Effect of automatic tube current modulation on radiation dose and image quality for low tube voltage multidetector row CT angiography: phantom study

RATIONALE AND OBJECTIVES: To evaluate the effect of automatic tube current modulation on radiation dose and image quality for low tube voltage computed tomography (CT) angiography. MATERIALS AND METHODS: An anthropomorphic phantom was scanned with a 64-section CT scanner using following tube voltages: 140 kVp (Protocol A), 120 kVp (Protocol B), 100 kVp (Protocol C), and 80 kVp (Protocol D). To achieve similar noise, combined z-axis and xy-axes automatic tube current modulation was applied. Effective dose (ED) for the four tube voltages was assessed. Three plastic vials filled with different concentrations of iodinated solution were placed on the phantom's abdomen to obtain attenuation measurements. The signal-to-noise ratio (SNR) was calculated and a figure of merit (FOM) for each iodinated solution was computed as SNR(2)/ED. RESULTS: The ED was kept similar for the four different tube voltages: (A) 5.4 mSv +/- 0.3, (B) 4.1 mSv +/- 0.6, (C) 3.9 mSv +/- 0.5, and (D) 4.2 mSv +/- 0.3 (P > .05). As the tube voltage decreased from 140 to 80 kVp, image noise was maintained (range, 13.8-14.9 HU) (P > .05). SNR increased as the tube voltage decreased, with an overall gain of 119% for the 80-kVp compared to the 140-kVp protocol (P < .05). The FOM results indicated that with a reduction of the tube voltage from 140 to 120, 100, and 80 kVp, at constant SNR, ED was reduced by a factor of 2.1, 3.3, and 5.1, respectively, (P < .001). CONCLUSIONS: As tube voltage decreases, automatic tube current modulation for CT angiography yields either a significant increase in image quality at constant radiation dose or a significant decrease in radiation dose at a constant image quality.

Effective Dose Estimation in Fast-kV Switch Dual Energy Computed Tomography

Purpose

The objective of our study was to test a new approach to approximating organ dose by using the effective energy of the combined 80kV/140kV beam used in fast kV switch dual-energy (DE) computed tomography (CT). The two primary focuses of the study were to first validate experimentally the dose equivalency between MOSFET and ion chamber (as a gold standard) in a fast kV switch DE environment, and secondly to estimate effective dose (ED) of DECT scans using MOSFET detectors and an anthropomorphic phantom.

Materials and Methods

A GE Discovery 750 CT scanner was employed using a fast-kV switch abdomen/pelvis protocol alternating between 80 kV and 140 kV. The specific aims of our study were to (1) Characterize the effective energy of the dual energy environment; (2) Estimate the f-factor for soft tissue; (3) Calibrate the MOSFET detectors using a beam with effective energy equal to the combined DE environment; (4) Validate our calibration by using MOSFET detectors and ion chamber to measure dose at the center of a CTDI body phantom; (5) Measure ED for an abdomen/pelvis scan using an anthropomorphic phantom and applying ICRP 103 tissue weighting factors; and (6) Estimate ED using AAPM Dose Length Product (DLP) method. The effective energy of the combined beam was calculated by measuring dose with an ion chamber under varying thicknesses of aluminum to determine half-value layer (HVL).

Results

The effective energy of the combined dual-energy beams was found to be 42.8 kV. After calibration, tissue dose in the center of the CTDI body phantom was measured at 1.71 ± 0.01 cGy using an ion chamber, and 1.73±0.04 and 1.69±0.09 using two separate MOSFET detectors. This result showed a -0.93% and 1.40 % difference, respectively, between ion chamber and MOSFET. ED from the dual-energy scan was calculated as 16.49 ± 0.04 mSv by the MOSFET method and 14.62 mSv by the DLP method.

Biokinetics and dosimetry of 111 In-DOTA-NOC-ATE compared with 111In-DTPA-Octreotide

Aim: Biokinetics and dosimetry of 111In-DOTA-NOC-ATE (NOCATE) and 111In-DTPA-octreotide (Octreoscan?, OCTREO) were comparatively studied in the same patients. Patients and Methods: Seventeen patients (10 males, 7 females), mean age 60 years referred for an Octreoscan? because of carcinoid (N=9), unspecified neurodendocrine tumors (N=6), thymoma (N=1) or medullary thyroid carcinoma (N=1) accepted a second study with NOCATE. Four patients had no detectable tumor at the time of scanning. Whole-body (WB) anterior-posterior scans were recorded 0.5 (100% reference scan), 4, 24 and 48 hrs (N=17) and 120 hrs (N=6) after injection. OCTREO (178±15 MBq) preceded NOCATE (108±14 MBq) imaging with 16±5 days in 16 patients while 1 patient had first NOCATE followed 14 days later by OCTREO. Blood samples were taken 5, 15, 30, 60, 240 and 1440 min after injection. Background corrected geometric mean counts of WB, lung, kidney, liver, spleen and blood counts expressed in % of the initial composite WB and blood counts, respectively were fitted to bi- or single exponential curves and dosimetry was performed for male and female patients using MIRDOSE3.1 and OLINDA/EXM. Results: Initially, WB, lung and kidney activity was similar but retention was significantly higher for NOCATE compared with OCTREO. Liver and spleen uptake of NOCATE was higher from beginning (p<0.001) and remained so over time. Activity in rest of body showed similar α and β half-lives, but the β half-life fraction of NOCATE was much higher than OCTREO (49% vs. 19%, respectively). Blood T1/2β was longer for NOCATE compared with OCTREO (19 vs. 6h). Residence times were similar in male and female patients while they were in both genders higher for NOCATE than OCTREO. Consequently, effective dose (ED) for NOCATE (ED 114 and 134 μSv/MBq for man and women, respectively) exceeded that of OCTREO (ED = 61 and 71 μSv/MBq), the latter results being close to the ICRP-published radiation dose of OCTREO (ED = 54 and 71 µSv/MBq, respectively). Differential activity measurement in blood cells and plasma showed that only a minor fraction of NOCATE and OCTREO (<5 % in the mean) was bound to globular blood components. Conclusions: NOCATE showed higher retention in normal organs and delivered roughly twice the radiation dose of OCTREO. The ED of OCTREO in these patients was similar to ICRP80 report when adopting a bladder voiding interval of 2 hours.

Caracterização fitoquímica e avaliação da atividade anti-inflamatória e antinociceptiva do óleo fixo de Euterpe oleracea Mart.

Euterpe oleracea Mart. é uma típica palmeira da Amazônia, que cresce espontaneamente nos estados do Pará e Amapá, apreciada por sua atrativa beleza e valor nutricional. O fruto de Euterpe oleracea, comumente conhecido como açaí, tem demonstrado exibir significante capacidade anti-oxidante in vitro, o que pode ter benefícios à saúde. Estudos químicos revelaram a presença de ácidos graxos, antocianinas e esteroides. O objetivo deste trabalho foi caracterizar fitoquimícamente o óleo fixo dos frutos desta espécie (OEO) e avaliar em modelos inflamatórios e hiperalgésicos in vivo, o possível envolvimento dos compostos nas respostas inflamatória e analgésica. Para tanto, os modelos experimentais usados foram: teste de contorção induzida por ácido acético, edema de pata de rato, teste do granuloma em ratos, permeabilidade vascular em ratos, migração leucocitária em ratos e eritema de orelha induzida por óleo de cróton em camundongos. Doses orais de 500, 1000 e 1500 mg/kg de OEO inibiu o número de contorções em 33,67%, 45,88% e 55,58, respectivamente. O OEO produziu efeito dose-dependente, e a dose média efetiva encontrada foi de 1226,8mg/kg. Com a administração oral da dose de 1226,8 mg/kg, o OEO inibiu o processo inflamatório em 29,18% quando comparado ao grupo controle. A administração diária de OEO por 6 dias inibiu a formação do tecido granulomatoso em 36,66%. No eritema de orelha por óleo de cróton, o OEO provocou efeito inibitório significativo em 37,9%. No teste de permeabilidade vascular, o OEO inibiu a permeabilidade vascular em 54,5%. Na peritonite induzida por carragenina, o OEO reduziu o número de neutrófilos quando comparado ao grupo controle (inibição de 80,14%). A partir dos resultados obtidos, sugere-se que o OEO apresenta atividade anti-inflamatória, sobre os processos inflamatórios agudo e crônico, e atividade antinociceptiva, provavelmente de origem periférica.

Avaliação da atividade antinociceptiva e anti-inflamatória de Mikania lindleyana DC: validação do uso na medicina popular

Mikania lindleyana (Asteraceae), popularmente conhecida como sucuriju, é uma espécie nativa da região amazônica, cujo chá das folhas é a principal forma de uso popular para tratamento de gastrite, infecção, dor e inflamação. Para validar a forma e a alegação de uso decidiu-se avaliar a toxicidade aguda e as atividades antinociceptiva e anti-inflamatória do extrato bruto aquoso liofilizado de Mikania lindleyana devidamente identificada (EAML), bem como investigar sua composição química. Na análise fitoquímica do EAML detectou-se a presença de saponinas, proteínas, aminoácidos, fenóis, taninos, ácidos orgânicos e flavonoides. Por cromatografia em camada delgada (CCD) foram observadas zonas de fluorescência azul características de ácido o-cumárico. Por cromatografia liquida acoplada à espectrometria de massa (CLAE-DAD-EM) foram encontrados compostos altamente glicosilados. O EAML na dose de 5000mg/kg não provocou morte nos animais. No teste de contorções abdominais, o EAML (nas doses 125, 250, 500, 750, 1000 e 1500mg/kg) promoveu redução no número de contorções de maneira significante e dose-dependente. A dose efetiva mediana (DE₅₀) de 692,6 mg/kg não prolongou o tempo de latência sobre a placa quente. No teste de formalina, o EAML reduziu o tempo no qual os animais permaneceram lambendo a pata injetada com formalina nas duas fases sendo este efeito revertido pelo antagonista opioide naloxona. A dose de 692,6 mg/kg inibiu a formação de eritema, mas não o edema provocado por dextrana. A mesma dose inibiu a formação do edema por carragenina a partir da 2ª hora e reduziu a migração de neutrófilos para a cavidade peritonial. Estes resultados sugerem que o EAML, nas doses utilizadas, apresenta atividade antinociceptiva na qual pode haver a participação do sistema opioide e, apresenta atividade anti-inflamatória que pode ser atribuída à ação sobre mediadores inflamatórios, como PGs, e, ainda sobre moléculas de adesão, cuja participação de citocinas pode ser crucial.

Toxicidade in vitro e in vivo do ortobenzamol, análogo do paracetamol

O paracetamol (PAR) é um dos medicamentos de venda livre mais utilizado em todo o mundo. Entretanto, doses elevadas do PAR produzem toxicidade hepática e/ou renal. No intuito de minimizar a toxicidade do PAR e obter melhor atividade analgésica e anti-inflamatória, um estudo prévio realizou modificações na estrutura química do PAR por modelagem molecular, dando origem ao ortobenzamol (OBZ) – análogo do PAR. Assim, o OBZ foi sintetizado e avaliado em modelos de nocicepção e inflamação em animais. O estudo demonstrou atividade analgésica central do OBZ, com potência superior ao PAR. Além disso, nos testes de inflamação, essa droga apresentou inibição significativa no processo inflamatório. Entretanto, para que o OBZ possa ser considerado uma alternativa terapêutica nova e importante para o tratamento da dor e/ou da inflamação é necessário determinar sua toxicidade. Assim, este estudo objetivou avaliar a toxicidade in vitro e in vivo do OBZ e, compará-la com a do PAR. Para isso, a neurotoxicidade foi avaliada in vitro em culturas primárias de neurônios corticais, através de ensaios de viabilidade celular, determinação dos níveis de glutationa total e reduzida, assim como a possível capacidade neuroprotetora frente ao estresse oxidativo. Foram realizados estudos in vivo em camundongos, iniciados pela determinação da dose efetiva mediana (DE₅₀) do PAR, a fim de compará-la com a do OBZ nos modelos de toxicidade estudados. Determinou-se o estresse oxidativo hepático e cerebral pela análise dos níveis de peroxidação lipídica e nitritos. A possível disfunção hepática e renal foi determinada, por meio da análise dos níveis plasmáticos das enzimas aspartato aminotransferase (AST), de alanina aminotransferase (ALT), gama glutamiltransferase (GGT) e, da creatinina no sangue. Avaliaram-se alterações nos parâmetros clínicos através do hemograma, leucograma e plaquetograma e, realizou-se a determinação da toxicidade aguda. Os resultados obtidos neste estudo demonstraram que o ortobenzamol é mais seguro que o paracetamol. Registrou-se ao ortobenzamol ausência de neurotoxicidade, menor potencial hepatotóxico e hematotóxico, ausência de nefrotoxicidade e, ainda, foi classificado como um xenobiótico de baixa toxicidade após a avaliação da toxicidade aguda. Portanto, o ortobenzamol pode ser considerado como uma futura alternativa terapêutica segura ao paracetamol, no tratamento da dor e inflamação.

Hypervascular liver tumors: low tube voltage, high tube current multi-detector row CT for enhanced detection--phantom study

PURPOSE: To prospectively evaluate, for the depiction of simulated hypervascular liver lesions in a phantom, the effect of a low tube voltage, high tube current computed tomographic (CT) technique on image noise, contrast-to-noise ratio (CNR), lesion conspicuity, and radiation dose. MATERIALS AND METHODS: A custom liver phantom containing 16 cylindric cavities (four cavities each of 3, 5, 8, and 15 mm in diameter) filled with various iodinated solutions to simulate hypervascular liver lesions was scanned with a 64-section multi-detector row CT scanner at 140, 120, 100, and 80 kVp, with corresponding tube current-time product settings at 225, 275, 420, and 675 mAs, respectively. The CNRs for six simulated lesions filled with different iodinated solutions were calculated. A figure of merit (FOM) for each lesion was computed as the ratio of CNR2 to effective dose (ED). Three radiologists independently graded the conspicuity of 16 simulated lesions. An anthropomorphic phantom was scanned to evaluate the ED. Statistical analysis included one-way analysis of variance. RESULTS: Image noise increased by 45% with the 80-kVp protocol compared with the 140-kVp protocol (P < .001). However, the lowest ED and the highest CNR were achieved with the 80-kVp protocol. The FOM results indicated that at a constant ED, a reduction of tube voltage from 140 to 120, 100, and 80 kVp increased the CNR by factors of at least 1.6, 2.4, and 3.6, respectively (P < .001). At a constant CNR, corresponding reductions in ED were by a factor of 2.5, 5.5, and 12.7, respectively (P < .001). The highest lesion conspicuity was achieved with the 80-kVp protocol. CONCLUSION: The CNR of simulated hypervascular liver lesions can be substantially increased and the radiation dose reduced by using an 80-kVp, high tube current CT technique.

Dosimetric optimization of CT protocols for the preoperative planning of hip arthroplasty

Radiation dose in x-ray computed tomography (CT) has become a topic of great interest due to the increasing number of CT examinations performed worldwide. In fact, CT scans are responsible of significant doses delivered to the patients, much larger than the doses due to the most common radiographic procedures. This thesis work, carried out at the Laboratory of Medical Technology (LTM) of the Rizzoli Orthopaedic Institute (IOR, Bologna), focuses on two primary objectives: the dosimetric characterization of the tomograph present at the IOR and the optimization of the clinical protocol for hip arthroplasty. In particular, after having verified the reliability of the dose estimates provided by the system, we compared the estimates of the doses delivered to 10 patients undergoing CT examination for the pre-operative planning of hip replacement with the Diagnostic Reference Level (DRL) for an osseous pelvis examination. Out of 10 patients considered, only for 3 of them the doses were lower than the DRL. Therefore, the necessity to optimize the clinical protocol emerged. This optimization was investigated using a human femur from a cadaver. Quantitative analysis and comparison of 3D reconstructions were made, after having performed manual segmentation of the femur from different CT acquisitions. Dosimetric simulations of the CT acquisitions on the femur were also made and associated to the accuracy of the 3D reconstructions, to analyse the optimal combination of CT acquisition parameters. The study showed that protocol optimization both in terms of Hausdorff distance and in terms of effective dose (ED) to the patient may be realized simply by modifying the value of the pitch in the protocol, by choosing between 0.98 and 1.37.

Misura ed elaborazione dei livelli di dose da radiazione diffusa su apparecchiature radiologiche in ambito sanitario

Obiettivo del presente lavoro consiste nell’elaborazione di curve di isodose relative ad alcuni apparecchi radiologici utilizzati in ambito medico partendo da misure effettuate sul campo in condizioni geometriche predefinite. Tali curve hanno consentito una mappatura dei campi di radiazione nei locali di impiego delle apparecchiature stesse, utili nelle valutazioni di radioprotezione degli operatori. In questo modo viene fornito al clinico uno strumento di consultazione per ottimizzare le proprie procedure da un punto di vista dell’esposizione al rischio delle radiazioni ionizzanti.

Studio degli effetti di citochine a basso dosaggio (LOW DOSE) su cellule di origine animale (3T3-L1) ed umana (hASC)

Nella sindrome metabolica l’insulino-resistenza e l’obesità rappresentano i fattori chiave nello sviluppo di tale patologia, ma il principale player risulta un’infiammazione cronica di basso grado (Chronic Low Grade Inflammation) a carico del tessuto adiposo. Lo scopo di questo progetto di ricerca è quindi stato quello di testare citochine a basso dosaggio come possibile trattamento dell’infiammazione cronica. Le citochine utilizzate (GUNA®-Interleukin 4 (IL-4), GUNA®-Interleukin 10 (IL-10), GUNA®-Melatonin, GUNA®-Melatonin+GUNA®-IL-4.) sono state fornite dall’azienda GUNA S.p.a. Poiché l’infiammazione cronica a basso grado inizia in seguito ad un aumento eccessivo del tessuto adiposo, inizialmente si è valutato l’effetto su una linea di preadipociti murini (3T3-L1). Questa prima parte dello studio ha messo in evidenza come le citochine a basso dosaggio non modificano la vitalità cellulare, anche se agiscono sull’espressione e la localizzazione di vimentina e E-caderina. Inoltre IL-4 e IL-10 sembrano avere una parziale attività inibitoria, non significativa, sull’adipogenesi ad eccezione dell’espressione dell’adiponectina che appare significativamente aumentata. In ultimo i trattamenti con IL-4 e IL-10 hanno mostrato una diminuzione del contenuto di ROS e una ridotta attività antiinfiammatoria dovuta alla diminuzione di IL-6 secreto. Un’altra popolazione cellulare principale nel tessuto adiposo è rappresentata dalle ASC (Adipose Stem Cell). Per tale motivo si è proseguito valutando l’effetto che le citochine low-dose su questo citotipo, evidenziando che il trattamento con le citochine non risulta essere tossico, anche se sembrerebbe rallentare la crescita cellulare, e determina un’inibizione del processo adipogenico. Inoltre il trattamento con IL-10 sembra stimolare le ASC a produrre fattori che inducono una maggiore vasculogenesi e le induce a produrre fattori chemiotattici che determinano una maggiore capacità di rigenerazione tissutale da parte di MSC da derma. Infine, il trattamento con IL-4 e IL-10 stimola probabilmente una minore produzione di citochine pro-infiammatorie che inducono in maniera significativa una minore mobilità di cellule MSC.

Copper filtration in pediatric digital X-ray imaging: its impact on image quality and dose.

The effect of copper (Cu) filtration on image quality and dose in different digital X-ray systems was investigated. Two computed radiography systems and one digital radiography detector were used. Three different polymethylmethacrylate blocks simulated the pediatric body. The effect of Cu filters of 0.1, 0.2, and 0.3 mm thickness on the entrance surface dose (ESD) and the corresponding effective doses (EDs) were measured at tube voltages of 60, 66, and 73 kV. Image quality was evaluated in a contrast-detail phantom with an automated analyzer software. Cu filters of 0.1, 0.2, and 0.3 mm thickness decreased the ESD by 25-32%, 32-39%, and 40-44%, respectively, the ranges depending on the respective tube voltages. There was no consistent decline in image quality due to increasing Cu filtration. The estimated ED of anterior-posterior (AP) chest projections was reduced by up to 23%. No relevant reduction in the ED was noted in AP radiographs of the abdomen and pelvis or in posterior-anterior radiographs of the chest. Cu filtration reduces the ESD, but generally does not reduce the effective dose. Cu filters can help protect radiosensitive superficial organs, such as the mammary glands in AP chest projections.

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

Early high-dose treatment: SCT results from the European High Risk Neuroblastoma Study

Aims: The HR-NBL1 Study of the European SIOP Neuroblastoma Group (SIOPEN) randomised two high dose regimens to learn about potential superiority and toxicity profiles.Patients and Methods: At interim analysis 1483 high risk neuroblastoma patients (893 males) were included since 2002 with either INSS stage 4 disease (1383 pts) above 1 year, or as infants (59 pts) and stage 2&3 of any age (145 pts) with MYCN amplification. The median age at diagnosis was 2.9 years (1 month-19.9 years) with a median follow up of 3 years. Response eligibility criteria prior randomisation after Rapid Cojec Induction (J Clin Oncol, 2010) ± 2 courses of TVD (Cancer, 2003) included complete bone marrow remission and at least partial response at skeletal sites with no more than 3, but improved mIBG positive spots and a PBSC harvest of at least 3x10E6 CD34/kgBW. The randomised regimens were BuMel [busulfan oral till 2006, 4x150mg/m² in 4 ED; or intravenous use according to body weight as licenced thereafter; melphalan 140mg/m²/day) and CEM [carboplatinum ctn. infusion (4x AUC 4.1mg/ml.min/day, etoposid ctn. infusion (4x 338mg/m²/day or [4x 200mg/m²/day]*, melphalan (3x70mg/m²/day; 3x60mg/m²/day*;*reduced dosis if GFR< 100ml/min/1.73m²). Supportive care followed institutional guidelines. VOD prophylaxis included ursadiol, but randomised patients were not eligible for the prophylactic defibrotide trial. Local control included surgery and radiotherapy of 21Gy.Results: Of 1483 patients, 584 were being randomised for the high dose question at data lock. A significant difference in event free survival (3-year EFS 49% vs. 33%, p<0.001) and overall survival (3-year OS 61% vs. 48%, p=0.003) favouring the BuMel regimen over the CEM regimen was demonstrated. The relapse/progression rate was significantly higher after CEM (0.60±0.03) than after BuMel (0.48±0.03)(p<0.001). Toxicity data had reached 80% completeness at last analysis. The severe toxicity rate up to day 100 (ICU and toxic deaths) was below 10%, but was significantly higher for CEM (p= 0.014). The acute toxic death rate was 3% for BuMel and 5% for CEM (NS). The acute HDT toxicity profile favours the BuMel regimen in spite of a total VOD incidence of 18% (grade 3:5%).Conclusions: The Peto rule of P<0.001 at interim analysis on the primary endpoint, EFS was met. Hence randomization was stopped with BuMel as recommended standard treatment in the HR-NBl1/SIOPEN trial which is still accruing for the randomised immunotherapy question.