Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies

Abstract

Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions.

Intracellular Water Lifetime as a Tumor Biomarker to Monitor Doxorubicin Treatment via FFC-Relaxometry in a Breast Cancer Model

“…As demonstrated both in the cell suspensions and in-vivo experiments, k io appears to be a good biomarker of tumor-cell status that can be exploited to non-invasively monitor the early effects of doxorubicin treatment. Therefore, k io can be measured in vivo using multi-relaxation rate measurements in the range 0.01-1 MHz and the 2SX model [6,18], without the need to use paramagnetic contrast agents. Figure 5B shows that a significant decrease (P=0.000207) in k io was observed 3 days after the first treatment, providing an early indication of the effect of doxorubicin on cell metabolism and vitality.…”

“…Currently, metabolic assessments that are based on the use of positron emission tomography (PET) tracers are widely used as they reflect the viability of cancer cells and other functional changes in the response to anticancer treatments ( 4 , 5 ). Moreover, the availability of advanced functional magnetic resonance imaging (fMRI) techniques has furnished new possibilities in the monitoring of therapeutic responses ( 6 ). There is a growing consensus that MRI protocols may provide powerful diagnostic tools in the field of oncology ( 7 ).…”

Development and validation of prediction models for neurocognitive disorders in adult patients admitted to the ICU with sleep disturbance

“…16 Although age has important associations with the development and progression of major drugs, may be conducive for the prevention of NCDs causing sleep disturbance in the ICU patients. Nevertheless, evidence suggests that nonsteroidal anti-inflammatory drugs are also associated with increased risk of delirium in the elderly, 40,41 but not in adults.…”

Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

“…Indeed, a large number of pharmaceuticals are available, which means that phMRI, compared to PET which requires specific radiolabels, is ideally suited for drug discovery. However, it is important to understand what aspects of the dopamine system the phMRI signal reflects [18]. Being a functional technique, the signal is likely more representative of mRNA levels [19], extrasynaptic dopamine concentration or cyclicAMP levels [11], than that it reflects measures such as receptor density for example.…”