Fast Quantitative Low-Field Magnetic Resonance Imaging with OPTIMUM : Optimized Magnetic Resonance Fingerprinting Using a Stationary Steady-State Cartesian Approach and Accelerated Acquisition Schedules

Peer reviewedPublisher PD

Low-Field MRI : How Low Can We Go? A Fresh View on an Old Debate

Funding This work was supported by the Swiss National Science Foundation (grants #PP00P2_170575; PCEFP2_186861)Peer reviewe

Biplanar quadrature coil for versatile low-field extremity MRI

Funding This work is supported by the Swiss National Science Foundation (Grant Numbers 170575, 186861, and 198905). Acknowledgments The authors warmly thank Prof. Dr. André Constantinesco for sharing his expertise in low-field technologies, as well as for his generosity and strong support especially during the early days of the AMT Center, when the platform was still in the making.Peer reviewedPublisher PD

Fast, interleaved, Look‐Locker–based T1 mapping with a variable averaging approach : Towards temperature mapping at low magnetic field

The authors thank COST Action CA15209 for insightful discussions. This research was funded by the Swiss National Science Foundation (Grant Nos. 170575, 186861, and 198905). Open access funding provided by Universitat Basel.Peer reviewedPublisher PD

Biplanar quadrature coil for versatile low-field extremity MRI

Biplanar magnets offer extended flexibility in MRI, particularly appealing due to unmatched accessibility to the patient. At low field strength (<0.2 T), such geometries could be particularly suitable for interventional settings or purpose-built applications such as musculoskeletal imaging. In the proposed work, we present a dual-channel, biplanar coil array for low-field MRI featuring almost fully open access when sited in a biplanar magnet. The proposed detector relies on the assembly of two orthogonal biplanar coils (single transmit channel, two receive channels in quadrature) respectively interfaced with custom inductive couplers. Simulations of the B1 field in each element were performed before the quadrature coil was built and used at ∼ 0.1 T (4.33 MHz). Once assembled, the best performance in our setup was achieved in undermatched conditions in place of conventional 50-Ω matching. Phantom images display the extended coverage of the quadrature coil, with similar SNR from each individual biplanar coil. The combined images show an expected SNR gain of 2 that confirms good decoupling between the two channels (−36 dB). To the best of our knowledge, the proposed coil represents the first implementation of a biplanar geometry at low field and the first quadrature detection for a biplanar design. The open design and overall good sensitivity of our biplanar design enabled fast and quasi-isotropic 3D imaging with (1.6 × 1.6 × 2.2) mm3 resolution in vivo in human extremities

Editorial : Innovations in MR Hardware from Ultra-Low to Ultra-High Field

Peer reviewedPublisher PD

Nanodiamond-enhanced MRI via in situ hyperpolarization

Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery and as highly biostable fluorescent markers for cellular tracking. Beyond optical techniques, however, options for noninvasive imaging of nanodiamonds in vivo are severely limited. Here, we demonstrate that the Overhauser effect, a proton–electron polarization transfer technique, can enable high-contrast magnetic resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra-low magnetic field. The technique transfers spin polarization from paramagnetic impurities at nanodiamond surfaces to 1H spins in the surrounding water solution, creating MRI contrast on-demand. We examine the conditions required for maximum enhancement as well as the ultimate sensitivity of the technique. The ability to perform continuous in situ hyperpolarization via the Overhauser mechanism, in combination with the excellent in vivo stability of nanodiamond, raises the possibility of performing noninvasive in vivo tracking of nanodiamond over indefinitely long periods of time

Quantitative MRI to Characterize the Nucleus Pulposus Morphological and Biomechanical Variation According to Sagittal Bending Load and Radial Fissure, an ex vivo Ovine Specimen Proof-of-Concept Study

Background and context: Low back pain is a dramatic burden worldwide. Discography studies have shown that 39% of chronic low back pain patients suffer from discogenic pain due to a radial fissure of intervertebral disc. This can have major implications in clinical therapeutic choices. The use of discography is restricted because of its invasiveness and interest in it remains low as it represents a static condition of the disc morphology. Magnetic Resonance Imaging (MRI) appears to be less invasive but does not describe the biomechanical dynamic behavior of the fissure.Purpose: We aimed to seek a quantitative MRI protocol combined with ex vivo sagittal loading to analyze the morphological and biomechanical changes of the intervertebral disc structure and stress distribution.Study design: Proof of concept.Methods: We designed a proof-of-concept ovine study including 3 different 3.0 T-MRI sequences (T2-weighted, T1 and T2 mapping). We analyzed 3 different mechanical states (neutral, flexion and extension) on a fresh ovine spine specimen to characterize an intervertebral disc before and after puncturing the anterior part of the annulus fibrosus. We used a mark tracking method to calculate the bending angles and the axial displacements of the discal structures. In parallel, we created a finite element model to calculate the variation of the axial stress and the maximal intensity shear stress, extrapolated from our experimental boundary conditions.Results: Thanks to an original combination of specific nuclear relaxation time quantifications (T1, T2) of the discal tissue, we characterized the nucleus movement/deformation into the fissure according to the synchronous mechanical load. This revealed a link between disc abnormality and spine segment range of motion capability. Our finite element model highlighted significant variations within the stress distribution between intact and damaged disc.Conclusion: Quantitative MRI appears to provide a new opportunity to characterize intra-discal structural morphology, lesions and stress changes under the influence of mechanical load. This preliminary work could have substantial implications for non-invasive disc exploration and could help to validate novel therapies for disc treatment

Imagerie quantitative du dépot d'aérosols dans les voies aériennes par résonance magnétique de l'hélium-3 hyperpolarisé

Inhalation therapy has broadened its field of application over the last two decades by considering the lung not only as an organ to cure, but also as a portal toward systemic circulation. This new approach is being made possible by the emergence of biotherapeutics and a greater understanding of the absorption properties of the lung. Systemic delivery across the oronasal route was then investigated for a number of indications including migraine, diabetes, pain, and cancer. However, progress into the market of systemic aerosolized drug delivery has been slowed down to-date by a number of confounding factors including rapid clearance, instability, long-term toxicity, and dosing issues. Final drug distribution in such complex geometries strongly depends on a variety of parameters like the aerosol administration protocol, particle size, density, and physicochemical properties, as well as the airway geometry. Independently of drug formulation and pharmacokinetic considerations, these parameters determine the deposition distribution throughout the lung. Quantification and spatial localization are primordially needed to better control and optimize drug concentration at specific or less- and nonspecific sites. Nuclear medicine techniques are currently the only available modalities that combine both aerosol quantification and regional localization. They are considered as reference techniques even though they remain limited by their spatial and temporal resolutions as well as by patient exposure to radiations. With regard to lung imaging, hyperpolarized helium-3 MRI has been developed as a powerful tool to quantitatively characterize the parenchyma and the organ function and morphology. The technique is innocuous and provides millimeter and sub-second resolutions with rather high signal to noise ratios. In this thesis, a new imaging modality was developed on the grounds of hyperpolarized helium-3 MRI to probe and quantify aerosol deposition in the airways. In the first part of the thesis, I describe the potential of helium-3 MRI to probe aerosol deposition by using superparamagnetic contrast agents. The second part mainly focuses on the validation of this new modality by comparing it to a reference technique, single photon emission computed tomography (SPECT), and computational fluid dynamics. The last part of the manuscript is dedicated to aerosol administration and in vivo measurements in rat lungs. This experiment was possible by designing and building an MR compatible gas administrator and ventilator dedicated to small animals, SAGAS (Small Animal Gas Administration System). Its complete hardware and software description is presented in the same chapter.Le paysage des thérapies inhalées connaît de profondes évolutions depuis les deux dernières décennies, avec pour objet la considération nouvelle du poumon comme un site de transfert des agents thérapeutiques vers le compartiment sanguin. Cette approche originale est apparue par la combinaison de développements théoriques et pratiques multiples impliqués dans la mise au point de nombreux médicaments, depuis le traitement de la douleur et du diabète jusqu'à la vaccination et le traitement de certains cancers. La quantité effective de médicament délivrée par aérosols est pondérée par de nombreux facteurs dont le mode et les conditions d’inhalation, les propriétés physiques des gaz en jeu, la morphologie des voies respiratoires ou encore les propriétés physico-chimiques des particules véhiculées. Les développements en cours ces quatre dernières années ont été conditionnés par des résultats encore mal compris, soulignant les limites des connaissances sur le transport et le dépôt d'aérosols dans le poumon. Ces manques mettent en avant le besoin d'outils performants pour l'évaluation du dépôt de particules dans les voies respiratoires.Les techniques d’imagerie permettent à la fois l’évaluation spatiale et quantitative du dépôt, avec pour seules références aujourd’hui, les techniques de médecine nucléaire. Outre l’aspect ionisant de ces techniques, elles bénéficient d’une sensibilité de détection encore inégalée. Elles demeurent néanmoins limitées par des résolutions spatiale et temporelle faibles, rendant le plus souvent difficile tant l’interprétation du dépôt que le rôle joué par les principaux mécanismes de clairance dans les voies aériennes. Depuis la fin des années 1990, les techniques de résonance magnétique imagent des noyaux hyperpolarisés (hélium-3 et xenon-129) et établissent de nouveaux standards dans l’exploration de la fonction pulmonaire.Cette thèse établit, sur la base de l’IRM de l’hélium-3 hyperpolarisé, une nouvelle modalité d’imagerie pour détecter et quantifier le dépôt d’aérosols dans les voies aériennes.Dans un premier temps, et dans un contexte où l’imagerie par résonance magnétique ne s’était pas encore penchée sur la problématique des aérosols thérapeutiques, un vaste travail d’investigation a été mené pour évaluer la sensibilité de l’IRM de l’hélium-3 hyperpolarisé au dépôt d’aérosols marqués à base d’oxyde de fer superparamagnétique. Le second volet de ce travail s’est porté sur la validation de notre méthode d’évaluation, et sur le développement de la quantification du dépôt d’aérosols. Nous avons enfin pu tester la reproductibilité de notre méthode d’évaluation du dépôt in vivo chez le rat, grâce à la réalisation d’une plateforme de ventilation et d’administration de gaz et d’aérosols dédiée, SAGAS

Hyperpolarized helium-3 MRI for detection and quantification of aerosol deposition in the airways

Le paysage des thérapies inhalées connaît de profondes évolutions depuis les deux dernières décennies, avec pour objet la considération nouvelle du poumon comme un site de transfert des agents thérapeutiques vers le compartiment sanguin. Cette approche originale est apparue par la combinaison de développements théoriques et pratiques multiples impliqués dans la mise au point de nombreux médicaments, depuis le traitement de la douleur et du diabète jusqu'à la vaccination et le traitement de certains cancers. La quantité effective de médicament délivrée par aérosols est pondérée par de nombreux facteurs dont le mode et les conditions d’inhalation, les propriétés physiques des gaz en jeu, la morphologie des voies respiratoires ou encore les propriétés physico-chimiques des particules véhiculées. Les développements en cours ces quatre dernières années ont été conditionnés par des résultats encore mal compris, soulignant les limites des connaissances sur le transport et le dépôt d'aérosols dans le poumon. Ces manques mettent en avant le besoin d'outils performants pour l'évaluation du dépôt de particules dans les voies respiratoires.Les techniques d’imagerie permettent à la fois l’évaluation spatiale et quantitative du dépôt, avec pour seules références aujourd’hui, les techniques de médecine nucléaire. Outre l’aspect ionisant de ces techniques, elles bénéficient d’une sensibilité de détection encore inégalée. Elles demeurent néanmoins limitées par des résolutions spatiale et temporelle faibles, rendant le plus souvent difficile tant l’interprétation du dépôt que le rôle joué par les principaux mécanismes de clairance dans les voies aériennes. Depuis la fin des années 1990, les techniques de résonance magnétique imagent des noyaux hyperpolarisés (hélium-3 et xenon-129) et établissent de nouveaux standards dans l’exploration de la fonction pulmonaire.Cette thèse établit, sur la base de l’IRM de l’hélium-3 hyperpolarisé, une nouvelle modalité d’imagerie pour détecter et quantifier le dépôt d’aérosols dans les voies aériennes.Dans un premier temps, et dans un contexte où l’imagerie par résonance magnétique ne s’était pas encore penchée sur la problématique des aérosols thérapeutiques, un vaste travail d’investigation a été mené pour évaluer la sensibilité de l’IRM de l’hélium-3 hyperpolarisé au dépôt d’aérosols marqués à base d’oxyde de fer superparamagnétique. Le second volet de ce travail s’est porté sur la validation de notre méthode d’évaluation, et sur le développement de la quantification du dépôt d’aérosols. Nous avons enfin pu tester la reproductibilité de notre méthode d’évaluation du dépôt in vivo chez le rat, grâce à la réalisation d’une plateforme de ventilation et d’administration de gaz et d’aérosols dédiée, SAGAS.Inhalation therapy has broadened its field of application over the last two decades by considering the lung not only as an organ to cure, but also as a portal toward systemic circulation. This new approach is being made possible by the emergence of biotherapeutics and a greater understanding of the absorption properties of the lung. Systemic delivery across the oronasal route was then investigated for a number of indications including migraine, diabetes, pain, and cancer. However, progress into the market of systemic aerosolized drug delivery has been slowed down to-date by a number of confounding factors including rapid clearance, instability, long-term toxicity, and dosing issues. Final drug distribution in such complex geometries strongly depends on a variety of parameters like the aerosol administration protocol, particle size, density, and physicochemical properties, as well as the airway geometry. Independently of drug formulation and pharmacokinetic considerations, these parameters determine the deposition distribution throughout the lung. Quantification and spatial localization are primordially needed to better control and optimize drug concentration at specific or less- and nonspecific sites. Nuclear medicine techniques are currently the only available modalities that combine both aerosol quantification and regional localization. They are considered as reference techniques even though they remain limited by their spatial and temporal resolutions as well as by patient exposure to radiations. With regard to lung imaging, hyperpolarized helium-3 MRI has been developed as a powerful tool to quantitatively characterize the parenchyma and the organ function and morphology. The technique is innocuous and provides millimeter and sub-second resolutions with rather high signal to noise ratios. In this thesis, a new imaging modality was developed on the grounds of hyperpolarized helium-3 MRI to probe and quantify aerosol deposition in the airways. In the first part of the thesis, I describe the potential of helium-3 MRI to probe aerosol deposition by using superparamagnetic contrast agents. The second part mainly focuses on the validation of this new modality by comparing it to a reference technique, single photon emission computed tomography (SPECT), and computational fluid dynamics. The last part of the manuscript is dedicated to aerosol administration and in vivo measurements in rat lungs. This experiment was possible by designing and building an MR compatible gas administrator and ventilator dedicated to small animals, SAGAS (Small Animal Gas Administration System). Its complete hardware and software description is presented in the same chapter