Phase contrast magnetic resonance imaging for idiopathic normal pressure hydrocephalus

While some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness ¹⁾

see Aqueductal stroke volume.

Forty-six patients with definite iNPH were included between January 2018 and January 2022. PC-MR was used to evaluate CSF peak velocity (PV), average velocity, aqueductal stroke volume (ASV), net ASV, and net flow. The modified Rankin Scale (mRS), iNPH grading scale (iNPHGS), Mini-Mental State Examination (MMSE), and Timed 3-m Up and Go Test (TUG) were used for clinical assessment. The primary endpoint was the improvement in the mRS score 1 year after surgery, and the secondary endpoints were the iNPHGS, MMSE, and TUG scores at 1 year. Differences between shunt improvement and non-improvement groups, based on the clinical outcomes, were compared using the Mann-Whitney U-test, logistic regression models, and receiver operating characteristic curves. Correlations between CSF flow parameters and the baseline clinical outcomes were assessed using Spearman's correlation coefficient.

Results: No CSF parameters significantly differed between shunt improvement and non-improvement groups based on mRS and secondary outcomes. And all CSF parameters showed significant overlap in both shunt improvement and non-improvement groups based on mRS and secondary outcomes. Significant correlations between the mRS and iNPHGS scores, and PV, ASV, and net ASV were observed.

Conclusion: While some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness ²⁾

Ringstad et al. tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of “true” normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43). Pulse pressure gradients were also similar in patients and healthy controls (P = .26), and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97). Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate marker for intracranial pressure pulsations ³⁾.

Seven patients with a median age of 73 years (range: 60-80) who underwent a primary endoscopic third ventriculostomy (ETV) for iNPH were included for analysis. Median follow-up was 39 months (range: 26-46). Post-ETV stoma and aqueductal and cisternal flows were confirmed via high resolution, gradient echo and phase contrast MRI. Post-ETV timed up and go (TUG) and Tinetti performance oriented mobility assessment scores were compared to pre- and post-lumbar puncture (LP) values. A second LP was performed if ETV failed to sustain the observed improvement after initial LP. Patients who demonstrated ETV failure were subsequently shunted. Compared to pre-LP TUG and Tinetti values of 14.00 seconds (range: 12.00-23.00) and 22 (range: 16-24), post-LP scores improved to 11.00 seconds (range: 8.64-15.00; p=0.06) and 25 (range: 24-28; p=0.02), respectively. ETV failed to sustain this improvement with slight worsening between pre-LP and post-ETV TUG and Tinetti scores. Improvement from pre-LP assessment was regained after shunting and at last follow-up with TUG and Tinetti scores of 12.97 seconds (range: 9.00-18.00; p=0.250) and 25 (range: 18-27; p=0.07), and 11.87 seconds (range: 8.27-18.50; p=0.152) and 23 (range: 18-26; p=0.382), respectively. Despite stoma patency, ETV failed to sustain functional improvement seen after LP, however, improvement was regained after subsequent shunting suggesting that shunt placement remains the preferred treatment for iNPH ⁴⁾.

Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image ⁵⁾.

Between January 2003 and April 2005, 61 patients with clinical symptoms fitting the Hakim triad and a dilated ventricular system on CT underwent a intrathecal infusion test and cerebrospinal tap test. All patients also had a phase contrast MRI to determine the CSF flow rate in the aqueduct. Shunted patients were followed postoperatively up to 12 months. The pre- and postoperative symptomatic condition was evaluated using the clinical Kiefer score. The outcome was calculated by the NPH Recovery Rate.

Patients were classified into 41 with iNPH and 20 patients with brain atrophy. Thirty-nine iNPH patients were shunted and two patients refused surgery. The mean Kiefer score of the shunted patients was statistically significantly lower after surgery. In patients screened for clinical symptoms and ventriculomegaly on CT imaging, an aqueduct-CSF flow rate greater than 24.5 ml/min was found to be statistically specific for a diagnosis of iNPH ⁶⁾.

Thirty-eight patients with suspected normal pressure hydrocephalus were included. Cerebrospinal fluid stroke volume (SV) was assessed using cine phase-contrast magnetic resonance imaging, and the results were kept blinded until postoperative follow-up after 7 +/- 5.8 months (mean +/- standard deviation). Selection to surgery was based on a positive lumbar infusion test or cerebrospinal fluid tap test, and outcome was evaluated with objective tests.

Six patients were excluded from SV measurements because of technical difficulties. Eight patients were not operated (negative lumbar infusion test and cerebrospinal fluid tap test). SV in the not operated patients (mean, 66 +/- 53 microl) did not differ from the operated patients (95 +/- 78 microl; P = 0.335). Operated patients showed statistically significant improvements in walk (P = 0.020), reaction time (P = 0.006), and memory (P = 0.001) tests. Patients were divided into three groups according to SV range: low (0-50 microl), middle (51-100 microl), and high (>100 microl). No statistically significant (P > 0.05) improvements in any of the objective tests were found in any of the SV ranges. The numbers of individually improved patients were similar in the different SV ranges: six out of seven in the low, nine out of nine in the middle, and five out of eight in the high range. Weak correlations were found between SV and the initial pulse amplitude (Rs = 0.043; P = 0.014) as well as the plateau pulse amplitude (Rs = 0.043; P = 0.014) as measured with the lumbar infusion test.

The data from this study show no evidence that cine phase-contrast magnetic resonance imaging measurements of SV in the cerebral aqueduct are useful for selecting patients with normal pressure hydrocephalus symptoms to shunt surgery ⁷⁾.

A total of 236 patients were studied, including 47 normal elderly patients, 115 patients with cognitive impairment (9 with mild cognitive impairment, 46 with Alzheimer's disease, and 60 with other cognitive impairment), 31 patients in whom NPH was suspected but ultimately excluded, and 43 patients with a final clinical diagnosis of NPH.

The intraobserver, interobserver, and intertrial measurement variations of 6.4, 5.4, and 8.8%, respectively, were substantially smaller than the wide variation observed among subjects. There was no statistically significant difference in flow between normal elderly patients and patients with cognitive impairment (P = 0.91). When these populations were pooled, the average flow was 8.47 ml/min (standard deviation, 4.23; range, 0.9-18.5 ml/min). The average flow rate in patients with a final clinical diagnosis of NPH was 27.4 ml/min (standard deviation, 15.3; range, 3.13-62.2 ml/min). This was significantly higher than the flow rate in each of the other three groups (all, P < 0.001).

CSF flow measurements of less than 18 ml/min with a sinusoidal flow pattern are normal. CSF flow of greater than 18 ml/min suggests idiopathic NPH ⁸⁾.