Extension of the intravoxel incoherent motion model to non-gaussian diffusion in head and neck cancer

PURPOSE: To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases. MATERIALS AND METHODS: The non-Gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from 8 patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model. RESULTS: For the 8 neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3% - 79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value. CONCLUSION: The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases

Noninvasive assessment of tumor microenvironment using dynamic contrast-enhanced magnetic resonance imaging and 18F-fluoromisonidazole positron emission tomography imaging in neck nodal metastases

PURPOSE: To assess noninvasively the tumor microenvironment of neck nodal metastases in patients with head-and-neck cancer by investigating the relationship between tumor perfusion measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and hypoxia measured by (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET). METHODS AND MATERIALS: Thirteen newly diagnosed head-and-neck cancer patients with metastatic neck nodes underwent DCE-MRI and (18)F-FMISO PET imaging before chemotherapy and radiotherapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from (18)F-FMISO PET, the nonparametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with (18)F-FMISO uptake and nodes with no (18)F-FMISO uptake using Mann-Whitney U tests. RESULTS: For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the (18)F-FMISO SUV (rho = 0.74, p < 0.001). There was a strong negative correlation between the median k(ep) (redistribution rate constant) value (rho = -0.58, p = 0.042) and the (18)F-FMISO SUV. Hypoxic nodes (moderate to severe (18)F-FMISO uptake) had significantly lower median K(trans) (volume transfer constant) (p = 0.049) and median k(ep) (p = 0.027) values than did nonhypoxic nodes (no (18)F-FMISO uptake). CONCLUSION: This initial evaluation of the preliminary results support the hypothesis that in metastatic neck lymph nodes, hypoxic nodes are poorly perfused (i.e., have significantly lower K(trans) and k(ep) values) compared with nonhypoxic nodes

TUMOR METABOLISM AND PERFUSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA: PRETREATMENT MULTIMODALITY IMAGING WITH H-1 MAGNETIC RESONANCE SPECTROSCOPY, DYNAMIC CONTRAST-ENHANCED MRI, AND [F-18]FDG-PET

PURPOSE: To correlate proton magnetic resonance spectroscopy ((1)H-MRS), dynamic contrast-enhanced MRI (DCE-MRI) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in nodal metastases of patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging (MMI) was evaluated for its efficacy in predicting short-term response to treatment. METHODS AND MATERIALS: Metastatic neck nodes were imaged with (1)H-MRS, DCE-MRI and (18)F-FDG PET in 16 patients with newly diagnosed HNSCC before treatment. Short-term radiological response was evaluated at 3–4 months. The correlations between (1)H-MRS (choline concentration, Cho/W), DCE-MRI (volume transfer constant, K(trans); volume fraction of the extravascular extracellular space, v(e); and redistribution rate constant, k(ep)) and (18)F-FDG PET (standard uptake value, SUV; and total lesion glycolysis, TLG) were calculated using non-parametric Spearman rank correlation. To predict the short-term response, logistic regression analysis was performed. RESULTS: A significant positive correlation was found between Cho/W and TLG (ρ = 0.599, p = 0.031). Cho/W correlated negatively with heterogeneity measures std(v(e)) (ρ = −0.691, p = 0.004) and std(k(ep)) (ρ = −0.704, p = 0.003). SUVmax values correlated strongly with MRI tumor volume (ρ = 0.643, p = 0.007). Logistic regression indicated that std(K(trans)) and SUVmean were significant predictors of short-term response (p < 0.07). CONCLUSION: Pretreatment multi-modality imaging using (1)H-MRS, DCE-MRI and (18)F-FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and (18)F-FDG PET parameters were predictive of short-term response to treatment

Comparing Primary Tumors and Metastatic Nodes in Head and Neck Cancer Using Intravoxel Incoherent Motion Imaging: A Preliminary Experience

OBJECTIVE: To use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and evaluating IVIM efficacy in predicting outcome. METHODS: Sixteen patients with HN cancer underwent IVIM DWI on a 1.5T MRI scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: In comparison to metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (p<0.0009), and lower diffusion coefficient (D) (p<0.0002). Patients with lower standard deviation for D had prolonged PFS and OS (p<0.05). CONCLUSION: Pretreatment IVIM measures were feasible in investigating the physiological differences between the two tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care

Quantitative Non-Gaussian Intravoxel Incoherent Motion Diffusion-Weighted Imaging Metrics and Surgical Pathology for Stratifying Tumor Aggressiveness in Papillary Thyroid Carcinomas

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1–2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and diffusion kurtosis coefficient (K) metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and D values than tumors without tumor-aggressive features (P &lt; .05). The absolute relative change was 46% in K metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1–2 cm) measured by ultrasonography, and the ADC and D were significantly different and able to differentiate between the 2 tumor types (P &lt; .05). ADC and D can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1–2 cm

Correlation of a priori DCE-MRI and H-1-MRS data with molecular markers in neck nodal metastases: Initial analysis

The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the "endogenous marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1?), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not show significant correlation. The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings