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.

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.

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.

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.

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.

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.

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.

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.

An optimal acquisition and post-processing pipeline for hybrid IVIM-DKI in head and neck.

PURPOSE: To optimize the diffusion-weighting b values and postprocessing pipeline for hybrid intravoxel incoherent motion diffusion kurtosis imaging in the head and neck region. METHODS: Optimized diffusion-weighting b value sets ranging between 5 and 30 b values were constructed by optimizing the Cramér-Rao lower bound of the hybrid intravoxel incoherent motion diffusion kurtosis imaging model. With this model, the perfusion fraction, pseudodiffusion coefficient, diffusion coefficient, and kurtosis were estimated. Sixteen volunteers were scanned with a reference b value set and 3 repeats of the optimized sets, of which 1 with volunteers swallowing on purpose. The effects of (1) b value optimization and number of b values, (2) registration type (none vs. intervolume vs. intra- and intervolume registration), and (3) manual swallowing artifact rejection on the parameter precision were assessed. RESULTS: The SD was higher in the reference set for perfusion fraction, diffusion coefficient, and kurtosis by a factor of 1.7, 1.5, and 2.3 compared to the optimized set, respectively. A smaller SD (factor 0.7) was seen in pseudodiffusion coefficient. The sets containing 15, 20, and 30 b values had comparable repeatability in all parameters, except pseudodiffusion coefficient, for which set size 30 was worse. Equal repeatability for the registration approaches was seen in all parameters of interest. Swallowing artifact rejection removed the bias when present. CONCLUSION: To achieve optimal hybrid intravoxel incoherent motion diffusion kurtosis imaging in the head and neck region, b value optimization and swallowing artifact image rejection are beneficial. The optimized set of 15 b values yielded the optimal protocol efficiency, with a precision comparable to larger b value sets and a 50% reduction in scan time.

Association Between T2* Relaxation Times Derived From Ultrashort Echo Time MRI and Symptoms During Exercise Therapy for Patellar Tendinopathy: A Large Prospective Study.

BACKGROUND: Exercise therapy is considered preferential treatment for patellar tendinopathy (PT). However, there is conflicting evidence for structural patellar tendon adaptation in response to exercise therapy and its association with symptoms is weak. PURPOSE: To assess the association between 1) T2* relaxation times and symptom severity; 2) baseline T2* and clinical outcome; and 3) longitudinal T2* changes and clinical outcome in athletes with PT performing exercise therapy. STUDY TYPE: Randomized controlled clinical trial. SUBJECTS: Seventy-six athletes (18-35 years) with clinically diagnosed and ultrasound-confirmed PT. FIELD STRENGTH/SEQUENCE: 3D gradient echo sequence (3.0 T). ASSESSMENT: Patients were enrolled in a randomized trial of progressive tendon-loading exercises (PTLE) versus eccentric exercise therapy (EET). Symptoms were assessed using the Victorian Institute of Sports Assessment (VISA-P) questionnaire. 3D-Ultrashort echo time (UTE)-MRI was acquired at baseline, 12 and 24 weeks. Voxel-wise T2* relaxation times were quantified using mono-exponential and bi-exponential models. T2* analysis was performed in three patellar tendon tissue compartments representing: aligned collagen, degenerative tissue, and interface. STATISTICAL TESTS: Adjusted general linear, mixed-linear models, and generalized estimating equations. RESULTS: We included 76 patients with PT (58 men, mean age 24 ± 4 years); 38 in the PTLE-group and 38 in the EET-group, of which 57 subjects remained eligible for analysis. T2* relaxation times were significantly associated with VISA-P in degenerative and interface tissues of the patellar tendon. No association was found between baseline T2* and VISA-P after 24 weeks (P > 0.29). The estimated mean T2* in degenerative tissue decreased from 14 msec (95%CI: 12-16) at baseline to 13 msec (95%CI: 11-15) at 12 weeks and to 13 msec (95%CI: 10-15) at 24 weeks. The significant decrease in T2* from baseline to 24 weeks was associated with improved clinical outcome. DATA CONCLUSION: Tissue-specific T2* relaxation times, identified with 3D-UTE-MRI, decreased significantly in athletes with patellar tendinopathy performing exercise therapy and this decrease was associated with improved clinical outcome. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Accelerated 3D whole-brain T1, T2, and proton density mapping: feasibility for clinical glioma MR imaging.

PURPOSE: Advanced MRI-based biomarkers offer comprehensive and quantitative information for the evaluation and characterization of brain tumors. In this study, we report initial clinical experience in routine glioma imaging with a novel, fully 3D multiparametric quantitative transient-state imaging (QTI) method for tissue characterization based on T1 and T2 values. METHODS: To demonstrate the viability of the proposed 3D QTI technique, nine glioma patients (grade II-IV), with a variety of disease states and treatment histories, were included in this study. First, we investigated the feasibility of 3D QTI (6:25 min scan time) for its use in clinical routine imaging, focusing on image reconstruction, parameter estimation, and contrast-weighted image synthesis. Second, for an initial assessment of 3D QTI-based quantitative MR biomarkers, we performed a ROI-based analysis to characterize T1 and T2 components in tumor and peritumoral tissue. RESULTS: The 3D acquisition combined with a compressed sensing reconstruction and neural network-based parameter inference produced parametric maps with high isotropic resolution (1.125 × 1.125 × 1.125 mm3 voxel size) and whole-brain coverage (22.5 × 22.5 × 22.5 cm3 FOV), enabling the synthesis of clinically relevant T1-weighted, T2-weighted, and FLAIR contrasts without any extra scan time. Our study revealed increased T1 and T2 values in tumor and peritumoral regions compared to contralateral white matter, good agreement with healthy volunteer data, and high inter-subject consistency. CONCLUSION: 3D QTI demonstrated comprehensive tissue assessment of tumor substructures captured in T1 and T2 parameters. Aiming for fast acquisition of quantitative MR biomarkers, 3D QTI has potential to improve disease characterization in brain tumor patients under tight clinical time-constraints.

Tissue-Specific T2 * Biomarkers in Patellar Tendinopathy by Subregional Quantification Using 3D Ultrashort Echo Time MRI.

BACKGROUND: Quantitative MRI of patellar tendinopathy (PT) can be challenging due to spatial variation of T2 * relaxation times. PURPOSE: 1) To compare T2 * quantification using a standard approach with analysis in specific tissue compartments of the patellar tendon. 2) To evaluate test-retest reliability of different methods for fitting ultrashort echo time (UTE)-relaxometry data. STUDY TYPE: Prospective. SUBJECTS: Sixty-five athletes with PT. FIELD STRENGTH/SEQUENCE: 3D UTE scans covering the patellar tendon were acquired using a 3.0T scanner and a 16-channel surface coil. ASSESSMENT: Voxelwise median T2 * was quantified with monoexponential, fractional-order, and biexponential fitting. We applied two methods for T2 * analysis: first, a standard approach by analyzing all voxels covering the proximal patellar tendon. Second, within subregions of the patellar tendon, by using thresholds on biexponential fitting parameter percentage short T2 * (0-30% for mostly long T2 *, 30-60% for mixed T2 *, and 60-100% for mostly short T2 *). STATISTICAL TESTS: Average test-retest reliability was assessed in three athletes using coefficients-of-variation (CV) and coefficients-of-repeatability (CR). RESULTS: With standard image analysis, we found a median [interquartile range, IQR] monoexponential T2 * of 6.43 msec [4.32-8.55] and fractional order T2 * 4.39 msec [3.06-5.78]. The percentage of short T2 * components was 52.9% [35.5-69.6]. Subregional monoexponential T2 * was 13.78 msec [12.11-16.46], 7.65 msec [6.49-8.61], and 3.05 msec [2.52-3.60] and fractional order T2 * 11.82 msec [10.09-14.44], 5.14 msec [4.25-5.96], and 2.19 msec [1.82-2.64] for 0-30%, 30-60%, and 60-100% short T2 *, respectively. Biexponential component short T2 * was 1.693 msec [1.417-2.003] for tissue with mostly short T2 * and long T2 * of 15.79 msec [13.47-18.61] for mostly long T2 *. The average CR (CV) was 2 msec (15%), 2 msec (19%) and 10% (22%) for monoexponential, fractional order and percentage short T2 *, respectively. DATA CONCLUSION: Patellar tendinopathy is characterized by regional variability in binding states of water. Quantitative multicompartment T2 * analysis in PT can be facilitated using a voxel selection method based on using biexponential fitting parameters. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:420-430.

Technical challenges of quantitative chest MRI data analysis in a large cohort pediatric study.

OBJECTIVES: This study was conducted in order to evaluate the effect of geometric distortion (GD) on MRI lung volume quantification and evaluate available manual, semi-automated, and fully automated methods for lung segmentation. METHODS: A phantom was scanned with MRI and CT. GD was quantified as the difference in phantom's volume between MRI and CT, with CT as gold standard. Dice scores were used to measure overlap in shapes. Furthermore, 11 subjects from a prospective population-based cohort study each underwent four chest MRI acquisitions. The resulting 44 MRI scans with 2D and 3D Gradwarp were used to test five segmentation methods. Intraclass correlation coefficient, Bland-Altman plots, Wilcoxon, Mann-Whitney U, and paired t tests were used for statistics. RESULTS: Using phantoms, volume differences between CT and MRI varied according to MRI positions and 2D and 3D Gradwarp correction. With the phantom located at the isocenter, MRI overestimated the volume relative to CT by 5.56 ± 1.16 to 6.99 ± 0.22% with body and torso coils, respectively. Higher Dice scores and smaller intraobject differences were found for 3D Gradwarp MR images. In subjects, semi-automated and fully automated segmentation tools showed high agreement with manual segmentations (ICC = 0.971-0.993 for end-inspiratory scans; ICC = 0.992-0.995 for end-expiratory scans). Manual segmentation time per scan was approximately 3-4 h and 2-3 min for fully automated methods. CONCLUSIONS: Volume overestimation of MRI due to GD can be quantified. Semi-automated and fully automated segmentation methods allow accurate, reproducible, and fast lung volume quantification. Chest MRI can be a valid radiation-free imaging modality for lung segmentation and volume quantification in large cohort studies. KEY POINTS: • Geometric distortion varies according to MRI setting and patient positioning. • Automated segmentation methods allow fast and accurate lung volume quantification. • MRI is a valid radiation-free alternative to CT for quantitative data analysis.

Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study.

OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). METHODS: The setting of the study was at the Alzheimer Center Reina Sofía Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. RESULTS: Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected). CONCLUSIONS: Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright © 2016 John Wiley & Sons, Ltd.

Multimodal description of whole brain connectivity: A comparison of resting state MEG, fMRI, and DWI.

Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion-weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood-oxygenation level-dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI-FC, and MEG-FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI-FC, and MEG-FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI-FC; SC and MEG-FC at theta, alpha, beta and gamma bands; and fMRI-FC and MEG-FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance.

Multi-atlas and label fusion approach for patient-specific MRI based skull estimation.

PURPOSE: MRI-based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1-weighted volume. METHODS: The skull is estimated using a multi-atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label-fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms. RESULTS: The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 ± 6.99%), a clinical CT-MR dataset (maximum overlap of 78.31 ± 6.97%), and a whole head CT-MRI pair (maximum overlap 78.68%). A qualitative evaluation has also been performed on MRI acquisition of volunteers. CONCLUSION: It is possible to automatically segment the complete skull from MRI data using a multi-atlas and label fusion approach. This will allow the creation of complete MRI-based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR.

SAR reduction in 7T C-spine imaging using a "dark modes" transmit array strategy.

PURPOSE: Local specific absorption rate (SAR) limits many applications of parallel transmit (pTx) in ultra high-field imaging. In this Note, we introduce the use of an array element, which is intentionally inefficient at generating spin excitation (a "dark mode") to attempt a partial cancellation of the electric field from those elements that do generate excitation. We show that adding dipole elements oriented orthogonal to their conventional orientation to a linear array of conventional loop elements can lower the local SAR hotspot in a C-spine array at 7 T. METHODS: We model electromagnetic fields in a head/torso model to calculate SAR and excitation B1 (+) patterns generated by conventional loop arrays and loop arrays with added electric dipole elements. We utilize the dark modes that are generated by the intentional and inefficient orientation of dipole elements in order to reduce peak 10g local SAR while maintaining excitation fidelity. RESULTS: For B1 (+) shimming in the spine, the addition of dipole elements did not significantly alter the B1 (+) spatial pattern but reduced local SAR by 36%. CONCLUSION: The dipole elements provide a sufficiently complimentary B1 (+) and electric field pattern to the loop array that can be exploited by the radiofrequency shimming algorithm to reduce local SAR.

Parallel transmit pulse design for patients with deep brain stimulation implants.

PURPOSE: Specific absorption rate (SAR) amplification around active implantable medical devices during diagnostic MRI procedures poses a potential risk for patient safety. In this study, we present a parallel transmit (pTx) strategy that can be used to safely scan patients with deep brain stimulation (DBS) implants. METHODS: We performed electromagnetic simulations at 3T using a uniform phantom and a multitissue realistic head model with a generic DBS implant. Our strategy is based on using implant-friendly modes, which are defined as the modes of an array that reduce the local SAR around the DBS lead tip. These modes are used in a spokes pulse design algorithm in order to produce highly uniform magnitude least-squares flip angle excitations. RESULTS: Local SAR (1 g) at the lead tip is reduced below 0.1 W/kg compared with 31.2 W/kg, which is obtained by a simple quadrature birdcage excitation without any sort of SAR mitigation. For the multitissue realistic head model, peak 10 g local SAR and global SAR are obtained as 4.52 W/kg and 0.48 W/kg, respectively. A uniform axial flip angle is also obtained (NRMSE <3%). CONCLUSION: Parallel transmit arrays can be used to generate implant-friendly modes and to reduce SAR around DBS implants while constraining peak local SAR and global SAR and maximizing flip angle homogeneity.

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.