Ingrid Mossige

• Mossige, Ingrid; Valnes, Lars Magnus; Storås, Tryggve Holck; Emblem, Kyrre Eeg; Eide, Per Kristian & Ringstad, Geir Andre (2026). Comparing Glymphatic Function Measures: Diffusion Tensor Image Analysis Along Perivascular Spaces (DTI-ALPS) versus Intrathecal Contrast-Enhanced MRI. Radiology. ISSN 0033-8419. 318(2). doi: 10.1148/radiol.252070. Full text in Research Archive Show summary

  Background Diffusion-tensor image (DTI) analysis along the perivascular space (ALPS) is a noninvasive but not well-validated method proposed to evaluate glymphatic function. Purpose To assess ALPS indexes across participant groups and compare them with measures of cerebrospinal fluid (CSF) tracer enrichment and clearance obtained by intrathecal contrast-enhanced MRI (glymphatic MRI [gMRI]). Materials and Methods This secondary analysis of a prospective observational study included participants who underwent clinical work-up for CSF disorders from September 2015 to December 2019. MRI scans were acquired before injection and 24 and 48 hours after intrathecal injection of 0.5 mmol of gadobutrol. DTI scans were preprocessed and segmented using the FMRIB Software Library. Intrathecal contrast-enhanced MRI (ie, gMRI) scans were registered to the baseline T1-weighted image, and cortex and white matter (WM) were segmented with FreeSurfer. ALPS indexes were compared with relative changes in normalized T1-weighted signal intensity at 24 and 48 hours in regions of the cortex, subcortical WM, and deep WM where the ALPS regions of interest are located by using regression analysis. Results A total of 56 participants were included (mean age, 48 years ± 20 [SD]; 36 women): 16 with idiopathic normal pressure hydrocephalus (iNPH), 10 with arachnoid cysts, 11 with idiopathic intracranial hypertension, and 19 reference participants. The ALPS index was lower in the iNPH group than in the reference group (ALPS index, 1.26 and 1.68, respectively; P < .001). Across groups, the ALPS index and degree of CSF tracer enrichment at 24 hours in deep WM were negatively associated (β = −48; P < .001). However, mean tracer enrichment in the ALPS regions of interest was low (10%), in some participants close to 0, whereas enrichment in the cortex ranged from 68% to 81%. Across groups, there was no evidence of associations between the ALPS index and measures of CSF tracer dynamics at 48 hours in any region (|β| ≤ 8; P ≥ .55). Conclusion CSF tracer enhancement in the ALPS regions of interest was sparse across groups, and the association between the ALPS index and gMRI markers of glymphatic function was limited.

• Storås, Tryggve Holck; Lian, Sofie Lysholm; Mossige, Ingrid; Riseth, Jørgen Nilsen; Svensson, Siri Fløgstad & Løvland, Grethe [Show all 10 contributors for this article] (2025). T2-Weighted T1 Mapping and Automated Segmentation of CSF: Assessment of Solute Gradients in the Healthy Brain. Journal of Magnetic Resonance Imaging. ISSN 1053-1807. 0, p. 1–10. doi: 10.1002/jmri.70169. Full text in Research Archive Show summary

  Background Cerebrospinal fluid (CSF) serves as a medium for nutrient delivery and waste clearance. The T1 relaxation rate, R1, can be used to measure the concentration of intrinsic solutes and extrinsic contrast agents. Purpose To implement a method for R1 mapping and segmentation of CSF and to use this method to explore how R1 of CSF relates to protein content and gadobutrol after intrathecal administration. Study Type Prospective cohort study, complemented by phantom analysis. Population Ten healthy control subjects (mean age 65.5 ± 4.4 years, range 57–72 years; five males and five females) and protein‐ and gadobutrol‐gradient phantom. Field Strength/Sequence 3 T Philips Ingenia scanner; 3D T2W mixed inversion recovery spin‐echo (T2W‐mixed IRSE) sequence and 3D T1W turbo field echo (3D T1W‐TFE). Assessment R1 maps were calculated by combining IR and SE data. An automated segmentation method derived from FreeSurfer employed SE data for CSF segmentation and T1W‐TFE for anatomical reference. CSF was collected by lumbar puncture for protein measurements, and 0.25 mmol gadobutrol was injected intrathecally. Post‐contrast assessments were performed at 3, 24, 48, and 72 h. Statistical Tests One‐way ANOVA, followed by a post hoc Tukey HSD test, and simple and multiple linear regression analysis; significance level of 0.05. Results R1 of ventricular CSF 0.216 ± 0.001 s −1 was significantly lower than that surrounding the cerebellum 0.225 ± 0.001 and cerebrum 0.228 ± 0.002 and correlated with lumbar protein concentration ( R 2  = 0.56). Peak gadobutrol concentrations were 101 ± 84 μM in ventricles, 185 ± 89 μM in cerebellar SAS and 166 ± 91 μM in cerebral SAS. Corresponding concentrations were 6 ± 4, 17 ± 8, and 37 ± 18 μM at 72 h. Data Conclusion Intrinsic R1 of CSF in the subarachnoid space correlated with protein content. Intracranial CSF enrichment after intrathecal administration of gadobutrol showed a large variation among healthy volunteers. Evidence Level 2. Technical Efficacy 3.

• Osch, Matthias J. P. van; Wåhlin, Anders; Scheyhing, Paul; Mossige, Ingrid; Hirschler, Lydiane & Eklund, Anders [Show all 16 contributors for this article] (2024). Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood. NMR in Biomedicine. ISSN 0952-3480. 37(9). doi: 10.1002/nbm.5159. Full text in Research Archive Show summary

  Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the “EU Joint Programme – Neurodegenerative Disease Research (JPND)” consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.

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