Multiparametric Mapping Research Articles

Relating quantitative 7T MRI across cortical depths to cytoarchitectonics, gene expression and connectomics.

Ultra‐high field MRI across the depth of the cortex has the potential to provide anatomically precise biomarkers and mechanistic insights into neurodegenerative disease like Huntington's disease that show layer‐selective vulnerability. Here we compare multi‐parametric mapping (MPM) measures across cortical depths for a 7T 500 μm whole brain acquisition to (a) layer‐specific cell measures from the von Economo histology atlas, (b) layer‐specific gene expression, using the Allen Human Brain atlas and (c) white matter connections using high‐fidelity diffusion tractography, at a 1.3 mm isotropic voxel resolution, from a 300mT/m Connectom MRI system. We show that R2*, but not R1, across cortical depths is highly correlated with layer‐specific cell number and layer‐specific gene expression. R1‐ and R2*‐weighted connectivity strength of cortico‐striatal and intra‐hemispheric cortical white matter connections was highly correlated with grey matter R1 and R2* across cortical depths. Limitations of the layer‐specific relationships demonstrated are at least in part related to the high cross‐correlations of von Economo atlas cell counts and layer‐specific gene expression across cortical layers. These findings demonstrate the potential and limitations of combining 7T MPMs, gene expression and white matter connections to provide an anatomically precise framework for tracking neurodegenerative disease.

Model-based multi-parameter mapping

Quantitative MR imaging is increasingly favoured for its richer information content and standardised measures. However, computing quantitative parameter maps, such as those encoding longitudinal relaxation rate (R1), apparent transverse relaxation rate (R2*) or magnetisation-transfer saturation (MTsat), involves inverting a highly non-linear function. Many methods for deriving parameter maps assume perfect measurements and do not consider how noise is propagated through the estimation procedure, resulting in needlessly noisy maps. Instead, we propose a probabilistic generative (forward) model of the entire dataset, which is formulated and inverted to jointly recover (log) parameter maps with a well-defined probabilistic interpretation (e.g., maximum likelihood or maximum a posteriori). The second order optimisation we propose for model fitting achieves rapid and stable convergence thanks to a novel approximate Hessian. We demonstrate the utility of our flexible framework in the context of recovering more accurate maps from data acquired using the popular multi-parameter mapping protocol. We also show how to incorporate a joint total variation prior to further decrease the noise in the maps, noting that the probabilistic formulation allows the uncertainty on the recovered parameter maps to be estimated. Our implementation uses a PyTorch backend and benefits from GPU acceleration. It is available at https://github.com/balbasty/nitorch.

Multi-parameter analysis and mapping of the levelised cost of energy from floating offshore wind in the Mediterranean Sea

Floating offshore wind, far less constrained by water depths than bottom-fixed, has great potential in the Mediterranean Basin. The levelised cost of energy (LCOE) is arguably the single most reliable metric to measure the viability of energy projects. In this work, the levelised cost of energy for floating offshore wind is mapped for the first time in the European and Eastern Mediterranean with a detailed cost breakdown and a focus on semi-submersible platforms. A multi-parameter analysis is conducted in a case study to discern the effects of specific elements on the LCOE. Expressions are formulated as functions of site-specific variables: distance to shore, water depth and annual energy production. The latter is estimated accurately by combining the power curve of an exemplar wind turbine with hindcast, site-specific wind data. The mapping shows the paramount importance of the wind climate, i.e., the resource, for the LCOE. The lowest values (~95 €/MWh) occur where the wind resource is most abundant, i.e., the Gulf of Lion and the Aegean Sea. The highest values (>250 €/MWh) are found where the resource is scarce, i.e., around the Balearic Islands and in the North Adriatic, Tyrrhenian and Levantine Seas. Moderate values of the LCOE (130–180 €/MWh) occur off South Spain (Alboran Sea), Sardinia, Sicily and Malta, and in the South Adriatic. In addition to the local wind resource, other parameters that play a relevant role in the LCOE are those related to the production of energy (number of turbines in the wind farm and installed power), on the one hand, and to substantial sources of costs (cost of turbines and substructure), on the other, as well as the project lifetime and discount rate. These results identify hotspots for the deployment of floating offshore wind in the Mediterranean and opportunities for cost reductions, and contribute to decision-making in a region much in need of renewable energy.

Nuclear Magnetic Resonance Microimaging for the Qualitative Assessment of Root Canal Treatment: An Ex Vivo Preliminary Study.

Aim: To assess the potential ability of nuclear magnetic resonance micro-imaging (mMRI) to visualize and identify soft tissue debris and unfilled spaces inside radicular canals in endodontic treated extracted teeth, for understanding the causes of treatment failure. Toward this goal, multi-parametric mMRI and cone beam computed tomography (CBCT) were compared. Methodology: A non-recoverable root treated human tooth was extracted due to endodontic failure and excessive mobility. It was examined with both CBCT and mMRI: CBCT was performed with 0.125 mm voxel size (GXCB-500, Kavo-Gendex, Brea, CA, USA) and mMRI was performed with a spectrometer operating at 9.4T magnetic field (Bruker Avance-400, Bruker, Billerica, MA, USA). The mMRI images were obtained with a microimaging probe. Relaxation times (T1 and T2) and diffusion-weighted acquisition sequences were used to obtain multi-parametric maps of the extracted tooth (slice thickness of 200 µm and in plane resolution of 30 × 30 µm2). Results: T1 and T2 maps identified unfilled spaces around and close to Gutta-percha cones instead of CBCT images that were not able to highlight this aspect. T1, T2 and apparent diffusion coefficient (ADC) assumed different values in dentine and in voids, characterized by different dimensions. Moreover, they were able to discriminate between infiltrations of water only and deposits of biological material. Because Gutta-percha cones are constituted of hard, non-porous material, they do not provide a signal and in mMRI images appear as zones of noise. Conclusions: Unlike the CBCT exam, mMRI can detect soft tissue debris and unfilled spaces inside radicular canals. Therefore, this in vitro study showed the potential of mMRI to evaluate the quality of the root canal treatment, suggesting its potential benefit in determining the causes of endodontic failure, without the use of ionizing radiation.

Microstructural plasticity in nociceptive pathways after spinal cord injury

ObjectiveTo track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury...

Simultaneous Mapping of Vasculature, Hypoxia, and Proliferation Using Dynamic Susceptibility Contrast MRI, 18F-FMISO PET, and 18F-FLT PET in Relation to Contrast Enhancement in Newly Diagnosed Glioblastoma.

Conventional MRI plays a key role in the management of patients with high-grade glioma, but multiparametric MRI and PET tracers could provide further information to better characterize tumor metabolism and heterogeneity by identifying regions having a high risk of recurrence. In this study, we focused on proliferation, hypervascularization, and hypoxia, all factors considered indicative of poor prognosis. They were assessed by measuring uptake of 18F-3'-deoxy-3'-18F-fluorothymidine (18F-FLT), relative cerebral blood volume (rCBV) maps, and uptake of 18F-fluoromisonidazole (18F-FMISO), respectively. For each modality, the volumes and high-uptake subvolumes (hot spots) were semiautomatically segmented and compared with the contrast enhancement (CE) volume on T1-weighted gadolinium-enhanced (T1w-Gd) images, commonly used in the management of patients with glioblastoma. Methods: Dynamic susceptibility contrast-enhanced MRI (31 patients), 18F-FLT PET (20 patients), or 18F-FMISO PET (20 patients), for a total of 31 patients, was performed on preoperative glioblastoma patients. Volumes and hot spots were segmented on SUV maps for 18F-FLT PET (using the fuzzy locally adaptive bayesian algorithm) and 18F-FMISO PET (using a mean contralateral image + 3.3 SDs) and on rCBV maps (using a mean contralateral image + 1.96 SDs) for dynamic susceptibility contrast-enhanced MRI and overlaid on T1w-Gd images. For each modality, the percentages of the peripheral volumes and the peripheral hot spots outside the CE volume were calculated. Results: All tumors showed highly proliferated, hypervascularized, and hypoxic regions. The images also showed pronounced heterogeneity of both tracers regarding their uptake and rCBV maps, within each individual patient. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularized, and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were 1.6%-155.5%, 1.5%-89.5%, and 3.1%-78.0% for 18F-FLT, rCBV, and 18F-FMISO, respectively. All patients had hyperproliferative hot spots outside the CE volume, whereas hypervascularized and hypoxic hot spots were detected mainly within the enhancing region. Conclusion: Spatial analysis of multiparametric maps with segmented volumes and hot spots provides valuable information to optimize the management and treatment of patients with glioblastoma.

Free-breathing abdominal T1 mapping using an optimized MR fingerprinting sequence.

In this work, we propose a free-breathing magnetic resonance fingerprinting (MRF) method that can be used to obtain B1+ -robust quantitative T1 maps of the abdomen in a clinically acceptable time. A three-dimensional MRF sequence with a radial stack-of-stars trajectory was implemented, and its k-space acquisition ordering was adjusted to improve motion-robustness in the context of MRF. The flip angle pattern was optimized using the Cramér-Rao Lower Bound, and the encoding efficiency of sequences with 300, 600, 900 and 1800 flip angles was evaluated. To validate the sequence, a movable multicompartment phantom was developed. Reference multiparametric maps were acquired under stationary conditions using a previously validated MRF method. Periodic motion of the phantom was used to investigate the motion-robustness of the proposed sequence. The best performing sequence length (600 flip angles) was used to image the abdomen during a free-breathing volunteer scan. When using a series of 600 or more flip angles, the estimated T1 values in the stationary phantom showed good agreement with the reference scan. Phantom experiments revealed that motion-related artifacts can appear in the quantitative maps and confirmed that a motion-robust k-space ordering is essential. The in vivo scan demonstrated that the proposed sequence can produce clean parameter maps while the subject breathes freely. Using this sequence, it is possible to generate B1+ -robust quantitative maps of T1 and B1+ next to M0 -weighted images under free-breathing conditions at a clinically usable resolution within 5 min.

Altered iron and myelin in premanifest Huntington's Disease more than 20 years before clinical onset: Evidence from the cross-sectional HD Young Adult Study.

BackgroundPathological processes in Huntington's disease (HD) begin many years prior to symptom onset. Recently we demonstrated that in a premanifest cohort approximately 24 years from predicted disease onset, despite intact function, there was evidence of subtle neurodegeneration. Here, we use novel imaging techniques to determine whether macro- and micro-structural changes can be detected across the whole-brain in the same cohort.Methods62 premanifest HD (PreHD) and 61 controls from the HD Young Adult Study (HD-YAS) were included. Grey and white matter volume, diffusion weighted imaging (DWI) measures of white matter microstructure, multiparametric maps (MPM) estimating myelin and iron content from magnetization transfer (MT), proton density (PD), longitudinal relaxation (R1) and effective transverse relaxation (R2*), and myelin g-ratio were examined. Group differences between PreHD and controls were assessed; associations between all imaging metrics and disease burden and CSF neurofilament light (NfL) were also performed. Volumetric and MPM results were corrected at a cluster-wise value of familywise error (FWE) 0.05. Diffusion and g-ratio results were corrected via threshold-free cluster enhancement at FWE 0.05.FindingsWe showed significantly increased R1 and R2*, suggestive of increased iron, in the putamen, globus pallidum and external capsule of PreHD participants. There was also a significant association between lower cortical R2*, suggestive of reduced myelin or iron, and higher CSF NfL in the frontal lobe and the parieto-occipital cortices. No other results were significant at corrected levels.InterpretationIncreased iron in subcortical structures and the surrounding white matter is a feature of very early PreHD. Furthermore, increases in CSF NfL were linked to microstructural changes in the posterior parietal-occipital cortex, a region previously shown to undergo some of the earliest cortical changes in HD. These findings suggest that disease related process are occurring in both subcortical and cortical regions more than 20 years from predicted disease onset.

Bright-blood and dark-blood phase sensitive inversion recovery late gadolinium enhancement and T1 and T2 maps in a single free-breathing scan: an all-in-one approach

BackgroundQuantitative cardiovascular magnetic resonance (CMR) T1 and T2 mapping are used to detect diffuse disease such as myocardial fibrosis or edema. However, post gadolinium contrast mapping often lacks visual contrast needed for assessment of focal scar. On the other hand, late gadolinium enhancement (LGE) CMR which nulls the normal myocardium has excellent contrast between focal scar and normal myocardium but has poor ability to detect global disease. The objective of this work is to provide a calculated bright-blood (BB) and dark-blood (DB) LGE based on simultaneous acquisition of T1 and T2 maps, so that both diffuse and focal disease may be assessed within a single multi-parametric acquisition.MethodsThe prototype saturation recovery-based SASHA T1 mapping may be modified to jointly calculate T1 and T2 maps (known as multi-parametric SASHA) by acquiring additional saturation recovery (SR) images with both SR and T2 preparations. The synthetic BB phase sensitive inversion recovery (PSIR) LGE may be calculated from the post-contrast T1, and the DB PSIR LGE may be calculated from the post-contrast joint T1 and T2 maps. Multi-parametric SASHA maps were acquired free-breathing (45 heartbeats). Protocols were designed to use the same spatial resolution and achieve similar signal-to-noise ratio (SNR) as conventional motion corrected (MOCO) PSIR. The calculated BB and DB LGE were compared with separate free breathing (FB) BB and DB MOCO PSIR acquisitions requiring 16 and 32 heart beats, respectively. One slice with myocardial infarction (MI) was acquired with all protocols within 4 min.ResultsMultiparametric T1 and T2 maps and calculated BB and DB PSIR LGE images were acquired for patients with subendocardial chronic MI (n = 10), acute MI (n = 3), and myocarditis (n = 1). The contrast-to-noise (CNR) between scar (MI and myocarditis) and remote was 26.6 ± 7.7 and 20.2 ± 7.4 for BB and DB PSIR LGE, and 31.3 ± 10.6 and 21.8 ± 7.6 for calculated BB and DB PSIR LGE, respectively. The CNR between scar and the left ventricualr blood pool was 5.2 ± 6.5 and 29.7 ± 9.4 for conventional BB and DB PSIR LGE, and 6.5 ± 6.0 and 38.6 ± 11.6 for calculated BB and DB PSIR LGE, respectively.ConclusionsA single free-breathing acquisition using multi-parametric SASHA provides T1 and T2 maps and calculated BB and DB PSIR LGE images for comprehensive tissue characterization.

Temporal trajectory of brain tissue property changes induced by electroconvulsive therapy

BackgroundAfter more than eight decades of electroconvulsive therapy (ECT) for pharmaco-resistant depression, the mechanisms governing its anti-depressant effects remain poorly understood. Computational anatomy studies using longitudinal T1-weighted magnetic resonance imaging (MRI) data have demonstrated ECT effects on hippocampus volume and cortical thickness, but they lack the interpretational specificity about underlying neurobiological processes. MethodsWe sought to fill in the gap of knowledge by acquiring quantitative MRI indicative for brain's myelin, iron and tissue water content at multiple time-points before, during and after ECT treatment. We adapted established tools for longitudinal spatial registration of MRI data to the relaxometry-based multi-parameter maps aiming to preserve the initial total signal amount and introduced a dedicated multivariate analytical framework. ResultsThe whole-brain voxel-based analysis based on a multivariate general linear model showed that there is no brain tissue oedema contributing to the predicted ECT-induced hippocampus volume increase neither in the short, nor in the long-term observations. Improvements in depression symptom severity over time were associated with changes in both volume estimates and brain tissue properties expanding beyond mesial temporal lobe structures to anterior cingulate cortex, precuneus and striatum. ConclusionThe obtained results stemming from multi-contrast MRI quantitative data provided a fingerprint of ECT-induced brain tissue changes over time that are contrasted against the background of established morphometry findings. The introduced data processing and statistical testing algorithms provided a reliable analytical framework for longitudinal multi-parameter brain maps. The results, particularly the evidence of lack of ECT impact on brain tissue water, should be considered preliminary considering the small sample size of the study.

Characterization of microenvironmental changes in the intervertebral discs of patients with chronic low back pain using multiparametric MRI contrasts extracted from Z-spectrum.

Z-spectral MRI data were analyzed to produce multiparametric metabolic and microenvironmental contrasts for identifying intervertebral discs with/without pain symptom and sore pain. Z-spectra data were collected from the lumbar discs of 26 patients with non-specific chronic low bck pain (CLBP) and 21 asymptomatic controls (AC) with a chemical exchange saturation transfer (CEST). Data were fitted to quantify the CEST effects from glycosaminoglycan, amide proton transfer (APT), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer contrast effects, and the direct saturation of water. Multiparametric maps were computed from the fitted peak amplitudes, and the average values were calculated from all five lumber discs. Those parameters were compared between the CLBP and AC groups and between the subgroups with and without (Nsore) sore pain. The discs in symptomatic patients have lower water content, collagen-bound water and collagen than the discs in AC (P < 0.05). Additionally, Z-sepctral MRI indicated that the discs in the sore subgroup had less water, collagen-bound water and collagen, and likely lower pH compared to the Nsore subgroup (P < 0.05). Lower pH as measured with reduced APT and NOE effects may be an important pathological factor causing sore pain of the back. Z-spectral MRI with its multiparametric metabolic and microenvironmental contrasts has been demonstrated to identify discs with and without pain symptom or sore pain, providing more important information of CLBP.

The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content.

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.

Quantitative Multi-Parameter Mapping Optimized for the Clinical Routine.

Using quantitative multi-parameter mapping (MPM), studies can investigate clinically relevant microstructural changes with high reliability over time and across subjects and sites. However, long acquisition times (20 min for the standard 1-mm isotropic protocol) limit its translational potential. This study aimed to evaluate the sensitivity gain of a fast 1.6-mm isotropic MPM protocol including post-processing optimized for longitudinal clinical studies. 6 healthy volunteers (35±7 years old; 3 female) were scanned at 3T to acquire the following whole-brain MPM maps with 1.6 mm isotropic resolution: proton density (PD), magnetization transfer saturation (MT), longitudinal relaxation rate (R1), and transverse relaxation rate (R2*). MPM maps were generated using two RF transmit field (B1+) correction methods: (1) using an acquired B1+ map and (2) using a data-driven approach. Maps were generated with and without Gibb's ringing correction. The intra-/inter-subject coefficient of variation (CoV) of all maps in the gray and white matter, as well as in all anatomical regions of a fine-grained brain atlas, were compared between the different post-processing methods using Student's t-test. The intra-subject stability of the 1.6-mm MPM protocol is 2–3 times higher than for the standard 1-mm sequence and can be achieved in less than half the scan duration. Intra-subject variability for all four maps in white matter ranged from 1.2–5.3% and in gray matter from 1.8 to 9.2%. Bias-field correction using an acquired B1+ map significantly improved intra-subject variability of PD and R1 in the gray (42%) and white matter (54%) and correcting the raw images for the effect of Gibb's ringing further improved intra-subject variability in all maps in the gray (11%) and white matter (10%). Combining Gibb's ringing correction and bias field correction using acquired B1+ maps provides excellent stability of the 7-min MPM sequence with 1.6 mm resolution suitable for the clinical routine.

Abstract 15710: Myocardial Ischaemia in Cardiac Amyloidosis, Changing Perspectives

Introduction: Cardiac involvement determines outcome in systemic amyloidosis, but the relationship between amyloid deposits and outcomes is poorly understood. Many clinical observations are not explained by the simple concept of physical, mechanical replacement of the interstitium by amyloid material. Hypothesis: Preliminary studies in patients with cardiac amyloidosis (CA) support the hypothesis that myocardial ischaemia contributes to cell damage. This study assesses the presence and mechanisms of myocardial ischaemia using CMR with multiparametric mapping and histopathological assessment. Methods: 92 patients with CA (41 AL, 51 ATTR) and 73 without CA (26 with unobstructed coronary arteries; 47 with 3VD) underwent CMR with T1, T2, Extracellular volume (ECV) mapping and adenosine stress with myocardial blood flow (MBF) mapping. 25 cardiac biopsies and 3 explanted hearts with CA were analysed histopathologically. Results: CA patients had severe reductions in stress MBF and myocardial perfusion reserve (MPR)- (1.03ml/g/min±0.50;1.54±0.59 ) compared to patients with unobstructed coronary arteries (2.82 ml/g/min±0.53; 2.94±0.59, p&lt;0.001), and comparable only to 3VD (1.32±0.47ml/g/min, p=0.04;1.49±0.44, p=1.00). Myocardial perfusion abnormalities correlated with amyloid burden, systolic function and blood biomarkers (p&lt;0.001). Biopsies showed evidence of diffuse hypoxia with abnormal VEGF staining in cardiomyocytes and endothelial cells. Amyloid infiltration in intramural arteries was associated with severe lumen reduction in 20% of vessels, with severe reduction in capillary density in areas with and without amyloid deposits. Conclusion: CA is associated with severe myocardial ischaemia demonstrable by histology and CMR perfusion mapping. Histological evaluation indicates a complex pathophysiology, where direct disruption of the vessels by amyloid deposits and reduction in epicardial flow contribute to myocardial ischaemia.

Time-resolved magnetic resonance fingerprinting for radiotherapy motion management.

This study aims to develop a novel time-resolved magnetic resonance fingerprinting (TR-MRF) technique for respiratory motion imaging applications. The TR-MRF technique consists of repeated MRF acquisitions using an unbalanced steady-state free precession sequence with spiral-in-spiral-out trajectory. Time-resolved magnetic resonance fingerprinting was first tested via computer simulation using a four-dimensional (4D) extended cardiac-torso (XCAT) phantom for both regular and irregular breathing profiles, and was tested in three healthy volunteers. Parametric TR-MRF maps at different respiratory phases were subsequently estimated using our TR-MRF sorting and reconstruction techniques. The resulting TR-MRF maps were evaluated using a set of metrices related to radiotherapy applications, including absolute difference in motion amplitude, error in the amplitude of diaphragm motion (ADM), tumor volume error (TVE), signal-to-noise ratio (SNR), and tumor contrast. TR-MRF maps with regular and irregular breathing were successfully generated in XCAT phantom. Numerical simulations showed that the TVE were 1.6±2.7% and 1.3±2.2%, the average absolute differences in tumor motion amplitude were 0.3±0.7mm and 0.3±0.6mm, and the ADM were 4.1±0.9% and 3.5±0.9% for irregular and regular breathing, respectively. The SNR of the T1 and T2 maps of the liver and the tumor were generally higher for regular breathing compared to irregular breathing, whereas tumor-to-liver contrast is similar between the two breathing patterns. The proposed technique was successfully implemented on the healthy volunteers. We have successfully demonstrated in both digital phantom and healthy subjects a novel TR-MRF technique capable of imaging respiratory motions with simultaneous quantification of MR multiparametric maps.

Three-dimensional whole-brain simultaneous T1, T2, and T1ρ quantification using MR Multitasking: Method and initial clinical experience in tissue characterization of multiple sclerosis.

To develop a 3D whole-brain simultaneous T1/T2/T1ρ quantification method with MR Multitasking that provides high quality, co-registered multiparametric maps in 9 min. MR Multitasking conceptualizes T1/T2/T1ρ relaxations as different time dimensions, simultaneously resolving all three dimensions with a low-rank tensor image model. The proposed method was validated on a phantom and in healthy volunteers, comparing quantitative measurements against corresponding reference methods and evaluating the scan-rescan repeatability. Initial clinical validation was performed in age-matched relapsing-remitting multiple sclerosis (RRMS) patients to examine the feasibility of quantitative tissue characterization and to compare with the healthy control cohort. The feasibility of synthesizing six contrast-weighted images was also examined. Our framework produced high quality, co-registered T1/T2/T1ρ maps that closely resemble the reference maps. Multitasking T1/T2/T1ρ measurements showed substantial agreement with reference measurements on the phantom and in healthy controls. Bland-Altman analysis indicated good in vivo repeatability of all three parameters. In RRMS patients, lesions were conspicuously delineated on all three maps and on four synthetic weighted images (T2-weighted, T2-FLAIR, double inversion recovery, and a novel "T1ρ-FLAIR" contrast). T1 and T2 showed significant differences for normal appearing white matter between patients and controls, while T1ρ showed significant differences for normal appearing white matter, cortical gray matter, and deep gray matter. The combination of three parameters significantly improved the differentiation between RRMS patients and healthy controls, compared to using any single parameter alone. MR Multitasking simultaneously quantifies whole-brain T1/T2/T1ρ and is clinically promising for quantitative tissue characterization of neurological diseases, such as MS.

MR-Linac Radiotherapy in Year One: Experience's in Imaging, Patient Treatment and Data Collection

To present our institutions initial clinical experience with a high field MR-Linac with regards to patients treated, data collected, functional imaging performed and general performance of the machine. From Aug 15, 2019 to Feb 7, 2020, thirty-three patients were treated on our 1.5 T MR-Linac with all patients enrolled in the MOMENTUM study (ClinicalTrials.gov, identifier: NCT04075305). Two types of workflows were used: one accounting for daily patient shifts only (adapt to position or ATP) and the other involving online plan adaptation through re-contouring and re-optimization based on daily MRI images (adapt to shape or ATS). Of the thirty-three patients, thirty were CNS brain patients (15 GBM and 15 other) treated using ATP and three were prostate cancer patients treated using ATS and SBRT to a dose of 40 Gy in 5 fractions. Imaging involved T1 (brain ATP) or T2 (prostate ATS) weighted scans captured online for registration/planning. Functional imaging sequences for brain ATP (DWI, MT, BOLD, CEST) were taken before, during and post irradiation in addition to T2-FLAIR. DWI was done for the prostate cases before, during and post irradiation. Timing was recorded for the various stages of the workflows. Machine performance was characterized in terms of unscheduled downtime events. A total of 540 fractions were delivered on the MR-Linac over its initial 25 weeks of use. The average session time (n = 200 fractions) for the brain ATP workflow (excluding post imaging) was 26.9 minutes (3.7 min setup, 5.5 min pre-tx imaging, 5.1 min image registration, 4.5 min plan optimization, 2.0 min physics QA, and 6.1 min beam on). The minimum session time was 24 minutes for the brain ATP. The average session time for the prostate ATS workflow (n = 10 fractions) was 47.7 minutes (6.6 min setup, 3.2 min pre-tx imaging, 3.5 min image registration, 15.1 min contouring, 5.6 min plan optimization, 1.5 min physics QA, 2.9 min verification imaging and 9.3 min beam on). Additional post beam research scans took, on average, 12.5 minutes for the prostate cases. The following multi-parametric imaging maps were generated for the brain patients: T1 and T2, ADC, T2-FLAIR, CEST asymmetry and Amide MTR. The brain T2-FLAIR signal, in some cases, reduced over the treatment course. Changes in ADC maps were observed for both brain and prostate over the treatment. In some instances, brain re-planning was done offline based on daily online T2-FLAIR imaging. In terms of downtime, patients were transferred to a standard Linac for 7.1 % of fractions due to either a magnetron change, modulator tank replacement, or a cooling issue. An MR-Linac program has been implemented at our institution involving a multi-disciplinary group with both machine data and patient data being captured. The current status, clinical and technical considerations, and most recent image-based findings will be presented.

Simultaneous voxel‐wise analysis of brain and spinal cord morphometry and microstructure within the SPM framework

To validate a simultaneous analysis tool for the brain and cervical cord embedded in the statistical parametric mapping (SPM) framework, we compared trauma‐induced macro‐ and microstructural changes in spinal cord injury (SCI) patients to controls. The findings were compared with results obtained from existing processing tools that assess the brain and spinal cord separately. A probabilistic brain‐spinal cord template (BSC) was generated using a generative semi‐supervised modelling approach. The template was incorporated into the pre‐processing pipeline of voxel‐based morphometry and voxel‐based quantification analyses in SPM. This approach was validated on T1‐weighted scans and multiparameter maps, by assessing trauma‐induced changes in SCI patients relative to controls and comparing the findings with the outcome from existing analytical tools. Consistency of the MRI measures was assessed using intraclass correlation coefficients (ICC). The SPM approach using the BSC template revealed trauma‐induced changes across the sensorimotor system in the cord and brain in SCI patients. These changes were confirmed with established approaches covering brain or cord, separately. The ICC in the brain was high within regions of interest, such as the sensorimotor cortices, corticospinal tracts and thalamus. The simultaneous voxel‐wise analysis of brain and cervical spinal cord was performed in a unique SPM‐based framework incorporating pre‐processing and statistical analysis in the same environment. Validation based on a SCI cohort demonstrated that the new processing approach based on the brain and cord is comparable to available processing tools, while offering the advantage of performing the analysis simultaneously across the neuraxis.

Multiparameter mapping of relaxation (R1, R2*), proton density and magnetization transfer saturation at 3 T: A multicenter dual-vendor reproducibility and repeatability study.

Multicenter clinical and quantitative magnetic resonance imaging (qMRI) studies require a high degree of reproducibility across different sites and scanner manufacturers, as well as time points. We therefore implemented a multiparameter mapping (MPM) protocol based on vendor's product sequences and demonstrate its repeatability and reproducibility for whole‐brain coverage. Within ~20 min, four MPM metrics (magnetization transfer saturation [MT], proton density [PD], longitudinal [R1], and effective transverse [R2*] relaxation rates) were measured using an optimized 1 mm isotropic resolution protocol on six 3 T MRI scanners from two different vendors. The same five healthy participants underwent two scanning sessions, on the same scanner, at each site. MPM metrics were calculated using the hMRI‐toolbox. To account for different MT pulses used by each vendor, we linearly scaled the MT values to harmonize them across vendors. To determine longitudinal repeatability and inter‐site comparability, the intra‐site (i.e., scan‐rescan experiment) coefficient of variation (CoV), inter‐site CoV, and bias across sites were estimated. For MT, R1, and PD, the intra‐ and inter‐site CoV was between 4 and 10% across sites and scan time points for intracranial gray and white matter. A higher intra‐site CoV (16%) was observed in R2* maps. The inter‐site bias was below 5% for all parameters. In conclusion, the MPM protocol yielded reliable quantitative maps at high resolution with a short acquisition time. The high reproducibility of MPM metrics across sites and scan time points combined with its tissue microstructure sensitivity facilitates longitudinal multicenter imaging studies targeting microstructural changes, for example, as a quantitative MRI biomarker for interventional clinical trials.

Imaging the aging brain: study design and baseline findings of the SENIOR cohort

BackgroundCurrent demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.MethodsThe SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3 T and 7 T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors.ResultsOne hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects.ConclusionsWe here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging.