A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics with Metabolism, Signaling Networks, and Biomechanics as Plug-In Component Models of a Cancer Digital Twin.

The massive amount of human biological, imaging, and clinical data produced by multiple and diverse sources necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell-signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels, as well as their orchestration and links, are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof-of-concept study cases. Personalized simulations of the actual anatomy of a patient have been conducted. The hypermodel has also been applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin-based clinical decision support system and as the core of future in silico trial platforms, although additional retrospective adaptation and validation are necessary.

Documenting the de-identification process of clinical and imaging data for AI for health imaging projects.

Artificial intelligence (AI) is revolutionizing the field of medical imaging, holding the potential to shift medicine from a reactive "sick-care" approach to a proactive focus on healthcare and prevention. The successful development of AI in this domain relies on access to large, comprehensive, and standardized real-world datasets that accurately represent diverse populations and diseases. However, images and data are sensitive, and as such, before using them in any way the data needs to be modified to protect the privacy of the patients. This paper explores the approaches in the domain of five EU projects working on the creation of ethically compliant and GDPR-regulated European medical imaging platforms, focused on cancer-related data. It presents the individual approaches to the de-identification of imaging data, and describes the problems and the solutions adopted in each case. Further, lessons learned are provided, enabling future projects to optimally handle the problem of data de-identification. CRITICAL RELEVANCE STATEMENT: This paper presents key approaches from five flagship EU projects for the de-identification of imaging and clinical data offering valuable insights and guidelines in the domain. KEY POINTS: ΑΙ models for health imaging require access to large amounts of data. Access to large imaging datasets requires an appropriate de-identification process. This paper provides de-identification guidelines from the AI for health imaging (AI4HI) projects.

Image Quality Assessment Tool for Conventional and Dynamic Magnetic Resonance Imaging Acquisitions.

Image quality assessment of magnetic resonance imaging (MRI) data is an important factor not only for conventional diagnosis and protocol optimization but also for fairness, trustworthiness, and robustness of artificial intelligence (AI) applications, especially on large heterogeneous datasets. Information on image quality in multi-centric studies is important to complement the contribution profile from each data node along with quantity information, especially when large variability is expected, and certain acceptance criteria apply. The main goal of this work was to present a tool enabling users to assess image quality based on both subjective criteria as well as objective image quality metrics used to support the decision on image quality based on evidence. The evaluation can be performed on both conventional and dynamic MRI acquisition protocols, while the latter is also checked longitudinally across dynamic series. The assessment provides an overall image quality score and information on the types of artifacts and degrading factors as well as a number of objective metrics for automated evaluation across series (BRISQUE score, Total Variation, PSNR, SSIM, FSIM, MS-SSIM). Moreover, the user can define specific regions of interest (ROIs) to calculate the regional signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), thus individualizing the quality output to specific use cases, such as tissue-specific contrast or regional noise quantification.

Public data homogenization for AI model development in breast cancer.

BACKGROUND: Developing trustworthy artificial intelligence (AI) models for clinical applications requires access to clinical and imaging data cohorts. Reusing of publicly available datasets has the potential to fill this gap. Specifically in the domain of breast cancer, a large archive of publicly accessible medical images along with the corresponding clinical data is available at The Cancer Imaging Archive (TCIA). However, existing datasets cannot be directly used as they are heterogeneous and cannot be effectively filtered for selecting specific image types required to develop AI models. This work focuses on the development of a homogenized dataset in the domain of breast cancer including clinical and imaging data. METHODS: Five datasets were acquired from the TCIA and were harmonized. For the clinical data harmonization, a common data model was developed and a repeatable, documented "extract-transform-load" process was defined and executed for their homogenization. Further, Digital Imaging and COmmunications in Medicine (DICOM) information was extracted from magnetic resonance imaging (MRI) data and made accessible and searchable. RESULTS: The resulting harmonized dataset includes information about 2,035 subjects with breast cancer. Further, a platform named RV-Cherry-Picker enables search over both the clinical and diagnostic imaging datasets, providing unified access, facilitating the downloading of all study imaging that correspond to specific series' characteristics (e.g., dynamic contrast-enhanced series), and reducing the burden of acquiring the appropriate set of images for the respective AI model scenario. CONCLUSIONS: RV-Cherry-Picker provides access to the largest, publicly available, homogenized, imaging/clinical dataset for breast cancer to develop AI models on top. RELEVANCE STATEMENT: We present a solution for creating merged public datasets supporting AI model development, using as an example the breast cancer domain and magnetic resonance imaging images. KEY POINTS: • The proposed platform allows unified access to the largest, homogenized public imaging dataset for breast cancer. • A methodology for the semantically enriched homogenization of public clinical data is presented. • The platform is able to make a detailed selection of breast MRI data for the development of AI models.

MI-Common Data Model: Extending Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM) for Registering Medical Imaging Metadata and Subsequent Curation Processes.

PURPOSE: The explosion of big data and artificial intelligence has rapidly increased the need for integrated, homogenized, and harmonized health data. Many common data models (CDMs) and standard vocabularies have appeared in an attempt to offer harmonized access to the available information, with Observational Medical Outcomes Partnership (OMOP)-CDM being one of the most prominent ones, allowing the standardization and harmonization of health care information. However, despite its flexibility, still capturing imaging metadata along with the corresponding clinical data continues to pose a challenge. This challenge arises from the absence of a comprehensive standard representation for image-related information and subsequent image curation processes and their interlinkage with the respective clinical information. Successful resolution of this challenge holds the potential to enable imaging and clinical data to become harmonized, quality-checked, annotated, and ready to be used in conjunction, in the development of artificial intelligence models and other data-dependent use cases. METHODS: To address this challenge, we introduce medical imaging (MI)-CDM-an extension of the OMOP-CDM specifically designed for registering medical imaging data and curation-related processes. Our modeling choices were the result of iterative numerous discussions among clinical and AI experts to enable the integration of imaging and clinical data in the context of the ProCAncer-I project, for answering a set of clinical questions across the prostate cancer's continuum. RESULTS: Our MI-CDM extension has been successfully implemented for the use case of prostate cancer for integrating imaging and curation metadata along with clinical information by using the OMOP-CDM and its oncology extension. CONCLUSION: By using our proposed terminologies and standardized attributes, we demonstrate how diverse imaging modalities can be seamlessly integrated in the future.

MRI Methods to Visualize and Quantify Adipose Tissue in Health and Disease.

MRI is the modality of choice for a vast range of pathologies but also a sensitive probe into human physiology and tissue function. For this reason, several methodologies have been developed and continuously evolve in order to non-invasively monitor underlying phenomena in human adipose tissue that were difficult to assess in the past through visual inspection of standard imaging modalities. To this end, this work describes the imaging methodologies used in medical practice and lists the most important quantitative markers related to adipose tissue physiology and pathology that are currently supporting diagnosis, longitudinal evaluation and patient management decisions. The underlying physical principles and the resulting markers are presented and associated with frequently encountered pathologies in radiology in order to set the frame of the ability of MRI to reveal the complex role of adipose tissue, not as an inert tissue but as an active endocrine organ.

A segmentation-based method improving the performance of N4 bias field correction on T2weighted MR imaging data of the prostate.

Magnetic Resonance (MR) images suffer from spatial inhomogeneity, known as bias field corruption. The N4ITK filter is a state-of-the-art method used for correcting the bias field to optimize MR-based quantification. In this study, a novel approach is presented to quantitatively evaluate the performance of N4 bias field correction for pelvic prostate imaging. An exploratory analysis, regarding the different values of convergence threshold, shrink factor, fitting level, number of iterations and use of mask, is performed to quantify the performance of N4 filter in pelvic MR images. The performance of a total of 240 different N4 configurations is examined using the Full Width at Half Maximum (FWHM) of the segmented periprostatic fat distribution as evaluation metric. Phantom T2weighted images were used to assess the performance of N4 for a uniform test tissue mimicking material, excluding factors such as patient related susceptibility and anatomy heterogeneity. Moreover, 89 and 204 T2weighted patient images from two public datasets acquired by scanners with a combined surface and endorectal coil at 1.5 T and a surface coil at 3 T, respectively, were utilized and corrected with a variable set of N4 parameters. Furthermore, two external public datasets were used to validate the performance of the N4 filter in T2weighted patient images acquired by various scanning conditions with different magnetic field strengths and coils. The results show that the set of N4 parameters, converging to optimal representations of fat in the image, were: convergence threshold 0.001, shrink factor 2, fitting level 6, number of iterations 100 and the use of default mask for prostate images acquired by a combined surface and endorectal coil at both 1.5 T and 3 T. The corresponding optimal N4 configuration for MR prostate images acquired by a surface coil at 1.5 T or 3 T was: convergence threshold 0.001, shrink factor 2, fitting level 5, number of iterations 25 and the use of default mask. Hence, periprostatic fat segmentation can be used to define the optimal settings for achieving T2weighted prostate images free from bias field corruption to provide robust input for further analysis.

Radiomics and Machine Learning Can Differentiate Transient Osteoporosis from Avascular Necrosis of the Hip.

Differentiation between transient osteoporosis (TOH) and avascular necrosis (AVN) of the hip is a longstanding challenge in musculoskeletal radiology. The purpose of this study was to utilize MRI-based radiomics and machine learning (ML) for accurate differentiation between the two entities. A total of 109 hips with TOH and 104 hips with AVN were retrospectively included. Femoral heads and necks with segmented radiomics features were extracted. Three ML classifiers (XGboost, CatBoost and SVM) using 38 relevant radiomics features were trained on 70% and validated on 30% of the dataset. ML performance was compared to two musculoskeletal radiologists, a general radiologist and two radiology residents. XGboost achieved the best performance with an area under the curve (AUC) of 93.7% (95% CI from 87.7 to 99.8%) among ML models. MSK radiologists achieved an AUC of 90.6% (95% CI from 86.7% to 94.5%) and 88.3% (95% CI from 84% to 92.7%), respectively, similar to residents. The general radiologist achieved an AUC of 84.5% (95% CI from 80% to 89%), significantly lower than of XGboost (p = 0.017). In conclusion, radiomics-based ML achieved a performance similar to MSK radiologists and significantly higher compared to general radiologists in differentiating between TOH and AVN.

Multicenter DSC-MRI-Based Radiomics Predict IDH Mutation in Gliomas.

To address the current lack of dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutations in gliomas, we present a multicenter study that featured an independent exploratory set for radiomics model development and external validation using two independent cohorts. The maximum performance of the IDH mutation status prediction on the validation set had an accuracy of 0.544 (Cohen's kappa: 0.145, F1-score: 0.415, area under the curve-AUC: 0.639, sensitivity: 0.733, specificity: 0.491), which significantly improved to an accuracy of 0.706 (Cohen's kappa: 0.282, F1-score: 0.474, AUC: 0.667, sensitivity: 0.6, specificity: 0.736) when dynamic-based standardization of the images was performed prior to the radiomics. Model explainability using local interpretable model-agnostic explanations (LIME) and Shapley additive explanations (SHAP) revealed potential intuitive correlations between the IDH-wildtype increased heterogeneity and the texture complexity. These results strengthened our hypothesis that DSC-MRI radiogenomics in gliomas hold the potential to provide increased predictive performance from models that generalize well and provide understandable patterns between IDH mutation status and the extracted features toward enabling the clinical translation of radiogenomics in neuro-oncology.

The Significance of Echo Time in fMRI BOLD Contrast: A Clinical Study during Motor and Visual Activation Tasks at 1.5 T.

Blood Oxygen Level Dependent (BOLD) is a commonly-used MR imaging technique in studying brain function. The BOLD signal can be strongly affected by specific sequence parameters, especially in small field strengths. Previous small-scale studies have investigated the effect of TE on BOLD contrast. This study evaluates the dependence of fMRI results on echo time (TE) during concurrent activation of the visual and motor cortex at 1.5 T in a larger sample of 21 healthy volunteers. The experiment was repeated using two different TE values (50 and 70 ms) in counterbalanced order. Furthermore, T2* measurements of the gray matter were performed. Results indicated that both peak beta value and number of voxels were significantly higher using TE = 70 than TE = 50 ms in primary motor, primary somatosensory and supplementary motor cortices (p < 0.007). In addition, the amplitude of activation in visual cortices and the dorsal premotor area was also higher using TE = 70 ms (p < 0.001). Gray matter T2* of the corresponding areas did not vary significantly. In conclusion, the optimal TE value (among the two studied) for visual and motor activity is 70 ms affecting both the amplitude and extent of regional hemodynamic activation.

Cerebral CT Perfusion in Acute Stroke: The Effect of Lowering the Tube Load and Sampling Rate on the Reproducibility of Parametric Maps.

The aim of this study was to define lower dose parameters (tube load and temporal sampling) for CT perfusion that still preserve the diagnostic efficiency of the derived parametric maps. Ninety stroke CT examinations from four clinical sites with 1 s temporal sampling and a range of tube loads (mAs) (100-180) were studied. Realistic CT noise was retrospectively added to simulate a CT perfusion protocol, with a maximum reduction of 40% tube load (mAs) combined with increased sampling intervals (up to 3 s). Perfusion maps from the original and simulated protocols were compared by: (a) similarity using a voxel-wise Pearson's correlation coefficient r with in-house software; (b) volumetric analysis of the infarcted and hypoperfused volumes using commercial software. Pearson's r values varied for the different perfusion metrics from 0.1 to 0.85. The mean slope of increase and cerebral blood volume present the highest r values, remaining consistently above 0.7 for all protocol versions with 2 s sampling interval. Reduction of the sampling rate from 2 s to 1 s had only modest impacts on a TMAX volume of 0.4 mL (IQR -1-3) (p = 0.04) and core volume of -1.1 mL (IQR -4-0) (p < 0.001), indicating dose savings of 50%, with no practical loss of diagnostic accuracy. The lowest possible dose protocol was 2 s temporal sampling and a tube load of 100 mAs.

Differentiating low from high-grade soft tissue sarcomas using post-processed imaging parameters derived from multiple DWI models.

PURPOSE: To investigate and histopathologically validate the role of model selection in the design of novel parametric meta-maps towards the discrimination of low from high-grade soft tissue sarcomas (STSs) using multiple Diffusion Weighted Imaging (DWI) models. METHODS: DWI data of 28 patients were quantified using the mono-exponential, bi-exponential, stretched-exponential and the diffusion kurtosis model. Akaike Weights (AW) were calculated from the corrected Akaike Information Criteria (AICc) to select the most suitable model for every pixel within the tumor volume. Pseudo-colorized classification maps were then generated to depict model suitability, hypothesizing that every single model underpins different tissue properties and cannot solely characterize the whole tumor. Single model parametric maps were turned into meta-maps using the classification map and a histological validation of the model suitability results was conducted on several subregions of different tumors. Several histogram metrics were calculated from all derived maps before and after model selection, statistical analysis was conducted using the Mann-Whitney U test, p-values were adjusted for multiple comparisons and performance of all statistically significant metrics was evaluated using the Receiver Operator Characteristic (ROC) analysis. RESULTS: The histologic analysis on several tumor subregions confirmed model suitability results on these areas. Only 3 histogram metrics, all derived from the meta-maps, were found to be statistically significant in differentiating low from high-grade STSs with an AUC higher than 89 %. CONCLUSION: Embedding model selection in the design of the diffusion parametric maps yields to histogram metrics of high discriminatory power in grading STSs.

Extended perfusion protocol for MS lesion quantification.

This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj-R 2 goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low k trans range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.

Multiexponential T2 relaxometry of benign and malignant adipocytic tumours.

BACKGROUND: We investigated a recently proposed multiexponential (Mexp) fitting method applied to T2 relaxometry magnetic resonance imaging (MRI) data of benign and malignant adipocytic tumours and healthy subcutaneous fat. We studied the T2 distributions of the different tissue types and calculated statistical metrics to differentiate benign and malignant tumours. METHODS: Twenty-four patients with primary benign and malignant adipocytic tumours prospectively underwent 1.5-T MRI with a single-slice T2 relaxometry (Carr-Purcell-Meiboom-Gill sequence, 25 echoes) prior to surgical excision and histopathological assessment. The proposed method adaptively chooses a monoexponential or biexponential model on a voxel basis based on the adjusted R2 goodness of fit criterion. Linear regression was applied on the statistical metrics derived from the T2 distributions for the classification. RESULTS: Healthy subcutaneous fat and benign lipoma were better described by biexponential fitting with a monoexponential and biexponential prevalence of 0.0/100% and 0.2/99.8% respectively. Well-differentiated liposarcomas exhibit 17.6% monoexponential and 82.4% biexponential behaviour, while more aggressive liposarcomas show larger degree of monoexponential behaviour. The monoexponential/biexponential prevalence was 47.6/52.4% for myxoid tumours, 52.8/47.2% for poorly differentiated parts of dedifferentiated liposarcomas, and 24.9/75.1% pleomorphic liposarcomas. The percentage monoexponential or biexponential model prevalence per patient was the best classifier distinguishing between malignant and benign adipocytic tumours with a 0.81 sensitivity and a 1.00 specificity. CONCLUSIONS: Healthy adipose tissue and benign lipomas showed a pure biexponential behaviour with similar T2 distributions, while decreased adipocytic cell differentiation characterising aggressive neoplasms was associated with an increased rate of monoexponential decay curves, opening a perspective adipocytic tumour classification.

Inverse Laplace transform and multiexponential fitting analysis of T2 relaxometry data: a phantom study with aqueous and fat containing samples.

BACKGROUND: The inverse Laplace transform (ILT) is the most widely used method for T2 relaxometry data analysis. This study examines the qualitative agreement of ILT and a proposed multiexponential (Mexp method) regarding the number of T2 components. We performed a feasibility study for the voxelwise characterisation of heterogeneous tissue with T2 relaxometry. METHODS: Eleven samples of aqueous, fatty and mixed composition were analysed using ILT and Mexp. The phantom was imaged using a 1.5-T system with a single slice T2 relaxometry 25-echo Carr-Purcell-Meiboom-Gill sequence in order to obtain the T2 decay curve with 25 equidistant echo times. The adjusted R2 goodness of fit criterion was used to determine the number of T2 components using the Mexp method on a voxel-based analysis. Comparison of mean and standard deviation of T2 values for both methods was performed by fitting a Gaussian function to the ILT resulting vector. RESULTS: Phantom results showed pure monoexponential decay for acetone and water and pure biexponential behaviour for corn oil, egg yolk, and 35% fat milk cream, while mixtures of egg whites and yolks as well as milk creams with 12-20% fatty composition exhibit mixed monoexponential and biexponential behaviour at different fractions. The number of T2 components by the Mexp method was compared to the ILT-derived spectrum as ground truth. CONCLUSIONS: Mexp analysis with the adjusted R2 criterion can be used for the detection of the T2 distribution of aqueous, fatty and mixed samples with the added advantage of voxelwise mapping.

Statistical and spatial correlation between diffusion and perfusion MR imaging parameters: A study on soft tissue sarcomas.

PURPOSE: The purpose of this study was to examine the correlation of diffusion and perfusion quantitative MR parameters, on patients with malignant soft tissue tumors. In addition, we investigated the spatial agreement of hallmarks of malignancy as indicated by diffusion and perfusion biomarkers respectively. METHODS: Nonlinear least squares were used for the quantification of the DWI and DCE derived parameters for 25 patients of histologically proven soft tissue sarcoma scanned at a 1.5 T scanner. 4D data were analyzed by an in house built software implemented in Python 3.5 resulting in voxel based parametric maps based on the Intra-Voxel Incoherent Motion (IVIM), Extended Toft's (ETM) and Gamma Capillary Transit time (GCTT) models. The root mean squared error (RMSE) was also used for assessing the accuracy of the DCE fitting models. RESULTS: A good Pearson's correlation (r > 0.5) was found between micro-perfusion fraction (f-IVIM) and plasma volume (vp-GCTT). There was no significant correlation between all other possible pairs of DCE and DWI derived parameters. Following thresholding the indicators of malignancy from both imaging methods, the percentage of volume overlap between regions of high cellularity and high vascular permeability ranged from 6% to 30%. CONCLUSION: A free correlation study among all DCE and DWI derived pairs of parameters, showed a linear relationship between f-IVIM and vp-GCTT in patients with soft tissue sarcomas. DCE in conjunction with DWI MRI can provide useful information on sites of aggressive characteristics for guiding the pre-operative biopsy and for overall treatment planning.

T2, T2* and spin coupling ratio as biomarkers for the study of lipomatous tumors.

BACKGROUND: Subcutaneous fat may have variable signal intensity on T2w images depending on the choice of imaging parameters. However, fatty components within tumors have a different degree of signal dependence on the acquisition scheme. This study examined the use of T2, T2* relaxometry and spin coupling related signal changes (Spin Coupling ratio, SCr) on two different imaging protocols as clinically relevant descriptors of benign and malignant lipomatous tumors. MATERIALS AND METHODS: 20 patients with benign lipomas or liposarcomas of variable histologic grade were examined at an 1.5 T scanner with Multi Echo Spin Echo (MESE) different echo spacing (ESP) in order to produce bright fat T2w images (ESP: 13.4 ms, 25 equidistant echoes) and dark fat images (ESP: 26.8 ms with 10 equidistant echoes). T2* relaxometry acquisition comprises 4 sets of in-opposed echoes (2.4-19.2 ms, ESP: 2.4 ms) Multi Echo Gradient Echo (MEGRE) sequence. All parametric maps were calculated on a pixel basis. RESULTS: Significant differences of SCr were found for five different types of lipomatous tumors (Pairwise t-test with Bonferroni correction): lipomas, well differentiated liposarcomas, myxoid liposarcomas, pleomorphic liposarcomas and poorly differentiated liposarcomas. SCr surpassed the classification performance of T2 and T2* relaxometry. DATA CONCLUSION: A novel biomarker based on spin coupling related signal loss, SCr, is indicative of lipomatous tumor histological grading. We concluded that T2, T2* and SCr can be used for the classification of fat containing tumors, which may be important for biopsy guidance in heterogeneous masses and treatment planning.

Investigating the Role of Model-Based and Model-Free Imaging Biomarkers as Early Predictors of Neoadjuvant Breast Cancer Therapy Outcome.

Imaging biomarkers (IBs) play a critical role in the clinical management of breast cancer (BRCA) patients throughout the cancer continuum for screening, diagnosis, and therapy assessment, especially in the neoadjuvant setting. However, certain model-based IBs suffer from significant variability due to the complex workflows involved in their computation, whereas model-free IBs have not been properly studied regarding clinical outcome. In this study, IBs from 35 BRCA patients who received neoadjuvant chemotherapy (NAC) were extracted from dynamic contrast-enhanced MR imaging (DCE-MRI) data with two different approaches, a model-free approach based on pattern recognition (PR), and a model-based one using pharmacokinetic compartmental modeling. Our analysis found that both model-free and model-based biomarkers can predict pathological complete response (pCR) after the first cycle of NAC. Overall, eight biomarkers predicted the treatment response after the first cycle of NAC, with statistical significance (p-value < 0.05), and three at the baseline. The best pCR predictors at first follow-up, achieving high AUC and sensitivity and specificity more than 50%, were the hypoxic component with threshold 2 (AUC 90.4%) from the PR method, and the median value of kep (AUC 73.4%) from the model-based approach. Moreover, the 80th percentile of ve achieved the highest pCR prediction at baseline with AUC 78.5%. The results suggest that the model-free DCE-MRI IBs could be a more robust alternative to complex, model-based ones such as kep and favor the hypothesis that the PR image-derived hypoxic image component captures actual tumor hypoxia information able to predict BRCA NAC outcome.

INN: Inflated Neural Networks for IPMN Diagnosis.

Intraductal papillary mucinous neoplasm (IPMN) is a precursor to pancreatic ductal adenocarcinoma. While over half of patients are diagnosed with pancreatic cancer at a distant stage, patients who are diagnosed early enjoy a much higher 5-year survival rate of 34% compared to 3% in the former; hence, early diagnosis is key. Unique challenges in the medical imaging domain such as extremely limited annotated data sets and typically large 3D volumetric data have made it difficult for deep learning to secure a strong foothold. In this work, we construct two novel "inflated" deep network architectures, InceptINN and DenseINN, for the task of diagnosing IPMN from multisequence (T1 and T2) MRI. These networks inflate their 2D layers to 3D and bootstrap weights from their 2D counterparts (Inceptionv3 and DenseNet121 respectively) trained on ImageNet to the new 3D kernels. We also extend the inflation process by further expanding the pre-trained kernels to handle any number of input modalities and different fusion strategies. This is one of the first studies to train an end-to-end deep network on multisequence MRI for IPMN diagnosis, and shows that our proposed novel inflated network architectures are able to handle the extremely limited training data (139 MRI scans), while providing an absolute improvement of 8.76% in accuracy for diagnosing IPMN over the current state-of-the-art. Code is publicly available at https://github.com/lalonderodney/INN-Inflated-Neural-Nets.

Investigating the Correlation of Ktrans With Semi-Quantitative MRI Parameters Towards More Robust and Reproducible Perfusion Imaging Biomarkers in Three Cancer Types.

MRI Imaging biomarkers (IBs) have the potential to deliver quantitative cancer descriptors of pathophysiology for non-invasively screening, diagnosing, and monitoring cancer patients across the cancer continuum. Despite a worldwide effort to standardize IBs involving major cancer organizations, significant variability of MR-based imaging biomarker across sites still hampers their clinical translation calling for more research in the field. To this end, in the present study quantitative and semi-quantitative approaches for perfusion biomarkers are compared in MRI data from three different cancer types. In particular, Ktrans a widely used but often variable across sites candidate biomarker is compared to a semi-quantitative perfusion MRI imaging biomarker (Wash-in WIN) in patients with breast, head, and neck and soft tissue sarcoma. Our results demonstrated a linear relationship between WIN and Ktrans in all cancer patients groups when a goodness of fit (high R2) criterion for ensuring adequate data quality and accuracy is met. This consistent correlation across three different cancer types indicates that the proposed semi-quantitative perfusion MRI IB can be a simpler, more robust and reproducible alternative to Ktrans for quantitative perfusion studies in oncology.