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1.
Mol Ther ; 32(3): 619-636, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38310355

RESUMEN

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.


Asunto(s)
Iduronato Sulfatasa , Mucopolisacaridosis II , Humanos , Animales , Ratones , Mucopolisacaridosis II/terapia , Mucopolisacaridosis II/tratamiento farmacológico , Iduronato Sulfatasa/genética , Iduronato Sulfatasa/metabolismo , Terapia Genética , Sistema Nervioso Central/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Células Madre Hematopoyéticas/metabolismo
2.
Neurobiol Dis ; 192: 106416, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38272141

RESUMEN

BACKGROUND: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD). METHODS: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores. RESULTS: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037). CONCLUSIONS: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans.


Asunto(s)
Enfermedad de Crohn , Humanos , Animales , Ratones , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/metabolismo , Plexo Coroideo/diagnóstico por imagen , Plexo Coroideo/metabolismo , Estudios Prospectivos , Eje Cerebro-Intestino , Biomarcadores/metabolismo , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Complejo de Antígeno L1 de Leucocito/metabolismo , Índice de Severidad de la Enfermedad , Inflamación/diagnóstico por imagen , Permeabilidad
3.
Neurosurg Focus ; 56(2): E6, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38301247

RESUMEN

OBJECTIVE: Surgery is the mainstay of treatment for low-grade glioma (LGG)-related epilepsy. However, the goal of achieving both oncological radical resection and seizure freedom can be challenging. PET with [11C]methionine (MET) has been recently introduced in clinical practice for the management of patients with LGGs, not only to monitor the response to treatments, but also as a preoperative tool to define the metabolic tumor extent and to predict tumor grading, type, and prognosis. Still, its role in defining tumor-related epilepsy and postoperative seizure outcomes is limited. The aim of this preliminary study was to investigate the role of MET PET in defining preoperative seizure characteristics and short-term postoperative seizure control in a cohort of patients with newly diagnosed temporal lobe low-grade gliomas (tLGGs). METHODS: Patients with newly diagnosed and histologically proven temporal lobe grade 2/3 gliomas (2021 WHO CNS tumor classification) who underwent resection at the authors' institution between July 2011 and March 2021 were included in this retrospective study. MET PET images were acquired, fused with MRI scans, and qualitatively and semiquantitatively analyzed. Any eventual PET/MRI involvement of the temporomesial area, seizure characteristics, and 1-year seizure outcomes were reported. RESULTS: A total of 52 patients with tLGGs met the inclusion criteria. MET PET was positive in 41 (79%) patients, with a median metabolic tumor volume of 14.56 cm3 (interquartile range [IQR] 6.5-28.2 cm3). The median maximum and mean tumor-to-background ratio (TBRmax, TBRmean) were 2.24 (IQR 1.58-2.86) and 1.53 (IQR 1.37-1.70), respectively. The metabolic tumor volume was found to be related to the presence of seizures at disease onset, but only in noncodeleted tumors (p = 0.014). Regarding patients with uncontrolled seizures at surgery, only the temporomesial area PET involvement showed a statistical correlation both in the univariate (p = 0.058) and in the multivariate analysis (p = 0.030). At 1-year follow-up, seizure control was correlated with MET PET-derived semiquantitative data. Particularly, higher TBRmax (p = 0.0192) and TBRmean (p = 0.0128) values were statistically related to uncontrolled seizures 1 year after surgery. CONCLUSIONS: This preliminary study suggests that MET PET may be used as a preoperative tool to define seizure characteristics and outcomes in patients with tLGGs. These findings need to be further validated in larger series with longer epileptological follow-ups.


Asunto(s)
Neoplasias Encefálicas , Epilepsia del Lóbulo Temporal , Epilepsia , Glioma , Humanos , Metionina , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Estudios Retrospectivos , Radioisótopos de Carbono , Glioma/complicaciones , Glioma/diagnóstico por imagen , Glioma/cirugía , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Convulsiones/cirugía , Racemetionina , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/cirugía , Tomografía de Emisión de Positrones , Resultado del Tratamiento , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía
4.
Eur Radiol ; 33(1): 207-208, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36305901

RESUMEN

KEY POINTS: • The ICI score derived from gene expression profile of immune cells infiltrating GBM correlates with overall survival and is an effective prognostic biomarker.• In this study, the authors developed a radiomics-based machine learning model able to identify gene expression profiles of GBM intratumoral stromal and immune cells and predict the ICI score on the preoperative MRI scans with high accuracy.• Radiogenomics could potentially be applied in primary brain tumors to noninvasively assess the specific tumor immune characteristics, predict patients' prognosis and identify those patients with higher probability to respond to immunotherapy.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Glioblastoma/mortalidad , Pronóstico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Imagen por Resonancia Magnética , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología
5.
Eur Radiol ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38057593

RESUMEN

OBJECTIVE: To quantify the distribution of cauda equina nerve roots in supine and upright positions using manual measurements and radiomics features both in normal subjects and in lumbar spinal canal stenosis (LSCS) patients. METHODS: We retrospectively recruited patients who underwent weight-bearing MRI in supine and upright positions for back pain. 3D T2-weighted isotropic acquisition (3D-HYCE) sequences were used to develop a 3D convolutional neural network for identification and segmentation of lumbar vertebrae. Para-axial reformatted images perpendicular to the spinal canal and parallel to each vertebral endplate were automatically extracted. From each level, we computed the maximum antero-posterior (AP) and latero-lateral (LL) dispersion of nerve roots; further, radiomics features were extracted to quantify standardized metrics of nerve root distribution. RESULTS: We included 16 patients with LSCS and 20 normal subjects. In normal subjects, nerve root AP dispersion significantly increased from supine to upright position (p < 0.001, L2-L5 levels), and radiomics features showed an increase in non-uniformity. In LSCS subjects, in the upright position AP dispersion of nerve roots and entropy-related features increased caudally to the stenosis level (p < 0.001) and decreased cranially (p < 0.001). Moreover, entropy-related radiomics features negatively correlated with pre-operative Pain Numerical Rating Scale. Comparison between normal subjects and LSCS patients showed a difference in AP dispersion and increase of variance cranially to the stenosis level (p < 0.001) in the upright position. CONCLUSIONS: Nerve root distribution inside the dural sac changed between supine and upright positions, and radiomics features were able to quantify the differences between normal and LSCS subjects. CLINICAL RELEVANCE STATEMENT: The distribution of cauda equina nerve roots and the redundant nerve root sign significantly varies between supine and upright positions in normal subjects and spinal canal stenosis patients, respectively. Radiomics features quantify nerve root dispersion and correlates with pain severity. KEY POINTS: • Weight-bearing MRI depicts spatial distribution of the cauda equina in both supine and upright positions in normal subjects and spinal stenosis patients. • Radiomics features can quantify the effects of spinal stenosis on the dispersion of the cauda equina in the dural sac. • In the orthostatic position, dispersion of nerve roots is different in lumbar spinal stenosis patients compared to that in normal subjects; entropy-related features negatively correlated with pre-operative Pain Numerical Rating Scale.

6.
Radiol Med ; 128(6): 744-754, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37147473

RESUMEN

PURPOSE: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. MATERIALS AND METHODS: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. RESULTS: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). CONCLUSION: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.


Asunto(s)
Enfermedades Óseas Metabólicas , Tomografía Computarizada por Rayos X , Humanos , Niño , Tomografía Computarizada por Rayos X/métodos , Vértebras Lumbares/diagnóstico por imagen , Estudios Retrospectivos
7.
Blood ; 134(3): 252-262, 2019 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-31118164

RESUMEN

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 µg/m2) afterward. This trial included 2 phases: an "explorative phase" addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid-single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an "expansion phase" with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Proteínas Recombinantes de Fusión/farmacocinética , Factor de Necrosis Tumoral alfa/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Barrera Hematoencefálica/diagnóstico por imagen , Antígenos CD13/metabolismo , Permeabilidad de la Membrana Celular , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/mortalidad , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/mortalidad , Masculino , Neuroimagen/métodos , Prednisona/efectos adversos , Prednisona/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proyectos de Investigación , Rituximab/efectos adversos , Rituximab/uso terapéutico , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico
8.
Eur Radiol ; 31(6): 4079-4086, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33201284

RESUMEN

OBJECTIVES: Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia, correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. We evaluated the prognostic relevance of TMT measured on brain MRIs acquired at diagnosis in patients affected by glioblastoma. METHODS: We retrospectively enrolled 51 patients in our Institution affected by methylated MGMT promoter, IDH1-2 wild-type glioblastoma, who underwent complete surgical resection and subsequent radiotherapy with concomitant and maintenance temozolomide, from January 1, 2015, to April 30, 2017. The last clinical/radiological follow-up date was set to September 3, 2019. TMT was measured bilaterally on reformatted post-contrast 3D MPRAGE images, acquired on our 3-T scanner no more than 2 days before surgery. The median, 25th, and 75th percentile TMT values were identified and population was subdivided accordingly; afterwards, statistical analyses were performed to verify the association among overall survival (OS) and TMT, sex, age, and ECOG performance status. RESULTS: In our cohort, the median OS was 20 months (range 3-51). Patients with a TMT ≥ 8.4 mm (median value) did not show a statistically significant increase in OS (Cox regression model: HR 1.34, 95% CI 0.68-2.63, p = 0.403). Similarly, patients with a TMT ≥ 9.85 mm (fourth quartile) did not differ in OS compared to those with TMT ≤ 7 mm (first quartile). The statistical analyses confirmed a significant association among TMT and sex (p = 0.0186), but none for age (p = 0.642) and performance status (p = 0.3982). CONCLUSIONS: In our homogeneous cohort of patients with glioblastoma at diagnosis, TMT was not associated with prognosis, age, or ECOG performance status. KEY POINTS: • Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia and has been correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. • We appraised the correlation among TMT and survival, sex, age at surgery, and performance status, measured on brain MRIs of patients affected by glioblastoma at diagnosis. • TMT did not show any significant correlation with prognosis, age at surgery, or performance status, and its usefulness might be restricted only to patients with brain metastases and recurrent or treated glioblastoma.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Sarcopenia , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Metilación de ADN , Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Glioblastoma/complicaciones , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Humanos , Pronóstico , Estudios Retrospectivos , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Sarcopenia/patología , Músculo Temporal/patología
10.
J Neurol Neurosurg Psychiatry ; 90(2): 211-218, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30150321

RESUMEN

In adulthood, spinal cord MRI abnormalities such as T2-weighted hyperintensities and atrophy are commonly associated with a large variety of causes (inflammation, infections, neoplasms, vascular and spondylotic diseases). Occasionally, they can be due to rare metabolic or genetic diseases, in which the spinal cord involvement can be a prominent or even predominant feature, or a secondary one. This review focuses on these rare diseases and associated spinal cord abnormalities, which can provide important but over-ridden clues for the diagnosis. The review was based on a PubMed search (search terms: 'spinal cord' AND 'leukoencephalopathy' OR 'leukodystrophy'; 'spinal cord' AND 'vitamin'), further integrated according to the authors' personal experience and knowledge. The genetic and metabolic diseases of adulthood causing spinal cord signal alterations were identified and classified into four groups: (1) leukodystrophies; (2) deficiency-related metabolic diseases; (3) genetic and acquired toxic/metabolic causes; and (4) mitochondrial diseases. A number of genetic and metabolic diseases of adulthood causing spinal cord atrophy without signal alterations were also identified. Finally, a classification based on spinal MRI findings is presented, as well as indications about the diagnostic work-up and differential diagnosis. Some of these diseases are potentially treatable (especially if promptly recognised), while others are inherited as autosomal dominant trait. Therefore, a timely diagnosis is needed for a timely therapy and genetic counselling. In addition, spinal cord may be the main site of pathology in many of these diseases, suggesting a tempting role for spinal cord abnormalities as surrogate MRI biomarkers.


Asunto(s)
Leucoencefalopatías/complicaciones , Enfermedades Metabólicas/complicaciones , Enfermedades Mitocondriales/complicaciones , Enfermedades de la Médula Espinal/genética , Enfermedades de la Médula Espinal/metabolismo , Adulto , Edad de Inicio , Humanos
12.
Brain ; 139(Pt 6): 1735-46, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27068048

RESUMEN

Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. Moreover, little is known about the subtle pathological changes that can characterize the brain of adrenomyeloneuropathy subjects in the early stages of the disease. We performed a cross-sectional study on 13 patients with adrenomyeloneuropathy and 12 age-matched healthy control subjects who underwent quantitative magnetic resonance imaging to assess the structural changes of the upper spinal cord and brain. Total cord areas from C2-3 to T2-3 level were measured, and diffusion tensor imaging metrics, i.e. fractional anisotropy, mean, axial and radial diffusivity values were calculated in both grey and white matter of spinal cord. In the brain, grey matter regions were parcellated with Freesurfer and average volume and thickness, and mean diffusivity and fractional anisotropy from co-registered diffusion maps were calculated in each region. Brain white matter diffusion tensor imaging metrics were assessed using whole-brain tract-based spatial statistics, and tractography-based analysis on corticospinal tracts. Correlations among clinical, structural and diffusion tensor imaging measures were calculated. In patients total cord area was reduced by 26.3% to 40.2% at all tested levels (P < 0.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P ≤ 0.0003) with a concomitant 9.7% axial diffusivity reduction (P < 0.009) and 34.5% radial diffusivity increase (P < 0.009) was observed, suggesting co-presence of axonal degeneration and demyelination. Brain tract-based spatial statistics showed a marked reduction of fractional anisotropy, increase of radial diffusivity (P < 0.001) and no axial diffusivity changes in several white matter tracts, including corticospinal tracts and optic radiations, indicating predominant demyelination. Tractography-based analysis confirmed the results within corticospinal tracts. No significant cortical volume and thickness reduction or grey matter diffusion tensor imaging values alterations were observed in patients. A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806, P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement.


Asunto(s)
Adrenoleucodistrofia/diagnóstico por imagen , Adrenoleucodistrofia/patología , Encéfalo/patología , Médula Espinal/patología , Adulto , Anisotropía , Estudios de Casos y Controles , Estudios Transversales , Imagen de Difusión Tensora/métodos , Imagen de Difusión Tensora/estadística & datos numéricos , Sustancia Gris/patología , Humanos , Masculino , Neuroimagen/estadística & datos numéricos , Sustancia Blanca/patología , Adulto Joven
15.
Blood ; 122(2): 243-52, 2013 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-23487026

RESUMEN

A productive immune response requires transient upregulation of the microRNA miR-155 in hematopoietic cells mediating innate and adaptive immunity. In order to investigate miR-155 in the context of tumor-associated immune responses, we stably knocked down (KD) miR-155 in the myeloid compartment of MMTV-PyMT mice, a mouse model of spontaneous breast carcinogenesis that closely mimics tumor-host interactions seen in humans. Notably, miR-155/KD significantly accelerated tumor growth by impairing classic activation of tumor-associated macrophages (TAMs). This created an imbalance toward a protumoral microenvironment as evidenced by a lower proportion of CD11c(+) TAMs, reduced expression of activation markers, and the skewing of immune cells within the tumor toward an macrophage type 2/T helper 2 response. This study highlights the importance of tumor-infiltrating hematopoietic cells in constraining carcinogenesis and establishes an antitumoral function of a prototypical oncomiR.


Asunto(s)
Inmunidad Innata/genética , Macrófagos/inmunología , Macrófagos/metabolismo , MicroARNs/genética , Neoplasias/genética , Neoplasias/inmunología , Animales , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Modelos Animales de Enfermedad , Activación Enzimática , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Orden Génico , Vectores Genéticos , Inflamación/genética , Inflamación/inmunología , Macrófagos/patología , Ratones , Células Mieloides/inmunología , Células Mieloides/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carga Tumoral/genética , Carga Tumoral/inmunología
17.
World J Clin Pediatr ; 13(2): 90641, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38947986

RESUMEN

The integration of 7 Tesla magnetic resonance imaging (7 T MRI) in adult patients has marked a revolutionary stride in radiology. In this article we explore the feasibility of 7 T MRI in paediatric practice, emphasizing its feasibility, applications, challenges, and safety considerations. The heightened resolution and tissue contrast of 7 T MRI offer unprecedented diagnostic accuracy, particularly in neuroimaging. Applications range from neuro-oncology to neonatal brain imaging, showcasing its efficacy in detecting subtle structural abnormalities and providing enhanced insights into neurological conditions. Despite the promise, challenges such as high cost, discomfort, and safety concerns necessitate careful consideration. Research suggests that, with precautions, 7 T MRI is feasible in paediatrics, yet ongoing studies and safety assessments are imperative.

18.
World J Radiol ; 16(7): 274-293, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39086607

RESUMEN

BACKGROUND: After approval for clinical use in 2017, early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated its feasibility as well as diagnostic capabilities in neuroimaging. However, there are no to few systematic reviews covering the entirety of its neurosurgical applications as well as the trends in the literature with regard to the aforementioned application. AIM: To assess the impact of 7-Tesla MRI (7T MRI) on neurosurgery, focusing on its applications in diagnosis, treatment planning, and postoperative assessment, and to systematically analyze and identify patterns and trends in the existing literature related to the utilization of 7T MRI in neurosurgical contexts. METHODS: A systematic search of PubMed was conducted for studies published between January 1, 2017, and December 31, 2023, using MeSH terms related to 7T MRI and neurosurgery. The inclusion criteria were: Studies involving patients of all ages, meta-analyses, systematic reviews, and original research. The exclusion criteria were: Pre-prints, studies with insufficient data (e.g., case reports and letters), non-English publications, and studies involving animal subjects. Data synthesis involved standardized extraction forms, and a narrative synthesis was performed. RESULTS: We identified 219 records from PubMed within our defined period, with no duplicates or exclusions before screening. After screening, 125 articles were excluded for not meeting inclusion criteria, leaving 94 reports. Of these, 2 were irrelevant to neurosurgery and 7 were animal studies, resulting in 85 studies included in our systematic review. Data were categorized by neurosurgical procedures and diseases treated using 7T MRI. We also analyzed publications by country and the number of 7T MRI facilities per country was also presented. Experimental studies were classified into comparison and non-comparison studies based on whether 7T MRI was compared to lower field strengths. CONCLUSION: 7T MRI holds great potential in improving the characterization and understanding of various neurological and psychiatric conditions that may be neurosurgically treated. These include epilepsy, pituitary adenoma, Parkinson's disease, cerebrovascular diseases, trigeminal neuralgia, traumatic head injury, multiple sclerosis, glioma, and psychiatric disorders. Superiority of 7T MRI over lower field strengths was demonstrated in terms of image quality, lesion detection, and tissue characterization. Findings suggest the need for accelerated global distribution of 7T magnetic resonance systems and increased training for radiologists to ensure safe and effective integration into routine clinical practice.

19.
Sci Rep ; 14(1): 19259, 2024 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164314

RESUMEN

Radiomics features (RFs) serve as quantitative metrics to characterize shape, density/intensity, and texture patterns in radiological images. Despite their promise, RFs exhibit reproducibility challenges across acquisition settings, thus limiting implementation into clinical practice. In this investigation, we evaluate the effects of different CT scanners and CT acquisition protocols (KV, mA, field-of-view, and reconstruction kernel settings) on RFs extracted from lumbar vertebrae of a cadaveric trunk. Employing univariate and multivariate Generalized Linear Models (GLM), we evaluated the impact of each acquisition parameter on RFs. Our findings indicate that variations in mA had negligible effects on RFs, while alterations in kV resulted in exponential changes in several RFs, notably First Order (94.4%), GLCM (87.5%), and NGTDM (100%). Moreover, we demonstrated that a tailored GLM model was superior to the ComBat algorithm in harmonizing CT images. GLM achieved R2 > 0.90 in 21 RFs (19.6%), contrasting ComBat's mean R2 above 0.90 in only 1 RF (0.9%). This pioneering study unveils the effects of CT acquisition parameters on bone RFs in cadaveric specimens, highlighting significant variations across parameters and scanner datasets. The proposed GLM model presents a robust solution for mitigating these differences, potentially advancing harmonization efforts in Radiomics-based studies across diverse CT protocols and vendors.


Asunto(s)
Radiómica , Tomografía Computarizada por Rayos X , Humanos , Algoritmos , Cadáver , Vértebras Lumbares/diagnóstico por imagen , Estándares de Referencia , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normas
20.
World J Radiol ; 16(1): 20-31, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38312348

RESUMEN

BACKGROUND: After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging (MRI) have demonstrated the feasibility as well as diagnostic capabilities of liver, kidney, and prostate MRI at 7-Tesla. However, the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks, primarily stemming from heightened artifacts and limitations in Specific Absorption Rate, etc. Furthermore, evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence. AIM: To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends, details relevant challenges, and provides a concise set of potential solutions. METHODS: This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A PubMed search, utilizing Medical Subject Headings terms such as "7-Tesla" and organ-specific terms, was conducted for articles published between January 1, 1985, and July 25, 2023. Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs, encompassing various study types (in-vivo/ex-vivo, method development, reviews/meta-analyses). Exclusion criteria involved animal studies and those lacking extractable data. Study selection involved initial identification via title/abstract, followed by a full-text review by two researchers, with discrepancies resolved through discussion. Data extraction covered publication details, study design, population, sample size, 7T MRI protocol, image characteristics, endpoints, and conclusions. RESULTS: The systematic review included a total of 21 studies. The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate (n = 8), followed by the kidney (n = 6) and the hepatobiliary system (n = 5). Studies on these organs, and in the pancreas, demonstrated clear advantages at 7T. However, small bowel studies showed no significant improvements compared to traditional MRI at 1.5T. The majority of studies evaluated originated from Germany (n = 10), followed by the Netherlands (n = 5), the United States (n = 5), Austria (n = 2), the United Kingdom (n = 1), and Italy (n = 1). CONCLUSION: Further increase of abdominal clinical MRI field strength to 7T demonstrated high imaging potential, yet also limitations mainly due to the inhomogeneous radiofrequency (RF) excitation field relative to lower field strengths. Hence, further optimization of dedicated RF coil elements and pulse sequences are expected to better optimize clinical imaging at high magnetic field strength.

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