# Predicting the Aqueductal Cerebrospinal Fluid Pulse: A Statistical Approach
## 4 Discussion
Indeed, subject 5010 was found to have turbulent and low flow in the left IJV (Figure 5A), as well as a particularly high aCSF stroke volume of 51 uL/beat (Table 1). By contrast, no morphological venous abnormalities were observed in subject 5031 (Figure 4C), although the profile of the venous flow signal in Figure 4A was atypical. While the reasons for this atypical behaviour are unknown, given that 70% of the intracerebral blood volume lies within the veins [39] and that these are thought to play an important role in regulating cerebral compliance [12; 35; 36; 37], it may be that the changes in the dynamics of the cerebral venous drainage system contributed to the low adjusted r\({}^{2}\) value in this subject. Intracranial compliance is dependent on the cerebral venous drainage system, which because it is 'open' allows fluid to move out of the cranium [36]. This process is however mediated by the interaction between the CSF and the cortical bridging veins in the subarachnoid space, which regulates the accumulation of venous blood in the cranium [20]. If for any reason this mechanism should become impaired, then it has the potential to alter both the dynamics of the intracranial fluidic system and the compliance of the intracranial space. However, while changes in the venous system may have contributed to the observed results for subjects 5010 and 5031, further work will be required to fully explain why the r\({}^{2}\) values observed for these subjects were appreciably lower than for the other subjects. Notwithstanding this, it should be noted that the low turbulent flow in the left IJV of subject 5010 would have resulted in a less precise PC MRI flow estimate for this vessel, something that might have contributed to a less accurate prediction of the aCSF pulse in this subject. With regard to this, it is noticeable that for subject 5006, who exhibited extensive collateral veins and posterior veins but no turbulence (Figure 5B), the model adjusted r\({}^{2}\) value was 0.894 (Table 4), further suggesting that the presence of turbulent flow might have a detrimental effect on the predictive accuracy of the aCSF model. Figure 4: (**A**) Arterial, venous, cCSF and aCSF flow rates for subject 5031 (atypical), together with (**B**) actual and predicted aCSF flow rates, and (**C**) TOF MR revenograph of the neck. (NB. The venous signal has been inverted in (A) for comparison purposes.) The aCSF flow was predicted from the arterial, venous and cCSF flow rates with an r\({}^{2}\) = 0.295). The dynamics of the aCSF pulse are an issue of clinical importance. Increased amplitude of the aCSF pulse has been shown to be associated with MS [3; 4; 5; 6; 7], NPH [8; 9; 10; 11; 12; 13], and early-stage WM changes [14; 15]. However, the mechanism linking aCSF pulse dynamics with these pathologies is poorly understood. Because the phenomenon has been linked with an increase in the'stiffness' of the brain tissue [2], it may be that increased aCSF stoke volume is a sign that the cerebral windkessel mechanism [40; 41; 42], which regulates blood flow through the parenchyma, has become impaired [43]. Impairment of the windkessel mechanism has been shown to occur with bilateral compression of the JIVs, resulting in increased pulsation in the pial arteries [44]. This has been linked with WM changes in elderly individuals, with increased pulsatility in the parenchymal vascular bed associated with WM microstructural changes [15], small vessel disease [45] and leukoaraiosis [43]. Increased aCSF stroke volume might also be associated with transependymal seepage of CSF into the parenchyma, reversing the normal direction of flow [46]. Being a semipermeable barrier between the brain parenchyma and the CSF in the ventricles [47] the ependymal wall is vulnerable to disruption [46]. Indeed, in NPH patients the periventricular tissue is characterized by disruption of the ependyma, and by oedema, neuronal degeneration, and ischemia [48].