Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? SUMMARY ANSWER: Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. WHAT IS KNOWN ALREADY: Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. LIMITATIONS, REASONS FOR CAUTION: The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. WIDER IMPLICATIONS OF THE FINDINGS: In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov. (NCT04108039).

Association of Endogenous Hormones and Bone Mineral Density in Postmenopausal Women.

Aim: The aim of this study was to examine the association between endogenous hormones and bone mineral density (BMD) in postmenopausal women. Materials and Methods: This was a cross-sectional study of 798 postmenopausal women aged 47-85 years. Data were collected on age, age at menopause, years since menopause, smoking status, body mass index, adiposity, BMD, physical activity, and Vitamin D supplementation. Measured hormonal parameters were: follicle-stimulating hormone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, ∆4-androstenedione, cortisol, insulin-like growth factor-1, 25-hydroxyvitamin D, and parathormone (PTH) levels. BMD was measured at the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. A directed acyclic graph was used to select potential confounding variables. Results: Multivariable analysis showed significant associations between cortisol and femoral neck BMD (ß: -0.02, 95% confidence interval [CI]: -0.03--0.00), and PTH with femoral neck BMD (ß: -0.01, 95% CI: -0.02--0.01) and total hip BMD (ß: -0.01, 95% CI: -0.01--0.00). Hormonal factors more likely associated with a higher risk of low BMD (osteopenia or osteoporosis) were FSH (odds ratio [OR]: 1.02, 95% CI: 1.01-1.03) and PTH (OR: 1.02, 95% CI: 1.01-1.04). Conclusions: Higher cortisol and PTH levels were inversely associated with BMD. Postmenopausal women with higher FSH or PTH levels were likely to have low BMD.

Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials.

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.

Effects of a hippotherapy intervention on muscle spasticity in children with cerebral palsy: A randomized controlled trial.

OBJECTIVE: The aim of the present study is to evaluate the effect of a 12 weeks hippotherapy intervention protocol on hip adductors spasticity in children with spastic cerebral palsy. DESIGN: Randomized controlled trial. SETTINGS/LOCATION: The intervention was conducted in an Equestrian and Therapeutic Association. Patients were recruited from a Rehabilitation Unit of Cerebral Palsy. SUBJECTS: A total of 44 children with spastic cerebral palsy (Gross Motor Function Classification System [GMFCS] levels IV-V; 28 boys and 16 girls; aged 8 years 10 months, SD 3 months) were assigned to a treatment (n = 22; mean age 9 years 6 months, SD 3 months) or a control group (n = 22; mean age 8 years 3 months, SD 3 months). INTERVENTIONS: The control group received conventional therapy, and the treatment group received hippotherapy in addition to their conventional treatment. The intervention consisted of a 12-weeks hippotherapy program (1 time/week, 45 min). OUTCOME MEASURES: Both groups were assessed before and after the full program with the Modified Ashworth Scale (MAS). RESULTS: There were significant differences in the MAS scores between the treatment and the control group in both adductors (left adductors: p = 0,040; right adductors: p = 0,047), after a 12-weeks hippotherapy intervention. CONCLUSIONS: A hippotherapy based treatment in addition to conventional therapy, in children with cerebral palsy, produces statistically significant changes in hip adductors spasticity after a 12-weeks intervention. Thus, it seems to produce benefits in the short-term.

Analytical determination of the reducing and stabilization agents present in different Zostera noltii extracts used for the biosynthesis of gold nanoparticles.

The objective of this work was to ascertain the nature of the components responsible for the reducing and stabilizing properties of Zostera noltii extracts that lead to gold nanoparticle formation using chemical techniques of analysis. In order to achieve this aim, we try the synthesis of AuNPs with three different extracts from plants collected in the Bay of Cádiz (Spain). The n-butanol extract produced the best results. Taking this into account, four fractions were isolated by Sephadex LH-20 column chromatography from this extract and we studied their activity. The chemical study of these fractions led to the isolation of several flavone sulfates and these were identified as the species' responsible for the formation and stabilization of the AuNPs. Flavone sulfates were purified by high performance liquid chromatography and the structures were established by means of spectroscopic methods nuclear magnetic resonance and mass spectroscopy. AuNPs have an average lifetime of about 16weeks. Additionally, the morphology and crystalline phase of the gold nanoparticles were characterized by transmission electron microscopy. The composition of the nanoparticles was evaluated by electron diffraction and energy dispersive X-ray spectroscopy. An 88% of the gold nanoparticles has a diameter in the range 20-35nm, with an average size of 26±2nm.

Impact of Nutritional Intervention on Length of Hospital Stay and Mortality among Hospitalized Patients with Malnutrition: A Clinical Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to evaluate the impact of a nutritional intervention on hospital stay and mortality among hospitalized patients with malnutrition. METHODS: Hospitalized patients with a diagnosis of malnutrition were enrolled and randomly allocated to either an intervention or control group. Participants in the intervention group received an individualized nutrition plan according to energy and protein (1.0-1.5 g/kg) intake requirements as well as dietary advice based on face-to-face interviews with patients and their caregivers or family members. Individuals in the control group received standard nutritional management according to the Hospital Nutrition Department. Nutritional status and disease severity were assessed using nutritional risk screening. Length of hospital stay was defined by the number of days of hospitalization from hospital admission to medical discharge. Reference to another service or death were criteria for study withdrawal. To evaluate mortality, individuals were followed up for 6 months after hospital discharge. Hospital stay and mortality were the intention-to-treat analysis. RESULTS: A total of 55 patients with an average age of 57.1 ± 20.7 years were included into intervention (n = 28) and control (n = 27) groups, respectively. At basal condition, nutritional status, measured by nutritional risk screening score, was similar between the study groups (4.1 ± 0.8 vs 4.2 ± 1.2, p = 0.6). The average hospital stay was lower in the intervention group compared to the control group (6.4 ± 3.0 vs 8.4 ± 4.0 days, p = 0.03). Finally, the mortality rate at 6 months of follow-up was similar in both groups (hazard ratio [HR] = 0.85; 95% confidence interval [CI], 0.17-4.21). CONCLUSIONS: Results of this study suggest that, in hospitalized patients with malnutrition, nutritional intervention and dietary advice decrease hospital stay but not mortality.

Carcinoma in situ de mama: análisis de los casos y evaluación de las recidivas en nuestro centro, 1999-2012 / Ductal carcinoma in situ: analysis of cases and assessment of recurrences in our center from 1999-2012

Objetivo. Analizar las recidivas de las pacientes diagnosticadas, tratadas y seguidas en nuestro centro por carcinoma ductal in situ de mama, y establecer qué variables se asocian a un mayor riesgo de desarrollarlas. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los casos de carcinoma ductal in situ diagnosticados y tratados en nuestro centro desde enero de 1999 hasta enero de 2012. Se excluyeron los casos en que coexistía componente infiltrante y aquellos con antecedente de neoplasia y/o radioterapia previa en la mama afecta. Las variables que se analizaron fueron: la edad de la paciente, el tamaño tumoral, el grado nuclear, el estado de los márgenes quirúrgicos, el tipo de cirugía y el tratamiento complementario (radioterapia y hormonoterapia). Resultados. Se estudiaron 162 casos de carcinomas in situ en el periodo 1999-2012. De estos, 117 (72,2%) fueron tratados con cirugía conservadora y 45 (27,7%) mediante mastectomía. Se produjeron 16 recidivas (9,9%) en el periodo estudiado. No se encuentran diferencias estadísticamente significativas en la tasa de recidivas en función del tamaño tumoral, la distancia quirúrgica al margen, el grado histológico ni la edad de la paciente. En el subgrupo de pacientes tratadas con tumorectomía, la supervivencia libre de enfermedad fue mayor en las que recibieron de forma complementaria radioterapia y hormonoterapia que en aquellas que solo recibieron uno o ninguno de los tratamientos (p=0,001). Conclusión. En el subgrupo de pacientes con carcinoma in situ tratadas con tumorectomía el riesgo de recidiva es 19 veces superior en los casos que no recibieron ningún tratamiento complementario que en aquellos tratados con tumorectomía, radioterapia y hormonoterapia (p=0,001) (AU)

Objective. To analyse recurrences in patients diagnosed, treated and followed up in our centre for ductal carcinoma in situ and to identify the variables associated with an increased risk of their development. Patients and methods. We performed a retrospective study of cases of ductal carcinoma in situ diagnosed and treated in our hospital from January 1999 to January 2012. We excluded cases with coexistence of an infiltrating component, a history of neoplasia, and/or prior radiation to the affected breast. The variables analysed were patient age, tumour size, nuclear grade, surgical margin status, type of surgery, and adjuvant therapy (radiation and hormone therapy). Results. We studied 162 cases of ductal carcinoma in situ occurring between 1999 and 2012. Of these, 117 cases (72.2%) were treated with conservative surgery and 45 (27.7%) by mastectomy. In that period, we found 16 recurrences (9.9%). We found no statistically significant difference in the recurrence rate according to tumour size, surgical distance from the margin, histological grade, or patient age. In the subgroup of patients treated with lumpectomy, disease-free survival was higher in patients receiving radiation therapy and hormone therapy as a complementary treatment than in those who received only one or no treatment at all (P=.001). Conclusion. In the subgroup of patients with ductal carcinoma in situ treated with lumpectomy, the recurrence risk was 19 times higher in patients who received no adjuvant treatment than in those treated with lumpectomy, radiation and hormone therapy (P=.001) (AU)

Cardiac Safety Research Consortium: can the thorough QT/QTc study be replaced by early QT assessment in routine clinical pharmacology studies? Scientific update and a research proposal for a path forward.

The International Conference on Harmonization E14 guidance for the clinical evaluation of QT/QTc interval prolongation requires almost all new drugs to undergo a dedicated clinical study, primarily in healthy volunteers, the so-called TQT study. Since 2005, when the E14 guidance was implemented in United States and Europe, close to 400 TQT studies have been conducted. In February 2012, the Cardiac Safety Research Consortium held a think tank meeting at Food and Drug Administration's White Oak campus to discuss whether "QT assessment" can be performed as part of routine phase 1 studies. Based on these discussions, a group of experts convened to discuss how to improve the confidence in QT data from early clinical studies, for example, the First-Time-in-Human trial, through collection of serial electrocardiograms and pharmacokinetic samples and the use of exposure response analysis. Recommendations are given on how to design such "early electrocardiogram assessment," and the limitation of not having a pharmacologic-positive control in these studies is discussed. A research path is identified toward collecting evidence to replace or provide an alternative to the dedicated TQT study.

Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance.

Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance, hyperphagia, reduced energy expenditure, and obesity. Pharmacological relieve of hypothalamic ER stress reversed these metabolic alterations. Our data establish MFN2 in POMC neurons as an essential regulator of systemic energy balance by fine-tuning the mitochondrial-ER axis homeostasis and function. This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance.

The evaluation and management of drug effects on cardiac conduction (PR and QRS intervals) in clinical development.

Recent advances in electrocardiographic monitoring and waveform analysis have significantly improved the ability to detect drug-induced changes in cardiac repolarization manifested as changes in the QT/corrected QT interval. These advances have also improved the ability to detect drug-induced changes in cardiac conduction. This White Paper summarizes current opinion, reached by consensus among experts at the Cardiac Safety Research Consortium, on the assessment of electrocardiogram-based safety measurements of the PR and QRS intervals, representing atrioventricular and ventricular conduction, respectively, during drug development.

Pediatric cardiovascular safety: challenges in drug and device development and clinical application.

Development of pediatric medications and devices is complicated by differences in pediatric physiology and pathophysiology (both compared with adults and within the pediatric age range), small patient populations, and practical and ethical challenges to designing clinical trials. This article summarizes the discussions that occurred at a Cardiac Safety Research Consortium-sponsored Think Tank convened on December 10, 2010, where members from academia, industry, and regulatory agencies discussed important issues regarding pediatric cardiovascular safety of medications and cardiovascular devices. Pediatric drug and device development may use adult data but often requires additional preclinical and clinical testing to characterize effects on cardiac function and development. Challenges in preclinical trials include identifying appropriate animal models, clinically relevant efficacy end points, and methods to monitor cardiovascular safety. Pediatric clinical trials have different ethical concerns from adult trials, including consideration of the subjects' families. Clinical trial design in pediatrics should assess risks and benefits as well as incorporate input from families. Postmarketing surveillance, mandated by federal law, plays an important role in both drug and device safety assessment and becomes crucial in the pediatric population because of the limitations of premarketing pediatric studies. Solutions for this wide array of issues will require collaboration between academia, industry, and government as well as creativity in pediatric study design. Formation of various epidemiologic tools including registries to describe outcomes of pediatric cardiac disease and its treatment as well as cardiac effects of noncardiovascular medications, should inform preclinical and clinical development and improve benefit-risk assessments for the patients. The discussions in this article summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further our knowledge and understanding of this topic.

Assessing proarrhythmic potential of drugs when optimal studies are infeasible.

Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.

The kelp macrocystis pyrifera as nutritional supplement for goats

The present study was aimed to evaluate Macrocystis pyrifera (MP) meal as a nutritional supplement for goats. There is an increasing interest to look at nutritional alternatives to guarantee a continuous supply of good quality forage for goats, in many communities around the world. Given its abundance and chemical composition, the algae M. pyrifera is an important potential resource as animal feed. Three diets with 10, 20, and 30% of MP meal concentrations and a control diet, with no algae, were evaluated. Four rumen cannulated goats, housed individually in metabolism cages, were used. The experimental design was a 4 x 4 Latin-Square. Feed and water intake, excreted urine and faeces, were measured. Digestibility in vivo, dry matter (DM) disappearance, and the metabolic variables of pH and ammoniacal nitrogen in the rumen, were determined. There was no significant difference in the feed intake but there was in water intake and urine excreted. No significant difference in digestibility in vivo among diets (P>0.05) was found. A significant difference (P<0.05) for degradability in situ was found for the algae diets containing 10 and 30 percent MP concentrations at 96 hours of sampling (78.3 and 82.2 percent). The raw algae in situ digestibility was 77 percent. A potential degradability of 87.3 percent was obtained with 30 percent MP diet. The highest effective degradation was obtained at an estimated rate of 0.02 h-1. Ruminal pH was higher (P<0.05) in all MP treatments (10 percent MP: 6.83, 20 percent MP: 6.85, 30 percent MP: 6.91). As suggested by the results, M. pyrifera represents a good unconventional feeding as a nutritional supplement for goats.

El objetivo de este trabajo fue evaluar Macrocystis pyrifera (MP) como suplemento alimenticio para cabras. Hay un interés creciente en buscar alternativas alimenticias para garantizar el suministro continuo de forraje de buena calidad para cabras en muchas comunidades del mundo. Dada su abundancia y composición química, el alga M. pyrifera es un recurso potencial importante como pienso para ganado. Se evaluaron tres dietas con concentraciones de 10, 20, y 30 por ciento de harina de MP, y una dieta control, sin las algas. Se utilizaron cuatro cabras canuladas dispuestas individualmente en jaulas metabólicas. El diseño experimental fue un Cuadrado Latino 4 x 4. El alimento y agua consumidos, la orina y las heces excretadas fueron medidas. Se determinaron la digestibilidad in vivo, la desaparición in situ de la materia seca y las variables metabólicas pH y nitrógeno amoniacal en rumen. No se encontró diferencia significativa en el alimento consumido, ni en la digestibilidad in vivo entre las dietas (P>0,05), pero si hubo diferencia significativa en el consumo de agua y la orina excretada (P<0,05). Se encontró diferencia significativa (P<0,05) para la digestibilidad in situ en las dietas que contenían el 10 y 30% del alga a la hora 96 del muestreo (78,3 y el 82,2 por ciento). La digestibilidad in situ del alga fue de 77 por ciento. Se obtuvo una degradabilidad potencial de 87,3 por ciento con la dieta que contiene 30 por ciento de MP. La mayor degradación efectiva se obtuvo a una tasa estimada de 0,02 h-1. El pH ruminal fue más alto (P<0,05) en todos los tratamientos con MP (10 por ciento de MP: 6,83, 20 por ciento de MP: 6,85, 30 por ciento de MP: 6,91). Los resultados obtenidos sugieren que M. pyrifera representa un buen suplemento nutricional no convencional para cabras.

Alumina sol-gel/sonogel-carbon electrode based on acetylcholinesterase for detection of organophosphorus pesticides.

Two new amperometric biosensors based on immobilization of acetylcholinesterase on a sonogel-carbon electrode for detection of organophosphorous compounds are proposed. The electrodes were prepared applying high-energy ultrasounds directly to the precursors. The first biosensor was obtained by simple entrapping acetylcholinesterase in Al(2)O(3) sol-gel matrix on the sonogel-carbon. The second biosensor was produced in a sandwich configuration. Its preparation involved adsorption of the enzyme and modification via a polymeric membrane such as polyethylene glycol and the ion-exchanger Nafion. The optimal enzyme loading was found to be 0.7 mIU. Both biosensors showed optimal activity in 0.2 M phosphate buffer, pH 7.0, at an operating potential of 210 mV. The detection limit achieved for chlorpyriphos-ethyl-oxon was 2.5x10(-10)M at a 10-min incubation time.

Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological results.

We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2-weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity. The MRS results show a statistically significant increase in inorganic phosphate and a significant decrease in phosphocreatine levels in the inflamed region. Image segmentation made with a self-organizing, neural-network map yielded a set of ordered representatives that remained constant for all animals during the inflammatory process, allowing a non-invasive, three-dimensional identification and quantification of the inflamed infected regions by MRI.