tumors grown in mice to approximately 5 mm diameter, alpha decreased remarkably from approximately 0.45 in superficial tumor to <0.25 in deeper (>100 mum) tumor. Fluorescent dye partitioning with microfiberoptic detection permits rapid, accurate, and anisotropy-insensitive determination of alpha-values in tissue slices.

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  • The distribution of light intensity in agarose brain phantom gels was well approximated by a hemispherical Gaussian distribution.

    “We validated our methodology by measuring the diffusion of FITC–dextrans of various molecular weights in agarose ‘brain phantom’ gels, modified to approximate the light-scattering and optical-absorption properties of brain tissue22 and found (Extended Data Fig. 1) that the distribution of light intensity was well approximated by a hemispherical Gaussian distribution.”

    From Brain clearance is reduced during sleep and anesthesia (2024) · cites this paper as [22]

    The Experimental validation section measures brain-tissue scattering and absorption and tests their effects on fluorescence, but does not describe a hemispherical Gaussian light-intensity distribution in agarose gels. Searches for that distribution and for optically modified agarose phantoms found no supporting passage. In the citing sentence, citation 22 appears attached to the brain-tissue optical properties; the Gaussian finding is presented as the citing authors’ own result. (LLM, conf=0.76)

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Research works printed but not linked: 39

  1. Syková, 2008, Diffusion in brain extracellular space, Physiol. Rev., 88, 1277, 10.1152/physrev.00027.2007 · DOI · Paper page
  2. Jain, 1997, Delivery of molecular and cellular medicine to solid tumors, Adv. Drug Deliv. Rev., 26, 71, 10.1016/S0169-409X(97)00027-6 · DOI
  3. Law, 1982, Techniques and applications of extracellular space determination in mammalian tissues, Experientia, 38, 411, 10.1007/BF01952615 · DOI
  4. Syková, 2004, Diffusion properties of the brain in health and disease, Neurochem. Int., 45, 453, 10.1016/j.neuint.2003.11.009 · DOI
  5. Nicholson, 1998, Extracellular space structure revealed by diffusion analysis, Trends Neurosci., 21, 207, 10.1016/S0166-2236(98)01261-2 · DOI · Paper page
  6. Nicholson, 1981, Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum, J. Physiol., 321, 225, 10.1113/jphysiol.1981.sp013981 · DOI
  7. Rosenberg, 1962, Extracellular space estimation in rat kidney slices using C saccharides and phlorizin, Am. J. Physiol., 202, 800, 10.1152/ajplegacy.1962.202.4.800 · DOI
  8. Jackson, 1970, Studies on intestinal fluid transport. I. Estimation of the extracellular space of everted sacs of rat small intestine, Biochim. Biophys. Acta, 211, 425, 10.1016/0005-2736(70)90248-8 · DOI
  9. Thiagarajah, 2006, Slowed diffusion in tumors revealed by microfiberoptic epifluorescence photobleaching, Nat. Methods, 3, 275, 10.1038/nmeth863 · DOI
  10. Magzoub, 2009, Extracellular space volume measured by two-color pulsed dye infusion with microfiberoptic fluorescence photodetection, Biophys. J., 96, 2382, 10.1016/j.bpj.2008.12.3916 · DOI
  11. Ma, 1997, Generation and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4, J. Clin. Invest., 100, 957, 10.1172/JCI231 · DOI
  12. Zador, 2008, Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain, FASEB J., 22, 870, 10.1096/fj.07-9468com · DOI
  13. Choi, 1988, Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1, 623, 10.1016/0896-6273(88)90162-6 · DOI
  14. Verkman, 2006, Three distinct roles of aquaporin-4 in brain function revealed by knockout mice, Biochim. Biophys. Acta, 1758, 1085, 10.1016/j.bbamem.2006.02.018 · DOI
  15. Binder, 2006, Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels, Glia, 53, 631, 10.1002/glia.20318 · DOI
  16. Yao, 2008, Aquaporin-4-deficient mice have increased extracellular space without tortuosity change, J. Neurosci., 28, 5460, 10.1523/JNEUROSCI.0257-08.2008 · DOI
  17. Blasberg, 1975, Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion, J. Pharmacol. Exp. Ther., 195, 73, 10.1016/S0022-3565(25)30311-3 · DOI
  18. Levin, 1970, Sucrose and inulin space measurements of cerebral cortex in four mammalian species, Am. J. Physiol., 219, 1528, 10.1152/ajplegacy.1970.219.5.1528 · DOI
  19. Rice, 1991, Diffusion characteristics and extracellular volume fraction during normoxia and hypoxia in slices of rat neostriatum, J. Neurophysiol., 65, 264, 10.1152/jn.1991.65.2.264 · DOI
  20. Mazel, 1998, Diffusion heterogeneity and anisotropy in rat hippocampus, Neuroreport, 9, 1299, 10.1097/00001756-199805110-00008 · DOI
  21. McBain, 1990, Regional variation of extracellular space in the hippocampus, Science, 249, 674, 10.1126/science.2382142 · DOI · Paper page
  22. Hrabetová, 2005, Extracellular diffusion is fast and isotropic in the stratum radiatum of hippocampal CA1 region in rat brain slices, Hippocampus, 15, 441, 10.1002/hipo.20068 · DOI
  23. Simonová, 1996, Changes of extracellular space volume and tortuosity in the spinal cord of Lewis rats with experimental autoimmune encephalomyelitis, Physiol. Res., 45, 11
  24. Prokopová, 1997, Heterogeneous and anisotropic diffusion in the developing rat spinal cord, Neuroreport, 8, 3527, 10.1097/00001756-199711100-00022 · DOI
  25. Hrabe, 2004, A model of effective diffusion and tortuosity in the extracellular space of the brain, Biophys. J., 87, 1606, 10.1529/biophysj.103.039495 · DOI
  26. Mori, 1999, The olfactory bulb: coding and processing of odor molecule information, Science, 286, 711, 10.1126/science.286.5440.711 · DOI
  27. Li, 2001, Impaired hearing in mice lacking aquaporin-4 water channels, J. Biol. Chem., 276, 31233, 10.1074/jbc.M104368200 · DOI
  28. Lu, 2008, Impaired olfaction in mice lacking aquaporin-4 water channels, FASEB J., 22, 3216, 10.1096/fj.07-104836 · DOI
  29. Li, 2002, Mildly abnormal retinal function in transgenic mice without Müller cell aquaporin-4 water channels, Invest. Ophthalmol. Vis. Sci., 43, 573
  30. Binder, 2004, In vivo measurement of brain extracellular space diffusion by cortical surface photobleaching, J. Neurosci., 24, 8049, 10.1523/JNEUROSCI.2294-04.2004 · DOI
  31. Jin, 2008, Random-walk model of diffusion in three dimensions in brain extracellular space: comparison with microfiberoptic photobleaching measurements, Biophys. J., 95, 1785, 10.1529/biophysj.108.131466 · DOI
  32. Karlsson, 1980, Intratumor distribution of vascular and extravascular spaces, Microvasc. Res., 19, 71, 10.1016/0026-2862(80)90084-9 · DOI
  33. Appelgren, 1973, Vascular and extravascular spaces in two transplantable tumors of the rat, Bibl. Anat., 12, 504
  34. Jain, 1987, Transport of molecules in the tumor interstitium: a review, Cancer Res., 47, 3039
  35. Krol, 1999, Available volume fraction of macromolecules in the extravascular space of a fibrosarcoma: implications for drug delivery, Cancer Res., 59, 4136
  36. Jakobsen, 1995, MRI of human tumor xenografts in vivo: proton relaxation times and extracellular tumor volume, Magn. Reson. Imaging, 13, 693, 10.1016/0730-725X(95)00019-D · DOI
  37. Zámecník, 2004, Extracellular matrix glycoproteins and diffusion barriers in human astrocytic tumours, Neuropathol. Appl. Neurobiol., 30, 338, 10.1046/j.0305-1846.2003.00541.x · DOI
  38. Vargová, 2003, Diffusion parameters of the extracellular space in human gliomas, Glia, 42, 77, 10.1002/glia.10204 · DOI
  39. Magzoub, 2008, Enhanced macromolecule diffusion deep in tumors after enzymatic digestion of extracellular matrix collagen and its associated proteoglycan decorin, FASEB J., 22, 276, 10.1096/fj.07-9150com · DOI

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Metadata

Authors
Zhang, H., & Verkman, A. S.
Affiliations
University of California, San Francisco (US)
Corresponding author
Verkman, A.S.
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2010-08
Volume
99
Issue
4
Pages
1284-1291
ISSN
0006-3495 (ISSN-L)
DOI
10.1016/j.bpj.2010.06.023
PMC
PMC2920647
OpenAlex
W2008457375
Cited by
49
References
0
Citations by year
2026: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 3 · 2018: 2 · 2017: 8 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 2
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL073856)
  • National Eye Institute (R01EY013574)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK035124, DK 35124, R37DK035124, RC1DK086125, P30DK072517)
  • National Institute of Biomedical Imaging and Bioengineering (R37EB000415, EB 00415, R01EB000415)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
alpha, brain slices, aquaporin-4, cell volume changes, tissue optical properties, fluorescence intensity ratio, mouse brain
MeSH terms
Animals, Brain, Brain Neoplasms, Extracellular Space, Fiber Optic Technology, Fluorescent Dyes, Reproducibility of Results, Gene Deletion, Cell Line, Tumor, Mice, Aquaporin 4

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