Quantitative MRI: Defining repeatability,reproducibility and accuracy for prostate cancer imaging biomarker development

IntroductionQuantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response.Materials and methodsADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms.ResultsOverall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between −8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners.ConclusionRepeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.     

Reproducibility and biases in high field brain diffusion MRI: An evaluation of acquisition and analysis variables

Diffusion tensor imaging (DTI) of in-vivo human brain provides insights into white matter anatomical connectivity, but little is known about measurement difference biases and reliability of data obtained with last generation high field scanners (> 3 T) as function of MRI acquisition and analyses variables. Here we assess the impact of acquisition (voxel size: 1.8 × 1.8 × 1.8, 2 × 2 × 2 and 2.5 × 2.5 × 2.5 mm³, b-value: 700, 1000 and 1300 s/mm²) and analysis variables (within-session averaging and co-registration methods) on biases and test-retest reproducibility of some common tensor derived quantities like fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity in a group of healthy subjects at 4 T in three regions: arcuate fasciculus, corpus callosum and cingulum. Averaging effects are also evaluated on a full-brain voxel based approach. The main results are: i) group FA and MD reproducibility errors across scan sessions are on average double of those found in within-session repetitions (≈ 1.3 %), regardless of acquisition protocol and region; ii) within-session averaging of two DTI acquisitions does not improve reproducibility of any of the quantities across sessions at the group level, regardless of acquisition protocol; iii) increasing voxel size biased MD, axial and radial diffusivities to higher values and FA to lower values; iv) increasing b-value biased all quantities to lower values, axial diffusivity showing the strongest effects; v) the two co-registration methods evaluated gave similar bias and reproducibility results. Altogether these results show that reproducibility of FA and MD is comparable to that found at lower fields, not significantly dependent on pre-processing and acquisition protocol manipulations, but that the specific choice of acquisition parameters can significantly bias the group measures of FA, MD, axial and radial diffusivities.     

Blood oxygenation level dependent magnetic resonance imaging and diffusion weighted MRI imaging for benign and malignant breast cancer discrimination

PurposeThe purpose of this study is to assess Blood oxygenation level dependent Magnetic Resonance Imaging (BOLD-MRI) and Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) in the differentiation of benign and malignant breast lesions.MethodsFifty-nine breast lesions (26 benign and 33 malignant lesions) pathologically proven in 59 patients were included in this retrospective study. As BOLD parameters were estimated basal signal S₀ and the relaxation rate R2*, diffusion and perfusion parameters were derived by DWI (pseudo-diffusion coefficient (Dp), perfusion fraction (fp) and tissue diffusivity (Dt)). Wilcoxon-Mann-Whitney U test and Receiver operating characteristic (ROC) analyses were calculated and area under ROC curve (AUC) was obtained. Moreover, pattern recognition approaches (linear discrimination analysis (LDA), support vector machine, k-nearest neighbours, decision tree) with least absolute shrinkage and selection operator (LASSO) method and leave one out cross validation approach were considered.ResultsA significant discrimination was obtained by the standard deviation value of S0, as BOLD parameter, that reached an AUC of 0.76 with a sensitivity of 65%, a specificity of 85% and an accuracy of 76%. No significant discrimination was obtained considering diffusion and perfusion parameters. Considering LASSO results, the features to use as predictors were all extracted parameters except that the mean value of R2* and the best result was obtained by a LDA that obtained an AUC = 0.83, with a sensitivity of 88%, a specificity of 77% and an accuracy of 83%.ConclusionsGood performance to discriminate benign and malignant lesions could be obtained using BOLD and DWI derived parameters with a LDA classification approach. However, these findings should be proven on larger and several dataset with different MR scanners.     

In vivo diffusion tensor imaging of thoracic and cervical rat spinal cord at 7 T

In vivo diffusion tensor imaging (DTI) of rat cervical and thoracic spinal cord was performed using a three-element phased array coil at 7 T. The magnetic field was shimmed over the spinal cord in real time using an in-house developed automatic algorithm. Echo planar imaging (EPI)-based diffusion-weighted images (DWIs) were acquired with 21 gradient encoding directions. The DWIs were tensor encoded, and diffusion tensor metrics, fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity (λ₀) and transverse diffusivity (λ) were determined for both white matter (WM) and gray matter (GM). The results on six normal rats indicated no significant differences in the diffusion tensor metrics between thoracic and cervical regions. However, the DTI-derived metrics in cervical spinal cord from our study are somewhat different from the published results in rats. The possible reasons for these differences are suggested.     

Ficoll as testing material for diffusion weighted imaging-quality assurance phantoms

PurposeThe aim of this work is to test the use of aqueous solutions of Ficoll®**, a highly branched polymer displaying crowding properties, to build a phantom suitable for Diffusion Weighted Imaging (DWI) in Magnetic Resonance Imaging (MRI).MethodsWe developed a test object made of a cylindrical plastic container with a precise geometrical arrangement suitable for measuring several samples at the same time. The container was designed to host single vials with variable geometry and number, and to fit inside common commercial head coils for MRI scanners.In our experiments, vials were filled with 8 aqueous solutions of Ficoll 70 and Ficoll 400 spanning a range of polymer concentration from 5 to 30% by weight. Vials containing ultra-pure water were also used as reference. Experiments were performed on both 1.5 and 3 T clinical scanners (GE, Philips and Siemens), under the conditions of a standard clinical examination.ResultsThe geometry of the phantom provided reduced imaging artifacts, especially image distortions at magnetic interfaces. We found that the Apparent Diffusion Coefficient (ADC) varied in the range of 0.00125–0.00223 mm²/s and decreased with Ficoll concentration. ADC vs Ficoll concentration exhibited a linear trend. Results were consistent over time and among different MRI clinical scanners, showing an average variability of 3% at 1.5 T and of 7.5% at 3 T. Moreover, no substantial difference was found between Ficoll 70 and 400. By varying Ficoll concentration, ADC can be modulated to approach tissue-mimicking values. Preliminary results for relaxation measurements proved that both T₁ and T₂ decreased with Ficoll concentration in the ranges 1.3–2.4 s and 150–800 ms respectively.ConclusionsIn this work, we propose a 3D phantom design based on the widespread crowding agent Ficoll, which is suitable for DWI quality assurance purposes in MRI acquisitions. Aqueous Ficoll solutions provide good performance in terms of stability, ease of preparation, and safety.     

In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model

ObjectivesTo assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model.MethodsFifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm²), 2 b values (0 and 500 s/mm²) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57–24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies.ResultsTrue diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381–0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD.ConclusionsMultiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.     

Image-based gradient non-linearity characterization to determine higher-order spherical harmonic coefficients for improved spatial position accuracy in magnetic resonance imaging

PurposeSpatial position accuracy in magnetic resonance imaging (MRI) is an important concern for a variety of applications, including radiation therapy planning, surgical planning, and longitudinal studies of morphologic changes to study neurodegenerative diseases. Spatial accuracy is strongly influenced by gradient linearity. This work presents a method for characterizing the gradient non-linearity fields on a per-system basis, and using this information to provide improved and higher-order (9th vs. 5th) spherical harmonic coefficients for better spatial accuracy in MRI.MethodsA large fiducial phantom containing 5229 water-filled spheres in a grid pattern is scanned with the MR system, and the positions all the fiducials are measured and compared to the corresponding ground truth fiducial positions as reported from a computed tomography (CT) scan of the object. Systematic errors from off-resonance (i.e., B0) effects are minimized with the use of increased receiver bandwidth (± 125 kHz) and two acquisitions with reversed readout gradient polarity. The spherical harmonic coefficients are estimated using an iterative process, and can be subsequently used to correct for gradient non-linearity. Test-retest stability was assessed with five repeated measurements on a single scanner, and cross-scanner variation on four different, identically-configured 3 T wide-bore systems.ResultsA decrease in the root-mean-square error (RMSE) over a 50 cm diameter spherical volume from 1.80 mm to 0.77 mm is reported here in the case of replacing the vendor's standard 5th order spherical harmonic coefficients with custom fitted 9th order coefficients, and from 1.5 mm to 1 mm by extending custom fitted 5th order correction to the 9th order. Minimum RMSE varied between scanners, but was stable with repeated measurements in the same scanner.ConclusionsThe results suggest that the proposed methods may be used on a per-system basis to more accurately calibrate MR gradient non-linearity coefficients when compared to vendor standard corrections.     

Normalizing data from GABA-edited MEGA-PRESS implementations at 3 Tesla

Standardization of results is an important milestone in the maturation of any truly quantitative methodology. For instance, a lack of measurement agreement across imaging platforms limits multisite studies, between-study comparisons based on the literature, and inferences based on and the generalizability of results. In GABA-edited MEGA-PRESS, two key sources of differences between implementations are: differences in editing efficiency of GABA and the degree of co-editing of macromolecules (MM). In this work, GABA editing efficiency κ and MM-co-editing μ constants are determined for three widely used MEGA-PRESS implementations (on the most common MRI platforms; GE, Philips, and Siemens) by phantom experiments. Implementation-specific κ,μ-corrections were then applied to two in vivo datasets, one consisted of 8 subject scanned on the three platforms and the other one subject scanned eight times on each platform. Manufacturer-specific κ and μ values were determined as: κ_GE = 0.436, κ_Siemens = 0.366 and κ_Philips = 0.394 and μ_GE = 0.83, μ_Siemens = 0.625 and μ_Philips = 0.75. Applying the κ,μ-correction on the Cr-referenced data decreased the coefficient of variation (CV) of the data for both in vivo data sets (multisubjects: uncorrected CV = 13%, κ,μ-corrected CV = 5%, single subject: uncorrected CV = 23%, κ,μ-corrected CV = 13%) but had no significant effect on mean GABA levels. For the water-referenced results, CV increased in the multisubject data (uncorrected CV = 6.7%, κ,μ-corrected CV = 14%) while it decreased in the single subject data (uncorrected CV = 24%, κ,μ-corrected CV = 21%) and manufacturer was a significant source of variance in the κ,μ-corrected data. Applying a correction for editing efficiency and macromolecule contamination decreases the variance between different manufacturers for creatine-referenced data, but other sources of variance remain.     

Assessing reproducibility of diffusion-weighted magnetic resonance imaging studies in a murine model of HER2 + breast cancer

Background and purpose

The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a surrogate biomarker of response in preclinical studies is increasing. However, before a biomarker can be reliably employed to assess treatment response, the reproducibility of the technique must be established. There is a paucity of literature that quantifies the reproducibility of DW-MRI in preclinical studies; thus, the purpose of this study was to investigate DW-MRI reproducibility in a murine model of HER2 + breast cancer.

Materials and methods

Test–Retest DW-MRI scans separated by approximately six hours were acquired from eleven athymic female mice with HER2 + xenografts using a pulsed gradient spin echo diffusion-weighted sequence with three b values [150, 500, and 800 s/mm²]. Reproducibility was assessed for the mean apparent diffusion coefficient (ADC) from tumor and muscle tissue regions.

Results

The threshold to reflect a change in tumor physiology in a cohort of mice is defined by the 95% confidence interval (CI), which was ± 0.0972 × 10^- 3 mm²/s (± 11.8%) for mean tumor ADC. The repeatability coefficient defines this threshold for an individual mouse, which was ± 0.273 × 10^- 3 mm²/s. The 95% CI and repeatability coefficient for mean ADC of muscle tissue were ± 0.0949 × 10^- 3 mm²/s (± 8.30%) and ± 0.266 × 10^- 3 mm²/s, respectively.

Conclusions

Mean ADC of tumors is reproducible and appropriate for detecting treatment-induced changes on both an individual and mouse cohort basis.     

Determination of Very Slow Diffusion of Paramagnetic Ions by NMR Spectroscopy

In this paper, we propose a new method of measuring the very slow paramagnetic ion diffusion coefficient using a commercial high-resolution spectrometer. If there are distinct paramagnetic ions influencing the hydrogen nuclear magnetic relaxation time differently, their diffusion coefficients can be measured separately. A cylindrical phantom filled with Fricke xylenol gel solution and irradiated with gamma rays was used to validate the method. The Fricke xylenol gel solution was prepared with 270 Bloom porcine gelatin, the phantom was irradiated with gamma rays originated from a ⁶⁰Co source and a high-resolution 200 MHz nuclear magnetic resonance (NMR) spectrometer was used to obtain the phantom ¹H profile in the presence of a linear magnetic field gradient. By observing the temporal evolution of the phantom NMR profile, an apparent ferric ion diffusion coefficient of 0.50 μm²/ms due to ferric ions diffusion was obtained. In any medical process where the ionizing radiation is used, the dose planning and the dose delivery are the key elements for the patient safety and success of treatment. These points become even more important in modern conformal radio therapy techniques, such as stereotactic radiosurgery, where the delivered dose in a single session of treatment can be an order of magnitude higher than the regular doses of radiotherapy. Several methods have been proposed to obtain the three-dimensional (3-D) dose distribution. Recently, we proposed an alternative method for the 3-D radiation dose mapping, where the ionizing radiation modifies the local relative concentration of Fe²⁺/Fe³⁺ in a phantom containing Fricke gel and this variation is associated to the MR image intensity. The smearing of the intensity gradient is proportional to the diffusion coefficient of the Fe³⁺ and Fe²⁺ in the phantom. There are several methods for measurement of the ionic diffusion using NMR, however, they are applicable when the diffusion is not very slow.     

Combination of integrated dynamic shimming and readout-segmented echo planar imaging for diffusion weighted MRI of the head and neck region at 3 Tesla

PurposeTo evaluate the performance of combined integrated slice-by-slice shimming and readout-segmented EPI (irsEPI) for diffusion-weighted MR imaging (DWI) of the neck at 3 Tesla.MethodsThis study was approved by the local ethics committee. An anthropometric phantom of the head/neck region incorporating compartments with different diffusivities was constructed. In vivo measurements were performed in 10 healthy volunteers. DWI of the phantom and volunteers was performed on a 3 Tesla MR scanner using single shot EPI (sEPI), a prototype single shot EPI with integrated slice-by-slice shimming (iEPI), readout segmented EPI (rsEPI) and a prototype readout segmented EPI with integrated shimming irsEPI. Apparent diffusion coefficients (ADC) and spatial distortions of phantom compartments were quantified. For phantom and volunteer measurements, the presence of geometric distortions, signal losses, ghosting artifacts as well as overall image quality were visually assessed on a 4-point scale by two radiologists in consensus. In addition, failure of fat saturation was assessed in volunteer data.ResultsQuantification of ADC within the phantom compartments was comparable using the different EPI techniques without significant variations. Using irsEPI, spatial distortions in phase-encoding direction were markedly reduced compared to iEPI, rsEPI and especially sEPI. irsEPI yielded significantly better overall image quality compared to sEPI, iEPI and rsEPI in phantom data as well as volunteer measurements. Markedly reduced geometric distortions and signal loss as well as better fat saturation were observed using irsEPI.ConclusionThe use of irsEPI significantly improves image quality and reduces artifacts caused by magnetic field inhomogeneities in EPI based DWI of the head/neck at 3 Tesla.     

The effect of the diffusion time and pulse gradient duration ratio on the diffraction pattern and the structural information estimated from q-space diffusion MR: experiments and simulations

q-Space diffusion MRI (QSI) provides a means of obtaining microstructural information about porous materials and neuronal tissues from diffusion data. However, the accuracy of this structural information depends on experimental parameters used to collect the MR data. q-Space diffusion MR performed on clinical scanners is generally collected with relatively long diffusion gradient pulses, in which the gradient pulse duration, δ, is comparable to the diffusion time, Δ. In this study, we used phantoms, consisting of ensembles of microtubes, and mathematical models to assess the effect of the ratio of the diffusion time and the duration of the diffusion pulse gradient, i.e., Δ/δ, on the MR signal attenuation vs. q, and on the measured structural information extracted therefrom. We found that for Δ/δ  1, the diffraction pattern obtained from q-space MR data are shallower than when the short gradient pulse (SGP) approximation is satisfied. For long δ the estimated compartment size is, as expected, smaller than the real size. Interestingly, for Δ/δ  1 the diffraction peaks are shifted to even higher q-values, even when δ is kept constant, giving the impression that the restricted compartments are even smaller than they are. When phantoms composed of microtubes of different diameters are used, it is more difficult to estimate the diameter distribution in this regime. Excellent agreement is found between the experimental results and simulations that explicitly account for the use of long duration gradient pulses. Using such experimental data and this mathematical framework, one can estimate the true compartment dimensions when long and finite gradient pulses are used even when Δ/δ  1.     

Inter-vender and test-retest reliabilities of resting-state functional magnetic resonance imaging: Implications for multi-center imaging studies

This prospective multi-center study aimed to evaluate the inter-vendor and test-retest reliabilities of resting-state functional magnetic resonance imaging (RS-fMRI) by assessing the temporal signal-to-noise ratio (tSNR) and functional connectivity. Study included 10 healthy subjects and each subject was scanned using three 3 T MR scanners (GE Signa HDxt, Siemens Skyra, and Philips Achieva) in two sessions. The tSNR was calculated from the time course data. Inter-vendor and test-retest reliabilities were assessed with intra-class correlation coefficients (ICCs) derived from variant component analysis. Independent component analysis was performed to identify the connectivity of the default-mode network (DMN). In result, the tSNR for the DMN was not significantly different among the GE, Philips, and Siemens scanners (P = 0.638). In terms of vendor differences, the inter-vendor reliability was good (ICC = 0.774). Regarding the test-retest reliability, the GE scanner showed excellent correlation (ICC = 0.961), while the Philips (ICC = 0.671) and Siemens (ICC = 0.726) scanners showed relatively good correlation. The DMN pattern of the subjects between the two sessions for each scanner and between three scanners showed the identical patterns of functional connectivity. The inter-vendor and test-retest reliabilities of RS-fMRI using different 3 T MR scanners are good. Thus, we suggest that RS-fMRI could be used in multicenter imaging studies as a reliable imaging marker.     

Verification of gamma knife based fractionated radiosurgery with newly developed head-thorax phantom

ObjectivePurpose of the study is to verify the Gamma Knife Extend™ system (ES) based fractionated stereotactic radiosurgery with newly developed head-thorax phantom.MethodsPhantoms are extensively used to measure radiation dose and verify treatment plan in radiotherapy. A human upper body shaped phantom with thorax was designed to simulate fractionated stereotactic radiosurgery using Extend™ system of Gamma Knife. The central component of the phantom aids in performing radiological precision test, dosimetric evaluation and treatment verification. A hollow right circular cylindrical space of diameter 7.0 cm was created at the centre of this component to place various dosimetric devices using suitable adaptors. The phantom is made of poly methyl methacrylate (PMMA), a transparent thermoplastic material. Two sets of disk assemblies were designed to place dosimetric films in (1) horizontal (xy) and (2) vertical (xz) planes. Specific cylindrical adaptors were designed to place thimble ionization chamber inside phantom for point dose recording along xz axis. EBT3 Gafchromic films were used to analyze and map radiation field. The focal precision test was performed using 4 mm collimator shot in phantom to check radiological accuracy of treatment. The phantom head position within the Extend™ frame was estimated using encoded aperture measurement of repositioning check tool (RCT). For treatment verification, the phantom with inserts for film and ion chamber was scanned in reference treatment position using X-ray computed tomography (CT) machine and acquired stereotactic images were transferred into Leksell Gammaplan (LGP). A patient treatment plan with hypo-fractionated regimen was delivered and identical fractions were compared using EBT3 films and in-house MATLAB codes.ResultsRCT measurement showed an overall positional accuracy of 0.265 mm (range 0.223 mm–0.343 mm). Gamma index analysis across fractions exhibited close agreement between LGP and film measured dose with ≥90% (max 93%) pixel pass rate at 1 mm of spatial and 1% of dosimetric tolerances. The focal precision test showed the variation of 0.465 mm between radiological and planned iso-centre.ConclusionsThe study demonstrated the suitability of newly developed head-thorax phantom for dosimetric verification of fractionated stereotactic radiosurgery using Extend™ system of Gamma Knife.     

Quantitative quality assurance in a multicenter HARDI clinical trial at 3 T

A phantom-based quality assurance (QA) protocol was developed for a multicenter clinical trial including high angular resolution diffusion imaging (HARDI). A total of 27 3 T MR scanners from 2 major manufacturers, GE (Discovery and Signa scanners) and Siemens (Trio and Skyra scanners), were included in this trial. With this protocol, agar phantoms doped to mimic relaxation properties of brain tissue are scanned on a monthly basis, and quantitative procedures are used to detect spiking and to evaluate eddy current and Nyquist ghosting artifacts. In this study, simulations were used to determine alarm thresholds for minimal acceptable signal-to-noise ratio (SNR). Our results showed that spiking artifact was the most frequently observed type of artifact. Overall, Trio scanners exhibited less eddy current distortion than GE scanners, which in turn showed less distortion than Skyra scanners. This difference was mainly caused by the different sequences used on these scanners. The SNR for phantom scans was closely correlated with the SNR from volunteers. Nearly all of the phantom measurements with artifact-free images were above the alarm threshold, suggesting that the scanners are stable longitudinally. Software upgrades and hardware replacement sometimes affected SNR substantially but sometimes did not. In light of these results, it is important to monitor longitudinal SNR with phantom QA to help interpret potential effects on in vivo measurements. Our phantom QA procedure for HARDI scans was successful in tracking scanner performance and detecting unwanted artifacts.     

Alterations of the optic pathway between unilateral and bilateral optic nerve damage in multiple sclerosis as revealed by the combined use of advanced diffusion kurtosis imaging and visual evoked potentials

ObjectivesWe investigated changes in the optic tract and optic radiation in patients with multiple sclerosis (MS) by comparing unilateral and bilateral optic nerve damage assessed based on visual evoked potentials (VEPs) using advanced diffusion MR metrics.MethodsIn 21 MS patients, diffusion MRI was performed. Maps of fractional anisotropy, apparent diffusion coefficient (ADC), and mean kurtosis (MK) were computed. On the basis of the P100 latency in VEPs, the MS patients were divided into three groups: bilateral (n = 7), unilateral (n = 7), and no abnormality (n = 7). Their optic tracts and optic radiations were analyzed with diffusion MRI-based fiber tracking. We also investigated the correlations between diffusion parameters and VEPs (n = 21).ResultsIn the optic tract, the diffusion changes in each of the three groups showed step-like changes. The diffusion changes in the optic radiations of the unilateral group were similar to those in the normal VEP group. Only the bilateral group showed significantly higher ADC and lower MK relative to the other two groups (P < 0.05, Steel–Dwass multiple-comparison test). A significant positive correlation between VEP latency and ADC and a significant negative correlation between VEP latency and MK were observed (P < 0.01, Spearman's correction).ConclusionsWe first evaluated the relationship between VEPs and DKI and concluded that the lateral geniculate nucleus may compensate for unilateral damage in the pre-geniculate optic pathway via neural plasticity.     

Diffusion MRI detects basal forebrain cholinergic abnormalities in the 3xTg-AD mouse model of Alzheimer's disease

Degeneration of the basal forebrain (BF) is detected early in the course of Alzheimer's disease (AD). Reduction in the number of BF cholinergic (ChAT) neurons associated with age-related hippocampal cholinergic neuritic dystrophy is described in the 3xTg-AD mouse model; however, no prior diffusion MRI (dMRI) study has explored the presence of BF alterations in this model. Here we investigated the ability of diffusion MRI (dMRI) to detect abnormalities in BF microstructure for the 3xTg-AD mouse model, along with related pathology in the hippocampus (HP) and white matter (WM) tracks comprising the septo-hippocampal pathway. 3xTg-AD and normal control (NC) mice were imaged in vivo using the specific dMRI technique known as diffusional kurtosis imaging (DKI) at 2, 8, and 15 months of age, and 8 dMRI parameters were measured at each time point. Our results revealed significant lower dMRI values in the BF of 2 months-old 3xTg-AD mice compared with NC mice, most likely related to the increased number of ChAT neurons seen in this AD mouse model at this age. They also showed significant age-related dMRI changes in the BF of both groups between 2 and 8 months of age, mainly a decrease in fractional anisotropy and axial diffusivity, and an increase in radial kurtosis. These dMRI changes in the BF may be reflecting the complex aging and pathological microstructural changes described in this region. Group differences and age-related changes were also observed in the HP, fimbria (Fi) and fornix (Fx). In the HP, diffusivity values were significantly higher in the 2 months-old 3xTg-AD mice, and the HP of NC mice showed a significant increase in axial kurtosis after 8 months, reflecting a normal pattern of increased fiber density complexity, which was not seen in the 3xTg-AD mice. In the Fi, mean and radial diffusivity values were significantly higher, and fractional anisotropy, radial kurtosis and kurtosis fractional anisotropy were significantly lower in the 2 months-old 3xTg-AD mice. The age trajectories for both NC and TG mice in the Fi and Fx were similar between 2 and 8 months, but after 8 months there was a significant decrease in diffusivity metrics associated with an increase in kurtosis metrics in the 3xTg-AD mice. These later HP, Fi and Fx dMRI changes probably reflect the growing number of dystrophic neurites and AD pathology progression in the HP, accompanied by WM disruption in the septo-hippocampal pathway. Our results demonstrate that dMRI can detect early cytoarchitectural abnormalities in the BF, as well as related aging and neurodegenerative changes in the HP, Fi and Fx of the 3xTg-AD mice. Since DKI is widely available on clinical scanners, these results also support the potential of the considered dMRI parameters as in vivo biomarkers for AD disease progression.     

Reproducibility and variation of diffusion measures in the squirrel monkey brain,in vivo and ex vivo

PurposeAnimal models are needed to better understand the relationship between diffusion MRI (dMRI) and the underlying tissue microstructure. One promising model for validation studies is the common squirrel monkey, Saimiri sciureus. This study aims to determine (1) the reproducibility of in vivo diffusion measures both within and between subjects; (2) the agreement between in vivo and ex vivo data acquired from the same specimen and (3) normal diffusion values and their variation across brain regions.MethodsData were acquired from three healthy squirrel monkeys, each imaged twice in vivo and once ex vivo. Reproducibility of fractional anisotropy (FA), mean diffusivity (MD), and principal eigenvector (PEV) was assessed, and normal values were determined both in vivo and ex vivo.ResultsThe calculated coefficients of variation (CVs) for both intra-subject and inter-subject MD were below 10% (low variability) while FA had a wider range of CVs, 2–14% intra-subject (moderate variability), and 3–31% inter-subject (high variability). MD in ex vivo tissue was lower than in vivo (30%–50% decrease), while FA values increased in all regions (30–39% increase). The mode of angular differences between in vivo and ex vivo PEVs was 12 degrees.ConclusionThis study characterizes the diffusion properties of the squirrel monkey brain and serves as the groundwork for using the squirrel monkey, both in vivo and ex vivo, as a model for diffusion MRI studies.     

Quantitative diffusion-weighted imaging and dynamic contrast-enhanced MR imaging for assessment of tumor aggressiveness in prostate cancer at 3T

PurposeTo compare diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MR imaging (DCE-MRI) for characterization of prostate cancer (PC).Methods104 PC patients who underwent prostate multiparametric MRI at 3T including DWI and DCE-MRI before MRI-guided biopsy or radical prostatectomy. Apparent diffusion coefficient (ADC) with histogram analysis (mean, 0–25th percentile, skewness, and kurtosis), intravoxel incoherent motion model including D and f; stretched exponential model including distributed diffusion coefficient (DDC) and a; and permeability parameters including K^trans, K_ep, and V_e were obtained from a region of interest placed on the dominant tumor of each patient.ResultsADC_mean, ADC_0–25, D, DDC, and V_e were significantly lower and K_ep was significantly higher in GS ≥ 3 + 4 tumors (n = 89) than in GS = 3 + 3 tumors (n = 15), and also in GS ≥ 4 + 3 tumors (n = 57) than in GS ≤ 3 + 4 tumors (n = 47) (P < 0.001 to P = 0.040). f was significantly lower in GS ≥ 4 + 3 tumors than in GS ≤ 3 + 4 tumors (P = 0.022), but there was no significant difference between GS = 3 + 3 tumors and GS ≥ 3 + 4 tumors, or between the remaining metrics in both comparisons. In metrics with area under the curve (AUC) >0.80, there was a significant difference in AUC between ADC_0–25 and D, and DDC for separating GS ≤ 3 + 4 tumors from GS ≥ 4 + 3 tumors (P = 0.040 and P = 0.022, respectively). There were no significant differences between metrics with AUC > 0.80 for separating GS = 3 + 3 tumors from GS ≥ 3 + 4 tumors. ADC_0–25 had the highest correlation with Gleason grade (ρ = −0.625, P < 0.001).ConclusionsDWI and DCE-MRI showed no apparent clinical superiority of non-Gaussian models or permeability MRI over the mono-exponential model for assessment of tumor aggressiveness in PC.     

The effect of morphological and microstructural integrity of the corpus callosum on cognition,fatigue and depression in mildly disabled MS patients

AimTo assess the value of callosal morphological and microstructural integrity in assessing different cognitive domains, fatigue and depression in mildly disabled multiple sclerosis (MS) patients.Materials and methodsWe assessed 29 mildly disabled MS patients and 15 healthy controls using 3T magnetic resonance images (T1-weighted, FLAIR and DTI) and neuropsychological tests assessing different cognitive functions, depression and fatigue. We compared the added value of morphological measures (corpus callosum area corrected for total intracranial volume, index, circularity and the more detailed thickness profile) and diffusion features (fractional anisotropy and mean diffusivity) in multilinear models including standard clinical and whole-brain parameters in assessing neuropsychological scores.ResultsEven in mildly disabled MS patients, a significant reduction of the corpus callosum (p < 0.001) was observed in comparison to healthy controls. Callosal area, index and circularity were significantly (p < 0.002) related to whole-brain white matter volume, T2 lesion load and deep grey matter volume, but not with cortical grey matter.The combination of commonly used imaging and clinical parameters explained between 7% (Fatigue) and 50% (processing speed, verbal memory) of the adjusted variance. Inclusion of the mean diffusivity increased the adjusted R² significantly to 69% (p = 0.004) and 71% (p = 0.002) for visuospatial and verbal memory respectively.ConclusionOur results show that callosal features may be used as an alternative to measuring whole-brain volumes. Furthermore, the microstructural integrity of the corpus callosum can help to predict an MS patient's memory performance.