Ziel: Bei der Translation neuartiger Radiotracer in die klinische Phase ist eine Abschätzung der Strahlenexposition am Menschen vor erstmaliger Anwendung notwendig. Hierbei soll die effektive Dosis (ED) am Tiermodell abgeschätzt werden, welche nach i.v. Injektion eines Radiotracers in den Menschen entsteht. Mit Hilfe von [18F]Flubatine und [18F]Fluspidine wurde in Mäusen erstmals mit einem Kleintier-PET/MRT sowie in Menschen mit einem konventionellen PET/CT die interne Dosimetrie berechnet und die PET/MR bildbasierte Methode evaluiert. Um den Einfluss von Speziesunterschieden zu untersuchen wurden weiterhin Ferkel (PET/CT) dosimetrisch untersucht. Methodik: Nach i.v. Injektion von (-) bzw. (+)[18F]Flubatine (a, b) oder (S)- bzw. (R)-[18F]Fluspidine (c,d) wurden (i) in vivo PET Scans (bis zu 7h p.i.) durchgeführt, die List-Mode Daten unter Nutzung der Standardkorrekturen in 10 Zeitframes rekonstruiert und die Organaktivitäten mit ROVER (ABX, Radeberg) in 3 Spezies bestimmt; (ii) ex vivo Organentnahme an Mäusen und anschließender Messung der Organaktivität in einem Gammacounter durchgeführt (Goldstandard). Nach Extrapolation der Tierdaten auf die menschliche Anatomie, wurde die ED mit OLINDA (v.1.1) für alle 3 Spezies berechnet. Ergebnisse: Die Dosimetrie für (a)/(b) ergab eine ED (µSv/MBq) von 12,5/12,1 (n=30 Mäuse), 13,4/14,3 (n=8 Ferkel), 22,3/23,0 (n=6 Menschen) und für (c)/(d) 12,9/14,0 (n=6 Mäuse), 21,0/n.a. (n=4 Menschen). Während (a) und (b) eine vergleichbare Biokinetik sowie ED zeigen, ist die ED von (c) und (d) signifikant (p=0,025) verschieden basierend auf Enantiomeren Unterschieden. Weiterhin besteht eine Unterschätzung der ED zum Menschen von 38% (Ferkel) bis 47% (Mäuse). Schlussfolgerung: Die Strahlenexposition nach i.v. Applikation von (a,b,c,d) liegt im Bereich anderen Fluor-18-markierter Radiotracer und damit im Schwankungsbereich der natürlichen Strahlenexposition. Die Abschätzung der ED unter Nutzung von Tiermodellen mit Hilfe eines Kleintier-PET/MRT ist unter Berücksichtigung der genannten Limitationen möglich und liefert vergleichbare Ergebnisse wie der ex vivo Goldstandard.

[18F]Fluorodeoxyglucose ([18F]FDG) Positron Emission Tomography/Computed Tomography (PET/CT) imaging is a powerful tool in the diagnosis of cancer and subsequent treatment planning. New state-of-the-art PET/CT scanners have the capacity to generate images of superb quality. The new scanners feature detectors with increased sensitivity and a new generation of reconstruction algorithms that produce higher quality images than the scanners they are replacing. In addition to the scanner, the scan duration, amount of administered [18F]FDG activity, and the anatomy of the patients themselves are also determining factors of image quality. There is evidence suggesting that [18F]FDG PET image quality is significantly reduced for larger patients, jeopardizing lesion detection. Two possible solutions to this problem are to (i) increase injected activity or (ii) increase scan duration. Increasing scan duration is preferable but not always possible in a busy clinic. Increasing injected activity is necessary but a proper scaling regimen with patient size must be determined in order to achieve consistent image quality. The aim of the work presented in this thesis was to achieve higher quantification accuracy and consistent image quality for all patients scanned with [18F]FDG PET. Because quantitative PET/CT images require corrections for image degrading effects, for which attenuation correction is the main contributor and is performed based on CT images, the first step in this project was to develop software tools to automate the analysis of phantom images for CT quality assurance. The next step was to optimize the reconstruction parameters for whole body [18F]FDG PET based on a phantom experiment. Finally, a retrospective study was conducted using patient [18F]FDG PET images to characterize the relationship between patient anatomical characteristics and image quality. This work concludes by suggesting optimized reconstruction parameters and a scaling regimen for injected [18F]FDG activity. With the implementation of these recommendations it can be possible to obtain images with increased quantitative value while delivering less dose to patients and maintaining a uniform level of image quality between different patients. / Graduate

Introduction 76Br is of interest for in vivo PET imaging applications. Its relatively long half-life (16.1 h) allows use not only on small molecules but also proteins which have slow excretion as carrier molecules. Irradiation using a low energy proton beam (~ 20 MeV) on an enriched Cu276Se target, followed by dry distillation with thermal chromatography, is one of the best methods to obtain sufficient amounts of 76Br for clinical applications1,2. However, the thermal chromatography is plagued by poor reproducibility and appears unsuitable for automation of its production, leading us to remove the thermal chroma-tography from the dry distillation. In this investigation we employed H2O solution to collect 76Br and optimized the distillation condition using a small amount of 77Br (57.0 h). We also produced large amount of 76Br under the optimized conditions to evaluate the dry distillation method. Material and Methods Target preparation and dry distillation were conducted based on the methods described in previous reports1,2. To produce 77Br, Cu2natSe target was irradiated with 20 MeV proton beams (5 µA) accelerated by AVF cyclotron in the Japan Atomic Energy Agency. The following two systems were used in the dry distillation optimization studies; (1) an initial system was composed of two furnaces, a main and an auxiliary furnace. Temperature of each furnace was set at 1050 °C (main) and 200 °C (auxiliary) respectively; (2) the second system was made of one large furnace composed of heating and cooling area. Temperature of the heating area was varied from 1050 to 1120 °C. In both systems PTFE tubing, leading to a H2O solution (15 mL), was inserted into the apparatus. The irradiated target was heated under streaming Ar gas (30 mL/min.). An enriched Cu276Se target (76Se enrichment: 99.67%) was used for 76Br production. Radioactivity was measured on a high-purity germanium (HPGe) detector coupled to a multichannel analyzer. TLC analyses were conducted on Al2O3 plates (Merck) using 7:1 acetone:H2O as the eluting solvent. Results and Conclusion Low efficiency (33 %) of 77Br recovery was ob-served in the initial system. Distribution of radioactivity inside the apparatus showed that 35 % was trapped in the PTFE tube and the quartz tube. The recovery yield was increased up to 54 % when the auxiliary furnace was turned off, indicating that the temperature gradient inside the quartz tube is suitable to carry 77Br effectively to the H2O trap. We initially used a quartz boat to place the irradiated target in the furnace, but found that using a reusable tungsten backing was better. However, we found that recovery yield was dramatically reduced to 18 %. The studies where the temperature was varied showed that releasing efficiency was increased up to 100 % at the temperature of 1120 °C. Good recovery yield (~ 77 %) was achieved after optimizing the temperature gradient (FIG. 1b). Using the optimized setup, 76Br production runs (n = 6) have been conducted, allowing us to recover up to 39.8 MBq/µAh (EOB) of 76Br. High specific activity (~4400 GBq/µmol) was obtained in the final solution. TLC analysis showed that chemical form obtained was bromide. We concluded that the dry distillation using H2O trap is capable of providing enough high purity 76Br for clinical applications.

Introduction The ISOTRACE™ Super-Conducting Cyclotron is PMB-Alcen’s redeveloped and modernized version of Oxford Instrument’s OSCAR superconducting cyclotron [1]. Its extracted 80+ mi-croamperes of 12 MeV protons are used for the production of PET radioisotopes. Following the philosophy of Dickie, Stevenson, Szlavik [2] for minimizing dose to personnel, and as developed by Dehnel et al [3,4], and Stokely et al [5], the ISOTRACE™ shall utilize an innovative, light-weight, integrated and self-supporting Mini-Beamline. This permits the relatively high residual radiation fields around PET targets to be moved ~1 metre away from the cyclotron, and facilitates the use of local shielding (around the targets) that limits prompt gammas and neutrons, but more importantly attenuates the residual target radiation, so that maintenance/research staff can work on the cyclotron in a relatively low activity environment. In addition, the mini-beamline for PET utilizes a compound quadrupole/steerer doublet that permits active and dynamic focusing/steering of the extracted proton beam for optimized production and minimized losses [3], so it improves on the successful work of Theroux et al [6]. The integrated beamline unit is extremely small, so that it is very unlike bulky traditional PET and SPECT beamlines that require substantial support structures, such as described by Dehnel in [7,8]. Material and Methods The ISOTRACE™ cyclotron is pictured in FIG. 1. The exit port flange and gate valve to which the integrated mini-beamline for PET shall be mounted is shown. Immediately upstream of the exit port, hidden from view, is a 4 jaw collimator (called BPI for Beam Position Indicator) with spilled beam current readbacks to the control system. TABLE 1 shows the nominal beam emittance and Twiss parameter values at the exit port flange location. This ion-optical information is necessary to simulate ion beam transport, develop the mini-beamline, and determine a nominal tune (i.e. magnet settings). Results and Conclusion TABLE 2 shows the ion-optical system parameters. FIGS. 2 and 3 show the horizontal and vertical beam profiles. The Horizontally focusing Quadrupole magnet (HQ), and Vertically focusing Quadrupole magnet (VQ) aperture diameter, 33 mm, was chosen to give sufficient beam acceptance. The focusing strength is a function of BL, so the effective length, L = 150 mm, was chosen to ensure Bmax less than 0.3 Tesla, while keeping overall magnet mass down. The quad-rupole magnets are fitted with water-cooled compound coils in which the copper/mylar strip wound portion of each coil is a winding for the quadrupole focusing function, and the wire wound portion is for the steering function. To increase beam acceptance and provide additional section strength for the pipe support function, the internal aperture of the low-activation aluminium beam pipe and the external shape are in the shape of a cross. FIG. 4 shows the beam crosssection at the mid-point of the downstream quadrupole magnet, and illustrates the additional acceptance as compared to a round beampipe. In order to machine the interior profile, the pipe is comprised of two premachined pieces that are friction stirwelded together. FIG. 5 is an isometric of the mini-beamline for PET. The four upstream HQ compound coils are excited with a 75A power supply for the horizontally focusing quadrupole magnet function, and a ± 10A power supply for a vertical steering function. The same power supplies are used for the four downstream VQ compound coils for the purpose of a vertically focusing quadrupole magnet function and horizontal steering function.

Introduction The goal of this work is to advance the production and use of 52Mn (t½ = 5.6 d, β+: 242 keV, 29.6%) as a radioisotope for in vivo preclinical nuclear imaging. More specifically, the aims of this study were: (1) to measure the excitation function for the natCr(p,n)52Mn reaction at low energies to verify past results [1–4]; (2) to measure binding constants of Mn(II) to aid the design of a method for isolation of Mn from an irradiated Cr target via ion-exchange chromatography, building upon previously published methods [1,2,5–7]; and (3) to perform phantom imaging by positron emission tomography/magnetic resonance (PET/MR) imaging with 52Mn and non-radioactive Mn(II), since Mn has potential dual-modality benefits that are beginning to be investigated [8]. Material and Methods Thin foils of Cr metal are not available commercially, so we fabricated these in a manner similar to that reported by Tanaka and Furukawa [9]. natCr was electroplated onto Cu discs in an industrial-scale electroplating bath, and then the Cu backing was digested by nitric acid (HNO3). The remaining thin Cr discs (~1 cm diameter) were weighed to determine their thickness (~ 75–85 μm) and arranged into stacked foil targets, along with ~25 μm thick Cu monitor foils. These targets were bombarded with ~15 MeV protons for 1–2 min at ~1–2 μA from a CS-15 cyclotron (The Cyclotron Corporation, Berkeley, CA, USA). The beamline was perpendicular to the foils, which were held in a machined 6061-T6 aluminum alloy target holder. The target holder was mounted in a solid target station with front cooling by a jet of He gas and rear cooling by circulating chilled water (T ≈ 2–5 °C). Following bombardment, these targets were disassembled and the radioisotope products in each foil were counted using a high-purity Ge (HPGe) detector. Cross-sections were calculated for the natCr(p,n)52Mn reaction. Binding constants of Mn(II) were measured by incubating 54Mn(II) (t½ = 312 d) dichloride with anion- or cation-exchange resin (AG 1-X8 (Cl− form) or AG 50W-X8 (H+ form), respectively; both: 200–400 mesh; Bio-Rad, Hercules, CA) in hydrochloric acid (HCl) ranging from 10 mM-8 M (anion-exchange) and from 1 mM-1 M (cation-exchange) or in sulfuric acid (H2SO4) ranging from 10 mM-8 M on cation-exchange resin only. The amount of unbound 54Mn(II) was measured using a gamma counter, and binding constants (KD) were calculated for the various concentrations on both types of ion-exchange resin. We have used the unseparated product for preliminary PET and PET/MR imaging. natCr metal was bombarded and then digested in HCl, resulting in a solution of Cr(III)Cl3 and 52Mn(II)Cl2. This solution was diluted and imaged in a glass scintillation vial using a microPET (Siemens, Munich, Germany) small animal PET scanner. The signal was corrected for abundant cascade gamma-radiation from 52Mn that could cause random false coincidence events to be detected, and then the image was reconstructed by filtered back-projection. Additionally, we have used the digested target to spike non-radioactive Mn(II)Cl2 solutions for simultaneous PET/MR phantom imaging using a Biograph mMR (Siemens) clinical scanner. The phantom consisted of a 4×4 matrix of 15 mL conical tubes containing 10 mL each of 0, 0.5, 1.0, and 2.0 mM concentrations of non-radioactive Mn(II)Cl2 with 0, 7, 14, and 27 μCi (at start of PET acquisition) of 52Mn(II)Cl2 from the digested target added. The concentrations were based on previous MR studies that measured spin-lattice relaxation time (T1) versus concentration of Mn(II), and the activities were based on calculations for predicted count rate in the scanner. The PET/MR imaging consisted of a series of two-dimensional inversion-recovery turbo spin echo (2D-IR-TSE) MR sequences (TE = 12 ms; TR = 3,000 ms) with a wide range of inversion times (TI) from 23–2,930 ms with real-component acquisition, as well as a 30 min. list-mode PET acquisition that was reconstructed as one static frame by 3-D ordered subset expectation maximization (3D-OSEM). Attenuation correction was performed based on a two-point Dixon (2PD) MR sequence. The DICOM image files were loaded, co-registered, and windowed using the Inveon Research Workplace software (Siemens).

Introduction The 80kD glycoprotein transferrin (TF) and its related receptor (TFR1) play a major role in the recruitment by cancer cells of factors for their multiplication, adhesion, invasion and metastatic potential. Though primarily designed to bind iron and then be internalised into cells with its receptor, TF can also bind most transition metals such as Co, Cr, Mn, Zr, Ni, Cu, V, In & Ga. Under certain conditions TF binds Ti (IV) even more tightly than it does Fe and that this occurs at the N-lobe (as distinct from C) of apoTF. Further, under physiological conditions the species Fe(C)Ti(N)-TF may provide the route for Ti entry into cells via TFR1 (1). Thus, the radiometal PET reporter isotope 45Ti with an ‘intermediate’ (~hrs) half-life suited to tracking cell-focused biological mechanisms is an attractive option for elucidating cellular mechanisms involving TF binding and internalisation, at least in (preclinical) animal models. 45Ti (T½ = 3.08 hr; + branching ratio = 85 %; mean β+ energy = 439keV, no significant dose-conferring non-511keV γ-emissions) was produced using the reaction 45Sc(p,n)45Ti by irradiating (monoisotopic) scandium discs with an energy-degraded proton beam produced by an 18MeV isochronous medical cyclotron. Separation and purification was achieved with an hydroxylamine hydrochloride functionalised resin. Comparative microPET imaging was performed in an immunodeficient mouse model, measuring biodistributions of the radiolabels 45Ti-oxalate and 45Ti-human-TF (45Ti-h-TF), out to 6hr post-injection. Materials and Methods High purity 15mm diameter scandium disc foils (99.5%, Goodfellow, UK) each thickness 0.100 ± 0.005 mm (55 mg) were loaded into an in-house constructed solid-targetry system mounted on a 300mm external beam line utilising helium-gas and chilled water to cool the target body (2). The proton beam was degraded to 11.7 MeV using a graphite disc integrated into the graphite collimator. This energy abolishes the competing ‘contaminant’ reactions 45Sc(p,n+p)44Sc and 45Sc(p,2n)44Ti. Beam current was measured using the well documented 65Cu(p,n)65Zn reaction. Calculations showed that the chosen energy is close to the optimal primary energy (~12 MeV) for maximising the (thin-target) yield from a 0.100 mm thick target. For separation of Ti from the Sc target two methods were examined; (i) ion exchange column separation using 2000 mg AG 50W-X8 resin conditioned with 10mL 9M HCl. Disc is dissolved in 1 mL of 9M HCl, which at completion of reaction is pipetted into column. Successive 1 mL volumes of 9M HCl are added, and subsequent elutions collected. (ii) Following Gagnon et al., (3) a method employing hydroxylamine hydro-chloride functionalised resin (’hydroxamate method’) was applied, similar to its use in our hands for purification and separation of 89Zr (2) following its original description for 89Zr by Holland et al., (4). Disc dissolved in 2mL 6M HCl, then diluted to 2M. Elute through column to waste fraction 1 (w1 – see FIG. 1). Then elute 6 mL of 2M HCl through column to w2, followed by 6 mL of traceSELECT H2O to w3. Finally, elute Ti into successive 1 mL product fractions (p1, 2 etc.) using 5 mL of 1M oxalic acid. This procedure takes approximate 1 hr. 45Ti in elution vials was measured using γ-spectroscopy. Sc in the same vials was determined later using ICP-MS. Results A typical production run using a beam current of 40 μA for 60min on a 0.100mm-thick disc produced an activity of 1.83 GBq. Radionuclidic analysis of an irradiated disc using calibrated cryo-HPGe γ-spectroscopy revealed T½ = 2.97–3.19 hr (95% CI) for 45Ti, and with contaminant 44Sc < 0.19 %, with no other isotopes detected. Despite systematic adjustments to column conditions satisfactory chemical separation was not achieved using the ion exchange column method (i), despite previous reports of its success (5). Typical results of separation using the successful hydroxamate method (ii) are shown on the FIGURE 1. It is seen that significant portion of 45Ti is lost in the initial washing steps leading to waste collection. N = 4 replicate experiments showed a variation (SD) of 10 % of the mean in each elu-tion fraction. Subsequent ICP-MS of the same elutions for (cold) Sc showed approximately 80 % by mass appeared in w1 and 20 % in w2, with negligible total mass (total fraction ~1/6000) of Sc in product (p1–4) vials. However, the FIG. 1 shows that a total of only 30% of the original activity of 45Ti (corrected to EOB) is available in the product vials, with the vial of highest specific activity (p1) containing 14 %. However, using a stack of 2×0.100mm thick Sc discs as a target yields isotope of adequate specific activity with-out need for concentration, for subsequent labelling and small-animal imaging purposes. In a ‘proof-of-principle’ experiment, two groups of healthy Balb/c-nu/nu female adult mice were administered with 45Ti radiotracers. The first group (N = 3) received approximately 20 MBq IP of 45Ti-oxalate buffered to pH = 7.0, and under-went microPET/CT imaging (Super Argus PET, Sedecal, Spain) out to 6hr post-injection, plus biodistribution analysis of radioactivity by dis-section at sacrifice (6hr). The second group (N = 3) received approximately 20 MBq IP of 45Ti-h-TF and were also studied to 6hr post-injection, followed by radioactive analysis after dissection at sacrifice. Organ and tissue biodistributions of the two groups at 6hr were similar but with 45Ti-oxalate showing slightly greater affinity for bone. Biodistribution by dissection results broadly confirmed the findings from PET images. However, TLC results suggested that similarity of radiolabel biodistributions of the two groups may be due to contamination of the TF radiolabel with non-conjugated Ti at time of injection. An alternative explanation is dechelation in vivo of 45Ti from 45Ti-h-TF. Conclusion Despite significant loss of 45Ti to the waste fractions of the separation process (total 53 %, corrected to EOB), 45Ti of acceptable specific activity and high radionuclidic purity has been produced from the reaction 45Sc(p,n)45Ti, with separation and purification of the product by hydroxamate column chemistry, confirming an earlier report. Though microPET in vivo imaging using 45Ti-based radiolabels was shown to be feasible, the similarity in the results for the label 45Ti-h-TF compared with ‘raw’ 45Ti-oxalate suggests further investigations. These may include a direct comparison of in vivo 45Ti-h-TF small-animal imaging plus post-dissection biodistribution with the same procedures using 89Zr labelled h-apotransferrin (6).

In-beam Positron Emission Tomography (PET) is a system for monitoring high precision radiation therapy which is in the most cases applied to the tumors near organs at risk. High quality and fast availability of in-beam PET images are, therefore, extremely important for successful verification of the dose delivery. Two main problems make an in-beam PET monitoring a challenging task. Firstly, in-beam PET measurements result in a very low counting statistics. Secondly, an integration of the PET scanner into the treatment facility requires significant reduction of the sensitive surface of the scanner and leads to a dual-head form resulting in imaging artifacts. The aim of this work is to bring the imaging process by means of in-beam PET to optimum quality and time scale. The following topics are under consideration: - analysis of image quality for in-beam PET; - image reconstruction; - solutions for building, testing, and integration of a PET monitoring system into the dedicated treatment facility.

Ces travaux de thèse portent sur la proposition de stratégies de segmentation des tumeurs cancéreuses dans un contexte multimodal et multitemporel. La multimodalité fait référence au couplage de données TEP/TDM pour exploiter conjointement les deux sources d’information pour améliorer les performances de la segmentation. La multitemporalité fait référence à la disposition des images acquises à différents dates, ce qui limite une correspondance spatiale possible entre elles.Dans une première méthode, une structure arborescente est utilisée pour traiter et pour extraire des informations afin d’alimenter une segmentation par marche aléatoire. Un ensemble d'attributs est utilisé pour caractériser les nœuds de l'arbre, puis le filtrer et projeter des informations afin de créer une image vectorielle. Un marcheur aléatoire guidé par les données vectorielles provenant de l'arbre est utilisé pour étiqueter les voxels à des fins de segmentation.La deuxième méthode traite le problème de la multitemporalité en modifiant le paradigme de voxel à voxel par celui de nœud à nœud. Deux arbres sont alors modélisés à partir de la TEP et de la TDM avec injection de contraste pour comparer leurs nœuds par une différence entre leurs attributs et ainsi correspondre à ceux considérés comme similaires en supprimant ceux qui ne le sont pas.Dans une troisième méthode, qui est une extension de la première, l'arbre calculé à partir de l'image est directement utilisé pour mettre en œuvre l'algorithme développé. Une structure arborescente est construite sur la TEP, puis les données TDM sont projetées sur l’arbre en tant qu’informations contextuelles. Un algorithme de stabilité de nœud est appliqué afin de détecter et d'élaguer les nœuds instables. Des graines, extraites de la TEP, sont projetées dans l'arbre pour fournir des étiquettes (pour la tumeur et le fond) à ses nœuds correspondants et les propager au sein de la hiérarchie. Les régions évaluées comme incertaines sont soumises à une méthode de marche aléatoire vectorielle pour compléter l'étiquetage de l'arbre et finaliser la segmentation. / This work focuses on the proposition of cancerous tumor segmentation strategies in a multimodal and multitemporal context. Multimodal scope refers to coupling PET/CT data in order to jointly exploit both information sources with the purpose of improving segmentation performance. Multitemporal scope refers to the use of images acquired at different dates, which limits a possible spatial correspondence between them.In a first method, a tree is used to process and extract information dedicated to feed a random walker segmentation. A set of region-based attributes is used to characterize tree nodes, filter the tree and then project data into the image space for building a vectorial image. A random walker guided by vectorial tree data on image lattice is used to label voxels for segmentation.The second method is geared toward multitemporality problem by changing voxel-to-voxel for node-to-node paradigm. A tree structure is thus applied to model two hierarchical graphs from PET and contrast-enhanced CT, respectively, and compare attribute distances between their nodes to match those assumed similar whereas discarding the others.In a third method, namely an extension of the first one, the tree is directly involved as the data-structure for algorithm application. A tree structure is built on the PET image, and CT data is then projected onto the tree as contextual information. A node stability algorithm is applied to detect and prune unstable attribute nodes. PET-based seeds are projected into the tree to assign node seed labels (tumor and background) and propagate them by hierarchy. The uncertain nodes, with region-based attributes as descriptors, are involved in a vectorial random walker method to complete tree labeling and build the segmentation.

Fluorodeoxyglucose Positron Emission Tomography (FDG PET) and Magnetic Resonance Imaging (MRI) are commonly used in a clinical setting as an examination in Alzheimer’s Disease (AD) patients. FDG PET is an imaging tool to evaluate hypometabolism; meanwhile, the MRI observes the brain volume. However, it is still unclear which examination better reflects the tau tangles, which have been known as the hallmark’s pathology of AD. Therefore, this study was conducted to compare FDG PET and MRI in assessing tau pathology in AD, by utilizing a database from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The presence of tau tangles was confirmed by using the Tau-PET images. In total, 275 cognitively impaired subjects were included as well as a subgroup of 147 subjects with positive amyloid status. Based on the analysis, it was observed that higher Tau-PET is significantly associated with FDG PET hypometabolism and MRI atrophy. A similar result was also seen in the amyloid positive subgroups. By comparing the spearman’s correlation coefficients, it was found that that the correlation was stronger between Tau PET and FDG PET (r=-0.414, p&lt;0.001, and r=-0.475, p&lt;0.001 in the positive amyloid subgroup) compared to Tau-PET and MRI (r=-0.331, p&lt;0.001 and r=-0.440, p&lt;0.001 in the positive amyloid subgroup). Inconclusion, FDG PET better reflects the tau pathology compared to MRI in AD.

Actualmente, las mascotas forman parte esencial de nuestras vidas. Cada vez más, las familias peruanas optan por tener a una mascota en su hogar, principalmente en las grandes ciudades. Esto se debe a que existe la tendencia a nivel mundial de que las familias cada vez tengan menos hijos, o incluso ninguno, es ahí donde estos pequeños y adorables seres llenan ese vacío de alguna manera y se vuelven un miembro más de la familia al que dedican todo su amor y atención. En este contexto, Nice Pets ofrece una alternativa a todas aquellas familias que deseen darle lo mejor en calidad y moda a sus mascotas, con diseños modernos e innovadores a la medida y gusto del cliente. Nuestra propuesta vas más allá de la venta, otorga asesoría y retroalimentación de especialistas en caso sea necesario. Cabe señalar que los rubros textil y moda están en auge y crecimiento en Perú, así como existe una poderosa tendencia mundial con los pet lovers, personas que aman a las mascotas y las consideran parte de la familia. Esta combinación de tendencias hace que nuestra propuesta tenga una gran oportunidad de éxito, más aún cuando hemos demostrado en el análisis financiero que nuestro negocio es rentable, con una inversión inicial de S/ 32,658, monto que será asumido completamente por los accionistas y recuperado en un horizonte de 5 años. La viabilidad de nuestro negocio reside principalmente en la calidad de nuestras prendas, así como nuestro dedicado servicio y atención a nuestros clientes. / Pets are now an essential part of our lives. Increasingly, Peruvian families choose to have a pet in their home, mainly in large cities. This is because there is a worldwide trend that families have fewer and fewer children, or even none at all, this is where these adorable little beings somehow fill that void and become one more member of the family that they dedicate all their love and attention. In this context, Nice Pets offers an alternative to all those families who wish to give the best in quality and fashion to their pets, with modern and innovative designs tailored to the client's taste and preferences. Our proposal goes beyond the sale, it provides advice and specialists feedback if necessary. It should be noted that the textile and fashion items are booming and growing in Peru, as well as there is a powerful global trend with pet lovers, people who love pets and consider them part of the family. This combination of trends makes our proposal a great opportunity for success, even more so when we have shown in the financial analysis that our business is profitable, with an initial investment of S / 32,658, an amount that will be fully assumed by the shareholders and recovered in a horizon of 5 years. The viability of our business resides mainly in the quality of our garments, as well as our dedicated service and attention to our clients. / Trabajo de investigación