Ferumoxytol magnetic resonance imaging for intracranial arteriovenous malformation

Ferumoxytol magnetic resonance imaging for intracranial arteriovenous malformation

Central nervous system vascular malformations (VMs) result from abnormal vascular- and/or angiogenesis. Cavernomas and arteriovenous malformations are also sites of active inflammation 1).

Inflammation is increasingly being recognized as contributing to the underlying pathophysiology of cerebral aneurysms and brain arteriovenous malformationFerumoxytol is being increasingly used for both its prolonged intravascular imaging characteristics and its utility as an inflammatory marker when imaged in a delayed fashion 2) 3) 4) 5).

Children with intracranial arteriovenous malformations (AVMs) undergo digital DSA for lesion surveillance following their initial diagnosis. However, DSA carries risks of radiation exposure, particularly for the growing pediatric brain and over lifetime. Huang et al. evaluated whether MRI enhanced with a blood pool ferumoxytol (Fe) contrast agent (Fe-MRI) can be used for surveillance of residual or recurrent AVMs.

A retrospective cohort was assembled of children with an established AVM diagnosis who underwent surveillance by both DSA and 3-T Fe-MRI from 2014 to 2016. Two neuroradiologists blinded to the DSA results independently assessed Fe-enhanced T1-weighted spoiled gradient recalled acquisition in steady state (Fe-SPGR) scans and, if available, arterial spin labeling (ASL) perfusion scans for residual or recurrent AVMs. Diagnostic confidence was examined using a Likert scale. Sensitivity, specificity, and intermodality reliability were determined using DSA studies as the gold standard. Radiation exposure related to DSA was calculated as total dose area product (TDAP) and effective dose.

Fifteen patients were included in this study (mean age 10 years, range 3-15 years). The mean time between the first surveillance DSA and Fe-MRI studies was 17 days (SD 47). Intermodality agreement was excellent between Fe-SPGR and DSA (κ = 1.00) but poor between ASL and DSA (κ = 0.53; 95% CI 0.18-0.89). The sensitivity and specificity for detecting residual AVMs using Fe-SPGR were 100% and 100%, and using ASL they were 72% and 100%, respectively. Radiologists reported overall high diagnostic confidence using Fe-SPGR. On average, patients received two surveillance DSA studies over the study period, which on average equated to a TDAP of 117.2 Gy×cm2 (95% CI 77.2-157.4 Gy×cm2) and an effective dose of 7.8 mSv (95% CI 4.4-8.8 mSv).

Fe-MRI performed similarly to DSA for the surveillance of residual AVMs. Future multicenter studies could further investigate the efficacy of Fe-MRI as a noninvasive alternative to DSA for monitoring AVMs in children 6).


The purpose of a study was to evaluate the performance of ferumoxytol-enhanced MRA using a high-resolution 3D volumetric sequence (fe-SPGR) for visualizing and grading pediatric brain AVMs in comparison with CTA and DSA, which is the current imaging gold standard. METHODS In this retrospective cohort study, 21 patients with AVMs evaluated by fe-SPGR, CTA, and DSA between April 2014 and August 2017 were included. Two experienced raters graded AVMs using Spetzler-Martin criteria on all imaging studies. Lesion conspicuity (LC) and diagnostic confidence (DC) were assessed using a 5-point Likert scale, and interrater agreement was determined. The Kruskal-Wallis test was performed to assess the raters’ grades and scores of LC and DC, with subsequent post hoc pairwise comparisons to assess for statistically significant differences between pairs of groups at p < 0.05. RESULTS Assigned Spetzler-Martin grades for AVMs on DSA, fe-SPGR, and CTA were not significantly different (p = 0.991). LC and DC scores were higher with fe-SPGR than with CTA (p < 0.05). A significant difference in LC scores was found between CTA and fe-SPGR (p < 0.001) and CTA and DSA (p < 0.001) but not between fe-SPGR and DSA (p = 0.146). A significant difference in DC scores was found among DSA, fe-SPGR, and CTA (p < 0.001) and between all pairs of the groups (p < 0.05). Interrater agreement was good to very good for all image groups (κ = 0.77-1.0, p < 0.001). CONCLUSIONS Fe-SPGR performed robustly in the diagnostic evaluation of brain AVMs, with improved visual depiction of AVMs compared with CTA and comparable Spetzler-Martin grading relative to CTA and DSA 7).

References

1)

Dósa E, Tuladhar S, Muldoon LL, Hamilton BE, Rooney WD, Neuwelt EA. MRI using ferumoxytol improves the visualization of central nervous system vascular malformations. Stroke. 2011 Jun;42(6):1581-8. doi: 10.1161/STROKEAHA.110.607994. Epub 2011 Apr 14. PubMed PMID: 21493906; PubMed Central PMCID: PMC3412426.
2)

Zanaty M, Chalouhi N, Starke RM, Jabbour P, Hasan D. Molecular Imaging in Neurovascular Diseases: The Use of Ferumoxytol to Assess Cerebral Aneurysms and Arteriovenous Malformations. Top Magn Reson Imaging. 2016 Apr;25(2):57-61. doi: 10.1097/RMR.0000000000000086. Review. PubMed PMID: 27049242.
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Chalouhi N, Jabbour P, Magnotta V, Hasan D. Molecular imaging of cerebrovascular lesions. Transl Stroke Res. 2014 Apr;5(2):260-8. doi: 10.1007/s12975-013-0291-0. Epub 2013 Oct 23. Review. PubMed PMID: 24323714.
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Chalouhi N, Jabbour P, Magnotta V, Hasan D. The emerging role of ferumoxytol-enhanced MRI in the management of cerebrovascular lesions. Molecules. 2013 Aug 13;18(8):9670-83. doi: 10.3390/molecules18089670. Review. PubMed PMID: 23945642; PubMed Central PMCID: PMC6270297.
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Hasan DM, Amans M, Tihan T, Hess C, Guo Y, Cha S, Su H, Martin AJ, Lawton MT, Neuwelt EA, Saloner DA, Young WL. Ferumoxytol-enhanced MRI to Image Inflammation within Human Brain Arteriovenous Malformations: A Pilot Investigation. Transl Stroke Res. 2012 Jul;3(Suppl 1):166-73. doi: 10.1007/s12975-012-0172-y. PubMed PMID: 23002401; PubMed Central PMCID: PMC3445332.
6)

Huang Y, Singer TG, Iv M, Lanzman B, Nair S, Stadler JA, Wang J, Edwards MSB, Grant GA, Cheshier SH, Yeom KW. Ferumoxytol-enhanced MRI for surveillance of pediatric cerebral arteriovenous malformations. J Neurosurg Pediatr. 2019 Jul 19:1-8. doi: 10.3171/2019.5.PEDS1957. [Epub ahead of print] PubMed PMID: 31323627.
7)

Iv M, Choudhri O, Dodd RL, Vasanawala SS, Alley MT, Moseley M, Holdsworth SJ, Grant G, Cheshier S, Yeom KW. High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations. J Neurosurg Pediatr. 2018 Sep;22(3):251-260. doi: 10.3171/2018.3.PEDS17723. Epub 2018 Jun 8. PubMed PMID: 29882734.

Optic nerve sheath diameter ultrasonography

Optic nerve sheath diameter ultrasonography

Optic nerve sheath diameter ultrasonography is strongly correlated with invasive ICPmeasurements and may serve as a sensitive and noninvasive method for detecting elevated ICP in TBI patients after decompressive craniectomy 1).

Optic nerve sheath diameter measured by transorbital ultrasound imaging is an accurate method for detecting intracranial hypertension that can be applied in a broad range of settings. It has the advantages of being a non-invasive, bedside test, which can be repeated multiple times for re-evaluation 2).

Evolution of ultrasound technology and the development of high frequency (> 7.5 MHz) linear probes with improved spatial resolution have enabled excellent views of the optic nerve sheath.

The optic nerve sheath diameter (ONSD), measured at a fixed distance behind the retina has been evaluated to diagnose and measure intracranial hypertension in traumatic brain injury and intracranial hemorrhage 3) 4).

The optic nerve sheath is fairly easy to visualize by ultrasonography by insonation across the orbit in the axial plane. A-mode ultrasonography was used to view the optic nerve sheath more than four decades ago; B-mode scanning was performed subsequently to assess intraocular lesions 5).

Shirodkar et al., studied the efficacy of ONSD measurement by ultrasonography to predict intracranial hypertension. The case mix studied included meningoencephalitis, stroke, intracranial hemorrhage and metabolic encephalopathy. Using cut-off values of 4.6 mm for females, and 4.8 mm for males, they found a high level of sensitivity and specificity for the diagnosis of intracranial hypertension as evident on CT or MRI imaging 6).

There is wide variation reported in the optimal cut-off values, when ONSD was compared with invasive ICP monitoring, ranging from 4.8 to 5.9 mm7) 8).


Padayachy et al present a method for assessment of optic nerve sheath ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP 9).


Of the studied ultrasound noninvasive intracranial pressure monitoringoptic nerve sheath diameter (ONSD), is the best estimator of ICP. The novel combination of optic nerve sheath diameter ultrasonography and venous transcranial Doppler (vTCD) of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension 10).

The optic nerve sheath diameter has been verified by various clinical studies as a non-invasive indicator of intracranial hypertension 11).

Correlations between ICP and Optic nerve sheath diameter (ONSD) using CT and MRI have been observed in adult populations.

Ultrasound methods has been proposed as an alternative safe technique for invasive ICP measuring methods 12).

Admission ONSD in decompressive craniectomy (DC) patients is high but does not predict mortality and unfavorable outcomes 13).

Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform 14).

Where pediatric patients present with an ONSD of over 6.1mm following a TBI, ICP monitoring should be implemented 15).

Padayachy et al present a method for assessment of ONS pulsatile dynamics using transorbital ultrasound imaging. A significant difference was noted between the patient groups, indicating that deformability of the ONS may be relevant as a noninvasive marker of raised ICP 16).

While the ultrasonographic mean binocular ONSD (>4.53 mm) was completely accurate in detecting elevated ICP, color Doppler indices of the ophthalmic arteries were of limited value 17).

Bedside ultrasound may be useful in the diagnosis of midline intracranial shift by measurement of ONSD 18).


In patients with SAH and acute hydrocephalus after aneurysm rupture, the ONSD remains expanded after normalization of ICP. This is most likely due to an impaired retraction capability of the optic nerve sheath. This finding should be considered when using transorbital sonography in the neuromonitoring of aneurysmal SAH 19).


ONSD >5.5 mm yielded a sensitivity of 98.77% (95% CI: 93.3%-100%) and a specificity of 85.19% (95% CI: 66.3%-95.8%).In conclusion, the optimal cut-off point of ONSD for identifying IICP was 5.5 mm. ONSD seen on ocular US can be a feasible method for detection and serial monitoring of ICP in Korean adult patients 20).

Systematic review

The aim of a systematic review and meta-analysis will be to examine the accuracy of ONSD sonography for increased ICP diagnosis.

Koziarz et al. will include published and unpublished randomised controlled trials, observational studies, and abstracts, with no publication type or language restrictions. Search strategies will be designed to peruse the MEDLINE, Embase, Web of Science, WHO Clinical Trials, ClinicalTrials.gov, CINAHL, and the Cochrane Library databases. We will also implement strategies to search grey literature. Two reviewers will independently complete data abstraction and conduct quality assessment. Included studies will be assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We will construct the hierarchical summary receiver operating characteristic curve for included studies and pool sensitivity and specificity using the bivariate model. We also plan to conduct prespecified subgroup analyses to explore heterogeneity. The overall quality of evidence will be rated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Research ethics board approval is not required for this study as it draws from published data and raises no concerns related to patient privacy. This review will provide a comprehensive assessment of the evidence on ONSD sonography diagnostic accuracy and is directed to a wide audience. Results from the review will be disseminated extensively through conferences and submitted to a peer-reviewed journal for publication 21).

Case series

References

1)

Wang J, Li K, Li H, Ji C, Wu Z, Chen H, Chen B. Ultrasonographic optic nerve sheath diameter correlation with ICP and accuracy as a tool for noninvasive surrogate ICP measurement in patients with decompressive craniotomy. J Neurosurg. 2019 Jul 19:1-7. doi: 10.3171/2019.4.JNS183297. [Epub ahead of print] PubMed PMID: 31323632.
2)

Beare NA, Kampondeni S, Glover SJ, Molyneux E, Taylor TE, Harding SP, Molyneux ME. Detection of raised intracranial pressure by ultrasound measurement of optic nerve sheath diameter in African children. Trop Med Int Health. 2008 Nov;13(11):1400-4. doi: 10.1111/j.1365-3156.2008.02153.x. Epub 2008 Oct 13. PubMed PMID: 18983275; PubMed Central PMCID: PMC3776606.
3)

Geeraerts T, Merceron S, Benhamou D, Vigué B, Duranteau J. Non-invasive assessment of intracranial pressure using ocular sonography in neurocritical care patients. Intensive Care Med. 2008;34:2062–7.
4)

Moretti R, Pizzi B. Optic nerve ultrasound for detection of intracranial hypertension in intracranial hemorrhage patients: Confirmation of previous findings in a different patient population. J Neurosurg Anesthesiol. 2009;21:16–20.
5)

Gangemi M, Cennamo G, Maiuri F, D’Andrea F. Echographic measurement of the optic nerve in patients with intracranial hypertension. Neurochirurgia (Stuttg) 1987;30:53–5.
6)

Shirodkar CG, Rao SM, Mutkule DP, Harde YR, Venkategowda PM, Mahesh MU. Optic nerve sheath diameter as a marker for evaluation and prognostication of intracranial pressure in Indian patients: An observational study. Ind J Crit Care Med. 2014;18:728–734
7)

Rajajee V, Vanaman M, Fletcher JJ, Jacobs TL. Optic nerve ultrasound for the detection of raised intracranial pressure. Neurocrit Care. 2011;15:506–15.
8)

Geeraerts T, Launey Y, Martin L, Pottecher J, Vigué B, Duranteau J, et al. Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury. Intensive Care Med. 2007;33:1704–11.
9) , 16)

Padayachy L, Brekken R, Fieggen G, Selbekk T. Pulsatile Dynamics of the Optic Nerve Sheath and Intracranial Pressure: An Exploratory In Vivo Investigation. Neurosurgery. 2016 Jul;79(1):100-7. doi: 10.1227/NEU.0000000000001200. PubMed PMID: 26813857; PubMed Central PMCID: PMC4900421.
10)

Robba C, Cardim D, Tajsic T, Pietersen J, Bulman M, Donnelly J, Lavinio A, Gupta A, Menon DK, Hutchinson PJA, Czosnyka M. Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: A prospective observational study. PLoS Med. 2017 Jul 25;14(7):e1002356. doi: 10.1371/journal.pmed.1002356. eCollection 2017 Jul. PubMed PMID: 28742869.
11)

Choi SH, Min KT, Park EK, Kim MS, Jung JH, Kim H. Ultrasonography of the optic nerve sheath to assess intracranial pressure changes after ventriculo-peritoneal shunt surgery in children with hydrocephalus: a prospective observational study. Anaesthesia. 2015 Nov;70(11):1268-73. doi: 10.1111/anae.13180. Epub 2015 Aug 24. PubMed PMID: 26299256.
12)

Karami M, Shirazinejad S, Shaygannejad V, Shirazinejad Z. Transocular Doppler and optic nerve sheath diameter monitoring to detect intracranial hypertension. Adv Biomed Res. 2015 Oct 22;4:231. doi: 10.4103/2277-9175.167900. eCollection 2015. PubMed PMID: 26645016; PubMed Central PMCID: PMC4647120.
13)

Waqas M, Bakhshi SK, Shamim MS, Anwar S. Radiological prognostication in patients with head trauma requiring decompressive craniectomy: Analysis of optic nerve sheath diameter and Rotterdam CT Scoring System. J Neuroradiol. 2016 Feb;43(1):25-30. doi: 10.1016/j.neurad.2015.07.003. Epub 2015 Oct 20. PubMed PMID: 26492980.
14)

Robba C, Bragazzi NL, Bertuccio A, Cardim D, Donnelly J, Sekhon M, Lavinio A, Duane D, Burnstein R, Matta B, Bacigaluppi S, Lattuada M, Czosnyka M. Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study. J Neurosurg Anesthesiol. 2016 Mar 18. [Epub ahead of print] PubMed PMID: 26998650.
15)

Young AM, Guilfoyle MR, Donnelly J, Scoffings D, Fernandes H, Garnett MR, Agrawal S, Hutchinson PJ. Correlating optic nerve sheath diameter with opening intracranial pressure in pediatric traumatic brain injury. Pediatr Res. 2016 Aug 11. doi: 10.1038/pr.2016.165. [Epub ahead of print] PubMed PMID: 27513519.
17)

Tarzamni MK, Derakhshan B, Meshkini A, Merat H, Fouladi DF, Mostafazadeh S, Rezakhah A. The diagnostic performance of ultrasonographic optic nerve sheath diameter and color Doppler indices of the ophthalmic arteries in detecting elevated intracranial pressure. Clin Neurol Neurosurg. 2016 Feb;141:82-8. doi: 10.1016/j.clineuro.2015.12.007. Epub 2015 Dec 15. PubMed PMID: 26771156.
18)

Kazdal H, Kanat A, Findik H, Sen A, Ozdemir B, Batcik OE, Yavasi O, Inecikli MF. Transorbital Ultrasonographic Measurement of Optic Nerve Sheath Diameter for Intracranial Midline Shift in Patients with Head Trauma. World Neurosurg. 2016 Jan;85:292-7. doi: 10.1016/j.wneu.2015.10.015. Epub 2015 Oct 17. PubMed PMID: 26485420.
19)

Bäuerle J, Niesen WD, Egger K, Buttler KJ, Reinhard M. Enlarged Optic Nerve Sheath in Aneurysmal Subarachnoid Hemorrhage despite Normal Intracranial Pressure. J Neuroimaging. 2016 Mar-Apr;26(2):194-6. doi: 10.1111/jon.12287. Epub 2015 Aug 17. PubMed PMID: 26278326.
20)

Lee SU, Jeon JP, Lee H, Han JH, Seo M, Byoun HS, Cho WS, Ryu HG, Kang HS, Kim JE, Kim HC, Jang KS. Optic nerve sheath diameter threshold by ocular ultrasonography for detection of increased intracranial pressure in Korean adult patients with brain lesions. Medicine (Baltimore). 2016 Oct;95(41):e5061. PubMed PMID: 27741121; PubMed Central PMCID: PMC5072948.
21)

Koziarz A, Sne N, Kegel F, Alhazzani W, Nath S, Badhiwala JH, Rice T, Engels P, Samir F, Healey A, Kahnamoui K, Banfield L, Sharma S, Reddy K, Hawryluk GWJ, Kirkpatrick AW, Almenawer SA. Optic nerve sheath diameter sonography for the diagnosis of increased intracranial pressure: a systematic review and meta-analysis protocol. BMJ Open. 2017 Aug 11;7(8):e016194. doi: 10.1136/bmjopen-2017-016194. PubMed PMID: 28801417.
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