Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer.

PURPOSE: Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. METHODS: 28 PCa patients (54-80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. RESULTS: The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. CONCLUSIONS: The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT.

[Treatment planning with functional MRI]. / Strahlentherapieplanung mit der funktionellen MRT.

CLINICAL/METHODICAL ISSUE: The aim of magnetic resonance imaging (MRI) guided radiotherapy is high precision in treatment delivery. With new developments it is possible to focus the high dose irradiation on the tumor while sparing the surrounding tissue. The achievements in precision of the treatment planning and delivery warrant equally precise tumor definition. STANDARD RADIOLOGICAL METHODS: In conventional radiation therapy it is necessary to carry out a planning computed tomography (CT). For many tumors there is also need for an additional morphological MRI because of more accurate tumor definition. In standard radiotherapy the tumor volume is irradiated with a homogeneous dose. METHODICAL INNOVATIONS: The aim of functional multiparametric MRI is to visualize and quantify biological, physiological and pathological processes at the cellular and molecular levels. Based on this information it is possible to elucidate tumor biology and identify subvolumes of more aggressive behavior. They are often radiotherapy-resistant, leading to tumor recurrence thus requiring further dose escalation. The concept of inhomogeneous tumor irradiation according to its biological behavior is called dose painting. PERFORMANCE: Dose painting is technically feasible. The expected clinical benefit is motivated by selective treatment adaptations based on biological tumor characteristics. Tumors show variable response to therapy underlining the need for individual treatment plans. This approach may lead not only to higher local control but also to better sparing of normal surrounding tissue. ACHIEVEMENTS: With the clinical implementation of dose painting, improvements in the therapeutic outcome can be expected. PRACTICAL RECOMMENDATIONS: Due to the existing technical challenges, extensive collaboration between radiation oncologists, radiologists, medical physicists and radiation biologists is needed.

An influence of hypothetical products of dimethylamine ozonation on N-nitrosodimethylamine formation.

The paper concerns formation of N-nitrosodimethylamine (NDMA) upon ozonation of dimethylamine (DMA) aqueous solutions. According to current hypothesis ozonated DMA is oxidized to N-dimethylhydroxylamine (DMHA), then to N-methylhydroxylamine (MHA) and finally to hydroxylamine (HA). HA subsequently reacts with the remain part of DMA to form unsymmetrical dimethylhydrazine (UDMH). Finally UDMH undergoes oxidation with ozone to form NDMA. HA is thought to be an important by-product that increases the NDMA formation. We decided to verify the hypothesis by an ozonation of DMA aqueous solutions in the presence of DMHA, MHA and HA. We have clearly proved that ozonation of DMA in the presence of DMHA and/or MHA does not increase NDMA formation. These results do not exclude the possibility of HA formation during DMA ozonation, but unambiguously show that even if HA is formed during this reaction, it does not have any impact on NDMA formation. In authors opinion the formation of MHA and HA is however doubtful since both compounds seem to be rather products of reduction than oxidation. Therefore HA-DMA reaction cannot be responsible for the formation of NDMA when DMA aqueous solution is ozonized.

N-nitrosodimethylamine formation during treatment with strong oxidants of dimethylamine containing water.

The aim of the paper is the evaluation of the possibility of NDMA formation, as a result of strong oxidants reacting with DMA. Summarized results of investigations on N-nitrosodimethylamine formation as a result of dimethylamine reactions with chlorine dioxide, ozone and hydrogen peroxide are presented. Preliminary results of experiments on NDMA formation as a result of DMA reactions with permanganate are also shown. The experiments on dimethylamine reactions with chlorine dioxide, hydrogen peroxide and permanganate were carried out at room temperature under static conditions. Ozonation experiments were carried out at room temperature in a semi-continuous mode. Water samples from all experiments described above were collected during the experiment itself and subsequently analyzed with HPLC-IE with UV-Vis detector at 230 nm. NDMA formation was also confirmed by GC-LRMS. NDMA forms as a result of chlorine dioxide, ozone, hydrogen peroxide or permanganate reactions with dimethylamine. both in the presence as well as in the absence of ammonia ions. The presence of nitrites and nitrates in a post-reaction mixture suggests that NDMA are formed as the result of DMA reactions with nitrites. Thus the mechanism of NDMA formation with these oxidants is different than that described by Mitch et al. and Choi et al. The results also showed a conversion ratio of DMA to NDMA of even up to a single percent (with relation to amines), a simultaneous decrease of NDMA formation potential with a decrease of pH, however, in the case of chlorine dioxide application, a maximum conversion ratio was observed, as well the NDMA formation potential is strongly dependent on the oxidant/DMA ratio.

Derivatization of the mutagen MX (3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone) with butyl alcohols prior to GC-MS analysis.

An extremely potent mutagen, 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is commonly present in chlorinated drinking water. Due to its high mutagenic activity and according to WHO guidelines its concentration should be controlled in drinking waters. Determination of MX is difficult due to the low (ppt) levels at which the compound usually exists in drinking waters. Results obtained with butanols as MX derivatization agents are shown and derivatization with sec-butanol is presented as a method which significantly lowers GC/MS detection levels of MX.

Application of sec-butanol to the derivatization of hydroxyfuranones.

This paper reports the use of sec-butanol for the derivatization of chlorinated hydroxyfuranones. The following hydroxyfuranones were investigated: 3,4-dichloro-5-hydroxy-2(5H)-furanone, 3,4-dibromo-5-hydroxy-2(5H)-furanone, 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone, and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone. Their derivatization products were analyzed by gas chromatography/mass spectrometry. The sec-butyl derivatives of the hydroxyfuranones investigated yield ions that are less abundant than those obtained for the corresponding isopropyl derivatives. However, sec-butyl derivatives are easily detectable in especially dirty matrixes because they produce double peaks in the chromatogram. The ion intensity of the first peak in the pair is lower than that of the second peak, but both are characterized by the same spectrum. The formation of multiple peaks is related to the formation of diastereoisomers during derivatization.

Temporary Changes in the dc ElectricalConductivity of MX (3-Chloro-4(Dichloromethyl)-5-Hydroxy-2(5H)-Furanone) Treated Collagen.

The influence of MX(3-Chloro-4(Dichloromethyl)-5-Hydroxy-2(5H)- Furanone), a stronglymutagenic compound, on the temperature dependence of the dcelectrical conductivity of collagen as a function of time was studied.Collagen was immersed in MX solution, next dried and pressed intotablets. The MX concentration was measured by HPLC analysis.The reduction of MX concentration to 10% of the initial value wasobserved in the presence of collagen in the solution, whereas in thecontrol solution concentration of MX decreased to 70% of the initialvalue. Measurements of electrical conductivity were performed for thetemperature range 295-453K and activation energies for the chargeconduction process were calculated. Within the temperature range295-340K, the presence of MX decreased electrical conductivity ofcollagen. Calculated activation energies were typical for dry proteins.Within the temperature range 295-320K activation energy decreasedwith time, probably due to the stronger interactions in thecollagen-water-MX system. For temperatures between 320-410 and430-450K the activation energy was not time dependent and theapplication of MX did not change the structure of the collagenmacromolecule. The temporary changes occurring at the lowertemperatures being due solely to changes in the collagen-waterinteractions.

New derivatization method for determination of 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone in water.

An extremely potent mutagen, 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is commonly present in chlorinated drinking water. Due to its high mutagenic activity and according to World Health Organization guidelines its concentration should be controlled in drinking waters. Determination of MX is difficult due to ppt levels at which the compound usually exists in drinking waters. Derivatization of MX with 2-propanol is presented as a method which significantly lowers the GC-MS detection level compared to other alcohol derivatization agents.

Association of depression with 10-year poststroke mortality.

OBJECTIVE: Depression has been linked to higher than expected mortality from natural causes, particularly among elderly patients with physical illness. The authors examined the effect of depression on mortality among a group of stroke patients followed up for 10 years. METHOD: A consecutive series of 103 patients was assessed for major or dysthymic (minor) depression approximately 2 weeks after stroke with the use of a structured mental status examination and DSM-III diagnostic criteria. Vital status was determined for 91 of these patients 10 years later. RESULTS: Forty-eight (53%) of the 91 patients had died. Patients with diagnoses of either major or minor depression were 3.4 times more likely to have died during the follow-up period than were nondepressed patients, and this relationship was independent of other measured risk factors such as age, sex, social class, type of stroke, lesion location, and level of social functioning. The mortality rate among depressed patients with few social contacts was especially high: over 90% had died. CONCLUSIONS: These results indicate that depressed mood following stroke is associated with an increased risk of subsequent mortality. Patients who are depressed and socially isolated seem to be particularly vulnerable.

Depression following myocardial infarction.

OBJECTIVE: Although many investigators have studied mood disorders following myocardial infarction, the prevalence, severity, and persistence of depression have been disputed, and standard rating scales and criteria for depressive disorders have infrequently been utilized. The authors' goal was to determine how frequently depressive disorders occur after myocardial infarction, and to investigate predisposing factors for such disorders. METHOD: Structured clinical interviews were administered to 129 inpatients within ten days of myocardial infarction. Patients were also evaluated using standardized rating scales for depression, social function, cognition, and physical impairment. DSM-III diagnoses were derived from the structured interview. RESULTS: Major depressive syndromes were present in 19 percent (n = 25) of the patients and were associated with prior history of mood disorder, female sex, large infarcts, and functional physical impairment. CONCLUSION: Major depression is common in the acute post-myocardial infarction period. Such disorders confer significant psychiatric morbidity and, if sustained, require psychiatric intervention.