A microscopic model of the dose distribution in hepatocellular carcinoma after selective internal radiation therapy.

The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images. METHODS: Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law. RESULTS: In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver. CONCLUSIONS: The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images.

Intravoxel incoherent motion and diffusion kurtosis imaging at 3T MRI: Application to ischemic stroke.

BACKGROUND AND PURPOSE: The DKI-IVIM model that incorporates DKI (diffusional kurtosis imaging) into the IVIM (Intravoxel Incoherent Motion) concept was investigated to assess its utility for both enhanced diffusion characterization and perfusion measurements in ischemic stroke at 3 T. METHODS: Fifteen stroke patients (71 ± 11 years old) were enrolled and DKI-IVIM analysis was performed using 9 b-values from 0 to 1500 s/mm2 chosen with the Cramer-Rao-Lower-Bound optimization approach. Pseudo-diffusion coefficient D*, perfusion fraction f, blood flow-related parameter fD*, the diffusion coefficient D and an additional parameter, the kurtosis, K were determined in the ischemic lesion and controlateral normal tissue based on a region of interest approach. The apparent diffusion coefficient (ADC) and arterial spin labelling (ASL) cerebral blood flow (CBF) parameters were also assessed and parametric maps were obtained for all parameters. RESULTS: Significant differences were observed for all diffusion parameters with a significant decrease for D (p < 0.0001), ADC (p < 0.0001), and a significant increase for K (p < 0.0001) in the ischemic lesions of all patients. f decreased significantly in these regions (p = 0.0002). The fD* increase was not significant (p = 0.56). The same significant differences were found with a motion correction except for fD* (p = 0.47). CBF significantly decreased in the lesions. ADC was significantly positively correlated with D (p < 0.0001) and negatively with K (p = 0.0002); K was also negatively significantly correlated with D (p = 0.01). CONCLUSIONS: DKI-IVIM model enables for simultaneous cerebral perfusion and enhanced diffusion characterization in an acceptable clinically acquisition time for the ischemic stroke diagnosis with the additional kurtosis factor estimation, that may better reflect the microstructure heterogeneity.

Impact of point-spread function reconstruction on dynamic and static 18F-DOPA PET/CT quantitative parameters in glioma.

BACKGROUND: Quantification of dynamic and static parameters extracted from 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA, FDOPA) positron emission tomography (PET)/computed tomography (CT) plays a critical role for glioma assessment. The objective of the present study was to investigate the impact of point-spread function (PSF) reconstruction on these quantitative parameters. METHODS: Fourteen patients with untreated gliomas and investigated with FDOPA PET/CT were analyzed. The distribution of the 14 cases was as follows: 6 astrocytomas-isocitrate dehydrogenase-mutant; 2 oligodendrogliomas/1p19q-codeleted-isocitrate dehydrogenase-mutant; and 6 isocitrate dehydrogenase-wild-type glioblastomas. A 0-20-min dynamic images (8×15, 2×30, 2×60, and 3×300 s post-injection) and a 0-20-min static image were reconstructed with and without PSF. Tumoral volumes-of-interest were generated on all of the PET series and the background volumes-of-interest were generated on the 0-20-min static image with and without PSF. Static parameters (SUVmax and SUVmean) of the tumoral and the background volumes-of-interest and kinetic parameters (K1 and k2) of the tumoral volumes-of-interest extracted from using full kinetic analysis were provided. PSF and non-PSF quantitative parameters values were compared. RESULTS: Thirty-three tumor volumes-of-interest and 14 background volumes-of-interest were analyzed. PSF images provided higher tumor SUVmax than non-PSF images for 23/33 VOIs [median SUVmax =3.0 (range, 1.4-10.2) with PSF vs. 2.7 (range, 1.4-9.1) without PSF; P<0.001] and higher tumor SUVmean for 13/33 volumes-of-interest [median SUVmean =2.0 (range, 0.8-7.6) with PSF vs. 2.0 (range, 0.8-7.4) without PSF; P=0.002]. K1 and k2 were significantly lower with PSF than without PSF [respectively median K1 =0.077 mL/ccm/min (range, 0.043-0.445 mL/ccm/min) with PSF vs. 0.101 mL/ccm/min (range, 0.055-0.578 mL/ccm/min) without PSF; P<0.001 and median k2 =0.070 min-1 (range, 0.025-0.146 min-1) with PSF vs. 0.081 min-1 (range, 0.027-0.180 min-1) without PSF; P<0.001]. Background SUVmax and SUVmean were statistically unaffected [respectively median SUVmax =1.7 (range, 1.3-2.0) with PSF vs. 1.7 (range, 1.3-1.9) without PSF; P=0.346 and median SUVmean =1.5 (range, 1.0-1.8) with PSF vs. 1.5 (range, 1.0-1.7) without PSF; P=0.371]. CONCLUSIONS: The present study confirms that PSF significantly increases tumor activity concentrations measured on PET images. PSF algorithms for quantitative PET/CT analysis should be used with caution, especially for quantification of kinetic parameters.

Toward an Intravoxel Incoherent Motion 2-in-1 Magnetic Resonance Imaging Sequence for Ischemic Stroke Diagnosis? An Initial Clinical Experience With 1.5T Magnetic Resonance.

OBJECTIVE: This initial study aimed to investigate the feasibility of simultaneously measuring perfusion and diffusion including kurtosis features in acute ischemic stroke with the combined intravoxel incoherent motion and non-Gaussian diffusional kurtosis imaging (DKI-IVIM). MATERIAL AND METHODS: Five ischemic stroke patients underwent a 4-minute diffusion weighted imaging (DWI) protocol, using 8 b values chosen with the Cramer-Rao-Lower-Bound optimization approach, in addition to conventional DWI and arterial spin labeling sequences. Regions of interest in pathological and control regions were analyzed with DKI-IVIM, and parametric maps were reconstructed. RESULTS: The IVIM diffusion coefficient (D) decreased (P < 0.0001) in the infarcted areas, whereas higher kurtosis coefficient values were found (P = 0.0002). Regarding the perfusion, the individual IVIM perfusion fraction f decreased in 3 matching cases with the cerebral blood flow estimated through arterial spin labeling and the fD* decreased only in 2 patients of those. CONCLUSIONS: When compared with conventional stroke imaging protocol, DKI-IVIM 4-minute 2-in-1 acquisition can provide diffusion results comparable with conventional DWI with complementary kurtosis estimations but a limited robustness regarding perfusion estimations for clinical purpose.

Additive Value of Dynamic FDOPA PET/CT for Glioma Grading.

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas. Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC). Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min-1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP). Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.

Voxel-based mapping of five MR biomarkers in the wrist bone marrow.

OBJECTIVE: MRI is a reliable and accurate technique to characterize rheumatoid arthritis. The aim of this study was to provide voxel-by-voxel 3D maps of the proton density fat fraction (PDFF), the T1 of water (T1W), the T1 of fat (T1F), the T2* of water (T2*W), the T2* of fat (T2*F) in the wrist bone marrow. MATERIALS AND METHODS: The experiments were conducted on 14 healthy volunteers (mean age: 24 ± 4). The data were acquired at 1.5 T using two optimized four-echo 3D 1.2 × 1.2 × 1.2 mm3-isotropic spoiled gradient sequences. A repeatability study was carried out. The measurements were done using a homemade parametric viewer software. RESULTS: The inter-volunteer results were, on average: PDFF = 86 ± 3%, T1W = 441 ± 113 ms, T1F = 245 ± 19 ms, T2*W = 6 ± 1 ms and T2*F = 16 ± 3 ms. The coefficients of variation were for fat based biomarkers CVPDFF < 5%, CVT1F < 15% and CVT2*F < 10% in the repeatability study. DISCUSSION: The protocol and quantification tool proposed in this study provide high-resolution voxel-by-voxel 3D maps of five biomarkers in the wrist in less than 4 min of acquisition.

High-resolution multi-T1 -weighted contrast and T1 mapping with low B1>+ sensitivity using the fluid and white matter suppression (FLAWS) sequence at 7T.

PURPOSE: To demonstrate that fluid and white matter suppression (FLAWS) imaging can be used for high-resolution T1 mapping with low transmitted bias field ( B1+ ) sensitivity at 7T. METHODS: The FLAWS sequence was optimized for 0.8-mm isotropic resolution imaging. The theoretical accuracy and precision of the FLAWS T1 mapping was compared with the one of the magnetization-prepared two rapid gradient echoes (MP2RAGE) sequence optimized for low B1+ sensitivity. FLAWS images were acquired at 7T on six healthy volunteers (21 to 48 years old; two women). MP2RAGE and saturation-prepared with two rapid gradient echoes (SA2RAGE) datasets were also acquired to obtain T1 mapping references and B1+ maps. The contrast-to-noise ratio (CNR) between brain tissues was measured in the FLAWS-hco and MP2RAGE-uni images. The Pearson correlation was measured between the MP2RAGE and FLAWS T1 maps. The effect of B1+ on FLAWS T1 mapping was assessed using the Pearson correlation. RESULTS: The FLAWS-hco images were characterized by a higher brain tissue CNR ( CNRWM/GM=5.5 , CNRWM/CSF=14.7 , CNRGM/CSF=10.3 ) than the MP2RAGE-uni images ( CNRWM/GM=4.9 , CNRWM/CSF=6.6 , CNRGM/CSF=3.7 ). The theoretical accuracy and precision of the FLAWS T1 mapping ( acc=91.9%;prec=90.2% ) were in agreement with those provided by the MP2RAGE T1 mapping ( acc=90.0%;prec=86.8% ). A good agreement was found between in vivo T1 values measured with the MP2RAGE and FLAWS sequences (r = 0.91). A weak correlation was found between the FLAWS T1 map and the B1+ map within cortical gray matter and white matter segmentations ( rWM=-0.026 ; rGM=0.081 ). CONCLUSION: The results from this study suggest that FLAWS is a good candidate for high-resolution T1 -weighted imaging and T1 mapping at the field strength of 7T.

Confounding factors in multi-parametric q-MRI protocol: A study of bone marrow biomarkers at 1.5 T.

OBJECT: The MRI tissue characterization of vertebral bone marrow includes the measurement of proton density fat fraction (PDFF), T1 and T2* relaxation times of the water and fat components (T1W, T1F, T2*W, T2*F), IVIM diffusion D, perfusion fraction f and pseudo-diffusion coefficient D*. However, the measurement of these vertebral bone marrow biomarkers (VBMBs) is affected with several confounding factors. In the current study, we investigated these confounding factors including the regional variation taking the example of variation between the anterior and posterior area in lumbar vertebrae, B1 inhomogeneity and the effect of fat suppression on f. MATERIALS AND METHODS: A fat suppressed diffusion-weighted sequence and two 3D gradient multi-echo sequences were used for the measurements of the seven VBMBs. A turbo flash B1 map sequence was used to estimate B1 inhomogeneities and thus, to correct flip angle for T1 quantification. We introduced a correction to perfusion fraction f measured with fat suppression, namely fPDFF. RESULTS: A significant difference in the values of PDFF, f and fPDFF, T1F, T2*W and D was observed between the anterior and posterior region. Although, little variations of flip angle were observed in this anterior-posterior direction in one vertebra but larger variations were observed in head-feet direction from L1 to L5 vertebrae. DISCUSSION: The regional difference in PDFF, fPDFF and T2*W can be ascribed to differences in the trabecular bone density and vascular network within vertebrae. The regional variation of VBMBs shows that care should be taken in reproducing the same region-of-interest location along a longitudinal study. The same attention should be taken while measuring f in fatty environment, and measuring T1. Furthermore, the MRI-protocol presented here allows for measurements of seven VBMBs in less than 6 min and is of interest for longitudinal studies of bone marrow diseases.

Optimization of time frame binning for FDOPA uptake quantification in glioma.

INTRODUCTION: 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA) uptake quantification in glioma assessment can be distorted using a non-optimal time frame binning of time-activity curves (TAC). Under-sampling or over-sampling dynamic PET images induces significant variations on kinetic parameters quantification. We aimed to optimize temporal time frame binning for dynamic FDOPA PET imaging. METHODS: Fourteen patients with 33 tumoral TAC with biopsy-proven gliomas were analysed. The mean SUVmax tumor-to-brain ratio (TBRmax) were compared at 20 min and 35 min post-injection (p.i). Five different time frame samplings within 20 min were compared: 11x10sec-6x15sec-5x20sec-3x300sec; 8x15sec- 2x30sec- 2x60sec- 3x300sec; 6x20sec- 8x60sec- 2x300sec; 10x30sec- 3x300sec and 4x45sec- 3x90sec- 5x150sec. The reversible single-tissue compartment model with blood volume parameter (VB) was selected using the Akaike information criterion. K1 values extracted from 1024 noisy simulated TAC using Monte Carlo method from the 5 different time samplings were compared to a target K1 value as the objective, which is the average of the K1 values extracted from the 33 lesions using an imaging-derived input function for each patient. RESULTS: The mean TBRmax was significantly higher at 20 min p.i. than at 35 min p.i (respectively 1.4 +/- 0.8 and 1.2 +/- 0.6; p <0.001). The target K1 value was 0.161 mL/ccm/min. The 8x15sec- 2x30sec- 2x60sec- 3x300sec time sampling was the optimal time frame binning. K1 values extracted using this optimal time frame binning were significantly different with K1 values extracted from the other time frame samplings, except with K1 values obtained using the 11x10sec- 6x15sec -5x20sec-3x300sec time frame binning. CONCLUSIONS: This optimal sampling schedule design (8x15sec- 2x30sec- 2x60sec- 3x300sec) could be used to minimize bias in quantification of FDOPA uptake in glioma using kinetic analysis.

Comparison of Deep Learning-Based and Patch-Based Methods for Pseudo-CT Generation in MRI-Based Prostate Dose Planning.

PURPOSE: Deep learning methods (DLMs) have recently been proposed to generate pseudo-CT (pCT) for magnetic resonance imaging (MRI) based dose planning. This study aims to evaluate and compare DLMs (U-Net and generative adversarial network [GAN]) using various loss functions (L2, single-scale perceptual loss [PL], multiscale PL, weighted multiscale PL) and a patch-based method (PBM). METHODS AND MATERIALS: Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer (78 Gy). T2-weighted MRIs were acquired in addition to planning CTs. The pCTs were generated from the MRIs using 7 configurations: 4 GANs (L2, single-scale PL, multiscale PL, weighted multiscale PL), 2 U-Net (L2 and single-scale PL), and the PBM. The imaging endpoints were mean absolute error and mean error, in Hounsfield units, between the reference CT (CTref) and the pCT. Dose uncertainties were quantified as mean absolute differences between the dose volume histograms (DVHs) calculated from the CTref and pCT obtained by each method. Three-dimensional gamma indexes were analyzed. RESULTS: Considering the image uncertainties in the whole pelvis, GAN L2 and U-Net L2 showed the lowest mean absolute error (≤34.4 Hounsfield units). The mean errors were not different than 0 (P ≤ .05). The PBM provided the highest uncertainties. Very few DVH points differed when comparing GAN L2 or U-Net L2 DVHs and CTref DVHs (P ≤ .05). Their dose uncertainties were ≤0.6% for the prostate planning target Volume V95%, ≤0.5% for the rectum V70Gy, and ≤0.1% for the bladder V50Gy. The PBM, U-Net PL, and GAN PL presented the highest systematic dose uncertainties. The gamma pass rates were >99% for all DLMs. The mean calculation time to generate 1 pCT was 15 s for the DLMs and 62 min for the PBM. CONCLUSIONS: Generating pCT for MRI dose planning with DLMs and PBM provided low-dose uncertainties. In particular, the GAN L2 and U-Net L2 provided the lowest dose uncertainties together with a low computation time.

Pseudo-CT Generation for MRI-Only Radiation Therapy Treatment Planning: Comparison Among Patch-Based, Atlas-Based, and Bulk Density Methods.

PURPOSE: Methods have been recently developed to generate pseudo-computed tomography (pCT) for dose calculation in magnetic resonance imaging (MRI)-only radiation therapy. This study aimed to propose an original nonlocal mean patch-based method (PBM) and to compare this PBM to an atlas-based method (ABM) and to a bulk density method (BDM) for prostate MRI-only radiation therapy. MATERIALS AND METHODS: Thirty-nine patients received a volumetric modulated arc therapy for prostate cancer. In addition to the planning computed tomography (CT) scans, T2-weighted MRI scans were acquired. pCTs were generated from MRIs using 3 methods: an original nonlocal mean PBM, ABM, and BDM. The PBM was performed using feature extraction and approximate nearest neighbor search in a training cohort. The PBM accuracy was evaluated in a validation cohort by using imaging and dosimetric endpoints. Imaging endpoints included mean absolute error and mean error between Hounsfield units of the pCT and the reference CT (CTref). Dosimetric endpoints were based on dose-volume histograms calculated from the CTref and the pCTs for various volumes of interest and on 3-dimensional gamma analyses. The PBM uncertainties were compared with those of the ABM and BDM. RESULTS: The mean absolute error and mean error obtained from the PBM were 41.1 and -1.1 Hounsfield units. The PBM dose-volume histogram differences were 0.7% for prostate planning target volume V95%, 0.5% for rectum V70Gy, and 0.2% for bladder V50Gy. Compared with ABM and BDM, PBM provided significantly lower dose uncertainties for the prostate planning target volume (70-78 Gy), the rectum (8.5-29 Gy, 40-48 Gy, and 61-73 Gy), and the bladder (12-78 Gy). The PBM mean gamma pass rate (99.5%) was significantly higher than that of ABM (94.9%) or BDM (96.1%). CONCLUSIONS: The proposed PBM provides low uncertainties with dose planned on CTref. These uncertainties were smaller than those of ABM and BDM and are unlikely to be clinically significant.

Comparison of 18F-Choline PET/CT and MRI functional parameters in prostate cancer.

AIM: 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. MATERIALS AND METHODS: Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. RESULTS: The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). CONCLUSIONS: No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Measurements of Diffusion and Perfusion in Vertebral Bone Marrow Using Intravoxel Incoherent Motion (IVIM) With Multishot, Readout-Segmented (RESOLVE) Echo-Planar Imaging.

BACKGROUND: A limited number of studies have used the intravoxel incoherent motion (IVIM) approach on bone marrow. In none of the previous studies were the effects of fat suppression on the IVIM parameters investigated. PURPOSE: To measure the water diffusion coefficient and the perfusion fraction in vertebral bone marrow using IVIM with multishot, readout-segmented (RESOLVE) echo-planar imaging and to assess the effects of different fat suppression techniques on the measurement of the IVIM parameters. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Six healthy volunteers (24.2 ± 4.3 years). FIELD STRENGTH/SEQUENCE: 1.5T, RESOLVE. ASSESSMENT: Four experiments were performed: 1) RESOLVE imaging without fat suppression, 2) with fat saturation (FS), 3) with spectral attenuated inversion recovery (SPAIR), and 4) with short-tau inversion recovery (STIR). The water diffusion coefficient D, pseudo-diffusion coefficient D*, and the perfusion fraction f were assessed in the vertebral bodies of the lumbar vertebrae. STATISTICAL TESTS: One-way repeated-measures analysis of variance (ANOVA) followed by Bonferroni's multiple comparison test. RESULTS: The RESOLVE IVIM protocol allowed for measurement of D, D*, and f in all volunteers. The signal of lipid protons affected the quantification of the IVIM diffusion coefficient: D = 0.24 ± 0.10 (×10-3 mm2 /s), no FS; D = 0.43 ± 0.07 (×10-3 mm2 /s), FS; D = 0.42 ± 0.07 (×10-3 mm2 /s), SPAIR; D = 0.35 ± 0.10 (×10-3 mm2 /s), STIR; and IVIM perfusion fraction f = 7.5 ± 1.9% no FS, f = 14.5 ± 5.4%, FS; f = 12.5 ± 2.6%, SPAIR; f = 18.1 ± 6.1%, STIR. No significant effect (P = 0.36) was found on the quantification of D*. DATA CONCLUSION: An IVIM-MRI protocol using the RESOLVE sequence was implemented for measurements of vertebral bone marrow diffusion and the perfusion. The comparison between the protocols with and without fat suppression indicates that the lipid signal results in an underestimation of both D and f. LEVEL OF EVIDENCE: Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;49:768-776.

fMRI-Based Brain Responses to Quinine and Sucrose Gustatory Stimulation for Nutrition Research in the Minipig Model: A Proof-of-Concept Study.

The minipig model is of high interest for brain research in nutrition and associated pathologies considering the similarities to human nutritional physiology, brain structures, and functions. In the context of a gustatory stimulation paradigm, fMRI can provide crucial information about the sensory, cognitive, and hedonic integration of exteroceptive stimuli in healthy and pathological nutritional conditions. Our aims were (i) to validate the experimental setup, i.e., fMRI acquisition and SPM-based statistical analysis, with a visual stimulation; (ii) to implement the fMRI procedure in order to map the brain responses to different gustatory stimulations, i.e., sucrose (5%) and quinine (10 mM), and (ii) to investigate the differential effects of potentially aversive (quinine) and appetitive/pleasant (sucrose) oral stimulation on brain responses, especially in the limbic and reward circuits. Six Yucatan minipigs were imaged on an Avanto 1.5-T MRI under isoflurane anesthesia and mechanical ventilation. BOLD signal was recorded during visual or gustatory (artificial saliva, sucrose, or quinine) stimulation with a block paradigm. With the visual stimulation, brain responses were detected in the visual cortex, thus validating our experimental and statistical setup. Quinine and sucrose stimulation promoted different cerebral activation patterns that were concordant, to some extent, to results from human studies. The insular cortex (i.e., gustatory cortex) was activated with both sucrose and quinine, but other regions were specifically activated by one or the other stimulation. Gustatory stimulation combined with fMRI analysis in large animals such as minipigs is a promising approach to investigate the integration of gustatory stimulation in healthy or pathological conditions such as obesity, eating disorders, or dysgeusia. To date, this is the first intent to describe gustatory stimulation in minipigs using fMRI.

Optimization of temporal sampling for 18F-choline uptake quantification in prostate cancer assessment.

BACKGROUND: Suboptimal temporal sampling of time-activity curves (TAC) from dynamic 18F-fluoromethylcholine (FCH) PET images may introduce bias in quantification of FCH uptake in prostate cancer assessment. We sought to define an optimal temporal sampling protocol for dynamic FCH PET imaging. Seven different time samplings were tested: 5 × 60″, 10 × 30″, 15 × 15″-1 × 75″, 6 × 10″-8 × 30″, 12 × 5″-8 × 30″; 10 × 5″-4 × 10″-3 × 20″-5 × 30″, and 8 × 3″-8 × 12″-6 × 30″. First, the irreversible and reversible one-tissue compartment model with blood volume parameter (VB) (respectively, 1T1K+VB and 1T2k+VB, with K1 = transfer coefficient from the arterial blood to the tissue compartment and k2 = transfer coefficient from the tissue compartment to the arterial blood) were compared for 37 lesions from 32 patients who underwent FCH PET imaging for initial or recurrence assessment of prostate cancer, and the model was selected using the Akaike information criterion. To determine the optimal time sampling, K1 values extracted from 1000 noisy-simulated TAC using Monte Carlo method from the seven different time samplings were compared to a target K1 value which is the average of the K1 values extracted from the 37 lesions using an imaging-derived input function for each patient. K1 values extracted with the optimal time sampling for each tumoral lesion were compared to K1 values extracted from each of the other time samplings for the 37 lesions. RESULTS: The 1T2k + VB model was selected. The target K1 value as the objective was 0.506 mL/ccm/min (range 0.216-1.246). Results showed a significant difference between K1 values from the simulated TAC with the seven different time samplings analyzed. The closest K1 value from the simulated TAC to the target K1 value was obtained by the 12 × 5″-8 × 30″ time sampling. Concerning the clinical validation, K1 values extracted from the optimal time sampling (12 × 5″-8 × 30″) were significantly different with K1 values extracted from the other time samplings, except for the comparison with K1 values extracted from the 10 × 5″-4 × 10″-3 × 20″-5 × 30″ time sampling. CONCLUSIONS: A two-phase framing of dynamic PET reconstruction with frame durations of 5 s (blood phase) and 30 s (tissue phase) could be used to sample the TAC for uptake quantification in prostate cancer assessment.

Comparison of choline influx from dynamic 18F-Choline PET/CT and clinicopathological parameters in prostate cancer initial assessment.

AIM: The aim of the study was to compare the kinetic analysis of 18F-labeled choline (FCH) uptake with static analysis and clinicopathological parameters in patients with newly diagnosed prostate cancer (PC). MATERIALS AND METHODS: Sixty-one patients were included. PSA was performed few days before FCH PET/CT. Gleason scoring (GS) was collected from systematic sextant biopsies. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition (from 0 to10 min post-injection) and late whole-body acquisition (60 min post-injection). PC volume of interest was drawn using an adaptative thresholding (40% of the maximal uptake) on the late acquisition and projected onto an early static frame of 10 min and each of the 20 reconstructed frames of 30 s. Kinetic analysis was performed using an imaging-derived plasma input function. Early kinetic parameter (K1 as influx) and static parameters (early SUVmean, late SUVmean, and retention index) were extracted and compared to clinicopathological parameters. RESULTS: K1 was significantly, but moderately correlated with early SUVmean (r = 0.57, p < 0.001) and late SUVmean (r = 0.43, p < 0.001). K1, early SUVmean, and late SUVmean were moderately correlated with PSA level (respectively, r = 0.36, p = 0.004; r = 0.67, p < 0.001; r = 0.51, p < 0.001). Concerning GS, K1 was higher for patients with GS ≥ 4 + 3 than for patients with GS < 4 + 3 (median value 0.409 vs 0.272 min- 1, p < 0.001). No significant difference was observed for static parameters. CONCLUSIONS: FCH influx index K1 seems to be related to GS and could be a non-invasive tool to gain further information concerning tumor aggressiveness.

Tissue oxygenation mapping by combined chemical shift and T1 magnetic resonance imaging.

PURPOSE: To propose a method for determining tissue oxygenation via the measurement of fat T1 . The method is based on a 2D fat/water chemical shift-encoded and T1 -weighted acquisition. THEORY AND METHODS: A 2D data set was acquired with a fast spin echo sequence with several echo asymmetries and repetition times, wherein one dimension is related to the fat/water phase modulation and the other to the T1 saturation recovery. A joint magnitude-based process of phase modulation and T1 evolution allowed for the collection of the fat fraction and T1 maps with resolved fat or water dominance ambiguity while avoiding the phased error problem. RESULTS: In vitro imaging allowed for the attribution of fat content for different water/oil emulsions that demonstrated longitudinal relaxation rate (R1 ) sensitivity to the oxygenated emulsion environment. The fat R1 values were subsequently compared to reference values, which were measured using low receiver bandwidth acquisition to enhance water and fat signal separations. In vivo feasibility of tissue oxygenation assessment was demonstrated by investigating interscapular brown adipose tissue modifications during an air/carbogen challenge in rats. CONCLUSION: The proposed method offers a precise and robust estimate of tissue oxygenation illustrated by the method's ability to detect-brown adipose tissue oxygenation modifications. Magn Reson Med 79:1981-1991, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Towards a patient-specific hepatic arterial modeling for microspheres distribution optimization in SIRT protocol.

Selective internal radiation therapy (SIRT) using Yttrium-90 loaded glass microspheres injected in the hepatic artery is an emerging, minimally invasive therapy of liver cancer. A personalized intervention can lead to high concentration dose in the tumor, while sparing the surrounding parenchyma. We propose a computational model for patient-specific simulation of entire hepatic arterial tree, based on liver, tumors, and arteries segmentation on patient's tomography. Segmentation of hepatic arteries down to a diameter of 0.5 mm is semi-automatically performed on 3D cone-beam CT angiography. The liver and tumors are extracted from CT-scan at portal phase by an active surface method. Once the images are registered through an automatic multimodal registration, extracted data are used to initialize a numerical model simulating liver vascular network. The model creates successive bifurcations from given principal vessels, observing Poiseuille's and matter conservation laws. Simulations provide a coherent reconstruction of global hepatic arterial tree until vessel diameter of 0.05 mm. Microspheres distribution under simple hypotheses is also quantified, depending on injection site. The patient-specific character of this model may allow a personalized numerical approximation of microspheres final distribution, opening the way to clinical optimization of catheter placement for tumor targeting.

Virtual phantom magnetic resonance imaging (ViP MRI) on a clinical MRI platform.

PURPOSE: The purpose of this study was to implement Virtual Phantom Magnetic Resonance Imaging (ViP MRI), a technique that allows for generating reference signals in MR images using radiofrequency (RF) signals, on a clinical MR system and to test newly designed virtual phantoms. METHODS: MRI experiments were conducted on a 1.5 T MRI scanner. Electromagnetic modelling of the ViP system was done using the principle of reciprocity. The ViP RF signals were generated using a compact waveform generator (dimensions of 26 cm × 18 cm × 16 cm), connected to a homebuilt 25 mm-diameter RF coil. The ViP RF signals were transmitted to the MRI scanner bore, simultaneously with the acquisition of the signal from the object of interest. Different types of MRI data acquisition (2D and 3D gradient-echo) as well as different phantoms, including the Shepp-Logan phantom, were tested. Furthermore, a uniquely designed virtual phantom - in the shape of a grid - was generated; this newly proposed phantom allows for the investigations of the vendor distortion correction field. RESULTS: High quality MR images of virtual phantoms were obtained. An excellent agreement was found between the experimental data and the inverse cube law, which was the expected functional dependence obtained from the electromagnetic modelling of the ViP system. Short-term time stability measurements yielded a coefficient of variation in the signal intensity over time equal to 0.23% and 0.13% for virtual and physical phantom, respectively. MR images of the virtual grid-shaped phantom were reconstructed with the vendor distortion correction; this allowed for a direct visualization of the vendor distortion correction field. Furthermore, as expected from the electromagnetic modelling of the ViP system, a very compact coil (diameter ~ cm) and very small currents (intensity ~ mA) were sufficient to generate a signal comparable to that of physical phantoms in MRI experiments. CONCLUSIONS: The ViP MRI technique was successfully implemented on a clinical MR system. One of the major advantages of ViP MRI over previous approaches is that the generation and transmission of RF signals can be achieved with a self-contained apparatus. As such, the ViP MRI technique is transposable to different platforms (preclinical and clinical) of different vendors. It is also shown here that ViP MRI could be used to generate signals whose characteristics cannot be reproduced by physical objects. This could be exploited to assess MRI system properties, such as the vendor distortion correction field.

Non-invasive measurement of liver iron concentration using 3-Tesla magnetic resonance imaging: validation against biopsy.

OBJECTIVES: To evaluate the performance and limitations of the R2* and signal intensity ratio (SIR) methods for quantifying liver iron concentration (LIC) at 3 T. METHODS: A total of 105 patients who underwent a liver biopsy with biochemical LIC (LICb) were included prospectively. All patients underwent a 3-T MRI scan with a breath-hold multiple-echo gradient-echo sequence (mGRE). LIC calculated by 3-T SIR algorithm (LICSIR) and by R2* (LICR2*) were correlated with LICb. Sensitivity and specificity were calculated. The comparison of methods was analysed for successive classes. RESULTS: LICb was strongly correlated with R2* (r = 0.95, p < 0.001) and LICSIR (r = 0.92, p < 0.001). In comparison to LICb, LICR2* and LICSIR detect liver iron overload with a sensitivity/specificity of 0.96/0.93 and 0.92/0.95, respectively, and a bias ± SD of 7.6 ± 73.4 and 14.8 ± 37.6 µmol/g, respectively. LICR2* presented the lowest differences for patients with LICb values under 130 µmol/g. Above this value, LICSIR has the lowest differences. CONCLUSIONS: At 3 T, R2* provides precise LIC quantification for lower overload but the SIR method is recommended to overcome R2* limitations in higher overload. Our software, available at www.mrquantif.org , uses both methods jointly and selects the best one. KEY POINTS: • Liver iron can be accurately quantified by MRI at 3 T • At 3 T, R2* provides precise quantification of slight liver iron overload • At 3 T, SIR method is recommended in case of high iron overload • Slight liver iron overload present in metabolic syndrome can be depicted • Treatment can be monitored with great confidence.