Pseudo-Leptomeningeal Contrast Enhancement at 3T in Pediatric Patients Sedated by Propofol

Discussion

Because MR imaging is noninvasive and does not use ionizing radiation, it is often a technique of choice for pediatric patients requiring neuroimaging. However, its potentially long imaging time often requires sedation in pediatric patients younger than 8 years of age. Thus, propofol is a lipid emulsion agent that is commonly the preferred anesthetic for children younger than 1 year of age who require intravenous sedation, due to its rapid onset, short duration, and infrequent side effects.^7⇓–9 Because the presence of truly abnormal LMCE would be of concern in children, this study set out to determine whether pseudo-LMCE is a sequence-dependent (SE TIWI versus GE TIWI), TTI-dependent (time to postcontrast T1WI), propofol dosage–dependent phenomenon, or whether it is related to demographics such as age and weight. Ultimately, it was found that overall, the degree of apparent LMCE is significantly greater on SE TIWI compared with GE TIWI and that the only factors that correlated (inversely) with the degree of LMCE were patient weight and age. Hence, the type of T1WI sequence and patient size may be factors to consider when a pattern of apparent LMCE (so-called pseudo-LMCE) is identified, to distinguish this phenomenon from true meningeal abnormalities. Because this study focused solely on children between 1 and 5 years of age, future studies would be necessary to evaluate whether this phenomenon also occurs to some degree in older children and juveniles.

The mechanism of how this pattern of pseudo-LMCE occurs is not yet known, but there are several plausible explanations. The various determinants of cerebral blood flow are the patient's age, cerebral metabolic rate for oxygen, cerebral perfusion pressure, arterial oxygen, and carbon dioxide tensions. First, children under propofol sedation breathe spontaneously, but propofol causes a decrease in the tidal volume with a maintained respiratory rate and mild reduction in the partial pressure of oxygen in the blood, as well as a mild reduction in the fraction of inspired oxygen. By this phenomenon, one likely mechanism of pseudo-LMCE may be cerebral vasodilation secondary to an increase in the partial pressure of carbon dioxide (due to smooth-muscle relaxation); this increase in the partial pressure of carbon dioxide is likely due to the lack of “breathing off” CO₂.^9,10 Another factor could be that the leptomeninges may be more reactive or sensitive (in a sense “immature”) in children compared with adults, an effect perhaps amplified by intravenous sedation. Additionally, because propofol sedation may affect respiration, studies have shown that the end-tidal volume of CO₂ has an inverse relationship with the degree of venous contrast, which could also contribute to LMCE.¹¹

Hence, on the basis of reviewing the images within this study as well as the authors' experience, the authors opine that pseudo-LMCE on cerebral postcontrast T1WI often represents prominent venous vasculature of the subarachnoid space in younger children, being anecdotally described previously as less common in older children and adults; because older ages were not included in this study, this should be proved by a prospective study comparing age groups.¹² However, the finding in the current study of a significant, inverse correlation between patient weight and the grade of pseudo-LMCE suggests that smaller and younger patients have more vasoreactivity, perhaps because their vasculature is not as mature. This theory may be supported by a study by Harreld et al,⁴ which noted that in propofol-sedated children, the usual age-related decreases in CBF were reversed and increases in CBF and CBV were weight-dependent.

Unfortunately, exuberant pseudo-LMCE in children may simulate serious disorders that have implications for diagnosis therapy, such as leading to an unnecessary lumbar puncture to exclude meningitis. A radiologist should use other available imaging sequences to exclude true leptomeningeal abnormalities before the patient leaves the MR imaging scanner. The authors commonly experience the scenario in which a child with an unrelated diagnosis (eg, developmental delay, autism, and so forth) is imaged during sedation with propofol, in which the presence of pseudo-LMCE is spurious and varies with the postcontrast T1WI sequence used and the findings of other tests such as a resultant lumbar puncture, serum culture, and so forth are negative. This phenomenon being more common and greater in degree on SE TIWI versus GE TIWI is thought to be related to GE TIWI having a longer TR and lower contrast-to-noise ratio than SE TIWI; these features have been confirmed by studies noting that GE TIWI has a lower lesion detectability and visibility of contrast enhancement for a similar slice thickness.^13⇓–15 While there was a small difference in slice gap between the 2 sequences in this study, the slice thickness and acquisition plane were coregistered between the 2 sequences, so this small gap is unlikely to account for the difference in the degree of LMCE.

Intravenous contrast is not required in most pediatric brain MR imaging examinations, and gadolinium-based contrast should be avoided when unnecessary due to the possibility of deposition within particular brain structures, especially with repeat administrations in children.^{16⇓⇓⇓–20} While this study did use a macrocyclic agent (the class of agents least likely to result in brain deposition), the use of most gadolinium-based agents is off-label for most gadolinium based intravenous contrast agents in the infantile population but is considered a standard of care in various clinical scenarios.^16⇓–18 For example, particular known or suspected pathologies that may require either gadolinium-based contrast for diagnosis or follow-up or to exclude related pathology including infectious disorders (eg, abscess, empyema, or meningoencephalitis), neoplasms, syndromic disorders (eg, phakomatoses), vascular malformations, or vasculitis, to name a few. Hence, while stewardship is critical to lessen the use of gadolinium-based contrast, there will continue to be subsets of patients that necessitate such contrast in the foreseeable future, and an awareness of this appearance of pseudo-LMCE may help prevent a misdiagnosis of leptomeningeal disease in children.

This study has several limitations, including its retrospective nature and the relatively small sample size of groups that underwent both T1WI sequences. The role of supplemental oxygen during sedation was not accounted for, which may also affect cerebral hemodynamics and alter subarachnoid signal intensity on other sequences, such as previously noted on FLAIR.²¹ In this regard, the authors found it difficult to obtain an accurate tabulation of the exact fractionation of oxygen and the length of time administered while the patient was under sedation, although the electronic record did note that there was titration of the supplemental oxygen in some patients. Thus, it is recommended that future studies prospectively tabulate the oxygen fraction accurately. Another potential limitation is that there was a small but significant difference between the TTI of both SE TIWI (12.6 minutes) and GE TIWI (11.0 minutes), which might create a bias toward having a greater LMCE score on SE TIWI; however, because no significant association was noted between the degree of LMCE and TTI, such bias (if present) was unlikely to affect the LMCE grade between sequences. Another limitation was that several factors such as CSF protein, fraction of inspired oxygen, end-tidal CO₂, and leakage of propofol across the BBB were not evaluated in this study. These factors, previously implicated on T2WI and FLAIR imaging, could be assessed with respect to T1WI in a future study.^21,22