MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Delayed intracranial hemorrhage after mild traumatic brain injury in patients on oral anticoagulants: is the juice worth the squeeze?

OBJECTIVE: Mild Traumatic Brain Injury (MTBI) in anticoagulated patients is a common challenge for Emergency Department (ED) Physicians. Anticoagulation is considered a risk factor for developing delayed intracranial hemorrhage (ICH) after MTBI. The occurrence of this event in patients on Vitamin K Antagonists (VKA) or Direct Oral Anticoagulants (DOACs) remains unclear. Primary endpoint: to analyze the role of anticoagulants as risk factors for developing delayed ICH after MTBI and evaluate the indications to repeat a cranial computed tomography (CT) after a period of observation. Secondary endpoint: to assess the difference in the prevalence rate of delayed ICH in patients on VKA versus those on DOACs. PATIENTS AND METHODS: We evaluated all consecutive patients admitted to our ED for MTBI, which had a control CT for late ICH after a negative CT at admission. We used a propensity score match (PSM) on factors affecting the need for oral anticoagulation to adjust the comparison between anticoagulated vs. non-anticoagulated patients for the baseline clinical characteristics. RESULTS: Among 685 patients enrolled, 15 (2.2%) developed ICH at control CT. After PSM, the incidence of ICH, although slightly higher, was not statistically different in anticoagulated patients vs. non-anticoagulated (2.3% vs. 0.6%, p=0.371). Among the 111 patients on VKA, 5 (4.5%) had a late ICH, compared to 4 out of 99 (4.0%) on DOACs; the difference was not statistically significant (p=0.868). CONCLUSIONS: The risk of developing delayed ICH after MTBI in patients on anticoagulation therapy is low. After correction for baseline covariates, the risk does not appear higher compared to non-anticoagulated patients. Thus, a routine control CT scan seems advisable only for patients presenting a clinical deterioration. Larger, prospective trials are required to clarify the safety profile of DOACs vs. VKA in MTBI.

Brain DSC MR Perfusion in Children: A Clinical Feasibility Study Using Different Technical Standards of Contrast Administration.

BACKGROUND AND PURPOSE: Dynamic susceptibility contrast MR perfusion imaging has limited results in children due to difficulties in reproducing technical standards derived from adults. This prospective, multicenter study aimed to determine DSC feasibility and quality in children using custom administration of a standard dose of gadolinium. MATERIALS AND METHODS: Eighty-three consecutive children with brain tumors underwent DSC perfusion with a standard dose of gadobutrol administered by an automated power injector. The location and size of intravenous catheters and gadobutrol volume and flow rates were reported, and local and/or systemic adverse effects were recorded. DSC was qualitatively evaluated by CBV maps and signal intensity-time curves and quantitatively by the percentage of signal drop and full width at half-maximum, and the data were compared with the standards reported for adults. Quantitative data were grouped by flow rate, and differences among groups were assessed by analysis of covariance and tested for statistical significance with a t test. RESULTS: No local or systemic adverse events were recorded independent of catheter location (63 arm, 14 hand, 6 foot), size (24-18 ga), and flow rates (1-5 mL/s). High-quality CBV maps and signal intensity-time curves were achieved in all patients, and quantitative evaluations were equal or superior to those reported for adults. No significant differences (P ≥ .05) were identified among the higher-flow-rate groups in the quantitative data. CONCLUSIONS: A custom administration of a standard dose of gadobutrol allows safe and high-quality DSC MR perfusion imaging in children.

Postoperative MR Imaging of Spontaneous Transdural Spinal Cord Herniation: Expected Findings and Complications.

BACKGROUND AND PURPOSE: Spontaneous transdural spinal cord herniation is no longer a rare cause of myelopathy. The high frequency of diagnoses has led to an increase in the number of surgical procedures. The purpose of this study was to describe the spectrum of postoperative MR imaging findings concerning spontaneous transdural spinal cord herniation and to provide a practical imaging approach for differentiating expected changes and complications after an operation. MATERIALS AND METHODS: We retrospectively reviewed MR images from 12 patients surgically treated for spontaneous transdural spinal cord herniation. Surgery comprised either dural defect enlargement or duraplasty procedures. Postoperative follow-ups included at least 3 (early, intermediate, late) MR imaging studies. MR images were analyzed with respect to 3 spinal compartments: intradural intramedullary, intradural extramedullary, and extradural. The meaning and reliability of changes detected on MR images were related to their radiologic and clinical evolution with time. RESULTS: Spinal cord realignment has been stable since the early study, whereas spinal cord signal and thickness evolved during the following scans. Most extramedullary and extradural changes gradually reduced in later MR images. Three patients treated with dural defect enlargements experienced the onset of new neurologic symptoms. In those patients, late MR images showed extradural fluid collection and the development of pial siderosis. CONCLUSIONS: Our findings demonstrate the spectrum of postoperative imaging findings in spontaneous transdural spinal cord herniation. Spinal cord thickness and signal intensity continued to evolve with time; most extramedullary postsurgical changes became stable. Changes observed in later images may be suggestive of complications.

Differential diagnosis of parotid gland tumours: which magnetic resonance findings should be taken in account?

Our aim was to define typical magnetic resonance (MRI) findings in malignant and benign parotid tumours. This study is based on retrospective evaluation of pre-surgical MRI of 94 patients with parotid gland tumours. Histology results were available for all tumours. There were 69 cases of benign (73%) and 25 cases of malignant (27%) tumours, including 44 pleomorphic adenomas, 18 Warthin's tumours, 7 various benign tumours, 6 squamous cell carcinomas, 3 carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 1 adenoid cystic carcinoma and 13 various malignant tumours. The following MRI parameters were evaluated: shape, site, size, margins, signal intensity (SI) on T1w and T2w images, contrast enhancement, signal of cystic content, presence or absence of a capsule, perineural spread, extraglandular growth pattern and cervical adenopathy. Statistical analysis was performed to identify the MRI findings most suggestive of malignancy, and to define the most typical MRI pattern of the most common histologies. Ill-defined margins (p < 0.001), adenopathies (p < 0.001) and infiltrative grown pattern (p < 0.001) were significantly predictive of malignancy. Typical findings of pleomorphic adenoma included hyperintensity on T2w images (p = 0.02), strong contrast enhancement (p < 0.001) and lobulated shape (p = 0.04). Typical findings of Warthin's tumour included hyperintense components on T1w images (p < 0.001), location in the parotid inferior process (p < 0.001) and mild or incomplete contrast enhancement (p = 0.01). SI on T1w and T2w images and contrast enhancement enables differential diagnosis between pleomorphic adenoma and Warthin's tumour.

Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities.

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p=0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p=0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

CT and MRI diagnosis of silent sinus syndrome.

PURPOSE: The purpose of this study was to determine computed tomography (CT) and magnetic resonance (MR) findings of silent sinus syndrome (SSS) - a rare clinical entity with the constellation of progressive enophthalmos and hypoglobus, facial asymmetry and possible diplopia - due to otherwise asymptomatic maxillary sinus disease. MATERIALS AND METHODS: We reviewed the pre- and postoperative CT and MR images of six patients with a definitive diagnosis of SSS and compared the radiological and clinical findings with those reported in the literature. RESULTS: The CT and MR studies demonstrated in all cases the most characteristic imaging features of SSS reported in the literature. CONCLUSIONS: Both CT and MR imaging enable a diagnosis of SSS to be made, but CT provides a better depiction of all features of SSS necessary for diagnosis and differentiation from other sinus conditions, even in patients without a clinical suspicion of SSS.

Magnetic resonance imaging of solitary brain metastases: main findings of nonmorphological sequences.

PURPOSE: This study was done to investigate the usefulness of diffusion-weighted (DWI), perfusion-weighted (PWI) and proton magnetic resonance (MR) spectroscopy imaging in characterising solitary brain metastases. MATERIALS AND METHODS: Fifty-nine solitary brain metastases were evaluated with conventional and nonmorphological MR imaging: DWI, PWI and MR spectroscopy. We evaluated size, signal intensity and contrast enhancement and calculated apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV), percentage of signal intensity recovery (PSR) and maximum values of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipids (Lip), NAA/Cr and Cho/Cr. The nonmorphological parameters were compared with those from the literature for brain lesions that frequently enter the differential diagnosis with metastases. RESULTS: Signal intensity and contrast enhancement patterns were variable. There was a wide range of ADC values: min:max 0.59×10(-3):1.88×10(-3). Compared with normal white matter, rCBV was higher in lesions (3.30±1.59) and lower in perilesional oedema (0.42±0.15). Mean and minimum PSR were 57% and 48%, respectively; lip and Cho were elevated and NAA reduced. CONCLUSIONS: Conventional MR findings of solitary metastases are heterogeneous, and some values of nonmorphological sequences are similar to those of other brain lesions. PWI seems to be the nonmorphological MR technique that may best contribute to the diagnosis of brain metastases.

Recurrent subarachnoid bleeding and superficial siderosis in a patient with histopathologically proven cerebral amyloid angiopathy.

A 68-year-old man with a history of hypertension presented with recurrent subarachnoid bleeding. Brain MRI showed superficial siderosis, and diagnostic cerebral angiograms did not show any intracranial vascular malformation or arterial aneurism. Post mortem neuropathological examination of the brain was consistent with a diagnosis of cerebral amyloid angiopathy. Clinicians should be aware that cerebral amyloid angiopathy should be considered in patients with unexplained recurrent subarachnoid bleeding, even in cases without familial clustering or transthyretin variant.

Trauma of the spine and spinal cord: imaging strategies.

Traumatic injuries of the spine and spinal cord are common and potentially devastating lesions. We present a comprehensive overview of the classification of vertebral fractures, based on morphology (e.g., wedge, (bi)concave, or crush fractures) or on the mechanism of injury (flexion-compression, axial compression, flexion-distraction, or rotational fracture-dislocation lesions). The merits and limitations of different imaging techniques are discussed, including plain X-ray films, multi-detector computed tomography (MDCT), and magnetic resonance imaging (MRI) for the detection. There is growing evidence that state-of-the-art imaging techniques provide answers to some of the key questions in the management of patients with spine and spinal cord trauma: is the fracture stable or unstable? Is the fracture recent or old? Is the fracture benign or malignant? In summary, we show that high-quality radiological investigations are essential in the diagnosis and management of patients with spinal trauma.

An optimized method to separate reticulocytes from peripheral blood for molecular analysis.

A method based on immunomagnetic sorting of reticulocytes from peripheral blood was set up and combined to a commercial extraction kit for the isolation of total RNA from whole blood. This procedure resulted in high-quality RNA samples suitable for molecular analysis. We used this procedure to analyse erythroid-specific transcripts, starting from peripheral blood samples, to search for differently expressed mRNAs in patients with hereditary persistence of foetal haemoglobin. After erythrocyte lysis, CD15(+)and CD45(+) peripheral cells were negatively sorted to remove leucocyte populations that could have affected the subsequent screening procedure. The cell sorting and RNA extraction procedure was completed within 1-2 h of erythrocyte lysis, which represents a consistent saving of time compared with other procedures. Moreover, it produced 1 microg of total RNA per ml of blood samples, which is sufficient for molecular analysis. Therefore, our method is a reliable and efficient tool to isolate RNA from specific cell subpopulations poorly represented in peripheral blood, particularly when accurate detection and characterization of highly unstable and poorly expressed molecules is required.

Lichen biomonitoring of ammonia emission and nitrogen deposition around a pig stockfarm.

Effects of high ammonia emissions and nitrogen deposition were investigated on lichens around a pig stockfarm (ca. 7,000 animals) in central Italy. Four sites were selected along a transect at 200, 400, 1000 and 2500 m from the stockfarm, the diversity of epiphytic lichens was measured and transplanted thalli of Xanthoria parietina and Flavoparmelia caperata exposed, together with passive NH3 (diffusion tubes) samplers. Ammonia dramatically decreased from the centre of the stockfarm to the sampled sites, where it was correlated with bark pH. Total lichen diversity was not associated with either NH3 concentrations or bark pH, but the diversity of strictly nitrophytic species was highly correlated with both parameters. Physconia grisea was the best indicator species for NH3 pollution. Total N accumulated in X. parietina and F. caperata was correlated with NH3 concentrations.

Effects of NO2 and NH3 from road traffic on epiphytic lichens.

The results of a survey aimed at investigating whether NO2 and NH3 emitted by road traffic can influence lichen diversity, lichen vitality and the accumulation of nitrogen in lichen thalli are reported. For this purpose, distance from a highway in a rural environment of central Italy was regarded as the main parameter to check this hypothesis. The results of the present survey indicated that road traffic is not a relevant source of NH3. On the other hand, NO2 concentrations, although rather low, were negatively correlated with distance from the highway according to a typical logarithmic function. No association between NO2 concentrations and the diversity of epiphytic lichens was found, probably because of the low NO2 values measured. Also bark properties were not influenced by distance from the highway. Accumulation of nitrogen, reduction in the content of chlorophyll a, chlorophyll b and total carotenoids were found in transplanted thalli of Evernia prunastri, but NO2 was not responsible for these changes, which were probably caused by applications of N-based fertilizers.

Radioecological survey at selected sites hit by depleted uranium ammunitions during the 1999 Kosovo conflict.

A field study, organised, coordinated and conducted under the responsibility of the United Nations Environment Programme (UNEP), took place in Kosovo in November 2000 to evaluate the level of depleted uranium (DU) released into the environment by the use of DU ammunition during the 1999 conflict. Representatives of six different scientific organisations took part in the mission and a total of approximately 350 samples were collected. During this field mission, the Italian National Environmental Protection Agency (ANPA) collected water, soil, lichen and tree bark samples from different sites. The samples were analysed by alpha-spectroscopy and in some cases by inductively coupled plasma-source mass spectrometry (ICP-MS). The 234U/238U and 235U/238U activity concentration ratios were used to distinguish natural from anthropogenic uranium. This paper reports the results obtained on these samples. All water samples had very low concentrations of uranium (much below the average concentration of drinking water in Europe). The surface soil samples showed a very large variability in uranium activity concentration, namely from approximately 20 Bq kg(-1) (environmental natural uranium) to approximately 2.3 x 10(5) Bq kg(-1) (approximately 18000 mg kg(-1) of depleted uranium), with concentrations above environmental levels always due to DU. The uranium isotope measurements refer to soil samples collected at places where DU ammunition had been fired; this variability indicates that the impact of DU ammunitions is very site-specific, reflecting both the physical conditions at the time of the impact of the DU ammunition and any physical and chemical alteration which occurred since then. The results on tree barks and lichens indicated the presence of DU in all cases, showing their usefulness as sensitive qualitative bio-indicators for the presence of DU dusts or aerosols formed at the time the DU ammunition had hit a hard target. This result is particularly interesting considering that at some sites, which had been hit by DU ammunition, no DU ground contamination could be detected.

Levels of depleted uranium in Kosovo soils.

The United Nations Environment Programme (UNEP) has performed a field survey at 11 sites located in Kosovo, where depleted uranium (DU) ammunitions were used by the North Atlantic Treaty Organization (NATO) during the last Balkans conflict (1999). Soil sampling was performed to assess the spread of DU ground contamination around and within the NATO target sites and the migration of DU along the soil profile. The 234U/238U and 235U/238U activity concentration ratios have been used as an indicator of natural against anthropogenic sources of uranium. The results show that levels of 238U activity concentrations in soils above 100 Bq x kg(-1) can be considered a 'tracer' of the presence of DU in soils. The results also indicate that detectable ground surface contamination by DU is limited to areas within a few metres from localised points of concentrated contamination caused by penetrator impacts. Vertical distribution of DU along the soil profile is measurable up to a depth of 10-20 cm. This latter aspect is of particular relevance for the potential risk of future contamination of groundwater.

Role of diagnostic imaging in abdominal lymphadenopathy.

Abdominal lymph node chains and route of lymph drainage of various organs (stomach, duodenum, liver, gallbladder, pancreas, small intestine, appendix, blind intestine, colon rectum) are analyzed according to their location. The role of conventional radiology and diagnostic imaging is evaluated in the study of abdominal lymphatic system with particular reference to lymphangiography and the new procedures of sonography, CT and MRI. Present methods used in inflammatory abdominal lymphadenopathy with special attention to tuberculous lymphadenitis, liver cirrhosis, neoplastic abdominal lymphadenopathy, colorectal and pancreatic cancer, are illustrated. Combined modality imaging is considered in gastric cancer based on the evolution of the classification of gastric lymph nodes. The role of sonography, endoscopic ultrasonography, spiral CT and MRI is assessed in gastric cancer N staging. A retrospective study is analyzed and perspectives for the application of a new CT protocol are proposed. PET potentialities in the study of abdominal lymph nodes are examined.