Quantitative differentiation of minimal-fat angiomyolipomas from renal cell carcinomas using grating-based x-ray phase-contrast computed tomography: An ex vivo study.

BACKGROUND: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. MATERIALS AND METHODS: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. RESULTS: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. CONCLUSIONS: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Qualitative and Quantitative Imaging Evaluation of Renal Cell Carcinoma Subtypes with Grating-based X-ray Phase-contrast CT.

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.

X-ray Dark-field Radiography - In-Vivo Diagnosis of Lung Cancer in Mice.

Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.

Dynamic contrast-enhanced magnetic resonance imaging measurements in renal cell carcinoma: effect of region of interest size and positioning on interobserver and intraobserver variability.

PURPOSE: The purpose of this study was to assess the influence of region of interest (ROI) size and positioning on perfusion and permeability parameters as well as on interobserver and intraobserver variability of dynamic contrast-enhanced (DCE-MRI) of primary renal cell carcinoma (RCC) and metastases. MATERIALS AND METHODS: Thirty-nine DCE-MRI examinations of 34 patients with primary RCC and 20 examinations of 9 patients with RCC metastases obtained at 1.5 T were evaluated. Pretreatment and posttreatment analysis with antiangiogenic therapy was performed in 4 patients with primary RCCs and 5 patients with metastases. The ROIs of the whole tumor (wROI), the circular edge (cROI), a user-defined arbitrary small region (sROI), and a semiautomated segmented ROI were independently defined by 2 readers on 1 slice on arterial phase DCE-MRI images or on parametric plasma-flow maps. Analysis with a 2-compartment exchange model provided 4 parameters: plasma flow (FP), plasma volume (vp), permeability-surface product (PS), and extravascular-extracellular volume (ve). Interobserver and intraobserver parameter correlations were calculated using the intraclass correlation coefficient, and within-subject variability were considered on the basis of the coefficient of variation. Differences in measurement values of variable ROI size were assessed with paired t test. RESULTS: Mean values of FP and vp with sROIs were significantly higher than those with wROI, cROI, and semiautomated segmented ROI placement in tumor or metastases. Values of ve showed no significant difference between ROI sizes. The highest interobserver and intraobserver correlation with 0.99/0.98 for metastases and 0.97/0.98 for primary RCCs, respectively, was observed for all parameters when defining wROIs on dynamic images. Perfusion parameters of wROI measurements for FP (dynamic, 0.97; parametric maps, 0.96) and vp (0.95/0.89) showed higher interobserver correlation than did permeability parameters ve (0.64/0.6) and PS (0.79/0.5) in primary RCCs. The wROIs showed also the lowest within-subject coefficients of variation for perfusion parameters FP and vp compared with cROI and sROIs in primary RCCs and metastases. CONCLUSIONS: The ROI size and positioning do substantially influence quantitative perfusion and permeability parameters in DCE-MRI. The best interobserver and intraobserver correlation can be obtained when defining a whole-tumor ROI. The perfusion parameters are the most reliable, whereas the permeability parameters are more susceptible to interobserver variability. No significant differences between placing ROIs on morphological or parametric images were observed.

Dynamic contrast-enhanced magnetic resonance imaging assessment of kidney function and renal masses: single slice versus whole organ/tumor.

OBJECTIVES: The aim of this study was to compare single-slice and 3-dimensional (3D) analysis for magnetic resonance renography (plasma flow [FP], plasma volume [VP], and glomerular filtration rate [GFR]) and for dynamic contrast-enhanced magnetic resonance imaging (MRI) of renal tumors (FP, VP, permeability-surface area product), respectively. MATERIAL AND METHODS: We prospectively included 22 patients (43 kidneys with 22 suspicious renal lesions) and performed preoperative and postoperative imaging before and after partial nephrectomy, respectively. Of the 22 renal lesions, 15 turned out to be renal cell carcinoma and were included in the tumor analysis, altogether leading to 86 renal and 15 tumor MRI scans, respectively. Dynamic contrast-enhanced MRI was performed with a time-resolved angiography with stochastic trajectories sequence (spatial resolution, 2.6 × 2.6 × 2.6 mm3; temporal resolution, 2.5 seconds) at 3 T (Magnetom Verio; Siemens Healthcare Sector) after injection of 0.05 mmol/kg body weight Gadobutrol (Bayer Healthcare Pharmaceuticals). Analysis was performed using regions of interest encompassing a single central slice and the whole kidney/tumor, respectively. A 2-compartment model yielding FP, VP, GFR, or tumor permeability-surface area product was used for kinetic modelling. Modelling was performed based on relative contrast enhancement to account for coil-related inhomogeneity. Significance in difference, agreement, and goodness of fit of the data to the curve was assessed with paired t tests, Bland-Altman plots, and χ2 test, respectively. RESULTS: Bland-Altman analysis revealed a good agreement between both types of measurement for kidneys and tumors, respectively. Results between single-slice and whole-kidney regions of interest showed significant differences for Fp (single slice, 256.1 ± 104.1 mL/100 mL/min; whole kidney, 217.2 ± 92.5 mL/100 mL/min; P < 0.01). Regarding VP and GFR, no significant differences were observed. The χ2 test showed a significantly better goodness of fit of the data to the curve for whole kidneys (0.30% ± 0.18%) than for single slices (0.43% ± 0.26%) (P < 0.01). In contrast to renal assessment, tumor analysis showed no significant differences regarding functional parameters and χ test, respectively. CONCLUSION: In dynamic contrast-enhanced MRI of the kidney, both 3D whole-organ/tumor and single-slice analyses provide roughly comparable values in functional analysis. However, 3D assessment is considerably more precise and should be preferred if available.

The role of functional imaging in the era of targeted therapy of renal cell carcinoma.

Antiangiogenic therapies interacting with tumor-specific pathways have been established for targeted therapy of renal cell carcinoma (RCC). However, evaluation of tumor response based on morphologic tumor diameter measurements has limitations, as tumor shrinkage may lag behind pathophysiological response. Functional imaging techniques such as dynamic contrast-enhanced (DCE) ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI), unenhanced diffusion-weighted MRI (DW-MRI), and also metabolic imaging with positron emission tomography (PET) have the ability to assess physiological parameters and to predict and monitor therapy response. Assessment of changes in vascularity, cellularity, oxygenation, and glucose uptake with functional imaging during targeted therapy may correlate with progression-free survival and can predict tumor response or progression. In this review, we explore the potential of functional imaging techniques for assessing the effects of targeted therapy of RCC and as well review the reproducibility and limitations.