The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

BACKGROUND: Aquaporin (AQP) water channels play a significant role in mesenchymal microvascular proliferation and infiltrative growth. AQPs are highly expressed in malignant astrocytomas, and a positive correlation is observed between their expression levels and histological tumor grade. OBJECTIVE: To examine the utility of aquaporin positron emission tomography (PET) for differentiating between astrocytoma grade III and grade IV using the AQP radioligand [ ¹¹ C]TGN-020. METHODS: Fifteen astrocytoma patients, grade III (n = 7) and grade IV (n = 8), and 10 healthy volunteers underwent [ ¹¹ C]TGN-020 aquaporin PET imaging. Surgical tissues of astrocytoma patients were examined for histopathological grading using the WHO classification standard and expression of AQP1 and AQP4 immunohistochemically. RESULTS: Mean standardized uptake values of astrocytoma grade III and IV (0.51 ± 0.11 vs 1.50 ± 0.44, respectively) were higher than normal white matter (0.17 ± 0.02, P < .001) for both tumor grades. Importantly, mean standardized uptake values of astrocytoma grade IV were significantly higher than grade III ( P < .01). CONCLUSION: Our study demonstrated that [ ¹¹ C]TGN-020 aquaporin PET imaging differentiated between astrocytoma grades III and IV. We suggest its clinical application as a noninvasive diagnostic tool would lead to advancements in the management of these malignant brain tumors.

The neural processes underlying self-initiated behavior (behavior that is initiated without an external stimulus trigger) are not well understood. This event-related fMRI study investigated the neural origins of self-initiated behaviors in humans, by identifying brain regions that increased in neural activities several seconds prior to self-initiated movements. Subjects performed a hand grasping task under two conditions: a free-timing and cued timing condition. The supplementary motor area (SMA) began to activate several seconds prior to self-initiated movement (accounting for hemodynamic delay), representing a potential blood oxygenation level-dependent (BOLD) signal correlate of the readiness potential (RP) on electroencephalogram (EEG), referred to here as “readiness BOLD signals.” Significant readiness BOLD signals were also observed in the right frontoparietal areas, precuneus, and insula, all of which are known to contribute to internally-generated behaviors, but with no prior evidence for such early and slow accumulation of neural activities. Moreover, visual and auditory cortices also exhibited clear readiness BOLD signals with similar early onsets, even absent external stimulation. Slow accumulation of neural activities throughout distributed cortical areas, including sensory, association, and motor cortices, underlies the generation of self-initiated behaviors. These findings warrant reconsideration of the prevailing view that the SMA or some other specific locus in frontoparietal cortex serves as the ultimate neural origin of self-initiated movement.

Objective: This study aimed to investigate brain developmental alterations in individuals exposed to childhood maltreatment (CM) with dissociative experiences and motor coordination symptoms using diffusion tensor imaging on a 3Tesla (3T) magnetic resonance (MR) system. Methods: Five individuals exposed to CM who manifest behavioral and developmental problems with dissociative experiences and motor coordination symptoms (age range: 14–18 years; all female), as well as seven age- and gender-matched normal control individuals, participated in the study using a 3T MR system. Diffusion characteristics, as indexed by fractional anisotropy (FA), were assessed for cerebral white matter structures. A preliminary whole brain analysis was performed complementary to an anatomically guided region of interest (ROI) analysis. Results: In individuals exposed to CM, scattered decreases in FA were detected in multiple brain regions over the frontoparietal and temporal areas in the whole brain map. ROI analysis subsequently identified significant decreases in FA (p < 0.05) in the right parietal white matter area as well as in the right prefrontal, bilateral premotor, bilateral orbitofrontal, and temporal white matter areas in CM-exposed individuals compared to that in controls. Conclusion: The observed altered diffusion characteristics indicate attendant developmental abnormalities within the white matter structures, which are associated with the observed clinical and behavioral patterns including dissociative experiences and coordination symptoms in individuals exposed to CM. The study provides objective evidence regarding the effects of CM on brain microstructure.

Background: Elucidation of the mechanism of amyloid-β accumulation plays an important role in therapeutic strategies for Alzheimer’s disease (AD). The aim of this study is to elucidate the relationship between the function of the blood–cerebrospinal fluid barrier (BCSFB) and the clearance of amyloid-β (Aβ). Methods: Twenty-five normal older adult volunteers (60–81 years old) participated in this PET study for clarifying the relationship between interstitial water flow and Aβ accumulation. Water dynamics were analyzed using two indices in [¹⁵O]H₂O PET, the influx ratio (IR) and drain rate (DR), and Aβ accumulation was assessed qualitatively by [¹⁸F]flutemetamol PET. Results: [¹⁵O]H₂O PET examinations conducted initially and after 2 years showed no significant changes in both indices over the 2-year period (IR: 1.03 ± 0.21 and 1.02 ± 0.20, DR: 1.74 ± 0.43 and 1.67 ± 0.47, respectively). In [¹⁸F]flutemetamol PET, on the other hand, one of the 25 participants showed positive results and two showed positive changes after 2 years. In these three participants, the two indices of water dynamics showed low values at both periods (IR: 0.60 ± 0.15 and 0.60 ± 0.13, DR: 1.24 ± 0.12 and 1.11 ± 0.10). Conclusions: Our results indicated that BCSFB function disturbances could be followed by Aβ accumulation, because the reduced interstitial flow preceded amyloid accumulation in the positive-change subjects, and amyloid accumulation was not observed in the older adults with sufficiently high values for the two indices. We believe that further elucidation of interstitial water flow will be the key to developing therapeutic strategies for AD, especially with regard to prevention.