Julia Cortés

In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan

&NA; In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well‐established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99mTc‐DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5 h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one‐phase decay and a half time of 262 min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay. Graphical abstract Figure. No caption available.

PET and MRI detection of early and progressive neurodegeneration in spinocerebellar ataxia type 36

The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal‐dominant degenerative diseases. In particular, SCA36 is characterized by a late‐onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG‐PET) and MRI scans.

Substraction acetazolamide SPECT co-registered to MRI in moyamoya disease: quantitative cerebrovascular reserve map.

A 48-year-old-woman suffering from recurrent left hemipalsy was referred to the hospital. MRI showed hyperintense lesions in periventricular white matter. Cerebral angiography revealed stenosis in the bilateral internal carotid and hypertrophic collateral vessels at the brain base, compatible with moyamoya syndrome. A visual comparison between perfusion SPECT with and without acetazolamide is employed in evaluation of these patients. Nevertheless, this traditional evaluation has some drawbacks associated with the variability between the 2 SPECT images and the lack of anatomical information. We propose a quantitative method based on the realigment, normalization, substraction, and co-registration of the 2 perfusion SPECT with MRI.

Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

INTRODUCTION Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. AIM This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. METHODS Twelve Sprague-Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. RESULTS Our analysis revealed a significant reduction of global FDG uptake after acute (-16.2%) and chronic (-23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p<0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. CONCLUSIONS The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this medication.

Incidental detection of gastrointestinal bleeding from an aortoenteric fistula on 99mTc leukocyte scintigraphy.

A 50-year-old-man with abdominal pain, who had undergone aortic aneurysm reconstructive surgery (aortic graft) 3 years before, was admitted to the hospital. A CT scan showed findings suggestive of perigraft infection. Scintigraphy with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes confirmed the diagnosis of aortic graft infection and documented an active concurrent bleeding in the gastrointestinal tract from a secondary aortoenteric fistula. This case illustrates the diagnosis of the precise location of the source of bleeding from aortoenteric fistula by leukocyte scintigraphy. The images aided the surgical team by revealing the aortic site of bleeding and the severity of the problem.

Familial hemiplegic migraine with prolonged global aura: Follow-up findings of subtraction ictal SPECT co-registered to MRI (SISCOM)

All authors contributed equally to this work. Susana Arias-Rivas wrote the main paper. Manuel Rodriguez-Yáñez investigated the supplementary data. Julia Cortés and Pablo Aguiar performed the nuclear image studies and analysed and described the neuroimaging results. María Pardo, Rogelio Leira and Jose Castillo jointly conceived the study, followed the patient and prepared the manuscript. Miguel Blanco discussed the results. All authors discussed the results and implications and commented on the manuscript at all stages.

Iterative Structural and Functional Synergistic Resolution Recovery (iSFS-RR) Applied to PET-MR Images in Epilepsy

Structural Functional Synergistic Resolution Recovery (SFS-RR) is a technique that uses supplementary structural information from MR or CT to improve the spatial resolution of PET or SPECT images. This wavelet-based method may have a potential impact on the clinical decision-making of brain focal disorders such as refractory epilepsy, since it can produce images with better quantitative accuracy and enhanced detectability. In this work, a method for the iterative application of SFS-RR (iSFS-RR) was firstly developed and optimized in terms of convergence and input voxel size, and the corrected images were used for the diagnosis of 18 patients with refractory epilepsy. To this end, PET/MR images were clinically evaluated through visual inspection, atlas-based asymmetry indices (AIs) and SPM (Statistical Parametric Mapping) analysis, using uncorrected images and images corrected with SFS-RR and iSFS-RR. Our results showed that the sensitivity can be increased from 78% for uncorrected images, to 84% for SFS-RR and 94% for the proposed iSFS-RR. Thus, the proposed methodology has demonstrated the potential to improve the management of refractory epilepsy patients in the clinical routine.

Resolution improvement of brain PET images using prior information from MRI: clinical application on refractory epilepsy

An important counterpart of clinical Positron Emission Tomography (PET) for early diagnosis of neurological diseases is its low resolution. This is particularly important when evaluating diseases related to small hypometabolisms such as epilepsy. The last years, new hybrid systems combining PET with Magnetic Resonance (MR) has been increasingly used for several different clinical applications. One of the advantages of MR is the production of high spatial resolution images and a potential application of PET-MR imaging is the improvement of PET resolution using MR information. A potential advantage of resolution recovery of PET images is the enhancement of contrast delivering at the same time better detectability of small lesions or hypometabolic areas and more accurate quantification over these areas. Recently, Shidahara et al (2009) proposed a new method using wavelet transforms in order to produce PET images with higher resolution. We optimised Shidahara’s method (SFS-RR) to take into account possible shortcomings on the particular clinical datasets, and applied it to a group of patients diagnosed with refractory epilepsy. FDG-PET and MRI images were acquired sequentially and then co-registered using software tools. A complete evaluation of the PET/MR images was performed before and after the correction, including different parameters related with PET quantification, such as atlas-based metabolism asymmetry coefficients and Statistical Parametric Mapping results comparing to a database of 87 healthy subjects. Furthermore, an experienced physician analyzed the results of non-corrected and corrected images in order to evaluate improvements of detectability on a visual inspection. Clinical outcome was used as a gold standard. SFS-RR demonstrated to have a positive impact on clinical diagnosis of small hypometabolisms. New lesions were detected providing additional clinically relevant information on the visual inspection. SPM sensitivity for the detection of small lesions was increased from 70% to 90%.