Interstitial fluid (ISF) refers to the fluid between the parenchymal cells and along the perivascular spaces (PVS). ISF plays a crucial role in delivering nutrients and clearing waste products from the brain. This narrative review focuses on the use of MRI techniques to measure various ISF characteristics in humans. The complementary value of contrast‐enhanced and noncontrast‐enhanced techniques is highlighted. While contrast‐enhanced MRI methods allow measurement of ISF transport and flow, they lack quantitative assessment of ISF properties. Noninvasive MRI techniques, including multi‐b‐value diffusion imaging, free‐water‐imaging, T₂‐decay imaging, and DTI along the PVS, offer promising alternatives to derive ISF measures, such as ISF volume and diffusivity. The emerging role of these MRI techniques in investigating ISF alterations in neurodegenerative diseases (eg, Alzheimer's disease and Parkinson's disease) and cerebrovascular diseases (eg, cerebral small vessel disease and stroke) is discussed. This review also emphasizes current challenges of ISF imaging, such as the microscopic scale at which ISF has to be measured, and discusses potential focus points for future research to overcome these challenges, for example, the use of high‐resolution imaging techniques. Noninvasive MRI methods for measuring ISF characteristics hold significant potential and may have a high clinical impact in understanding the pathophysiology of neurodegenerative and cerebrovascular disorders, as well as in evaluating the efficacy of ISF‐targeted therapies in clinical trials.Level of Evidence: 3Technical Efficacy: Stage 2

Focal epilepsy is a common and severe neurologic disorder. Neuroimaging aims to identify the epileptogenic zone (EZ), preferably as a macroscopic structural lesion. For approximately a third of patients with chronic drug-resistant focal epilepsy, the EZ cannot be precisely identified using standard 3.0-T MRI. This may be due to either the EZ being undetectable at imaging or the seizure activity being caused by a physiologic abnormality rather than a structural lesion. Computational image processing has recently been shown to aid radiologic assessments and increase the success rate of uncovering suspicious regions by enhancing their visual conspicuity. While structural image analysis is at the forefront of EZ detection, physiologic image analysis has also been shown to provide valuable information about EZ location. This narrative review summarizes and explains the current state-of-the-art computational approaches for image analysis and presents their potential for EZ detection. Current limitations of the methods and possible future directions to augment EZ detection are discussed.

Background: In temporal lobe epilepsy (TLE), locally reduced glucose metabolism (i.e., hypometabolism) is indicative of the epileptogenic onset zone (EZ). Here, we investigate the potential value of resting-state fMRI (rs-fMRI) for localizing the EZ with fluorodeoxyglucose positron emission tomography (FDG-PET) as ground truth. Methods: Twelve PET-positive patients (34.1 ± 13.1 y; 5 females) with unilateral drug-resistant TLE were included. FDG-PET and rs-fMRI were acquired simultaneously at a hybrid 3T PET-MR scanner. Hypometabolic regions were identified on the FDG-PET images by a nuclear medicine expert. The FDG-PET images were compared with a clinical FDG-PET control dataset with normal glucose uptake distribution. The output z-score maps were thresholded at z < −2 to produce a binary mask of the significantly hypometabolic regions. The hypometabolism masks were mirrored onto the contralateral hemisphere for the asymmetry comparison. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) were calculated from the rs-fMRI in conventional (0.01–0.1 Hz) and slow-3 (0.073–0.198 Hz) frequency bands. Asymmetry indices (AIs) were calculated using the ipsilateral and contralateral hypometabolic masks in the PET-positive subjects and assessed via the one-sample Wilcoxon test and Spearman correlation coefficients. Results: The AIs of conventional fALFF were significantly lower in the hypometabolic zone (p < 0.05). A significant negative correlation was found between the AIs of FDG-PET and fALFF in the slow-3 band (r = −0.62; p < 0.05). Conclusions: Conventional and slow-3 band fALFF showed a potential to mimic the FDG-PET findings in terms of EZ localization. Further research with extended cohorts and histopathological validation is required to determine the clinical value.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is the most frequent neurological complication following chimeric antigen receptor (CAR)-T cell therapy. Long-term cognitive effects remain controversial, even in the absence of clinical neurotoxicity. CAR-T cell-associated neurotoxicity often involves the medial temporal lobe (MTL), yet conventional structural magnetic resonance imaging (MRI) frequently remains normal. There is a need for markers of subclinical neurotoxicity that may predict long-term cognitive outcomes. Therefore, we established an imaging protocol integrating 3 Tesla (T) and 7 T perfusion and functional connectivity MRI of the MTL in patients receiving CAR-T cells for B cell malignancies. Longitudinal data from four patients is presented here. Two of the four patients developed ICANS (grade 1 and grade 3), and these patients also experienced mild cytokine release syndrome (CRS, grade 1). No structural abnormalities of the MTL were detected at baseline or during follow-up. CAR-T cell expansion varied markedly between patients. Regardless of ICANS, CRS, or CAR-T cell expansion, patients showed increased MTL perfusion and functional connectivity, most prominently at days 10-14. These data suggest an early, clinically silent inflammatory response in the MTL with potential implications for long-term cognitive function, which requires further investigation.

Purpose: Through its global and extensive connections with multiple brain structures, the thalamus can play an important role in seizure propagation. This study investigated volumetric and functional connectivity alterations of the thalamus and more specifically the thalamic nuclei subgroups using 7T MRI in patients with MRI-negative drug-resistant focal epilepsy (DRE). Methods: Twenty-nine patients with MRI-negative DRE and 49 healthy controls underwent 7T MRI, including T1-weighted and resting-state functional MRI sequences. Thalamic nuclei segmentations were derived using automated segmentation tools and split into anterior (ANT), medial, ventral, and posterior nuclei groups. Functional connectivity with the rest of the brain was assessed using degree centrality (DC). Linear regression models evaluated group differences and relationships with epilepsy characteristics while controlling for age and sex. Asymmetry indices assessed the ipsi- vs. contralateral differences in the patient cohort. Results: Patients showed decreased bilateral medial and increased bilateral ventral relative volumes, alongside a right-sided ANT volume increase, compared with controls. DC was increased in the left posterior and ventral nuclei. Both volume and DC in the medial, ventral, and whole-thalamic ROIs were related to epilepsy duration, while ventral and whole-thalamic DC asymmetry distinguished patients by seizure type and seizure duration. Conclusions: Both structural and functional alterations of the thalamic nuclei groups in patients with DRE were observed. Ventral, medial, and posterior nuclei metrics show promise as imaging biomarkers of disease burden and seizure severity, thus encouraging further research into both structural and functional properties of thalamic nuclei in focal epilepsy.