Unlocking multimodal PET-MR synergies for geoscience

The recent combination of positron emission tomography (PET) and magnetic resonance (MR) imaging modalities in one clinical diagnostic tool represents a scientific advancement with high potential impact in geoscientific research; by enabling simultaneous and explicit quantification of up to three distinct fluids in the same porous system. Decoupled information from PET-MR imaging was used here, for the first time, to quantify spatial and temporal porous media fluid flow. Three-dimensional fluid distribution was quantified simultaneously and independently by each imaging modality, and fluid phases were correlated with high reproducibility between modalities and repetitive fluid injections.publishedVersio

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.publishedVersio

Unlocking multimodal PET-MR synergies for geoscience

The recent combination of positron emission tomography (PET) and magnetic resonance (MR) imaging modalities in one clinical diagnostic tool represents a scientific advancement with high potential impact in geoscientific research; by enabling simultaneous and explicit quantification of up to three distinct fluids in the same porous system. Decoupled information from PET-MR imaging was used here, for the first time, to quantify spatial and temporal porous media fluid flow. Three-dimensional fluid distribution was quantified simultaneously and independently by each imaging modality, and fluid phases were correlated with high reproducibility between modalities and repetitive fluid injections

Of rats and rocks: using pre-clinical PET imaging facilities in core analysis

Positron emission tomography (PET) is routinely used for medical imaging; a current surge in published geoscientific research utilizing this modality also infer increasing interest for in-situ PET imaging in core analysis. Excellent signal to noise ratio coupled with high temporal and spatial resolution suggest that PET might become the new method-of-choice for core analysis. Obstacles related to production, transfer and handling of radioactive fluids and gases must, however, be dealt with for PET to become a widely used core scale imaging technique. This paper describes an ongoing, true multidisciplinary collaboration, where pre-clinical PET imaging facilities are routinely used in core analysis to investigate dynamic fluid flow at high pressure conditions. We detail challenges and opportunities related to porous media research in established pre-clinical laboratory facilities designed for small-animal imaging, and demonstrate the significant potential of PET imaging in core scale analysis in a context related to long-term porous media carbon storage. Explicit imaging of several fluid phases is possible by PET imaging using a range of readily available radiotracers. Relevant radiotracers to carbon storage in porous media are e.g. the carbon radioisotope 11C and water-soluble tracer 18F. These are both short-lived tracers (20 - 110 min) and must be used in high doses of radiation, which present challenges related to safe transfer and handling. Although there are several obstacles to conduct advanced core analysis in hospital imaging facilities (some of which are detailed in this paper), significant advantages include trained personnel on-site to operate a local cyclotron, procedures in place to ensure safe and efficient transfer of short-lived radiopharmaceuticals from the cyclotron, and advanced image analysis capabilities available. Cyclotrons are widely available worldwide (currently more than 1200 operating cyclotrons), often located in close proximity to medical and pre-clinical imaging facilities and academic institutions. Similar collaborations may therefore also be possible elsewhere, reducing the need for allocated geophysical PET-scanners and lowering the threshold for routinely using PET imaging in core analysis

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-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-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

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

Orthotopic injection of Ishikawa^Luc cells results in weight loss and reduced survival.

<p>Mice injected with Ishikawa^Luc cells were monitored weekly for signs of disease development. Weight loss (A) was detected as an early sign of disease. Mice developing symptoms of severe disease were sacrificed and the overall survival is visualized in a Kaplan-Meier survival plot (B).</p

Multimodal imaging of the same mouse by MRI, ¹⁸F-FDG PET, ¹⁸F-FLT PET and BLI.

<p>MRI three weeks presacrificed (A) depicting large uterine tumour tissue in the left uterine horn (thin arrows) with intrauterine fluid cranial of the tumour (filled large arrow) and small amounts of free intraperitoneal fluid cranial to the right kidney (K) (small arrows). The tumour tissue is moderately enhancing on T1-weighted series after contrast and the tumour exhibits restricted diffusion with hyperintensity on high b-value DWI with corresponding low apparent diffusion coefficient (ADC) value (1.11 x 10⁻³ mm²/s) on the ADC map (A). BLI 4 to 1 weeks presacrificed (B) shows increasing BLI signal corresponding to the tumour of the left uterine horn; the corresponding tumour tissue was evident macroscopically and confirmed microscopically at necropsy (B). ¹⁸F-FDG PET-CT two weeks presacrificed (C) depicts a large ¹⁸F-FDG-avid tumour in the left uterine horn (arrows) with estimated metabolic tumour volume of 33 ml. ¹⁸F-FLT PET-CT one week presacrificed (D) depicts large ¹⁸F-FLT-avid tumour in the left uterine horn (arrows) with estimated metabolic tumour volume of 44 ml. ¹⁸F-FDG/¹⁸F-FLT-avidity in a VOI in the nuchal muscular tissue (C and D; small arrows) was used as reference tissue to define a threshold for likely tumour tissue (activity of x2 and of x6 for ¹⁸F-FLT and ¹⁸F-FDG, respectively) to be included in the estimated metabolic tumour volume. B: bladder; H: heart.</p

Histological evaluations of tumour characteristics and spread of disease.

<p>Organs were fixed in formaldehyde, sectioned and stained with HE to confirm presence of tumour tissue and for histological characterization of tumour. Sections from a representative mouse depict a large tumour mass in the left uterine horn (A) with necrotic tissue in the centre. Normal uterine morphology is seen in the right uterine horn with endometrial glands and normal stroma and myometrium. Detail of tumour in the left uterine horn (B) reveals solid growing tumour, resembling a grade 3 endometrioid endometrial cancer. Solid tumour masses were also detected in ovaries (C). Inguinal lymph node, macroscopically suspected to be metastatic, was confirmed to represent a metastasis (D), however, without visible surrounding lymphoid tissue. Solid tumour components are depicted in the pancreas (E) with tumour tissue infiltrating surrounding fat tissue. Metastasis is observed on the outer surface of the liver (F), and tumour tissue is also detected in blood vessels of the lung (G), the latter indicating hematogenous spread.</p

Tumour growth monitored by Bioluminescence Imaging (BLI).

<p>Tumour growth was monitored weekly by <i>in vivo</i> BLI and an increase in the net bioluminescence versus time was observed (A, B). Organs were also examined by BLI post-mortem to visualize metastatic spread (C). Strong BLI signals were detected at site of injection (left uterine horn; luh), right ovary (o), connective tissue surrounding the uterine horn (ct), pancreas (p) and metastatic node (mn). Spot signals were detected in the liver (l), spleen (s), kidneys (k), heart (h) and lung (lu). No signal was detected in adrenal gland (a).</p