T2-hyperintense lesions are the key imaging marker of multiple sclerosis (MS). Previous studies have shown that the white matter surrounding such lesions is often also affected by MS. Our aim was... Show moreT2-hyperintense lesions are the key imaging marker of multiple sclerosis (MS). Previous studies have shown that the white matter surrounding such lesions is often also affected by MS. Our aim was to develop a new method to visualize and quantify the extent of white matter tissue changes in MS based on relaxometry properties.We applied a fast, multi-parametric quantitative MRI approach and used a multi-component MR Fingerprinting (MC-MRF) analysis. We assessed the differences in the MRF component representing prolongedrelaxation time between patients with MS and controls and studied the relation between this component’s volume and structural white matter damage identified on FLAIR MRI scans in patients with MS.A total of 48 MS patients at two different sites and 12 healthy controls were scanned with FLAIR and MRF-EPI MRI scans. MRF scans were analyzed with a joint-sparsity multi-component analysis to obtain magnetization fraction maps of different components, representing tissues such as myelin water, white matter, gray matter and cerebrospinal fluid. In the MS patients, an additional component was identified with increased transverse relaxation times compared to the white matter, likely representing changes in free water content. Patients with MS had a higher volume of the long- component in the white matter of the brain compared to healthy controls (B (95%-CI) = 0.004 (0.0006–0.008), p = 0.02). Furthermore, this MRF component had a moderate correlation (correlation coefficient R 0.47) with visible structural white matter changes on the FLAIR scans. Also, the component was found to be more extensive compared to structural white matter changes in 73% of MS patients.In conclusion, our MRF acquisition and analysis captured white matter tissue changes in MS patients compared to controls. In patients these tissue changes were more extensive compared to visually detectable white matter changes on FLAIR scans. Our method provides a novel way to quantify the extent of white matter changes in MS patients, which is underestimated using only conventional clinical MRI scans. Show less
Myasthenia gravis (MG) is a neuromuscular disorder in which patients experience fluctuating and fatigable muscle weakness. Ocular muscle weakness and bulbar weakness are most common, with ocular... Show moreMyasthenia gravis (MG) is a neuromuscular disorder in which patients experience fluctuating and fatigable muscle weakness. Ocular muscle weakness and bulbar weakness are most common, with ocular symptoms such as double vision (diplopia) and drooping eyelids (ptosis) often being prominent. The aim was to develop new methods to improve clinical care for ocular MG patients. In this thesis, I investigated the eye muscles using muscle electrophysiology, orthoptic measurements, and quantitative MRI. I have made several advancements in the areas of diagnostics, understanding refractory ocular symptoms, and the development of objective measurements of ocular muscle weakness in MG. Show less
Newly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI... Show moreNewly introduced hybrid systems that combine an MRI scanner with a linear accelerator for radiation treatment, called MR-linacs, provide an opportunity for the daily acquisition of quantitative MRI (qMRI) without increasing patient burden. This allows for the measurement of changes in quantitative MRI biomarkers over time, that may indicate a response to the radiation treatment. In this thesis, the performance of the Unity MR-linac with regards to several qMRI sequences was characterized, showing results similar to diagnostic systems in terms of accuracy and repeatability. Additionally, we found changes in qMRI parameters in patients early during treatment, which indicates potential as biomarkers for treatment outcome. Show less
Objective To implement magnetic resonance fingerprinting (MRF) on a permanent magnet 50 mT low-field system deployable as a future point-of-care (POC) unit and explore the quality of the parameter... Show moreObjective To implement magnetic resonance fingerprinting (MRF) on a permanent magnet 50 mT low-field system deployable as a future point-of-care (POC) unit and explore the quality of the parameter maps.Materials and methods 3D MRF was implemented on a custom-built Halbach array using a slab-selective spoiled steadystate free precession sequence with 3D Cartesian readout. Undersampled scans were acquired with different MRF flip angle patterns and reconstructed using matrix completion and matched to the simulated dictionary, taking excitation profile and coil ringing into account. MRF relaxation times were compared to that of inversion recovery ( IR) and multi-echo spin echo (MESE) experiments in phantom and in vivo. Furthermore, -B0 inhomogeneities were encoded in the MRF sequence using an alternating TE pattern, and the estimated map was used to correct for image distortions in the MRF images using a modelbased reconstruction.Results Phantom relaxation times measured with an optimized MRF sequence for low field were in better agreement with reference techniques than for a standard MRF sequence. In vivo muscle relaxation times measured with MRF were longer than those obtained with an IR sequence (T-1: 182 +/- 21.5 vs 168 +/- 9.89 ms) and with an MESE sequence (T-2: 69.8 +/- 19.7 vs 46.1 +/- 9.65 ms). In vivo lipid MRF relaxation times were also longer compared with IR (T-1: 165 +/- 15.1 ms vs 127 +/- 8.28 ms) and with MESE (T-2: 160 +/- 15.0 ms vs 124 +/- 4.27 ms). Integrated Delta B-0 estimation and correction resulted in parameter maps with reduced distortions.Discussion It is possible to measure volumetric relaxation times with MRF at 2.5 x 2.5 x 3.0 -mm(3) resolution in a 13 min scan time on a 50 mT permanent magnet system. The measured MRF relaxation times are longer compared to those measured with reference techniques, especially for T-2. This discrepancy can potentially be addressed by hardware, reconstruction and sequence design, but long-term reproducibility needs to be further improved. Show less
MR fingerprinting (MRF) is a promising method for quantitative characterization of tissues. Often, voxel-wise measurements are made, assuming a single tissue-type per voxel. Alternatively, the... Show moreMR fingerprinting (MRF) is a promising method for quantitative characterization of tissues. Often, voxel-wise measurements are made, assuming a single tissue-type per voxel. Alternatively, the Sparsity Promoting Iterative Joint Non-negative least squares Multi-Component MRF method (SPIJN-MRF) facilitates tissue parameter estima-tion for identified components as well as partial volume segmentations. The aim of this paper was to evaluate the accuracy and repeatability of the SPIJN-MRF parameter estimations and partial volume segmentations. This was done (1) through numerical simulations based on the BrainWeb phantoms and (2) using in vivo acquired MRF data from 5 subjects that were scanned on the same week-day for 8 consecutive weeks. The partial volume segmen-tations of the SPIJN-MRF method were compared to those obtained by two conventional methods: SPM12 and FSL. SPIJN-MRF showed higher accuracy in simulations in comparison to FSL-and SPM12-based segmentations: Fuzzy Tanimoto Coefficients (FTC) comparing these segmentations and Brainweb references were higher than 0.95 for SPIJN-MRF in all the tissues and between 0.6 and 0.7 for SPM12 and FSL in white and gray matter and between 0.5 and 0.6 in CSF. For the in vivo MRF data, the estimated relaxation times were in line with literature and minimal variation was observed. Furthermore, the coefficient of variation (CoV) for estimated tissue volumes with SPIJN-MRF were 10.5% for the myelin water, 6.0% for the white matter, 5.6% for the gray matter, 4.6% for the CSF and 1.1% for the total brain volume. CoVs for CSF and total brain volume measured on the scanned data for SPIJN-MRF were in line with those obtained with SPM12 and FSL. The CoVs for white and gray mat-ter volumes were distinctively higher for SPIJN-MRF than those measured with SPM12 and FSL. In conclusion, the use of SPIJN-MRF provides accurate and precise tissue relaxation parameter estimations taking into account intrinsic partial volume effects. It facilitates obtaining tissue fraction maps of prevalent tissues including myelin water which can be relevant for evaluating diseases affecting the white matter. Show less
The recent FLAME trial has demonstrated improved local control of intermediate to high-risk prostate cancer after focal dose escalation of the visible tumor. To visualize the tumor, MRI... Show moreThe recent FLAME trial has demonstrated improved local control of intermediate to high-risk prostate cancer after focal dose escalation of the visible tumor. To visualize the tumor, MRI examinations were taken in which prostate tissue characteristics were visualized. Since this treatment strategy improves the clinical outcome of the patient, a technical analysis of the FLAME dataset is useful for the further optimization of focal dose escalation strategies.Delineation of the prostate tumor appeared to be performed differently in the participating radiotherapy departments. Considering the impact on the realized tumor dose, this analysis demonstrated the need for guidelines of tumor delineation on MRI. Due to the complex nature of the treatment plans, in addition a prediction model was developed, which identified patients for which a higher tumor dose could be planned.The application of MRI was also investigated for ‘dose painting by numbers’, in which MRI values are translated to prescription dose without interference of manual tumor delineations. Dose prescription based on MRI appeared robust to daily patient variations, a prerequisite for further development of ‘dose painting by numbers’. However, because of the absence of significant tumor changes during the treatment course, MRI was considered not suitable for early adaptive treatment. Show less
The aim of this thesis was to evaluate quantitative MRI techniques in reno-cardiovascular health, and to study the links between obesity and reno-cardiovascular health using quantitative MRI... Show moreThe aim of this thesis was to evaluate quantitative MRI techniques in reno-cardiovascular health, and to study the links between obesity and reno-cardiovascular health using quantitative MRI metrics. Furthermore, we aimed to address novel insights on the safety of contrast media with regard to the use of gadolinium. The general introduction (Chapter 1) of this thesis introduces the concept of quantitative MRI, its application in epidemiological research, reno-cardiovascular health, and in obesity. In addition, the general introduction addresses the safety of gadolinium as an MRI contrast agent. Following the general introduction a review of the clinical application and technical considerations of quantitative MRI using T1 and T2(*) mapping in cardiac and renal imaging was provided in Chapter 2. Part 1 of this thesis focused on the reproducibility and clinical validity of T1 mapping and proton magnetic resonance spectroscopy (1H-MRS) in renal imaging. Part 2, described different studies evaluating the association between obesity and reno-cardiovascular function which was analyzed in population-based imaging studies using different quantitative MRI metrics. Part 3, provides an overview of the safety profile of gadolinium containing contrast agents, and reflection on the recent EMA recommendations. Show less
PurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker... Show morePurposeSystems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker discovery using quantitative MRI (qMRI). Here, the performance of a 1.5 T MR-linac regarding qMRI was assessed on phantoms. Additionally, we show the feasibility of qMRI in a prostate cancer patient on this system for the first time.Materials and methodsFour 1.5 T MR-linac systems from four institutes were included in this study. T1 and T2 relaxation times, and apparent diffusion coefficient (ADC) maps, as well as dynamic contrast enhanced (DCE) images were acquired. Bland–Altman statistics were used, and accuracy, repeatability, and reproducibility were determined.ResultsMedian accuracy for T1 ranged over the four systems from 2.7 to 14.3%, for T2 from 10.4 to 14.1%, and for ADC from 1.9 to 2.7%. For DCE images, the accuracy ranged from 12.8 to 35.8% for a gadolinium concentration of 0.5 mM and deteriorated for higher concentrations. Median short-term repeatability for T1 ranged from 0.6 to 5.1%, for T2 from 0.4 to 1.2%, and for ADC from 1.3 to 2.2%. DCE acquisitions showed a coefficient of variation of 0.1–0.6% in the signal intensity. Long-term repeatability was 1.8% for T1, 1.4% for T2, 1.7% for ADC, and 17.9% for DCE. Reproducibility was 11.2% for T1, 2.9% for T2, 2.2% for ADC, and 18.4% for DCE.ConclusionThese results indicate that qMRI on the Unity MR-linac is feasible, accurate, and repeatable which is promising for treatment response monitoring and treatment plan adaptation based on daily qMRI. Show less
