Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time.

Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 min) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3-4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.

Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas.

PURPOSE: Radiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors. METHODS: Twenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals. RESULTS: Conventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively. CONCLUSIONS: Using APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment.

Estimation of diffusion, perfusion and fractional volumes using a multi-compartment relaxation-compensated intravoxel incoherent motion (IVIM) signal model.

Compartmental diffusion MRI models that account for intravoxel incoherent motion (IVIM) of blood perfusion allow for estimation of the fractional volume of the microvascular compartment. Conventional IVIM models are known to be biased by not accounting for partial volume effects caused by free water and cerebrospinal fluid (CSF), or for tissue-dependent relaxation effects. In this work, a three-compartment model (tissue, free water and blood) that includes relaxation terms is introduced. To estimate the model parameters, in vivo human data were collected with multiple echo times (TE), inversion times (TI) and b-values, which allowed a direct relaxation estimate alongside estimation of perfusion, diffusion and fractional volume parameters. Compared to conventional two-compartment models (with and without relaxation compensation), the three-compartment model showed less effects of CSF contamination. The proposed model yielded significantly different volume fractions of blood and tissue compared to the non-relaxation-compensated model, as well as to the conventional two-compartment model, suggesting that previously reported parameter ranges, using models that do not account for relaxation, should be reconsidered.

Separating blood and water: Perfusion and free water elimination from diffusion MRI in the human brain.

The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b-shells, demonstrated an expected non-zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b-shells.

Intravoxel incoherent motion (IVIM) imaging at different magnetic field strengths: what is feasible?

BACKGROUND: Due to limited SNR the cerebral applications of the intravoxel incoherent motion (IVIM) concept have been sparse. MRI hardware developments have resulted in improved SNR and this may justify a reassessment of IVIM imaging for non-invasive quantification of the cerebral blood volume (CBV) as a first step toward determining the optimal field strength. PURPOSE: To investigate intravoxel incoherent motion imaging for its potential to assess cerebral blood volume (CBV) at three different MRI field strengths. MATERIALS AND METHODS: Four volunteers were scanned twice at 1.5 T, 3 T as well as 7 T. By correcting for field-strength-dependent effects of relaxation, estimates of corrected CBV (cCBV) were obtained in deep gray matter (DGM), frontal gray matter (FGM) and frontal white matter (FWM), using Bayesian analysis. In addition, simulations were performed to facilitate the interpretation of experimental data. RESULTS: In DGM, FGM and FWM we obtained cCBV estimates of 2.2 ml/100 ml, 2.7 ml/100 ml, 1.4 ml/100 ml at 1.5 T; 3.7 ml/100 ml, 5.0 ml/100 ml, 3.2 ml/100 ml at 3 T and 15.5 ml/100 ml, 20.3 ml/100 ml, 7.0 ml/100 ml at 7 T. CONCLUSION: Quantitative cCBV values obtained at 1.5 T and 3 T corresponded better to physiological reference values, while 7 T showed the largest deviation from expected values. Simulations of synthetic tissue voxels indicated that the discrepancy at 7 T can partly be explained by SNR issues. Results were generally more repeatable at 7 T (intraclass correlation coefficient, ICC=0.84) than at 1.5 T (ICC=0.68) and 3 T (ICC=0.46).

Effects of restricted diffusion in a biological phantom: a q-space diffusion MRI study of asparagus stems at a 3T clinical scanner.

INTRODUCTION: The aim of this work was to study the effects of restricted diffusion in a biological phantom consisting of green asparagus stems using q-space MRI at a clinical scanner. METHOD: Measurements of the full width at half maximum (FWHM) of the displacement distribution were performed with varied diffusion time (Td). The accuracy of the measurements was investigated with respect to the degree of violation of the short gradient pulse (SGP) condition, partial volume effects and a FWHM-based tensor model. RESULTS: The measurements showed a reasonably constant FWHM perpendicular to the capillaries in the vascular bundles and an increased FWHM parallel with the bundles when the Td was increased. A 15% decrease in FWHM perpendicular to the bundles was observed when the diffusion encoding duration was prolonged from 24 to 74 ms, owing to the violation of the SGP condition. For a population of different confinement sizes, simulations indicated that the FWHM reflects the smaller sizes rather then the mean size of the confinements. CONCLUSION: A new method allowing tensor analysis of FWHM was derived and yielded accurate results. In conclusion, we found it possible to measure the effects of restricted diffusion with q-space MRI using a clinical MRI scanner.