A novel voluntary weightlifting model in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway.

Our understanding of the molecular mechanisms underlying adaptations to resistance exercise remains elusive despite the significant biological and clinical relevance. We developed a novel voluntary mouse weightlifting model, which elicits squat-like activities against adjustable load during feeding, to investigate the resistance exercise-induced contractile and metabolic adaptations. RNAseq analysis revealed that a single bout of weightlifting induced significant transcriptome responses of genes that function in posttranslational modification, metabolism, and muscle differentiation in recruited skeletal muscles, which were confirmed by increased expression of fibroblast growth factor-inducible 14 (Fn14), Down syndrome critical region 1 (Dscr1) and Nuclear receptor subfamily 4, group A, member 3 (Nr4a3) genes. Long-term (8 weeks) voluntary weightlifting training resulted in significantly increases of muscle mass, protein synthesis (puromycin incorporation in SUnSET assay) and mTOR pathway protein expression (raptor, 4e-bp-1, and p70S6K proteins) along with enhanced muscle power (specific torque and contraction speed), but not endurance capacity, mitochondrial biogenesis, and fiber type transformation. Importantly, weightlifting training profound improved whole-body glucose clearance and skeletal muscle insulin sensitivity along with enhanced autophagy (increased LC3 and LC3-II/I ratio, and decreased p62/Sqstm1). These data suggest that resistance training in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway.

Dynamic FDG-PET in localization of focal epilepsy: A pilot study.

Epilepsy surgery remains underutilized, in part because non-invasive methods of potential seizure foci localization are inadequate. We used high-resolution, parametric quantification from dynamic 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography (dFDG-PET) imaging to locate hypometabolic foci in patients whose standard clinical static PET images were normal. We obtained dFDG-PET brain images with simultaneous EEG in a one-hour acquisition on seven patients with no MRI evidence of focal epilepsy to record uptake and focal radiation decay. Images were attenuation- and motion-corrected and co-registered with high-resolution T1-weighted patient MRI and segmented into 18 regions of interest (ROI) per hemisphere. Tracer uptake was calibrated with a model corrected blood input function with partial volume (PV) corrections to generate tracer parametric maps compared between mean radiation values between hemispheres with z-scores. We identified ROI with the lowest negative z scores (<-1.65 SD) as hypometabolic. Dynamic 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography ( found focal regions of altered metabolism in all cases in which standard clinical FDG-PET found no abnormalities. This pilot study of dynamic FDG-PET suggests that further research is merited to evaluate whether glucose dynamics offer improved clinical utility for localization of epileptic foci over standard static techniques.

Determination of Fatty Acid Metabolism with Dynamic [11C]Palmitate Positron Emission Tomography of Mouse Heart In Vivo.

The goal of this study was to establish a quantitative method for measuring fatty acid (FA) metabolism with partial volume (PV) and spill-over (SP) corrections using dynamic [(11)C]palmitate positron emission tomographic (PET) images of mouse heart in vivo. Twenty-minute dynamic [(11)C]palmitate PET scans of four 18- to 20-week-old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus F-120 PET scanner. A model-corrected blood input function, by which the input function with SP and PV corrections and the metabolic rate constants (k1-k5) are simultaneously estimated from the dynamic [(11)C]palmitate PET images of mouse hearts in a four-compartment tracer kinetic model, was used to determine rates of myocardial fatty acid oxidation (MFAO), myocardial FA esterification, myocardial FA use, and myocardial FA uptake. The MFAO thus measured in C57BL/6 mice was 375.03 ± 43.83 nmol/min/g. This compares well to the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmol/g/min and 400 nmol/min/g. FA metabolism was measured for the first time in mouse heart in vivo using dynamic [(11)C]palmitate PET in a four-compartment tracer kinetic model. MFAO obtained with this model was validated by results previously obtained with mouse hearts ex vivo.

Guidance for methods descriptions used in preclinical imaging papers.

Preclinical molecular imaging is a rapidly growing field, where new imaging systems, methods, and biological findings are constantly being developed or discovered. Imaging systems and the associated software usually have multiple options for generating data, which is often overlooked but is essential when reporting the methods used to create and analyze data. Similarly, the ways in which animals are housed, handled, and treated to create physiologically based data must be well described in order that the findings be relevant, useful, and reproducible. There are frequently new developments for metabolic imaging methods. Thus, specific reporting requirements are difficult to establish; however, it remains essential to adequately report how the data have been collected, processed, and analyzed. To assist with future manuscript submissions, this article aims to provide guidelines of what details to report for several of the most common imaging modalities. Examples are provided in an attempt to give comprehensive, succinct descriptions of the essential items to report about the experimental process.

A novel near-infrared fluorescence imaging probe for in vivo neutrophil tracking.

The development and validation of a multiscopic near-infrared fluorescence (NIRF) probe, cinnamoyl-F-(D)L-F-(D)L-F-PEG-cyanine7 (cFlFlF-PEG-Cy7), that targets formyl peptide receptor on neutrophils using a mice ear inflammation model is described. Acute inflammation was induced in mice by topical application of phorbol-12-myristate-13-acetate to left ears 24 hours before probe administration. Noninvasive NIRF imaging was longitudinally performed up to 24 hours following probe injection. The in vivo neutrophil-targeting specificity of the probe was characterized by a blocking study with preadministration of excess nonfluorescent peptide cFlFlF-PEG and by an imaging study with a scrambled peptide probe cLFFFL-PEG-Cy7. NIRF imaging of mice injected with cinnamoyl-L-F-F-F-L-PEG-cyanine7 (cFlFlF-PEG-Cy7) revealed that the fluorescence intensity for inflamed left ears was approximately fourfold higher than that of control right ears at 24 hours postinjection. In comparison, the ratios acquired with the scrambled probe and from the blocking study were 1.5- and 2-fold at 24 hours postinjection, respectively. Moreover, a microscopic immunohistologic study confirmed that the NIRF signal of cFlFlF-PEG-Cy7 was associated with activated neutrophils in the inflammatory tissue. With this probe, in vivo neutrophil chemotaxis could be correlatively imaged macroscopically in live animals and microscopically at tissue and cellular levels.

T2 -weighted MRI of post-infarct myocardial edema in mice.

T(2) -weighted, cardiac magnetic resonance imaging (T(2) w CMR) can be used to noninvasively detect and quantify the edematous region that corresponds to the area at risk (AAR) following myocardial infarction (MI). Previously, CMR has been used to examine structure and function in mice, expediting the study of genetic manipulations. To date, CMR has not been applied to imaging of post-MI AAR in mice. We developed a whole-heart, T(2) w CMR sequence to quantify the AAR in mouse models of ischemia and infarction. The ΔB(0) and ΔB(1) environment around the mouse heart at 7 T were measured, and a T(2) -preparation sequence suitable for these conditions was developed. Both in vivo T(2) w and late gadolinium enhanced CMR were performed in mice after 20-min coronary occlusions, resulting in measurements of AAR size of 32.5 ± 3.1 (mean ± SEM)% left ventricular mass, and MI size of 50.1 ± 6.4% AAR size. Excellent interobserver agreement and agreement with histology were also found. This T(2) w imaging method for mice may allow for future investigations of genetic manipulations and novel therapies affecting the AAR and salvaged myocardium following reperfused MI.

A nonpeptide angiotensin II type 2 receptor agonist does not attenuate postmyocardial infarction left ventricular remodeling in mice.

Cardiac overexpression of the angiotensin II type 2 receptor (AT2 R) attenuates left ventricular (LV) remodeling after myocardial infarction (MI) in transgenic mice. We hypothesized that a novel nonpeptide AT2 R agonist, compound 21 (C21), would attenuate post-MI LV remodeling. Fifty-nine mice were studied for 28 days after 1-hour surgical occlusion-reperfusion of the left anterior descending coronary artery. Immediately thereafter, 23 mice received 0.3 mg·kg·d of C21 via Alzet osmotic minipump, 16 received 10 mg·kg·d of the AT1 R antagonist candesartan in drinking water, and 20 were untreated controls. Cardiac magnetic resonance imaging measured ejection fraction (EF), LV end-systolic, and end-diastolic volumes (ESVI and EDVI) indexed to weight serially post MI. Infarct size was measured on day 1 by late gadolinium-enhanced cardiac magnetic resonance imaging. At baseline, heart rate, blood pressure, EDVI, ESVI, and EF were similar between groups. Mean infarct size (42%-45% of LV mass) was similar between groups. C21-treated animals demonstrated adverse LV remodeling (increased EDVI and ESVI at all post-MI time points) compared with control. Candesartan therapy preserved left ventricular EF at day 28 compared with the C21-treated group. Thus, direct stimulation of the AT2 R by C21 at 0.3 mg·kg·d does not attenuate post-MI LV remodeling in reperfused MI in mice.

Percutaneous intervention in peripheral artery disease improves calf muscle phosphocreatine recovery kinetics: a pilot study.

We hypothesized that percutaneous intervention in the affected lower extremity artery would improve calf muscle perfusion and cellular metabolism in patients with claudication and peripheral artery disease (PAD) as measured by magnetic resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD (mean ± SD: age 57 ± 9 years; ankle-brachial index (ABI) 0.62 ± 0.17; seven males) were studied 2 months before and 10 months after lower extremity percutaneous intervention. Calf muscle phosphocreatine recovery time constant (PCr) in the revascularized leg was measured by (31)P MRS immediately after symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and treadmill test were performed. The PCr recovery time constant improved significantly following intervention (91 ± 33 s to 52 ± 34 s, p < 0.003). Rest ABI also improved (0.62 ± 0.17 to 0.93 ± 0.25, p < 0.003). There was no difference in MRI-measured tissue perfusion or exercise parameters, although the study was underpowered for these endpoints. In conclusion, in this pilot study, successful large vessel percutaneous intervention in patients with symptomatic claudication, results in improved ABI and calf muscle phosphocreatine recovery kinetics.

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma.

Phagocytic immunotherapies such as CD47 blockade have emerged as promising strategies for glioblastoma (GB) therapy, but the blood brain/tumor barriers (BBB/BTB) pose a persistent challenge for mCD47 delivery that can be overcome by focused ultrasound (FUS)-mediated BBB/BTB disruption. We here leverage immuno-PET imaging to determine how timing of [89Zr]-mCD47 injection relative to FUS impacts antibody penetrance into orthotopic murine gliomas. We then design and implement a rational paradigm for combining FUS and mCD47 for glioma therapy. We demonstrate that timing of antibody injection relative to FUS BBB/BTB disruption is a critical determinant of mCD47 access, with post-FUS injection conferring superlative antibody delivery to gliomas. We also show that mCD47 delivery across the BBB/BTB with repeat sessions of FUS can significantly constrain tumor outgrowth and extend survival in glioma-bearing mice. This study generates provocative insights for ongoing pre-clinical and clinical evaluations of FUS-mediated antibody delivery to brain tumors. Moreover, our results confirm that mCD47 delivery with FUS is a promising therapeutic strategy for GB therapy.

Neutrophil targeting heterobivalent SPECT imaging probe: cFLFLF-PEG-TKPPR-99mTc.

A new heterobivalent peptide ligand specifically targeting polymorphonuclear leukocytes (PMNs) with favorable pharmacological parameters to monitor sites of inflammation for imaging is designed. The detailed synthesis, characterization, and pharmacological evaluation of the ligands are reported here. Two separate peptide binding ligands for formyl peptide and tuftsin receptors were chosen to link together based on the high expression levels of the two receptors on activated PMNs The heterobivalency and pegylated links were incorporated in the structural design to improve the sensitivity of the detection and to improve the bioavailability along with blood clearance profile, respectively. Two chemical constructs, cFLFLF-(PEG)(n)-TKPPR-(99m)Tc (n = 4, 12), were evaluated in vitro with human PMNs for binding affinity and bioavailability. As a result, cFLFLF-(PEG)(12)-TKPPR-(99m)Tc was found to have more favorable pharmacological properties and was therefore used for further in vivo studies. Preliminary in vivo assessment of the agent was performed using single gamma emission computed tomography (SPECT) imaging of a mouse model of ear inflammation. The results of these studies indicate cFLFLF-(PEG)(12)-TKPPR-(99m)Tc may be a desirable imaging agent for binding to PMNs to identify sites of inflammation by SPECT.

Therapeutic Efficacy of Alpha-Lipoic Acid against Acute Myocardial Infarction and Chronic Left Ventricular Remodeling in Mice.

BACKGROUND: We hypothesized that daily administration of a potent antioxidant (α-lipoic acid: ALA) would protect the heart against both acute myocardial infarction (AMI) and left ventricular remodeling (LVR) post-AMI. METHODS AND RESULTS: Two separate studies were conducted. In the AMI study, C57Bl/6 mice were fed ALA daily for 7 d prior to a 45-minute occlusion of the left coronary artery (LCA). Mean infarct size in control mice (fed water) was 60 ± 2%. Mean infarct size in ALA-treated mice was 42 ± 3% in the 15 mg/kg·d group and 39 ± 3% in the 75 mg/kg·d group (both P < 0.05 vs. control). In the LVR study, AMI increased LV end-systolic volume (LVESV) and reduced LV ejection fraction (LVEF) to a similar extent in both groups when assessed by cardiac MRI 1 day after a 2-hour LCA occlusion. Treatment with ALA (75 mg/kg·d) or H2O was initiated 1 day post-AMI and continued until study's end. Both LVESV and LVEF in ALA-treated mice were significantly improved over control when assessed 28 or 56 days post-AMI. Furthermore, the survival rate in ALA-treated mice was 63% better than in control mice by 56 days post-AMI. CONCLUSIONS: Daily oral ingestion of ALA not only protects mice against AMI but also attenuates LVR and preserves contractile function in the months that follow.

Calibration Methodology of an Edgeless PET System Prototype.

Instrumentation research in small animal Positron Emission Tomography (PET) imaging is driven by improving timing, spatial resolution and sensitivity. Conventional PET scanners are built of multiple detectors placed in a cylindrical geometry with gaps between them in both the transaxial and axial planes. These gaps decrease sensitivity and degrade spatial resolution towards the edges of the system field of view (FOV). To mitigate these problems, we have designed and validated an edgeless pre-clinical PET system based on a single LYSO annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2 each. The scintillation light is read out using the row and columns of Silicon Photomultipliers (SiPMs) mounted in magnetic-field compatible PCBs. The objective of this work is to provide a calibration method for this system. The particular design of the annulus produces some undesirable effects in the light distributions (LD) at the module joints, which needs to be addressed. Nevertheless, after calibration, the system allows one to properly retrieve both, the energy and 3D photon impact positions.

Mechanoceutics Alters Alzheimer's Disease Phenotypes in Transgenic Rats: A Pilot Study.

Current advancements in neurovascular biology relates a mechanoceutics treatment, known as cranial osteopathic manipulation (COM), Alzheimer's disease (AD). COM could be used as an evidence-based treatment strategy to improve the symptoms of AD if molecular mechanisms, which currently remain unclear, are elucidated. In the present pilot study, using transgenic rats, we have identified COM mediated changes in behavioral and biochemical parameters associated with AD phenotypes. We expect these changes may have functional implications that might account for improved clinical outcomes of COM treatment. Further investigations on COM will be helpful to establish an adjunct treatment for AD.

A novel neutrophil-specific PET imaging agent: cFLFLFK-PEG-64Cu.

UNLABELLED: The synthesis and validation of a new, highly potent (64)Cu-labeled peptide, cFLFLFK-PEG-(64)Cu, that targets the formyl peptide receptor (FPR) on leukocytes is described. The peptide ligand is an antagonist of the FPR, designed not to elicit a chemotactic response resulting in neutropenia. Evidence for the selective binding of this synthesized ligand to neutrophils is provided. PET properties of the compound were evaluated in a mouse model of lung inflammation. METHODS: The FPR-specific peptide, cinnamoyl-F-(D)L-F-(D)L-FK (cFLFLF), was sequentially conjugated with a bifunctional polyethylene glycol moiety (PEG, 3.4 kD) and a 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) through a lysine (K) spacer and finally labeled with (64)Cu-CuCl(2) to form cFLFLFK-PEG-(64)Cu. The binding affinity and stimulation potency of the ligand toward human neutrophils were assessed in vitro. Blood kinetic and organ biodistribution properties of the peptide were studied in the mouse. Ten male C57BL/6 mice were used in this study; 4 control mice and 6 administered Klebsiella pneumonia. PET/CT scans were performed to assess the localization properties of the labeled peptide in lungs 18 h after tracer administration. Lung standardized uptake values (SUVs) were correlated with lung neutrophil activity as measured by myeloperoxidase assays. Immunohistochemistry was performed to confirm that neutrophils constitute the majority of infiltrating leukocytes in lung tissue 24 h after Klebsiella exposure. RESULTS: In vitro binding assays of the compound cFLFLFK-PEG-(64)Cu to the neutrophil FPR yielded a dissociation constant of 17.7 nM. The functional superoxide stimulation assay exhibited negligible agonist activity of the ligand with respect to neutrophil superoxide production. The pegylated peptide ligand exhibited a blood clearance half-life of 55 +/- 8 min. PET 18 h after tracer administration revealed mean lung SUVs and lung myeloperoxidase activities for Klebsiella-infected mice that were 5- and 6-fold higher, respectively, than those for control mice. Immunohistochemistry staining confirmed that the cellular infiltrate in lungs of Klebsiella-infected mice was almost exclusively neutrophils at the time of imaging. CONCLUSION: This new radiolabeled peptide targeting the FPR binds to neutrophils in vitro and accumulates at sites of inflammation in vivo. This modified peptide may prove to be a useful tool to probe inflammation or injury.

Effect of Osteopathic Cranial Manipulative Medicine on an Aged Rat Model of Alzheimer Disease.

CONTEXT: In the aging brain, reduction in the pulsation of cerebral vasculature and fluid circulation causes impairment in the fluid exchange between different compartments and lays a foundation for the neuroinflammation that results in Alzheimer disease (AD). The knowledge that lymphatic vessels in the central nervous system play a role in the clearance of brain-derived metabolic waste products opens an unprecedented capability to increase the clearance of macromolecules such as amyloid ß proteins. However, currently there is no pharmacologic mechanism available to increase fluid circulation in the aging brain. OBJECTIVE: To demonstrate the influence of an osteopathic cranial manipulative medicine (OCMM) technique, specifically, compression of the fourth ventricle, on spatial memory and changes in substrates associated with mechanisms of metabolic waste clearance in the central nervous system using the naturally aged rat model of AD. RESULTS: Significant improvement was found in spatial memory in 6 rats after 7 days of OCMM sessions. Live animal positron emission tomographic imaging and immunoassays revealed that OCMM reduced amyloid ß levels, activated astrocytes, and improved neurotransmission in the aged rat brains. CONCLUSION: These findings demonstrate the molecular mechanism of OCMM in aged rats. This study and further investigations will help physicians promote OCMM as an evidence-based adjunctive treatment for patients with AD.

Topoisomerase Inhibition Accelerates Gene Expression after Adeno-associated Virus-mediated Gene Transfer to the Mammalian Heart.

Utility of adeno-associated virus 2 (AAV2) vectors for cardiac gene therapy is limited by the prolonged lag phase before maximal gene expression. Topoisomerase inhibition can induce AAV2-mediated gene expression in vivo, but with variable success in different tissues. In this study, we demonstrate that topoisomerase inhibition can accelerate AAV2-mediated gene expression in the mouse heart. We used an AAV2 vector expressing firefly luciferase and monitored expression kinetics using non-invasive bioluminescence imaging. In the group receiving vector alone, cardiac luciferase activity was evident from week 2 onward and increased progressively to reach a steady plateau by 9 weeks postinjection. In the group receiving vector and camptothecine (CPT), luciferase expression was evident from days 2 to 4 onward and increased rapidly to reach a steady plateau by 3-4 weeks postinjection, nearly three times faster than in the absence of CPT (P<0.05). Southern blot analysis of AAV2 genomes in cardiac tissue showed rapid conversion of the AAV2 genome from its single-stranded to double-stranded form in CPT-treated mice. Non-invasive determinations of luciferase expression correlated well with in vitro luciferase assays. Direct injection of the AAV2 vector and long-term luciferase gene expression had no detectable effects on normal cardiac function as assessed by magnetic resonance imaging.

Deep learning-based quantification of abdominal fat on magnetic resonance images.

Obesity is increasingly prevalent and associated with increased risk of developing type 2 diabetes, cardiovascular diseases, and cancer. Magnetic resonance imaging (MRI) is an accurate method for determination of body fat volume and distribution. However, quantifying body fat from numerous MRI slices is tedious and time-consuming. Here we developed a deep learning-based method for measuring visceral and subcutaneous fat in the abdominal region of mice. Congenic mice only differ from C57BL/6 (B6) Apoe knockout (Apoe-/-) mice in chromosome 9 that is replaced by C3H/HeJ genome. Male congenic mice had lighter body weight than B6-Apoe-/- mice after being fed 14 weeks of Western diet. Axial and coronal T1-weighted sequencing at 1-mm-thickness and 1-mm-gap was acquired with a 7T Bruker ClinScan scanner. A deep learning approach was developed for segmenting visceral and subcutaneous fat based on the U-net architecture made publicly available through the open-source ANTsRNet library-a growing repository of well-known neural networks. The volumes of subcutaneous and visceral fat measured through our approach were highly comparable with those from manual measurements. The Dice score, root-mean-square error (RMSE), and correlation analysis demonstrated the similarity between two methods in quantifying visceral and subcutaneous fat. Analysis with the automated method showed significant reductions in volumes of visceral and subcutaneous fat but not non-fat tissues in congenic mice compared to B6 mice. These results demonstrate the accuracy of deep learning in quantification of abdominal fat and its significance in determining body weight.

Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver Tumor Growth.

Rodent models of liver tumorigenesis have reproducibly shown that dietary sugar intake is a powerful driver of liver tumor initiation and growth. In contrast, dietary sugar restriction with ketogenic diets or calorie restriction generally prevents liver tumor formation. Ketogenic diet is viewed positively as a therapeutic adjuvant; however, most ketogenic diet studies described to date have been performed in prevention mode rather than treatment mode. Therefore, it remains unclear whether a ketogenic diet can be administered in late stages of disease to stall or reverse liver tumor growth. To model the clinically relevant treatment mode, we administered a ketogenic diet to mice after liver tumor initiation and monitored tumor growth by magnetic resonance imaging (MRI). Male C57BL/6 mice were injected with diethylnitrosamine (DEN) at 2 weeks of age and fed a chow diet until 39 weeks of age, when they underwent MRI imaging to detect liver tumors. Mice were then randomised into two groups and fed either a chow diet or switched to a ketogenic diet from 40⁻48 weeks of age. Serial MRIs were performed at 44 and 48 weeks of age. All mice had tumors at study completion and there were no differences in total tumor burden between diet groups. Although a ketogenic diet has marked protective effects against DEN-induced liver tumourigenesis in this mouse model, these data demonstrate that ketogenic diet cannot stop the progression of established liver tumors.

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube.

There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.