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Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we performed an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed 2 distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug-related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing patients with ILD, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a noninvasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes.
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Indóis , Proteômica , Fibrose Pulmonar , Animais , Indóis/uso terapêutico , Indóis/farmacologia , Camundongos , Humanos , Proteômica/métodos , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Antifibróticos/farmacologia , Antifibróticos/uso terapêutico , Modelos Animais de Doenças , Feminino , Masculino , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/metabolismo , Matriz Extracelular/metabolismoRESUMO
BCG vaccination affects other diseases beyond tuberculosis by unknown-potentially immunomodulatory-mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or without routine neonatal BCG vaccination to identify vaccine-associated alterations. Ghanaian long-term T1D patients (n = 108) and matched healthy controls (n = 214) were evaluated for disease-related clinical, metabolic, and immunophenotypic parameters and compared based on their neonatal BCG vaccination status. The majority of study participants were BCG-vaccinated at birth and no differences in vaccination rates were detected between the study groups. Notably, glycemic control metrics, i.e., HbA1c and IDAA1c, showed significantly lower levels in BCG-vaccinated as compared to unvaccinated patients. Immunophenotype comparisons identified higher expression of the T cell activation marker CD25 on CD8+ T cells from BCG-vaccinated T1D patients. Correlation analysis identified a negative correlation between HbA1c levels and CD25 expression on CD8+ T cells. In addition, we observed fractional increases in glycolysis metabolites (phosphoenolpyruvate and 2/3-phosphoglycerate) in BCG-vaccinated T1D patients. These results suggest that neonatal BCG vaccination is associated with better glycemic control and increased activation of CD8+ T cells in T1D patients.
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Optical frequency combs have revolutionized precision measurement, time-keeping and molecular spectroscopy1-7. A substantial effort has developed around 'microcombs': integrating comb-generating technologies into compact photonic platforms5,7-9. Current approaches for generating these microcombs involve either the electro-optic10 or Kerr mechanisms11. Despite rapid progress, maintaining high efficiency and wide bandwidth remains challenging. Here we introduce a previously unknown class of microcomb-an integrated device that combines electro-optics and parametric amplification to yield a frequency-modulated optical parametric oscillator (FM-OPO). In contrast to the other solutions, it does not form pulses but maintains operational simplicity and highly efficient pump power use with an output resembling a frequency-modulated laser12. We outline the working principles of our device and demonstrate it by fabricating the complete optical system in thin-film lithium niobate. We measure pump-to-comb internal conversion efficiency exceeding 93% (34% out-coupled) over a nearly flat-top spectral distribution spanning about 200 modes (over 1 THz). Compared with an electro-optic comb, the cavity dispersion rather than loss determines the FM-OPO bandwidth, enabling broadband combs with a smaller radio-frequency modulation power. The FM-OPO microcomb offers robust operational dynamics, high efficiency and broad bandwidth, promising compact precision tools for metrology, spectroscopy, telecommunications, sensing and computing.
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Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking.
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Processamento de Imagem Assistida por Computador , Radiômica , Humanos , Reprodutibilidade dos Testes , Biomarcadores , Imagem MultimodalRESUMO
PURPOSE: In the surgical treatment of kidney stones, decreased access to healthcare has been shown to exacerbate stone burden, often requiring more invasive and extensive procedures. The objective of this study is to evaluate the effects of preventative health screening on kidney stone surgical treatment patterns. METHODS: We performed a retrospective analysis of data from the Healthcare Cost and Utilization Project (HCUP) Florida state-wide dataset and the PLACES Local Data for Better Health dataset from the Centers of Disease Control and Prevention (CDC). ZIP Code Tabulation Areas (ZCTAs) identified from the PLACES data were merged with the HCUP dataset to create a single dataset of community-level stone outcomes and community health measures. We included adult patients 18 years or older who underwent at least one urologic stone procedure from 2016 to 2020. RESULTS: 128,038 patients from 885 communities were included in the study. Patients underwent an average of 1.42 surgeries (Median = 1.39, SD = 0.16). Increased core preventative screening was associated with increased surgical frequency (Estimate: 0.51, P < 0.001). The low core preventative screening group had a higher prevalence of PNL than SWL while the high core preventative screening group had a low PNL prevalence compared to SWL. CONCLUSION: Increased core preventative screenings are associated with less invasive kidney stone surgeries, suggesting that preventative screenings detect stones at an earlier stage.
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Cálculos Renais , Humanos , Cálculos Renais/cirurgia , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Florida/epidemiologia , Programas de Rastreamento/métodos , Idoso , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Cirúrgicos UrológicosRESUMO
Inflammatory myofibroblastic tumors of the bladder (IMTB) are rare neoplasms that can occur in children. These tumors have uncertain malignant potential and can present similarly to bladder sarcomas. It is important to differentiate between IMTB and bladder sarcomas using a careful immunohistochemical approach. We report a case of IMTB in a 12-year-old girl who presented with presyncope and gross hematuria. IMTB was diagnosed through immunohistochemical analysis, and clinical improvement was observed after resection of the tumor.
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In this paper, we report the absolute measurement of the spectral sensitivity of a bilamellar tube x-ray streak camera (XRSC) over the 0.1-10 keV range equipped with a CsI photocathode for Laser MégaJoule (LMJ) fusion experiments. This calibration of the XRSC is performed in static mode by using two multi-anode x-ray generators. Two silicon drift detectors (SDDs) previously calibrated at the Physikalisch-Technische-Bundesanstalt radiometric laboratory are used as secondary standards. Both x-ray generators work with a specific monochromator for radiometric measurements. In the sub-keV region, a 1 m-grazing incidence Rowland geometry monochromator specifically developed to handle LMJ's x-ray camera is used, whereas for higher energies (>2 keV), a double-crystal monochromator is employed. The absolute spectral sensitivity of the XRSC is obtained by comparing the CCD counts of the XRSC output with the output counts in x-ray lines recorded by the SDD. The results obtained below 1.2 keV are, to our knowledge, the first measurements of the spectral sensitivity of an XRSC in the soft x-ray range with a CsI photocathode. Comparison with a model describing the spectral dependence of the sensitivity of the XRSC revealed that measurements obtained in the sub-keV region are greater than expected, whereas they agree with the model above 4.5 keV. There may be several contributors to this behavior, including the grain morphology of the CsI layer and exposure to air.
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The quantum noise of light, attributed to the random arrival time of photons from a coherent light source, fundamentally limits optical phase sensors. An engineered source of squeezed states suppresses this noise and allows phase detection sensitivity beyond the quantum noise limit (QNL). We need ways to use quantum light within deployable quantum sensors. Here we present a photonic integrated circuit in thin-film lithium niobate that meets these requirements. We use the second-order nonlinearity to produce a squeezed state at the same frequency as the pump light and realize circuit control and sensing with electro-optics. Using 26.2 milliwatts of optical power, we measure (2.7 ± 0.2)% squeezing and apply it to increase the signal-to-noise ratio of phase measurement. We anticipate that photonic systems like this, which operate with low power and integrate all of the needed functionality on a single die, will open new opportunities for quantum optical sensing.
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Óxidos , Fótons , Registros , Razão Sinal-RuídoRESUMO
Background: Interstitial lung disease (ILD) defines a group of parenchymal lung disorders, characterized by fibrosis as their common final pathophysiological stage. To improve diagnosis and treatment of ILD, there is a need for repetitive non-invasive characterization of lung tissue by quantitative parameters. In this study, we investigated whether CT image patterns found in mice with bleomycin induced lung fibrosis can be translated as prognostic factors to human patients diagnosed with ILD. Methods: Bleomycin was used to induce lung fibrosis in mice (n_control = 36, n_experimental = 55). The patient cohort consisted of 98 systemic sclerosis (SSc) patients (n_ILD = 65). Radiomic features (n_histogram = 17, n_texture = 137) were extracted from microCT (mice) and HRCT (patients) images. Predictive performance of the models was evaluated with the area under the receiver-operating characteristic curve (AUC). First, predictive performance of individual features was examined and compared between murine and patient data sets. Second, multivariate models predicting ILD were trained on murine data and tested on patient data. Additionally, the models were reoptimized on patient data to reduce the influence of the domain shift on the performance scores. Results: Predictive power of individual features in terms of AUC was highly correlated between mice and patients (r = 0.86). A model based only on mean image intensity in the lung scored AUC = 0.921 ± 0.048 in mice and AUC = 0.774 (CI95% 0.677-0.859) in patients. The best radiomic model based on three radiomic features scored AUC = 0.994 ± 0.013 in mice and validated with AUC = 0.832 (CI95% 0.745-0.907) in patients. However, reoptimization of the model weights in the patient cohort allowed to increase the model's performance to AUC = 0.912 ± 0.058. Conclusion: Radiomic signatures of experimental ILD derived from microCT scans translated to HRCT of humans with SSc-ILD. We showed that the experimental model of BLM-induced ILD is a promising system to test radiomic models for later application and validation in human cohorts.
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Thin-film lithium niobate (TFLN) is an emerging platform for compact, low-power nonlinear-optical devices, and has been used extensively for near-infrared frequency conversion. Recent work has extended these devices to mid-infrared wavelengths, where broadly tunable sources may be used for chemical sensing. To this end, we demonstrate efficient and broadband difference frequency generation between a fixed 1-µm pump and a tunable telecom source in uniformly-poled TFLN-on-sapphire by harnessing the dispersion-engineering available in tightly-confining waveguides. We show a simultaneous 1-2 order-of-magnitude improvement in conversion efficiency and â¼5-fold enhancement of operating bandwidth for mid-infrared generation when compared to equal-length conventional lithium niobate waveguides. We also examine the effects of mid-infrared loss from surface-adsorbed water on the performance of these devices.
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Integrated photonics operating at visible-near-infrared (VNIR) wavelengths offer scalable platforms for advancing optical systems for addressing atomic clocks, sensors, and quantum computers. The complexity of free-space control optics causes limited addressability of atoms and ions, and this remains an impediment on scalability and cost. Networks of Mach-Zehnder interferometers can overcome challenges in addressing atoms by providing high-bandwidth electro-optic control of multiple output beams. Here, we demonstrate a VNIR Mach-Zehnder interferometer on lithium niobate on sapphire with a CMOS voltage-level compatible full-swing voltage of 4.2 V and an electro-optic bandwidth of 2.7 GHz occupying only 0.35 mm2. Our waveguides exhibit 1.6 dB/cm propagation loss and our microring resonators have intrinsic quality factors of 4.4 × 105. This specialized platform for VNIR integrated photonics can open new avenues for addressing large arrays of qubits with high precision and negligible cross-talk.
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Second-order nonlinear optical processes convert light from one wavelength to another and generate quantum entanglement. Creating chip-scale devices to efficiently control these interactions greatly increases the reach of photonics. Existing silicon-based photonic circuits utilize the third-order optical nonlinearity, but an analogous integrated platform for second-order nonlinear optics remains an outstanding challenge. Here we demonstrate efficient frequency doubling and parametric oscillation with a threshold of tens of micro-watts in an integrated thin-film lithium niobate photonic circuit. We achieve degenerate and non-degenerate operation of the parametric oscillator at room temperature and tune its emission over one terahertz by varying the pump frequency by hundreds of megahertz. Finally, we observe cascaded second-order processes that result in parametric oscillation. These resonant second-order nonlinear circuits will form a crucial part of the emerging nonlinear and quantum photonics platforms.
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Four adult dogs weighing <10 kg presented for the evaluation of severe mitral valve stenosis with clinical signs. Owing to the size of the dogs, a hybrid surgical and interventional approach was utilized for balloon valvuloplasty. A left lateral thoracotomy was performed to allow direct entry through the left atrial wall. Transesophageal echocardiography was utilized for the entirety of the procedure in all dogs, and fluoroscopy was additionally used in two dogs. One dog had mild to moderate intra-operative bleeding from the left atrial wall during the procedure, but no other intra-operative complications were observed. No dogs developed a clinically relevant amount of worsened mitral regurgitation. Based on mitral leaflet mobility and transmitral flow profiles, there was perceived improvement in all four dogs. One dog died 6 h after extubation due to respiratory arrest. The remaining dogs survived to discharge and had resolution of clinical signs at home and discontinuation of heart failure medications. One dog died of an unknown cause at five months and another developed atrial fibrillation, and the owners elected to euthanize at ten months after the procedure. One dog continues to do well six months after the procedure as of the time of this writing. Hybrid balloon valvuloplasty can be a viable management option for small breed dogs with severe mitral stenosis exhibiting clinical signs, and both transesophageal echocardiography and fluoroscopy can be used intra-operatively to assist in successful procedural outcomes.
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Fibrilação Atrial , Valvuloplastia com Balão , Estenose da Valva Mitral , Animais , Fibrilação Atrial/complicações , Fibrilação Atrial/veterinária , Valvuloplastia com Balão/veterinária , Ecocardiografia Transesofagiana/veterinária , Átrios do Coração/diagnóstico por imagem , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/cirurgia , Estenose da Valva Mitral/veterináriaRESUMO
The strength of interactions between photons in a χ(2) nonlinear optical waveguide increases at shorter wavelengths. These larger interactions enable coherent spectral translation and light generation at a lower power, over a broader bandwidth, and in a smaller device: all of which open the door to new technologies spanning fields from classical to quantum optics. Stronger interactions may also grant access to new regimes of quantum optics to be explored at the few-photon level. One promising platform that could enable these advances is thin-film lithium niobate (TFLN), due to its broad optical transparency window and possibility for quasi-phase matching and dispersion engineering. In this Letter, we demonstrate second harmonic generation of blue light on an integrated thin-film lithium niobate waveguide and observe a conversion efficiency of η0 = 33, 000%/W-cm2, significantly exceeding previous demonstrations.
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Purpose: We explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated with immune checkpoint inhibition. Materials and Methods: 94 consecutive metastatic melanoma patients treated with immune checkpoint inhibition were included into this study. PET/CT imaging was available at baseline (Tp0), 3 months (Tp1) and 6 months (Tp2) after start of immunotherapy. Radiological response at Tp2 was evaluated using iRECIST. Total tumor burden (TB) at each time-point was measured and relative change of TB compared to baseline was calculated. LDH, CRP and S-100B were also analyzed. Cox proportional hazards model and logistic regression were used for survival analysis. Results: iRECIST at Tp2 was significantly associated with overall survival (OS) with C-index=0.68. TB at baseline was not associated with OS, whereas TB at Tp1 and Tp2 provided similar predictive power with C-index of 0.67 and 0.71, respectively. Appearance of new metastatic lesions during follow-up was an independent prognostic factor (C-index=0.73). Elevated LDH and S-100B ratios at Tp2 were significantly associated with worse OS: C-index=0.73 for LDH and 0.73 for S-100B. Correlation of LDH with TB was weak (r=0.34). A multivariate model including TB change, S-100B, and appearance of new lesions showed the best predictive performance with C-index=0.83. Conclusion: Our analysis shows only a weak correlation between LDH and TB. Additionally, baseline TB was not a prognostic factor in our cohort. A multivariate model combining early blood and imaging biomarkers achieved the best predictive power with regard to survival, outperforming iRECIST.
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OBJECTIVES: The lack of standardized X-ray imaging remains a challenge for comparative studies on spatial scans acquired from different clinic-specific X-ray scanners. The central objectives of this study are: 1) to delineate mineral density (MD) values, and 2) generate spatial MD maps of various physiologic and pathologic biominerals, and 3) propose a standardization protocol within the safe-operating zone of a CT scanner that underpins normalization of absorbed dose to shape and density of tissues. METHODS: A systematic approach to propose a standardization protocol for CT imaging in vivo included: 1) estimation of pathologic MD ranges by performing a comparative meta-analysis on 2009-2019 data from the PubMed database; 2) calibration of cone-beam CT (CBCT) and micro-CT scanners with phantoms of known mineral densities (0, 250, 500, 750 and 3000â¯mg/cc) and shapes (cylinders and polyhedrons); 3) scanning craniofacial bones (Nâ¯=â¯5) and dental tissues (Nâ¯=â¯5), and ectopic minerals from humans (Nâ¯=â¯3 each, pulp, salivary gland, kidney and prostrate stones, and penile and vascular plaques); 4) underscoring the effect of shape-factor (surface area-to-volume ratio) on MD of biominerals. RESULTS: Higher MDs of physiologic and pathologic cortical bones (504-1009â¯mg/cc) compared to trabecular bone (82-212â¯mg/cc) were observed. An increase in shape-factor increased the CBCT error in MD measurement and revealed that the scanner resolution is dependent on the absorbed dose and shape-factor of detectable features. SIGNIFICANCE: CT scanners should be calibrated with phantoms containing segments of known shape-factors and mineral densities to identify safe-operating zones. The calibrated approach will narrow the gap between length-scale dependent measurements, and will permit spatiotemporal quantitative and reliable detection of pathologies.
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Osso e Ossos , Tomografia Computadorizada de Feixe Cônico , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Minerais , Padrões de Referência , Microtomografia por Raio-X/métodosRESUMO
BACKGROUND AND PURPOSE: MR-guided radiotherapy (MRgRT) allows real-time beam-gating to compensate for intra-fractional target position variations. This study investigates the dosimetric impact of beam-gating and the impact of PTV margin on prostate coverage for prostate cancer patients treated with online-adaptive MRgRT. MATERIALS AND METHODS: 20 consecutive prostate cancer patients were treated with online-adaptive MRgRT SBRT with 36.25 Gy in 5 fractions (PTV D95% ≥ 95% (N = 5) and PTV D95% ≥ 100% (N = 15)). Sagittal 2D cine MRIs were used for gating on the prostate with a 3 mm expansion as the gating window. We computed motion-compensated dose distributions for (i) all prostate positions during treatment (simulating non-gated treatments) and (ii) for prostate positions within the gating window (gated treatments). To evaluate the impact of PTV margin on prostate coverage, we simulated coverage with smaller margins than clinically applied both for gated and non-gated treatments. Motion-compensated fraction doses were accumulated and dose metrics were compared. RESULTS: We found a negligible dosimetric impact of beam-gating on prostate coverage (median of 0.00 Gy for both D95% and Dmean). For 18/20 patients, prostate coverage (D95% ≥ 100%) would have been ensured with a prostate-to-PTV margin of 3 mm, even without gating. The same was true for all but one fraction. CONCLUSION: Beam-gating has negligible dosimetric impact in online-adaptive MRgRT of prostate cancer. Accounting for motion, the clinically used prostate-to-PTV margin could potentially be reduced from 5 mm to 3 mm for 18/20 patients.
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Neoplasias da Próstata , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes and inactivates inorganic pyrophosphate (PPi), a potent inhibitor of calcification; therefore, TNAP inhibition is a potential target to treat ectopic calcification. These two first-in-human studies evaluated safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single (SAD) and multiple-ascending doses (MAD) of DS-1211, a TNAP inhibitor. Healthy adults were randomized 6:2 to DS-1211 or placebo, eight subjects per dose cohort. SAD study subjects received one dose of DS-1211 (range, 3-3000 mg) or placebo, whereas MAD study subjects received DS-1211 (range, 10-300 mg) once daily, 150 mg twice daily (b.i.d.), or placebo for 10 days. Primary end points were safety and tolerability. PK and PD assessments included plasma concentrations of DS-1211, alkaline phosphatase (ALP) activity, and TNAP substrates (PPi, pyridoxal 5'-phosphate [PLP], and phosphoethanolamine [PEA]). A total of 56 (DS-1211: n = 42; placebo: n = 14) and 40 (DS-1211: n = 30; placebo: n = 10) subjects enrolled in the SAD and MAD studies, respectively. In both studies, adverse events were mild or moderate and did not increase with dose. PKs of DS-1211 were linear up to 100 mg administered as a single dose and 150 mg b.i.d. administered as a multiple-dose regimen. In multiple dosing, there was minimal accumulation of DS-1211. Increased DS-1211 exposure correlated with dose-dependent ALP inhibition and concomitant increases in PPi, PLP, and PEA. In two phase I studies, DS-1211 appeared safe and well-tolerated. Post-treatment PD assessments were consistent with exposure-dependent TNAP inhibition. These data support further evaluation of DS-1211 for ectopic calcification diseases.
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Fosfatase Alcalina , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , HumanosRESUMO
BACKGROUND: Radiomic features calculated from routine medical images show great potential for personalised medicine in cancer. Patients with systemic sclerosis (SSc), a rare, multiorgan autoimmune disorder, have a similarly poor prognosis due to interstitial lung disease (ILD). Here, our objectives were to explore computed tomography (CT)-based high-dimensional image analysis ("radiomics") for disease characterisation, risk stratification and relaying information on lung pathophysiology in SSc-ILD. METHODS: We investigated two independent, prospectively followed SSc-ILD cohorts (Zurich, derivation cohort, n=90; Oslo, validation cohort, n=66). For every subject, we defined 1355 robust radiomic features from standard-of-care CT images. We performed unsupervised clustering to identify and characterise imaging-based patient clusters. A clinically applicable prognostic quantitative radiomic risk score (qRISSc) for progression-free survival (PFS) was derived from radiomic profiles using supervised analysis. The biological basis of qRISSc was assessed in a cross-species approach by correlation with lung proteomic, histological and gene expression data derived from mice with bleomycin-induced lung fibrosis. RESULTS: Radiomic profiling identified two clinically and prognostically distinct SSc-ILD patient clusters. To evaluate the clinical applicability, we derived and externally validated a binary, quantitative radiomic risk score (qRISSc) composed of 26 features that accurately predicted PFS and significantly improved upon clinical risk stratification parameters in multivariable Cox regression analyses in the pooled cohorts. A high qRISSc score, which identifies patients at risk for progression, was reverse translatable from human to experimental ILD and correlated with fibrotic pathway activation. CONCLUSIONS: Radiomics-based risk stratification using routine CT images provides complementary phenotypic, clinical and prognostic information significantly impacting clinical decision making in SSc-ILD.