Differences in Gaussian diffusion tensor imaging and non-Gaussian diffusion kurtosis imaging model-based estimates of diffusion tensor invariants in the human brain.

PURPOSE: An increasing number of studies have aimed to compare diffusion tensor imaging (DTI)-related parameters [e.g., mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] to complementary new indexes [e.g., mean kurtosis (MK)/radial kurtosis (RK)/axial kurtosis (AK)] derived through diffusion kurtosis imaging (DKI) in terms of their discriminative potential about tissue disease-related microstructural alterations. Given that the DTI and DKI models provide conceptually and quantitatively different estimates of the diffusion tensor, which can also depend on fitting routine, the aim of this study was to investigate model- and algorithm-dependent differences in MD/FA/RD/AD and anisotropy mode (MO) estimates in diffusion-weighted imaging of human brain white matter. METHODS: The authors employed (a) data collected from 33 healthy subjects (20-59 yr, F: 15, M: 18) within the Human Connectome Project (HCP) on a customized 3 T scanner, and (b) data from 34 healthy subjects (26-61 yr, F: 5, M: 29) acquired on a clinical 3 T scanner. The DTI model was fitted to b-value =0 and b-value =1000 s/mm(2) data while the DKI model was fitted to data comprising b-value =0, 1000 and 3000/2500 s/mm(2) [for dataset (a)/(b), respectively] through nonlinear and weighted linear least squares algorithms. In addition to MK/RK/AK maps, MD/FA/MO/RD/AD maps were estimated from both models and both algorithms. Using tract-based spatial statistics, the authors tested the null hypothesis of zero difference between the two MD/FA/MO/RD/AD estimates in brain white matter for both datasets and both algorithms. RESULTS: DKI-derived MD/FA/RD/AD and MO estimates were significantly higher and lower, respectively, than corresponding DTI-derived estimates. All voxelwise differences extended over most of the white matter skeleton. Fractional differences between the two estimates [(DKI - DTI)/DTI] of most invariants were seen to vary with the invariant value itself as well as with MK/RK/AK values, indicating substantial anatomical variability of these discrepancies. In the HCP dataset, the median voxelwise percentage differences across the whole white matter skeleton were (nonlinear least squares algorithm) 14.5% (8.2%-23.1%) for MD, 4.3% (1.4%-17.3%) for FA, -5.2% (-48.7% to -0.8%) for MO, 12.5% (6.4%-21.2%) for RD, and 16.1% (9.9%-25.6%) for AD (all ranges computed as 0.01 and 0.99 quantiles). All differences/trends were consistent between the discovery (HCP) and replication (local) datasets and between estimation algorithms. However, the relationships between such trends, estimated diffusion tensor invariants, and kurtosis estimates were impacted by the choice of fitting routine. CONCLUSIONS: Model-dependent differences in the estimation of conventional indexes of MD/FA/MO/RD/AD can be well beyond commonly seen disease-related alterations. While estimating diffusion tensor-derived indexes using the DKI model may be advantageous in terms of mitigating b-value dependence of diffusivity estimates, such estimates should not be referred to as conventional DTI-derived indexes in order to avoid confusion in interpretation as well as multicenter comparisons. In order to assess the potential and advantages of DKI with respect to DTI as well as to standardize diffusion-weighted imaging methods between centers, both conventional DTI-derived indexes and diffusion tensor invariants derived by fitting the non-Gaussian DKI model should be separately estimated and analyzed using the same combination of fitting routines.

Progression of microstructural damage in spinocerebellar ataxia type 2: a longitudinal DTI study.

BACKGROUND AND PURPOSE: The ability of DTI to track the progression of microstructural damage in patients with inherited ataxias has not been explored so far. We performed a longitudinal DTI study in patients with spinocerebellar ataxia type 2. MATERIALS AND METHODS: Ten patients with spinocerebellar ataxia type 2 and 16 healthy age-matched controls were examined twice with DTI (mean time between scans, 3.6 years [patients] and 3.3 years [controls]) on the same 1.5T MR scanner. Using tract-based spatial statistics, we analyzed changes in DTI-derived indices: mean diffusivity, axial diffusivity, radial diffusivity, fractional anisotropy, and mode of anisotropy. RESULTS: At baseline, the patients with spinocerebellar ataxia type 2, as compared with controls, showed numerous WM tracts with significantly increased mean diffusivity, axial diffusivity, and radial diffusivity and decreased fractional anisotropy and mode of anisotropy in the brain stem, cerebellar peduncles, cerebellum, cerebral hemisphere WM, corpus callosum, and thalami. Longitudinal analysis revealed changes in axial diffusivity and mode of anisotropy in patients with spinocerebellar ataxia type 2 that were significantly different than those in the controls. In patients with spinocerebellar ataxia type 2, axial diffusivity was increased in WM tracts of the right cerebral hemisphere and the corpus callosum, and the mode of anisotropy was extensively decreased in hemispheric cerebral WM, corpus callosum, internal capsules, cerebral peduncles, pons and left cerebellar peduncles, and WM of the left paramedian vermis. There was no correlation between the progression of changes in DTI-derived indices and clinical deterioration. CONCLUSIONS: DTI can reveal the progression of microstructural damage of WM fibers in the brains of patients with spinocerebellar ataxia type 2, and mode of anisotropy seems particularly sensitive to such changes. These results support the potential of DTI-derived indices as biomarkers of disease progression.

Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. MATERIALS AND METHODS: Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. RESULTS: Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. CONCLUSIONS: Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease.

Adenoma, advanced adenoma and colorectal cancer prevalence in asymptomatic 40- to 49-year-old subjects with a first-degree family history of colorectal cancer.

AIM: First-degree relatives (FDRs) of patients with colorectal cancer (CRC) have an increased CRC risk. Few studies have addressed if adenoma and advanced adenoma risk is increased among individuals, 40-49 years of age, with a family history of CRC. Therefore, the aim of the study was to define the prevalence and location of adenoma, advanced adenoma and CRC, according to age, in asymptomatic individuals with a family history of CRC. METHOD: Retrospective study of asymptomatic FDRs, 40 to ≥70 years of age undergoing first screening colonoscopy over a 3-year period, of CRC patients. RESULTS: Among 464 individuals studied, the prevalence of adenoma and advanced adenoma was 18.1% and 6.4%, respectively. According to age intervals, the prevalences of adenoma and advanced adenoma were 14% and 3.5%, respectively, in subjects 40-49 years of age; 14.4% and 6.3%, respectively, in subjects 50-59 years of age; 27% and 8%, respectively, in subjects 60-69 years of age; and 25% and 14%, respectively, in subjects ≥70 years of age; no significant difference was found among the four groups. No difference in lesion location was found, with similar numbers of preneoplastic lesions being present in the right colon and the left colon. CRC was diagnosed in three (0.64%) subjects, one of whom was in the 40-49 years age group. CONCLUSION: In our population of FDRs of CRC patients, 40-49 years of age, the prevalences of adenoma and advanced adenoma were similar to those observed in older subjects with the same CRC risk. Our data support the current indication to perform screening colonoscopy earlier than 45 years of age in subjects at high CRC risk.

Magnetization transfer MR imaging demonstrates degeneration of the subcortical and cortical gray matter in Huntington disease.

BACKGROUND AND PURPOSE: GM is typically affected in HD since the presymptomatic stage. Our aim was to investigate with MT MR imaging the microstructural changes of the residual brain subcortical and cortical GM in carriers of the HD gene and to preliminarily assess their correlation with the clinical features. MATERIALS AND METHODS: Fifteen HD gene carriers with a range of clinical severity and 15 age- and sex-matched healthy controls underwent MT MR imaging on a 1.5T scanner. The MT ratio was measured automatically in several subcortical and cortical GM regions (striatal nuclei; thalami; and the neocortex of the frontal, temporal, parietal, and occipital lobes) by using FLS tools. RESULTS: The MT ratio was significantly (P < .05 with Bonferroni correction for multiple comparison) decreased in all subcortical structures except the putamen and decreased diffusely in the cerebral cortex of HD carriers compared with controls. Close correlation was observed between the subcortical and cortical regional MT ratios and several clinical variables, including disease duration, motor disability, and scores in timed neuropsychological tests. CONCLUSIONS: MT imaging demonstrates degeneration of the subcortical and cortical GM in HD carriers and might serve, along with volumetric assessment, as a surrogate marker in future clinical trials of HD.

Regional distribution and clinical correlates of white matter structural damage in Huntington disease: a tract-based spatial statistics study.

BACKGROUND AND PURPOSE: HD entails damage of the WM. Our aim was to explore in vivo the regional volume and microstructure of the brain WM in HD and to correlate such findings with clinical status of the patients. MATERIALS AND METHODS: Fifteen HD gene carriers in different clinical stages of the disease and 15 healthy controls were studied with T1-weighted images for VBM and DTI for TBSS. Maps of FA, MD, and λ∥ and λ⊥ were reconstructed. RESULTS: Compared with controls, in addition to neostriatum and cortical GM volume loss, individuals with HD showed volume loss in the genu of the internal capsule and subcortical frontal WM bilaterally, the right splenium of the corpus callosum, and the left corona radiata. TBSS revealed symmetrically decreased FA in the corpus callosum, fornix, external/extreme capsule, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Areas of increased MD were more extensive and included arciform fibers of the cerebral hemispheres and cerebral peduncles. Increase of the λ∥ and a comparatively more pronounced increase of the λ⊥ underlay the decreased FA of the WM in HD. Areas of WM atrophy, decreased FA, and increased MD correlated with the severity of the motor and cognitive dysfunction, whereas only the areas with increased MD correlated with disease duration. CONCLUSIONS: Microstructural damage accompanies volume decrease of the WM in HD and is correlated with the clinical deficits and disease duration. MR imaging-based measures could be considered as a biomarker of neurodegeneration in HD gene carriers.

Early structural changes in individuals at risk of familial Alzheimer's disease: a volumetry and magnetization transfer MR imaging study.

Presenilin 1 (PS1) mutation carriers provide the opportunity to asses early features of neurodegeneration in familial Alzheimer's disease (AD). Gray matter (GM) regional volume loss and decrease of magnetization transfer ratio (MTR) consistent with microstructural changes have been reported in sporadic AD. We performed a regional volumetric and MTR analysis in carriers of PS1 mutations. Six non-demented mutated PS1 carriers (5 with memory deficits) and 14 healthy subjects were examined with high resolution T1-weighted images for volumetry and with T2* weighted images for MTR. Cortical GM volume and MTR values were derived. Compared to healthy controls, the GM volume of the left temporal and inferior parietal cortex and the MTR of the temporal cortex bilaterally were significantly decreased in PS1 gene carriers. In the latter, the temporal lobe MTR showed a trend for correlation with memory and executive function scores. Early neurodegeneration in non-demented subjects at risk for familial AD may be associated with atrophy and decreased MTR in the temporal cortex.

Diffusion-weighted imaging in patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system due to JC polyoma virus infection of oligodendrocytes. PML develops in patients with impaired T-cell function as occurs in HIV, malignancy or immunosuppressive drugs users. Until now no imaging methods have been reported to correlate with clinical status. Diffusion-weighted imaging (DWI) is a robust MRI tool in investigating white matter architecture and diseases. The aim of our work was to assess diffusion abnormalities in focal white matter lesions in patients with PML and to correlate the lesion load measured with conventional MRI and DWI to clinical variables. We evaluated eight patients with a biopsy or laboratory-supported diagnosis of PML. All patients underwent MRI including conventional sequences (fluid attenuated inversion recovery-FLAIR) and DWI. Mean diffusivity (MD) maps were used to quantify diffusion on white matter lesions. Global lesion load was calculated by manually tracing lesions on FLAIR images, while total, central core and peripheral lesion loads were calculated by manually tracing lesions on DWI images. Lesion load obtained with the conventional or DWI-based methods were correlated with clinical variables such as disease duration, disease severity and survival. White matter focal lesions are characterized by a central core with low signal on DWI images and high MD (1.853 x 10(-3) mm2/s), surrounded by a rim of high signal intensity on DWI and lower MD (1.1 x 10(-3) mm2/s). The MD value of normal-appearing white matter is higher although not statistically significant (0.783 x 10(-3) mm2/s) with respect to control subjects (0.750 x 10(-3) mm2/s). Inter-rater correlations of global lesion load between FLAIR (3.96%) and DWI (3.43%) was excellent (ICC=0.87). Global lesion load on FLAIR and DWI correlates with disease duration and severity (respectively, p=0.037, p=0.0272 with Karnofsky scale and p=0.0338 with EDSS on FLAIR images; p=0.043, p=0.0296 with Karnofsky scale and p=0.0365 with EDSS on DW images). Central core lesion load on DWI correlates with disease duration and severity (respectively p=0.043, p=0.0103 with Karnofsky scale and p=0.0112 with EDSS), while peripheral lesion load does not correlate with any clinical variable. The global lesion load in PML correlates with disease duration and severity. DWI images, which can distinguish within lesions a central core from a peripheral rim, reveal that a larger central core component correlates to a worsened clinical status and longer disease duration. On the other hand the peripheral rim lesion load visualized on DWI images does not correlate with clinical variables and does not achieve obtaining further prognostic information with respect to conventional imaging.

A whole-brain analysis in de novo Parkinson disease.

BACKGROUND AND PURPOSE: Widespread cerebral changes are observed in advanced stages of Parkinson disease (PD), suggesting that PD is a multisystem disorder. We investigated with MR imaging whether global brain changes are present in early clinical stages of PD and correlated the findings with the type of clinical presentation. MATERIALS AND METHODS: T1-weighted images and mean diffusivity and fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) were obtained in 27 patients with de novo drug-naïve PD, who were classified according to the clinical features in tremor-dominant type (n = 13), akinetic-rigid type (n = 11), and mixed type (n = 3). Sixteen healthy subjects provided control data. With SIENAX software, total brain, gray matter (GM), and white matter (WM) volumes were computed from T1-weighted images, whereas brain histograms were obtained from mean diffusivity and FA maps. RESULTS: Total brain, GM and WM volumes were not significantly different in patients as a whole or subgroups and controls. As compared with controls, patients with PD as a whole and patients with the akinetic-rigid type showed an increase (P

Brain structural damage in Friedreich's ataxia.

OBJECTIVE: Neuropathological descriptions of the brain in Friedreich's ataxia (FRDA) were obtained before availability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative analysis of differences in gray matter (GM) and white matter (WM) volume. METHODS: Using VBM, we assessed the brain structural damage in 22 patients with genetically confirmed FRDA and 25 healthy controls. The results were correlated with the disease duration and the severity of the patients' clinical deficits--evaluated using the International Cerebellar Ataxia Rating Scale and Inherited Ataxia Clinical Rating Scale. RESULTS: In patients with FRDA, VBM showed a symmetrical volume loss in dorsal medulla, infero-medial portions of the cerebellar hemispheres, the rostral vermis and in the dentate region. No volume loss in cerebral hemispheres was observed. The atrophy of the cerebellum and medulla correlated with the severity of the clinical deficit and disease duration. CONCLUSIONS: In patients with FRDA, significant GM and WM loss was observed only in the cerebellum and dorsal medulla. These structural changes correlate with the severity of the clinical deficit and disease duration.

Effect of chlorhexidine digluconate on different cell types: a molecular and ultrastructural investigation.

Although several studies have shown that chlorhexidine digluconate (CHX) has bactericidal activity against periodontal pathogens and exerts toxic effects on periodontal tissues, few have been directed to evaluate the mechanisms underlying its adverse effects on these tissues. Therefore, the aim of the present study was to investigate the in vitro cytotoxicity of CHX on cells that could represent common targets for its action in the surgical procedures for the treatment of periodontitis and peri-implantitis and to elucidate its mechanisms of action. Osteoblastic, endothelial and fibroblastic cell lines were exposed to various concentrations of CHX for different times and assayed for cell viability and cell death. Also analysis of mitochondrial membrane potential, intracellular Ca2+ mobilization and reactive oxygen species (ROS) generation were done in parallel, to correlate CHX-induced cell damage with alterations in key parameters of cell homeostasis. CHX affected cell viability in a dose and time-dependent manners, particularly in osteoblasts. Its toxic effect consisted in the induction of apoptotic and autophagic/necrotic cell deaths and involved disturbance of mitochondrial function, intracellular Ca2+ increase and oxidative stress. These data suggest that CHX is highly cytotoxic in vitro and invite to a more cautioned use of the antiseptic in the oral surgical procedures.

Whole-brain histogram and voxel-based analyses of diffusion tensor imaging in patients with leukoaraiosis: correlation with motor and cognitive impairment.

BACKGROUND AND PURPOSE: Cerebral white matter changes, termed leukoaraiosis (LA), appearing as areas of increased signal intensity in T2-weighted MR images, are common in elderly subjects, but the possible correlation of LA with cognitive or motor deficit has not been established. We hypothesized that histogram and voxel-based analyses of whole-brain mean diffusivity (MD) and fractional anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) could be more sensitive tools than visual scales to investigate the clinical correlates of LA. MATERIALS AND METHODS: Thirty-six patients of the Leukoaraiosis and Disability Study were evaluated with fluid-attenuated inversion recovery for LA extension, T1-weighted images for volume, and DTI for MD and FA. The extent of LA was rated visually. The normalized total, gray, and white matter brain volumes were computed, as well as the 25th percentile, 50th percentile, kurtosis, and skewness of the MD and FA maps of the whole brain. Finally, voxel-based analysis on the maps of gray and white matter volume, MD, and FA was performed with SPM2 software. Correlation analyses between visual or computerized data and motor or neuropsychologic scale scores were performed using the Spearman rank test and the SPM2 software. RESULTS: The visual score correlated with some MD and FA histogram metrics (P<.01). However, only the 25th and 50th percentiles, kurtosis, and skewness of the MD and FA histograms correlated with motor or neuropsychologic deficits. Voxel-based analysis revealed a correlation (P<.05 corrected for multiple comparisons) between a large cluster of increased MD in the corpus callosum and pericallosal white matter and motor deficit. CONCLUSIONS: These results are consistent with the hypothesis that histogram and voxel-based analyses of the whole-brain MD and FA maps are more sensitive tools than the visual evaluation for clinical correlation in patients with LA.

Quantitative diffusion-weighted MR imaging in the differential diagnosis of breast lesion.

The role of diffusion-weighted magnetic resonance imaging (DWI) to differentiate breast lesions in vivo was evaluated. Sixty women (mean age, 53 years) with 81 breast lesions were enrolled. A coronal echo planar imaging (EPI) sequence sensitised to diffusion (b value=1,000 s/mm(2)) was added to standard MR. The mean diffusivity (MD) was calculated. Differences in MD among cysts, benign lesions and malignant lesions were evaluated, and the sensitivity and specificity of DWI to diagnose malignant and benign lesions were calculated. The diagnosis was 18 cysts, 21 benign and 42 malignant nodules. MD values (mean +/- SD x 10(-3) mm(2)/s) were (1.48 +/- 0.37) for benign lesions, (0.95 +/- 0.18) for malignant lesions and (2.25 +/- 0.26) for cysts. Different MD values characterized different malignant breast lesion types. A MD threshold value of 1.1 x 10(-3) mm(2)/s discriminated malignant breast lesions from benign lesions with a specificity of 81% and sensitivity of 80%. Choosing a cut-off of 1.31 x 10(-3) mm(2)/s (MD of malignant lesions -2 SD), the specificity would be 67% with a sensitivity of 100%. Thus, MD values, related to tumor cellularity, provide reliable information to differentiate malignant breast lesions from benign ones. Quantitative DWI is not time-consuming and can be easily inserted into standard clinical breast MR imaging protocols.

[Investigation on health status of silica exposed workers in "cotto Fiorentino" companies]. / Indagine sullo stato di salute degli esposti a silice nelle aziende del cotto Fiorentino.

The manufactured in "cotto" is typical of Chianti Fiorentino with about 400 employees. In 2005. the UF PISLL encountered an exposure to silica more than TLV, particularly for some tasks; were prescribed interventions of prevention and was undertaken an investigation of the occupational health status with occupational health physician. We observed 227 workers, 208 males and 19 females, with average age of 43 years and average age working of 15 years. The habit of smoking tobacco was higher than for the general population. The assessment of exposure to silica has been detected for 59 workers (mean 0.05 mg / mc); at pulmonary function testing resulted: 10 with airway obstruction and 4 airflow limitation; by 140 chest X - ray acquired 1 was interstitial pulmonary disease and 1 was bronchopneumonia. Among the diseases not related to exposure to silica, emerging 42 cases of low back pain, 28 hearing loss, 7 with hypertension. Non uniformity in health surveillance and diagnostic criteria highlights the need to cooperate between occupational doctor in public prevention and control service and qualified occupational doctor to ensure a standard of quality in the prevention of disease in exposed to silica.

The effect of temperament and character on response to selective serotonin reuptake inhibitors in panic disorder.

OBJECTIVE: In this prospective study, temperament and character were evaluated in patients with panic disorder (PD), before 1 year of medication therapy, to verify whether these factors influenced the outcome of treatment. METHOD: Seventy-one PD patients were evaluated with the SCID-IV, the Temperament and Character Inventory (TCI), the SCL-90, the Ham-A and the Ham-D. Patients were treated with pharmacotherapy and were evaluated monthly over 1 year. RESULTS: Before treatment, non-remitted patients showed higher levels of harm avoidance (HA) and lower levels of persistence (P), self-directedness (SD) and cooperativeness (C), whereas remitted patients showed only higher levels of HA. After controlling the effect of the confounding variables, the likelihood to achieve remission was positively related to SD score (OR = 1.12; P = 0.002), particularly 'self-acceptance' SD dimension (OR = 1.30; P = 0.02). CONCLUSIONS: Our data suggest that in PD: i) the evaluation of personality, using the Cloninger's model, confirms the presence of personality pathology as one predictor of non-response to treatment; ii) in patients with low SD a combination of medication and cognitive-behaviour therapy should be the most effective treatment.

Predictors of symptom resolution in panic disorder after one year of pharmacological treatment: a naturalistic study.

OBJECTIVE: In this naturalistic and prospective study, patients with panic disorder (PD) were treated for one year 1) to verify the rate of patients achieving the resolution of full-symptom attacks, limited-symptom attacks, anticipatory anxiety, phobic avoidance and depression; and 2) to identify the predictors of symptom resolution for each domain. METHOD: One hundred patients with PD, according to DSM-IV criteria, participated in the study. In all patients, a baseline and a follow-up with monthly evaluations of SCL-90, Ham-A, Ham-D and panic diaries were carried out over a one-year period. All patients were treated with paroxetine or citalopram. RESULTS: Seventy-one patients completed the study, whereas the remaining 29 dropped out. Among completers, remission of full- and limited-symptom panic attacks was observed in 76 % of patients, whereas complete remission (resolution of panic attacks, anticipatory anxiety, phobic anxiety, and depression) was achieved by only 46 % of patients. Predictors of absence of symptom remissions were obsessive-compulsive disorder (OCD) and recurrent major depression (MD) comorbidity (for panic attacks), pre-treatment severity of anxious symptoms (for anticipatory anxiety), phobic anxiety (for phobic avoidance), and depressive symptoms (for depression). CONCLUSION: This naturalistic study shows that the high comorbidity of OCD and MD and the greater pre-treatment severity of anxious, phobic and depressive symptoms reduced the likelihood of achieving complete remission of symptoms in PD patients who completed the protocol, even though they were adequately treated with SSRI medication.

Ion recombination correction for very high dose-per-pulse high-energy electron beams.

The parallel-plate ionization chamber is the recommended tool for the absorbed dose measurement in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value less then 0.1 cGy/pulse. In this range the factor to correct the response of an ionization chamber for the lack of complete charge collection due to ion recombination (ksat) can be properly evaluated with the standard "two voltage" method proposed by the international dosimetric reports. Very high dose-per-pulse electron beams are employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy (IORT). The high dose-per-pulse values (3-13 cGy/pulse) characterizing the IORT electron beams allow to deliver the therapeutic dose (10-20 Gy) in less than a minute. This considerably reduces the IORT procedure time, but some dosimetric problems arise because the standard method to evaluate ksat overestimates its value by 20%. Moreover, if the dose-per-pulse value >1 cGy/pulse, the dependence of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry. In this work the dependence of ksat on the dose-per-pulse value is derived, based on the general equation that describes the ion recombination in the Boag theory. A new equation for ksat, depending on known or measurable quantities, is presented. The new ksat equation is experimentally tested by comparing the absorbed doses to water measured with parallel-plate ionization chambers (Roos and Markus) to that measured using dose-per-pulse independent dosimeters, such as radiochromic films and chemical Fricke dosimeters. These measurements are performed in the high dose-per-pulse (3-13 cGy/pulse) electron beams of the IORT dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements made using the parallel-plate chambers and those made using the dose-per-pulse independent dosimeters are in good agreement (<3%). This demonstrates the possibility of using the parallel-plate ionization chambers also for the very high dose-per-pulse (> 1 cGy/pulse) electron-beam dosimetry.