Dose–volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

BACKGROUND AND PURPOSE: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. MATERIALS AND METHODS: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. RESULTS: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP=5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. CONCLUSIONS: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT.     

Interactions between Associative Synaptic Potentials in the Piriform Cortex of the In Vitro Isolated Guinea Pig Brain

The interaction between synaptic potentials generated by the activation of separate sets of associative fibres was investigated in the piriform cortex of an in vitro isolated guinea pig brain preparation. Restricted regions of the piriform cortex served by separate contingents of afferent fibres of the lateral olfactory tract were isolated surgically. The activity generated by these patches of cortex in response to afferent stimulation propagates to remote cortical regions along cortico-cortical associative fibres. Current source density (CSD) analysis of field potential laminar profiles evoked by lateral olfactory tract stimulation confirmed that the synaptic sinks induced by distinct associative fibre contingents converge on the apical dendrites of piriform cortex neurons in the superficial lb layer. Pairing between potentials evoked by activation of two separate sets of associative fibres resulted in an almost linear summation when the two responses coincided. For interstimulus intervals of <100 ms, heterosynaptic pairing of independent associative inputs induced a facilitation of the conditioned associative potential, which correlated with an increase in the associative sink located in layer lb, as demonstrated by CSD analysis. The evaluation of the pairing intervals suggests that the heterosynaptic facilitation of the conditioned associative potentials may be due to the summation of local and remote associative synaptic events. It is concluded that separate associative inputs converge on the apical dendrites of piriform cortex pyramidal neurons to generate synaptic potentials through the activation of spatially close but independent synapses. The role of associative synaptic integration in the functional organization of the olfactory cortex is discussed.     

Double-blind stereo-EEG and FDG PET study in severe partial epilepsies: Are the electric and metabolic findings related?

The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[¹⁸F]FDG images in all the subjects in the study, there was poor agreement between PET/[¹⁸F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[¹⁸F]FDG studies in patients with medically refractory partial seizures.     

MELD score versus conventional UNOS status in predicting short-term mortality after liver transplantation.

The Model for End-stage Liver Disease (MELD) provides a score able to predict short-term mortality in patients awaiting liver transplantation (LT). In the early 2002, United Network for Organ Sharing (UNOS) has proposed to replace the conventional statuses 3, 2B, and 2A with a modified MELD score. However, the accuracy of the MELD model to predict post-transplantation outcome is fairly elusive. In the present study we investigated the predictive value of the MELD score for short-term patient and graft mortality in comparison with conventional UNOS status. Sixty-nine patients listed at UNOS status 3 (n = 5), 2B (n = 55) or 2A (n = 9) who underwent LT were enrolled according to strict criteria. No donor-related parameters affected 3-month patient survival. Through univariate Cox regression, pretransplantation international normalized ratio (P = 0.049) and activated partial thromboplastin time (P = 0.032) were significantly associated with 3-month patient survival, although not in the subsequent multivariate analysis. The overall MELD score was 17 +/- 6.63 (median: 16, range: 4-34), increasing from UNOS Status 3 to 2A (r(2) = 0.171, P = 0.0001). No significant difference occurred in the median MELD score between patients who underwent a second LT and those who did not (P =0.458). The inter-rate agreement between UNOS status and MELD score after categorization for clinical urgency showed a fair agreement (kappa = 0.244). The 3-month patient and graft mortality was 15.94% and 20.29% respectively. The concordance statistic did not find significance between UNOS status and MELD score for 3-month patient (P = 0.283) or graft mortality (P = 0.957), although the MELD score revealed a major sensitivity for short-term patient mortality (0.637; 95%CI: 0.513-0.75). These findings suggest the need to implement MELD model accuracy for both inter-rate agreement with UNOS Status and patient outcome.     

Role of hepatitis delta virus infection in hepatocellular carcinoma

Hepatitis B virus (HBV) DNA integrates into the host DNA and shows a series of potentially oncogenetic properties, but HBV is not an acutely transforming virus, because HCC develops decades after infection. Other factors, namely cirrhosis, inflammation, alcohol intake, and viral superinfections, could promote the oncogenetic process induced by HBV-DNA integration. We studied the impact of HDV infection in the pathogenesis of HCC in 62 consecutive patients. Their mean age was 59 years (range 25–75 years), 54 were male and eight female; 58 had cirrhosis. The findings suggest that HBsAg-positive patients with HDV superinfection developed cirrhosis and HCC at an earlier age than HBsAg carriers without HDV infection. HDV appears to represent a promotion factor for HCC in subjects with an oncogenic risk induced by HBV. A long-lasting necroinflammatory lesion of the liver substained by productive HBV and HDV infections may be a major pathogenetic mechanism.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

Neurological Signs at the First Psychotic Episode as Correlates of Long-Term Outcome: Results From the AESOP-10 Study

Minor neurological signs are subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts present in excess in the early stages of psychosis. Still, it remains unclear whether at least some of these signs represent trait or state markers for psychosis and whether they are markers of long-term disease outcome of clinical utility. We examined the relationship between neurological function at illness onset assessed with the Neurological Evaluation Scale and subsequent illness course in 233 patients from AESOP-10 (Aetiology and Ethnicity in Schizophrenia and Other Psychoses), a 10-year follow-up study of a population-based cohort of individuals recruited at the time of their first episode of psychosis in the United Kingdom. In 56 of these patients, we also explored changes in neurological function over time. We included a group of 172 individuals without psychosis as controls. After 10 years, 147 (63%) patients had developed a non-remitting course of illness, and 86 (37%) a remitting course. Already at first presentation, patients who developed a non-remitting course had significantly more primary, motor coordination, and total signs than both remitting patients and healthy controls. While Motor Coordination signs did not change over time, rates of Primary, Sensory Integration, and Total signs increased, independently of illness course type. These findings suggest that motor coordination problems could be a useful early, quick, and easily detectable marker of subsequent clinical outcome. With other motor abnormalities, a measure of motor incoordination could contribute to the identification of the most vulnerable individuals, who could benefit from targeted and more assertive treatment approaches.     

Comparative study of autofluorescence in flat and tapered optical fibers towards application in depth-resolved fluorescence lifetime photometry in brain tissue

As the scientific community seeks efficient optical neural interfaces with sub-cortical structures of the mouse brain, a wide set of technologies and methods is being developed to monitor cellular events through fluorescence signals generated by genetically encoded molecules. Among these technologies, tapered optical fibers (TFs) take advantage of the modal properties of narrowing waveguides to enable both depth-resolved and wide-volume light collection from scattering tissue, with minimized invasiveness with respect to standard flat fiber stubs (FFs). However, light guided in patch cords as well as in FFs and TFs can result in autofluorescence (AF) signal, which can act as a source of time-variable noise and limit their application to probe fluorescence lifetime in vivo. In this work, we compare the AF signal of FFs and TFs, highlighting the influence of the cladding composition on AF generation. We show that the autofluorescence signal generated in TFs has a peculiar coupling pattern with guided modes, and that far-field detection can be exploited to separate functional fluorescence from AF. On these bases, we provide evidence that TFs can be employed to implement depth-resolved fluorescence lifetime photometry, potentially enabling the extraction of a new set of information from deep brain regions, as time-correlating single photon counting starts to be applied in freely-moving animals to monitor the intracellular biochemical state of neurons.