Bias Field Correction in Magnetic Resonance Images of a Rat Brain

Magnetic Resonance Imaging (MRI) is nowadays a widely used medical tool, as it is a non-invasive and non-harmful way to study inner soft tissues. One of the characteristics of this method is the bias field, also called Intensity In-homogeneity (IIH), which is an artifact that affects quantitative image analysis consisting in a low frequency variation of the brightness through all the image acquired. This undesired effect makes difficult medical functions such as visual inspection or also intensity-based segmentation [1]. The bias field is a deterministic function tied to complex physical interactions between the magnetic and electric fields and the living tissues, and this is why in this paper this bias field is directly corrected from the corrupt image data, using all the a priori information at our disposal. We will speciffically work on surface-coil images acquired at 9.4T, where the inhomogeneity effect is even stronger [2]

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson's disease

The dual-hit hypothesis of Parkinson's disease (PD) originally postulated that a neurotropic pathogen leads to formation of alpha-synuclein pathology in the olfactory bulb (OB) and dorsal motor nucleus of the vagus (DMV) and then invades the brain from these two entry points. Little work has been conducted to validate an important underlying premise for the dual-hit hypothesis, namely that the initial Lewy pathology does arise simultaneously in the OB and the enteric nervous system (ENS) plexuses and DMV at the earliest disease stage. We conducted a focused re-analysis of two postmortem datasets, which included large numbers of mild Lewy body disease (LBD) cases. We found that cases with alpha-synuclein pathology restricted to the peripheral autonomic nervous system and/or lower brainstem (early body-first LBD cases) very rarely had any OB pathology, suggesting that Lewy pathology commonly arises in the ENS without concomitant involvement of the OB. In contrast, cases with mild amygdala-predominant Lewy pathology (early brain-first LBD cases) nearly always showed OB pathology. This is compatible with the first pathology being triggered in the OB or amygdala followed by secondary spreading to connected structures, but without early involvement of the ENS or lower brainstem. These observations support that the pathologic process starts in either the olfactory bulb or the ENS, but rarely in the olfactory bulb and gut simultaneously. More studies on neuropathological datasets are warranted to reproduce these findings. The agreement between the revised single-hit hypothesis and the recently proposed brain-first vs. body-first model of LBD is discussed.Peer reviewe

Impact of aging on animal models of Parkinson's disease

Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models

Thymidine Metabolism as Confounding Factor of 3'-Deoxy-3'-[18F]Fluorothymidine Uptake after Therapy in a Colorectal Cancer Model.

Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which was accompanied by increases in markers for proliferation (Ki67, TK1) and for activated DNA damage response (DDR; γH2AX), whereas the effect on cell death was minimal. As tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrate that [18F]FLT PET can non-invasively monitor molecular alterations induced by a cancer treatment, including thymidine metabolism and DDR. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements

Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years

Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial–interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance

MRI techniques for non-invasively investigating the characteristics of tumour vasculature

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Proton functional magnetic resonance spectroscopy in rodents

International audienceProton functional magnetic resonance spectroscopy (H-1-fMRS) in the human brain is able to assess and quantify the metabolic response due to localized brain activity. Currently, H-1-fMRS of the human brain is complementary to functional magnetic resonance imaging (fMRI) and a recommended technique at high field strengths (>7 T) for the investigation of neurometabolic couplings, thereby providing insight into the mechanisms underlying brain activity and brain connectivity. Understanding typical healthy brain metabolism during a task is expected to provide a baseline from which to detect and characterize neurochemical alterations associated with various neurological or psychiatric disorders and diseases. It is of paramount importance to resolve fundamental questions related to the regulation of neurometabolic processes. New techniques such as optogenetics may be coupled to fMRI and fMRS to bring more specificity to investigations of brain cell populations during cerebral activation thus enabling a higher link to molecular changes and therapeutic advances. These rather novel techniques are mainly available for rodent applications and trigger renewed interest in animal fMRS. However, rodent fMRS remains fairly confidential due to its inherent low signal-to-noise ratio and its dependence on anesthesia. For instance, the accurate determination of metabolic concentration changes during stimulation requires robust knowledge of the physiological environment of the measured region of interest linked to anesthesia in most cases. These factors may also have a strong influence on B0 homogeneity. Therefore, a degree of calibration of the stimulus strength and duration may be needed for increased knowledge of the underpinnings of cerebral activity. Here, we propose an early review of the current status of H-1-fMRS in rodents and summarize current difficulties and future perspectives