Reliable estimation of brain intravoxel incoherent motion parameters using denoised diffusion‐weighted MRI

In this study, we evaluate whether diffusion‐weighted magnetic resonance imaging (DW‐MRI) data after denoising can provide a reliable estimation of brain intravoxel incoherent motion (IVIM) perfusion parameters. Brain DW‐MRI was performed in five healthy volunteers on a 3 T clinical scanner with 12 different b‐values ranging from 0 to 1000 s/mm². DW‐MRI data denoised using the proposed method were fitted with a biexponential model to extract perfusion fraction (PF), diffusion coefficient (D) and pseudo‐diffusion coefficient (D*). To further evaluate the accuracy and precision of parameter estimation, IVIM parametric images obtained from one volunteer were used to resimulate the DW‐MRI data using the biexponential model with the same b‐values. Rician noise was added to generate DW‐MRI data with various signal‐to‐noise ratio (SNR) levels. The experimental results showed that the denoised DW‐MRI data yielded precise estimates for all IVIM parameters. We also found that IVIM parameters were significantly different between gray matter and white matter (P < 0.05), except for D* (P = 0.6). Our simulation results show that the proposed image denoising method displays good performance in estimating IVIM parameters (both bias and coefficient of variation were <12% for PF, D and D*) in the presence of different levels of simulated Rician noise (SNR_b=0 = 20‐40). Simulations and experiments show that brain DW‐MRI data after denoising can provide a reliable estimation of IVIM parameters.     

Reliability and precision of pseudo‐continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O‐water PET in elderly subjects at risk for Alzheimer's disease

Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo‐continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received ¹⁵O‐water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross‐modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = –0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional ¹⁵O‐water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non‐invasive in vivo examination of early pathophysiological changes in AD. Copyright © 2009 John Wiley & Sons, Ltd.     

Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift‐off test of varying duration

Intravoxel incoherent motion (IVIM) MRI is a method to extract microvascular blood flow information out of diffusion‐weighted images acquired at multiple b‐values. We hypothesized that IVIM can identify the muscles selectively involved in a specific task, by measuring changes in activity‐induced local muscular perfusion after exercise. We tested this hypothesis using a widely used clinical maneuver, the lift‐off test, which is known to assess specifically the subscapularis muscle functional integrity. Twelve shoulders from six healthy male volunteers were imaged at 3 T, at rest, as well as after a lift‐off test hold against resistance for 30 s, 1 and 2 min respectively, in three independent sessions. IVIM parameters, consisting of perfusion fraction (f), diffusion coefficient (D), pseudo‐diffusion coefficient D* and blood flow‐related fD*, were estimated within outlined muscles of the rotator cuff and the deltoid bundles. The mean values at rest and after the lift‐off tests were compared in each muscle using a one‐way ANOVA. A statistically significant increase in fD* was measured in the subscapularis, after a lift‐off test of any duration, as well as in D. A fD* increase was the most marked (30 s, +103%; 1 min, +130%; 2 min, +156%) and was gradual with the duration of the test (in 10^‐3 mm²/s: rest, 1.41 ± 0.50; 30 s, 2.86 ± 1.17; 1 min, 3.23 ± 1.22; 2 min, 3.60 ± 1.21). A significant increase in fD* and D was also visible in the posterior bundle of the deltoid. No significant change was consistently visible in the other investigated muscles of the rotator cuff and the other bundles of the deltoid. In conclusion, IVIM fD* allows the demonstration of a task‐related microvascular perfusion increase after a specific task and suggests a direct relationship between microvascular perfusion and the duration of the effort. It is a promising method to investigate non‐invasively skeletal muscle physiology and clinical perfusion‐related muscular disorders. Copyright © 2015 John Wiley & Sons, Ltd.     

Magnetic resonance temperature imaging‐based quantification of blood flow‐related energy losses

This study presents a new approach for evaluating bioheat transfer equation (BHTE) models used in treatment planning, control and evaluation of all thermal therapies. First, 3D magnetic resonance temperature imaging (MRTI) data are used to quantify blood flow‐related energy losses, including the effects of perfusion and convection. Second, this information is used to calculate parameters of a BHTE model: in this paper the widely used Pennes BHTE. As a self‐consistency check, the BHTE parameters are utilized to predict the temperatures from which they were initially derived. The approach is evaluated with finite‐difference simulations and implemented experimentally with focused ultrasound heating of an ex vivo porcine kidney perfused at 0, 20 and 40 ml/min (n = 4 each). The simulation results demonstrate accurate quantification of blood flow‐related energy losses, except in regions of sharp blood flow discontinuities, where the transitions are spatially smoothed. The smoothed transitions propagate into estimates of the Pennes perfusion parameter but have limited effect on the accuracy of temperature predictions using these estimates. Longer acquisition time periods mitigate the effects of MRTI noise, but worsen the effect of flow discontinuities. For the no‐flow kidney experiments the estimates of a uniform, constant Pennes perfusion parameter are approximately zero, and at 20 and 40 ml/min the average estimates increase with flow rate to 3.0 and 4.2 kg/m³/s, respectively. When Pennes perfusion parameter values are allowed to vary spatially, but remain temporally constant, BHTE temperature predictions are more accurate than when using spatially uniform, constant Pennes perfusion values, with reductions in RMSE values of up to 79%. Locations with large estimated perfusion values correspond to high flow regions of the kidney observed in T₁‐weighted MR images. This novel, MRTI‐based technique holds promise for improving understanding of thermal therapy biophysics and for evaluating biothermal models. Copyright © 2015 John Wiley & Sons, Ltd.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

The effect of noise and lipid signals on determination of Gaussian and non‐Gaussian diffusion parameters in skeletal muscle

This work characterizes the effect of lipid and noise signals on muscle diffusion parameter estimation in several conventional and non‐Gaussian models, the ultimate objectives being to characterize popular fat suppression approaches for human muscle diffusion studies, to provide simulations to inform experimental work and to report normative non‐Gaussian parameter values. The models investigated in this work were the Gaussian monoexponential and intravoxel incoherent motion (IVIM) models, and the non‐Gaussian kurtosis and stretched exponential models. These were evaluated via simulations, and in vitro and in vivo experiments. Simulations were performed using literature input values, modeling fat contamination as an additive baseline to data, whereas phantom studies used a phantom containing aliphatic and olefinic fats and muscle‐like gel. Human imaging was performed in the hamstring muscles of 10 volunteers. Diffusion‐weighted imaging was applied with spectral attenuated inversion recovery (SPAIR), slice‐select gradient reversal and water‐specific excitation fat suppression, alone and in combination. Measurement bias (accuracy) and dispersion (precision) were evaluated, together with intra‐ and inter‐scan repeatability. Simulations indicated that noise in magnitude images resulted in <6% bias in diffusion coefficients and non‐Gaussian parameters (α, K), whereas baseline fitting minimized fat bias for all models, except IVIM. In vivo, popular SPAIR fat suppression proved inadequate for accurate parameter estimation, producing non‐physiological parameter estimates without baseline fitting and large biases when it was used. Combining all three fat suppression techniques and fitting data with a baseline offset gave the best results of all the methods studied for both Gaussian diffusion and, overall, for non‐Gaussian diffusion. It produced consistent parameter estimates for all models, except IVIM, and highlighted non‐Gaussian behavior perpendicular to muscle fibers (α ~ 0.95, K ~ 3.1). These results show that effective fat suppression is crucial for accurate measurement of non‐Gaussian diffusion parameters, and will be an essential component of quantitative studies of human muscle quality.     

Partial volume correction of brain perfusion estimates using the inherent signal data of time‐resolved arterial spin labeling

Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross‐contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high‐resolution T₁‐weighted morphological image volume that is coregistered to the low‐resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low‐resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T₁‐based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high‐resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra‐subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low‐resolution partial volume estimation in connection with ASL perfusion estimation is feasible, and provides a promising tool for decoupling perfusion and tissue volume. Copyright © 2014 John Wiley & Sons, Ltd.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

An intravoxel oriented flow model for diffusion‐weighted imaging of the kidney

By combining intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) we introduce a new diffusion model called intravoxel oriented flow (IVOF) that accounts for anisotropy of diffusion and the flow‐related signal. An IVOF model using a simplified apparent flow fraction tensor (IVOF_f) is applied to diffusion‐weighted imaging of human kidneys. The kidneys of 13 healthy volunteers were examined on a 3 T scanner. Diffusion‐weighted images were acquired with six b values between 0 and 800 s/mm² and 30 diffusion directions. Diffusivity and flow fraction were calculated for different diffusion models. The Akaike information criterion was used to compare the model fit of the proposed IVOF_f model to IVIM and DTI. In the majority of voxels the proposed IVOF_f model with a simplified apparent flow fraction tensor performs better than IVIM and DTI. Mean diffusivity is significantly higher in DTI compared with models that account for the flow‐related signal. The fractional anisotropy of diffusion is significantly reduced when flow fraction is considered to be anisotropic. Anisotropy of the apparent flow fraction tensor is significantly higher in the renal medulla than in the cortex region. The IVOF_f model describes diffusion‐weighted data in the human kidney more accurately than IVIM or DTI. The apparent flow fraction in the kidney proved to be anisotropic.     

Pattern recognition analysis of directional intravoxel incoherent motion MRI in ischemic rodent brains

This study aimed to demonstrate a reliable automatic segmentation method for independently separating reduced diffusion and decreased perfusion areas in ischemic stroke brains using constrained nonnegative matrix factorization (cNMF) pattern recognition in directional intravoxel incoherent motion MRI (IVIM‐MRI). First, the feasibility of cNMF‐based segmentation of IVIM signals was investigated in both simulations and in vivo experiments. The cNMF analysis was independently performed for S₀‐normalized and scaled (by the difference between the maximum and minimum) IVIM signals, respectively. Segmentations of reduced diffusion (from S₀‐normalized IVIM signals) and decreased perfusion (from scaled IVIM signals) areas were performed using the corresponding cNMF pattern weight maps. Second, Monte Carlo simulations were performed for directional IVIM signals to investigate the relationship between the degree of vessel alignment and the direction of the diffusion gradient. Third, directional IVIM‐MRI experiments (x, y and z diffusion‐gradient directions, 20 b values at 7 T) were performed for normal (n = 4), sacrificed (n = 1, no flow) and ischemic stroke models (n = 4, locally reduced flow). The results showed that automatic segmentation of the hypoperfused lesion using cNMF analysis was more accurate than segmentation using the conventional double‐exponential fitting. Consistent with the simulation, the double‐exponential pattern of the IVIM signals was particularly strong in white matter and ventricle regions when the directional flows were aligned with the applied diffusion‐gradient directions. cNMF analysis of directional IVIM signals allowed robust automated segmentation of white matter, ventricle, vascular and hypoperfused regions in the ischemic brain. In conclusion, directional IVIM signals were simultaneously sensitive to diffusion and aligned flow and were particularly useful for automatically segmenting ischemic lesions via cNMF‐based pattern recognition.     

Diffusion‐weighted MRI with intravoxel incoherent motion modeling for assessment of muscle perfusion in the thigh during post‐exercise hyperemia in younger and older adults

Aging is associated with impaired endothelium‐dependent vasodilation that leads to muscle perfusion impairment and contributes to organ dysfunction. Impaired muscle perfusion may result in inadequate delivery of oxygen and nutrients during and after muscle contraction, leading to muscle damage. The ability to study the relationship between perfusion and muscle damage has been limited using traditional muscle perfusion measures, which are invasive and risky. To overcome this limitation, we optimized a diffusion‐weighted MRI sequence and validated an intravoxel incoherent motion (IVIM) analysis based on Monte Carlo simulation to study muscle perfusion impairment with aging during post‐exercise hyperemia. Simulation results demonstrated that the bias of IVIM‐derived perfusion fraction (f_p ) and diffusion of water molecules in extra‐vascular tissue (D ) ranged from ?3.3% to 14% and from ?16.5% to 0.002%, respectively, in the optimized experimental condition. The dispersion in f_p and D ranged from 3.2% to 9.5% and from 0.9% to 1.1%, respectively. The mid‐thigh of the left leg of four younger (21–30 year old) and four older (60–90 year old) healthy females was studied using the optimized protocol at baseline and at seven time increments occurring every 3.25 min following in‐magnet dynamic knee extension exercise performed using a MR‐compatible ergometer with a workload of 0.4 bar for 2.5 min. After exercise, both f_p and D significantly increased in the rectus femoris (active muscle during exercise) but not in adductor magnus (inactive muscle), reflecting the fact that the local increase in perfusion with both groups showed a maximum value in the second post‐exercise time‐point. A significantly greater increase in perfusion from the baseline (p < 0.05) was observed in the younger group (37 ± 12.05%) compared with the older group (17.57 ± 15.92%) at the first post‐exercise measurement. This work establishes a reliable non‐invasive method that can be used to study the effects of aging on dynamic changes in muscle perfusion as they relate to important measures of physical function.     

Evaluation of segmented 3D acquisition schemes for whole‐brain high‐resolution arterial spin labeling at 3 T

Recent technical developments have significantly increased the signal‐to‐noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole‐brain high‐resolution perfusion imaging, combining pseudo‐continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in‐plane k‐space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in‐plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack‐Of‐Spirals). High‐resolution perfusion images (2 × 2 × 4 mm³) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray‐to‐white matter contrast. Point‐spread‐function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in‐plane segmented 3D readouts and BS provided high‐SNR high‐resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack‐Of‐Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through‐plane blurring due to its inherent oversampling of the central k‐space region, its reduced effective T_E and shorter total readout time, at the expense of a slight increase in the effective in‐plane voxel size. Copyright © 2014 John Wiley & Sons, Ltd.     

Demonstration of asymmetric muscle perfusion of the back after exercise in patients with adolescent idiopathic scoliosis using intravoxel incoherent motion (IVIM) MRI

The purpose of this work was to quantify muscular perfusion patterns of back muscles after exercise in patients with adolescent idiopathic scoliosis (AIS) using intravoxel incoherent motion (IVIM) MR perfusion imaging. The paraspinal muscles of eight patients with AIS (Cobb angle 35 ± 10°, range [25‐47°]) and nine healthy volunteers were scanned with a 1.5 T MRI, at rest and after performing a symmetric back muscle exercise on a Roman chair. An IVIM sequence with 16 b‐values from 0 to 900 s/mm² was acquired, and the IVIM bi‐exponential signal equation model was fitted in two steps. Perfusion asymmetries were evaluated using the blood flow related IVIM fD* parameter in regions of interest placed within the paraspinal muscles. Statistical significance was assessed using a Student t‐test. The observed perfusion pattern after performing a Roman chair muscle exercise differed consistently in patients with AIS compared with healthy normal volunteers, and consisted of an asymmetrical increase in IVIM fD* [10^?3 mm²/s] above the lumbar convexity from 6.5 ± 5.8 to 28.8 ± 26.8 (p < 0.005), with no increase in the concavity (decrease from 6.5 ± 10.0 to 3.2 ± 1.5 (p = 0.19)), compared with a bilateral symmetric increase in the healthy volunteers (right, increase from 3.3 ± 2.1 to 10.1 ± 4.6 (p < 0.05); left, 6.7 ± 10.7 to 13.3 ± 7.0 (p < 0.05)). In conclusion, patients with AIS exhibit significant asymmetric muscle perfusion over the convexity of the scoliotic curvature after Roman chair exercise.     

Dynamic intravoxel incoherent motion imaging of skeletal muscle at rest and after exercise

The purpose of this work was to demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for non‐invasive quantification of perfusion and diffusion effects in skeletal muscle at rest and following exercise. After IRB approval, eight healthy volunteers underwent diffusion‐weighted MRI of the forearm at 3 T and eight different b values between 0 and 500 s/mm² with a temporal resolution of 57 s per dataset. Dynamic images were acquired before and after a standardized handgrip exercise. Diffusion (D) and pseudodiffusion (D*) coefficients as well as the perfusion fraction (F_P) were measured in regions of interest in the flexor digitorum superficialis and profundus (FDS/FDP), brachioradialis, and extensor carpi radialis longus and brevis muscles by using a multi‐step bi‐exponential analysis in MATLAB. Parametrical maps were calculated voxel‐wise. Differences in D, D*, and F_P between muscle groups and between time points were calculated using a repeated measures analysis of variance with post hoc Bonferroni tests. Mean values and standard deviations at rest were the following: D*, 28.5 ± 11.4 × 10^?3 mm²/s; F_P, 0.03 ± 0.01; D, 1.45 ± 0.09 × 10^?3 mm²/s. Changes of IVIM parameters were clearly visible on the parametrical maps. In the FDS/FDP, D* increased by 289 ± 236% (p < 0.029), F_P by 138 ± 58% (p < 0.01), and D by 17 ± 9% (p < 0.01). A significant increase of IVIM parameters could also be detected in the brachioradialis muscle, which however was significantly lower than in the FDS/FDP. After 20 min, all parameters were still significantly elevated in the FDS/FDP but not in the brachioradialis muscle compared with the resting state. The IVIM approach allows simultaneous quantification of muscle perfusion and diffusion effects at rest and following exercise. It may thus provide a useful alternative to other non‐invasive methods such as arterial spin labeling. Possible fields of interest for this technique include perfusion‐related muscle diseases, such as peripheral arterial occlusive disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Correlative assessment of tumor microcirculation using contrast‐enhanced perfusion MRI and intravoxel incoherent motion diffusion‐weighted MRI: is there a link between them?

The purpose of this study was to correlate intravoxel incoherent motion (IVIM) imaging with classical perfusion‐weighted MRI metrics in human gliomas. Parametric images for slow diffusion coefficient (D), fast diffusion coefficient (D*), and fractional perfusion‐related volume (f) in patients with high‐grade gliomas were generated. Maps of F_p (plasma flow), v_p (vascular plasma volume), PS (permeability surface–area product), v_e (extravascular, extracellular volume), E (extraction ratio), k_e (influx ratio into the interstitium), and t_c (vascular transit time) from dynamic contrast‐enhanced (DCE) and dynamic susceptibility contrast‐enhanced (DSC) MRI were also generated. A region‐of‐interest analysis on the contralateral healthy white matter and on the tumor areas was performed and the extracted parameter values were tested for any significant differences among tumor grades or any correlations. Only f could be significantly correlated to DSC‐derived v_p and t_c in healthy brain tissue. Concerning the tumor regions, F_p was significantly positively correlated with D* and inversely correlated with f in DSC measurements. The D*, f, and f × D* values in the WHO grade III gliomas were non‐significantly different from those in the grade IV gliomas. There was a trend to significant negative correlations between f and PS as well as between f × D* and k_e in DCE experiments. Presumably due to different theoretical background, tracer properties and modeling of the tumor vasculature in the IVIM theory, there is no clearly evident link between D*, f and DSC‐ and DCE‐derived metrics. Copyright © 2014 John Wiley & Sons, Ltd.     

Stroke assessment with intravoxel incoherent motion diffusion‐weighted MRI

Intravoxel incoherent motion (IVIM) diffusion‐weighted MRI can simultaneously measure diffusion and perfusion characteristics in a non‐invasive way. This study aimed to determine the potential utility of IVIM in characterizing brain diffusion and perfusion properties for clinical stroke. The multi‐b‐value diffusion‐weighted images of 101 patients diagnosed with acute/subacute ischemic stroke were retrospectively evaluated. The diffusion coefficient D, representing the water apparent diffusivity, was obtained by fitting the diffusion data with increasing high b‐values to a simple mono‐exponential model. The IVIM‐derived perfusion parameters, pseudodiffusion coefficient D*, vascular volume fraction f and blood flow‐related parameter fD*, were calculated with the bi‐exponential model. Additionally, the apparent diffusion coefficient (ADC) was fitted according to the mono‐exponential model using all b‐values. The diffusion parameters for the ischemic lesion and normal contralateral region were measured in each patient. Statistical analysis was performed using the paired Student t‐test and Pearson correlation test. Diffusion data in both the ischemic lesion and normal contralateral region followed the IVIM bi‐exponential behavior, and the IVIM model showed better goodness of fit than the mono‐exponential model with lower Akaike information criterion values. The paired Student t‐test revealed significant differences for all diffusion parameters (all P < 0.001) except D* (P = 0.218) between ischemic and normal areas. For all patients in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001) and f (r = 0.541, P < 0.001; r = 0.262, P = 0.008); significant correlation was also found between ADC and fD* in the ischemic region (r = 0.254, P = 0.010). For all pixels within the region of interest from a representative subject in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001), f (r = 0.823, P < 0.001; r = 0.652, P < 0.001) and fD* (r = 0.294, P < 0.001; r = 0.340, P < 0.001). These findings may have clinical implications for the use of IVIM imaging in the assessment and management of acute/subacute stroke patients. Copyright © 2016 John Wiley & Sons, Ltd.     

Multi‐centre reproducibility of diffusion MRI parameters for clinical sequences in the brain

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice–water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub‐regions. A mixed effect model was used to measure the intra‐ and inter‐scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra‐ and inter‐scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra‐scanner CV of 8.4% and inter‐scanner CV of 24.8%. No major difference in the inter‐scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra‐scanner reproducibility, with the inter‐scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter‐scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi‐centre clinical studies and trials. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

Gaussian mixture model‐based classification of dynamic contrast enhanced MRI data for identifying diverse tumor microenvironments: preliminary results

Tumor hypoxia develops heterogeneously, affects radiation sensitivity and the development of metastases. Prognostic information derived from the in vivo characterization of the spatial distribution of hypoxic areas in solid tumors can be of value for radiation therapy planning and for monitoring the early treatment response. Tumor hypoxia is caused by an imbalance between the supply and consumption of oxygen. The tumor oxygen supply is inherently linked to its vasculature and perfusion which can be evaluated by dynamic contrast enhanced (DCE‐) MRI using the contrast agent Gd‐DTPA. Thus, we hypothesize that DCE‐MRI data may provide surrogate information regarding tumor hypoxia. In this study, DCE‐MRI data from a rat prostate tumor model were analysed with a Gaussian mixture model (GMM)‐based classification to identify perfused, hypoxic and necrotic areas for a total of ten tumor slices from six rats, of which one slice was used as training data for GMM classifications. The results of pattern recognition analyzes were validated by comparison to corresponding Ak_ep maps defining the perfused area (0.84 ± 0.09 overlap), hematoxylin and eosin (H&E)‐stained tissue sections defining necrosis (0.64 ± 0.15 overlap) and pimonidazole‐stained sections defining hypoxia (0.72 ± 0.17 overlap), respectively. Our preliminary data indicate the feasibility of a GMM‐based classification to identify tumor hypoxia, necrosis and perfusion/permeability from non‐invasively acquired, in vivo DCE‐MRI data alone, possibly obviating the need for invasive procedures, such as biopsies, or exposure to radioactivity, such as positron emission tomography (PET) exams. Copyright © 2013 John Wiley & Sons, Ltd.     

Measurement of glycine in healthy and tumorous brain by triple‐refocusing MRS at 3 T in vivo

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors. The precise measurement of Gly is challenging largely as a result of the spectral overlap with myo‐inositol (mI). We report a new triple‐refocusing sequence for the reliable co‐detection of Gly and mI at 3 T and for the evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density‐matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of the mI signal between 3.5 and 3.6 ppm and, consequently, well‐defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In vivo ¹H magnetic resonance spectroscopy (MRS) data were acquired from the gray matter (GM)‐dominant medial occipital and white matter (WM)‐dominant left parietal regions in six healthy subjects, and analyzed with LCModel using in‐house‐calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM‐rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63 ± 0.05 and 8.6 ± 0.6 mM for the medial occipital and 0.34 ± 0.05 and 5.3 ± 0.8 mM for the left parietal regions, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratios between pure GM and pure WM were estimated to be 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher than those of healthy brain. Gly elevation was more extensive in a post‐contrast enhancing region than in a non‐enhancing region. The data indicate that the optimized triple‐refocusing sequence may provide reliable co‐detection of Gly and mI, and alterations of Gly in brain tumors can be precisely evaluated.