Relating pre-treatment non-Gaussian intravoxel incoherent motion diffusion-weighted imaging to human papillomavirus status and response in oropharyngeal carcinoma.

Background and purpose: Diffusion-weighted imaging (DWI) is a promising technique for response assessment in head-and-neck cancer. Recently, we optimized Non-Gaussian Intravoxel Incoherent Motion Imaging (NG-IVIM), an extension of the conventional apparent diffusion coefficient (ADC) model, for the head and neck. In the current study, we describe the first application in a group of patients with human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma. The aim of this study was to relate ADC and NG-IVIM DWI parameters to HPV status and clinical treatment response. Materials and methods: Thirty-six patients (18 HPV-positive, 18 HPV-negative) were prospectively included. Presence of progressive disease was scored within one year. The mean pre-treatment ADC and NG-IVIM parameters in the gross tumor volume were compared between HPV-positive and HPV-negative patients. In HPV-negative patients, ADC and NG-IVIM parameters were compared between patients with and without progressive disease. Results: ADC, the NG-IVIM diffusion coefficient D, and perfusion fraction f were significantly higher, while pseudo-diffusion coefficient D* and kurtosis K were significantly lower in the HPV-negative compared to HPV-positive patients. In the HPV-negative group, a significantly lower D was found for patients with progressive disease compared to complete responders. No relation with ADC was observed. Conclusion: The results of our single-center study suggest that ADC is related to HPV status, but not an independent response predictor. The NG-IVIM parameter D, however, was independently associated to response in the HPV-negative group. Noteworthy in the opposite direction as previously thought based on ADC.

Advanced Diffusion-Weighted MRI for Cancer Microstructure Assessment in Body Imaging, and Its Relationship With Histology.

Diffusion-weighted magnetic resonance imaging (DW-MRI) aims to disentangle multiple biological signal sources in each imaging voxel, enabling the computation of innovative maps of tissue microstructure. DW-MRI model development has been dominated by brain applications. More recently, advanced methods with high fidelity to histology are gaining momentum in other contexts, for example, in oncological applications of body imaging, where new biomarkers are urgently needed. The objective of this article is to review the state-of-the-art of DW-MRI in body imaging (ie, not including the nervous system) in oncology, and to analyze its value as compared to reference colocalized histology measurements, given that demonstrating the histological validity of any new DW-MRI method is essential. In this article, we review the current landscape of DW-MRI techniques that extend standard apparent diffusion coefficient (ADC), describing their acquisition protocols, signal models, fitting settings, microstructural parameters, and relationship with histology. Preclinical, clinical, and in/ex vivo studies were included. The most used techniques were intravoxel incoherent motion (IVIM; 36.3% of used techniques), diffusion kurtosis imaging (DKI; 16.7%), vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT; 13.3%), and imaging microstructural parameters using limited spectrally edited diffusion (IMPULSED; 11.7%). Another notable category of techniques relates to innovative b-tensor diffusion encoding or joint diffusion-relaxometry. The reviewed approaches provide histologically meaningful indices of cancer microstructure (eg, vascularization/cellularity) which, while not necessarily accurate numerically, may still provide useful sensitivity to microscopic pathological processes. Future work of the community should focus on improving the inter-/intra-scanner robustness, and on assessing histological validity in broader contexts. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 2.

The Influence of Nonaerated Paranasal Sinuses on DTI Parameters of the Brain in 6- to 9-Year-Old Children.

BACKGROUND AND PURPOSE: DTI is prone to susceptibility artifacts. Air in the paranasal sinuses can cause field inhomogeneity, thus affecting measurements. Children often have mucus in their sinuses or no pneumatization of them. This study investigated the influence of lack of air in the paranasal sinuses on measurements of WM diffusion characteristics. MATERIALS AND METHODS: The study was embedded in the Generation R Study, a prospective population-based birth cohort in Rotterdam (the Netherlands). Brain MR imaging studies (1070 children, 6-9 years of age) were evaluated for mucosal thickening of the paranasal sinuses. Nonaeration of the paranasal sinuses (modified Lund-Mackay score) was compared with that in a randomly selected control group. The relationship between nonaerated paranasal sinuses and fractional anisotropy and mean diffusivity in the DTI fiber tracts was evaluated using ANCOVA and independent t tests. RESULTS: The prevalence of mucosal thickening was 10.2% (109/1070). The mean modified Lund-Mackay score was 6.87 (SD, 3.76). In 52.3% (57/109), ≥ 1 paranasal sinus was not pneumatized. The results are reported in effect sizes (Cohen's d). Lower mean fractional anisotropy values were found in the uncinate fasciculus (right uncinate fasciculus/right frontal sinus, d = -0.60), superior longitudinal fasciculus (right superior longitudinal fasciculus/right ethmoid sinus, d = -0.56; right superior longitudinal fasciculus/right sphenoid sinus, d = -2.09), and cingulate bundle (right cingulum bundle/right sphenoid sinus, d = -1.28; left cingulum bundle/left sphenoid sinus, d = -1.49). Higher mean diffusivity values were found in the forceps major/right and left sphenoid sinuses, d = 0.78. CONCLUSIONS: Nonaeration of the paranasal sinuses is a common incidental finding on pediatric MR imaging brain scans. The amount of air in the paranasal sinuses can influence fractional anisotropy and, to a lesser degree, mean diffusivity values of WM tracts and should be considered in DTI studies in pediatric populations.

Quantitative MRI protocol and decision model for a 'one stop shop' early-stage Parkinsonism diagnosis: Study design.

Differentiating among early-stage parkinsonisms is a challenge in clinical practice. Quantitative MRI can aid the diagnostic process, but studies with singular MRI techniques have had limited success thus far. Our objective is to develop a multi-modal MRI method for this purpose. In this review we describe existing methods and present a dedicated quantitative MRI protocol, a decision model and a study design to validate our approach ahead of a pilot study. We present example imaging data from patients and a healthy control, which resemble related literature.

Comprehensive dose evaluation of a Deep Learning based synthetic Computed Tomography algorithm for pelvic Magnetic Resonance-only radiotherapy.

BACKGROUND AND PURPOSE: Magnetic Resonance (MR)-only radiotherapy enables the use of MR without the uncertainty of MR-Computed Tomography (CT) registration. This requires a synthetic CT (sCT) for dose calculations, which can be facilitated by a novel Zero Echo Time (ZTE) sequence where bones are visible and images are acquired in 65 seconds. This study evaluated the dose calculation accuracy for pelvic sites of a ZTE-based Deep Learning sCT algorithm developed by GE Healthcare. MATERIALS AND METHODS: ZTE and CT images were acquired in 56 pelvic radiotherapy patients in the radiotherapy position. A 2D U-net convolutional neural network was trained using pairs of deformably registered CT and ZTE images from 36 patients. In the remaining 20 patients the dosimetric accuracy of the sCT was assessed using cylindrical dummy Planning Target Volumes (PTVs) positioned at four different central axial locations, as well as the clinical treatment plans (for prostate (n = 10), rectum (n = 4) and anus (n = 6) cancers). The sCT was rigidly and deformably registered, the plan recalculated and the doses compared using mean differences and gamma analysis. RESULTS: Mean dose differences to the PTV D98% were ≤ 0.5% for all dummy PTVs and clinical plans (rigid registration). Mean gamma pass rates at 1%/1 mm were 98.0 ± 0.4% (rigid) and 100.0 ± 0.0% (deformable), 96.5 ± 0.8% and 99.8 ± 0.1%, and 95.4 ± 0.6% and 99.4 ± 0.4% for the clinical prostate, rectum and anus plans respectively. CONCLUSIONS: A ZTE-based sCT algorithm with high dose accuracy throughout the pelvis has been developed. This suggests the algorithm is sufficiently accurate for MR-only radiotherapy for all pelvic sites.

MR Vascular Fingerprinting with Hybrid Gradient-Spin Echo Dynamic Susceptibility Contrast MRI for Characterization of Microvasculature in Gliomas.

Characterization of tumor microvasculature is important in tumor assessment and studying treatment response. This is possible by acquiring vascular biomarkers with magnetic resonance imaging (MRI) based on dynamic susceptibility contrast (DSC). We propose magnetic resonance vascular fingerprinting (MRVF) for hybrid echo planar imaging (HEPI) acquired during the first passage of the contrast agent (CA). The proposed approach was evaluated in patients with gliomas, and we simultaneously estimated vessel radius and relative cerebral blood volume. These parameters were also compared to the respective values estimated using the previously introduced vessel size imaging (VSI) technique. The results of both methods were found to be consistent. MRVF was also found to be robust to noise in the estimation of the parameters. DSC-HEPI-based MRVF provides characterization of microvasculature in gliomas with a short acquisition time and can be further improved in several ways to increase our understanding of tumor physiology.

Multi-echo gradient echo pulse sequences: which is best for PRFS MR thermometry guided hyperthermia?

PURPOSE: MR thermometry (MRT) enables noninvasive temperature monitoring during hyperthermia treatments. MRT is already clinically applied for hyperthermia treatments in the abdomen and extremities, and devices for the head are under development. In order to optimally exploit MRT in all anatomical regions, the best sequence setup and post-processing must be selected, and the accuracy needs to be demonstrated. METHODS: MRT performance of the traditionally used double-echo gradient-echo sequence (DE-GRE, 2 echoes, 2D) was compared to multi-echo sequences: a 2D fast gradient-echo (ME-FGRE, 11 echoes) and a 3D fast gradient-echo sequence (3D-ME-FGRE, 11 echoes). The different methods were assessed on a 1.5 T MR scanner (GE Healthcare) using a phantom cooling down from 59 °C to 34 °C and unheated brains of 10 volunteers. In-plane motion of volunteers was compensated by rigid body image registration. For the ME sequences, the off-resonance frequency was calculated using a multi-peak fitting tool. To correct for B0 drift, the internal body fat was selected automatically using water/fat density maps. RESULTS: The accuracy of the best performing 3D-ME-FGRE sequence was 0.20 °C in phantom (in the clinical temperature range) and 0.75 °C in volunteers, compared to DE-GRE values of 0.37 °C and 1.96 °C, respectively. CONCLUSION: For hyperthermia applications, where accuracy is more important than resolution or scan-time, the 3D-ME-FGRE sequence is deemed the most promising candidate. Beyond its convincing MRT performance, the ME nature enables automatic selection of internal body fat for B0 drift correction, an important feature for clinical application.

Multidelay pseudocontinuous arterial spin labeling to measure blood flow in the head and neck.

Perfusion MRI is promising for the assessment, prediction, and monitoring of radiation toxicity in organs at risk in head and neck cancer. Arterial spin labeling (ASL) may be an attractive alternative for conventional perfusion MRI, that does not require the administration of contrast agents. However, currently, little is known about the characteristics and performance of ASL in healthy tissues in the head and neck region. Therefore, the purpose of this study was to optimize and evaluate multidelay pseudocontinuous ASL (pCASL) for the head and neck region and to explore nominal values and measurement repeatability for the blood flow (BF), and the transit time and T1 values needed for BF quantification in healthy tissues. Twenty healthy volunteers underwent a scan session consisting of four repeats of multidelay pCASL (postlabel delays: 1000, 1632, 2479 ms). Regions of interest were defined in the parotid glands, submandibular glands, tonsils, and the cerebellum (as a reference). Nominal values of BF were calculated as the average over four repeats per volunteer. The repeatability coefficient and within-subject coefficient of repeatability (wCV) of BF were calculated. The effect of T1 (map vs. cohort average) and transit time correction on BF was investigated. The mean BF (± SE) was 55.7 ± 3.1 ml/100 g/min for the parotid glands, 41.2 ± 2.8 ml/100 g/min for the submandibular glands, and 32.3 ± 2.2 ml/100 g/min for the tonsils. The best repeatability was found in the parotid glands (wCV = 13.3%-16.1%), followed by the submandibular glands and tonsils (wCV = 20.0%-24.6%). On average, the effect of T1 and transit time correction on BF was limited, although substantial bias occurred in individual acquisitions. In conclusion, we demonstrated the feasibility of BF measurements in the head and neck region using multidelay pCASL and reported on nominal BF values, BF repeatability, the effect of T1, and transit time in various tissues in the head and neck region.

Using MRI to measure position and anatomy changes and assess their impact on the accuracy of hyperthermia treatment planning for cervical cancer.

PURPOSE: We studied the differences between planning and treatment position, their impact on the accuracy of hyperthermia treatment planning (HTP) predictions, and the relevance of including true treatment anatomy and position in HTP based on magnetic resonance (MR) images. MATERIALS AND METHODS: All volunteers were scanned with an MR-compatible hyperthermia device, including a filled waterbolus, to replicate the treatment setup. In the planning setup, the volunteers were scanned without the device to reproduce the imaging in the current HTP. First, we used rigid registration to investigate the patient position displacements between the planning and treatment setup. Second, we performed HTP for the planning anatomy at both positions and the treatment mimicking anatomy to study the effects of positioning and anatomy on the quality of the simulated hyperthermia treatment. Treatment quality was evaluated using SAR-based parameters. RESULTS: We found an average displacement of 2 cm between planning and treatment positions. These displacements caused average absolute differences of ∼12% for TC25 and 10.4%-15.9% in THQ. Furthermore, we found that including the accurate treatment position and anatomy in treatment planning led to an improvement of 2% in TC25 and 4.6%-10.6% in THQ. CONCLUSIONS: This study showed that precise patient position and anatomy are relevant since these affect the accuracy of HTP predictions. The major part of improved accuracy is related to implementing the correct position of the patient in the applicator. Hence, our study shows a clear incentive to accurately match the patient position in HTP with the actual treatment.

Pre-contrast MAGiC in treated gliomas: a pilot study of quantitative MRI.

Quantitative MR imaging is becoming more feasible to be used in clinical work since new approaches have been proposed in order to substantially accelerate the acquisition and due to the possibility of synthetically deriving weighted images from the parametric maps. However, their applicability has to be thoroughly validated in order to be included in clinical practice. In this pilot study, we acquired Magnetic Resonance Image Compilation scans to obtain T1, T2 and PD maps in 14 glioma patients. Abnormal tissue was segmented based on conventional images and using a deep learning segmentation technique to define regions of interest (ROIs). The quantitative T1, T2 and PD values inside ROIs were analyzed using the mean, the standard deviation, the skewness and the kurtosis and compared to the quantitative T1, T2 and PD values found in normal white matter. We found significant differences in pre-contrast T1 and T2 values between abnormal tissue and healthy tissue, as well as between T1w-enhancing and non-enhancing regions. ROC analysis was used to evaluate the potential of quantitative T1 and T2 values for voxel-wise classification of abnormal/normal tissue (AUC = 0.95) and of T1w enhancement/non-enhancement (AUC = 0.85). A cross-validated ROC analysis found high sensitivity (73%) and specificity (73%) with AUCs up to 0.68 on the a priori distinction between abnormal tissue with and without T1w-enhancement. These results suggest that normal tissue, abnormal tissue, and tissue with T1w-enhancement are distinguishable by their pre-contrast quantitative values but further investigation is needed.

The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study.

INTRODUCTION: The locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment would provide opportunities for personalised treatment. Currently, there are no accurate predictive models available for correct OPSCC patient selection. Apparently, the pivotal driving forces that determine how a OPSCC responds to treatment, have yet to be elucidated. Therefore, the holistiC early respOnse assessMent for oroPharyngeaL cancer paTiEnts study focuses on a holistic approach to gain insight in novel potential prognostic biomarkers, acquired before and early during treatment, to predict response to treatment in HPV-negative patients with OPSCC. METHODS AND ANALYSIS: This single-centre prospective observational study investigates 60 HPV-negative patients with OPSCC scheduled for primary radiotherapy (RT) with cisplatin or cetuximab, according to current clinical practice. A holistic approach will be used that aims to map the macroscopic (with Intra Voxel Incoherent Motion Diffusion Kurtosis Imaging (IVIM-DKI); before, during, and 3 months after RT), microscopic (with biopsies of the primary tumour acquired before treatment and irradiated ex vivo to assess radiosensitivity), and molecular landscape (with circulating tumour DNA (ctDNA) analysed before, during and 3 months after treatment). The main end point is locoregional control (LRC) 2 years after treatment. The primary objective is to determine whether a relative change in the mean of the diffusion coefficient D (an IVIM-DKI parameter) in the primary tumour early during treatment, improves the performance of a predictive model consisting of tumour volume only, for 2 years LRC after treatment. The secondary objectives investigate the potential of other IVIM-DKI parameters, ex vivo sensitivity characteristics, ctDNA, and combinations thereof as potential novel prognostic markers. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of Erasmus Medical Center. The main results of the trial will be presented in international meetings and medical journals. TRIAL REGISTRATION NUMBER: NL8458.

Time efficiency analysis for undersampled quantitative MRI acquisitions.

To realize Quantitative MRI (QMRI) with clinically acceptable scan time, acceleration factors achieved by conventional parallel imaging techniques are often inadequate. Further acceleration is possible using model-based reconstruction. We propose a theoretical metric called TEUSQA: Time Efficiency for UnderSampled QMRI Acquisitions to inform sequence design and sample pattern optimisation. TEUSQA is designed for a particular class of reconstruction techniques that directly estimate tissue parameters, possibly using prior information to regularize the estimation. TEUSQA can be used to evaluate undersampling patterns for multi-contrast QMRI sequences targeting any tissue parameter. To verify the time efficiency predicted by TEUSQA, we performed Monte Carlo simulations and an accelerated parameter mapping with two sequences (Inversion prepared fast spin echo for T1 and T2 mapping and 3D GRASE for T2 and B0 inhomogeneity mapping). Using TEUSQA, we assessed several ways to generate undersampling patterns in silico, providing insight into the relation between sample distribution and time efficiency for different acceleration factors. The time efficiency predicted by TEUSQA was within 15% of that observed in the Monte Carlo simulations and the prospective acquisition experiment. The assessment of undersampling patterns showed that a class of good patterns could be obtained by low-discrepancy sampling. We believe that TEUSQA offers a valuable instrument for developers of novel QMRI sequences pushing the boundaries of acceleration to achieve clinically feasible protocols. Finally, we applied a time-efficient undersampling pattern selected using TEUSQA for a 32-fold accelerated scan to map T1 & T2 mapping of a healthy volunteer.

3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T.

OBJECTIVE: Clinical application of chemical exchange saturation transfer (CEST) can be performed with investigation of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects. Here, we investigated APT- and NOE-weighted imaging based on advanced CEST metrics to map tumor heterogeneity of non-enhancing glioma at 3 T. MATERIALS AND METHODS: APT- and NOE-weighted maps based on Lorentzian difference (LD) and inverse magnetization transfer ratio (MTRREX) were acquired with a 3D snapshot CEST acquisition at 3 T. Saturation power was investigated first by varying B1 (0.5-2 µT) in 5 healthy volunteers then by applying B1 of 0.5 and 1.5 µT in 10 patients with non-enhancing glioma. Tissue contrast (TC) and contrast-to-noise ratios (CNR) were calculated between glioma and normal appearing white matter (NAWM) and grey matter, in APT- and NOE-weighted images. Volume percentages of the tumor showing hypo/hyperintensity (VPhypo/hyper,CEST) in APT/NOE-weighted images were calculated for each patient. RESULTS: LD APT resulting from using a B1 of 1.5 µT was found to provide significant positive TCtumor,NAWM and MTRREX NOE (B1 of 1.5 µT) provided significant negative TCtumor,NAWM in tissue differentiation. MTRREX-based NOE imaging under 1.5 µT provided significantly larger VPhypo,CEST than MTRREX APT under 1.5 µT. CONCLUSION: This work showed that with a rapid CEST acquisition using a B1 saturation power of 1.5 µT and covering the whole tumor, analysis of both LD APT and MTRREX NOE allows for observing tumor heterogeneity, which will be beneficial in future studies using CEST-MRI to improve imaging diagnostics for non-enhancing glioma.

Dependency of R2 and R2 * relaxation on Gd-DTPA concentration in arterial blood: Influence of hematocrit and magnetic field strength.

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R2(*) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time-consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R2(*) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open-source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient-echo sequence (proof-of-concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient-echo and spin-echo sequences. The results show that for both gradient-echo and spin-echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R2(*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.

Experimental Validation of the MRcollar: An MR Compatible Applicator for Deep Heating in the Head and Neck Region.

Clinical effectiveness of hyperthermia treatments, in which tumor tissue is artificially heated to 40-44 °C for 60-90 min, can be hampered by a lack of accurate temperature monitoring. The need for noninvasive temperature monitoring in the head and neck region (H&N) and the potential of MR thermometry prompt us to design an MR compatible hyperthermia applicator: the MRcollar. In this work, we validate the design, numerical model, and MR performance of the MRcollar. The MRcollar antennas have low reflection coefficients (<-15 dB) and the intended low interaction between the individual antenna modules (<-32 dB). A 10 °C increase in 3 min was reached in a muscle-equivalent phantom, such that the specifications from the European Society for Hyperthermic Oncology were easily reached. The MRcollar had a minimal effect on MR image quality and a five-fold improvement in SNR was achieved using the integrated coils of the MRcollar, compared to the body coil. The feasibility of using the MRcollar in an MR environment was shown by a synchronous heating experiment. The match between the predicted SAR and measured SAR using MR thermometry satisfied the gamma criteria [distance-to-agreement = 5 mm, dose-difference = 7%]. All experiments combined show that the MRcollar delivers on the needs for MR-hyperthermia in the H&N and is ready for in vivo investigation.

MR imaging for the quantitative assessment of brain iron in aceruloplasminemia: A postmortem validation study.

AIMS: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R2* as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype. METHODS: Tissue samples from 50 gray- and white matter regions of a postmortem aceruloplasminemia brain and control subject were scanned at 1.5 T to obtain R2*, and biochemically analyzed with inductively coupled plasma mass spectrometry. For gray matter samples of the aceruloplasminemia brain, sample R2* values were compared with postmortem in situ MRI data that had been obtained from the same subject at 3 T - in situ R2*. Relationships between R2* and tissue iron concentration were determined by linear regression analyses. RESULTS: Median iron concentrations throughout the whole aceruloplasminemia brain were 10 to 15 times higher than in the control subject, and R2* was linearly associated with iron concentration. For gray matter samples of the aceruloplasminemia subject with an iron concentration up to 1000 mg/kg, 91% of variation in R2* could be explained by iron, and in situ R2* at 3 T and sample R2* at 1.5 T were highly correlated. For white matter regions of the aceruloplasminemia brain, 85% of variation in R2* could be explained by iron. CONCLUSIONS: R2* is highly sensitive to variations in iron concentration in the severely iron-loaded brain, and might be used as a non-invasive measure of brain iron content in aceruloplasminemia and potentially other NBIA disorders.

Accuracy and repeatability of QRAPMASTER and MRF-vFA.

Our purpose is to evaluate bias and repeatability of the quantitative MRI sequences QRAPMASTER, based on steady-state imaging, and variable Flip Angle MRF (MRF-VFA), based on the transient response. Both techniques are assessed with a standardized phantom and five volunteers on 1.5 T and 3 T clinical scanners. All scans were repeated eight times in consecutive weeks. In the phantom, the mean bias±95% confidence interval for T1 values with QRAPMASTER was 10 ± 10% on 1.5 T and 4 ± 13% on 3.0 T. The mean bias for T1 values with MRF-vFA was 21 ± 17% on 1.5 T and 9 ± 9% on 3.0 T. For T2 values the mean bias with QRAPMASTER was 12 ± 3% on 1.5 T and 23 ± 1% on 3.0 T. For T2 values the mean bias with MRF-vFA was 17 ± 1% on 1.5 T and 19 ± 2% on 3.0 T. QRAPMASTER estimated lower T1 and T2 values than MRF-vFA. Repeatability was good with low coefficients of variation (CoV). Mean CoV ± 95% confidence interval for T1 were 3.2 ± 0.4% on 1.5 T and 4.5 ± 0.8% on 3.0 T with QRAPMASTER and 2.7% ± 0.2% on 1.5 T and 2.5 ± 0.2% on 3.0 T with MRF-vFA. For T2 were 3.3 ± 1.9% on 1.5 T and 3.2 ± 0.6% on 3.0 T with QRAPMASTER and 2.0 ± 0.4% on 1.5 T and 5.7 ± 1.0% on 3.0 T with MRF-vFA. The in-vivo T1 and T2 are in the range of values previously reported by other authors. The in-vivo mean CoV ± 95% confidence interval in gray matter were for T1 1.7 ± 0.2% using QRAPMASTER and 0.7 ± 0.5% using MRF-vFA and for T2 were 0.9 ± 0.4% using QRAPMASTER and 2.4 ± 0.5% using MRF-vFA. In white matter were for T1 0.9 ± 0.3% using QRAPMASTER and 1.3 ± 1.1% using MRF-vFA and for T2 were 0.7 ± 0.4% using QRAPMASTER and 2.4 ± 0.4% using MRF-vFA. A GLM analysis showed that the variations in T1 and T2 mainly depend on the field strength and the subject, but not on the follow-up repetition in different days. This confirms the high repeatability of QRAPMASTER and MRF-vFA. In summary, QRAPMASTER and MRF-vFA on both systems were highly repeatable with moderate accuracy, providing results comparable to standard references. While repeatability was similar for both methods, QRAPMASTER was more accurate. QRAPMASTER is a tested commercial product but MRF-vFA is 4.77 times faster, which would ease the inclusion of quantitative relaxometry.

From signal-based to comprehensive magnetic resonance imaging.

We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response-including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T1, T2) and proton density (PD) and experimental conditions such as radiofrequency field (B1) and constant/homogeneous magnetic field (B0) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

Partial volume correction in arterial spin labeling perfusion MRI: A method to disentangle anatomy from physiology or an analysis step too far?

The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, 'uncorrected', images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.