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@Article { CalcinaghiWJSKWFBMW2013,
   title = {Multimodal Imaging in Rats Reveals Impaired Neurovascular Coupling in Sustained Hypertension},
   journal = {Stroke},
   year = {2013},
   month = {6},
   volume = {Epub ahead},
   abstract = {BACKGROUND AND PURPOSE:
Arterial hypertension is an important risk factor for cerebrovascular diseases, such as transient ischemic attacks or stroke, and represents a major global health issue. The effects of hypertension on cerebral blood flow, particularly at the microvascular level, remain unknown.
METHODS:
Using the spontaneously hypertensive rat (SHR) model, we examined cortical hemodynamic responses on whisker stimulation applying a multimodal imaging approach (multiwavelength spectroscopy, laser speckle imaging, and 2-photon microscopy). We assessed the effects of hypertension in 10-, 20-, and 40-week-old male SHRs and age-matched male Wistar Kyoto rats (CTRL) on hemodynamic responses, histology, and biochemical parameters. In 40-week-old animals, losartan or verapamil was administered for 10 weeks to test the reversibility of hypertension-induced impairments.
RESULTS:
Increased arterial blood pressure was associated with a progressive impairment in functional hyperemia in 20- and 40-week-old SHRs; baseline capillary red blood cell velocity was increased in 40-week-old SHRs compared with age-matched CTRLs. Antihypertensive treatment reduced baseline capillary cerebral blood flow almost to CTRL values, whereas functional hyperemic signals did not improve after 10 weeks of drug therapy. Structural analyses of the microvascular network revealed no differences between normo- and hypertensive animals, whereas expression analyses of cerebral lysates showed signs of increased oxidative stress and signs of impaired endothelial homeostasis upon early hypertension.
CONCLUSIONS:
Impaired neurovascular coupling in the SHR evolves upon sustained hypertension. Antihypertensive monotherapy using verapamil or losartan is not sufficient to abolish this functional impairment. These deficits in neurovascular coupling in response to sustained hypertension might contribute to accelerate progression of neurodegenerative diseases in chronic hypertension.},
   department = {Department Logothetis},
   web_url = {http://stroke.ahajournals.org/content/early/2013/06/04/STROKEAHA.111.000185.abstract},
   DOI = {10.1161/STROKEAHA.111.000185},
   author = {Calcinaghi, N and Wyss, MT and Jolivet, R and Singh, A and Keller, AL and Winnik, S and Fritschy, JM and Buck, A and Matter, CM and Weber, B}
}

@Article { 6999,
   title = {Vascularization of Cytochrome Oxidase-Rich Blobs in the Primary Visual Cortex of Squirrel and Macaque Monkeys},
   journal = {Journal of Neuroscience},
   year = {2011},
   month = {1},
   volume = {31},
   number = {4},
   pages = {1246-1253},
   abstract = {The close correlation between energy supply by blood vessels and energy consumption by cellular processes in the brain is the basis of blood flow-related functional imaging techniques. Regional differences in vascular density can be detected using high-resolution functional magnetic resonance imaging. Therefore, inhomogeneities in vascularization might help to identify anatomically distinct areas noninvasively in vivo. It was reported previously that cytochrome oxidase-rich blobs in the striate cortex of squirrel monkeys are characterized by a notably higher vascular density (42\% higher than interblob regions). However, blobs have so far never been identified in vivo on the basis of their vascular density. Here, we analyzed blobs of the primary visual cortex of squirrel monkeys and macaques with respect to the relationship between vascularization and cytochrome oxidase activity. By double staining with cytochrome oxidase enzyme histochemistry to define the blobs and collagen type IV immunohistochemistry to quantify the blood vessels, a close correlation between oxidative metabolism and vascularization was confirmed and quantified in detail. The vascular length density in cytochrome oxidase blobs was on average 4.5\% higher than in the interblob regions, a difference almost one order of magnitude smaller than previously reported. Thus, the vascular density that is closely associated with local average metabolic activity is a structural equivalent of cerebral metabolism and blood flow. However, the quantitative differences in vascularization between blob and interblob regions are small and below the detectability threshold of the noninvasive hemodynamic imaging methods of today.},
   department = {Department Logothetis},
   web_url = {http://www.jneurosci.org/cgi/reprint/31/4/1246},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   language = {en},
   DOI = {10.1523/JNEUROSCI.2765-10.2011},
   author = {Keller, AL and Sch{\"u}z, A and Logothetis, NK and Weber, B}
}

@Article { 6168,
   title = {Vascular graph model to simulate the cerebral blood flow in realistic vascular networks},
   journal = {Journal of Cerebral Blood Flow and Metabolism},
   year = {2009},
   month = {8},
   volume = {29},
   number = {8},
   pages = {1429-1443},
   abstract = {At its most fundamental level, cerebral blood flow (CBF) may be modeled as fluid flow driven through a network of resistors by pressure gradients. The composition of the blood as well as the cross-sectional area and length of a vessel are the major determinants of its resistance to flow. Here, we introduce a vascular graph modeling framework based on these principles that can compute blood pressure, flow and scalar transport in realistic vascular networks. By embedding the network in a computational grid representative of brain tissue, the interaction between the two compartments can be captured in a truly three-dimensional manner and may be applied, among others, to simulate oxygen extraction from the vessels. Moreover, we have devised an upscaling algorithm that significantly reduces the computational expense and eliminates the need for detailed knowledge on the topology of the capillary bed. The vascular graph framework has been applied to investigate the effect of local vascular dilation and occlusion on
the flow in the surrounding network.},
   department = {Department Logothetis},
   web_url = {http://www.nature.com/jcbfm/journal/v29/n8/pdf/jcbfm200958a.pdf},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   language = {en},
   DOI = {10.1038/jcbfm.2009.58},
   author = {Reichold, J and Stampanoni, M and Keller, AL and Buck, A and Jenny, P and Weber, B}
}

@Article { 4901,
   title = {The microvascular system of the striate and extrastriate visual cortex of the macaque},
   journal = {Cerebral Cortex},
   year = {2008},
   month = {10},
   volume = {18},
   number = {10},
   pages = {2318-2330},
   abstract = {In functional neuroimaging, neurovascular coupling is used to generate maps of hemodynamic changes that are assumed to be surrogates of regional neural activation. The aim of this study was to characterize the microvascular system of the primate cortex as a basis for understanding the constraints imposed on a region's hemodynamic response by the vascular architecture, density, as well as area- and layer-specific variations. In the macaque visual cortex, an array of anatomical techniques has been applied, including corrosion casts, immunohistochemistry, and cytochrome oxidase (COX) staining. Detailed measurements of regional vascular length density, volume fraction, and surface density revealed a similar vascularization in different visual areas. Whereas the lower cortical layers showed a positive correlation between the vascular and cell density, this relationship was very weak in the upper layers. Synapse density values taken from the literature also displayed a very moderate correlation with the vascular density. However, the vascular density was strongly correlated with the steady-state metabolic demand as measured by COX activity. This observation suggests that although the number of neurons and synapses determines an upper bound on an area's integrative capacity, its vascularization reflects the neural activity of those subpopulations that represent a “default” mode of brain steady state.},
   department = {Department Logothetis},
   web_url = {http://cercor.oxfordjournals.org/cgi/reprint/18/10/2318},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   language = {en},
   DOI = {10.1093/cercor/bhm259},
   author = {Weber, B and Keller, AL and Reichold, J and Logothetis, NK}
}

@Article { 4894,
   title = {Magnetic Resonance Imaging of Cortical Connectivity in vivo},
   journal = {Neuroimage},
   year = {2008},
   month = {4},
   volume = {40},
   number = {2},
   pages = {458-472},
   department = {Department Logothetis},
   web_url = {http://www.sciencedirect.com/science?_ob=MImg\&_imagekey=B6WNP-4RC6R7X-4-S\&_cdi=6968\&_user=29041\&_orig=search\&_coverDate=04\%2F01\%2F2008\&_sk=999599997\&view=c\&wchp=dGLbVtz-zSkzS\&md5=dabfb44094d1137121dd895184e159cc\&ie=/sdarticle.pdf},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   language = {en},
   DOI = {10.1016/j.neuroimage.2007.12.007},
   author = {Canals, S and Beyerlein, M and Keller, AL and Murayama, Y and Logothetis, NK}
}

@Poster { 6289,
   title = {Capillary unisotropy in the rat and monkey cerebral cortex},
   year = {2009},
   month = {10},
   volume = {39},
   number = {672.13},
   abstract = {Although at the basis of cerebral blood flow (CBF) control and neurovascular coupling, very little is known about the exact topology of the cerebrovascular network. Furthermore, a better understanding of the cerebral vascular network is essential for numerical simulations of CBF (Reichold et al., 2009, J Cereb Blood Flow Metab and additional poster at this symposium).
Arterioles that branch off the pial vessels plunge into the cerebral cortex where they form collaterals at various cortical depths, which further divide unto capillary level. The capillary bed is the major site of exchange where nutrients and oxygen are delivered to the parenchyma and metabolites and heat are removed. The capillaries rejoin to form the draining veins which penetrate the cortex towards its surface. It is generally accepted that the large cortical vessels run orthogonally to cortical surface, whereas the capillaries are oriented isotropically.
Deeply anaesthetized rats and macaque monkeys were transcardially perfused with heparinized phosphate buffered saline followed by paraformaldehyde. Then, a dispersed suspension of barium sulfate was injected. After removal of the brain, cylindrical samples of from the somatosensory and visual cortex were punched out and embedded in EPON. The samples were then imaged using monochromatic X-rays with a beam energy set to 20 keV to maximize absorption contrast and to provide sufficient photon flux to penetrate the large sample. The optical magnification was 20x, resulting in isotropic voxels of 700 nm for the reconstructed images. The tomographic images were used to reconstruct and analyse the vascular network.
We show that the capillaries are not, as previously assumed, oriented isotropically but are rather designed for mass transport parallel to the cortical surface. This property is not readily apparent due to the tortuosity of the vessels. If, however, one replaces the individual capillaries by straight cylindrical segments that connect points of bifurcation, so as to look at the effective directionality of blood flow, the overwhelming dominance of horizontally oriented segments (with respect to the cortical surface) is striking. Within the cortical gray matter, this dominance increases with the cortical depth. The fraction of capillary segments with angles between 0 and 45 degrees to the cortical surface can reach values of more than 80\%. As both feeding arteries and draining veins sport higher numbers of side branches at larger cortical depths, the capillary orientation specificity thus is proportional to the frequency of non-capillary vessels that are orthogonal to the cortical surface and accomplish the vertical mass transport.},
   department = {Department Logothetis},
   web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=e5c57598-6c32-4a6f-ad00-6d5b5fa2f8c4\&cKey=63192534-c1c3-4fdc-b1c7-44469034c9ea},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   event_place = {Chicago, IL, USA},
   event_name = {39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009)},
   language = {en},
   author = {Reichold, J and Stampanoni, M and Keller, AL and Logothetis, NK and Jenny, P and Weber, S}
}

@Poster { 6170,
   title = {Systematic Investigation of Vascular Corrosion Casts of the Macaque Monkey Brain},
   year = {2008},
   month = {7},
   volume = {6},
   number = {130.8},
   abstract = {Introduction: In the past, the structural properties of the cerebral microvasculature have been analyzed using a wide range of anatomical methods, each revealing differential aspects of this system. Here, we used the corrosion cast technique to characterize the arrangement and organization of the blood vessels and the ratio of arteries and veins in different parts of the macaque’s brain.
Methods: Following standard perfusion with saline, two adult monkeys (Macaca nemestrina) were injected with Batson’s \#17 resin. After polymerization the brains were extracted, deep-frozen and serial 5 mm thick slabs were cut coronally or horizontally with a dedicated tissue knife. The cut surface was matched with the monkey brain atlas (Saleem, 2006). The slabs were then macerated using 5\% KOH until all tissue was removed, frozen in distilled water and trimmed with a sliding microtome to obtain an even surface. After complete drying, anatomical areas were identified and cut from the slabs, sputter coated with gold and imaged with the use of a scanning electron microscope.
Results: The general vascular organization was found to be very similar to that of the human brain as described by Duvernoy (1981). The same classes of vessels (depending on penetration depth and branching points) could be identified. The mean ratio of cortical arteries and veins was found to be 1: \verb=~=1.6, with arteries being the more numerous vessel type. The average irrigation volume of a large penetrating artery was estimated to be 0.44 mm*, whereas the draining volume of a large cortical vein was found to be 0.70 mm*. Different subcortical regions (e. g. LGN) could be identified solely on the basis of the arrangement of blood vessels that clearly followed the shape of the structure.
Discussion: The applied method allows for a qualitative description of the general organization principles of the brain’s vasculature, as well as for the estimation of the ratio between arterial and venous vessels.},
   url = {http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/fens2008_[0].pdf},
   department = {Department Logothetis},
   web_url = {http://fens2008.neurosciences.asso.fr/},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   event_place = {Geneva, Switzerland},
   event_name = {6th Forum of European Neuroscience (FENS 2008)},
   author = {Keller, AL and Weber, B and Logothetis, NK}
}

@Poster { 4616,
   title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing},
   year = {2007},
   month = {5},
   volume = {2007},
   number = {2464},
   pages = {481},
   abstract = {One of the main problems in systems biology is to obtain information between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge the applicability of this technique. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. On the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to
produce detectable contrast and reliable connectivity maps.Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps.},
   department = {Department Logothetis},
   web_url = {http://www.ismrm.org/07/},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   institution = {International Society of Magnetic Resonance in Medicine},
   event_place = {Berlin, Germany},
   event_name = {2007 Joint Annual Meeting ISMRM-ESMRMB},
   language = {en},
   author = {Canals, S and Beyerlein, M and Keller, AL and Murayama, Y and Logothetis, NK}
}

@Poster { 4302,
   title = {In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing},
   journal = {Neuroforum},
   year = {2007},
   month = {4},
   volume = {13},
   number = {Supplement},
   pages = {1221},
   abstract = {One of the main problems in systems biology is to obtain information on signal processing between
interconnected groups of neurons in highly distributed networks. The recently introduced technique of
manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to
these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations
produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is
proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to
produce detectable contrast and reliable connectivity maps.
Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and
extension of the obtained connectivity maps.
The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing
solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10
and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in
Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of
Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection,
T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time
points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl
staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons,
respectively) were performed in the brain sections to examine cellular toxicity.
All injections produced connectivity maps consistent with the known anterograde projections of SI cortex
based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the
effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered
and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand
contra-lateral corticocortical connections were evident in all animal injected with those solutions but not
with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions
containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection
point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in
isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be
advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1
contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the
projection fields.
We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and
preserves tissue viability, assuring the application of this technique in longitudinal experiments.},
   url = {http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/T38-4C_4302[0].pdf},
   department = {Department Logothetis},
   web_url = {http://www.neuro.uni-goettingen.de/nbc.php?sel=archiv},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   event_place = {G{\"o}ttingen, Germany},
   event_name = {31st G{\"o}ttingen Neurobiology Conference},
   language = {en},
   author = {Canals, S and Beyerlein, M and Keller, AL and Murayama, Y and Logothetis, NK}
}

@Poster { BeedKGSLw2007,
   title = {Topological tree-analysis of the microvascular system in macaque visual cortex},
   journal = {Neuroforum},
   year = {2007},
   month = {4},
   volume = {13},
   number = {Supplement},
   pages = {736},
   abstract = {For a profound understanding of functional brain imaging in research and in clinical applications,
investigations of neurovascular coupling are mandatory. Three-dimensional tree-analysis of cortical
vasculature elucidates the structural aspects of neurovascular coupling such as the organization of the cortical
vasculature and network topology. Here we report a technique to obtain high resolution tomographic images
of the cerebral vasculature, accurate reconstructions of the whole vasculature and extraction of vessel
attributes to reliably quantitate large vascular networks. Non-human primate (Macaca mulatta) brains were
collected and processed. Samples were punched from the primary visual cortex and scanned at the material
science beamline of the Swiss Light Source to yield X-ray tomographic images for 3D reconstruction of the
vasculature. Key vessel parameters have been evaluated for different levels of analysis (from single samples to
grouped data). The diameter and length distributions of the cortical vessels indicated a high percentage of
capillaries. Layer 4c\(\beta\) had the highest density of capillary and noncapillary vessels in comparison to the other
cortical layers. Mean volume fraction was 2.5\% for cortical gray matter. Extravascular distance measure
yielded an average mesh size of 56 \(\mu\)m. Branching pattern analyses have been performed for single vessels
extracted from whole networks for investigation of network geometry. In conclusion, these results indicate the
reliability of the technique in studying cortical vasculature. The results were in good agreement with
histological data as well as with data from the literature. Quantitative three-dimensional morphometry of
vascular networks is critical for future blood flow modeling in the cerebral cortex.},
   department = {Department Logothetis},
   web_url = {http://www.neuro.uni-goettingen.de/nbc.php?sel=archiv},
   event_place = {G{\"o}ttingen, Germany},
   event_name = {31st G{\"o}ttingen Neurobiology Conference},
   author = {Beed, P and Keller, AL and Groso, A and Stampanoni, M and Logothetis, NK and Weber, B}
}

@Poster { 4242,
   title = {Vascular density in regions of different levels of oxidative metabolism within the macaque primary visual cortex},
   year = {2006},
   month = {10},
   volume = {36},
   number = {363.8},
   abstract = {Introduction: The primary visual cortex of the primate shows distinct regions of increased cytochrome oxidase activity, the so called “blobs”. When visualized in tangential sections the blobs form a pattern of regularly distributed patches which are most prominent in the third cortical layer. Since cytochrome oxidase is an enzyme of the oxidative chain, increased local enzyme activity indicates an increased metabolic activity of a given region. It has been shown in the squirrel monkey cortex that this metabolic difference is reflected in the density of the cortical vascularization. The aim of this study was to replicate and extend this finding with a quantitative and layer specific assessment of the vascular density in blob and interblob regions.
Methods: Formalin-fixed frozen sections of 2 animals (M. mulatta) were first stained with the classical cytochrome oxidase staining method that uses the enzyme activity to precipitate DAB. The sections were then further processed for fluorescence immunohistochemistry. They were incubated with anti-collagen type IV and a Cy3-conjugated secondary antibody to stain for blood vessels. Epifluorescence micrographs were taken and the vessels were manually and automatically delineated. The length density (mm/mm³) and volume fraction (mm³/mm³) of vessels was taken as a measure for the vascular density. The blobs were determined in the corresponding brightfield micrograph of the same section on the basis of the cytochrome oxidase stain.
Results: The vascular length density and volume fraction was significantly higher inside the blobs as compared to the interblob regions (paired t-test, p<0.001). The absolute values were 535.2 +/-57.8 mm/mm&sup3; (mean +/- SD of 2 animals) for the blobs and 485.5 +/- 51.2 mm/mm&sup3; for interblob areas, which is 108.7 \% for blobs and 98.1 \% for interblobs of the overall mean vascular length density in V1. The blob-interblob difference was most prominent in cortical layer IV.
Conclusion: In summary, the blobs&rsquo; vascular density is significantly higher as compared to the surrounding cortex in V1. This reflects an adaptation of blood supply in these metabolically and most likely also functionally different regions of V1. However, the measured difference is considerably smaller when compared to the previously published data. This discrepancy could be due inter-species or methodological differences between the studies.},
   url = {http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/SfN2006_AnnaLenaKeller_4242[0].pdf},
   department = {Department Logothetis},
   web_url = {http://www.sfn.org/index.aspx?pagename=abstracts_ampublications},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   event_place = {Atlanta, GA, USA},
   event_name = {36th Annual Meeting of the Society for Neuroscience (Neuroscience 2006)},
   language = {en},
   author = {Keller, AL and Logothetis, NK and Weber, B}
}

@Poster { 4243,
   title = {Quantitative aspects of the microvascular system in macaque visual cortex},
   year = {2006},
   month = {7},
   volume = {5},
   number = {A179.27},
   pages = {179},
   abstract = {The basic principle of the most frequently used functional neuroimaging methods is the brain&rsquo;s local dynamic regulation of blood flow. For a correct interpretation of neuroimaging results the structural and functional neurovascular coupling underlying this regulation must be well understood. Here we report quantitative anatomical data of the microvasculature in the macaque visual cortex.
Formalin-fixed frozen sections of 4 animals (M. mulatta) were processed for double fluorescence immunohistochemistry. Sections were incubated with anti-collagen type IV and DAPI to stain for vessels and cell nuclei. In one additional animal, the anti-collagen procedure was combined with cytochrome oxidase staining in V1. The length density (LD), surface density (SD), volume fraction (VF) and diameter (D) of the vessels were stereologically determined. Furthermore, synchrotron-based computed tomographies (SRCT) of formalin-fixed and barium sulfate-perfused brain samples from another 2 animals were used to corroborate the histological results.
In V1, the vascular density was highest in layer IVc- (LD 674.7 mm/mm3, SD 15.2 mm2/mm3, VF 2.6 \%, D 7.2 microns) and lowest in layer I (LD 461.5 mm/mm3, SD 10.9 mm2/mm3, VF 1.9 \%, D 7.5 microns). In all extrastriate visual areas analyzed (V2, V3, V4, V5), the vascular density was generally lower, and the difference between layer IV and the remaining layers was less prominent when compared to V1. These density values were similar compared to the ones tomographically obtained from SRCT. The vascular density in cytochrome oxidase rich blobs in V1 was 14 \% higher as compared to the interblob region.
In summary, V1 is different from all extrastriate areas analyzed with respect to the laminar vessel distribution and overall vascular density. Differences between extrastriate areas were negligible. The overall vascular volume fraction in visual cortex derived from immunostaining was approximately 2 \%, a value that was well reproduced by the SRCT.},
   url = {http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/FENS2006_BrunoWeber_4243[0].pdf},
   department = {Department Logothetis},
   web_url = {http://fens2006.neurosciences.asso.fr/},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   event_place = {Wien, Austria},
   event_name = {5th Forum of European Neuroscience (FENS 2006)},
   language = {en},
   author = {Weber, B and Keller, AL and Groso, A and Stampanoni, M and Logothetis, NK}
}

@Poster { 3842,
   title = {Area- and layer-specific vascular density in the macaque striate and extrastriate cortex},
   year = {2005},
   month = {11},
   volume = {35},
   number = {456.9},
   abstract = {Introduction: Most functional neuroimaging methods, including fMRI, rely on the hemodynamic response following neural activation. Consequently in order to correctly interpret the results of neuroimaging experiments both the functional and the structural neurovascular coupling must be well understood. The former includes the degree and density of cortical vascularization. Here we studied the layer and area specific vascular differences in areas V1, V2, V3, V4 and V5 in the macaque monkey.
Methods: Formalin-fixed frozen sections of 4 animals (M. mulatta) were processed for double fluorescence immunohistochemistry. Sections were incubated with anti-collagen type IV and DAPI to stain for vessels and cell nuclei. The length density (mm/mm&sup3;) of vessels was taken as a measure for vascular density. Layer and area specific regions of interest were determined on the basis of the DAPI stain and if necesary with the help of consecutive Nissl and myelin stains.
Results: The procedure yielded high quality vessel-specific images with excellent reproducibility within and between animals. In V1, the vascular density was highest in layer IVc-\(\beta\) (871.9 +/- 47.1 mm/mm&sup3;, mean +/- sd of 4 animals) and lowest in layer I (587.17 +/- 31.7 mm/mm&sup3;). In all extrastriate visual areas analyzed, the vascular density was generally lower, and the difference between layer IV and the remaining layers was less prominent when compared to V1. The vascular length density in V2 was 674.0 +/- 31.8 mm/mm&sup3; in layer IV and 585.1 +/- 40.0 mm/mm&sup3; in layer I. As a further example, in V5 672.7 +/- 41.6 mm/mm&sup3; was measured in layer IV and 584.0 +/- 52.0 mm/mm&sup3; in layer I.
Conclusion: In summary, V1 was clearly different from all extrastriate areas analyzed with respect to the laminar vessel distribution and the overall vascular density. Differences between extrastriate areas were negligible. The influence of differences in vascularization on the neuroimaging signals remains largely unknown. However, this study suggests that caution is advised particularly when response patterns are compared between V1 and extrastriate areas.},
   department = {Department Logothetis},
   web_url = {http://www.sfn.org/absarchive/},
   institute = {Biologische Kybernetik},
   organization = {Max-Planck-Gesellschaft},
   institution = {Society for Neuroscience},
   event_place = {Washington, DC, USA},
   event_name = {35th Annual Meeting of the Society for Neuroscience (Neuroscience 2005)},
   language = {en},
   author = {Weber, B and Keller, AL and Logothetis, NK}
}