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Background: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs). Methods: Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response. Results: Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ. Conclusion: Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients. [ABSTRACT FROM AUTHOR]

Key points: The blood–brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system.BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward.Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki.Here evidence is provided that Ki as measured by DCE‐MRI behaves as expected for a marker of overall BBB leakage.These results support the use of DCE‐MRI for in vivo studies of human BBB permeability in health and disease. Blood–brain barrier (BBB) leakage can be measured using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) as the influx constant Ki. To validate this method we compared measured Ki with biological expectations, namely (1) higher Ki in healthy individual grey matter (GM) versus white matter (WM), (2) GM/WM cerebral blood volume (CBV) ratio close to the histologically established GM/WM vascular density ratio, (3) higher Ki in visibly enhancing multiple sclerosis (MS) lesions versus MS normal appearing white matter (NAWM), and (4) higher Ki in MS NAWM versus healthy individual NAWM. We recruited 13 healthy individuals and 12 patients with MS and performed whole‐brain 3D DCE‐MRI at 3 T. Ki and CBV were calculated using Patlak modelling for manual regions of interest (ROI) and segmented tissue masks. Ki was higher in control GM versus WM (P = 0.001). CBV was higher in GM versus WM (P = 0.005, mean ratio 1.9). Ki was higher in visibly enhancing MS lesions versus MS NAWM (P = 0.002), and in MS NAWM versus controls (P = 0.014). Bland–Altman analysis showed no significant difference between ROI and segmentation methods (P = 0.638) and an intra‐class correlation coefficient showed moderate single measure consistency (0.610). Ki behaves as expected for a compound marker of permeability and surface area. The GM/WM CBV ratio measured by this technique is in agreement with the literature. This adds evidence to the validity of Ki measured by DCE‐MRI as a marker of overall BBB leakage. Key points: The blood–brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system.BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward.Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant Ki.Here evidence is provided that Ki as measured by DCE‐MRI behaves as expected for a marker of overall BBB leakage.These results support the use of DCE‐MRI for in vivo studies of human BBB permeability in health and disease. [ABSTRACT FROM AUTHOR]

Purpose: Capillary transit time heterogeneity, measured as CTH, may set the upper limit for extraction of substances in brain tissue, e.g., oxygen. The purpose of this study was to investigate the feasibility of dynamic contrast-enhanced T1 weighted MRI (DCE-MRI) at 3 Tesla (T), in estimating CTH based on a gamma-variate model of the capillary transit time distribution. In addition, we wanted to investigate if a subtle increase of the blood-brain barrier permeability can be incorporated into the model, still allowing estimation of CTH.Materials and Methods: Twenty-three healthy subjects were scanned at 3.0T MRI system applying DCE-MRI and using a gamma-variate model to estimate CTH as well as cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability of the blood-brain barrier, measured as the influx constant Ki . For proof of principle we also investigated three patients with recent thromboembolic events and a patient with a high grade brain tumor.Results: In the healthy subjects, we found a narrow symmetric delta-like capillary transit time distribution in basal ganglia gray matter with median CTH of 0.93 s and interquartile range of 1.33 s. The corresponding residue impulse response function was compatible with the adiabatic tissue homogeneity model. In two patients with complete occlusion of the internal carotid artery and in the patient with a brain tumor CTH was increased with values up to 6 s in the affected brain tissue, with an exponential like residue impulse response function.Conclusion: Our results open the possibility of characterizing brain perfusion by the capillary transit time distribution using DCE-MRI, theoretically a determinant of efficient blood to brain transport of important substances.Level Of Evidence: 2 J. MAGN. RESON. IMAGING 2017;45:1809-1820. [ABSTRACT FROM AUTHOR]