physics considerations and electromagnetic field simulations up to 23.5 Tesla (1GHz)

Background Glioblastoma multiforme is the most common and most aggressive malign brain tumor. The 5-year survival rate after tumor resection and adjuvant chemoradiation is only 10 %, with almost all recurrences occurring in the initially treated site. Attempts to improve local control using a higher radiation dose were not successful so that alternative additive treatments are urgently needed. Given the strong rationale for hyperthermia as part of a multimodal treatment for patients with glioblastoma, non-invasive radio frequency (RF) hyperthermia might significantly improve treatment results. Methods A non-invasive applicator was constructed utilizing the magnetic resonance (MR) spin excitation frequency for controlled RF hyperthermia and MR imaging in an integrated system, which we refer to as thermal MR. Applicator designs at RF frequencies 300 MHz, 500 MHz and 1GHz were investigated and examined for absolute applicable thermal dose and temperature hotspot size. Electromagnetic field (EMF) and temperature simulations were performed in human voxel models. RF heating experiments were conducted at 300 MHz and 500 MHz to characterize the applicator performance and validate the simulations. Results The feasibility of thermal MR was demonstrated at 7.0 T. The temperature could be increased by ~11 °C in 3 min in the center of a head sized phantom. Modification of the RF phases allowed steering of a temperature hotspot to a deliberately selected location. RF heating was monitored using the integrated system for MR thermometry and high spatial resolution MRI. EMF and thermal simulations demonstrated that local RF hyperthermia using the integrated system is feasible to reach a maximum temperature in the center of the human brain of 46.8 °C after 3 min of RF heating while surface temperatures stayed below 41 °C. Using higher RF frequencies reduces the size of the temperature hotspot significantly. Conclusion The opportunities and capabilities of thermal magnetic resonance for RF hyperthermia interventions of intracranial lesions are intriguing. Employing such systems as an alternative additive treatment for glioblastoma multiforme might be able to improve local control by “fighting fire with fire”. Interventions are not limited to the human brain and might include temperature driven targeted drug and MR contrast agent delivery and help to understand temperature dependent bio- and physiological processes in-vivo

Fiber-orientation independent component of R2* obtained from single-orientation MRI measurements in simulations and a post-mortem human optic chiasm

The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R2* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R2,iso*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used. Its linear time-dependent parameter, β1, can be biophysically related to R2,iso* when neglecting the myelin water (MW) signal in the hollow cylinder fibre model (HCFM). Here, we examined the performance of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We found that the fitted β1 can estimate R2,iso* using meGRE with long maximum-echo time (TEmax ≈ 54 ms), but not accurately captures its microscopic dependence on the g-ratio (error 84%). We proposed a new heuristic expression for β1 that reduced the error to 12% for ex vivo compartmental R2 values. Using the new expression, we could estimate an MW fraction of 0.14 for fibres with negligible dispersion in a fixed human optic chiasm for the ex vivo compartmental R2 values but not for the in vivo values. M2 and the HCFM-based simulations failed to explain the measured R2*-orientation-dependence around the magic angle for a typical in vivo meGRE protocol (with TEmax ≈ 18 ms). In conclusion, further validation and the development of movement-robust in vivo meGRE protocols with TEmax ≈ 54 ms are required before M2 can be used to estimate R2,iso* in subjects

Fiber-orientation independent component of R2* obtained from single-orientation MRI measurements in simulations and a post-mortem human optic chiasm

The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R2* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R2,iso*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used. Its linear time-dependent parameter, β1, can be biophysically related to R2,iso* when neglecting the myelin water (MW) signal in the hollow cylinder fibre model (HCFM). Here, we examined the performance of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We found that the fitted β1 can estimate R2,iso* using meGRE with long maximum-echo time (TEmax ≈ 54 ms), but not accurately captures its microscopic dependence on the g-ratio (error 84%). We proposed a new heuristic expression for β1 that reduced the error to 12% for ex vivo compartmental R2 values. Using the new expression, we could estimate an MW fraction of 0.14 for fibres with negligible dispersion in a fixed human optic chiasm for the ex vivo compartmental R2 values but not for the in vivo values. M2 and the HCFM-based simulations failed to explain the measured R2*-orientation-dependence around the magic angle for a typical in vivo meGRE protocol (with TEmax ≈ 18 ms). In conclusion, further validation and the development of movement-robust in vivo meGRE protocols with TEmax ≈ 54 ms are required before M2 can be used to estimate R2,iso* in subjects

Correction to: Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

Correction to: Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

The article Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

Development of diffusion weighted magnetic resonance methodology and its application in renal imaging

Kidney diseases are a major health issue. To address this clinical need, non-invasive imaging may provide markers to inform on the different stages of pathophysiology. Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive imaging technique sensitive to tissue water movement and can be used to differentiate between tissue properties. DWI studies commonly make use of single-shot Echo-Planar Imaging (ss-EPI) techniques that are prone to suffering from geometric distortion. Fast spin-echo imaging techniques (e.g. Rapid Acquisition Relaxation Enhancement - RARE) are less susceptible image distortions and can be an alternative to ss-EPI. Renal-DWI studies commonly use a mono or bi-exponential signal decay model which does not differentiate between the different water diffusion sources. Firstly, this thesis focuses in the implementation of a novel image acquisition technique: diffusion sensitized split-echo RARE technique. Secondly, show the feasibility of a novel image analysis approach: continuum modeling, using non-negative least squares (NNLS) for separate the different renal water diffusion sources.Nierenerkrankungen sind ein großes Gesundheitsproblem. Um diesen dringenden, ungedeckten klinischen Bedarf zu decken, kann die nicht-invasive Bildgebung Marker liefern, die über die verschiedenen Stadien der Pathophysiologie informieren. Die Diffusionsgewichtete Bildgebung (DWI) ist ein nicht-invasives Verfahren, das auf die Wasserbewegung im Gewebe reagiert. Die DWI kann zur Differenzierung von Gewebeeigenschafte beitragen. Bei DWI-Studien werden üblicherweise single-shot-echo-planar-imaging (ss-EPI)-Techniken verwendet, die anfällig für geometrische Verzerrungen sind. Schnelle Spin-Echo-Bildgebungstechniken (z. B. Rapid Acquisition Relaxation Enhancement - RARE) sind weniger anfällig für B0-Inhomogenitäts-bedingte Bildverzerrungen und können eine gute Alternative zu ss-EPI sein. Nieren-DWI-Studien verwenden üblicherweise ein mono- oder bi-exponentielles Signalabklingmodell, das nicht zwischen den verschiedenen Wasserdiffusionsquellen unterscheidet. Diese Arbeit konzentriert sich erstens auf die Implementierung einer neuartigen Bildaufnahmetechnik: die diffusionssensibilisierte Split-Echo-RARE-Technik. Zweitens wird die Machbarkeit eines neuartigen Bildanalyseansatzes aufgezeigt: Kontinuumsmodellierung unter Verwendung der non-negative least squares (NNLS) zur Trennung der verschiedenen renalen Wasserdiffusionsquellen. Methoden Die Stejskal-Tanner-Vorbereitung wurde verwendet, um eine Diffusionssensibilisierung in eine RARE-Variante einzuführen, die eine Nieren DWI frei von geometrischer Verzerrung für präklinisches DWI im Hochfeld bei 9.4 T ermöglicht. Es wurden Validierungsstudien in Standardflüssigkeiten und in vivo durchgeführt, um die Implementierung von DW Split-Echo RARE zu validieren. Es wurden numerische Simulationen durchgeführt, um die Leistung des datengesteuerten NNLS-Ansatzes unter Verwendung der konventionellen least-square Anpassung (LS) als Referenz zu bewerten. Die Simulationen zielten darauf ab, die renalen DWI Protokolle (Anzahl der Messpunkte auf dem Signalabfall, SNR, Stärke der letzten Diffusionswichtung) für die Trennung der verschiedenen renalen Wasserdiffusionsquellen für zwei physiologische Bedingungen zu bewerten. Ergebnisse Validierungsstudien lieferten Diffusionskoeffizienten, die mit den berichteten Werten aus der Literatur übereinstimmen. Die Split-Echo-RARE übertraf den konventionellen ss-EPI, wobei der ss-EPI eine 3.5-mal größere geometrische Verzerrung (2.60 vs. 0.75) hat. Die NNLS zeigte den gleichen hohen Grad an Zuverlässigkeit wie die LS, da sie in der Lage ist, die drei wichtigsten renalen Wasserdiffusionsquellen zu trennen. Der mittlere relative Fehler (MAPE) der tubulären Volumenfraktion (ftubuli) nahm mit zunehmendem SNR ab. Die Fixierung Dblood und Dtissue reduzierte die Unsicherheiten der Volumenfraktionen sehr stark. NNLS in der Lage, das (vierte) fibrotische Kompartiment zu erkennen und zwischen 10 % und 30 % Fibrose zu unterscheiden. Fazit In dieser Arbeit habe ich die Machbarkeit des Split-Echo-RARE als Alternative zur üblichen ss-EPI Technik in DWI Studien demonstriert. Diese Arbeit demonstriert die Durchführbarkeit der Kontinuummodellierung mit NNLS, einem datengesteuerten Ansatz für renale DWI als eine Alternative zur Trennung der verschiedenen renalen Wasserdiffusionsquellen unter verschiedenen (patho)physiologischen Bedingungen, einschließlich eines erhöhten tubulären Volumenanteils und verschiedener Fibrosegrade

Transient enlargement of brain ventricles during relapsing-remitting multiple sclerosis and experimental autoimmune encephalomyelitis

The brain ventricles are part of the fluid compartments bridging the CNS with the periphery. Using MRI, we previously observed a pronounced increase in ventricle volume (VV) in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here, we examined VV changes in EAE and MS patients in longitudinal studies with frequent serial MRI scans. EAE mice underwent serial MRI for up to 2 months, with gadolinium contrast as a proxy of inflammation, confirmed by histopathology. We performed a time-series analysis of clinical and MRI data from a prior clinical trial in which RRMS patients underwent monthly MRI scans over 1 year. VV increased dramatically during preonset EAE, resolving upon clinical remission. VV changes coincided with blood-brain barrier disruption and inflammation. VV was normal at the termination of the experiment, when mice were still symptomatic. The majority of relapsing-remitting MS (RRMS) patients showed dynamic VV fluctuations. Patients with contracting VV had lower disease severity and a shorter duration. These changes demonstrate that VV does not necessarily expand irreversibly in MS but, over short time scales, can expand and contract. Frequent monitoring of VV in patients will be essential to disentangle the disease-related processes driving short-term VV oscillations from persistent expansion resulting from atrophy