A novel anthropomorphic breathing phantom with a pneumatic MR-safe actuator for tissue deformation studies during MRI and radiotherapy.

A novel MR-safe anthropomorphic torso phantom with an MR-conditional pneumatic respiration system and inflatable lungs for tissue deformation studies is proposed. The phantom consists of a pair of lungs made from sponges encased in flexible polyurethane. The lung phantom also contains a set of silicone tubes of various diameters to mimic the larger vasculature and airways of the lungs. The lungs are surrounded by a plastic ribcage and immersed in a gelatine hydrogel within a flexible polyurethane skin. A plastic pneumatic pump system was constructed to inflate and deflate the lungs. A fibre optic rotary encoder was constructed to determine the volume of displaced air in the lungs. The pneumatic pump and rotary encoder were constructed of plastic materials to allow placement within the bore of the MR scanner with minimal interaction with the magnetic field. Breath-gated scans and rapid imaging scans (2.5 s per image) were taken of the phantom in the stationary state and during inflation/deflation, and with Cartesian and BLADE k-space sampling. It was found that BLADE shows the least motion artifacts during breathing. This phantom and respiration system shows potential for quality assurance of MRI incorporating breathing corrections and for radiotherapy applications in tracking a moving target.

Radiation Dosimetry by Use of Radiosensitive Hydrogels and Polymers: Mechanisms, State-of-the-Art and Perspective from 3D to 4D.

Gel dosimetry was developed in the 1990s in response to a growing need for methods to validate the radiation dose distribution delivered to cancer patients receiving high-precision radiotherapy. Three different classes of gel dosimeters were developed and extensively studied. The first class of gel dosimeters is the Fricke gel dosimeters, which consist of a hydrogel with dissolved ferrous ions that oxidize upon exposure to ionizing radiation. The oxidation results in a change in the nuclear magnetic resonance (NMR) relaxation, which makes it possible to read out Fricke gel dosimeters by use of quantitative magnetic resonance imaging (MRI). The radiation-induced oxidation in Fricke gel dosimeters can also be visualized by adding an indicator such as xylenol orange. The second class of gel dosimeters is the radiochromic gel dosimeters, which also exhibit a color change upon irradiation but do not use a metal ion. These radiochromic gel dosimeters do not demonstrate a significant radiation-induced change in NMR properties. The third class is the polymer gel dosimeters, which contain vinyl monomers that polymerize upon irradiation. Polymer gel dosimeters are predominantly read out by quantitative MRI or X-ray CT. The accuracy of the dosimeters depends on both the physico-chemical properties of the gel dosimeters and on the readout technique. Many different gel formulations have been proposed and discussed in the scientific literature in the last three decades, and scanning methods have been optimized to achieve an acceptable accuracy for clinical dosimetry. More recently, with the introduction of the MR-Linac, which combines an MRI-scanner and a clinical linear accelerator in one, it was shown possible to acquire dose maps during radiation, but new challenges arise.

A multi-modality medical imaging head and neck phantom: Part 2. Medical imaging.

The head and neck phantom discussed in an accompanying paper (part 1), is imaged with MRI, X-ray CT, PET and ultrasound. MRI scans show a distinct image contrast between the brain compartment and other anatomical regions of the head. The silicone matrix that was used to create a porous brain compartment has a relatively high proton density and a spin-spin relaxation time (T2) that is long enough to provide an MRI signal. While the longitudinal magnetization was found to recover according to a mono-exponential, a bi-exponential decay was observed for the transverse relaxation with a slow T2 relaxation component corresponding to the perfusate and a fast T2 relaxation component corresponding to the silicone. The fraction of the slow T2 relaxation component increases upon perfusion. A dynamic contrast enhanced (DCE) MRI experiment is conducted in which the injection rate of the contrast agent is varied. Parametric DCE maps are created and reveal regional differences in contrast agent kinetics as a result of differences in porosity. The skull, vertebra and the brain compartment are clearly visible on X-ray CT. Dynamic PET scanning has been performed while the carotic arterial input function is monitored by use of a Geiger-Müller counter. Similar regions of perfusion are found in the PET study as in the DCE MRI study. By doping the perfusate with a lipid micelle emulsion, the phantom is applicable for carotic Doppler ultrasound demonstration and validation.

Tuneable manganese oxide nanoparticle based theranostic agents for potential diagnosis and drug delivery.

Among various magnetic nanoparticles, manganese oxide nanoparticles are considered as established T 1 magnetic resonance imaging (MRI) contrast agents for preclinical research. The implications of their degradation properties and use as therapeutic carriers in drug delivery systems have not been explored. In addition, how the chemical composition and size of manganese oxide nanoparticles, as well as the surrounding environment, influence their degradation and MRI contrast properties (T 1 vs. T 2) have not been studied in great detail. A fundamental understanding of their characteristic properties, such as degradation, is highly desirable for developing simultaneous diagnosis and therapeutic solutions. Here, we demonstrate how the precursor type and reaction environment affect the size and chemical composition of manganese oxide nanoparticles and evaluate their influence on the nanoparticle degradability and release of the drug l-3,4-dihydroxyphenylalanine (l-dopa). The results show that the degradation rate (and the associated release of drug l-dopa molecules) of manganese oxide nanoparticles depends on their size, composition and the surrounding environment (aqueous or biometric fluid). The dependence of MRI relaxivities of manganese oxide nanoparticles on the size, chemical composition and nanoparticle degradation in water is also established. A preliminary cell viability study reveals the cytocompatible properties of l-dopa functionalized manganese oxide nanoparticles. Overall, this work provides new insights into smartly designed manganese oxide nanoparticles with multitasking capabilities to target bioimaging and therapeutic applications.

The effect of experimental low back pain on lumbar muscle activity in people with a history of clinical low back pain: a muscle functional MRI study.

In people with a history of low back pain (LBP), structural and functional alterations have been observed at several peripheral and central levels of the sensorimotor pathway. These existing alterations might interact with the way the sensorimotor system responds to pain. We examined this assumption by evaluating the lumbar motor responses to experimental nociceptive input of 15 participants during remission of unilateral recurrent LBP. Quantitative T2 images (muscle functional MRI) were taken bilaterally of multifidus, erector spinae, and psoas at several segmental levels (L3 upper and L4 upper and lower endplate) and during several conditions: 1) at rest, 2) upon trunk-extension exercise without pain, and 3) upon trunk-extension exercise with experimental induced pain at the clinical pain-side (1.5-ml intramuscular hypertonic saline injections in erector spinae). Following experimental pain induction, muscle activity levels similarly reduced for all three muscles, on both painful and nonpainful sides, and at multiple segmental levels (P = 0.038). Pain intensity and localization from experimental LBP were similar as during recalled clinical LBP episodes. In conclusion, unilateral and unisegmental experimental LBP exerts a generalized and widespread decrease in lumbar muscle activity during remission of recurrent LBP. This muscle response is consistent with previous observed patterns in healthy people subjected to the same experimental pain paradigm. It is striking that similar inhibitory patterns in response to pain could be observed, despite the presence of preexisting alterations in the lumbar musculature during remission of recurrent LBP. These results suggest that motor output can modify along the course of recurrent LBP.

Evaluation of radiochromic gel dosimetry and polymer gel dosimetry in a clinical dose verification.

A quantitative comparison of two full three-dimensional (3D) gel dosimetry techniques was assessed in a clinical setting: radiochromic gel dosimetry with an in-house developed optical laser CT scanner and polymer gel dosimetry with magnetic resonance imaging (MRI). To benchmark both gel dosimeters, they were exposed to a 6 MV photon beam and the depth dose was compared against a diamond detector measurement that served as golden standard. Both gel dosimeters were found accurate within 4% accuracy. In the 3D dose matrix of the radiochromic gel, hotspot dose deviations up to 8% were observed which are attributed to the fabrication procedure. The polymer gel readout was shown to be sensitive to B0 field and B1 field non-uniformities as well as temperature variations during scanning. The performance of the two gel dosimeters was also evaluated for a brain tumour IMRT treatment. Both gel measured dose distributions were compared against treatment planning system predicted dose maps which were validated independently with ion chamber measurements and portal dosimetry. In the radiochromic gel measurement, two sources of deviations could be identified. Firstly, the dose in a cluster of voxels near the edge of the phantom deviated from the planned dose. Secondly, the presence of dose hotspots in the order of 10% related to inhomogeneities in the gel limit the clinical acceptance of this dosimetry technique. Based on the results of the micelle gel dosimeter prototype presented here, chemical optimization will be subject of future work. Polymer gel dosimetry is capable of measuring the absolute dose in the whole 3D volume within 5% accuracy. A temperature stabilization technique is incorporated to increase the accuracy during short measurements, however keeping the temperature stable during long measurement times in both calibration phantoms and the volumetric phantom is more challenging. The sensitivity of MRI readout to minimal temperature fluctuations is demonstrated which proves the need for adequate compensation strategies.

On the validity of 3D polymer gel dosimetry: I. reproducibility study.

The intra- and inter-batch accuracy and precision of MRI (polyacrylamide gelatin gel fabricated at atmospheric conditions) polymer gel dosimeters are assessed in full 3D. In the intra-batch study, eight spherical flasks were filled with the same polymer gel along with a set of test tubes that served as calibration phantoms. In the inter-batch study, the eight spherical flasks were filled with different batches of gel. For each spherical phantom, a separate set of calibration phantoms was used. The spherical phantoms were irradiated using a three-field coplanar beam configuration in a very reproducible manner. The calibration phantoms were irradiated to known doses to obtain a dose-R2 calibration plot which was applied on the corresponding R2 maps of all spherical phantoms on an individual basis. The intra-batch study showed high dosimetric precision (3.1%) notwithstanding poor accuracy (mean dose discrepancies up to 13.0%). In the inter-batch study, a similar dosimetric precision (4.3%) and accuracy (mean dose discrepancies up to 13.7%) were found. The poor dosimetric accuracy was attributed to a systematic fault that was related to the calibration method. Therefore, the dose maps were renormalized using an independent ion chamber dose measurement. It is illustrated that with this renormalization, excellent agreement between the gel measured and TPS calculated 3D dose maps is achievable: 97% and 99% of the pixels meet the 3%/3 mm criteria for the intra- and inter-batch experiments, respectively. However renormalization will result in significant dose deviations inside a realistically sized anthropomorphic phantom as will be shown in a concurrent paper.

On the validity of 3D polymer gel dosimetry: II. physico-chemical effects.

This study quantifies some major physico-chemical factors that influence the validity of MRI (PAGAT) polymer gel dosimetry: temperature history (pre-, during and post-irradiation), oxygen exposure (post-irradiation) and volumetric effects (experiment with phantom in which a small test tube is inserted). Present results confirm the effects of thermal history prior to irradiation. By exposing a polymer gel sample to a linear temperature gradient of ∼2.8 °C cm⁻¹ and following the dose deviation as a function of post-irradiation time new insights into temporal variations were added. A clear influence of the temperature treatment on the measured dose distribution is seen during the first hours post-irradiation (resulting in dose deviations up to 12%). This effect diminishes to 5% after 54 h post-irradiation. Imposing a temperature offset (maximum 6 °C for 3 h) during and following irradiation on a series of calibration phantoms results in only a small dose deviation of maximum 4%. Surprisingly, oxygen diffusing in a gel dosimeter up to 48 h post-irradiation was shown to have no effect. Volumetric effects were studied by comparing the dose distribution in a homogeneous phantom compared to the dose distribution in a phantom in which a small test tube was inserted. This study showed that the dose measured inside the test tube was closer to the ion chamber measurement in comparison to the reference phantom without test tube by almost 7%. It is demonstrated that physico-chemical effects are not the major causes for the dose discrepancies encountered in the reproducibility study discussed in the concurrent paper (Vandecasteele and De Deene 2013a Phys. Med. Biol. 58 19-42). However, it is concluded that these physico-chemical effects are important factors that should be addressed to further improve the dosimetric accuracy of 3D MRI polymer gel dosimetry.

On the validity of 3D polymer gel dosimetry: III. MRI-related error sources.

In MRI (PAGAT) polymer gel dosimetry, there exists some controversy on the validity of 3D dose verifications of clinical treatments. The relative contribution of important sources of uncertainty in MR scanning to the overall accuracy and precision of 3D MRI polymer gel dosimetry is quantified in this study. The performance in terms of signal-to-noise and imaging artefacts was evaluated on three different MR scanners (two 1.5 T and a 3 T scanner). These include: (1) B0-field inhomogeneity, (2) B1-field inhomogeneity, (3) dielectric effects (losses and standing waves) and (4) temperature inhomogeneity during scanning. B0-field inhomogeneities that amount to maximum 5 ppm result in dose deviations of up to 4.3% and deformations of up to 5 pixels. Compensation methods are proposed. B1-field inhomogeneities were found to induce R2 variations in large anthropomorphic phantoms both at 1.5 and 3 T. At 1.5 T these effects are mainly caused by the coil geometry resulting in dose deviations of up to 25%. After the correction of the R2 maps using a heuristic flip angle-R2 relation, these dose deviations are reduced to 2.4%. At 3 T, the dielectric properties of the gel phantoms are shown to strongly influence B1-field homogeneity, hence R2 homogeneity, especially of large anthropomorphic phantoms. The low electrical conductivity of polymer gel dosimeters induces standing wave patterns resulting in dose deviations up to 50%. Increasing the conductivity of the gel by adding NaCl reduces the dose deviation to 25% after which the post-processing is successful in reducing the remaining inhomogeneities caused by the coil geometry to within 2.4%. The measurements are supported by computational modelling of the B1-field. Finally, temperature fluctuations of 1 °C frequently encountered in clinical MRI scanners result in dose deviations up to 15%. It is illustrated that with adequate temperature stabilization, the dose uncertainty is reduced to within 2.58%.

Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: a 1H-MRS study.

OBJECTIVE: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). MATERIALS AND METHODS: Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18-76 years, mean±SD, 48.4±16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. RESULTS: Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P<0.05 and P≤0.001, respectively), and in the HC (P<0.01 for both). An increased tCr/H2O was only observed in the PCC (P<0.01). Following absolute quantification based on the internal water signal, significantly increased concentrations of Ins and tCr in the PCC confirmed the relative findings (P<0.01 for both). CONCLUSION: Age-related increases of tCr and Ins are found in the PCC, whereas this holds only true for Ins in the HC, indicating possible gliosis in the ageing brain. No age-dependent NAA decreases were observed in the PCC nor the HC. The 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

First order correction for T2*-relaxation in determining contrast agent concentration from spoiled gradient echo pulse sequence signal intensity.

PURPOSE: To investigate the accuracy of a method neglecting T(2)*-relaxation, for the conversion of spoiled gradient echo pulse sequence signal intensity to contrast agent (CA) concentration, in dynamic contrast enhanced MRI studies. In addition a new closed form conversion expression is proposed that accounts for a first order approximation of T(2)*-relaxation. MATERIALS AND METHODS: The accuracy of both conversion methods is compared theoretically by means of simulations for four pulse sequences from literature. Both methods are tested in vivo against the numerical conversion method for measuring the arterial input function in mice. RESULTS: Simulations show that the T(2)*-neglecting method underestimates typical tissue CA concentrations (0 mM to 2 mM) up to 6%, while the errors for arterial concentrations (0 mM to 10 mM) range up to 43%. The results from our first order method are numerically indistinguishable from the simulation input values in tumor tissue, while for arterial concentrations the error is reduced up to a factor 10. In vivo, peak Gd-DOTA concentration is underestimated up to 14% with the T(2)*-neglecting method and up to 0.9% with our first order method. CONCLUSION: Our conversion method reduces the underestimation of CA concentration severely in a broad physiological concentration range and is easy to perform in any clinical setting.

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study.

Proton magnetic resonance spectroscopy ((1)H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS ((31)P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional (1)H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1-0.2 µmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.

31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients.

BACKGROUND: Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy ((31)P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by (31)P-MRS at 3 tesla. METHODS: Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls. RESULTS: A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([P(i)]) and magnesium ([Mg(2+)]) concentrations were not significantly different between MwoA patients and controls. CONCLUSIONS: The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.

Precision analysis of kinetic modelling estimates in dynamic contrast enhanced MRI.

OBJECT: Dynamic contrast enhanced MRI and pharmacokinetic modelling provide a powerful tool for tumour diagnosis and treatment evaluation. However, several studies show low reproducibility of the technique and poor precision of the transendothelial transfer constant K (trans). This work proposes a theoretical framework describing how finite signal-noise-ratio (SNR) in the MR images is propagated throughout the measurement protocol to uncertainty on the kinetic parameter estimates. MATERIALS AND METHODS: After deriving a distribution for the contrast agent concentration, a maximum likelihood estimator (MLM) is proposed that exhibits Cramer-Rao lower bounds (CRLB). An analytical expression is derived for the CRLB that can be used to determine confidence intervals for kinetic parameters and to investigate the influence of protocol parameters as scan time and temporal resolution on K (trans)-precision. RESULTS: K (trans)-uncertainty can be reduced up to 30% by using MLM in comparison with least square estimator. K (trans)-precision is proportional to the SNR and depends strongly on the kinetic parameter values themselves. Minimal scan time and temporal resolution were found to be 15 min and 15 s, respectively, for Gd-DTPA. Temporal resolution should be enhanced by decreasing the NEX parameter (NEX ≤ 1). CONCLUSION: CRLB provide a golden standard to construct 95% confidence intervals, which can be used to perform protocol optimization and to test the statistical significance of K (trans)-changes in treatment evaluation.

(1)H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique.

OBJECTIVE: Several studies have demonstrated differences in migraine patients when performing (1)H-MRS; however, no studies have performed (1)H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this (1)H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification. MATERIALS AND METHODS: (1)H-MRS was performed in 22 MwoA patients and 25 control subjects. Absolute quantification was based on the phantom replacement technique. Corrections were made for T (1) and T (2) relaxation effects, CSF content, coil loading and temperature. The method was validated by phantom measurements and in vivo measurements in the occipital visual cortex. RESULTS: After calibration of the quantification procedure and the implementation of the required correction factors, measured absolute concentrations in the visual cortex of MwoA patients showed no significant differences compared to controls, in contrast to relative results obtained in earlier studies. CONCLUSION: In this study, we demonstrate the implementation of quantitative in vivo (1)H-MRS spectroscopy in migraine patients. Despite rigorous quantification, no spectroscopic abnormalities could be found in patients with migraine without aura.

An oxygen-consuming phantom simulating perfused tissue to explore oxygen dynamics and (19)F MRI oximetry.

OBJECTIVE: This study presents a reproducible phantom which mimics oxygen-consuming tissue and can be used for the validation of (19)F MRI oximetry. MATERIALS AND METHODS: The phantom consists of a haemodialysis filter of which the outer compartment is filled with a gelatin matrix containing viable yeast cells. Perfluorocarbon emulsions can be added to the gelatin matrix to simulate sequestered perfluorocarbons. A blood-substituting perfluorocarbon fluid is pumped through the lumen of the fibres in the filter. (19)F relaxometry MRI is performed with a fast 2D Look-Locker imaging sequence on a clinical 3T scanner. RESULTS: Acute and perfusion-related hypoxia were simulated and imaged spatially and temporally using the phantom. CONCLUSIONS: The presented experimental setup can be used to simulate oxygen consumption by somatic cells in vivo and for validating computational biophysical models of hypoxia, as measured with (19)F MRI oximetry.

MRI-based attenuation correction for PET/MRI using ultrashort echo time sequences.

UNLABELLED: One of the challenges in PET/MRI is the derivation of an attenuation map to correct the PET image for attenuation. Different methods have been suggested for deriving the attenuation map from an MR image. Because the low signal intensity of cortical bone on images acquired with conventional MRI sequences makes it difficult to detect this tissue type, these methods rely on some sort of anatomic precondition to predict the attenuation map, raising the question of whether these methods will be usable in the clinic when patients may exhibit anatomic abnormalities. METHODS: We propose the use of the transverse relaxation rate, derived from images acquired with an ultrashort echo time sequence to classify the voxels into 1 of 3 tissue classes (bone, soft tissue, or air), without making any assumptions on patient anatomy. Each voxel is assigned a linear attenuation coefficient corresponding to its tissue class. A reference CT scan is used to determine the voxel-by-voxel accuracy of the proposed method. The overall accuracy of the MRI-based attenuation correction is evaluated using a method that takes into account the nonlocal effects of attenuation correction. RESULTS: As a proof of concept, the head of a pig was used as a phantom for imaging. The new method yielded a correct tissue classification in 90% of the voxels. Five human brain PET/CT and MRI datasets were also processed, yielding slightly worse voxel-by-voxel performance, compared to a CT-derived attenuation map. The PET datasets were reconstructed using the segmented MRI attenuation map derived with the new method, and the resulting images were compared with segmented CT-based attenuation correction. An average error of around 5% was found in the brain. CONCLUSION: The feasibility of using the transverse relaxation rate map derived from ultrashort echo time MR images for the estimation of the attenuation map was shown on phantom and clinical brain data. The results indicate that the new method, compared with CT-based attenuation correction, yields clinically acceptable errors. The proposed method does not make any assumptions about patient anatomy and could therefore also be used in cases in which anatomic abnormalities are present.

Modelling optical scattering artefacts for varying pathlength in a gel dosimeter phantom.

A gelatin phantom containing an optically scattering funnel-shaped region of elevated optical density (OD) was used to examine light-scattering-induced artefacts in a cone-beam optical CT scanner used for gel dosimetry. To simulate polymer gel dosimeters, the opacity was introduced by adding a colloidal scatterer to the gelatin. Scatter results in an underestimate of OD (hence dose). In line profiles of OD taken from 3D reconstructions of the funnel, those profiles with a long pathlength through high OD regions exhibited a 'dishing' (or 'cupping') artefact, while those of short pathlength exhibited the opposite effect-'doming'. These phenomena are accounted for by a model that includes the effect of stray, scattered light.

The design of anisotropic diffusion phantoms for the validation of diffusion weighted magnetic resonance imaging.

Diffusion weighted magnetic resonance imaging offers a non-invasive tool to explore the three-dimensional structure of brain white matter in clinical practice. Anisotropic diffusion hardware phantoms are useful for the quantitative validation of this technique. This study provides guidelines on how to manufacture anisotropic fibre phantoms in a reproducible way and which fibre material to choose to obtain a good quality of the diffusion weighted images. Several fibre materials are compared regarding their effect on the diffusion MR measurements of the water molecules inside the phantoms. The diffusion anisotropy influencing material properties are the fibre density and diameter, while the fibre surface relaxivity and magnetic susceptibility determine the signal-to-noise ratio. The effect on the T(2)-relaxation time of water in the phantoms has been modelled and the diffusion behaviour inside the fibre phantoms has been quantitatively evaluated using Monte Carlo random walk simulations.

Simulation and experimental verification of the diffusion in an anisotropic fiber phantom.

Diffusion weighted magnetic resonance imaging enables the visualization of fibrous tissues such as brain white matter. The validation of this non-invasive technique requires phantoms with a well-known structure and diffusion behavior. This paper presents anisotropic diffusion phantoms consisting of parallel fibers. The diffusion properties of the fiber phantoms are measured using diffusion weighted magnetic resonance imaging and bulk NMR measurements. To enable quantitative evaluation of the measurements, the diffusion in the interstitial space between fibers is modeled using Monte Carlo simulations of random walkers. The time-dependent apparent diffusion coefficient and kurtosis, quantifying the deviation from a Gaussian diffusion profile, are simulated in 3D geometries of parallel fibers with varying packing geometries and packing densities. The simulated diffusion coefficients are compared to the theory of diffusion in porous media, showing a good agreement. Based on the correspondence between simulations and experimental measurements, the fiber phantoms are shown to be useful for the quantitative validation of diffusion imaging on clinical MRI-scanners.