Default-mode network functional connectivity is closely related to metabolic activity.

Over the last decade, the brain's default-mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood-oxygen level-dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2-deoxy-2-[(18) F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy ((1) H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG-uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal.

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Enhancing PSMA-PET/CT with intravenous contrast: Improved tracer clearance in the prostate bed.

AIMS: We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. METHODS: Among 128 patients imaged with [18F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [18F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUVpost/SUVant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [18F]PSMA-1007, while a control flask was shaken at the start of the experiment. RESULTS: Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33-62) for [18F]PSMA-1007 and 73 % (52-67) for [18F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. CONCLUSION: When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR.

The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.

Short and long-term effects of single and multiple sessions of electroconvulsive therapy on brain gray matter volumes.

BACKGROUND: Electroconvulsive therapy (ECT) has been shown to induce broadly distributed cortical and subcortical volume increases, more prominently in the amygdala and the hippocampus. Structural changes after one ECT session and in the long-term have been understudied. OBJECTIVE: The aim of this study was to describe short-term and long-term volume changes induced in cortical and subcortical regions by ECT. METHODS: Structural brain data were acquired from depressed patients before and 2 h after their first ECT session, 7-14 days after the end of the ECT series and at 6 months follow up (N = 34). Healthy, age and gender matched volunteers were scanned according to the same schedule (N = 18) and patients affected by atrial fibrillation were scanned 1-2 h before and after undergoing electrical cardioversion (N = 16). Images were parcelled using FreeSurfer and estimates of cortical gray matter volume and subcortical volume changes were obtained using Quarc. RESULTS: Volume increase was observable in most of gray matter regions after 2 h from the first ECT session, with significant results in brain stem, bilateral hippocampi, right putamen and left thalamus, temporal and occipital regions in the right hemisphere. At the end of treatment series, widespread significant volume changes were observed. After six months, the right amygdala volume was still significantly increased. No significant changes were observed in the comparison groups. CONCLUSIONS: Volume increases in gray matter areas can be detected 2 h after a single ECT session. Further studies are warranted to explore the underlying molecular mechanisms.

Multispectral analysis of multimodal images.

INTRODUCTION: An increasing number of multimodal images represent a valuable increase in available image information, but at the same time it complicates the extraction of diagnostic information across the images. Multispectral analysis (MSA) has the potential to simplify this problem substantially as unlimited number of images can be combined, and tissue properties across the images can be extracted automatically. MATERIALS AND METHODS: We have developed a software solution for MSA containing two algorithms for unsupervised classification, an EM-algorithm finding multinormal class descriptions and the k-means clustering algorithm, and two for supervised classification, a Bayesian classifier using multinormal class descriptions and a kNN-algorithm. The software has an efficient user interface for the creation and manipulation of class descriptions, and it has proper tools for displaying the results. RESULTS: The software has been tested on different sets of images. One application is to segment cross-sectional images of brain tissue (T1- and T2-weighted MR images) into its main normal tissues and brain tumors. Another interesting set of images are the perfusion maps and diffusion maps, derived images from raw MR images. The software returns segmentations that seem to be sensible. DISCUSSION: The MSA software appears to be a valuable tool for image analysis with multimodal images at hand. It readily gives a segmentation of image volumes that visually seems to be sensible. However, to really learn how to use MSA, it will be necessary to gain more insight into what tissues the different segments contain, and the upcoming work will therefore be focused on examining the tissues through for example histological sections.

Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma.

BACKGROUND: Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy. METHODS: After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer. RESULTS: Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue. CONCLUSIONS: We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.