Advances in 3D bioprinting have enabled the fabrication of large and complex engineered tissues, but their increasing size demands non-invasive tools for monitoring structure, maturation, and perfusion. Magnetic Resonance Imaging (MRI) offers unique multiparametric capabilities, yet high-field systems remain costly and inaccessible for most laboratories. In this study, we evaluate the potential of low-field (LF, 0.3 T) MRI as an affordable and versatile alternative to high-field (HF, 7 T) MRI for characterizing bioprinted tissue constructs. Using standardized PLA and hydrogel scaffolds within a custom-designed perfusion chamber, we compared LF and HF imaging performance for morphology and flow visualization. Both modalities successfully resolved internal scaffold features, with morphometric deviations from reference CAD models remaining within quality control tolerances. Flow imaging demonstrated that LF MRI could capture velocity distributions consistent with HF measurements and computational fluid dynamics simulations, even revealing fabrication-induced defects such as channel collapse or occlusion. Finally, we applied LF MRI for longitudinal monitoring of a perfused adipose tissue construct over 34 days. This approach enabled repeated non-destructive assessments of morphology and perfusion, with final histological analyses confirming homogeneous adipogenic differentiation and extracellular matrix deposition. Together, these results establish LF MRI as a powerful tool for real-time, non-invasive evaluation of biofabricated tissues. By combining affordability, portability, and multiparametric imaging capacity, LF MRI broadens access to advanced monitoring strategies in tissue engineering and regenerative medicine, supporting both quality control and functional assessment of large-scale engineered constructs.
In tissue engineering (TE) and regenerative medicine (RM), challenges persist in achieving optimal tissue maturation due to uncontrolled physicochemical environments and the necessity for a dynamic nutrient supply. Real-time monitoring tools are crucial to address these challenges effectively. Our study evaluates nondestructive qualification tools for pre-implantation tissue assessment, aiming to enhance their quality assessment capabilities and broaden their biomedical applications. These tools target internal tissue structure, nutritive medium flow paths, and tissue metabolic state. We extend the capabilities of tissue culture monitoring by integrating advanced bioprocess technologies like Raman spectroscopy or in-vivo imaging tools like magnetic resonance imaging (MRI). Through comparative analysis with Computational Fluid Dynamics (CFD) simulations and MRI velocity mapping, we highlight the synergistic relationship between simulation-based and experimental approaches in optimising tissue feeding and oxygenation. MRI emerges as a precious tool for longitudinal tissue development monitoring, surpassing traditional destructive methods. Our findings underscore the importance of dynamic regulation in tissue culture protocols, facilitated by continuous monitoring and adjustment of the physicochemical tissue environment. Based on evidence from industrial cell-culture processes, Raman spectroscopy emerges as a standard tool for monitoring metabolic tissue. These advancements significantly propel RM and TE, paving the way for comprehensive studies and quantitative analyses essential for developing functional engineered tissues across diverse biomedical applications.
In the last few years, there has been an increasing interest from the scientific community in the fabrication of flexible coils. Several methods can be used for the manufacture of flexible coil, mainly screen-printed coils on flexible substrates. In this work, three different screen printing coils with different layers of silver ink were manufactured and their quality factors were measured on bench. A MR-coil combining screen-printed process with electrodeposition step was also built. The additional manufacture step allowed improving drastically Q factor of our screen-printed coil with more than one order of magnitude while maintaining good flexibility of the substrate.
Tissue engineering for regenerative medicine have been developing for a few decades now and the number of applications is increasing to tackle the shortage of organ donors. To date, only few systems can allow both monitoring and 3D characterization of tissue constructs during their growth. In this study, we decided to focus on following the Apparent Diffusion Coefficient (ADC) known to be a marker of cell density and built a MR-Bioreactor to probe the ADC of a growing tissue. In this preliminary work, we were able to follow the cell density of a tumor tissue model using our dedicated MR-bioreactor.
3D Plastronics is a technology capable of improving the integration of heterogeneous functions in or on polymer packages of electronic devices by implementation of conductive patterns and electronic components. Among 3D Plastronics technologies, In-Mold Electronics (IME) is a fast-growing emerging manufacturing process for mass production of plastronic devices. It is based on the screen printing of a thermoplastic film (printed electronic process), followed by a 3D shaping using thermoforming and finally a step of overmolding by injection of a thermoplastic polymer. Nowadays, IME is mainly based on PolyCarbonate (PC), which is thus a reference material. The paper focuses on Poly(Lactic Acid) (PLA), a biosourced and biodegradable polymer to reduce the environmental impact of IME manufacturing. The thermal and mechanical properties of the PLA materials are investigated to optimize the IME process parameters and to take into account the glass transition temperature Tg around 55–60 °C of PLA. Thermal properties of inks are then considered to adapt drying to the polymer substrate, with the results being a good adhesion (category 0 of the ISO 2409 standard) and sufficient electrical resistivity (290 µΩ.cm) of the ink on PLA. Electronic components are connected to the circuit with conductive and structural pastes giving a shear stress of 9.1 N/mm 2 on PLA. The next steps of the IME process are also studied, thermoforming and injection molding. An electronic circuit is designed as a demonstration vehicle combining the IME process with PLA as the main structural material.
Magnetic resonance elastography (MRE) is an elasticity imaging technique for quantitatively assessing the stiffness of human tissues. In MRE, finite element method (FEM) is widely used for modeling wave propagation and stiffness reconstruction. However, in front of inclusions with complex interfaces, FEM can become burdensome in terms of the model partition and computationally expensive. In this work, we implement a formulation of FEM, known as the eXtended finite element method (XFEM), which is a method used for modeling discontinuity like crack and heterogeneity. Using a level-set method, it makes the interface independent of the mesh, thus relieving the meshing efforts. We investigate this method in two studies: wave propagation across an oblique linear interface and stiffness reconstruction of a random-shape inclusion. In the first study, numerical results by XFEM and FEM models revealing the wave conversion rules at linear interface are presented and successfully compared to the theoretical predictions. The second study, investigated in a pseudo-practical application, demonstrates further the applicability of XFEM in MRE and the convenience, accuracy, and speed of XFEM with respect to FEM. XFEM can be regarded as a promising alternative to FEM for inclusion modeling in MRE.
Dissolution dynamic nuclear polarization (dDNP) has become a hyperpolarization method of choice for enhancing nuclear magnetic resonance (NMR) signals. Nuclear spins are polarized in solid frozen samples (in a so-called polarizer) that are subsequently dissolved and transferred to an NMR spectrometer for high sensitivity detection. One of the critical challenges of dDNP is that it requires both a fast transfer to limit nuclear spin relaxation losses as well as stability to guarantee high resolution (no bubbles nor turbulences). Here we describe the design, construction and performances of such a transfer and injection system, that features a 5 m/s speed and sub-Hz spectral resolution upon arrival at the detection spot. We demonstrate the use of such a system for inter-magnet distances of up to 10 m.
Since 1995, Magnetic Resonance Elastography (MRE) has been constantly developed as a non-invasive diagnostic tool for quantitative mapping of mechanical properties of biological tissues. Indeed, mechanical properties of tissues vary over five orders of magnitude (the shear stiffness is ranging from 10 2 Pa for fat to 10 7 Pa for bones). Additionally, these properties depend on the physiological state which explains the granted benefit of MRE for staging liver fibrosis and its potential in numerous medical and biological domains. In comparison to the other modalities used to perform such measurement, Magnetic Resonance (MR) techniques offer the advantages of acquiring 3D high spatial resolution images at high penetration depth. However, performing MRE tissue characterization requires low frequency shear waves propagating in the tissue. Inducing them is the role of a mechanical actuator specifically designed to operate under Magnetic Resonance Imaging (MRI) specific restrictions in terms of electromagnetic compatibility. Facing these restrictions, many different solutions have been proposed while keeping a common structure: a vibration generator, a coupling device transmitting the vibration and a piston responsible for the mechanical coupling of the actuator with the tissue. The following review details the MRI constraints and how they are shaping the existing actuators. An emphasis is put on piezoelectric solutions as they solve the main issues encountered with other actuator technologies. Finally, flexible electroactive materials are reviewed as they could open great perspectives to build new type of mechanical actuators with better adaptability, greater ease-of-use and more compactness of dedicated actuators for MRE of small soft samples and superficial organs such as skin, muscles or breast.
MEMS (Micro Electro Mechanical System) switches were assessed and compared to PIN diode in fulfilling the task of active decoupling of Receiver Endoluminal Coils (RECs). Three prototype RECs with the PIN diode in parallel (pPIN), MEMS in parallel (pMEMS) and MEMS in series (sMEMS) with the REC loop were built. Quality factors (Q-values), decoupling efficiency and switching delays were characterized on bench and Signal-to-Noise Ratios (SNRs) established on images at 1.5 T. Q-values were equal to 62.5, 41.2 and 65.1 for pPIN, sMEMS and pMEMS, respectively. In the decoupled state, reflection coefficients S 11 and S 21 at resonance frequency both indicated proper decoupling. Switching delays were less than 0.7 μs and 10 μs for pPIN and MEMS RECs, respectively. Decoupling/coupling delays of MEMS remained compatible with most Magnetic Resonance (MR) clinical applications. For all prototypes, MR images displayed no signal saturation and similar elliptical image sensitivity patterns. No artifacts due to active decoupling failure were observed. Mean SNR values obtained with pMEMS REC were higher than those obtained with sMEMS REC but lower than with pPIN REC because of the use of additional instrumentation to render the scanner compatible with the MEMS utilization. MEMS in parallel are an interesting alternative to PIN diode for decoupling and could lead to better SNR with a compatible MR system (dedicated control signal). The MEMS in series can be used for both decoupling and reconfiguration of the REC loop geometry for colon wall examination.
Over the last four decades, magnetic resonance imaging has become the gold standard imaging technique in many medical diagnoses for brain, cardiac, and liver disease. However, due to low critical mass and great scientific challenges, instrumentation dedicated to preclinical MRI imaging has lagged behind instrumentation for clinical applications. The aim of this paper is to demonstrate that a set of new technologies such as the 3D Molded Interconnect Devices technology preferably named below as 3D Plastronics, 3D Printing, and Microfluidics may be considered to provide a completely new way for designing preclinical MRI setups, i.e., the 3D prototyping and manufacturing of the MR coil, the sample holder, and the peripherals, all together. The fabricated MRI setup can be used both for MRI of small biological samples and for in vivo imaging of a mouse brain. This work is the first step toward the full 3D manufacturing of tailor-made multifunctional MRI probes.
Several biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal‐like properties of fibrils to separate them from nonaggregated proteins using a multi‐frequency MRE power law exponent in a phantom study. Two types of fibril, α‐synuclein (α‐Syn) and amyloid‐β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D‐direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α‐Syn and Aβ inclusions showed significantly higher y values than control inclusions (P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α‐Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi‐frequency MRE than with single frequency‐derived parameters.
Fibrils are biomarkers for early stages of dementia. In this work, α-synuclein fibrils were injected in rat striatum. Brains were imaged ex-vivo using multi-frequency MR Elastography. Estimation of the real part k r of the complex wave number was made for each studied frequency in ROIs surrounding the inclusion, a contralateral control injection and the whole brain. Exponent of the frequency power law was derived from k r maps acquired at different frequencies. No difference was observed between k r values for the different ROIs, but the exponent was more important at the fibrils location, potentially indicating that multi-frequency MRE can detect fibrils.
En 2015, une enquête menée par la Fondation pour l'Université de Lyon (1), auprès d’une centaine d’entreprises françaises, a montré que l'un des freins majeurs au développement de l’électronique sur substrat polymère, plus communément appelé plastronique, était le manque d'ingénieurs qualifiés ayant des compétences transdisciplinaires. Cela a été attribué à la nature intrinsèquement multi-physiques du sujet, impliquant de nombreux aspects qu’un ingénieur, non formé, peut difficilement gérer. En effet, la plastronique allie des compétences aussi bien en électronique, en plasturgie, en mécatronique, en sciences des matériaux, en chimie, etc. Une autre conclusion de cette enquête est que les entreprises ont besoin d’ingénieurs spécialisés dans tous ces domaines, mais également de responsables techniques capables de mener un projet en coopération avec les spécialistes concernés. Le défi consiste alors à proposer, en lien étroit avec les entreprises, des profils de collaborateurs appropriés capables de transcender le potentiel d'innovation de ces nouvelles technologies. Dans cet article, nous illustrerons un exemple de mini-projet réalisé sur la plateforme d’enseignement et de recherche dédiée à la plastronique sur Lyon-Saint-Etienne.
BackgroundIn contrast to classical pulsed gradient diffusion‐weighted MRI, oscillating gradient diffusion‐weighted MR imaging (DWI) is sensitive to short distance diffusion changes at the intracellular level.PurposeTo compare the diagnostic performance of pulsed and oscillating DWI for characterizing hepatocellular nodules in a rat model of hepatic cirrhosis.Study TypeProspective, experimental study.Animal ModelCirrhosis was induced by weekly intraperitoneal injection of diethylnitrosamine in Wistar rats.Field Strength/SequenceEx vivo liver MRI was performed at 7T with T1‐weighted, T2‐weighted, pulsed, and oscillating gradient diffusion‐weighted sequences.AssessmentApparent diffusion coefficient from pulsed (ADCpulsed) and oscillating gradient (ADCoscillating) sequences was calculated in 82 nodules identified on the T1/T2‐weighted images and on pathological examination. Two pathologists classified the nodules in three categories: benign (regenerative and low‐grade dysplastic nodules), with intermediate malignancy (high‐grade dysplastic nodules and early hepatocellular carcinomas) and overtly malignant (progressed hepatocellular carcinomas).Statistical TestsDifferences between groups were assessed with Kruskal–Wallis and Mann–Whitney tests.ResultsADC, mainly ADCoscillating, increased in the group of nodules with intermediate malignancy (ADCpulsed: 0.75 ± 0.25 × 10‐3 mm2/s vs. 0.64 ± 0.07 × 10‐3 mm2/s in benign nodules, P = 0.025; ADCoscillating: 0.81 ± 0.20 × 10‐3 mm2/s vs. 0.65 ± 0.13 × 10‐3 mm2/s, P = 0.0008) and ADCpulsed decreased in the group of progressed hepatocellular carcinomas (ADCpulsed: 0.60 ± 0.08 × 10‐3 mm2/s, P = 0.042; ADCoscillating: 0.68 ± 0.08 × 10‐3 mm2/s, P = 0.1).Data ConclusionADC during hepatocarcinogenesis in rats increased in nodules with intermediate malignancy and decreased in progressed hepatocellular carcinomas. Our results suggest that oscillating gradient DWI is more sensitive to the early steps of hepatocarcinogenesis and might be useful for differentiating between high‐grade dysplastic nodules / early hepatocellular carcinomas and regenerating nodules / low‐grade dysplastic nodules.Level of Evidence: 2Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2020;51:1065–1074.