The potential of tumour tracking for active spot-scanned proton therapy was assessed. Using a 4D-dose calculation and simulated target motion, a tumour tracking algorithm has been implemented and ...applied to a simple target volume in both homogenous and heterogeneous in silico phantoms. For tracking and retracking (a hybrid solution combining tumour tracking and rescanning), three tracking modes were analysed: 'no tracking' (uncorrected irradiation of a moving target), 'perfect tracking' (no time delays and exact knowledge of target position) and 'imperfect tracking' (simulated time delays or position prediction errors). For all plans, dose homogeneity in the target volume was assessed as the difference between D5 and D95 in the CTV. For the homogeneous phantom, perfect tracking could retrieve nominal dose homogeneity for all motion phases and amplitudes while severe deterioration of treatment outcomes was found for imperfect tracking. The use of retracking reduced the sensitivity to position errors significantly in the homogeneous phantom. In the heterogeneous phantoms (simulated rib proximal to target), the nominal dose homogeneity could not be obtained with perfect tracking. Adjustments in pencil beam positions could cause pencil beams to deform under the influence of the bone, resulting in loss of dose homogeneity. As retracking was not capable of reducing these effects, rescanning provided the best treatment outcomes for moving heterogeneous targets in this study.
Today, small-animal multi-pinhole single photon emission computed tomography (SPECT) can reach sub-half-millimeter image resolution. Recently we have shown that dedicated multi-pinhole collimators ...can also image PET tracers at sub-mm level. Simulations play a vital role in the design and optimization of such collimators. Here we propose and validate an efficient simulator that models the whole imaging chain from emitted positron to detector signal. This analytical simulator for pinhole positron emission computed tomography (ASPECT) combines analytical models for pinhole and detector response with Monte Carlo (MC)-generated kernels for positron range. Accuracy of ASPECT was validated by means of a MC simulator (MCS) that uses a kernel-based step for detector response with an angle-dependent detector kernel based on experiments. Digital phantom simulations with ASPECT and MCS converge to almost identical images. However, ASPECT converges to an equal image noise level three to four orders of magnitude faster than MCS. We conclude that ASPECT could serve as a practical tool in collimator design and iterative image reconstruction for novel multi-pinhole PET.
Sesquiterpene lactones are organic compounds derived mainly from plants that exhibit anti-inflammatory and antitumor activities being one of the key mechanism of action of NF-kB pathway and synthesis ...of cytokines such as IL-1 and TNF- α.
The overall objective of the present study was to evaluate the anti-inflammatory action of a sesquiterpene lactone diacethylpiptocarphol (DPC) from Vernonia scorpioides (Lam.) Pers. and parthenolide (PTH) in Balb-c mice with DSS-induced colitis.
The anti-inflammatory effects of Intraperitonial administration of DPC (5 mg/kg/day) were evaluated in Balb/c mice with DSS-induced colitis, and further the body weight measurement, TNF-α and TGF-β level was determined.
After intraperitoneal treatment for one week, DSS-induced colitis was significantly reduced in mice treated with either of both sesquiterpenes lactones, as witnessed by reduced cellular infiltration, tissue damage, TNF-α production, and enhanced production of TGF-β.
Sesquiterpene lactone DPC, isolated from Vernonia scorpioides showed anti-inflammatory activity, in this experimental model of colitis the sesquiterpene lactones DPC and PTH exhibit equal anti-inflammatory activity.
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A two-dimensional position sensitive dosimetry system based on a scintillating gas detector has been developed for pre-treatment verification of dose distributions in hadron therapy. The dosimetry ...system consists of a chamber filled with an Ar/CF4 scintillating gas mixture, inside which two cascaded gas electron multipliers (GEMs) are mounted. A GEM is a thin kapton foil with copper cladding structured with a regular pattern of sub-mm holes. The primary electrons, created in the detector's sensitive volume by the incoming beam, drift in an electric field towards the GEMs and undergo gas multiplication in the GEM holes. During this process, photons are emitted by the excited Ar/CF4 gas molecules and detected by a mirror-lens-CCD camera system. Since the amount of emitted light is proportional to the dose deposited in the sensitive volume of the detector by the incoming beam, the intensity distribution of the measured light spot is proportional to the 2D hadron dose distribution. For a measurement of a 3D dose distribution, the scintillating gas detector is mounted at the beam exit side of a water-bellows phantom, whose thickness can be varied in steps. In this work, the energy dependence of the output signal of the scintillating gas detector has been verified in a 250 MeV/u clinical 12C ion beam by means of a depth-dose curve measurement. The underestimation of the measured signal at the Bragg peak depth is only 9% with respect to an air-filled ionization chamber. This is much smaller than the underestimation found for a scintillating Gd2O2S:Tb ('Lanex') screen under the same measurement conditions (43%). Consequently, the scintillating gas detector is a promising device for verifying dose distributions in high LET beams, for example to check hadron therapy treatment plans which comprise beams with different energies.
High spatial resolution γ-imaging can be achieved with scintillator readout by low-noise, fast, electron-multiplying charge-coupled devices (EMCCDs). Previously we have shown that false-positive ...events due to EMCCD noise can be rejected by using the sum signal from silicon photomultipliers (SiPMs) mounted on the sides of the scintillator. Here we launch a next generation hybrid CCD-SiPM camera that utilizes the individual SiPM signals and maximum likelihood estimation (MLE) pre-localization of events to discriminate between true and false events in CCD frames. In addition, SiPM signals are utilized for improved energy discrimination. The performance of this hybrid detector was tested for a continuous CsI:Tl crystal at 140 keV. With a pre-localization accuracy of 1.06 mm (full-width-at-half-maximum) attained with MLE the signal-to-background ratio (SBR) was improved by a factor of 5.9, 4.0 or 2.2 compared to the EMCCD-only readout, at the cost of rejecting, respectively, 47%, 9% or 4% of the events. Combining the pre-localization and SiPM energy estimation improved the energy resolution from 50% to (19 ± 3)% while maintaining the spatial resolution at 180 µm.
A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for pre-treatment verification of dose distributions in particle therapy. The dosimetry ...system consists of a chamber filled with an Ar/CF(4) scintillating gas mixture, inside which two gas electron multiplier (GEM) structures are mounted (Seravalli et al 2008b Med. Phys. Biol. 53 4651-65). Photons emitted by the excited Ar/CF(4) gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD camera system. The intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the characterization of the scintillating GEM detector in terms of those properties that are of particular importance in relative dose measurements, e.g. response reproducibility, dose dependence, dose rate dependence, spatial and time response, field size dependence, response uniformity. The experiments were performed in a 150 MeV proton beam. We found that the detector response is very stable for measurements performed in succession (sigma = 0.6%) and its response reproducibility over 2 days is about 5%. The detector response was found to be linear with the dose in the range 0.05-19 Gy. No dose rate effects were observed between 1 and 16 Gy min(-1) at the shallow depth of a water phantom and 2 and 38 Gy min(-1) at the Bragg peak depth. No field size effects were observed in the range 120-3850 mm(2). A signal rise and fall time of 2 micros was recorded and a spatial response of <or=1 mm was measured.
Electron-multiplying charge-coupled devices (EMCCDs) coupled to scintillation crystals can be used for high-resolution imaging of gamma rays in scintillation counting mode. However, the detection of ...false events as a result of EMCCD noise deteriorates the spatial and energy resolution of these gamma cameras and creates a detrimental background in the reconstructed image. In order to improve the performance of an EMCCD-based gamma camera with a monolithic scintillation crystal, arrays of silicon photon-multipliers (SiPMs) can be mounted on the sides of the crystal to detect escaping scintillation photons, which are otherwise neglected. This will provide a priori knowledge about the correct number and energies of gamma interactions that are to be detected in each CCD frame. This information can be used as an additional detection criterion, e.g. for the rejection of otherwise falsely detected events. The method was tested using a gamma camera based on a back-illuminated EMCCD, coupled to a 3 mm thick continuous CsI:Tl crystal. Twelve SiPMs have been mounted on the sides of the CsI:Tl crystal. When the information of the SiPMs is used to select scintillation events in the EMCCD image, the background level for (99m)Tc is reduced by a factor of 2. Furthermore, the SiPMs enable detection of (125)I scintillations. A hybrid SiPM-/EMCCD-based gamma camera thus offers great potential for applications such as in vivo imaging of gamma emitters.
We have developed an 80-channel readout system for gamma cameras which acquires PMT signals and stores them in list-mode format on a computer. The system combines low noise and a large signal range ...to handle PMT signals from a wide range of SPECT and PET tracers simultaneously (27 to 511 keV). All channels of the read-out system have a gated integrator to determine the charge per event. Each 16 channels are multiplexed to a 12-bit 40 MS/s pipelined ADCs. Using multiplexing only 5 ADCs are needed which share a commercial USB 2.0 interface board to send the event data to the computer. The signal input range is up to 120 pC with a noise level of 57 fC. The integral non-linearity is better than 1% for all channels, while the channel response has a gain non-uniformity less than 2.4% for the different channels. The crosstalk between channels is better than 64 dB. The dead time is 2.5 μs, including a 760 ns integration period. The system can handle a sustained event rate of 155 kcps on the USB 2.0 bus. Connected to a clinical gamma camera we show that the isotopes 125 I (27-35 keV), 99m Tc (140.5 keV) and 22 Na (511 keV) can all be imaged without electronic adjustments thus enabling, for instance, simultaneous pinhole PET/SPECT. With this PMT list-mode acquisition system, advanced offline event positioning and energy estimation with e.g. maximum likelihood methods are enabled.
Charge Coupled Devices (CCDs) optically coupled to scintillation crystals can be used to construct high resolution gamma cameras. Previously, several groups have reported intrinsic detector spatial ...resolutions below 100 microns. When the CCD images can be read out fast enough, the energy and interaction position of individual gamma quanta can be estimated by a real-time image analysis of the scintillation light flashes. The Electron-Multiplying CCD (EMCCD) is well-suited for fast read out, since even at high frame rates it has extremely low readout noise. However, due to the often very low light levels present in scintillation gamma cameras, further reduction of noise is desirable. Here, the EMCCD is optically coupled to a 1000-mum-thick columnar CsI(Tl) crystal for Tc-99m and 1-125 imaging. We investigate noise reduction through summing of signals in pixels before the gain register and readout circuit of the EMCCD ("pixel binning"). We compare the energy and spatial resolution, photopeak efficiency (PE) and signal-to-noise ratio (SNR) of an EMCCD-based gamma camera for the case of binning vs. non-binning. When pixels were read out simultaneously in groups of 4 the spatial resolution is slightly worse in the direction of binning, but the number of false-positive counts resulting from background noise for 1-125 was reduced by 74% compared to the no binning case. We conclude that the use of charge binning when reading out EMCCDs may significantly improve the energy spectra and noise properties of CCD-based high-resolution gamma cameras.
We report on the first observation of time-reversal symmetry violation through a comparison of the probabilities of
K
0
transforming into K
0 and K
0 into
K
0
as a function of the neutral-kaon ...eigentime
t. The comparison is based on the analysis of the neutral-kaon semileptonic decays recorded in the CPLEAR experiment. There, the strangeness of the neutral kaon at time
t=0 was tagged by the kaon charge in the reaction
p
p
→
K
±π
∓
K
0
(
K
0
)
at rest, whereas the strangeness of the kaon at the decay time
t=
τ was tagged by the lepton charge in the final state. An average decay-rate asymmetry
〈
R(
K
0
t=0→
e
+
π
−
ν
t=τ)−R(
K
0
t=0→
e
−
π
+
ν
t=τ)
R(
K
0
t=0→
e
+
π
−
ν
t=τ)+R(
K
0
t=0→
e
−
π
+
ν
t=τ)
〉=(6.6±1.3
stat
±1.0
syst
)×10
−3
was measured over the interval
1
τ
S
<τ<20
τ
S
, thus leading to evidence for time-reversal non-invariance.