Preclinical MRI Scanner Research Articles

Localized Shims Enable Low-Field Simultaneous Multinuclear NMR Spectroscopy.

This Article introduces a smart localized shimset, integrated with a radiofrequency (RF) microsolenoid and optimized as a single unit to locally achieve high-resolution NMR spectroscopy, as a significant advancement toward achieving parallel NMR spectroscopy. The shimset, consisting exclusively of linear shims, demonstrates the capability to improve NMR line width from 84 to 4 Hz in a 1.05 T preclinical MRI scanner. This enhancement enables the resolution of j-couplings in the sample while requiring a total power of 545 mW. Furthermore, a novel method is presented for concurrently obtaining multinuclear NMR spectra using a single RF channel. This approach allows for the utilization of high-sensitivity NMR signals as a reference to correct field drift, facilitating signal averaging in a permanent magnet NMR scanner that is prone to significant temperature-dependent drift.

On the correction of spiral trajectories on a preclinical MRI scanner with a high-performance gradient insert.

This study aimed to examine different trajectory correction methods for spiral imaging on a preclinical scanner with high-performance gradients with respect to image quality in a phantom and in vivo. The gold standard method of measuring the trajectories in a separate experiment is compared to an isotropic delay-correction, a correction using the gradient system transfer function (GSTF), and a combination of the two. Three different spiral trajectories, with 96, 16, and three interleaves, are considered. The best image quality is consistently achieved when determining the trajectory in a separate phantom measurement. However, especially for the spiral with 96 interleaves, the other correction methods lead to almost comparable results. Remaining imperfections in the corrected gradient waveforms and trajectories are attributed to asymmetrically occurring undulations in the actual, generated gradients, suggesting that the underlying assumption of linearity is violated. In conclusion, images of sufficient quality can be acquired on preclinical small-animal scannersusing spiral k-space trajectories without the need to carry out separate trajectory measurements each time. Depending on the trajectory, a simple isotropic delay-correction or a GSTF-based correction can provide images of similar quality.

3D MR fingerprinting for dynamic contrast-enhanced imaging of whole mouse brain.

Quantitative MRI enables direct quantification of contrast agent concentrations in contrast-enhanced scans. However, the lengthy scan times required by conventional methods are inadequate for tracking contrast agent transport dynamically in mouse brain. We developed a 3D MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping across the whole mouse brain with 4.3-min temporal resolution. We designed a 3D MRF sequence with variable acquisition segment lengths and magnetization preparations on a 9.4T preclinical MRI scanner. Model-based reconstruction approaches were employed to improve the accuracy and speed of MRF acquisition. The method's accuracy for T1 and T2 measurements was validated in vitro, while its repeatability of T1 and T2 measurements was evaluated in vivo (n = 3). The utility of the 3D MRF sequence for dynamic tracking of intracisternally infused gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) in the whole mouse brain was demonstrated (n = 5). Phantom studies confirmed accurate T1 and T2 measurements by 3D MRF with an undersampling factor of up to 48. Dynamic contrast-enhancedMRF scans achieved a spatial resolution of 192 × 192 × 500 μm3 and a temporal resolution of 4.3 min, allowing for the analysis and comparison of dynamic changes in concentration and transport kinetics of intracisternally infused Gd-DTPA across brain regions. The sequence also enabled highly repeatable, high-resolution T1 and T2 mapping of the whole mouse brain (192 × 192 × 250 μm3) in 30 min. We present the first dynamic and multi-parametric approach for quantitatively tracking contrast agent transport in the mouse brain using 3D MRF.

Toward Ultra-High-Quality-Factor Wireless Masing Magnetic Resonance Sensing.

It has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1-13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio-frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22-fold (to 1,670) via parametric pumping. This active-feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated.

Toward Ultra‐High‐Quality‐Factor Wireless Masing Magnetic Resonance Sensing

AbstractIt has recently been shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to maser signals, potentially enabling new ways of sensing hyperpolarized contrast media, including most notably [1‐13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio‐frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22‐fold (to 1,670) via parametric pumping. This active‐feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in a preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of the MR detector (up to 1 million) were also demonstrated.

Sodium triple quantum MR signal extraction using a single-pulse sequence with single quantum time efficiency.

Sodium triple quantum (TQ) signal has been shown to be a valuable biomarker for cell viability. Despite its clinical potential, application of Sodium TQ signal is hindered by complex pulse sequences with long scan times. This study proposes a method to approximate the TQ signal using a single excitation pulse without phase cycling. The proposed method is based on a single excitation pulse and a comparison of the free induction decay (FID) with the integral of the FID combined with a shifting reconstruction window. The TQ signal is calculated from this FID only. As a proof of concept, the method was also combined with a multi-echo UTE imaging sequence on a 9.4 T preclinical MRI scanner for the possibility of fast TQ MRI. The extracted Sodium TQ signals of single-pulse and spin echo FIDs were in close agreement with theory and TQ measurement by traditional three-pulse sequence (TQ time proportional phase increment [TQTPPI)]. For 2%, 4%, and 6% agar samples, the absolute deviations of the maximum TQ signals between SE and theoretical (time proportional phase increment TQTPPI) TQ signals were less than 1.2% (2.4%), and relative deviations were less than 4.6% (6.8%). The impact of multi-compartment systems and noise on the accuracy of the TQ signal was small for simulated data. The systematic error was <3.4% for a single quantum (SQ) SNR of 5 and at maximum <2.5% for a multi-compartment system. The method also showed the potential of fast in vivo SQ and TQ imaging. Simultaneous SQ and TQ MRI using only a single-pulse sequence and SQ time efficiency has been demonstrated. This may leverage the full potential of the Sodium TQ signal in clinical applications.

Quantitative 1H Magnetic Resonance Imaging on Normal and Pathologic Rat Bones by Solid-State 1H ZTE Sequence with Water and Fat Suppression.

Osteoporosis (OP) and osteomalacia (OM) are metabolic bone diseases characterized by mineral and matrix density changes. Quantitative bone matrix density differentiates OM from OP. MRI is a noninvasive and nonionizing imaging technique that can measure bone matrix density quantitatively in ex vivo and in vivo. To demonstrate water + fat suppressed 1H MRI to compute bone matrix density in ex vivo rat femurs in the preclinical model. Prospective. Fifteen skeletally mature female Sprague-Dawley rats, five per group (normal, ovariectomized (OVX), partially nephrectomized/vitamin D (Vit-D) deficient), 250-275 g, ∼15 weeks old. 7T, zero echo time sequence with water + fat (VAPOR) suppression capability, μCT imaging, and gravimetric measurements. Cortical and trabecular bone segments from normal and disease models were scanned in the same coil along with a dual calibration phantom for quantitative assessment of bone matrix density. ANOVA and linear regression were used for data analysis, with P-values <0.05 statistically significant. The MRI-derived three-density PEG pellet densities have a strong linear relationship with physical density measures (r2 = 0.99). The Vit-D group had the lowest bone matrix density for cortical bone (0.47 ± 0.16 g cm-3), whereas the OVX had the lowest bone matrix density for trabecular bone (0.26 ± 0.04 g cm-3). Gravimetry results confirmed these MRI-based observations for Vit-D cortical (0.51 ± 0.07 g cm-3) and OVX trabecular (0.26 ± 0.03 g cm-3) bone groups. Rat femur images were obtained using a modified pulse sequence and a custom-designed double-tuned (1H/31P) transmit-receive solenoid-coil on a 7T preclinical MRI scanner. Phantom experiments confirmed a strong linear relation between MRI-derived and physical density measures and quantitative bone matrix densities in rat femurs from normal, OVX, and Vit-D deficient/partially nephrectomized animals were computed. 2 TECHNICAL EFFICACY: Stage 2.

Blood-pool MRI assessment of myocardial microvascular reactivity.

The ability to non-invasively image myocardial microvascular dilation and constriction is essential to assessing intact function and dysfunction. Yet, conventional measurements based on blood oxygenation are not specific to changes in blood volume. The purpose of this study was to extend to the heart a blood-pool MRI approach for assessing vasomodulation in the presence of blood gas changes and investigate if sex-related differences exist. Animals [five male and five female healthy Sprague Dawley rats (200-500 g)] were intubated, ventilated, and cycled through room air (normoxia) and hypercapnia (10% CO2) in 10-minute cycles after i.v. injection of blood-pool agent Ablavar (0.3 mmol/kg). Pre-contrast T1 maps and T1-weighted 3D CINE were acquired on a 3 Tesla preclinical MRI scanner, followed by repeated 3D CINE every 5 min until the end of the gas regime. Invasive laser Doppler flowmetry of myocardial perfusion was performed to corroborate MRI results. Myocardial microvascular dilation to hypercapnia and constriction to normoxia were readily visualized on T1 maps. Over 10 min of hypercapnia, female myocardial T1 reduced by 20% (vasodilation), while no significant change was observed in the male myocardium. After return to normoxia, myocardial T1 increased (vasoconstriction) in both sexes (18% in females and 16% in males). Laser Doppler perfusion measurements confirmed vasomodulatory responses observed on MRI. Blood-pool MRI is sensitive and specific to vasomodulation in the myocardial microcirculation. Sex-related differences exist in the healthy myocardium in response to mild hypercapnic stimuli.

Repeatability and reproducibility of apparent exchange rate measurements in yeast cell phantoms using filter-exchange imaging

ObjectivesDevelopment of a protocol for validation and quality assurance of filter-exchange imaging (FEXI) pulse sequences with well-defined and reproducible phantoms.Materials and methodsA FEXI pulse sequence was implemented on a 7 T preclinical MRI scanner. Six experiments in three different test categories were established for sequence validation, demonstration of the reproducibility of phantoms and the measurement of induced changes in the apparent exchange rate (AXR). First, an ice–water phantom was used to investigate the consistency of apparent diffusion coefficient (ADC) measurements with different diffusion filters. Second, yeast cell phantoms were utilized to validate the determination of the AXR in terms of repeatability (same phantom and session), reproducibility (separate but comparable phantoms in different sessions) and directionality of diffusion encodings. Third, the yeast cell phantoms were, furthermore, used to assess potential AXR bias because of altered cell density and temperature. In addition, a treatment experiment with aquaporin inhibitors was performed to evaluate the influence of these compounds on the cell membrane permeability in yeast cells.ResultsFEXI-based ADC measurements of an ice–water phantom were performed for three different filter strengths, showed good agreement with the literature value of 1.099 × 10–3 mm2/s and had a maximum coefficient of variation (CV) of 0.55% within the individual filter strengths. AXR estimation in a single yeast cell phantom and imaging session with five repetitions resulted in an overall mean value of (1.49 ± 0.05) s−1 and a CV of 3.4% between the chosen regions of interest. For three separately prepared phantoms, AXR measurements resulted in a mean value of (1.50 ± 0.04) s−1 and a CV of 2.7% across the three phantoms, demonstrating high reproducibility. Across three orthogonal diffusion directions, a mean value of (1.57 ± 0.03) s−1 with a CV of 1.9% was detected, consistent with isotropy of AXR in yeast cells. Temperature and AXR were linearly correlated (R2 = 0.99) and an activation energy EA of 37.7 kJ/mol was determined by Arrhenius plot. Furthermore, a negative correlation was found between cell density (as determined by the reference ADC/fe) and AXR (R2 = 0.95). The treatment experiment resulted in significantly decreased AXR values at different temperatures in the treated sample compared to the untreated control indicating an inhibiting effect.ConclusionsUsing ice–water and yeast cell-based phantoms, a protocol for the validation of FEXI pulse sequences was established for the assessment of stability, repeatability, reproducibility and directionality. In addition, a strong dependence of AXR on cell density and temperature was shown. As AXR is an emerging novel imaging biomarker, the suggested protocol will be useful for quality assurance of AXR measurements within a study and potentially across multiple sites.

Development of cardiac phantom which mimics the heart function using a 4.7t preclinical MRI system for cardiac imaging

Cardiac MRI was one of the first MRI applications in the 1980s, which helps in the human study of different cardiovascular diseases. MRI is a noninvasive imaging technique that can be used for diagnosis and has advantages over other imaging techniques since it does not rely on radiation like X-rays, PET, and SPECT. Modern clinical methods do not require much scanning time, it revels good contrast between tissues and can compensate for patient movement during the scan. The scanner used is a 300mm internal diameter superconducting magnet (Magnex Uk) 4.7T preclinical MRI system, in the Biomedical Physics building at the University of Aberdeen. The cardiac phantom is made of a balloon filled with water, connected via a nylon T-piece to two 5 m lengths of rigid pvc tubing of 3 mm internal diameter to a 12 V water pump and solenoid valve located outside the 4.7 T MRI system’s 5 Gauss stray field contour. The balloon part of the phantom was fixed on the 4.7 T MRI system’s animal bed, directly over a 30mm diameter surface coil normally used to image the rat heart. The flow system was primed with water to mimic blood and the bed was loaded into the MRI magnet for imaging. The cardiac phantom has successfully been developed using a small balloon to represent a heart chamber and imaged in a 4.7T preclinical MRI scanner. Images acquired with gradient echo pulse sequence with shorter TE of 5 ms and using surface coil displayed improved image contrast and have useful signal-to-noise ratio as compared to images acquired with birdcage coil which show ghosting artifact.

Abstract 2470: Comparison of H-scan ultrasound and diffusion-weighted magnetic resonance imaging of head and neck cancer undergoing neoadjuvant chemotherapy

Abstract Introduction: The use of ultrasound (US) for tumor tissue characterization remains an exciting prospect. The purpose of this research project was to introduce a 3-dimensional (3-D) H-scan US imaging system, which links information in the backscattered US signals to various-sized tissue structures in volume space, and evaluate use for monitoring early response of head and neck cancer to neoadjuvant chemotherapy. Methods: Studies were conducted using female mice (N = 20) implanted in the mammary fat pad with 1 million breast cancer cells (MDA-MB-231). Once tumors reached about 0.8 cm in size, animals were divided into three groups so that mean tumor size in each were comparable. Animals underwent H-scan US and diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and again at days 1, 3, and 7. After baseline imaging, animals were administered neoadjuvant treatment injections, namely: (1) 0.3 mg sterile saline (control), (2) 5 mg/kg of cisplatin, or (3) 25 mg/kg cisplatin. In vivo US imaging was performed using a Vevo 3100 system (FUJIFILM VisualSonics Inc) equipped with an MX201 linear array transducer. Volume acquisitions contained 400 frames of US image data spaced 50 μm apart. To generate the H-scan US images, Gaussian-weighted Hermite polynomial filters were convolved with the radiofrequency (RF) data to measure the relative strength of the backscattered US signals. In short, the lower frequency signals were assigned to a red (R) channel and the higher frequency components to a blue (B) channel. The unfiltered original RF signal was assigned to the green (G) channel to complete the RGB colormap. Animals were also imaged using a preclinical MRI scanner (BioSpec 3T, Bruker) using a DW-MRI sequence for generation of apparent diffusion coefficient (ADC) maps as a measure of intratumoral water diffusion. After the last day of imaging, animals were euthanized and tumor tissue excised for ex vivo analysis. Results: In vivo results demonstrated that 3-D H-scan US imaging was considerably more sensitive to tumor changes after neoadjuvant treatment as compared to B-scan US. While there was no difference at baseline (p &amp;gt; 0.60), H-scan US images from the cisplatin treated tumors exhibited increased intensity at day 7 (15.6 ± 1.9% and 17.2 ± 3.2% for low and high dosed groups, respectively; p &amp;lt; 0.05) indicating a decrease in aggregate US scatterer size. Furthermore, longitudinal trends found using H-scan US imaging matched those from DW-MRI (p &amp;lt; 0.05). Collectively, these observations were attributed to cancer cell nuclear condensation and apoptotic activity as confirmed by histological analysis. Conclusions: 3-D H-scan US imaging is a promising new tool for monitoring cancer response to neoadjuvant therapy. In vivo results matched those found using DW-MRI, which is an established modality for assessing anticancer treatment using apoptosis-inducing drugs. Citation Format: Haowei Tai, Ryan Margolis, Junjie Li, Brian Trinh, Jane Song, Kenneth Hoyt. Comparison of H-scan ultrasound and diffusion-weighted magnetic resonance imaging of head and neck cancer undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2470.

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN-Neuroimaging Network.

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures.

Hybrid polyphenolic Network/SPIONs aggregates with potential synergistic effects in MRI applications

the development of novel and more efficient contrast agents for diagnostic applications is necessary to lower the dosage of such substances that might accumulate in patients with toxic effects and to define new agents which effect could go beyond the simplified scheme of T1 or T2 relaxation properties. Within this context, novel directions for MRI contrast agents based on magnetic nanoparticles entrapped inside a polyphenolic network to gain water dispersibility, were explored. Investigation about the possible realization of dual-mode contrast agents chelating Gd3+ ions on the nanoparticles coating, with tunable T1 and T2 relaxivity, has been performed. Two synthetic routes were explored, based on covalently bound Tannic Acid (TA) covering magnetic nanoparticles, or PEGylated TA entangling the magnetic systems. Hybrid aggregates having optimal stability in aqueous medium, were characterized through FT-IR, DLS, ICP-MS, XPS, TGA and STEM, confirming the formation of a stable coating around the magnetic nanoparticles, able to carry Gd species. Afterwards, their longitudinal (r1) and transverse (r2) relaxivity values were measured with a 1 T preclinical MRI scanner, as preliminary test for further MRI application. This contribute represents the first step for the preparation of tunable dual-mode contrast agents, with modifiable positive-to-negative contrast according to specific diagnostic needs, aiming to a more patient-tailorable medicinal diagnosis.

BIMG-21. DEUTERIUM METABOLIC IMAGING (DMI), A NEW, MRI-BASED TECHNIQUE FOR MAPPING BRAIN TUMOR METABOLISM IN VIVO

Deuterium Metabolic Imaging (DMI) combines 3D deuterium (2H) magnetic resonance spectroscopic imaging (MRSI) with administration of a 2H-labeled substrate to map uptake and metabolism of the substrate. DMI has been implemented on a 4 Tesla clinical research MRI scanner, and on an 11.7 Tesla preclinical MRI scanner, and has been used with 2H-labeled glucose, acetate and choline. DMI data are presented as color maps of concentration of the 2H-labeled substrate and its metabolites, overlaid on anatomical MR images. In rat and mouse models of glioblastoma, DMI data acquired at 5 to 8 uL resolution following intravenous 2H-glucose infusion clearly showed the Warburg effect in the tumor lesions. The Warburg effect is indicated by the ratio of 2H-labeled lactate/glutamate+glutamine (Glx). High levels of 2H-labeled lactate and low levels of 2H-labeled Glx are the result of a high rate of glycolysis and low rate of oxidative glucose metabolism. Because DMI detects both glucose and its downstream metabolism, the technique does not suffer from low image contrast with normal brain, as is the case with FDG-PET that detects glucose uptake only. For clinical research studies patients orally consumed 0.75g/kg of 2H-glucose dissolved in water. The observations made in the animal models were confirmed in several patients with recurrent GBM, showing hotspots in the lac/Glx maps (8 mL resolution), coinciding with the area of the tumor lesion. In patients with meningioma, no Warburg effect was detected using DMI. Furthermore, DMI data acquired in a patient with GBM one week after finishing 30 days of radiation therapy, also showed no high levels of 2H-labeled lactate in the lesion. These data indicate that the presence of the Warburg effect could correlate with tumor grade and/or aggressiveness, and that DMI of glucose metabolism could potentially be a biomarker of therapy effect.

Longitudinal study of sub-regional cerebral viscoelastic properties of 5XFAD Alzheimer's disease mice using multifrequency MR elastography.

To study sub-regional, longitudinal changes occurring inside brains of 5XFAD mice, an Alzheimer's disease (AD) model, based on viscoelastic parameters derived using MR elastography and their spatial variation. Female 5XFAD and non-transgenic B6SJLF1/J mice as controls (n = 9 for both groups) were used for the study. Scans were performed inside a 9.4T preclinical MRI scanner using SampLe Interval Modulation-magnetic resonance elastography (SLIM-MRE). Experiments were performed at ages 2, 4, and 6 mo, and by using three actuation frequencies: 900, 1000, and 1100 Hz. Multifrequency dual elasto-visco (MDEV) reconstruction was used to combine 3D multifrequency MRE data and calculate magnitude , and phase angle φ, of the complex shear modulus . Mean values were measured for the overall brain and sub-regions associated with the early onset of AD, to check for the effect of aging and mouse model. Spatial coefficient of variation (CV) of both parameters across different age-groups were analyzed. and φ values reduced with age for overall brain in 5XFAD mice with significant difference in mean between 5XFAD and control mice at 6 mo (P = .029). Analyzing values from the hippocampal region highlighted drop in mean and φ values. The CV of inside hippocampus enabled differentiation at 4 mo with it being significantly lower in 5XFAD mice (P = .0007). Multifrequency 3D MRE revealed longitudinal viscoelastic changes in 5XFAD mice and the CV of in brain sub-regions may qualify as biomarker for early diagnosis of AD.

Optimizing diffusion MRI acquisition efficiency of rodent brain using simultaneous multislice EPI.

Diffusion tensor imaging (DTI) of the brain provides essential information on the white matter integrity and structural connectivity. However, it suffers from a low signal-to-noise ratio (SNR) and requires a long scan time to achieve high spatial and/or diffusion resolution and wide brain coverage. With recent advances in parallel and simultaneous multislice (multiband) imaging, the SNR efficiency has been improved by reducing the repetition time (TR ). However, due to the limited number of RF coil channels available on preclinical MRI scanners, simultaneous multislice acquisition has not been practical. In this study, we demonstrate the ability of multiband DTI to acquire high-resolution data of the mouse brain with 84 slices covering the whole brain in 0.2 mm isotropic resolution without a coil array at 9.4 T. Hadamard-encoding four-band pulses were used to acquire four slices simultaneously, with the reduction in the TR maximizing the SNR efficiency. To overcome shot-to-shot phase variations, Hadamard decoding with a self-calibrated phase was developed. Compared with single-band DTI acquired with the same scan time, the multiband DTI leads to significantly increased SNR by 40% in the white matter. This SNR gain resulted in reduced variations in fractional anisotropy, mean diffusivity, and eigenvector orientation. Furthermore, the cerebrospinal fluid signal was attenuated, leading to reduced free-water contamination. Without the need for a high-density coil array or parallel imaging, this technique enables highly efficient preclinical DTI that will facilitate connectome studies.

Magnetic resonance imaging of mean cell size in human breast tumors.

Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell-cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging. There is a need to develop cell-size imaging for clinical applications. We propose a clinically feasible IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) approach that can characterize mean cell sizes in solid tumors. We report the use of a combination of pulse sequences, using different gradient waveforms implemented on clinical MRI scanners and analytical equations based on these waveforms to analyze diffusion-weighted MRI signals and derive specific microstructural parameters such as cell size. We also describe comprehensive validations of this approach using computer simulations, cell experiments in vitro, and animal experiments in vivo and demonstrate applications in preoperative breast cancer patients. With fast acquisitions (~7 minutes), IMPULSED can provide high-resolution (1.3 mm in-plane) mapping of mean cell size of human tumors in vivo on clinical 3T MRI scanners. All validations suggest that IMPULSED provides accurate and reliable measurements of mean cell size. The proposed IMPULSED method can assess cell-size variations in tumors of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

Ultra-high resolution and multi-shell diffusion MRI of intact ex vivo human brains using kT-dSTEAM at 9.4T

Diffusion MRI (dMRI) in ex vivo human brain specimens is an important research tool for neuroanatomical investigations and the validation of dMRI techniques. Many ex vivo dMRI applications have benefited from very high dMRI resolutions achievable on small-bore preclinical or animal MRI scanners for small tissue samples. However, the investigation of entire human brains post mortem provides the important context of entire white matter (WM) network systems and entire gray matter (GM) areas connected through these systems. The investigation of intact ex vivo human brains in large bore systems creates challenges due to the limited gradient performance and transmit radio-frequency (B1+) inhomogeneities, specially at ultra-high field (UHF, 7T and higher). To overcome these issues, it is necessary to tailor ex vivo diffusion-weighted sequences specifically for high resolution and high diffusion-weighting. Here, we present kT-dSTEAM, which achieves B1+ homogenization across whole human brain specimens using parallel transmit (pTx) on a 9.4T MR system. We use kT-dSTEAM to obtain multi-shell high b-value and high resolution diffusion-weighted data in ex vivo whole human brains. Isotropic whole brain data can be acquired at high b-value (6000–8000 s/mm2) at high resolution (1000 μm) and at moderate b-value (3000 s/mm2) at ultra-high isotropic resolution (400 μm). As an illustration of the advantages of the ultra-high resolution, tractography across the WM/GM border shows less of the unwanted gyral crown bias, and more high-curvature paths connecting the sulcal wall than at lower resolution. The kT-dSTEAM also allows for acquisition of T1 and T2 weighted images suitable for estimating quantitative T1 and T2 maps. Finally, multi-shell analysis of kT-dSTEAM data at variable mixing time (TM) is shown as an approach for ex vivo data analysis which is adapted to the strengths of STEAM diffusion-weighting. Here, we use this gain for multi-orientation modelling and crossing-fiber tractography. We show that multi-shell data allows superior multiple orientation tractography of known crossing fiber structures in the brain stem.

Gadolinium labeled polyelectrolyte nanocarriers for theranostic application

Here, we designed a novel Gadolinium (Gd) labeled drug-loaded polyelectrolyte nanocarriers for theranostics. The nanocarriers were formed via layer-by-layer technique with biodegradable polyelectrolytes: PLL (Poly-L-lysine), PLL-Gd (Gadolinium-labeled Poly-L-lysine) and PGA (Poly-L-glutamic acid). Anticancer drug (Paclitaxel) was encapsulated in the formed nanocarriers. The average size of synthesized nanocarriers was around 150 nm. The empty gadolinium labeled nanocarriers did not show any deleterious effects on tested cells (CT26-CEA, B16F10, 4T1 and PBMC), whereas encapsulated paclitaxel retained its cytotoxic/cytostatic activity. Using T2 and T1 NMR relaxation measurements with 9.4 T preclinical MRI scanner, we demonstrated that gadolinium labeled nanocarriers can be detected due to a locally altered contrast in the MR image. Thus, they may become a promising platform for future theranostic applications.

Persistent Quantitative Vitality of Stem Cell Graft Is Necessary for Stabilization of Functional Brain Networks After Stroke.

Stem cell treatment after stroke has demonstrated substantial outcome improvement. However, monitoring of stem cell fate in vivo is still challenging and not routinely performed, yet important to quantify the role of the implanted stem cells on lesion improvement; in several studies even mortality of the graft has been reported. Resting state functional magnetic resonance imaging (rs-fMRI) is a highly sensitive imaging modality to monitor the brain-wide functional network alterations of many brain diseases in vivo. We monitor for 3 months the functional connectivity changes after intracortical stem cell engraftment in large, cortico-striatal (n = 9), and in small, striatal (n = 6) ischemic lesions in the mouse brain with non-invasive rs-fMRI on a 9.4T preclinical MRi scanner with GE-EPI sequence. Graft vitality is continuously recorded by bioluminescence imaging (BLI) roughly every 2 weeks after implantation of 300 k neural stem cells. In cortico-striatal lesions, the lesion extension induces graft vitality loss, in consequence leading to a parallel decrease of functional connectivity strength after a few weeks. In small, striatal lesions, the graft vitality is preserved for the whole observation period and the functional connectivity is stabilized at values as in the pre-stroke situation. But even here, at the end of the observation period of 3 months, the functional connectivity strength is found to decrease despite preserved graft vitality. We conclude that quantitative graft viability is a necessary but not sufficient criterion for functional neuronal network stabilization after stroke. Future studies with even longer time periods after stroke induction will need to identify additional players which have negative influence on the functional brain networks.