Clinical trial NCT06335004: Evaluation of Brain Waste Clearance Pathways Using Magnetic Resonance Imaging in Pediatric Patients With White Matter Diseases
Official title: Valutazione Delle Vie "Glinfatiche" Utilizzando la Risonanza Magnetica Nelle Malattie Della Sostanza Bianca
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Glymphatic System
White Matter Disease
Pediatric Disorder
Perivascular Disease
Keywords: Glymphatic system
white matter disease
perivascular space
diffusion tensor imaging
gadolinium
rare disease
Lead sponsor: IRCCS Eugenio Medea
Sponsor class: OTHER
First posted: 2024-03-28
Enrollment: 100
Sex: ALL
Minimum age (years): 9
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with white matter disease on T2 and FLAIR sequences are included in this study. New MR sequences that can further identify subtle signal intensity changes within these white matter lesions will allow to further characterise them. Some patients will require intravenous gadolinium as part of their diagnostic MR work-up. Research MR sequences will also be acquired after gadolinium admininstration to further improve characterisation of the composition of white matter lesions.

Brief summary: The dilation of perivascular spaces can be the result of various etiopathogenetic processes. White matter atrophy can cause enlargement of these perivascular spaces (PVS) but also obstruction of fluid drainage systems (interstitial fluid, ISF) and metabolites, as evidenced by some recent studies. Focal stagnation of liquids and deposition of toxic material induce tissue hypoxia and neuroglial dysfunction. Dilation of PVS can be associated with changes in white matter and microhemorrhages. We want to study these etiopathogenetic phenomena by implementing specific MRI methods.

Detailed description: Primary objective: the quantification of indirect magnetic resonance markers of altered waste drainage systems using validated scales in patients with white matter disease. Secondary objective: the evaluation of white matter alterations in relation to the known anatomical glymphatic pathways by analyzing both structural and diffusion data.

Eligibility criteria: Inclusion Criteria:

* patients with and without white matter disease
* patients willing to participate in research with signed consent form
* no age limit (results will be age matched)

Exclusion Criteria:

* unwilling to participate in research

Primary outcomes:
measure: Extent of white matter lesions
timeFrame: once at recruitment
measure: Number of perivascular spaces
timeFrame: once at recruitment
measure: Volume of parasagittal dural space
timeFrame: once at recruitment
Secondary outcomes:
Other outcomes:
Locations:
city: Bosisio Parini
country: Italy
facility: Scientific Institute IRCCS Eugenio Medea
state: Lecco
Study officials:
References:
citation: Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.
citation: Ma YJ, Fan S, Shao H, Du J, Szeverenyi NM, Young IR, Bydder GM. Use of Multiplied, Added, Subtracted and/or FiTted Inversion Recovery (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Jun;10(6):1334-1369. doi: 10.21037/qims-20-568.
citation: Ma YJ, Shao H, Fan S, Lu X, Du J, Young IR, Bydder GM. New options for increasing the sensitivity, specificity and scope of synergistic contrast magnetic resonance imaging (scMRI) using Multiplied, Added, Subtracted and/or FiTted (MASTIR) pulse sequences. Quant Imaging Med Surg. 2020 Oct;10(10):2030-2065. doi: 10.21037/qims-20-795.
citation: Naganawa S, Nakane T, Kawai H, Taoka T. Lack of Contrast Enhancement in a Giant Perivascular Space of the Basal Ganglion on Delayed FLAIR Images: Implications for the Glymphatic System. Magn Reson Med Sci. 2017 Apr 10;16(2):89-90. doi: 10.2463/mrms.ci.2016-0114. Epub 2017 Jan 25. No abstract available.
citation: Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018 Nov;17(11):1016-1024. doi: 10.1016/S1474-4422(18)30318-1.
citation: Hawkes CA, Hartig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO. Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol. 2011 Apr;121(4):431-43. doi: 10.1007/s00401-011-0801-7. Epub 2011 Jan 23.