The Glioma-IRE project - Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach.

BACKGROUND: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment. METHODS: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients' clinic characteristics and treatment outcomes. RESULTS: Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status. CONCLUSION: Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit "Regina Elena" National Cancer Institute.

BACKGROUND: The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and short duration response rate. Although clinical trials represent the "gold standard" for providing evidence on efficacy of specific treatment strategies, real-world data can be considered more representative of the "real" GBM population. OBJECTIVE: To describe the management of GBM recurrence in a large real-world sample. METHODS: We analysed retrospectively the data stored in the database of the Neuro-oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. We considered only data of patients with histological diagnosis of GBM and disease recurrence during their follow-up. We excluded patients who did not receive treatment after the diagnosis. RESULTS: We analysed 422 patients (64% males, 36% females) with a mean age of 59.6 (range 16-87) years. At GBM recurrence, 135 (32.0%) patients underwent palliative care, and 287 (68.0%) underwent other treatments. Patients on palliative care were older, had a worse performance status, and a shorter time between GBM diagnosis and its recurrence. Patients who received chemotherapy in combination with other treatments (surgery and/or radiation therapy) at GBM recurrence had a longer survival than those in palliative care (p < 0.001). Surgery or radiation therapy alone did not have any effect on survival as compared with palliative care (p < 0.001). CONCLUSION: This study confirms the importance of a multidisciplinary approach even at GBM recurrence, suggesting that combination treatments play a key role in management of disease.

Craniosynostosis-microphthalmia syndrome belongs to the spectrum of BCOR-related disorders.

Craniosynostosis-microphthalmia linked to BCOR haploinsufficiency.

Degenerative and Vascular Fluent Aphasia: Looking for Differences.

OBJECTIVE: To investigate whether the characteristics of language disorders of degenerative and vascular aphasias depend on the underlying neuropathology. METHODS: Logopenic variant/mixed primary progressive aphasics (lvmPPA; n=18) and poststroke fluent aphasics (PSA; n=11) underwent a neuropsychological examination and an assessment of the macro- and microlinguistic aspects of language. A principal component analysis and a cluster analysis applying a two-group solution were performed on the scores obtained from the neuropsychological and language examination. RESULTS: Global cognition, lexical-semantic, and morphosyntactic components, and two components loading macrolinguistic variables, were extracted by the principal component analysis. A first cluster of 18 participants (14 lvmPPA and 4 PSA) and a second cluster of 11 participants (4 lvmPPA and 7 PSA) were identified. Participants in the first cluster were significantly more impaired than those in the second cluster in global cognition, lexical-semantic, and morphosyntactic components. Macrolinguistic components did not differentiate the two clusters. lvmPPA in the first cluster showed bilateral cortical thinning (greater on the left), whereas lvmPPA in the second cluster showed atrophy only in the left. Participants with PSA in both clusters showed vascular lesions encompassing the posterior left perisylvian regions. Underestimation of the severity of the leukoencephalopathy and damage of the interhemispheric connectivity might be responsible for the inclusion of PSA individuals in the first cluster, despite a unilateral lesion. CONCLUSIONS: Lesion localization is the main factor that determines the characteristics of aphasic deficits. Etiology indirectly acts through a different sensitivity of the brain regions to various pathologies.

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.

Feasibility study of reduced field of view diffusion-weighted magnetic resonance imaging in head and neck tumors.

Background Reduced field of view (rFOV) imaging may be used to improve the quality of diffusion-weighted imaging (DWI) in the head and neck (HN) region. Purpose To evaluate the feasibility of rFOV-DWI in patients affected by HN tumors, through a comparison with conventional full FOV (fFOV) DWI. Material and Methods Twenty-two patients with histologically-proven malignant or benign tumors of the head and neck were included in a retrospective study. All patients underwent pre-treatment magnetic resonance imaging (MRI) studies including rFOV-DWI and fFOV-DWI. The apparent diffusion coefficient (ADC) value distributions inside tumor and muscle were derived and the mean, standard deviation (SD), and kurtosis were calculated. Image distortion was quantitatively and qualitatively evaluated, as well as the capability of lesion identification. The Wilcoxon test was used to compare all variables. Agreements between the ADC estimations were assessed by Bland-Altman plots. Results Image distortion and lesion identification scores were both higher for rFOV-DWI compared to fFOV-DWI. A reduction in ADC values with rFOV-DWI emerged for both lesion and muscle, with a mean percentage difference in ADC of 6.2% in the lesions and 24.9% in the muscle. The difference in SD of ADC was statistically significant in the lesions, indicating a higher ADC homogeneity for rFOV DWI ( P = 0.005). Conclusion The application of rFOV DWI in patients affected by HN tumors is feasible and promising, based on both qualitative and quantitative analyses. This technique has potential for improving the diagnostic accuracy of fFOV-DWI for the study of specific tumoral areas.

Early radiation-induced changes evaluated by intravoxel incoherent motion in the major salivary glands.

PURPOSE: To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands. MATERIALS AND METHODS: Thirty-four patients with head-neck cancer were included in a prospective study. All patients underwent three serial IVIM-MRI: before, half-way through, and at the end of radiotherapy (RT). Apparent diffusion coefficient (ADC), ADClow derived in the low b-value range, perfusion fraction f, and pure diffusion coefficient D were estimated. Pretreatment values and early changes of diffusion parameters were correlated with parotid mean dose (Dmean ) and volume reduction after RT. RESULTS: Changes in diffusion parameters over time were all significant (P < 0.001 for ADC, ADClow , and D, P = 0.003 for f). Variations of ADC, ADClow , and f were not correlated with Dmean (P = 0.089, P = 0.252 and P = 0.884, respectively), whereas a significant relationship was found between changes in D and Dmean (r = 0.197 with CI95% = 0.004-0.375, P = 0.046). Pretreatment f and Dmean were the best independent predictors for the percentage shrinkage (P = 0.0003 and 0.0597 respectively; R(2) = 0.391). CONCLUSION: Early changes of irradiated major salivary glands can be noninvasively evaluated by IVIM-MRI. Perfusion-related coefficients in conjunction with dosimetric information increase our capability to predict the change in parotid volume and hence, if further validated, guide treatment strategy in RT.

Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas.

INTRODUCTION: The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. METHODS: Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. RESULTS: Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS. CONCLUSION: Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.

Assessment of diffusion parameters by intravoxel incoherent motion MRI in head and neck squamous cell carcinoma.

The objectives of this study were to assess the diffusion parameters derived from intravoxel incoherent motion (IVIM) MRI in head and neck squamous cell carcinoma (HNSCC) and to investigate the agreement between different methods of tumor delineation and two numerical methods to extract the perfusion fraction f. Thirty-seven untreated patients with histopathologically confirmed primary HNSCC were included retrospectively in the study. The entire volume of the primary tumor was outlined on diffusion-weighted images using co-registered morphological images as a guide to the tumor location. Apparent diffusion coefficient (ADC) and IVIM diffusion parameters were estimated considering the largest tumor section as well as the entire tumor volume. A bi-exponential fit was implemented to extract f, D (pure diffusion coefficient) and D* (pseudo-diffusion coefficient). A second simplified method, based on an asymptotic extrapolation, was used to determine f. The agreement between ADC and IVIM diffusion parameters derived from the delineation of single and multiple slices, and between the two f estimations, was assessed by Bland-Altman plots. The inter-slice variability of ADC and IVIM diffusion parameters was evaluated. The Kruskal-Wallis test was used to investigate whether the tumor location had a statistically significant influence on the values of the parameters. Comparing the tumor delineation methods, a better accordance was found for ADC and D, with a mean percentage difference of less than 2%. Larger discrepancies were found for f and D*, with mean differences of 4.5% and 5.5%, respectively. When comparing the two f estimation methods, small mean differences were found (<3.5%), suggesting that the two methods may be considered as equivalent for the assessment of f in our patient population. The observed ADC and IVIM diffusion parameters were dependent on the anatomic site of the lesion, carcinoma of the nasopharynx showing more homogeneous and dissimilar estimations than other HNSCCs.

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.

Surgical treatment of cerebellar metastases in elderly patients: A threshold that moves forward?

The impact of surgery for cerebellar brain metastases in elderly population has been the object of limited studies in literature. Given the increasing burden of their chronic illnesses, the decision to recommend surgery remains difficult. All patients aged ≥65 years, who underwent surgical resection of a cerebellar brain metastasis from May 2000 and May 2021 at IRCCS National Cancer Institute "Regina Elena", were analyzed. The study cohort includes 48 patients with a mean age of 70.8 years. 7 patients belonged to the II Class according to the RPA classification, 41 to the III Class; the median GPA classification was 1.5. Median pre-operative and post-operative KPS was 60. Median Charlson Comorbidity Index (CCI) was 11; median 5-variable modified Frailty Index was 2. Overall, 14 patients (29%) presented perioperative neurologic and systemic complications. 34 patients (71%) were able to perform adjuvant therapies as RT and/or CHT after surgery. A higher CCI predicted complications occurrence (p = 0.044), while significant factors for a post-operative KPS ≥70, were i) hemispheric location of the metastasis, ii) higher pre-operative KPS, iii) RPA II classification. Median Overall Survival was 7 months. A post-operative KPS <70 (p = 0.004) and a short time interval between diagnosis of the primary tumor and cerebellar metastasis appearance, were predictive for a worse outcome (p = 0.012). Our study suggests that selected elderly patients with cerebellar metastases may benefit from microsurgery to continue their adjuvant therapies, although a high complications rate should be taken in account.

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.

Brain atrophy pattern in patients with mild cognitive impairment: MRI study.

We evaluated the accuracy of the quantitative and semiquantitative analysis in detecting regional atrophy patterns and differentiating mild cognitive impairment patients who remain stable (aMCI-S) from patients who develop Alzheimer's disease (aMCI-AD) at clinical follow-up. Baseline magnetic resonance imaging was used for quantitative and semiquantitative analysis using visual rating scales. Visual rating scores were related to gray matter thicknesses or volume measures of some structures belonging to the same brain regions. Receiver operating characteristic (ROC) analysis was performed to assess measures' accuracy in differentiating aMCI-S from aMCI-AD. Comparing aMCI-S and aMCI-AD patients, significant differences were found for specific rating scales, for cortical thickness belonging to the middle temporal lobe (MTL), anterior temporal (AT), and fronto-insular (FI) regions, for gray matter volumes belonging to MTL and AT regions. ROC curve analysis showed that middle temporal atrophy, AT, and FI visual scales showed better diagnostic accuracy than quantitative measures also when thickness measures were combined with hippocampal volumes. Semiquantitative evaluation, performed by trained observers, is a fast and reliable tool in differentiating, at the early stage of disease, aMCI patients that remain stable from those patients that may progress to AD since visual rating scales may be informative both about early hippocampal volume loss and cortical thickness reduction.

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.

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.

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).

Acute cerebellar stroke and middle cerebral artery stroke exert distinctive modifications on functional cortical connectivity: A comparative study via EEG graph theory.

OBJECTIVE: We tested whether acute cerebellar stroke may determine changes in brain network architecture as defined by cortical sources of EEG rhythms. METHODS: Graph parameters of 41 consecutive stroke patients (<5 days from the event) were studied using eLORETA EEG sources. Network rearrangements of stroke patients were investigated in delta, alpha 2, beta 2 and gamma bands in comparison with healthy subjects. RESULTS: The delta network remodeling was similar in cerebellar and middle cerebral artery strokes, with a reduction of small-worldness. Beta 2 and gamma small-worldness, in the right hemisphere of patients with cerebellar stroke, increase respect to healthy subjects, while alpha 2 small-worldness increases only among patients with a middle cerebral artery stroke. CONCLUSIONS: The network remodeling characteristics are independent on the size of the ischemic lesion. In the early post-acute stages cerebellar stroke differs from the middle cerebral artery one because it does not cause alpha 2 network remodeling while it determines a high frequency network reorganization in beta 2 and gamma bands with an increase of small-worldness characteristics. SIGNIFICANCE: These findings demonstrate changes in the balance of local segregation and global integration induced by cerebellar acute stroke in high EEG frequency bands. They need to be integrated with appropriate follow-up to explore whether further network changes are attained during post-stroke outcome stabilization.

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.