Magnetic resonance imaging-based prediction models for tumor stage and cervical lymph node metastasis of tongue squamous cell carcinoma.

Purpose: To evaluate the ability of preoperative MRI-based measurements to predict the pathological T (pT) stage and cervical lymph node metastasis (CLNM) via machine learning (ML)-driven models trained in oral tongue squamous cell carcinoma (OTSCC). Materials and methods: 108 patients with a new diagnosis of OTSCC were enrolled. The preoperative MRI study included post-contrast high-resolution T1-weighted images acquired in all patients. MRI-based depth of invasion (DOI) and tumor dimension-together with shape-based and intensity-based features-were extracted from the lesion volume segmentation. The entire dataset was randomly divided into a training set and a validation set, and the performances of different types of ML algorithms were evaluated and compared. Results: MRI-based DOI and tumor dimension together with several shape-based and intensity-based signatures significantly discriminated the pT stage and LN status. The overall accuracy of the model for predicting the pT stage was 0.86 (95%CI, 0.78-0.92) and 0.81 (0.64-0.91) in the training and validation sets, respectively. There was no improvement in the model performance upon including shape-based and intensity-based features. The model for predicting CLNM based on DOI and tumor dimensions had a fair accuracy of 0.68 (0.57-0.78) and 0.69 (0.51-0.84) in the training and validation sets, respectively. The shape-based and intensity-based signatures have shown potential for improving the model sensitivity, with a comparable accuracy. Conclusion: MRI-based models driven by ML algorithms could stratify patients with OTSCC according to the pT stages. They had a moderate ability to predict cervical lymph node metastasis.

Predictors of Outcome after (Chemo)Radiotherapy for Node-Positive Oropharyngeal Cancer: The Role of Functional MRI.

The prognosis of a subset of patients with locally advanced oropharyngeal cancer (LA-OPC) is still poor despite improvements in patient selection and treatment. Identifying specific patient- and tumor-related factors can help to select those patients who need intensified treatment. We aimed to assess the role of historical risk factors and novel magnetic resonance imaging (MRI) biomarkers in predicting outcomes in these patients. Patients diagnosed with LA-OPC were studied with diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline and at the 10th radiotherapy (RT) fraction. Clinical information was collected as well. The endpoint of the study was the development of disease progression, locally or distantly. Of the 97 patients enrolled, 68 were eligible for analysis. Disease progression was recorded in 21 patients (11 had loco-regional progression, 10 developed distant metastases). We found a correlation between N diameter and disease control (p = 0.02); features such as p16 status and extranodal extension only showed a trend towards statistical significance. Among perfusion MRI features, higher median values of Kep both in primary tumor (T, p = 0.016) and lymph node (N, p = 0.003) and lower median values of ve (p = 0.018 in T, p = 0.004 in N) correlated with better disease control. Kep P90 and N diameter were identified by MRMR algorithm as the best predictors of outcome. In conclusion, the association of non-invasive MRI biomarkers and patients and tumor characteristics may help in predicting disease behavior and patient outcomes in order to ensure a more customized treatment.

Microenvironmental Factors in Oral Cavity Squamous Cell Carcinoma Undergoing Surgery: Correlation with Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced MRI.

BACKGROUND: In this prospective study, we hypothesized that magnetic resonance imaging (MRI) may represent not only the tumor but also the microenvironment, reflecting the heterogeneity and microstructural complexity of neoplasms. We investigated the correlation between both diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced (DCE)-MRI with the pathological factors in oral cavity squamous cell carcinomas (OSCCs). METHODS: A total of 37 patients with newly diagnosed OSCCs underwent an MR examination on a 3T system. The diffusion coefficient (D), the kurtosis parameter (K), the transfer constants Ktrans and Kep and the volume of extravascular extracellular space ve were quantified. A histogram-based approach was proposed to investigate the associations between the imaging and the pathological factors based on the histology and immunochemistry. RESULTS: Significant differences in the DCE-MRI and DKI parameters were found in relation to the inflammatory infiltrate, tumor grading, keratinization and desmoplastic reaction. Relevant relationships emerged between tumor-infiltrating lymphocytes (TILs) and DKI, with lower D and higher K values being associated with increased TILs. CONCLUSION: Although a further investigation is needed, these findings provide a more comprehensive biological characterization of OSCCs and may contribute to a better understanding of DKI-derived parameters, whose biophysical meaning is still not well-defined.

The Role of Patient- and Treatment-Related Factors and Early Functional Imaging in Late Radiation-Induced Xerostomia in Oropharyngeal Cancer Patients.

The advent of quantitative imaging in personalized radiotherapy (RT) has offered the opportunity for a better understanding of individual variations in intrinsic radiosensitivity. We aimed to assess the role of magnetic resonance imaging (MRI) biomarkers, patient-related factors, and treatment-related factors in predicting xerostomia 12 months after RT (XER12) in patients affected by oropharyngeal squamous cell carcinoma (OSCC). Patients with locally advanced OSCC underwent diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI at baseline; DWI was repeated at the 10th fraction of RT. The Radiation Therapy Oncology Group (RTOG) toxicity scale was used to evaluate salivary gland toxicity. Xerostomia-related questionnaires (XQs) were administered weekly during and after RT. RTOG toxicity ≥ grade 2 at XER12 was considered as endpoint to build prediction models. A Decision Tree classification learner was applied to build the prediction models following a five-fold cross-validation. Of the 89 patients enrolled, 63 were eligible for analysis. Thirty-six (57.1%) and 21 (33.3%) patients developed grade 1 and grade 2 XER12, respectively. Including only baseline variables, the model based on DCE-MRI and V65 (%) (volume of both glands receiving doses ≥ 65 Gy) had a fair accuracy (77%, 95% CI: 66.5-85.4%). The model based on V65 (%) and XQ-Intmid (integral of acute XQ scores from the start to the middle of RT) reached the best accuracy (81%, 95% CI: 71-88.7%). In conclusion, non-invasive biomarkers from DCE-MRI, in combination with dosimetric variables and self-assessed acute XQ scores during treatment may help predict grade 2 XER12 with a fair to good accuracy.

Comparison of rigid and deformable coregistration between mpMRI and CT images in radiotherapy of prostate bed cancer recurrence.

PURPOSE: To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. MATERIALS AND METHOD: Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. RESULTS: Deformable registration did not change volumes, (p = 0.92 MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d = (5.6 ± 3.1) mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. CONCLUSIONS: Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

Multiparametric MRI Evaluation of Oropharyngeal Squamous Cell Carcinoma. A Mono-Institutional Study.

The aim of this paper is to define the pre-treatment radiological characteristics of oropharyngeal squamous cell carcinoma (OPSCC) using morphological and non-morphological magnetic resonance imaging (MRI), based on HPV status, in a single-institution cohort. In total, 100 patients affected by OPSCC were prospectively enrolled in the present study. All patients underwent 1.5T MR with standard sequences, including diffusion-weighted imaging with and intravoxel incoherent motion (IVIM-DWI) technique and a dynamic contrast-enhanced (DCE) MRI. For all patients, human papillomavirus (HPV) status was available. No statistically significant differences in the volume of primary tumors (PTs) and lymph nodes (LNs) were observed based on HPV status. When comparing the two patient groups, no significant differences were found for the PT radiologic characteristics (presence of well-defined borders, exophytic growth, ulceration, and necrosis) and LN morphology (solid/cystic/necrotic). Tumor subsite, smoking status, and alcohol intake significantly differed based on HPV status, as well as ADC and Dt values of both PTs and LNs. We detected no significant difference in DCE-MRI parameters by HPV status. Based on a multivariate logistic regression model, the combination of clinical factors, such as tumor subsite and alcohol habits, with the perfusion-free diffusion coefficient Dt of LNs, may help to accurately discriminate OPSCC by HPV status.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

MRI-Based Radiomics to Differentiate between Benign and Malignant Parotid Tumors With External Validation.

BACKGROUND: The differentiation between benign and malignant parotid lesions is crucial to defining the treatment plan, which highly depends on the tumor histology. We aimed to evaluate the role of MRI-based radiomics using both T2-weighted (T2-w) images and Apparent Diffusion Coefficient (ADC) maps in the differentiation of parotid lesions, in order to develop predictive models with an external validation cohort. MATERIALS AND METHODS: A sample of 69 untreated parotid lesions was evaluated retrospectively, including 37 benign (of which 13 were Warthin's tumors) and 32 malignant tumors. The patient population was divided into three groups: benign lesions (24 cases), Warthin's lesions (13 cases), and malignant lesions (32 cases), which were compared in pairs. First- and second-order features were derived for each lesion. Margins and contrast enhancement patterns (CE) were qualitatively assessed. The model with the final feature set was achieved using the support vector machine binary classification algorithm. RESULTS: Models for discriminating between Warthin's and malignant tumors, benign and Warthin's tumors and benign and malignant tumors had an accuracy of 86.7%, 91.9% and 80.4%, respectively. After the feature selection process, four parameters for each model were used, including histogram-based features from ADC and T2-w images, shape-based features and types of margins and/or CE. Comparable accuracies were obtained after validation with the external cohort. CONCLUSIONS: Radiomic analysis of ADC, T2-w images, and qualitative scores evaluating margins and CE allowed us to obtain good to excellent diagnostic accuracies in differentiating parotid lesions, which were confirmed with an external validation cohort.

Stereotactic body radiotherapy for T1 glottic cancer: dosimetric data in 27 consecutive patients.

AIM: Because the clinical feasibility of stereotactic body radiotherapy (SBRT) for early glottic cancer (T1) is controversial, we report dosimetric results in 27 consecutive patients from a prospective phase I and II study that started in 2017. METHODS: In our approach, only the parts of the true vocal cord containing cancer and those immediately adjacent are planned to be treated to 36 Gy and 30 Gy, respectively, in 3 fractions. Several dosimetric metrics for both target volumes and organs at risk were extracted from individual plans and results were compared to those achieved by other authors in a similar setting. RESULTS: Proper coverage was reached at planning in 2/3 of planning treatment volume 30 Gy, but only 4 planning treatment volume 36 Gy; conversely, the maximum dose objective was met for most of the patients on either arytenoid cartilage, but this was not the case for 51.9% and 96.3% of cricoid and thyroid cartilages, respectively. Our dosimetric results are similar to if not better than those achieved by others. CONCLUSION: SBRT in 3 fractions for T1 glottic lesions is dosimetrically challenging. Clinical validation is awaited.

Response on DCE-MRI predicts outcome of salvage radiotherapy for local recurrence after radical prostatectomy.

OBJECTIVE: To assess the predictive role of response on dynamic contrast enhancement on magnetic resonance imaging (DCE-MRI) of visible local lesions in the setting of salvage radiotherapy (sRT) after radical prostatectomy. METHODS: All patients referred for sRT for biochemical failure after radical prostatectomy from February 2014 to September 2016 were considered eligible if they had been restaged with DCE-MRI and had been found to have a visible lesion in the prostatic bed, but no distant/nodal disease on choline positron emission tomography (PET)-computed tomography (CT). Eligible patients were contacted during follow-up and offered reimaging with serial DCE-MRI until lesion resolution. Complete response (CR) was defined as the disappearance of the target lesion on DCE-MRI; prostate-specific antigen (PSA) recurrence was defined as a 0.2 ng/mL PSA rise above the nadir. Median follow-up after sRT was 41.5 months (range, 12.1-61.2 months). RESULTS: Fifty-nine patients agreed to undergo repeated DCE-MRI for a total of 64 studied lesions. Overall, 57 lesions (89.1%) showed a CR after 1 (51 patients) or 2 (6 patients) scans, while 7 lesions did not show any change (no response [NR]). At 42 months, no evidence of biochemical disease (bNED) survival was 74.7±6.4% and 64.3±21.0% for patients with CR and NR lesions, respectively (hazard ratio [HR], 3.181; 95% confidence interval [CI], 0.157-64.364; p = 0.451). When only patients treated with sRT without androgen deprivation were selected (n = 41), bNED survival rates at 42 months were 72.1±8.0% and 0, respectively (HR, 52.830; 95% CI, 1.893-1474.110; p = 0.020). CONCLUSIONS: Patients whose lesions disappear during follow-up have a better outcome than those with unchanged lesions after sRT alone.

Diffusion kurtosis imaging in head and neck cancer: A correlation study with dynamic contrast enhanced MRI.

PURPOSE: To investigate the biophysical meaning of Diffusion Kurtosis Imaging (DKI) parameters via correlations with the perfusion parameters obtained from a long Dynamic Contrast Enhanced MRI scan, in head and neck (HN) cancer. METHODS: Twenty two patients with newly diagnosed HN tumor were included in the present retrospective study. Some patients had multiple lesions, therefore a total of 26 lesions were analyzed. DKI was acquired using 5b values at 0, 500, 1000,1500 and 2000 s/mm2. DCE-MRI was obtained with 130 dynamic volumes, with a temporal resolution of 5 s, to achieve a long scan time (>10 min). The apparent diffusion coefficient Dapp and apparent diffusional kurtosis Kapp were calculated voxel-by-voxel, removing the point at b value = 0 to eliminate possible perfusion effects on the parameter estimations. The transfer constants Ktrans and Kep, ve, and the histogram-based entropy (En) and interquartile range (IQR) of each DCE-MRI parameter were quantified. Correlations between all variables were investigated by the Spearman's Rho correlation test. RESULTS: Moderate relationships emerged between Dapp and Kep (Rho =  - 0.510, p = 0.009), and between Dapp and ve (Rho = 0.418, p = 0.038). En(Kep) was significantly related to Kapp (Rho = 0.407, p = 0.043), while IQR(Kep) showed an inverse association with Dapp (Rho = -0.422, p = 0.035). CONCLUSIONS: A weak to intermediate correlation was found between DKI parameters and both Kep and ve. The kurtosis was associated to the intratumoral heterogeneity and complexity of the capillary permeability, expressed by En(Kep).

Correlation between histogram-based DCE-MRI parameters and 18F-FDG PET values in oropharyngeal squamous cell carcinoma: Evaluation in primary tumors and metastatic nodes.

OBJECTIVES: To investigate the correlation between histogram-based Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI) parameters and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) values in oropharyngeal squamous cell carcinoma (OPSCC), both in primary tumors (PTs) and in metastatic lymph nodes (LNs). METHODS: 52 patients with a new pathologically-confirmed OPSCC were included in the present retrospective cohort study. Imaging including DCE-MRI and 18F-FDG PET/CT scans were acquired in all patients. Both PTs and the largest LN, if present, were volumetrically contoured. Quantitative parameters, including the transfer constants, Ktrans and Kep, and the volume of extravascular extracellular space, ve, were calculated from DCE-MRI. The percentiles (P), P10, P25, P50, P75, P90, and skewness, kurtosis and entropy were obtained from the histogram-based analysis of each perfusion parameter. Standardized uptake values (SUV), SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated applying a SUV threshold of 40%. The correlations between all variables were investigated with the Spearman-rank correlation test. To exclude false positive results under multiple testing, the Benjamini-Hockberg procedure was applied. RESULTS: No significant correlations were found between any parameters in PTs, while significant associations emerged between Ktrans and 18F-FDG PET parameters in LNs. CONCLUSIONS: Evident relationships emerged between DCE-MRI and 18F-FDG PET parameters in OPSCC LNs, while no association was found in PTs. The complex relationships between perfusion and metabolic biomarkers should be interpreted separately for primary tumors and lymph-nodes. A multiparametric approach to analyze PTs and LNs before treatment is advisable in head and neck squamous cell carcinoma (HNSCC).

Refinement & validation of rectal wall dose volume objectives for prostate hypofractionation in 20 fractions.

BACKGROUND AND PURPOSE: Dose-volume objectives for the rectum have been proposed to limit long term toxicity after moderately hypofractionated radiotherapy (MHRT) for localized prostate cancer. The purpose of the present study is to validate and possibly refine dose volume objective for the rectal wall after 20-fraction MHRT. MATERIALS AND METHODS: All patients treated by 20-fraction MHRT at a single Institution were identified and relative rectal wall (%RW) DVH retrieved. The endpoint of the study is the development of grade 2+ late rectal bleeding (LRB) according to a modified RTOG scale. Clinical and dosimetric predictors of LRB were investigated at both uni- and multi-variable analysis. RESULTS: 293 patients were identified and analyzed. Of them, 35 (12%) developed the endpoint. At univariable analysis, antithrombotic drug usage (yes vs no), technique (3DCRT vs IMRT/VMAT) and several %RW DVH cut-points were significantly correlated with LRB. However, within patients treated by 3DCRT (N = 106), a bi-variable model including anti-thrombotic drug usage and selected %RW dose/volume metrics failed to identify independent dosimetric predictors of LRB. Conversely, within patients treated with intensity modulation (N = 187), the same model showed a progressively higher impact of the percent of RW receiving doses above 40 Gy. Based on this model, we were able to confirm (V32), refine (V60) and identify a novel (V50) cut-point for the %RW. CONCLUSION: We recommend the following dose volume objectives for the %RW in order to minimize the risk of LRB after 20-fraction MHRT: V32 ≤ 50%; V50 ≤ 25.8% and V60 ≤ 10%.

Intravoxel incoherent motion diffusion-weighted imaging for oropharyngeal squamous cell carcinoma: Correlation with human papillomavirus Status.

PURPOSE: To investigate the relationships between imaging parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and HPV status in oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: 73 patients with a new diagnosis of OPSCC were enrolled in the present study. MRI including IVIM-DWI with nine b value (range 0-800 s/mm2) was acquired in all patients. Primary tumor (PT) and the largest metastatic lymph node (LN), if present, were volumetrically contoured and the tissue diffusion coefficient Dt, perfusion fraction f and perfusion-related diffusion coefficient D* were estimated by a bi-exponential fit. The apparent diffusion coefficient (ADC) was also estimated by a mono-exponential fit. The predictive power of the most relevant patient/tumor characteristics and image-based features in determining the HPV status was assessed. RESULTS: 67 PTs and 67 metastatic LNs were analyzed. Significant differences in ADC and Dt values among HPV-positive and HPV-negative patients were found for PTs (p = 0.003 and p < 0.001, respectively), while a trend toward significance in Dt was reported for LNs (p = 0.066). The perfusion-related parameters, f, D* and D*× f, were not related to HPV status. The best predictive model for HPV positivity was obtained combining alcohol intake and smoke habits with Dt values of PTs (accuracy = 80.8%, sensitivity = 85.7%, specificity = 64.7%). CONCLUSION: Significant correlations were found between IVIM-DWI and HPV status in OPSCCs. The perfusion-free diffusion coefficient, Dt, may better reflect the HPV-related tumor differences compared to ADC, whereas the perfusion-related parameters were not able to reliably discriminate HPV-positive from HPV-negative OPSCC.

Cervical lymphadenopathy: can the histogram analysis of apparent diffusion coefficient help to differentiate between lymphoma and squamous cell carcinoma in patients with unknown clinical primary tumor?

PURPOSE: To retrospectively evaluate the value of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck nodes. METHODS: A total of 39 patients, 20 affected by lymphoma and 19 affected by metastatic non-nasopharyngeal SCC, were included in this retrospective study. All patients underwent MR imaging with a 1.5 T scanner system, including diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and 800 s/mm2). The entire tumor volume was manually delineated on the ADC maps, using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion location. The Mann-Whitney rank-sum test for independent samples was performed to compare the histogram parameters of patients with lymphoma and SCC. RESULTS: The SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean) values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis and skewness without reaching significance (p = 0.066 and 0.148, respectively). The ADCmean and ADCmedian had the best discriminative powers for differentiating lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The optimal cutoff values for ADCmean and ADCmedian as predictors for lymphoma were ≤ 0.83 × 10-3 mm2/s and ≤ 0.73 × 10-3 mm2/s, respectively. CONCLUSIONS: The whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown clinical primary tumor.

Radiation-induced parotid changes in oropharyngeal cancer patients: the role of early functional imaging and patient-/treatment-related factors.

BACKGROUND: Functional magnetic resonance imaging may provide several quantitative indices strictly related to distinctive tissue signatures with radiobiological relevance, such as tissue cellular density and vascular perfusion. The role of Intravoxel Incoherent Motion Diffusion Weighted Imaging (IVIM-DWI) and Dynamic Contrast-Enhanced (DCE) MRI in detecting/predicting radiation-induced volumetric changes of parotids both during and shortly after (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) was explored. METHODS: Patients with locally advanced oropharyngeal SCC were accrued within a prospective study offering both IVIM-DWI and DCE-MRI at baseline; IVIM-DWI was repeated at the 10th fraction of treatment. Apparent diffusion coefficient (ADC), tissue diffusion coefficient Dt, perfusion fraction f and perfusion-related diffusion coefficient D* were estimated both at baseline and during RT. Semi-quantitative and quantitative parameters, including the transfer constant Ktrans, were calculated from DCE-MRI. Parotids were contoured on T2-weighted images at baseline, 10th fraction and 8th weeks after treatment end and the percent change of parotid volume between baseline/10th fr (∆Vol10fr) and baseline/8th wk. (∆Volpost) computed. Correlations among volumetric changes and patient-, treatment- and imaging-related features were investigated at univariate analysis (Spearman's Rho). RESULTS: Eighty parotids (40 patients) were analyzed. Percent changes were 18.2 ± 10.7% and 31.3 ± 15.8% for ∆Vol10fr and ∆Volpost, respectively. Among baseline characteristics, ∆Vol10fr was correlated to body mass index, patient weight as well as the initial parotid volume. A weak correlation was present between parotid shrinkage after the first 2 weeks of treatment and dosimetric variables, while no association was found after radiotherapy. Percent changes of both ADC and Dt at the 10th fraction were also correlated to ∆Vol10fr. Significant relationships were found between ∆Volpost and baseline DCE-MRI parameters. CONCLUSIONS: Both IVIM-DWI and DCE-MRI can help to detect/predict early (during treatment) and shortly after treatment completion the parotid shrinkage. They may contribute to clarify the correlations between volumetric changes of parotid glands and patient-/treatment-related variables by assessing individual microcapillary perfusion and tissue diffusivity.

Diffusional kurtosis imaging in head and neck cancer: On the use of trace-weighted images to estimate indices of non-Gaussian water diffusion.

PURPOSE: While previous studies have demonstrated the feasibility and potential usefulness of quantitative non-Gaussian diffusional kurtosis imaging (DKI) of the brain, more recent research has focused on oncological application of DKI in various body regions such as prostate, breast, and head and neck (HN). Given the need to minimize scan time during most routine magnetic resonance imaging (MRI) acquisitions of body regions, diffusion-weighted imaging (DWI) with only three orthogonal diffusion weighting directions (x, y, z) is usually performed. Moreover, as water diffusion within malignant tumors is generically thought to be almost isotropic, DWI with only three diffusion weighting directions is considered sufficient for oncological application and it represents the de facto standard in body DKI. In this context, since the kurtosis tensor and diffusion tensor cannot be obtained, the averages of the three directional (Kx , Ky , Kz ) and (Dx , Dy , Dz ) - namely K and D, respectively - represent the best-possible surrogates of directionless DKI-derived indices of kurtosis and diffusivity, respectively. This would require fitting the DKI model to the diffusion-weighted images acquired along each direction (x, y, z) prior to averaging. However, there is a growing tendency to perform only a single fit of the DKI model to the geometric means of the images acquired with diffusion-sensitizing gradient along (x, y, z), referred to as trace-weighted (TW) images. To the best of our knowledge, no in vivo studies have evaluated how TW images affect estimates of DKI-derived indices of K and D. Thus, the aim of this study was to assess the potential bias and error introduced in estimated K and D by fitting the DKI model to the TW images in HN cancer patients. METHODS: Eighteen patients with histologically proven malignant tumors of the HN were enrolled in the study. They underwent pretreatment 3 T MRI, including DWI (b-values: 0, 500, 1000, 1500, 2000 s/mm2 ). Some patients had multiple lesions, and thus a total of 34 lesions were analyzed. DKI-derived indices were estimated, voxel-by-voxel, using single diffusion-weighted images along (x, y, z) as well as TW images. A comparison between the two estimation methods was performed by calculating the percentage error in D (Derr ) and K (Kerr ). Also, diffusivity anisotropy (Danis ) and diffusional kurtosis anisotropy (Kanis ) were estimated. Agreements between the two estimation methods were assessed by Bland-Altman plots. The Spearman rank correlation test was used to study the correlations between Kerr /Derr and Danis /Kanis. RESULTS: The median (95% confidence interval) Kerr and Derr were 5.1% (0.8%, 32.6%) and 1.7% (-2.5%, 5.3%), respectively. A significant relationship was observed between Kerr  and Danis (correlation coefficient R = 0.694, P < 0.0001), as well as between Kerr and Kanis (R = 0.848, P < 0.0001). CONCLUSIONS: In HN cancer, the fit of the DKI model to TW images can introduce bias and error in the estimation of K and D, which may be non-negligible for single lesions, and should hence be adopted with caution.

Dependence of apparent diffusion coefficient measurement on diffusion gradient direction and spatial position - A quality assurance intercomparison study of forty-four scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose an MRI quality assurance procedure that can be used for routine controls and multi-centre comparison of different MR-scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 44 MR-scanners with different field strengths (1 T, 1.5 T and 3 T) were included in the study. DWI acquisitions (b-value range 0-1000 s/mm2), with three different orthogonal diffusion gradient directions, were performed for each MR-scanner. All DWI acquisitions were performed by using a standard spherical plastic doped water phantom. Phantom solution ADC value and its dependence with temperature was measured using a DOSY sequence on a 600 MHz NMR spectrometer. Apparent diffusion coefficient (ADC) along each diffusion gradient direction and mean ADC were estimated, both at magnet isocentre and in six different position 50 mm away from isocentre, along positive and negative AP, RL and HF directions. RESULTS: A good agreement was found between the nominal and measured mean ADC at isocentre: more than 90% of mean ADC measurements were within 5% from the nominal value, and the highest deviation was 11.3%. Away from isocentre, the effect of the diffusion gradient direction on ADC estimation was larger than 5% in 47% of included scanners and a spatial non uniformity larger than 5% was reported in 13% of centres. CONCLUSION: ADC accuracy and spatial uniformity can vary appreciably depending on MR scanner model, sequence implementation (i.e. gradient diffusion direction) and hardware characteristics. The DWI quality assurance protocol proposed in this study can be employed in order to assess the accuracy and spatial uniformity of estimated ADC values, in single- as well as multi-centre studies.

The prediction of the treatment response of cervical nodes using intravoxel incoherent motion diffusion-weighted imaging.

PURPOSE: To investigate the predictive role of Intravoxel Incoherent Motion Diffusion-Weighted Imaging (IVIM-DWI) parameters on cervical nodal response to chemo-radiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Patients with pathologically confirmed HNSCC were included in the present prospective study, having at least one positive cervical lymph node (LN). They received concomitant CRT and underwent three serial IVIM-DWI investigations: before, at mid-treatment and after treatment completion. Tissue diffusion coefficient D, perfusion-related diffusion coefficient D* and perfusion fraction f were calculated by a bi-exponential fit. The two-sided Mann-Whitney rank test was used to compare the imaging parameters of patients with regional failure (RF) and regional control (RC). A p value lower than 0.05 was considered to be statistically significant. RESULTS: Thirty-four patients were accrued. Twenty-four out of 34 LN (70.6%) showed persistent RC after a median follow-up time of 27.6 months (range: 12.0-50.2 months), while ten cases of RF (29.4%) were confirmed with a median time of 6.8 months (range: 1.5-19.5 months). Patients with RC showed significantly lower pre-treatment D values compared to the RF patients (p=0.038). At mid-treatment, the patients with RF showed significantly higher D values (p=0.025), and exhibited larger percent reductions in f and the product D*×f from the baseline (p=0.008 and <0.001, respectively). No additional information was provided by the examination at the end of treatment. CONCLUSION: Pre-treatment and mid-treatment IVIM-DWI showed potential for prediction of treatment response of cervical LN in HNSCC patients.