Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.

PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Ultrafast Charge Transfer Dynamics in a Slip-Stacked Donor-Acceptor-Acceptor System.

Photoexcitation of molecular electron donor and/or acceptor chromophore aggregates can greatly affect their charge-transfer dynamics. Excitonic coupling not only alters the energy landscape in the excited state but may also open new photophysical pathways, such as symmetry-breaking charge separation (SB-CS). Here, we investigate the impact of excitonic coupling on a covalent donor-acceptor-acceptor system comprising a perylene donor (Per) and two perylenediimide (PDI) acceptor chromophores in which the three components are π-stacked in a geometry that is slipped along their long axes (Per-PDI2). Following selective photoexcitation of PDI, femtosecond transient absorption data for Per-PDI2 is compared to that for the single-donor, single-acceptor Per-PDI system, and the PDI2 dimer, which both have the same interchromophore geometry as Per-PDI2. The data show that electron transfer from Per to the lower exciton state of the PDI dimer is slower than that of the single PDI acceptor system. This is due to the lower free energy of the reaction for charge separation because of the electronic stabilization afforded by the excitonic coupling between the PDIs. While PDI2 was shown previously to undergo ultrafast SB-CS, the strong π-π electronic interaction of Per with the adjacent PDI in Per-PDI2 breaks the electronic symmetry of the PDI dimer, resulting in the oxidation of Per rather than SB-CS. These results show that the electronic coupling between molecules designed to accept charges produced by SB-CS in molecular dimers and the chromophores comprising the dimer must be balanced to favor SB-CS.

Coherent Vibronic Wavepackets Show Structure-Directed Charge Flow in Host-Guest Donor-Acceptor Complexes.

Designing and controlling charge transfer (CT) pathways in organic semiconductors are important for solar energy applications. To be useful, a photogenerated, Coulombically bound CT exciton must further separate into free charge carriers; direct observations of the detailed CT relaxation pathways, however, are lacking. Here, photoinduced CT and relaxation dynamics in three host-guest complexes, where a perylene (Per) electron donor guest is incorporated into two symmetric and one asymmetric extended viologen cyclophane acceptor hosts, are presented. The central ring in the extended viologen is either p-phenylene (ExV2+) or electron-rich 2,5-dimethoxy-p-phenylene (ExMeOV2+), resulting in two symmetric cyclophanes with unsubstituted or methoxy-substituted central rings, ExBox4+ and ExMeOBox4+, respectively, and an asymmetric cyclophane with one of the central viologen rings being methoxylated ExMeOVBox4+. Upon photoexcitation, the asymmetric host-guest ExMeOVBox4+ ⊃ Per complex exhibits directional CT toward the energetically unfavorable methoxylated side due to structural restrictions that facilitate strong interactions between the Per donor and the ExMeOV2+ side. The CT state relaxation pathways are probed using ultrafast optical spectroscopy by focusing on coherent vibronic wavepackets, which are used to identify CT relaxations along charge localization and vibronic decoherence coordinates. Specific low- and high-frequency nuclear motions are direct indicators of a delocalized CT state and the degree of CT character. Our results show that the CT pathway can be controlled by subtle chemical modifications of the acceptor host in addition to illustrating how coherent vibronic wavepackets can be used to probe the nature and time evolution of the CT states.

Encapsulating Semiconductor Quantum Dots in Supramolecular Cages Enables Ultrafast Guest-Host Electron and Vibrational Energy Transfer.

In the field of supramolecular chemistry, host-guest systems have been extensively explored to encapsulate a wide range of substrates, owing to emerging functionalities in nanoconfined space that cannot be achieved in dilute solutions. However, host-guest chemistry is still limited to encapsulation of small guests. Herein, we construct a water-soluble metallo-supramolecular hexagonal prism with a large hydrophobic cavity by anchoring multiple polyethylene glycol chains onto the building blocks. Then, assembled prisms are able to encapsulate quantum dots (QDs) with diameters of less than 5.0 nm. Furthermore, we find that the supramolecular cage around each QD strongly modifies the photophysics of the QD by universally increasing the rates of QD relaxation processes via ultrafast electron and vibrational energy transfer. Taken together, these efforts expand the scope of substrates in host-guest systems and provide a new approach to tune the optical properties of QDs.

Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM.

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community.

Two-Dimensional Electronic Spectroscopy Reveals Vibrational Modes Coupled to Charge Transfer in a Julolidine-BODIPY Dyad.

Understanding charge transfer (CT) dynamics in molecular donor-acceptor (D-A) dyads can provide insight into developing efficient D-A molecules for capturing solar energy. Here, we characterize the excited-state evolution of a julolidine-BODIPY (Jul-BD) D-A system with an emissive CT state using time-resolved fluorescence, femtosecond transient absorption, and two-dimensional electronic spectroscopies. Comparison of these results with those from phenyl-BODIPY (Ph-BD) allows us to identify the dynamics at play during CT state formation and its subsequent conversion to either a fully charge-separated or triplet state. Photoexcitation of Jul-BD in tetrahydrofuran results in the formation of an initial emissive CT state that relaxes before fully charge-separating. In contrast, Jul-BD in toluene exhibits similar CT state dynamics, albeit at slower timescales, before decaying to a terminal triplet species. Quantum beat analysis at early times in both solvents shows several vibronic modes, which are corroborated using density functional theory (DFT) calculations. For Ph-BD, a single 220 cm-1 compression mode about the single bond linking the phenyl to BODIPY modulates their orbital overlap. Three active vibronic modes, 147, 174, and 214 cm-1, are found in Jul-BD, regardless of the dielectric constant of the medium. These motions correspond to compression and torsional motions along the single bond joining Jul to BD and are responsible for the evolution of the spontaneous and stimulated emission features in the time-resolved spectroscopic data, which is further supported by time-dependent DFT calculations of the steady-state absorption spectrum of the Jul-BD as a function of increasing D-A dihedral core angle. These findings show how torsional and compression motions can play a pivotal role in intramolecular CT between a D and an A linked by a single bond.

Local density dependent potentials for an underlying van der Waals equation of state: A simulation and density functional theory analysis.

There is an ever increasing use of local density dependent potentials in the mesoscale modeling of complex fluids. Questions remain, though, about the dependence of the thermodynamic and structural properties of such systems on the cutoff distance used to calculate these local densities. These questions are particularly acute when it comes to the stability and structure of the vapor/liquid interface. In this article, we consider local density dependent potentials derived from an underlying van der Waals equation of state. We use simulation and density functional theory to examine how the bulk thermodynamic and interfacial properties vary with the cutoff distance, rc, used to calculate the local densities. We show quantitatively how the simulation results for bulk thermodynamic properties and vapor-liquid equilibrium approach the van der Waals limit as rc increases and demonstrate a scaling law for the radial distribution function in the large rc limit. We show that the vapor-liquid interface is stable with a well-defined surface tension and that the interfacial density profile is oscillatory, except for temperatures close to critical. Finally, we show that in the large rc limit, the interfacial tension is proportional to rc and, therefore, unlike the bulk thermodynamic properties, does not approach a constant value as rc increases. We believe that these results give new insights into the properties of local density dependent potentials, in particular their unusual interfacial behavior, which is relevant for modeling complex fluids in soft matter.

Influence of Vibronic Coupling on Ultrafast Singlet Fission in a Linear Terrylenediimide Dimer.

Singlet fission (SF) is a photophysical process capable of boosting the efficiency of solar cells. Recent experimental investigations into the mechanism of SF provide evidence for coherent mixing between the singlet, triplet, and charge transfer basis states. Up until now, this interpretation has largely focused on electronic interactions; however, nuclear motions resulting in vibronic coupling have been suggested to support rapid and efficient SF in organic chromophore assemblies. Further information about the complex interactions between vibronic excited states is needed to understand the potential role of this coupling in SF. Here, we report mixed singlet and correlated triplet pair states giving rise to sub-50 fs SF in a terrylene-3,4:11,12-bis(dicarboximide) (TDI) dimer in which the two TDI molecules are covalently linked by a direct N-N connection at one of their imide positions, leading to a linear dimer with perpendicular TDI π systems. We observe the transfer of low-frequency coherent wavepackets between the initial predominantly singlet states to the product triplet-dominated states. This implies a non-negligible dependence of SF on nonadiabatic coupling in this dimer. We interpret our experimental results in the framework of a modified Holstein Hamiltonian, which predicts that vibronic interactions between low-frequency singlet modes and high-frequency correlated triplet pair motions lead to mixing of the pure basis states. These results highlight how nonadiabatic mixing can shape the complex potential energy landscape underlying ultrafast SF.

A model selection framework to quantify microvascular liver function in gadoxetate-enhanced MRI: Application to healthy liver, diseased tissue, and hepatocellular carcinoma.

PURPOSE: We introduce a novel, generalized tracer kinetic model selection framework to quantify microvascular characteristics of liver and tumor tissue in gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI). METHODS: Our framework includes a hierarchy of nested models, from which physiological parameters are derived in 2 regimes, corresponding to the active transport and free diffusion of gadoxetate. We use simulations to show the sensitivity of model selection and parameter estimation to temporal resolution, time-series duration, and noise. We apply the framework in 8 healthy volunteers (time-series duration up to 24 minutes) and 10 patients with hepatocellular carcinoma (6 minutes). RESULTS: The active transport regime is preferred in 98.6% of voxels in volunteers, 82.1% of patients' non-tumorous liver, and 32.2% of tumor voxels. Interpatient variations correspond to known co-morbidities. Simulations suggest both datasets have sufficient temporal resolution and signal-to-noise ratio, while patient data would be improved by using a time-series duration of at least 12 minutes. CONCLUSIONS: In patient data, gadoxetate exhibits different kinetics: (a) between liver and tumor regions and (b) within regions due to liver disease and/or tumor heterogeneity. Our generalized framework selects a physiological interpretation at each voxel, without preselecting a model for each region or duplicating time-consuming optimizations for models with identical functional forms.

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study.

BACKGROUND: Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers. METHODS: A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p = 0.025). CONCLUSIONS: In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

Incorporating radiomics into clinical trials: expert consensus endorsed by the European Society of Radiology on considerations for data-driven compared to biologically driven quantitative biomarkers.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. KEY POINTS: • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Radiomics in Oncology: A Practical Guide.

Radiomics refers to the extraction of mineable data from medical imaging and has been applied within oncology to improve diagnosis, prognostication, and clinical decision support, with the goal of delivering precision medicine. The authors provide a practical approach for successfully implementing a radiomic workflow from planning and conceptualization through manuscript writing. Applications in oncology typically are either classification tasks that involve computing the probability of a sample belonging to a category, such as benign versus malignant, or prediction of clinical events with a time-to-event analysis, such as overall survival. The radiomic workflow is multidisciplinary, involving radiologists and data and imaging scientists, and follows a stepwise process involving tumor segmentation, image preprocessing, feature extraction, model development, and validation. Images are curated and processed before segmentation, which can be performed on tumors, tumor subregions, or peritumoral zones. Extracted features typically describe the distribution of signal intensities and spatial relationship of pixels within a region of interest. To improve model performance and reduce overfitting, redundant and nonreproducible features are removed. Validation is essential to estimate model performance in new data and can be performed iteratively on samples of the dataset (cross-validation) or on a separate hold-out dataset by using internal or external data. A variety of noncommercial and commercial radiomic software applications can be used. Guidelines and artificial intelligence checklists are useful when planning and writing up radiomic studies. Although interest in the field continues to grow, radiologists should be familiar with potential pitfalls to ensure that meaningful conclusions can be drawn. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Impact of hypoxia on cervical cancer outcomes.

The annual global incidence of cervical cancer is approximately 604 000 cases/342 000 deaths, making it the fourth most common cancer in women. Cervical cancer is a major healthcare problem in low and middle income countries where 85% of new cases and deaths occur. Secondary prevention measures have reduced incidence and mortality in developed countries over the past 30 years, but cervical cancer remains a major cause of cancer deaths in women. For women who present with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO 2018) stages IB3 or upwards, chemoradiation is the established treatment. Despite high rates of local control, overall survival is less than 50%, largely due to distant relapse. Reducing the health burden of cervical cancer requires greater individualization of treatment, identifying those at risk of relapse and progression for modified or intensified treatment. Hypoxia is a well known feature of solid tumors and an established therapeutic target. Low tumorous oxygenation increases the risk of local invasion, metastasis and treatment failure. While meta-analyses show benefit, many individual trials targeting hypoxia failed in part due to not selecting patients most likely to benefit. This review summarizes the available hypoxia-targeted strategies and identifies further research and new treatment paradigms needed to improve patient outcomes. The applications and limitations of hypoxia biomarkers for treatment selection and response monitoring are discussed. Finally, areas of greatest unmet clinical need are identified to measure and target hypoxia and therefore improve cervical cancer outcomes.

Diffusion model comparison identifies distinct tumor sub-regions and tracks treatment response.

PURPOSE: MRI biomarkers of tumor response to treatment are typically obtained from parameters derived from a model applied to pre-treatment and post-treatment data. However, as tumors are spatially and temporally heterogeneous, different models may be necessary in different tumor regions, and model suitability may change over time. This work evaluates how the suitability of two diffusion-weighted (DW) MRI models varies spatially within tumors at the voxel level and in response to radiotherapy, potentially allowing inference of qualitatively different tumor microenvironments. METHODS: DW-MRI data were acquired in CT26 subcutaneous allografts before and after radiotherapy. Restricted and time-independent diffusion models were compared, with regions well-described by the former hypothesized to reflect cellular tissue, and those well-described by the latter expected to reflect necrosis or oedema. Technical and biological validation of the percentage of tissue described by the restricted diffusion microstructural model (termed %MM) was performed through simulations and histological comparison. RESULTS: Spatial and radiotherapy-related variation in model suitability was observed. %MM decreased from a mean of 64% at baseline to 44% 6 days post-radiotherapy in the treated group. %MM correlated negatively with the percentage of necrosis from histology, but overestimated it due to noise. Within MM regions, microstructural parameters were sensitive to radiotherapy-induced changes. CONCLUSIONS: There is spatial and radiotherapy-related variation in different models' suitability for describing diffusion in tumor tissue, suggesting the presence of different and changing tumor sub-regions. The biological and technical validation of the proposed %MM cancer imaging biomarker suggests it correlates with, but overestimates, the percentage of necrosis.

Reliability and prognostic value of radiomic features are highly dependent on choice of feature extraction platform.

OBJECTIVE: To investigate the effects of Image Biomarker Standardisation Initiative (IBSI) compliance, harmonisation of calculation settings and platform version on the statistical reliability of radiomic features and their corresponding ability to predict clinical outcome. METHODS: The statistical reliability of radiomic features was assessed retrospectively in three clinical datasets (patient numbers: 108 head and neck cancer, 37 small-cell lung cancer, 47 non-small-cell lung cancer). Features were calculated using four platforms (PyRadiomics, LIFEx, CERR and IBEX). PyRadiomics, LIFEx and CERR are IBSI-compliant, whereas IBEX is not. The effects of IBSI compliance, user-defined calculation settings and platform version were assessed by calculating intraclass correlation coefficients and confidence intervals. The influence of platform choice on the relationship between radiomic biomarkers and survival was evaluated using univariable cox regression in the largest dataset. RESULTS: The reliability of radiomic features calculated by the different software platforms was only excellent (ICC > 0.9) for 4/17 radiomic features when comparing all four platforms. Reliability improved to ICC > 0.9 for 15/17 radiomic features when analysis was restricted to the three IBSI-compliant platforms. Failure to harmonise calculation settings resulted in poor reliability, even across the IBSI-compliant platforms. Software platform version also had a marked effect on feature reliability in CERR and LIFEx. Features identified as having significant relationship to survival varied between platforms, as did the direction of hazard ratios. CONCLUSION: IBSI compliance, user-defined calculation settings and choice of platform version all influence the statistical reliability and corresponding performance of prognostic models in radiomics. KEY POINTS: • Reliability of radiomic features varies between feature calculation platforms and with choice of software version. • Image Biomarker Standardisation Initiative (IBSI) compliance improves reliability of radiomic features across platforms, but only when calculation settings are harmonised. • IBSI compliance, user-defined calculation settings and choice of platform version collectively affect the prognostic value of features.

Cancer heterogeneity and imaging.

There is interest in identifying and quantifying tumor heterogeneity at the genomic, tissue pathology and clinical imaging scales, as this may help better understand tumor biology and may yield useful biomarkers for guiding therapy-based decision making. This review focuses on the role and value of using x-ray, CT, MRI and PET based imaging methods that identify, measure and map tumor heterogeneity. In particular we highlight the potential value of these techniques and the key challenges required to validate and qualify these biomarkers for clinical use.

Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.

Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (∆R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ∆R1 were compared with values of R2* and ∆R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ∆R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ∆R1 and ∆R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec-1 vs 81.7 sec-1) and greater negative ∆R2* (-22.9 sec-1 vs -5.4 sec-1), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.