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Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

Molecular imaging techniques have rapidly progressed over recent decades providing unprecedented in vivo characterization of metabolic pathways and molecular biomarkers. Many of these new techniques have been successfully applied in the field of neuro-oncological imaging to probe tumor biology. Targeting specific signaling or metabolic pathways could help to address several unmet clinical needs that hamper the management of patients with brain tumors. This review aims to provide an overview of the recent advances in brain tumor imaging using molecular targeting with positron emission tomography and magnetic resonance imaging, as well as the role in patient management and possible therapeutic implications.

Mood disorders (MD) are important and frequent psychiatric illness. The management of patients affected by these conditions represents an important factor of disability as well as a significant social and economic burden. The "in-vivo" studies can help researchers to understand the first developmental events of the pathology and to identify the molecular and non-molecular targets of therapies. However, they have strong limitations due to the fact that human brain circuitry can not be reproduced in animal models. In addition, these neural pathways are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques. All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently hinder the analysis of the effects of pharmacological and non-pharmacological therapies, which have been demonstrated effective in clinical settings. In this review, we will focus our attention on the current state of the art of imaging in the assessment of treatment efficacy in MD. We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging methods used in research and clinical activity, the current knowledge about the neural models at the base of MD. Finally the last part of the review will focus on the analysis of the main markers of response to treatment.

The tumor microenvironment is characteristically acidic and this extracellular acidosis is known to play a role in carcinogenesis and metastasis and can affect tumor chemosensitivity and radiosensitivity. Intracellular pH has been used as a possible biomarker of salvageable tissue in ischemic stroke. A non-invasive MRI-based approach for the determination and imaging of cerebral pH would be a powerful tool in cancer diagnosis and monitoring, as well as stroke treatment planning. Several pH-based MRI imaging approaches have been proposed but for these to be useful, disentangling the effects of pH from other parameters which may affect the measured MRI signal is crucial to ensure accuracy and specificity. R1 relaxation in the rotating frame (R1ρ) is an example of a method that has been proposed to probe pH in vivo using MRI. In this study, we have investigated the relationship between R1ρ, pH, and macromolecular density in vitro using phantoms and in human volunteers. Here we show that the rate of R1ρ relaxation (=1/T1ρ) varies with pH but only in the presence of macromolecules. At constant pH, phantom macromolecular density inversely correlated with R1ρ. R1ρ imaging of the normal human brain demonstrated regional heterogeneity with significant differences between structurally distinct regions, which are likely to be independent of pH. For example, R1ρ was higher in the basal ganglia compared to grey matter and higher in grey matter compared to white matter. We conclude that R1ρ cannot be reliably used to image tissue pH without deconvolution from the effects of local tissue macromolecular composition.

Background BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes. Patients and methods The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients’ clinical characteristics. Kaplan–Meier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. Results A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P = 0.017), to melanoma thickness according to Clark levels, (level V versus III, P = 0.004; level V versus IV, P = 0.04), to lymph node metastases rather than cutaneous (P = 0.04) or visceral (P = 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P = 0.04; PFS P = 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P = 0.014 and P = 0.003, respectively). Conclusion These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition., Highlights • In melanoma the response to anti-BRAF targeted therapies is heterogeneous and influenced by several features. • The role of the BRAF VAF as provider of sensitivity to target therapies is debated. • We found that high BRAF VAFs are associated with patient age, melanoma thickness, non-brisk TILs and lymph node metastases. • We proved the independent prognostic value of high BRAF VAFs in melanoma patients treated with targeted therapies. • The quantitative evaluation of BRAF mutations allows stratifying melanoma patients to the BRAF/MEK targeted treatment.

Fully-quantitative MR imaging methods are useful for longitudinal characterization of disease and assessment of treatment efficacy. However, current quantitative MRI protocols have not been widely adopted in the clinic, mostly due to lengthy scan times. Magnetic Resonance Fingerprinting (MRF) is a new technique that can reconstruct multiple parametric maps from a single fast acquisition in the transient state of the MR signal. Due to the relative novelty of this technique, the repeatability and reproducibility of quantitative measurements obtained using MRF has not been extensively studied. Our study acquired test/retest data from the brains of nine healthy volunteers, each scanned on five MRI systems (two at 3.0 T and three at 1.5 T, all from a single vendor) located at two different centers. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived M0, T1 and T2 maps to an anatomical atlas, coefficients-of-variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated an excellent repeatability (CVs of 2-3% for T1, 5-8% for T2, 3% for normalized-M0) and a good reproducibility (CVs of 3-8% for T1, 8-14% for T2, 5% for normalized-M0) in grey and white matter.

Aim To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. Material and methods Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. Results Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets ( p >0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p =0.001; mixed versus 140 kVp, p =0.001; 80 kVp versus mixed, p =0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets ( p Conclusions The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

Sodium MRI (23Na-MRI) has been used to non-invasively quantify tissue sodium but has been limited by low spatial resolution. Here we demonstrate for the first time that high resolution 23Na-MRI reveals the spatial heterogeneity of sodium concentration within a multiple sclerosis (MS) lesion. A patient with treatment-naïve relapsing-remitting MS and a ring-enhancing lesion was imaged using 23Na-MRI. The periphery of the lesion demonstrated an elevated total sodium content compared to the normal appearing white and grey matter (p

Over the past two decades, systemic neoadjuvant chemotherapy (NAC) has been used in patients with non-metastatic breast cancers [1]. The concept of NAC for operable breast cancers evolved from experience in locally advanced inoperable breast cancer. The goals of NAC in breast cancer are to treat occult systemic disease, decrease the tumor volume reducing the extent of local surgery, and increase long term survival. There are several reasons that support the advantages of NAC. First of all, systemic therapy given prior to surgery might sterilize areas of micrometastases and prevent further cancer growth after the primary tumor is resected [2]. This would be especially true considering the hypothesis that breast surgery could release tumor cells and stimulate the growth of occult micro-metastases through mechanisms such as angiogenesis [3,4]. Another positive aspect of NAC is the possibility to reduce the size of the primary tumor, which allows higher rates of breast-conserving surgery and/or reduces local recurrence rates. Last, the efficacy of NAC can be used as an in vivo assay of drug sensitivity/resistance. In fact, NAC requires an optimal assessment of response to cytotoxic drugs in vivo, which is not only clinically relevant but also critical in terms of research efforts directed to the assessment of chemo resistance and response. Accurate assessment of the neoadjuvant response is a critical element in monitoring and assessing treatment strategies. Considering the high toxicity of chemotherapeutic drugs, early assessment of therapeutic response of the tumor is essential for patient management, as NAC is associated with significant morbidity and reduced quality of life [5,6]. Nowadays, contrast enhanced MRI is considered the most reliable imaging technique in the early assessment of response to NACand it is commonly used in many centers in monitoring NACresponse in patients affected by breast cancer. Several studies have

BRAF(V600E) mutation has been frequently reported in different types of melanocytic lesions, but its role in melanomagenesis is poorly understood, having been associated with either the proliferative-induced MAPK pathway activation or the acquisition of oncogene-driven senescence. The presence of BRAF alterations has been related to sun exposure, although the molecular mechanisms underlying this event are only partly known. To elucidate the relationships among BRAF/NRAS alterations, MAPK pathway activation, and sun exposure, we examined 22 acquired nevi and 18 cutaneus melanomas from 38 patients. Microdissected tissues from each lesion were subjected to BRAF/NRAS mutation analysis by sequencing, allele-specific PCR and pyrosequencing assay. The same lesions were also examined for the expression of phosphorylated ERK1/2. Phototype and an accurate history of sun exposure were evaluated for each patient. BRAF(V600E) mutation was detected in 50% of the acquired nevi and in 70% of the cutaneus melanomas in the absence of NRAS alterations. The fraction of alleles carrying BRAF(V600E) substitution was variable but strongly associated with sun exposure. In contrast, no relationship was evidenced between the presence of this mutation and patients' phototype, phosphorylated ERK1/2 expression, or Clark's level. Our findings indicate that in melanocytic lesions, BRAF(V600E) mutation can affect a subset of the cells and is associated with the type and quantity of sun exposure. This mutation is independent of the nevo-melanoma progression and unrelated to ERK phosphorylation, suggesting that alternative mechanisms to the MAPK activation are also involved in this type of transformation.

The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with Sezary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP. (J Am Acad Dermatol 2001;44:40-7.)

Incense is a hardened rubbery resin that runs from subtropical plants; propolis is a resinous, rubbery and balsamic substance collected by bees from the buds of trees. These two substances have common origins and composition and their content may differ, depending on plants from which they are collected by humans man or bees; terpenes are prevalent in incense; flavanoids, aromatic acids and esters in propolis. The use of incense and propolis for the treatment of human and animal diseases has been well-known since the earliest times. In a previous report we demonstrated that the diffusion of incense and propolis can reduce the bacterial load in a school classroom; on this basis, we evaluated the effectiveness of incense and propolis in reducing the bacterial load in other two closed environments, that is a pig and a poultry farm. After spreading propolis in these two environments, the number of colony forming units in the samples collected both from the pig farm and the poultry farm was significantly lower. A further reduction in the bacterial load was relieved, when propolis and incense were used together. On the basis of these preliminary data, we conclude that propolis (especially when containing a high concentration of sesquiterpenes) and incense can be employed in zootechnology, to sanitise the closed environments of breeding farms.