Evaluation of penetration and scattering components in conventional pinhole SPECT: phantom studies using Monte Carlo simulation

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with 201Tl, 99mTc, 123I and 131I solutions. For the hotspot phantom, the penetration levels with respect to total counts for a 1 mm pinhole aperture were 78%, 28% and 23% for 131I, 123I and 99mTc, respectively. For a 2 mm aperture, these values were 65% for 131I, 16% for 123I and 12% for 99mTc. For all pinholes, 201Tl penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the 1 mm pinhole was 24%, 16%, 18% and 13% for 201Tl, 99mTc, 123I and 131I, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for 131I. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but 201Tl.     

Quantitative dynamic contrast-enhanced MRI for mouse models using automatic detection of the arterial input function

Dynamic contrast-enhanced MRI (DCE-MRI) is widely accepted for the evaluation of cancer. DCE-MRI, a noninvasive measurement of microvessel permeability, blood volume and blood flow, is extremely useful for understanding disease mechanisms and monitoring therapeutic responses in preclinical research. For the accurate quantification of pharmacokinetic parameters using DCE-MRI, determination of the arterial input function (AIF) from a large arterial vessel near the tumor is required. However, a manual determination of AIF in mouse MR images is often difficult because of the small spatial dimensions or the location of the tumor. In this study, we propose an algorithm for the automatic detection of AIF from mouse DCE-MR images using Kendall's coefficient of concordance. The proposed method was tested with computer simulations and then applied to tumor-bearing mice (n = 8). Results from computer simulations showed that the proposed algorithm is capable of categorizing simulated AIF signals according to their noise levels. We found that the resulting pharmacokinetic parameters computed from our method were comparable with those from the manual determination of AIF, with acceptable differences in K(trans) (5.14 ± 3.60%), v(e) (6.02 ± 3.22%), v(p) (5.10 ± 7.05%) and k(ep) (5.38 ± 4.72%). The results of the current study suggest the usefulness of an automatically defined AIF using Kendall's coefficient of concordance for quantitative DCE-MRI in mouse models for cancer evaluation.     

Noninvasive determination of the arterial input function of an anticancer drug from dynamic PET scans using the population approach

For the application of a kinetic model to PET data, it is generally necessary to obtain the arterial input function (AIF). It was the aim of the present study to introduce a method suitable for the determination of the AIF of a substance that undergoes biochemical transformation from noisy PET data: the population approach. F-18 labeled 5-fluorouracil (5-[18F]FU) was administered i.v. to eight patients suffering from liver metastases of colorectal carcinoma. Radioactivity concentrations in liver and aorta were dynamically measured with PET over 120 min. Pharmacokinetic analysis was carried out by applying a five-compartment model to individual activity-time data for the eight patients or to the mean activity-time data among the eight patients. The mean values of all parameters describing 5-FU transport and catabolism, i.e., volumes of distribution and clearances, as well as interindividual coefficients of variation (CV) were calculated according to both approaches. With our model, we were able to separate the concentration-time course of 5-FU in plasma, i.e., the AIF, from that of its major catabolite alpha-fluoro-beta-alanine (FBAL). As far as the mean parameter estimates are concerned, the differences between both approaches are not significant. For the liver data, the CV's are almost the same for both approaches. For the parameters concerning the aorta, however, there is a decrease in the CV's by using the population approach. For example, the CV of the central distribution volume of 5-FU was 30% for the individual approach and 18% for the population approach. With the population approach, it is possible to determine the AIF of drugs that undergo metabolic conversion, such as anticancer drugs, from the abdominal aorta visualized on PET images. The population approach helps to overcome noise in individual data. Since no measurements are needed in addition to the PET examination, the suggested method helps to reduce risk and pain for the patients as well as cost and thus facilitates large scale patient studies.     

Noise correlation in PET,CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data,reconstructed using FBP and OSEM

Background  

Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone.     

Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases

Background

We evaluated the repeatability of the calculation of myocardial blood flow (MBF) at rest and pharmacological stress, and calculated the coronary flow reserve (CFR) utilizing ⁸²Rb PET imaging. The aim of the research was to prove high repeatability for global MBF and CFR values and good repeatability for regional MBF and CFR values. The results will have significant impact on cardiac PET imaging in terms of making it more affordable and increasing its use.

Methods

12 normal volunteers were imaged at rest and during pharmacological stress, with 2220 MBq of ⁸²Rb each. A GE Advance PET system was used to acquire dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland). Two differential equations, describing a 2-compartmental model, were solved by numerical integration and using Levenberg-Marquardt's method for fitting data. The PMOD program defines 16 standard segments and calculates myocardial flow for each segment, as well as average septal, anterior, lateral, inferior and global flow. Repeatability was evaluated according to the method of Bland and Altman.

Results

Global rest and stress MBF, as well as global CFR, showed very good repeatability. No significant differences were found between the paired resting global MBF (0.63 ± 0.13 vs. 0.64 ± 0.13 mL/min/g; mean difference, -1.0% ± 2.6%) and the stress global MBF (1.37 ± 0.23 vs. 1.37 ± 0.24; mean difference, 0.1% ± 2.3%). Global CFR was highly reproducible (2.25 ± 0.56 vs. 2.22 ± 0.54, P = not statistically significant; mean difference, 1.3% ± 14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown good reproducibility. The average per sector repeatability coefficients for rest MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average repeatability coefficient for CFR was 0.25 (10.6%).

Conclusion

The results of the study show that software calculation of MBF and CFR with ⁸²Rb myocardial PET imaging is highly repeatable for global values and has good repeatability for regional values.     

New estimation methods that directly use the time accumulated counts in the input function in quantitative dynamic PET studies

In cardiac dynamic PET studies, the input function can be obtained directly from the reconstructed images. Therefore, there is a need to convert the time accumulated count to the time-activity curve (TAC). Conventionally, this is done by dividing the total counts in a localized region on the reconstructed image obtained during each scan frame period by its frame duration. This conversion, however, can significantly bias the estimates of rate constants of a compartmental model describing the dynamics of a PET tracer. Three new methods are formulated in this study. These new methods either use the accumulated counts in the input function directly or convert the accumulated counts to the input function more accurately. Computer simulation results show, for C-11 acetate and F-18 fluoro-2-deoxy-D-glucose (FDG), that the three new methods proposed can improve significantly the parameter estimates over the ones obtained by the conventional method.     

Fast modelling of the collimator-detector response in Monte Carlo simulation of SPECT imaging using the angular response function

Interactions of incident photons with the collimator and detector, including septal penetration, scatter and x-ray fluorescence, are significant sources of image degradation in applications of SPECT including dual isotope imaging and imaging using radioisotopes that emit high- or medium-energy photons. Modelling these interactions using full Monte Carlo (MC) simulations is computationally very demanding. We present a new method based on the use of angular response functions (ARFs). The ARF is a function of the incident photon's direction and energy and represents the probability that a photon will either interact with or pass through the collimator, and be detected at the intersection of the photon's direction vector and the detection plane in an energy window of interest. The ARFs were pre-computed using full MC simulations of point sources that include propagation through the collimator-detector system. We have implemented the ARF method for use in conjunction with the SimSET/PHG MC code to provide fast modelling of both interactions in the patient and in the collimator-detector system. Validation results in the three cases studied show that there was good agreement between the projections generated using the ARF method and those from previously validated full MC simulations, but with hundred to thousand fold reductions in simulation time.     

Factor analysis of dynamic function studies using a priori physiological information

The computation of physiological factors and factor images by factor analysis in dynamic structures using the constraints of positive factors and spatial distribution of these factors (FADS), currently used by a number of research workers, is investigated. While the positivity constraints used may be quite acceptable physically, they cannot be strictly said to have direct correlations with the underlying physiological mechanisms in a dynamic study. In principle, FADS estimates the underlying model in the absence of a priori physiological information, and therefore, it is possible that in some situations an incorrect model is extracted. A procedure called IBFADS (information-based factor analysis in dynamic structures) is described which incorporates the IM (intersection method) technique previously developed into FADS, in order to reduce the error in the estimation of the correct model. IM uses a constraint based on physiology of one of the dynamic structures in the model. A computer simulated dynamic phantom study is used to demonstrate IBFADS.     

An estimation of noise levels in HMPAO RCBF SPECT images using simulation and phantom data; comparison with results obtained from repeated normal controls

The purpose of this work was to determine noise levels in HMPAO RCBF SPECT images. Eight simulated images of a uniform sphere of activity were made at each of three different count levels. Three images of the Amersham brain phantom were obtained at each of three count levels, roughly corresponding to the simulation levels. Image reconstruction involved a modified Shepp-Logan filter with and without attenuation correction. The scaling constant in the Budinger equation was shown to vary little over the count range used with a mean value of 23 for uncorrected phantom data and 27 for corrected phantom data, corresponding to RMS noise levels of 7%-15%. The variance due to noise was calculated as a percentage of the variance obtained for 53 normal control studies following image registration and normalization. Values of 54% for uncorrected images and 67% for corrected images were obtained. For 10 normal controls a repeated study was performed. The ratio of within-subject to (single sample) between-subject variance was determined as 73% for uncorrected images and 78% for corrected images.     

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 +/- 52.0%) and lower partition coefficients (-31.6 +/- 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.     

Study of the point spread function (PSF) for 123I SPECT imaging using Monte Carlo simulation

The iterative reconstruction algorithms employed in brain single-photon emission computed tomography (SPECT) allow some quantitative parameters of the image to be improved. These algorithms require accurate modelling of the so-called point spread function (PSF). Nowadays, most in vivo neurotransmitter SPECT studies employ pharmaceuticals radiolabelled with 123I. In addition to an intense line at 159 keV, the decay scheme of this radioisotope includes some higher energy gammas which may have a non-negligible contribution to the PSF. The aim of this work is to study this contribution for two low-energy high-resolution collimator configurations, namely, the parallel and the fan beam. The transport of radiation through the material system is simulated with the Monte Carlo code PENELOPE. We have developed a main program that deals with the intricacies associated with tracking photon trajectories through the geometry of the collimator and detection systems. The simulated PSFs are partly validated with a set of experimental measurements that use the 511 keV annihilation photons emitted by a 18F source. Sensitivity and spatial resolution have been studied, showing that a significant fraction of the detection events in the energy window centred at 159 keV (up to approximately 49% for the parallel collimator) are originated by higher energy gamma rays, which contribute to the spatial profile of the PSF mostly outside the 'geometrical' region dominated by the low-energy photons. Therefore, these high-energy counts are to be considered as noise, a fact that should be taken into account when modelling PSFs for reconstruction algorithms. We also show that the fan beam collimator gives higher signal-to-noise ratios than the parallel collimator for all the source positions analysed.     

Contrasting properties of gold nanoparticles for optical coherence tomography: phantom, in vivo studies and Monte Carlo simulation

The possibility of using silica-gold nanoshells with 150 nm silica core size and 25 nm thick gold shell as contrasting agents for optical coherence tomography (OCT) is analyzed. Experiments on agar biotissue phantoms showed that the penetration of nanoshells into the phantoms increases the intensity of the optical coherence tomography (OCT) signal and the brightness of the corresponding areas of the OCT image. In vivo experiments on rabbit skin demonstrated that the application of nanoshells onto the skin provides significant contrasting of the borders between the areas containing nanoshells and those without. This effect of nanoshells on skin in vivo is manifested by the increase in intensity of the OCT signal in superficial parts of the skin, boundary contrast between superficial and deep dermis and contrast of hair follicles and glands. The presence of nanoshells in the skin was confirmed by electron microscopy. Monte Carlo simulations of OCT images confirmed the possibility of contrasting skin-layer borders and structures by the application of gold nanoshells. The Monte Carlo simulations were performed for two skin models and exhibit effects of nanoparticles similar to those obtained in the experimental part of the study, thus proving that the effects originate exactly from the presence of nanoparticles.     

Fast,reproducible measurement of the vascular input function in mice using constrained reconstruction and cardiac sampling

Dynamic contrast‐enhanced MRI is often used to assess the response to therapy in small animal models of cancer. Rigorous quantification of dynamic contrast‐enhanced MRI data using common pharmacokinetic models requires dynamic determination of the concentration of contrast in tumor tissue and in blood. Measurement of the blood concentration, or vascular input function (VIF), requires high temporal resolution and is prone to distortion as a result of flow and partial volume artifacts when measured in local blood vessels. We have developed a strategy for the robust measurement of VIF in mice that uses a constrained reconstruction algorithm to enable sampling from the left ventricle of the heart. The feasibility of the algorithm and its resistance to cardiac motion are demonstrated in vivo and through numerical simulations. VIF sampling is interleaved with slices dedicated to tumor coverage to yield a fast VIF sampling period (81 ms) that is decoupled from the temporal resolution of tumor data (3.9 s). The algorithm provides results that agree with fully encoded measurements in the slowly varying component of VIF to within a 4% root‐mean‐square signal difference. Analysis of a parametric representation of VIFs measured in a population of mice showed a significant reduction in variations observed within subjects (5%–58% over four parameters; p < 0.05) and a reduction in variations between subjects (19%–62%) when using this technique. Preliminary dynamic measurements in an orthotopic xenograft model of anaplastic thyroid cancer revealed a decrease in the variation of pharmacokinetic parameters between mice by a factor of two. Copyright © 2010 John Wiley & Sons, Ltd.     

Measurement of vascular water transport in human subjects using time‐resolved pulsed arterial spin labelling

Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non‐compartmental model, and no measurements need to be added to a common time‐resolved ASL experiment. Brownian motion of labelled spins in a potential was described by a one‐dimensional general Langevin equation as the starting point, and as a Fokker–Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi‐inversion time (multi‐TI) ASL data were acquired in 14 healthy subjects on two occasions in a test–retest design, using a pulsed ASL sequence and three‐dimensional gradient and spin echo (3D‐GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow‐up of cerebral conditions or diseases characterised by a disrupted blood–brain barrier or disturbed capillary blood flow. Copyright © 2015 John Wiley & Sons, Ltd.     

Assessment of the effect of haematocrit-dependent arterial input functions on the accuracy of pharmacokinetic parameters in dynamic contrast-enhanced MRI

The detection and prognosis of prostate cancer in its early stages are critically important. It is therefore essential to improve the existing dynamic contrast-enhanced MRI (DCE MRI) techniques commonly used for the assessment of the tumour vascular environment. The goal of this study was to describe a method for the estimation of the arterial input function (AIF) in DCE MRI by measuring R(2) * values in the femoral artery of patients with early-stage prostate cancer. The calculation of contrast agent concentrations was based on calibration curves determined in whole blood samples for a range of normal haematocrit (HCT) values (HCT = 0.35-0.525). Individual AIFs corrected for HCT were compared with individual AIFs calibrated with a mean whole blood [R(2)*-Gd-DTPA-BMA] [Gd-DTPA-BMA, gadolinium diethylenetriaminepentaacetate-bis(methylamide) (gadodiamide)] curve at an assumed HCT = 0.44, as well as a population AIF at an assumed HCT = 0.45. The area under the curve of the first-pass bolus ranged between 0.6 min mM at HCT = 0.53 and 1.3 min mM at HCT = 0.39. Significant differences in magnitude at peak contrast agent concentrations (HCT = 0.36, [Gd-DTPA-BMA](max) = 9 ± 0.4 mM; HCT = 0.46, [Gd-DTPA-BMA](max) = 4.0 ± 0.2 mM) were found. Using model-based simulations, the accuracy of the kinetic parameters estimated using individual AIFs corrected for HCT demonstrated that, for the use of individual calibration curves with HCT values differing by more than 10%, K(trans) and k(ep) values were largely underestimated (up to 60% difference for K(trans)). Moreover, blood volume estimates were severely underestimated. Estimates of kinetic parameters in early-stage prostate cancer patients demonstrated that the efflux rate constant (k(ep)) was influenced significantly by the definition of AIF. Regardless of whether an individually calibrated AIF or a population AIF (average of all individually calibrated AIFs) was used, pixel-by-pixel mapping of k(ep) and v(b) in the prostate gland appeared to be more sensitive than with the usual biexponential approach.     

Increased occurrence of asthma and allergy: critical appraisal of studies using allergic sensitization, bronchial hyper-responsiveness and lung function measurements

BACKGROUND: Many studies have reported an increase in the occurrence of asthma and respiratory allergies in recent decades, but this increase is mostly based on studies using rather subjective measurements of asthma and allergies, such as questionnaires and doctor's diagnosis. None of the reviews specifically focused on studies using more 'objective' measurements, such as sensitization (specific IgE or skin prick testing (SPT)), bronchial hyper-responsiveness (BHR) or lung function (LF). OBJECTIVE: To review articles studying a time trend of occurrence of these 'more objective' measurements. METHODS: A MEDLINE-search (1966-February 2000) was performed. The following criteria were used: population-based, using IgE, SPT, BHR or LF measurements in the same age-group at least twice, with at least 2 years between and using similar methods. RESULTS: The MEDLINE-search resulted in only 16 articles, performed in 13 populations in seven different countries. Nine articles used the same objective measurements twice in the whole population. Three of these reported a non-significant increase or decrease. The other six articles found a significant increase in at least one objective measurement and of these only three reported a consistent significant increase. CONCLUSIONS: The increase in the occurrence of reported asthma and allergy is supported by only a few articles confirming these results with 'more objective measurements'.     

Asymmetry of the discrimination function for temporal durations in human subjects

Ten human subjects were comparing durations of pairs of visual stimuli in a two-way forced-choice task. Mean durations of presented time intervals were -3 s ("short") or -6 s ("long"); the duration ratio was varied at nine levels. The Weber fractions for the short and long durations were approximately equal, -0.22. The ratio of subjective equality was almost exactly unity for the short durations, but it was significantly reduced (-0.76) for the long durations. This asymmetry of the discrimination function indicates time-dependent change of internal representations of past durations, and is well compatible with the "dual klepsydra model". Model-based estimates of the internal time representation loss rate, derived from the present data, are in a good agreement with values obtained from earlier studies on duration reproduction.     

Electron microscopic studies on human basophils from atopic and nonatopic subjects, using horse radish peroxidase labelled anti-IgE.

In previous studies, quantitative differences in cell-bound IgE on the basophils from various donors were measured by means of a quantitative immunofluorescence technique. In this study, cell-bound IgE was demonstrated on basophilic granulocytes by immunoelectron microscopy, using horse radish peroxidase labelled anti-IgE. The distribution of IgE on the basophils was studied in both atopic and nonatopic subjects. The intensity of the peroxidase staining on the basophils varied and appeared to correlate with the amount of cell-bound IgE, as estimated by quantitative immunofluorescence.