Noninvasive Assessment of Intracranial Pressure Status in Idiopathic Intracranial Hypertension Using Displacement Encoding with Stimulated Echoes (DENSE) MRI: A Prospective Patient Study with Contemporaneous CSF Pressure Correlation

Discussion

This study prospectively used a protocol that tightly coupled DENSE MR imaging with the CSF opening pressure and closing pressure measured by LP and CSF manometry. We chose IIH as a model for elevated ICP because there is no intracranial abnormality such as a mass lesion that would vary in size or effect between patients. We hypothesized that elevated ICP would constrain peak brain motion because vascular pulsations may be less able to drive brain motion in a high-pressure state. We specifically evaluated the foot-to-head direction of motion and the brain stem because this had previously been the direction and location of the highest brain motion in healthy volunteers⁶ (compared with the anteroposterior direction, presumably related to increased compliance of the spinal canal from the presence of neural foraminal openings and epidural fat). The midpons was chosen as an easily identifiable landmark for ROI placement where there would not be partial volume effects with CSF flow. In comparison with healthy control subjects, patients with IIH had significantly decreased pontine displacement. Reducing CSF pressure through CSF removal resulted in within-subject increase in pontine displacement for all patients with IIH, with mean post-LP pontine displacement similar to that of healthy control subjects. Establishing this relationship between pressure and pontine displacement by using DENSE raises the potential for its use for noninvasive assessment of ICP status. Merits to the technique include a very short acquisition time and simple postprocessing, which could easily be automated for inline real-time clinical use. Specifically, the technique could be used to noninvasively track patients after a baseline DENSE measurement to assess for therapy failure in IIH and potentially other conditions (eg, CSF shunt failure as a cause of recurrent headache).

The reference standard for ICP measurement is direct ICP monitoring, which is highly invasive and not practical or necessary for most patients because CSF pressure by LP generally agrees with ICP.¹³ Orbital, skull base, dural venous sinus, and other imaging findings^{8⇓⇓⇓–12} have been described in IIH, but are not of sufficient accuracy to be diagnostic of elevated ICP^14,15 and may persist after pressure reduction.¹⁶ Clinical examination of papilledema by using the Frisén scale varies among medical specialists,¹⁷ and the absence of papilledema does not exclude ICP elevation. Transcranial Doppler sonography and optic nerve ultrasonography have shown variable results for the assessment of ICP.^18,19 An MR imaging approach derived from transcranial CSF flow and blood volumetric flow rates has been used to differentiate between normal and elevated ICP^20,21; however, this approach is complex for clinical use and requires further investigation in a larger cohort.

There are several limitations to this study, including the relatively small number of patients evaluated. We attempted to minimize time lags between pressure and DENSE measurements; however, transport and procedural time precluded tighter coupling of the steps. Because CSF is regenerated over time, it could increase pressure post-LP above the measured closing pressure, introducing systematic error into the post-LP DENSE. Variability in the timing interval between DENSE and pressure measurement across patients could introduce additional error. Patients and control subjects differed in demographic features, so it is difficult to exclude the contributions of these and other variables to the comparisons between IIH and control groups. Next, there is substantial variability between patients in baseline pontine displacement and in their extent of change after LP and CSF removal. A variety of factors, including the extent and duration of elevated ICP and variations in potential adaptive responses related to the elevated ICP, could be responsible for this finding; therefore, the degree of change in pontine displacement through CSF pressure reduction may vary by patient-specific factors. We did not use a head immobilization device or correct in postprocessing for any bulk head motion, and this would perhaps further improve the robustness of the results in terms of interpatient differences and differences pre- to post-LP. An LP was not performed on healthy control subjects, so their exact ICP status is not known; however, the selection of nonobese control subjects without self-reported symptoms of elevated ICP makes it extremely unlikely that they have undiagnosed IIH. Finally, it is unclear how DENSE would perform in the setting of an intracranial mass, hydrocephalus, or other important brain abnormality or in circumstances where there is only mild elevation of ICP. Future extension to a larger cohort with normal and abnormally elevated ICP, as well as to other scanner systems and patients with other etiologies of abnormal ICP, will be required to determine the broader applicability of the DENSE technique.