88
L. E. Bilston
and cerebral perfusion pressure. A recent study comparing in vivo and ex vivo brain
properties using MRE indicates that brain stiffness declines after death, but also
that frequency dependence is different in vivo compared to ex vivo [89], further
emphasising the difficulties of extrapolating from ex vivo data to in vivo brain
properties. Others show an increase in shear modulus beyond 6 hours for samples
tested ex vivo [90], while indentation tests have shown no effect on overall stiffness
when comparing in vivo to in situ but decreases in shear modulus ex vivo (within
6 hours of death) compared to in vivo and in situ [91]. It seems likely on the basis
of this data that there are drops in apparent tissue stiffness immediately after death,
and possibly increases at longer times post mortem. Since the ex vivo studies in the
literature have used a range of times after death up to days, this may be a significant
factor in differences in reported data, and such data should be viewed with caution.
A recent MRE study suggested that venous pressure, as manipulated by constriction
of jugular outflow from the head, can also influence brain mechanical properties
[92].
Few studies have directly compared different species under the same testing
protocols. The studies that have been done show that properties are similar, at least
between human and porcine brains and human [86] and human and rhesus monkey
[51].
4.6.2 Methodological Considerations
As mentioned throughout the above sections, characterisation of brain tissue
properties has been plagued by differences in results arising from differences in test
methods. These differences fall into three main categories – sample preparation,
post-mortem time, and testing conditions.
The issue of post-mortem time is discussed in the previous sections above, but it
is likely that much of the data in the literature conducted at long times after death is
of limited value due to significant changes in tissue properties post mortem.
Sample preparation has received less attention, but it is also of importance.
Delicate brain tissue is easily dehydrated and is also subject to osmotic swelling
if bathed in fluids with inappropriate osmotic content [47]. Despite this, a range of
bathing fluids have been used, including PBS [90], simple saline [50], and silicon
oil [15] in addition to artificial CSF [47], which has a similar osmotic content to
CSF. Ensuring that the sample has suitable dimensions to minimise the influence
of edge effects, slip at gripping surfaces or test platens, and sample inertial effects
at high loading rates is also essential. These issues are often not fully considered
in published studies. Liu [93] showed that sample thickness affects measured shear
moduli in a parallel plate configuration, and similar results were observed by Garo
et al. [90]. Recently, storage temperature has also been suggested to affect the
measured properties [94].
Sample preconditioning processes have not been studied in detail in brain tissue,
although several studies have noted the effects of previous strain loading cycles
L. E. Bilston
and cerebral perfusion pressure. A recent study comparing in vivo and ex vivo brain
properties using MRE indicates that brain stiffness declines after death, but also
that frequency dependence is different in vivo compared to ex vivo [89], further
emphasising the difficulties of extrapolating from ex vivo data to in vivo brain
properties. Others show an increase in shear modulus beyond 6 hours for samples
tested ex vivo [90], while indentation tests have shown no effect on overall stiffness
when comparing in vivo to in situ but decreases in shear modulus ex vivo (within
6 hours of death) compared to in vivo and in situ [91]. It seems likely on the basis
of this data that there are drops in apparent tissue stiffness immediately after death,
and possibly increases at longer times post mortem. Since the ex vivo studies in the
literature have used a range of times after death up to days, this may be a significant
factor in differences in reported data, and such data should be viewed with caution.
A recent MRE study suggested that venous pressure, as manipulated by constriction
of jugular outflow from the head, can also influence brain mechanical properties
[92].
Few studies have directly compared different species under the same testing
protocols. The studies that have been done show that properties are similar, at least
between human and porcine brains and human [86] and human and rhesus monkey
[51].
4.6.2 Methodological Considerations
As mentioned throughout the above sections, characterisation of brain tissue
properties has been plagued by differences in results arising from differences in test
methods. These differences fall into three main categories – sample preparation,
post-mortem time, and testing conditions.
The issue of post-mortem time is discussed in the previous sections above, but it
is likely that much of the data in the literature conducted at long times after death is
of limited value due to significant changes in tissue properties post mortem.
Sample preparation has received less attention, but it is also of importance.
Delicate brain tissue is easily dehydrated and is also subject to osmotic swelling
if bathed in fluids with inappropriate osmotic content [47]. Despite this, a range of
bathing fluids have been used, including PBS [90], simple saline [50], and silicon
oil [15] in addition to artificial CSF [47], which has a similar osmotic content to
CSF. Ensuring that the sample has suitable dimensions to minimise the influence
of edge effects, slip at gripping surfaces or test platens, and sample inertial effects
at high loading rates is also essential. These issues are often not fully considered
in published studies. Liu [93] showed that sample thickness affects measured shear
moduli in a parallel plate configuration, and similar results were observed by Garo
et al. [90]. Recently, storage temperature has also been suggested to affect the
measured properties [94].
Sample preconditioning processes have not been studied in detail in brain tissue,
although several studies have noted the effects of previous strain loading cycles