Combining Multiple Magnetic Resonance Imaging Sequences Provides Independent Reproducible Radiomics Features.

To evaluate the relative contribution of different Magnetic Resonance Imaging (MRI) sequences for the extraction of radiomics features in a cohort of patients with lacrimal gland tumors. This prospective study was approved by the Institutional Review Board and signed informed consent was obtained from all participants. From December 2015 to April 2017, 37 patients with lacrimal gland lesions underwent MRI before surgery, including axial T1-WI, axial Diffusion-WI, coronal DIXON-T2-WI and coronal post-contrast DIXON-T1-WI. Two readers manually delineated both lacrimal glands to assess inter-observer reproducibility, and one reader performed two successive delineations to assess intra-observer reproducibility. Radiomics features were extracted using an in-house software to calculate 85 features per region-of-interest (510 features/patient). Reproducible features were defined as features presenting both an intra-class correlation coefficient ≥0.8 and a concordance correlation coefficient ≥0.9 across combinations of the three delineations. Among these features, the ones yielding redundant information were identified as clusters using hierarchical clustering based on the Spearman correlation coefficient. All the MR sequences provided reproducible radiomics features (range 14(16%)-37(44%)) and non-redundant clusters (range 5-14). The highest numbers of features and clusters were provided by the water and in-phase DIXON T2-WI and water and in-phase post-contrast DIXON T1-WI (37, 26, 26 and 26 features and 14,12, 9 and 11 clusters, respectively). A total of 145 reproducible features grouped into 51 independent clusters was provided by pooling all the MR sequences. All MRI sequences provided reproducible radiomics features yielding independent information which could potentially serve as biomarkers.

Real time shear waves elastography monitoring of thermal ablation: in vivo evaluation in pig livers.

BACKGROUND: Thermal ablation is a widely used minimally invasive treatment modality for different cancers. However, lack of a real-time imaging system for accurate evaluation of the procedure is one of the reasons of local recurrences. Shear waves elastography (SWE) is a new ultrasound (US) imaging modality to quantify tissue stiffness. The aim of the study was to assess the feasibility and accuracy of US elastography for quantitative monitoring of thermal ablation and to determine the elasticity threshold predictive of coagulation necrosis. METHODS: A total of 29 in vivo thermal lesions were performed in pig livers with radiofrequency system. SWE and B-mode images were acquired simultaneously. Liver elasticity was quantified by using SWE data and expressed in kilopascal. After the procedure, pathologic analysis of treated tissues was compared with US images. The sensitivity and positive predictive value of the SWE maps of tissue elasticity were calculated and compared with the boundaries of the pale coagulation necrosis areas found at pathology. RESULTS: The liver mean elasticity values before and after thermal therapy were 6.4 ± 0.3 and 38.1 ± 2.5 kPa, respectively (P < 0.0001). For a threshold of 20 kPa, sensitivity (i.e., the rate of pixels correctly detected as necrosed tissue) was 0.8, and the positive predictive value (i.e., the rate of pixels in the elastographic map >20 kPa that actually developed coagulation necrosis) was 0.83. CONCLUSIONS: Tissue areas with coagulation necrosis are significantly stiffer than the surrounding tissue. SWE permits the real-time detection of coagulation necrosis produced by radiofrequency and could potentially be used to monitor US-guided thermal ablation.

MR perfusion for pelvic female imaging.

Perfusion MRI of the female pelvis is based on a T1-weighted imaging acquired repeatedly at high temporal resolution. Post-processing can be carried out either from a visual analysis, by description of the curves or by compartmental modeling. Many studies have shown this method to be useful in detecting cervical cancers (initial tumor or identification of recurrence), and in staging endometrial cancers (assessment of cervical invasion). More recent studies have described perfusion MRI as a tool for characterizing adnexal tumors based on the properties of the microvascular wall. When it is combined with morphological MRI findings and diffusion sequences, it incorporates a decision-making algorithm which has a diagnostic performance of 95.4% in characterizing complex adnexal masses (Thomassin-Naggara et al., 2011).

Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

Dynamic contrast enhanced optical imaging of capillary leakage.

We studied in vivo the vascular permeability of two fluorescent contrast agents in three types of capillary, using a fibered confocal fluorescence microscopy system. Mice were imaged after injection of a macromolecular (albumin FITC 68,000 daltons) or low-molecular-weight contrast agent (FITC 389 daltons). We studied continuous capillaries in muscles (FITC n = 4, albumin FITC n = 6), fenestrated capillaries in mesenteries (FITC n = 8, albumin FITC n = 10), and discontinuous capillaries in xenografted tumors (FITC n = 2, albumin FITC n = 4). Signal intensity (SI) was measured in capillary and interstitial regions, and time-enhancement curves were drawn. Two-compartment models were constructed to determine quantitative microcirculation parameters. The arrival of the bolus of the two different contrast agents was observed in mesentery and muscle capillaries but not in tumor capillaries. Interstitial leakage of the low-molecular-weight contrast agent was observed almost instantaneously, whereas the macromolecular agent remained within the vessels. Signal intensity declined over the observation period, specifically in the tumor. No quantitative microcirculation parameters could be obtained with either of two bi compartmental models, owing to model instability. This study shows that the microcirculation can be reproducibly observed in different types of capillary in vivo with this fibered fluorescence imaging device. Further work is required to quantify microvascular parameters.

Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: In metastatic renal cell carcinoma (mRCC), antiangiogenic treatments rarely achieve a reduction of -30% in the sum of longest diameters (SLD) of target lesions required by RECIST for an 'objective response', although they objectively improve progression-free survival (PFS). We sought to determine a threshold for the computed tomography evaluation of these patients' best reflecting patient outcome. PATIENTS AND METHODS: In 334 mRCC patients treated with sunitinib, we tested thresholds from -45% to +10%. We classified patients as 'responders' when the best relative variation of the sum of longest diameters (DeltaSLD) reached the tested threshold and as 'nonresponders' otherwise. For each tested threshold, the median PFS of the two groups were compared. Receiver operating characteristic (ROC) analysis was also carried out among the 103 patients that progressed during follow-up. Finally, the 'optimal' threshold was retested on an independent cohort of 39 patients. RESULTS: The DeltaSLD threshold of -10% gave the most significant difference. It divided patients into 256 responders and 78 nonresponders (median PFS 11.1 and 5.6 months). The same -10% threshold was found using the ROC analysis. Results were confirmed on the external validation cohort. CONCLUSION: A variation of -10% in the SLD accurately and rapidly identifies mRCC patients benefiting from sunitinib.

Tumor angiogenesis: pathophysiology and implications for contrast-enhanced MRI and CT assessment.

The process of tumor neoangiogenesis plays a central role in the growth and spread of tumors. It is currently a leading theme in oncology, and many new drugs targeting the tumor neoangiogenic process are under development. Expanding tumors become hypoxic and tumor cells express transcription factors, such as the hypoxia-inducible factor (HIF), which induce the release of proangiogenic growth factors such as vascular endothelial growth factors (VEGF) and transforming growth factors that promote the formation of new capillaries by recruiting, activating, and stimulating endothelial cells. Activated endothelial cells secrete matrix metalloproteases, which degrade the basement membrane and the extracellular matrix, and adhesion receptors such as integrins alphavbeta(3), which allow their migration into the extracellular matrix toward the tumor cells. The newly grown vessels are immature and differ from normal capillaries. They are tortuous and irregular, resulting in poorly efficient perfusion, they are leaky (especially to macromolecules), and they are independent of the normal mechanisms of regulation of the capillary blood flow. Moreover, tumor microcirculation is heterogeneous. Evaluation of angiogenesis can be used as a prognostic marker to evaluate the aggressiveness of tumor and as a potential predictive marker of antiangiogenic treatment response. Histopathologic techniques of microvascular density indexes require invasive tissue sampling and need to be standardized. Hemodynamic characteristics of immature neovessels can be noninvasively assessed by dynamic contrast-enhanced magnetic resonance imaging or computed tomography. Tissue enhancement depends on arterial input function, kinetic of distribution of blood into the capillary bed, leakage across the capillary walls, and volume of the interstitial space. Pharmacodynamic models allow the evaluation of microvascular parameters of tissue blood flow, tissue blood volume, tissue interstitial volume, mean transit time, and permeability by surface of capillary wall. Methods based on dynamic contrast enhancement have been shown to correlate with conventional outcome methods such as histopathologic studies and survival. Radiologists must be convinced that, by using this emerging and promising approach, it is becoming possible to gain functional information during routine tumor imaging.