Extravascular Extracellular Volume Research Articles

OA048] Analysis of diffusion and haemodynamic maps from multi-parametric MRI of prostate cancer

Purpose Multi-parametric MRI (mp-MRI) is being introduced in radiotherapy (RT) of prostate cancer for tumour delineation in focal boosting strategies. It has been shown that the apparent diffusion coefficient (ADC) from diffusion weighted MRI (DW-MRI) may reflect cell density. Apart from tumour volume and cell densities, tumour hypoxia is also an important determinant of RT response. In this study we investigate the patterns of ADC and haemodynamic maps, and the relations between them, inside the index lesion. Methods ADC and perfusion maps from 10 prostate cancer patients were used, with the prostate and index lesion delineated by an experienced uro-radiologist. Associations between different ADC and perfusion histogram parameters inside the index lesion were evaluated with the Pearson’s correlation coefficient (PCC). In the voxel-wise analysis, scatter plots of ADC vs perfusion were analysed for voxels in the index lesion, again with the associations quantified with the PCC. Voxels that were in the lower quartile of both ADC and the forward transport rate constant ( K trans ) were assumed to be poorly oxygenated. Results ADC and the extravascular-extracellular volume fraction ( V e ) were overall lower inside the index lesion than outside. The opposite was observed for K trans that was higher inside the index lesion than outside. In the distribution analysis, the maximum K trans was significantly correlated with the maximum ADC (rho = 0.85). At the voxel level inside the index lesion, significant inverse correlation between ADC and K trans and significant positive correlation between ADC and V e were observed for nine of ten patients. According to our definition, 8% of the index lesion was poorly oxygenated. Conclusions A general negative correlation was seen in the index lesion between ADC and K trans while a general positive correlation was seen in the index lesion for ADC vs. V e . A method of estimating poor oxygenation in the index lesion was developed, based on diffusion and haemodynamic maps.

A Chief Resident-Driven Curriculum Designed to Improve Core Exam Performance at a Small Community Radiology Residency Program

To compare the value of dynamic contrast-enhanced magnetic resonance imaging-pharmacokinetic (PK) parameters vs tumor volume in predicting breast cancer neoadjuvant chemotherapy response (NACR) and patient survival.Sixty-six patients with locally advanced breast cancer who underwent breast MRI monitoring of NACR were retrospectively analyzed. We compared baseline transfer constant (Ktrans), reflux rate contrast (kep), and extracellular extravascular volume fraction (ve) with the same parameters obtained at early postchemotherapy MRI, and examined model-independent changes in time-intensity curves (maximum slope, contrast enhancement ratio, and IAUC90). Tumor size changes (tumor volume, single dimension, and Response Evaluation Criteria in Solid Tumors [RECIST]) were also analyzed. The Spearman correlation test was used to assess the association between size and PK parameters, and regression analysis to assess the association with 5-year disease-free survival.Higher ve values at baseline were associated with greater decreases in tumor size (P = 0.008). Changes in Ktrans and IAUC90 were the strongest predictors of NACR. Changes in IAUC90 (P = 0.04) and RECIST (P = 0.003) were independently associated with pathologic response. The only parameter significantly associated with 5-year survival was change in RECIST (P = 0.001). However, there was a trend toward statistical significance for changes in ve and Ktrans, with greater changes associated with longer survival.Changes in PK and dynamic contrast-enhanced magnetic resonance imaging kinetic parameters may have a role in predicting NACR in breast tumors. Although changes in Ktrans and IAUC90 are helpful in predicting NACR, they do not show significant association with survival. Early RECIST size change measured by MRI remains the strongest predictor of overall patient survival.

DCE-MRI in Human Gliomas: A Surrogate for Assessment of Invasive Hypoxia Marker HIF-1Α Based on MRI-Neuronavigation Stereotactic Biopsies

The purpose of this study was to correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with data from a specific marker of hypoxia, hypoxia-inducible factor 1α (HIF-1α), in human gliomas on a point-to-point basis by using coregistered magnetic resonance imaging and frameless stereotactic biopsies. Thirty-four patients with treatment-naive gliomas underwent DCE, axial T1-weighted, T2-weighted, T2-weighted fluid acquisition of inversion recovery, and three-dimensional T1-weighted brain volume with gadolinium contrast enhancement sequences on a 3.0-T magnetic resonance scanner before stereotactic surgery. Quantitative perfusion indices such as endothelial transfer constant, fractional extravascular extracellular space volume, fractional plasma volume, and reflux rate were measured at corresponding stereotactic biopsy sites. Each sample was considered an independent measurement, and its histology grade was diagnosed. HIF-1α expression was quantified from the point-to-point biopsy tissues. Analyses of receiver operating characteristic curves were done for HIF-1α to discriminate different grades of glioma. To look for correlations between immunohistochemical parameters and DCE indices, Spearman's correlation coefficient was used. Seventy biopsy samples from 34 subjects were included in the analysis. Mean immunoreactivity scores of HIF-1α were 2.75 ± 1.11 for grade II (n = 24), 6.20 ± 2.33 for grade III (n = 20), and 10.46 ± 2.42 for grade IV (n = 26). HIF-1α showed very good-to-excellent accuracy in discriminating grade II from III, III from IV, and II from IV (area under the curve = 0.838, 0.862, and 0.994, respectively). Endothelial transfer constant and fractional extravascular extracellular space volume showed a significantly positive correlation with HIF-1α expression (r = 0.686, P < .001; r = 0.549, P < .001, respectively). Our study demonstrated HIF-1α to be a significant predictor of different grades of gliomas with high sensitivity and specificity. DCE-MRI is a useful, noninvasive imaging tool for quantitative evaluation of HIF-1α, and its parameters may be used as a surrogate for HIF-1α expression.

Can dynamic contrast-enhanced MRI evaluate VEGF expression in brain glioma? An MRI-guided stereotactic biopsy study

PurposeTo investigate whether pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to evaluate vascular endothelial growth factor (VEGF) expression in brain glioma based on a point-to-point basis. Materials and methodsForty-seven patients with treatment-naïve glioma received preoperative DCE-MRI before stereotactic biopsy. We histologically quantified VEGF from section of stereotactic biopsies, and co-registered biopsy locations with localized measurements of DCE-MRI parameters including volume transfer coefficient (Ktrans), reverse reflux rate constant (Kep), extracellular extravascular volume fraction (Ve) and blood plasma volume (Vp). The correlations between DCE-MRI parameters (Ktrans, Kep, Ve and Vp) and VEGF were determined using Spearman correlation coefficient. P≤.05 was considered statistically significant. ResultsSeventy-nine biopsy samples were obtained and graded into 45 high-grade gliomas (HGGs) and 34 low-grade gliomas (LGGs). Ktrans showed a significant positive correlation with VEGF expression in HGGs group (ρ=0.505, P<0.001) and in combined group (LGGs+HGGs) (ρ=0.549, P<0.001), but not in LGGs group (P>0.05). Kep, Ve or Vp was not correlated with VEGF even though a positive trend showed (P>0.05). ConclusionsDCE-MRI is a useful, non-invasive imaging technique for quantitative evaluation of VEGF, and its parameter Ktrans other than Kep, Ve or Vp may be used as a surrogate for VEGF expression in brain gliomas.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Permeability Parameters Monitor the Early Response to Bevacizumab Plus Chemotherapy in Colorectal Cancer Patients with Liver Metastases

Objective To investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) permeability parameters in monitoring the early response to bevacizumab plus chemotherapy in colorectal cancer patients with liver metastases. Methods Magnetic resonance examinations including plain and DCE-MRI were performed in 28 colorectal cancer patients with liver metastases. The permeability parameters including the volume transfer constant (Ktrans),extravascular extracellular volume fraction (Ve),reverse volume transfer constant (Kep),and percentage of plasma volume (Vp) were measured before chemotherapy and at the first chemotherapy cycle. All the target lesions were grouped into the hypersensitivity and hyposensitivity groups,and t test was used to calculate the statistical significance between these two groups. The receiver operating characteristic (ROC) curve analysis was also performed for evaluating the diagnostic efficacy in monitoring the early response to chemotherapy. Results Totally 64 target lesions,including 29 lesions in the hypersensitivity group and 35 lesions in the hyposensitivity group,were confirmed. The Ktrans0 and Kep0 values of the hypersensitivity group were significantly higher than those of the hyposensitivity group before chemotherapy (P=0.040,P=0.049),whereas the Ve0and Vp0 values showed no significant change between these two groups (P>0.05). When the Ktrans0 value was 1.129 min-1,the area under curve was 0.726,the sensitivity was 65.5%,and the specificity was 71.4%. Conclusion The DCE-MRI permeability parameters is useful for monitoring the early response to chemotherapy,and the Ktrans value can be a quantitative indicator to predict early response.

Relationship between functional imaging and immunohistochemical markers and prediction of breast cancer subtype: a PET/MRI study.

The aim of this study was to determine if functional parameters extracted from the hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) correlate with the immunohistochemical markers of breast cancer (BC) lesions, to assess their ability to predict BC subtype. This prospective study was approved by the institution's Ethics Committee, and all patients provided written informed consent. A total of 50BC patients at diagnosis underwent PET/MRI before pharmacological and surgical treatment. For each primary lesion, the following data were extracted: morphological data including tumour-node-metastasis stage and lesion size; apparent diffusion coefficient (ADC); perfusion data including forward volume transfer constant (Ktrans), reverse efflux volume transfer constant (Kep) and extravascular extracellular space volume (Ve); and metabolic data including standardized uptake value (SUV), lean body mass (SUL), metabolic tumour volume and total lesion glycolysis. Immunohistochemical reports were used to determine receptor status (oestrogen, progesterone, and human epidermal growth factor receptor 2), cellular differentiation status (grade), and proliferation index (Ki67) of the tumour lesions. Correlation studies (Mann-Whitney U test and Spearman's test), receiver operating characteristic (ROC) curve analysis, and multivariate analysis were performed. Association studies were performed to assess the correlations between imaging and histological prognostic markers of BC. Imaging biomarkers, which significantly correlated with biological markers, were selected to perform ROC curve analysis to determine their ability to discriminate among BC subtypes. SUVmax, SUVmean and SUL were able to discriminate between luminal A and luminal B subtypes (AUCSUVmean = 0.799; AUCSUVmax = 0.833; AUCSUL = 0.813) and between luminal A and nonluminal subtypes (AUCSUVmean = 0.926; AUCSUVmax = 0.917; AUCSUL = 0.945), and the lowest SUV and SUL values were associated with the luminal A subtype. Kepmax was able to discriminate between luminal A and luminal B subtypes (AUC = 0.779), and its highest values were associated with the luminal B subtype. Ktransmax (AUC = 0.881) was able to discriminate between luminal A and nonluminal subtypes, and the highest perfusion values were associated with the nonluminal subtype. In addition, ADC (AUC = 0.877) was able to discriminate between luminal B and nonluminal subtypes, and the lowest ADCmean values were associated with the luminal B subtype. Multivariate analysis was performed to develop a prognostic model, and the best predictive model included Ktransmax and SUVmax parameters. Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktransmax and SUVmax was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%).

Grading of pancreatic neuroendocrine neoplasms using pharmacokinetic parameters derived from dynamic contrast-enhanced MRI.

The present study aimed to evaluate the diagnostic efficacy of pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in prospective evaluation of pancreatic neuroendocrine neoplasms (pNENs) grading. A total of 25 histologically proven patients with pNENs (30 lesions in total) who underwent DCE-MRI were enrolled. Lesions were divided into G1, G2 neuroendocrine tumor (NET) and G3 NET/neuroendocrine carcinoma (NEC) groups based on their histological findings according to 2017 World Health Organization Neuroendocrine Tumor Classification Guideline. In addition, the same numbers of tumor-free regions were selected using as normal control group. For each group, pharmacokinetic DCE parameters: volume transfer constant (Ktrans); contrast transfer rate constant (kep); extravascular extracellular space volume fraction (ve); and plasma volume fraction (vp) were calculated with Extended Tofts Linear model. Receiver operator characteristics analysis was conducted to assess the diagnostic efficacy of these parameters in pNENs grading. There were significant differences of Ktrans, kep, ve and vp between tumor-free areas and G1, G2 NET (P<0.001). The Ktrans and kep of G1 NET were significantly lower compared with those of G2 ones (P<0.005). The area under the curve of Ktrans and kep in differentiating G2 from G1 NET were 0.767 and 0.846, respectively. When Ktrans was >0.667 and kep >1.644, the sensitivity of diagnosing G2 NET was the lowest (53.85%), but the specificity was the highest (93.75%). When Ktrans was >0.667 or kep >1.644, the sensitivity of diagnosing G2 NET was 92.31%, but the specificity was 75.00%. Pharmacokinetic parameters of DCE-MRI, particularly the quantitative values of Ktrans and kep, are helpful for differentiating G2 NET from G1 ones.

Comparing the Performances of Magnetic Resonance Imaging Size vs Pharmacokinetic Parameters to Predict Response to Neoadjuvant Chemotherapy and Survival in Patients With Breast Cancer

To compare the value of dynamic contrast-enhanced magnetic resonance imaging-pharmacokinetic (PK) parameters vs tumor volume in predicting breast cancer neoadjuvant chemotherapy response (NACR) and patient survival. Sixty-six patients with locally advanced breast cancer who underwent breast MRI monitoring of NACR were retrospectively analyzed. We compared baseline transfer constant (Ktrans), reflux rate contrast (kep), and extracellular extravascular volume fraction (ve) with the same parameters obtained at early postchemotherapy MRI, and examined model-independent changes in time-intensity curves (maximum slope, contrast enhancement ratio, and IAUC90). Tumor size changes (tumor volume, single dimension, and Response Evaluation Criteria in Solid Tumors [RECIST]) were also analyzed. The Spearman correlation test was used to assess the association between size and PK parameters, and regression analysis to assess the association with 5-year disease-free survival. Higher ve values at baseline were associated with greater decreases in tumor size (P = 0.008). Changes in Ktrans and IAUC90 were the strongest predictors of NACR. Changes in IAUC90 (P = 0.04) and RECIST (P = 0.003) were independently associated with pathologic response. The only parameter significantly associated with 5-year survival was change in RECIST (P = 0.001). However, there was a trend toward statistical significance for changes in ve and Ktrans, with greater changes associated with longer survival. Changes in PK and dynamic contrast-enhanced magnetic resonance imaging kinetic parameters may have a role in predicting NACR in breast tumors. Although changes in Ktrans and IAUC90 are helpful in predicting NACR, they do not show significant association with survival. Early RECIST size change measured by MRI remains the strongest predictor of overall patient survival.

Quantitative analysis of dynamic contrast-enhanced MRI in conjunction with diffusion weighted imaging for differentiating benign and malignant orbital lymphoproliferative disorder

Objective To evaluate the value of quantitative analysis of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) for differentiating malignant from benign orbital lymphoproliferative disorder (OLPD). Methods Forty-three patients with OLPDs (20 patients with benign OLPDs and 23 patients with orbital lymphoma) confirmed by histopathology or clinical follow-up were enrolled in this retrospective study. Quantitative parameters of DCE-MRI including volume transfer constant (Ktrans), flux rate constant (Kep), and extravascular extracellular volume fraction (Ve) and mean apparent diffusion coefficient (ADC) values were obtained. χ2 test and t test were used to compare the differences of qualitative and quantitative parameters between two groups. Receiver operating characteristic (ROC) curve analyses were used to evaluate the diagnostic ability of each parameter and its combination. Results Malignant group showed significantly lower mean ADC values and higher Kep values than benign group [ADC: (0.674±0.126) ×10-3 mm2/s vs (1.030±0.304) ×10-3 mm2/s, P<0.001;Kep: (1.299±0.566)/min vs (0.787±0.311)/min, P= 0.001], while no significant differences was found on Ktrans (P= 0.637) and Ve (P= 0.023). ROC analyses results indicated that, a sensitivity of 95.7%, specificity of 80.0% and area under curve (AUC) of 0.896 could be obtained, when using ADC= 0.809 ×10-3 mm2/s as the cut-off value. Setting the Kep value of0.863/min as the cut-off value, a sensitivity of 91.3%, specificity of 75.0% and AUC of 0.848 could be obtained. When combination of mean ADC and Kep was used, optimal diagnostic performance could be obtained (AUC, 0.926;sensitivity, 91.3%;specificity, 90.0%). Conclusion Mean ADC values and Kep are significant variables in predicting malignant OLPDs. Combination of DWI and DCE-MRI can further improve the diagnostic capability in differentiating malignant from benign OLPDs. Key words: Orbit; Lymphoma; Lymphoproliferative disorders; Diffusion magnetic resonance imaging; Dynamic contrast-enhanced

Multiparametric Analysis of Permeability and ADC Histogram Metrics for Classification of Pediatric Brain Tumors by Tumor Grade

Accurate tumor grading is essential for treatment planning of pediatric brain tumors. We hypothesized that multiparametric analyses of a combination of permeability metrics and ADC histogram metrics would differentiate high- and low-grade tumors with high accuracy. DTI and dynamic contrast-enhanced MR imaging using T1-mapping with flip angles of 2°, 5°, 10°, and 15°, followed by a 0.1-mmol/kg body weight gadolinium-based bolus was performed on all patients in addition to standard MR imaging. Permeability data were processed and transfer constant from the blood plasma into the extracellular extravascular space, rate constant from the extracellular extravascular space back into blood plasma, extravascular extracellular volume fraction, and fractional blood plasma volume were calculated from 3D tumor volumes. Apparent diffusion coefficient histogram metrics were calculated for 3 separate tumor volumes derived from T2-FLAIR sequences, T1 contrast-enhanced sequences, and permeability maps, respectively. Results from 41 patients (0.3-16.76 years of age; mean, 6.22 years) with newly diagnosed contrast-enhancing brain tumors (16 low-grade; 25 high-grade) were included in the institutional review board-approved retrospective analysis. Wilcoxon tests showed a higher transfer constant from blood plasma into extracellular extravascular space and rate constant from extracellular extravascular space back into blood plasma, and lower extracellular extravascular volume fraction (P < .001) in high-grade tumors. The mean ADCs of FLAIR and enhancing tumor volumes were significantly lower in high-grade tumors (P < .001). ROC analysis showed that a combination of extravascular volume fraction and mean ADC of FLAIR volume differentiated high- and low-grade tumors with high accuracy (area under receiver operating characteristic curve = 0.918). ADC histogram metrics combined with permeability metrics differentiate low- and high-grade pediatric brain tumors with high accuracy.

Diffusion Weighted and Dynamic Contrast-Enhanced MRI as a Predictor of Treatment Response in Head and Neck Cancer to Chemoradiotherapy: The Role of Early Intratreatment Scanning

Background: In locoregionally advanced Head and Neck Squamous Cell Carcinoma (HNSCC), intra-treatment scanning early during the course of Concomitant Chemoradiotherapy (CRT) with advanced functional Magnetic Resonance Imaging (MRI) could potentially allow for modification of treatment to maximize the chance of favourable outcome. The aim of this prospective study was to assess the predictive value of parameters derived from Dynamic Contrast-Enhanced (DCE) and Diffusion Weighted (DW) MRI for treatment response early during the course of CRT in patients with HNSCC.Methods: MRI scans were performed in 20 patients with locoregionally advanced HNSCC at baseline, after 10 Grays (Gy) and 40 Gy of CRT. DW and DCE derived parameters as well as the volumes were measured from primary tumours and lymph nodes. Tumour kinetic parameters (volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve) and plasma volume fraction (Vp)) were assessed using the extended Tofts model. Relative changes in studied parameters from baseline to 10 Gy and 40 Gy were calculated. Factors predictive for treatment response were identified by the Firth logistic regression. Spearman’s rank correlation coefficient was used to investigate correlations among the parameters.Results: Responders showed a significant decrease in Ktrans after 10 Gy (median, -50.2 %; range, -25.1 to -90.9 %; P = 0.047). In addition, decreased ve after 10 Gy (median, -26.9%; range -76.7 to -126.8%) and increased apparent diffusion coefficient (ADC) after 40 Gy (median, 73.4%; range, 17.8 - 121.6%) were borderline significant (P=0.066 and P=0.079, respectively). Positive correlation between Ktrans and ve after 10 Gy (r = 0.823, P <0.05) was noticed.Conclusion: In HNSCC, early changes in DCE- and DWI-MRI derived parameters appear to predict tumour response before the actual morphologic changes occur.

Assessment of the zonal variation of perfusion parameters in the femoral head: a 3-T dynamic contrast-enhanced MRI pilot study.

The objective was to describe MR perfusion characteristics of the femoral head, with a focus on the subchondral bone. This prospective monocentric study was approved by our local Ethics Committee. Written informed consent was obtained from all subjects. Dynamic contrast-enhanced MRI of the right hip was performed in 59 adults with suspected spondyloarthritis (32 women, 28 men). Mean age was 37.5 (±12.5) years. Regions of interest were drawn in the femoral head epiphysis, in the subchondral areas the most exposed to mechanical load (superolateral, anterosuperior, and posterior zones) and in areas less exposed to mechanical load (inferior subchondral zone and center of the femoral head). Semi-quantitative and pharmacokinetic parameters were calculated using the Tofts model. Statistical analysis was performed with a linear mixed model to compare the perfusion parameters in the different femoral head zones. Extravascular extracellular volume and area under the curve were lower in the superolateral zone than in the inferior zone (p=0.0135 and p<0.0001 respectively) and the central zone (p=0.007 and p=0.0134 respectively). Extravascular extracellular volume and rate constant were lower in the anterosuperior zone than in the inferior zones (p=0.011 and p=0.029). In the anterosuperior zone, extravascular extracellular volume was lower, and time to peak was higher than in the central zones (p=0.0056 and p=0.0013 respectively). No significant differences were found for any values between other paired zones. The perfusion of femoral head subchondral bone assessed with dynamic contrast-enhanced magnetic resonance imaging is not homogeneous: the areas exposed to more mechanical loading are less perfused.

The effects of intravoxel contrast agent diffusion on the analysis of DCE-MRI data in realistic tissue domains.

Quantitative evaluation of dynamic contrast enhanced MRI (DCE-MRI) allows for estimating perfusion, vessel permeability, and tissue volume fractions by fitting signal intensity curves to pharmacokinetic models. These compart mental models assume rapid equilibration of contrast agent within each voxel. However, there is increasing evidence that this assumption is violated for small molecular weight gadolinium chelates. To evaluate the error introduced by this invalid assumption, we simulated DCE-MRI experiments with volume fractions computed from entire histological tumor cross-sections obtained from murine studies. A 2D finite element model of a diffusion-compensated Tofts-Kety model was developed to simulate dynamic T1 signal intensity data. Digitized histology slices were segmented into vascular (vp ), cellular and extravascular extracellular (ve ) volume fractions. Within this domain, Ktrans (the volume transfer constant) was assigned values from 0 to 0.5 min-1 . A representative signal enhancement curve was then calculated for each imaging voxel and the resulting simulated DCE-MRI data analyzed by the extended Tofts-Kety model. Results indicated parameterization errors of -19.1% ± 10.6% in Ktrans , -4.92% ± 3.86% in ve , and 79.5% ± 16.8% in vp for use of Gd-DTPA over 4 tumor domains. These results indicate a need for revising the standard model of DCE-MRI to incorporate a correction for slow diffusion of contrast agent. Magn Reson Med 80:330-340, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

T2*-Correction in Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Glioblastoma From a Half Dose of High-Relaxivity Contrast Agent.

The aim of this study was to evaluate the arterial input function (AIF) and tissue enhancement time curve (tissue function [TF]) obtained after the administration of a half-dose gadobenate dimeglumine (0.05-mmol/kg body weight [bw]) compared with a full dose (0.1-mmol/kg bw) of a standard-relaxivity contrast agent. We enrolled 40 adult patients with glioblastoma in an interindividual comparative study. Patients were randomized to 1 of the 2 study arms: 20 patients received 0.1-mmol/kg bw of gadoterate; the other 20 patients received 0.05-mmol/kg bw of gadobenate. The patients underwent dynamic contrast-enhanced magnetic resonance imaging examinations. Arterial input function, tissue enhancement time curve (TF), tumor transfer rate (K), and tumor extracellular-extravascular volume fraction (Ve) were calculated for each patients. Averaged AIF, TF, K, and Ve of both groups were compared. A significant difference (P = 0.001) between the peak AIF values obtained with the 2 different gadolinium-based contrast agents was observed. No difference was found between TFs (P = 0.35). Comparison on kinetic parameters revealed a significant difference for K (P = 0.047) but no difference for Ve (P = 0.74). The administration of half dose of the high-relaxivity contrast agent gadobenate is effective in improving AIF by reducing T2*-shortening effects on dynamic contrast-enhanced magnetic resonance imaging and ensuring at the same time an adequate signal enhancement in tumor tissue. The use of 0.05-mmol/kg bw of gadobenate not only is feasible but also can lead to a better estimation of K based on a more accurate AIF assessment.

Correlation of quantitative parameters of magnetic resonance perfusion-weighted imaging with vascular endothelial growth factor, microvessel density and hypoxia-inducible factor-1α in nasopharyngeal carcinoma: Evaluation on radiosensitivity study.

To investigate the correlation of parameters of magnetic resonance perfusion-weighted imaging (MR-PWI) with the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and microvessel density (MVD) in nasopharyngeal carcinoma (NPC) so as to explore the value of predicting radiosensitivity. A prospective study. Department of Head-and-neck radiotherapy in Hunan Cancer Hospital. Ninety-four patients of NPC were included between December 2013 and December 2014. The expression of VEGF, MVD and HIF-1α was studied by immunohistochemistry, and magnetic resonance perfusion-weighted imaging (MR-PWI) was performed before and after undergoing radiotherapy (20Gy dose). Parameters of MR-PWI, volume of primary tumour and rate of tumour remission were measured and calculated. Patients with primary local tumour were then divided into completely response group (CR group) and partially response group (non-CR group) according to tumour regression condition. Relevant parameters were analysed by Spearman, and diagnostic efficiency of radiosensitivity was analysed by receiver operating characteristic curve (ROC). The expression of VEGF was positively correlated with MVD (r=.322,P<.05), but the expression of HIF-1α was no significant correlations with VEGF and MVD. The expression VEGF was in positive correlation with fractional plasma volume (fpv) (r=.339, P=.05) before radiotherapy. There was a significant difference in the quantitative parameters of MR-PWI between CR group and non-CR group during the course of radiotherapy and at the end of radiotherapy treatment. The change of blood reflux constant (Δkep20) and extravascular extracellular space volume fraction (ΔVe20) before and after treatment was positively correlated with primary local tumour remission condition after 3month treatment; Δkep and ΔVe were negatively correlated with primary local tumour remission condition after 3months. Tumour regression rate was only positively correlated with Ve and the average volume of primary tumour after 2week treatment (V1). ROC curve showed that R20≥65.69%, and was considered as a threshold to predict primary local tumour remission, with a sensitivity of 0.84 and specificity of 0.69, and area under the curve was 0.819 (P=.000). The parameters of MR-PWI with the expression of VEGF, HIF-1α and MVD could be guidance for predicting radiosensitivity in NPC.

Effects of sampling frequency on the accuracy of phenomenological and pharmacokinetic parameters derived from dynamic contrast enhanced MRI data

The sampling frequencies (fs) at which dynamic contrast enhanced (DCE) MRI data are acquired is known to affects the accuracy of derived parameters. Phenomenological parameters empirically characterise the shape and structure of the signal-time curves, whereas pharmacokinetic approaches estimate physiologically relevant parameters from the concentration-time curves, such as the volume-transfer constant (Ktrans) and the extravascular-extracellular fractional volume (ve). Both of these approaches have shown promise in the detection of prostate cancer, however to date a method has been lacking to quantitatively compare MR-measured to known ‘ground truth’ parameter values. In the present work, a newly developed anthropomorphic DCE-MRI prostate phantom was utilised to this end. Precisely known ‘healthy’ and ‘tumorous’ curves were measured using a 3T scanner (Philips, Netherlands) and 32-channel detector coil (3D-SPGR, TR/TE = 4.3/1.4 ms, α = 10°, FOV = 224 × 224 × 80 mm3, voxels = 1 × 1 × 4 mm3) at fs = 0.5, 0.26, 0.19, 0.12, 0.061, and 0.041 Hz. Phenomenological analysis revealed that wash-in was measured with the lowest errors ( 15%) at fs ⩾ 0.12 Hz, whereas wash-out gave comparatively higher errors (up to 27%) across this same range of fs. Lowest errors in time-to-peak ( 11%) were measured using fs = 2 s and 8.1 s. Pharmacokinetic analysis using the Tofts model gave errors in Ktrans and ve values 14% and 10%, for acquisitions with fs ⩾ 0.12 Hz and fs ⩾ 0.061 respectively, with errors increasing dramatically (up to 172%) with fs 0.061 Hz. Quantitative phantom-based approaches, such as the one used herein, offers the prospect of a standardisation in the way DCE-MRI is performed in the prostate, and possibly a wider acceptance of the technique for routine clinical use. Acknowledgement This work is funded by Irish Cancer Society Research Scholarship CRS13KNI (supported by Movember).

The value of DCE-MRI in assessing histopathological and molecular biological features in induced rat epithelial ovarian carcinomas

BackgroundTo investigate dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for assessing histopathological and molecular biological features in induced rat epithelial ovarian carcinomas (EOCs).Methods7,12-dimethylbenz[A]anthracene (DMBA) was applied to induce EOCs in situ in 46 SD rats. Conventional MRI and DCE-MRI were performed to evaluate the morphology and perfusion features of the tumors, including the time-signal intensity curve (TIC), volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume ratio (Ve) and initial area under the curve (IAUC). DCE-MRI parameters were correlated with histological grade, microvascular density (MVD), vascular endothelial growth factor (VEGF) and fraction of Ki67-positive cells and the serum level of cancer antigen 125 (CA125).ResultsThirty-five of the 46 rats developed EOCs. DCE-MRI showed type III TIC more frequently than type II (29/35 vs. 6/35, p < 0.001) in EOCs. The two types of TIC of tumors had significant differences in the histological grade, MVD, expression of VEGF and Ki67, and the serum level of CA125 (all p < 0.01). Ktrans, Kep and IAUC values showed significant differences in different histological grades in overall and pairwise comparisons except for IAUC in grade 2 vs. grade 3 (all p < 0.01). There was no significant difference in Ve values among the three grade groups (p > 0.05). Ktrans, Kep and IAUC values were positively correlated with MVD, VEGF and Ki67 expression (all p < 0.01). Ve was not significantly correlated with MVD, VEGF expression, Ki67 expression and the CA125 level (all p > 0.05).ConclusionsTIC types and perfusion parameters of DCE-MRI can reflect tumor grade, angiogenesis and cell proliferation to some extent, thereby helping treatment planning and predicting prognosis.

Early Posttreatment Assessment of MRI Perfusion Biomarkers Can Predict Long-Term Response of NSCLC Brain Metastases to SRS: A Longitudinal Analysis

Optimizing patient selection and identification of patients who may not respond to brain metastasis treatment is critical in personalizing therapy. MRI-based imaging biomarkers using perfusion MRI (pMRI) may satisfy this crucial unmet need. The aim of this study is to identify early post-treatment perfusion MRI changes and correlate to long-term outcomes after treatment of lung cancer brain metastases (BM) with stereotactic radiosurgery (SRS). Pre-treatment and post-treatment pMRI within 8 weeks was obtained in patients treated with SRS for an intact non-small cell lung cancer (NSCLC) brain metastasis. Time-dependent leakage (Ktrans), blood plasma volume (Vp), and extravascular extracellular volume (Ve) were calculated on regions of interest delineated on pMRI. Patients were followed longitudinally with serial MRI until death, progression, or intervention (whole brain radiation or surgery). Genotyping was performed on a biopsy of each patient’s primary or metastatic lesion with the Sequenom MassARRAY system. We hypothesize that early post SRS quantitative analysis of perfusion imaging can predict whether or not lung cancer BMs will ultimately respond or fail treatment Fifty-three lesions were included from 41 total patients. All lesions were treated with SRS with median dose 21 Gy (range = 18-22 Gy). Median follow-up after treatment was 11 months. Actuarial local control at 1 year was 85%. Univariate analysis showed that there is a significant difference in post-RT Ktrans standard deviation (STD) between patients with progressive disease (PD) (mean = 0.0317) and without progressive disease (mean = 0.0219) (P = 0.032). We additionally determined a cutoff value for predicting PD and non-PD using Ktrans STD. ROC curve analysis resulted in the area under the curve (AUC) = 0.73, sensitivity = 89%, and specificity = 67%, with a cutoff value 0.017. Pre-treatment Ve was significantly lower in KRAS mutants vs nonmutants (P = 0.0428). Using a median value of 0.1334 as a cutoff, Ve was able to significantly predict KRAS mutant status compared to the Sequenom reference standard (AUC = 0.71, sensitivity = 81.8%, specificity = 61.9%). Post-RT Ktrans STD may be used as an early post treatment (within 8 weeks) imaging biomarker to help predict long-term response of lung BMs to SRS. This can help identify patients who will ultimately fail SRS in a timelier manner and allow for early adjustment in treatment approach. We determine that Ve from pMRI can identify KRAS mutation status with >80% sensitivity. This study demonstrates promising evidence of the utility of early assessment of post-treatment imaging biomarkers. These data are to be validated in another cohort of patients and also in other histologies.

DCE- and DW-MRI as early imaging biomarkers of treatment response in a preclinical model of triple negative breast cancer.

This work evaluates quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI) parameters as early biomarkers of response in a preclinical model of triple negative breast cancer (TNBC). The standard Tofts' model of DCE-MRI returns estimates of the volume transfer constant (Ktrans ) and the extravascular extracellular volume fraction (ve ). DW-MRI returns estimates of the apparent diffusion coefficient (ADC). Mice (n=38) were injected subcutaneously with MDA-MB-231. Tumors were grown to approximately 275mm3 and sorted into the following groups: saline controls, low-dose Abraxane (15mg/kg) and high-dose Abraxane (25mg/kg). Animals were imaged at days zero, one and three. On day three, tumors were extracted for immunohistochemistry. The positive percentage change in ADC on day one was significantly higher in both treatment groups relative to the control group (p<0.05). In addition, the positive percentage change in Ktrans was significantly higher than controls (p<0.05) on day one for the high-dose group and on days one and three for the low-dose group. The percentage change in tumor volume was significantly different between the high-dose and control groups on day three (p=0.006). Histology confirmed differences at day three through reduced numbers of proliferating cells (Ki67 staining) in the high-dose group (p=0.03) and low-dose group (p=0.052) compared with the control group. Co-immunofluorescent staining of vascular maturity [using von Willebrand Factor (vWF) and α-smooth muscle actin (α-SMA)] indicated significantly higher vascular maturation in the low-dose group compared with the controls on day three (p=0.03), and trending towards significance in the high-dose group compared with controls on day three (p=0.052). These results from quantitative imaging with histological validation indicate that ADC and Ktrans have the potential to serve as early biomarkers of treatment response in murine studies of TNBC.

Dynamic contrast-enhanced and diffusion-weighted MR imaging in the characterisation of small, non-palpable solid testicular tumours.

To explore the role of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), using semiquantitative and quantitative parameters, and diffusion-weighted (DW) MRI in differentiating benign from malignant small, non-palpable solid testicular tumours. We calculated the following DCE-MRI parameters of 47 small, non-palpable solid testicular tumours: peak enhancement (PE), time to peak (TTP), percentage of peak enhancement (Epeak), wash-in-rate (WIR), signal enhancement ratio (SER), volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space volume fraction (Ve) and initial area under the curve (iAUC). DWI signal intensity and apparent diffusion coefficient (ADC) values were evaluated. Epeak, WIR, Ktrans , Kep and iAUC were higher and TTP shorter in benign compared to malignant lesions (p < 0.05). All tumours had similar ADC values (p > 0.07). Subgroup analysis limited to the most frequent histologies - Leydig cell tumours (LCTs) and seminomas - replicated the findings of the entire set. Best diagnostic cutoff value for identification of seminomas: Ktrans ≤0.135 min-1, Kep ≤0.45 min-1, iAUC ≤10.96, WIR ≤1.11, Epeak ≤96.72, TTP >99 s. DCE-MRI parameters are valuable in differentiating between benign and malignant small, non-palpable testicular tumours, especially when characterising LCTs and seminomas. • DCE-MRI may be used to differentiate benign from malignant non-palpable testicular tumours. • Seminomas show lower Ktrans, Kep and iAUC values. • ADC values are not valuable in differentiating seminomas from LCTs. • Semiquantitative DCE-MRI may be used to characterise small, solid testicular tumours.