Biomedical Engineering Reference
In-Depth Information
cerebral blood flow (CBF), blood volume (CBV) or blood oxy-
genation, quantities that act as indirect surrogate markers of focal
neuronal activity
(5)
. Through the “cerebrovascular coupling”,
homeostasis of the brain parenchyma is maintained by regulation
of CBF on a precise spatial and temporal domain
(6-8)
. Because
the spatial and temporal resolution of neuroimaging modalities
is ultimately determined by the spatial and temporal specificity
of the underlying hemodynamic signals, characterization of the
spatial and temporal profiles of the hemodynamic response to
focal brain stimulation is of paramount importance for the cor-
rect interpretation and quantification of functional data
(5)
and
significant effort has been placed on understanding the nature of
the cerebrovascular coupling
(9, 10)
.
In the spatial domain, the CBF response to neural activity is
well localized within the active cortex. In rat primary somatosen-
sory cortex (S1), for example, elemental vascular units supply
individual whisker barrels
(11-13)
. The units are functionally
linked for precise focal regulation of CBF, with the highest rest-
ing values and the highest changes being localized in layer IV
(14)
. The physiological basis of the differences in CBF increments
between different layers may be pericytes placed strategically to
regulate capillary blood flow to meet local demands
(15, 16)
,
or differences in capillary density accompanying differences in
synaptic function
(12, 17, 18)
. The match between microvascu-
lar structures and neural columns
(13)
ensures the CBF response
is spatially specific to the activated column
(19)
. Indeed, since the
mid 1990's, several fMRI and OIS studies successfully mapped
elemental functional units in the cortex, such as individual whisker
barrels in rat S1
(20-22)
, individual digits in human sensorimotor
cortex
(23, 24)
, cortical laminae in olfactory bulb
(25, 26)
and S1
(27-29)
of rodents, and ocular dominance or orientation columns
in the cat and human visual cortex
(19, 30-39)
.
In the temporal domain, the hemodynamic response con-
sists of several processes with different time scales. Through cere-
brovascular coupling, local decreases in vascular resistance lead to
an increase in local blood volume and flow. The increase in blood
flow results in hyperoxygenation of the capillary bed that drains
into the veins, causing a signal that forms the basis of BOLD
contrast
(2)
. The increased hyperoxygenation becomes promi-
nent in medium to large draining veins, and thus this response
is often considered to be spatially nonspecific. Upon cessation of
the increased electrical activity, the neurovascular coupling causes
restoration of the capillary and arteriolar volume, resulting in
restoration of local CBF and of the imaging signal, once the
transit of oxyhemoglobin across the local cerebral vasculature is
completed
(40)
. Thus, the temporal resolution of neuroimag-
ing techniques is limited by vascular transit times. Recently,
much effort has been placed on determining the “hemodynamic
