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The lncRNA Xist forms â¼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain â¼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.
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Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Mitocondriais/metabolismo , RNA Longo não Codificante/metabolismo , Cromossomo X/metabolismo , Animais , Linhagem Celular , Células-Tronco Embrionárias , Fibroblastos , Inativação Gênica , Humanos , Camundongos , Ligação Proteica , Inativação do Cromossomo XRESUMO
In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.
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Proteínas Ativadoras de GTPase/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Redes Reguladoras de Genes/genética , Animais , Padronização Corporal/genética , Diferenciação Celular/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Proteínas Ativadoras de GTPase/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Modelos Genéticos , Fatores de Transcrição/metabolismoRESUMO
Cell-fate decisions are central to the survival and development of both uni- and multicellular organisms. It remains unclear when and to what degree cells can decide on future fates prior to commitment. This uncertainty stems from experimental and theoretical limitations in measuring and integrating multiple signals at the single-cell level during a decision process. Here, we combine six-color live-cell imaging with the Bayesian method of statistical evidence to study the meiosis/quiescence decision in budding yeast. Integration of multiple upstream metabolic signals predicts individual cell fates with high probability well before commitment. Cells "decide" their fates before birth, well before the activation of pathways characteristic of downstream cell fates. This decision, which remains stable through several cell cycles, occurs when multiple metabolic parameters simultaneously cross cell-fate-specific thresholds. Taken together, our results show that cells can decide their future fates long before commitment mechanisms are activated.
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Redes e Vias Metabólicas/fisiologia , Saccharomycetales/metabolismo , Saccharomycetales/fisiologia , Teorema de Bayes , Meiose/fisiologiaRESUMO
Transient changes in intracellular pH (pHi) regulate normal cell behaviors, but roles for spatiotemporal pHi dynamics in single-cell behaviors remain unclear. Here, we mapped single-cell spatiotemporal pHi dynamics during mammalian cell cycle progression both with and without cell cycle synchronization. We found that single-cell pHi is dynamic throughout the cell cycle: pHi decreases at G1/S, increases in mid-S, decreases at late S, increases at G2/M and rapidly decreases during mitosis. Importantly, although pHi is highly dynamic in dividing cells, non-dividing cells have attenuated pHi dynamics. Using two independent pHi manipulation methods, we found that low pHi inhibits completion of S phase whereas high pHi promotes both S/G2 and G2/M transitions. Our data also suggest that low pHi cues G1 exit, with decreased pHi shortening G1 and increased pHi elongating G1. Furthermore, dynamic pHi is required for S phase timing, as high pHi elongates S phase and low pHi inhibits S/G2 transition. This work reveals that spatiotemporal pHi dynamics are necessary for cell cycle progression at multiple phase transitions in single human cells.
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Mamíferos , Mitose , Animais , Humanos , Ciclo Celular , Interfase , Fase S , Concentração de Íons de HidrogênioRESUMO
Rationale: Chest computed tomography (CT) scans are essential to diagnose and monitor bronchiectasis (BE). To date, few quantitative data are available about the nature and extent of structural lung abnormalities (SLAs) on CT scans of patients with BE. Objectives: To investigate SLAs on CT scans of patients with BE and the relationship of SLAs to clinical features using the EMBARC (European Multicenter Bronchiectasis Audit and Research Collaboration) registry. Methods: CT scans from patients with BE included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). The subscores of this instrument are expressed as percentages of total lung volume. The items scored are atelectasis/consolidation, BE with and without mucus plugging (MP), airway wall thickening, MP, ground-glass opacities, bullae, airways, and parenchyma. Four composite scores were calculated: total BE (i.e., BE with and without MP), total MP (i.e., BE with MP plus MP alone), total inflammatory changes (i.e., atelectasis/consolidation plus total MP plus ground-glass opacities), and total disease (i.e., all items but airways and parenchyma). Measurements and Main Results: CT scans of 524 patients with BE were analyzed. Mean subscores were 4.6 (range, 2.3-7.7) for total BE, 4.2 (1.2-8.1) for total MP, 8.3 (3.5-16.7) for total inflammatory changes, and 14.9 (9.1-25.9) for total disease. BE associated with primary ciliary dyskinesia was associated with more SLAs, whereas chronic obstructive pulmonary disease was associated with fewer SLAs. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and nontuberculous mycobacterial infections, and severe exacerbations were all independently associated with worse SLAs. Conclusions: The type and extent of SLAs in patients with BE are highly heterogeneous. Strong relationships between radiological disease and clinical features suggest that CT analysis may be a useful tool for clinical phenotyping.
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Bronquiectasia , Pulmão , Fenótipo , Tomografia Computadorizada por Raios X , Humanos , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/fisiopatologia , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Sistema de Registros , AdultoRESUMO
The functional topography of the human primary somatosensory cortex hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether the underlying 3D structural architecture also shows a topographic organization. We used 7 Tesla (7T) magnetic resonance imaging (MRI) data to quantify layer-specific myelin, iron, and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is nontopographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity.SIGNIFICANCE STATEMENT Using ultra-high-field MRI, we provide the first comprehensive in vivo description of the 3D structural architecture of the human BA 3b hand area in relation to functional population receptive field maps. High similarity of precise finger-specific 3D profiles, together with an absence of structural differences and an absence of low-myelin borders between individual fingers, reveals the 3D structural architecture of the human hand area to be nontopographic. This suggests reduced structural limitations to cortical plasticity and reorganization and allows for shared representational features across fingers.
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Mãos , Córtex Somatossensorial , Adulto , Humanos , Masculino , Feminino , Dedos , Córtex Cerebral , Imageamento por Ressonância Magnética , Mapeamento Encefálico/métodosRESUMO
Macrophages must respond appropriately to pathogens and other pro-inflammatory stimuli in order to perform their roles in fighting infection. One way in which inflammatory stimuli can vary is in their dynamics-that is, the amplitude and duration of stimulus experienced by the cell. In this study, we performed long-term live cell imaging in a microfluidic device to investigate how the pro-inflammatory genes IRF1, CXCL10, and CXCL9 respond to dynamic interferon-gamma (IFNγ) stimulation. We found that IRF1 responds to low concentration or short duration IFNγ stimulation, whereas CXCL10 and CXCL9 require longer or higherconcentration stimulation to be expressed. We also investigated the heterogeneity in the expression of each gene and found that CXCL10 and CXCL9 have substantial cell-to-cell variability. In particular, the expression of CXCL10 appears to be largely stochastic with a subpopulation of nonresponding cells across all the stimulation conditions tested. We developed both deterministic and stochastic models for the expression of each gene. Our modeling analysis revealed that the heterogeneity in CXCL10 can be attributed to a slow chromatin-opening step that is on a similar timescale to that of adaptation of the upstream signal. In this way, CXCL10 expression in individual cells can remain stochastic in response to each pulse of repeated stimulation, which we also validated by experiments. Together, we conclude that pro-inflammatory genes in the same signaling pathway can respond to dynamic IFNγ stimulus with very different response features and that upstream signal adaptation can contribute to shaping heterogeneous gene expression.
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Quimiocina CXCL10 , Quimiocina CXCL9 , Regulação da Expressão Gênica , Fator Regulador 1 de Interferon , Macrófagos , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/genética , Quimiocina CXCL9/metabolismo , Interferon gama/farmacologia , Macrófagos/metabolismo , Transdução de Sinais/genética , Células RAW 264.7 , Animais , Camundongos , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Simulação por Computador , Análise de Célula Única , Adjuvantes Imunológicos/farmacologiaRESUMO
While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.
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Aprendizado Profundo , Doença de Fabry , Leucoaraiose , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Fabry/diagnóstico por imagem , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , BiomarcadoresRESUMO
Zebrafish provide an excellent model for in vivo cell biology studies because of their amenability to live imaging. Protein visualization in zebrafish has traditionally relied on overexpression of fluorescently tagged proteins from heterologous promoters, making it difficult to recapitulate endogenous expression patterns and protein function. One way to circumvent this problem is to tag the proteins by modifying their endogenous genomic loci. Such an approach is not widely available to zebrafish researchers because of inefficient homologous recombination and the error-prone nature of targeted integration in zebrafish. Here, we report a simple approach for tagging proteins in zebrafish on their N or C termini with fluorescent proteins by inserting PCR-generated donor amplicons into non-coding regions of the corresponding genes. Using this approach, we generated endogenously tagged alleles for several genes that are crucial for epithelial biology and organ development, including the tight junction components ZO-1 and Cldn15la, the trafficking effector Rab11a, the apical polarity protein aPKC and the ECM receptor Integrin ß1b. Our approach facilitates the generation of knock-in lines in zebrafish, opening the way for accurate quantitative imaging studies.
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Técnicas de Introdução de Genes/métodos , Proteínas de Fluorescência Verde/genética , Proteínas de Peixe-Zebra/genética , Animais , Proteínas de Fluorescência Verde/metabolismo , Mutagênese Insercional , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismoRESUMO
PURPOSE: To demonstrate the feasibility and robustness of the Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) framework for fast, high SNR relaxometry at 7T. METHODS: To deploy MR-STAT on 7T-systems, we designed optimized flip-angles using the BLAKJac-framework that incorporates the SAR-constraints. Transmit RF-inhomogeneities were mitigated by including a measured B 1 + $$ {B}_1^{+} $$ -map in the reconstruction. Experiments were performed on a gel-phantom and on five volunteers to explore the robustness of the sequence and its sensitivity to B 1 + $$ {B}_1^{+} $$ inhomogeneities. The SNR-gain at 7T was explored by comparing phantom and in vivo results to MR-STAT at 3T in terms of SNR-efficiency. RESULTS: The higher SNR at 7T enabled two-fold acceleration with respect to current 2D MR-STAT protocols at lower field strengths. The resulting scan had whole-brain coverage, with 1 x 1 x 3 mm3 resolution (1.5 mm slice-gap) and was acquired within 3 min including the B 1 + $$ {B}_1^{+} $$ -mapping. After B 1 + $$ {B}_1^{+} $$ -correction, the estimated T1 and T2 in a phantom showed a mean relative error of, respectively, 1.7% and 4.4%. In vivo, the estimated T1 and T2 in gray and white matter corresponded to the range of values reported in literature with a variation over the subjects of 1.0%-2.1% (WM-GM) for T1 and 4.3%-5.3% (WM-GM) for T2. We measured a higher SNR-efficiency at 7T (R = 2) than at 3T for both T1 and T2 with, respectively, a 4.1 and 2.3 times increase in SNR-efficiency. CONCLUSION: We presented an accelerated version of MR-STAT tailored to high field (7T) MRI using a low-SAR flip-angle train and showed high quality parameter maps with an increased SNR-efficiency compared to MR-STAT at 3T.
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Encéfalo , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Razão Sinal-Ruído , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Adulto , Masculino , FemininoRESUMO
PURPOSE: To develop a framework for simultaneous three-dimensional (3D) mapping of T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and fat signal fraction in the liver at 0.55 T. METHODS: The proposed sequence acquires four interleaved 3D volumes with a two-echo Dixon readout. T 1 $$ {\mathrm{T}}_1 $$ and T 2 $$ {\mathrm{T}}_2 $$ are encoded into each volume via preparation modules, and dictionary matching allows simultaneous estimation of T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and M 0 $$ {M}_0 $$ for water and fat separately. 2D image navigators permit respiratory binning, and motion fields from nonrigid registration between bins are used in a nonrigid respiratory-motion-corrected reconstruction, enabling 100% scan efficiency from a free-breathing acquisition. The integrated nature of the framework ensures the resulting maps are always co-registered. RESULTS: T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and fat-signal-fraction measurements in phantoms correlated strongly (adjusted r 2 > 0 . 98 $$ {r}^2>0.98 $$ ) with reference measurements. Mean liver tissue parameter values in 10 healthy volunteers were 427 ± 22 $$ 427\pm 22 $$ , 47 . 7 ± 3 . 3 ms $$ 47.7\pm 3.3\;\mathrm{ms} $$ , and 7 ± 2 % $$ 7\pm 2\% $$ for T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and fat signal fraction, giving biases of 71 $$ 71 $$ , - 30 . 0 ms $$ -30.0\;\mathrm{ms} $$ , and - 5 $$ -5 $$ percentage points, respectively, when compared to conventional methods. CONCLUSION: A novel sequence for comprehensive characterization of liver tissue at 0.55 T was developed. The sequence provides co-registered 3D T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and fat-signal-fraction maps with full coverage of the liver, from a single nine-and-a-half-minute free-breathing scan. Further development is needed to achieve accurate proton-density fat fraction (PDFF) estimation in vivo.
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PURPOSE: To develop a self-supervised learning method to retrospectively estimate T1 and T2 values from clinical weighted MRI. METHODS: A self-supervised learning approach was constructed to estimate T1, T2, and proton density maps from conventional T1- and T2-weighted images. MR physics models were employed to regenerate the weighted images from the network outputs, and the network was optimized based on loss calculated between the synthesized and input weighted images, alongside additional constraints based on prior information. The method was evaluated on healthy volunteer data, with conventional mapping as references. The reproducibility was examined on two 3.0T scanners. Performance in tumor characterization was inspected by applying the method to a public glioblastoma dataset. RESULTS: For T1 and T2 estimation from three weighted images (T1 MPRAGE, T1 gradient echo sequences, and T2 turbo spin echo), the deep learning method achieved global voxel-wise error ≤9% in brain parenchyma and regional error ≤12.2% in six types of brain tissues. The regional measurements obtained from two scanners showed mean differences ≤2.4% and correlation coefficients >0.98, demonstrating excellent reproducibility. In the 50 glioblastoma patients, the retrospective quantification results were in line with literature reports from prospective methods, and the T2 values were found to be higher in tumor regions, with sensitivity of 0.90 and specificity of 0.92 in a voxel-wise classification task between normal and abnormal regions. CONCLUSION: The self-supervised learning method is promising for retrospective T1 and T2 quantification from clinical MR images, with the potential to improve the availability of quantitative MRI and facilitate brain tumor characterization.
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PURPOSE: Quantitative MRI techniques such as MR fingerprinting (MRF) promise more objective and comparable measurements of tissue properties at the point-of-care than weighted imaging. However, few direct cross-modal comparisons of MRF's repeatability and reproducibility versus weighted acquisitions have been performed. This work proposes a novel fully automated pipeline for quantitatively comparing cross-modal imaging performance in vivo via atlas-based sampling. METHODS: We acquire whole-brain 3D-MRF, turbo spin echo, and MPRAGE sequences three times each on two scanners across 10 subjects, for a total of 60 multimodal datasets. The proposed automated registration and analysis pipeline uses linear and nonlinear registration to align all qualitative and quantitative DICOM stacks to Montreal Neurological Institute (MNI) 152 space, then samples each dataset's native space through transformation inversion to compare performance within atlas regions across subjects, scanners, and repetitions. RESULTS: Voxel values within MRF-derived maps were found to be more repeatable (σT1 = 1.90, σT2 = 3.20) across sessions than vendor-reconstructed MPRAGE (σT1w = 6.04) or turbo spin echo (σT2w = 5.66) images. Additionally, MRF was found to be more reproducible across scanners (σT1 = 2.21, σT2 = 3.89) than either qualitative modality (σT1w = 7.84, σT2w = 7.76). Notably, differences between repeatability and reproducibility of in vivo MRF were insignificant, unlike the weighted images. CONCLUSION: MRF data from many sessions and scanners can potentially be treated as a single dataset for harmonized analysis or longitudinal comparisons without the additional regularization steps needed for qualitative modalities.
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Encéfalo , Imageamento por Ressonância Magnética , Humanos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodosRESUMO
OBJECTIVE: Paraplegia is one of the most feared complications after thoracoabdominal aortic aneurysm repair. The purpose of this study is to determine whether aortic thrombus characteristics are associated with spinal cord ischemia (SCI) after branched endovascular aneurysm repair (BEVAR). METHODS: From April 2011 to April 2020, 62 patients underwent elective BEVAR for thoracoabdominal aortic aneurysm and pararenal aortic aneurysms using a low-profile device and had a complete preoperative computed tomography angiography of the aorta from the sinotubular junction to the aortic bifurcation. Aortic thrombus was evaluated for thrombus thickness ≥5 mm, thrombus >2/3 of aortic circumference, and the presence of an ulcer-like thrombus. One point was assigned at each 5 mm axial image if all 3 criteria were met, resulting in a total "shaggy score" for the entire aorta. Data on demographics, procedural details, and outcomes were collected prospectively. All patients underwent a standard spinal cord protection protocol, including routine cerebrospinal fluid drainage. In July 2016, an insulin infusion protocol (IIP) was initiated to maintain postoperative blood glucose levels <120 mg/dL for 48 hours. The primary clinical end point was postoperative SCI. RESULTS: 10 (16%) patients developed postoperative SCI: 6 with transient paraparesis, 2 with persistent paraparesis, and 2 with persistent paraplegia. Patients with SCI were older, had higher shaggy scores, and were less likely to have been on an IIP. There were no significant differences in demographics, aneurysm type, or operative parameters. In a logistic multivariate regression model for SCI, age (odds ratio [OR]: 1.2 [1.1-1.4], P = .02) and shaggy score (OR: 1.2 [1.1-1.4], P = .02) were independently associated with increased risk of SCI, whereas treatment with the IIP was associated with lower risk of SCI (OR: 0.04 [0.006-0.50], P = .05). Of the individual components of the shaggy score, higher descending thoracic aortic ulcer scores were the most strongly associated with postoperative SCI (P = .009). CONCLUSIONS: Preoperative characterization of aortic wall thrombus is an important adjunctive tool for individualized clinical decision-making and patient counseling about the risk of SCI after BEVAR.
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Aneurisma da Aorta Abdominal , Aneurisma da Aorta Torácica , Aneurisma da Aorta Toracoabdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Isquemia do Cordão Espinal , Trombose , Humanos , Correção Endovascular de Aneurisma , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações , Úlcera/cirurgia , Implante de Prótese Vascular/efeitos adversos , Fatores de Risco , Isquemia do Cordão Espinal/diagnóstico , Isquemia do Cordão Espinal/etiologia , Isquemia do Cordão Espinal/prevenção & controle , Paraplegia/diagnóstico , Paraplegia/etiologia , Paraparesia/etiologia , Trombose/etiologia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70-0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.
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Tubos Torácicos , Biópsia Guiada por Imagem , Pneumotórax , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/epidemiologia , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Idoso , Enfisema Pulmonar/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Fatores de Risco , RadiômicaRESUMO
Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.
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Neoplasias Ósseas , Osteossarcoma , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/patologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The choice between different diffusion-weighted imaging (DWI) techniques is difficult as each comes with tradeoffs for efficient clinical routine imaging and apparent diffusion coefficient (ADC) accuracy. PURPOSE: To quantify signal-to-noise-ratio (SNR) efficiency, ADC accuracy, artifacts, and distortions for different DWI acquisition techniques, coils, and scanners. STUDY TYPE: Phantom, in vivo intraindividual biomarker accuracy between DWI techniques and independent ratings. POPULATION/PHANTOMS: NIST diffusion phantom. 51 Patients: 40 with prostate cancer and 11 with head-and-neck cancer at 1.5 T FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI): 1.5 T and 3 T Siemens; 3 T Philips. Distortion-reducing: RESOLVE (1.5 and 3 T Siemens); Turbo Spin Echo (TSE)-SPLICE (3 T Philips). Small field-of-view (FOV): ZoomitPro (1.5 T Siemens); IRIS (3 T Philips). Head-and-neck and flexible coils. ASSESSMENT: SNR Efficiency, geometrical distortions, and susceptibility artifacts were quantified for different b-values in a phantom. ADC accuracy/agreement was quantified in phantom and for 51 patients. In vivo image quality was independently rated by four experts. STATISTICAL TESTS: QIBA methodology for accuracy: trueness, repeatability, reproducibility, Bland-Altman 95% Limits-of-Agreement (LOA) for ADC. Wilcoxon Signed-Rank and student tests on P < 0.05 level. RESULTS: The ZoomitPro small FOV sequence improved b-image efficiency by 8%-14%, reduced artifacts and observer scoring for most raters at the cost of smaller FOV compared to EPI. The TSE-SPLICE technique reduced artifacts almost completely at a 24% efficiency cost compared to EPI for b-values ≤500 sec/mm2 . Phantom ADC 95% LOA trueness were within ±0.03 × 10-3 mm2 /sec except for small FOV IRIS. The in vivo ADC agreement between techniques, however, resulted in 95% LOAs in the order of ±0.3 × 10-3 mm2 /sec with up to 0.2 × 10-3 mm2 /sec of bias. DATA CONCLUSION: ZoomitPro for Siemens and TSE SPLICE for Philips resulted in a trade-off between efficiency and artifacts. Phantom ADC quality control largely underestimated in vivo accuracy: significant ADC bias and variability was found between techniques in vivo. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
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Cabeça , Pescoço , Masculino , Humanos , Reprodutibilidade dos Testes , Imagens de Fantasmas , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodosRESUMO
OBJECTIVE: Radiation necrosis (RN) can be difficult to radiographically discern from tumor progression after stereotactic radiosurgery (SRS). The objective of this study was to investigate the utility of radiomics and machine learning (ML) to differentiate RN from recurrence in patients with brain metastases treated with SRS. METHODS: Patients with brain metastases treated with SRS who developed either RN or tumor reccurence were retrospectively identified. Image preprocessing and radiomic feature extraction were performed using ANTsPy and PyRadiomics, yielding 105 features from MRI T1-weighted post-contrast (T1c), T2, and fluid-attenuated inversion recovery (FLAIR) images. Univariate analysis assessed significance of individual features. Multivariable analysis employed various classifiers on features identified as most discriminative through feature selection. ML models were evaluated through cross-validation, selecting the best model based on area under the receiver operating characteristic (ROC) curve (AUC). Specificity, sensitivity, and F1 score were computed. RESULTS: Sixty-six lesions from 55 patients were identified. On univariate analysis, 27 features from the T1c sequence were statistically significant, while no features were significant from the T2 or FLAIR sequences. For clinical variables, only immunotherapy use after SRS was significant. Multivariable analysis of features from the T1c sequence yielded an AUC of 76.2% (standard deviation [SD] ± 12.7%), with specificity and sensitivity of 75.5% (± 13.4%) and 62.3% (± 19.6%) in differentiating radionecrosis from recurrence. CONCLUSIONS: Radiomics with ML may assist the diagnostic ability of distinguishing RN from tumor recurrence after SRS. Further work is needed to validate this in a larger multi-institutional cohort and prospectively evaluate it's utility in patient care.
Assuntos
Neoplasias Encefálicas , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Necrose , Recidiva Local de Neoplasia , Lesões por Radiação , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Masculino , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Idoso , Radiocirurgia , Adulto , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , RadiômicaRESUMO
PURPOSE: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory. METHODS: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL). RESULTS: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores. CONCLUSIONS: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).
Assuntos
Neurofibromatose 2 , Neuroma Acústico , Humanos , Biomarcadores , Everolimo , Neurofibromatose 2/diagnóstico por imagem , Neurofibromatose 2/tratamento farmacológico , Neurofibromatose 2/complicações , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/tratamento farmacológico , Neuroma Acústico/etiologia , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVES: Fat-signal suppression is essential for breast diffusion magnetic resonance imaging (or diffusion-weighted MRI, DWI) as the very low diffusion coefficient of fat tends to decrease absolute diffusion coefficient (ADC) values. Among several methods, the STIR (short-tau inversion recovery) method is a popular approach, but signal suppression/attenuation is not specific to fat contrary to other methods such as SPAIR (spectral adiabatic (or attenuated) inversion recovery). This article focuses on those two techniques to illustrate the importance of appropriate fat suppression in breast DWI, briefly presenting the pros and cons of both approaches. METHODS AND RESULTS: We show here through simulation and data acquired in a dedicated breast DWI phantom made of vials with water and various concentrations of polyvinylpyrrolidone (PVP) how ADC values obtained with STIR DWI may be biased toward tissue components with the longest T1 values: ADC values obtained with STIR fat suppression may be over/underestimated depending on the T1 and ADC profile within tissues. This bias is also illustrated in two clinical examples. CONCLUSION: Fat-specific methods should be preferred over STIR for fat-signal suppression in breast DWI, such as SPAIR which also provides a higher sensitivity than STIR for lesion detection. One should remain aware, however, that efficient fat-signal suppression with SPAIR requires good B0 shimming to avoid ADC underestimation from residual fat contamination. CLINICAL RELEVANCE STATEMENT: The spectral adiabatic (or attenuated) inversion recovery (SPAIR) method should be preferred over short-tau inversion recovery (STIR) for fat suppression in breast DWI. KEY POINTS: Fat-signal suppression is essential for breast DWI; the SPAIR method is recommended. Short-tau inversion recovery (STIR) is not specific to fat; as a result, SNR is decreased and ADC values may be over- or underestimated. The STIR fat-suppression method must not be used after the injection of gadolinium-based contrast agents.