Preclinical Scanner Research Articles

A Comparison of the Sensitivity of Contrast-Specific Imaging Modes on Clinical and Preclinical Ultrasound Scanners.

Ultrasonic contrast agents are used routinely to aid clinical diagnosis. All premium- and mid-range scanners utilise contrast-specific imaging techniques to preferentially isolate and display the nonlinear signals generated from the microbubbles when insonated with a series of ultrasound pulses. In this manuscript the abilities of four premium ultrasound scanners to detect and display the ultrasound signal from two commercially available contrast agents—SonoVue and DEFINITY®—are compared. A flow phantom was built using tubes with internal diameters of 1.6 mm and 3.2 mm, suspended at depths of 1, 5 and 8 cm and embedded in tissue-mimicking material. Dilute solutions of SonoVue and DEFINITY® were pumped through the phantom at 0.25 mL/s and 1.5 mL/s. Four transducers were used to scan the tubes—a GE Logiq E9 (C2-9) curvilinear probe, a Philips iU22 L9-3 linear array probe, an Esaote MyLab Twice linear array LA523 (4–13 MHz) and a Fujifilm VisualSonics Vevo3100 MX250 (15–30 MHz) linear array probe. We defined a new parameter to compare the ability of the ultrasound scanners to display the contrast enhancement. This was defined as the ratio of grey-scale intensity ratio in contrast-specific imaging mode relative to the B-mode intensity from the same region-of-interest within the corresponding B-mode image. The study demonstrated that the flow rates used in this study had no effect on the contrast-specific imaging mode to B-mode (CSIM-BM) ratio for the three clinical scanners studied, with SonoVue demonstrating broadly similar CSIM-BM ratios across all 3 clinical scanners. DEFINITY® also displayed similar results to SonoVue except when insonated with the Esaote MyLab Twice LA523 transducer, where it demonstrated significantly higher CSIM-BM ratios at superficial depths.

RF shielding designs for birdcage coils for preclinical MRI at 9.4 T

Birdcage coils are widely used in preclinical MRI as they perform well, allow for quadrature drive, and can provide a homogeneous transmit field. Unlike in larger bore scanners, an RF shield is essential to avoid strong cross-talk with gradient coils that are in close proximity. However, gradient switching induces eddy currents that heat the shield and coil and impair the temporal signal-to-noise ratio (tSNR). The motivation of this study is to investigate the performance of different designs of RF shields on a birdcage coil used for high resolution functional MRI of small primates at 9.4 T. We found the choice of materials for RF shields significantly affected ghosting and tSNR in fMRI scans. Both ultrathin foils and a slotted pattern reduce eddy currents and improve imaging quality. Our results also demonstrate that a 9-um-thick copper foil is sufficiently thin to reduce the eddy current effects for high-resolution fMRI scans and there is no need for high-cost 4-um-thick foil. For slotted shields, our results demonstrate that the number of slots should be carefully considered, and an excessive number of slots can lead to a lower SNR and tSNR. We believe the results from this study can be used as a reference to design future RF coil shields selection for preclinical scanners.

Deep learning facilitates fully automated brain image registration of optoacoustic tomography and magnetic resonance imaging.

Multispectral optoacoustic tomography (MSOT) is an emerging optical imaging method providing multiplex molecular and functional information from the rodent brain. It can be greatly augmented by magnetic resonance imaging (MRI) which offers excellent soft-tissue contrast and high-resolution brain anatomy. Nevertheless, registration of MSOT-MRI images remains challenging, chiefly due to the entirely different image contrast rendered by these two modalities. Previously reported registration algorithms mostly relied on manual user-dependent brain segmentation, which compromised data interpretation and quantification. Here we propose a fully automated registration method for MSOT-MRI multimodal imaging empowered by deep learning. The automated workflow includes neural network-based image segmentation to generate suitable masks, which are subsequently registered using an additional neural network. The performance of the algorithm is showcased with datasets acquired by cross-sectional MSOT and high-field MRI preclinical scanners. The automated registration method is further validated with manual and half-automated registration, demonstrating its robustness and accuracy.

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 > 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 < 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 < 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.

Correcting for imaging gradients-related bias of T2 relaxation times at high-resolution MRI.

PurposeHigh‐resolution animal imaging is an integral part of preclinical drug development and the investigation of diseases' pathophysiology. Quantitative mapping of T2 relaxation times (qT2) is a valuable tool for both preclinical and research applications, providing high sensitivity to subtle tissue pathologies. High‐resolution T2 mapping, however, suffers from severe underestimation of T2 values due to molecular diffusion. This affects both single‐echo and multi‐echo spin echo (SSE and MESE), on top of the well‐known contamination of MESE signals by stimulated echoes, and especially on high‐field and preclinical scanners in which high imaging gradients are used in comparison to clinical scanners.MethodsDiffusion bias due to imaging gradients was analyzed by quantifying the effective b‐value for each coherence pathway in SSE and MESE protocols, and incorporating this information in a joint T2‐diffusion reconstruction algorithm. Validation was done on phantoms and in vivo mouse brain using a 9.4T and a 7T MRI scanner.ResultsUnderestimation of T2 values due to strong imaging gradients can reach up to 70%, depending on scan parameters and on the sample's diffusion coefficient. The algorithm presented here produced T2 values that agreed with reference spectroscopic measurements, were reproducible across scan settings, and reduced the average bias of T2 values from −33.5 ± 20.5% to −0.1 ± 3.6%.ConclusionsA new joint T2‐diffusion reconstruction algorithm is able to negate imaging gradient–related underestimation of T2 values, leading to reliable mapping of T2 values at high resolutions.

A supervised deep neural network approach with standardized targets for enhanced accuracy of IVIM parameter estimation from multi-SNR images.

Extraction of intravoxel incoherent motion (IVIM) parameters from noisy diffusion‐weighted (DW) images using a biexponential fitting model is computationally challenging, and the reliability of the estimated perfusion‐related quantities represents a limitation of this technique. Artificial intelligence can overcome the current limitations and be a suitable solution to advance use of this technique in both preclinical and clinical settings. The purpose of this work was to develop a deep neural network (DNN) approach, trained on numerical simulated phantoms with different signal to noise ratios (SNRs), to improve IVIM parameter estimation. The proposed approach is based on a supervised fully connected DNN having 3 hidden layers, 18 inputs and 3 targets with standardized values. 14 × 103 simulated DW images, based on a Shepp–Logan phantom, were randomly generated with varying SNRs (ranging from 10 to 100). 7 × 103 images (1000 for each SNR) were used for training. Performance accuracy was assessed in simulated images and the proposed approach was compared with the state‐of‐the‐art Bayesian approach and other DNN algorithms. The DNN approach was also evaluated in vivo on a high‐field MRI preclinical scanner. Our DNN approach showed an overall improvement in accuracy when compared with the Bayesian approach and other DNN methods in most of the simulated conditions. The in vivo results demonstrated the feasibility of the proposed approach in real settings and generated quantitative results comparable to those obtained using the Bayesian and unsupervised approaches, especially for D and f, and with lower variability in homogeneous regions. The DNN architecture proposed in this work outlines two innovative features as compared with other studies: (1) the use of standardized targets to improve the estimation of parameters, and (2) the implementation of a single DNN to enhance the IVIM fitting at different SNRs, providing a valuable alternative tool to compute IVIM parameters in conditions of high background noise.

X-Ray Dark-field radiography: Does this carry potential for diagnosing gout in exotic pets?

The aim of this study is to evaluate whether X-ray dark-field (DF) radiography is useful for the diagnosis of gout in birds and reptiles and whether this preclinical model could be helpful to establish this non-invasive imaging method in human medicine. A total of 18 limbs originating from 11 birds (7 different species) and 7 reptiles (4 different species) with and without suspected joint gout were measured using a grating-based X-ray dark-field setup and conventional X-ray examination, respectively. Each image acquisition generated a dark-field and a conventional absorption x-ray image. The results of the individual scans were compared with the results of a pathological examination and arthrocentesis. In 5 of the birds and 4 of the reptiles examined, gout was detected by pathologic examination. In each group, uric acid crystals were found in the joints of 3 animals by means of arthrocentesis. The uric acid crystals were detectable in 2 bird and 2 reptile limbs in the dark-field image. The study demonstrated that the urate crystals evoke a clearly visible dark field signal, whereas this was not the case in the conventional radiographs. The results obtained show that uric acid crystal detection using less invasive imaging methods in an animal model with birds and reptiles may expand gout diagnostics not only in veterinary medicine but also in human medicine and possibly replace arthrocentesis if a DF signal is detectable. Preclinical scanners which use X-ray dark-field and phase-contrast radiography already exist for hands and mammography.

The Imaging Performance of Preclinical Ultrasound Scanners Using the Edinburgh Pipe Phantom

The greyscale imaging performance of a total of 17 preclinical transducer/scanner combinations were measured over a period of 10 years. These comprised nine single element transducers and eight array transducers with nominal central frequencies ranging between 15 and 55 MHz, and were from four commercially-available preclinical ultrasound scanners. Performance was assessed using a single figure of merit, the resolution integral, using measurements acquired from images of a test-object, the Edinburgh Pipe Phantom. Two further parameters were derived from the resolution integral: characteristic resolution and depth-of-field. Our results demonstrate that 1) resolution integral values of the array transducers were greater than single-element transducers, and 2) the array transducers demonstrated greater depths of field than the single-element transducers of the same nominal frequency. Moreover we demonstrate that use of this single figure-of-merit enabled identification and quantification of changes in imaging performance of preclinical transducers over a 10-years period.

Bimodal Interventional Instrument Markers for Magnetic Particle Imaging and Magnetic Resonance Imaging-A Proof-of-Concept Study.

The purpose of this work was to develop instrument markers that are visible in both magnetic particle imaging (MPI) and magnetic resonance imaging (MRI). The instrument markers were based on two different magnetic nanoparticle types (synthesized in-house KLB and commercial Bayoxide E8706). Coatings containing one of both particle types were fabricated and measured with a magnetic particle spectrometer (MPS) to estimate their MPI performance. Coatings based on both particle types were then applied on a segment of a nonmetallic guidewire. Imaging experiments were conducted using a commercial, preclinical MPI scanner and a preclinical 1 tesla MRI system. MPI image reconstruction was performed based on system matrices measured with dried KLB and Bayoxide E8706 coatings. The bimodal markers were clearly visible in both methods. They caused circular signal voids in MRI and areas of high signal intensity in MPI. Both the signal voids as well as the areas of high signal intensity were larger than the real marker size. Images that were reconstructed with a Bayoxide E8706 system matrix did not show sufficient MPI signal. Instrument markers with bimodal visibility are essential for the perspective of monitoring cardiovascular interventions with MPI/MRI hybrid systems.

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.

Stay on the Beat With Tensor-Valued Encoding: Time-Dependent Diffusion and Cell Size Estimation in ex vivo Heart

Diffusion encoding with free gradient waveforms can provide increased microstructural specificity in heterogeneous tissues compared to conventional encoding approaches. This is achieved by considering specific aspects of encoding, such as b-tensor shape, sensitivity to bulk motion and to time-dependent diffusion (TDD). In tensor-valued encoding, different b-tensor shapes are used, such as in linear tensor encoding (LTE) or spherical tensor encoding (STE). STE can be employed for estimation of mean diffusivity (MD) or in combination with LTE to probe average microscopic anisotropy unconfounded by orientation dispersion. While tensor-valued encoding has been successfully applied in the brain and other organs, its potential and limitations have not yet been fully explored in cardiac applications. To avoid artefacts due to motion, which are particularly challenging in cardiac imaging, arbitrary b-tensors can be designed with motion compensation, i.e. gradient moment nulling, while also nulling the adverse effects of concomitant gradients. Encoding waveforms with varying degrees of motion compensation may however have significantly different sensitivities to TDD. This effect can be prominent in tissues with relatively large cell sizes such as in the heart and can be used advantageously to provide further tissue information. To account for TDD in tensor-valued encoding, the interplay between asynchronous gradients simultaneously applied along different directions needs to be considered. As the first step toward in vivo cardiac applications, our overarching goal was to explore the feasibility of acceleration compensated tensor-valued encoding on preclinical and clinical scanners ex vivo. We have demonstrated strong and predictable variation of MD due to TDD in mouse and pig hearts using a wide range of LTE and STE with progressively increasing degrees of motion compensation. Our preliminary data from acceleration compensated STE and LTE at high b-values, attainable on the preclinical scanner, indicate that TDD needs to be considered in experiments with varying b-tensor shapes. We have presented a novel theoretical framework, which enables cell size estimation, helps to elucidate limitations and provides a basis for further optimizations of experiments probing both mean diffusivity and microscopic anisotropy in the heart.

A snapshot of the vast array of diamagnetic CEST MRI contrast agents.

Since the inception of CEST MRI in the 1990s, a number of compounds have been identified as suitable for generating contrast, including paramagnetic lanthanide complexes, hyperpolarized atom cages and, most interesting, diamagnetic compounds. In the past two decades, there has been a major emphasis in this field on the identification and application of diamagnetic compounds that have suitable biosafety profiles for usage in medical applications. Even in the past five years there has been a tremendous growth in their numbers, with more and more emphasis being placed on finding those that can be ultimately used for patient studies on clinical 3 T scanners. At this point, a number of endogenous compounds present in tissue have been identified, and also natural and synthetic organic compounds that can be administered to highlight pathology via CEST imaging. Here we will provide a very extensive snapshot of the types of diamagnetic compound that can generate CEST MRI contrast, together with guidance on their utility on typical preclinical and clinical scanners and a review of the applications that might benefit the most from this new technology.

Three-dimensional high-resolution T1 and T2 mapping of whole macaque brain at 9.4 T using magnetic resonance fingerprinting.

Quantitative T1 and T2 mapping in non-human primates with whole-brain coverage is challenged by the requirement of sub-millimeter resolution and the inhomogeneity of the transmit magnetic field (B1+ ) covering a large field of view. The goal of the current study is to develop a magnetic resonance fingerprinting (MRF) method for simultaneous T1 and T2 mapping of the entire macaque brain within feasible scan time. A three-dimensional (3D) MRF sequence with both inversion- and T2 -preparation modules was developed and evaluated on a 9.4 T preclinical scanner. Data acquisition used a 3D stack-of-spirals trajectory, with undersampling along both the in-plane and the through-plane directions. The effect of B1+ inhomogeneity was accounted for by matching the acquired fingerprint to a dictionary simulated with the B1+ factors measured from a separate scan. In vitro and ex vivo studies were performed to evaluate the accuracy and the undersampling capacity of the MRF method. The application of the MRF method for in vivo, brain-wide T1 and T2 mapping was demonstrated on macaques at 4, 6, and 12years of age. The MRF method enabled highly repeatable T1 and T2 mapping at high spatial resolution (0.35 × 0.35 × 1 mm3 ) with an acceleration factor of 24. In vivo studies showed significant age-related T2 reduction in deep gray nuclei including the globus pallidus, the putamen, and the caudate nucleus. This study demonstrates the first MRF study for brain-wide, multi-parametric quantification in non-human primates with sub-millimeter resolution.

Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals.

Background Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing 99mTc-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as [(maximum count − minimum count)/(maximum count + minimum count) × 100], with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [99mTc]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.

Feasibility of Non-invasive Measurement of Tumour NAD(H) by In Vivo Phosphorus-31 Magnetic Resonance Spectroscopy.

Importance of the redox status of nicotinamide adenine dinucleotide (NAD), including its oxidized (NAD+) and reduced (NADH) forms, has been shown in many biological processes. However, NAD(H) redox status assessment is traditionally limited to biochemical assays in vitro or optical redox imaging (ORI) for superficial tissues in vivo and for deep tissues ex vivo. In recent years, phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was utilized to quantify NAD+, NADH, and the redox ratio NAD+/NADH in normal tissues in vivo. The quantification is based on the spectral fitting of the upfield shoulder of the αATP peak that contains signals of NAD+ (a quartet) and NADH (a singlet), assuming pH-independence of peak positions. To evaluate the feasibility of measuring tumour NAD(H) redox status in vivo, we fitted single voxel 31P-MR spectra of subcutaneous mouse xenografts of human breast cancer cell lines acquired on a 9.4-T horizontal bore preclinical MR scanner. We found larger variations in the chemical shift offsets of NAD+ and NADH from αATP in these tumours than the literature values of normal tissues. Furthermore, our 31P-MR spectra of αATP, NAD+, and NADH solution phantoms indicated that the chemical shift of αATP and thus the offsets between NAD(H) and αATP were pH dependent. Therefore, whether tumour pH should be incorporated into the spectral fitting model should be further evaluated. Additionally, spectral resolution and signal-to-noise ratio should be improved by optimising 31P-MRS protocols, increasing data acquisition time, and using a more sensitive coil for signal detection.

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.

Brain Activity after Intermittent Hypoxic Brain Condition in Rats.

Hypoxic brain injury is accompanied by a decrease in various functions. It is also known that obstructive sleep apnea (OSA) can cause hypoxic brain injury. This study aimed to produce a model of an intermittent hypoxic brain condition in rats and determine the activity of the brain according to the duration of hypoxic exposure. Forty male Sprague–Dawley rats were divided into four groups: the control group (n = 10), the 2 h per day hypoxia exposure group (n = 10), the 4 h per day hypoxia exposure group (n = 10), and the 8 h per day hypoxia exposure group (n = 10). All rats were exposed to a hypoxic chamber containing 10% oxygen for five days. Positron emission tomography–computed tomography (PET-CT) brain images were acquired using a preclinical PET-CT scanner to evaluate the activity of brain metabolism. All the rats were subjected to normal conditions. After five days, PET-CT was performed to evaluate the recovery of brain metabolism. Western blot analysis and immunohistochemistry were performed with vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The mean SUV was elevated in the 2 h per day and 4 h per day groups, and all brain regions showed increased metabolism except the amygdala on the left side, the auditory cortex on the right side, the frontal association cortex on the right side, the parietal association cortex on the right side, and the somatosensory cortex on the right side immediately after hypoxic exposure. However, there was no difference between 5 days rest after hypoxic exposure and control group. Western blot analysis revealed the most significant immunoreactivity for VEGF in the 2, 4, and 8 h per day groups compared with the control group and quantification of VEGF immunohistochemistry showed more expression in 2 and 4 h per day groups compared with the control group. However, there was no significant difference in immunoreactivity for BDNF among the groups. The duration of exposure to hypoxia may affect the activity of the brain due to angiogenesis after intermittent hypoxic brain conditions in rats.

Pulmonary Arteriovenous Pressure Gradient and Time-Averaged Mean Velocity of Small Pulmonary Arteries Can Serve as Sensitive Biomarkers in the Diagnosis of Pulmonary Arterial Hypertension: A Preclinical Study by 4D-Flow MRI.

(1) Background: Pulmonary arterial hypertension (PAH) is a serious condition that is associated with many cardiopulmonary diseases. Invasive right heart catheterization (RHC) is currently the only method for the definitive diagnosis and follow-up of PAH. In this study, we sought a non-invasive hemodynamic biomarker for the diagnosis of PAH. (2) Methods: We applied prospectively respiratory and cardiac gated 4D-flow MRI at a 9.4T preclinical scanner on three different groups of Sprague Dawley rats: baseline (n = 11), moderate PAH (n = 8), and severe PAH (n = 8). The pressure gradients as well as the velocity values were analyzed from 4D-flow data and correlated with lung histology. (3) Results: The pressure gradient between the pulmonary artery and vein on the unilateral side as well as the time-averaged mean velocity values of the small pulmonary arteries were capable of distinguishing not only between baseline and severe PAH, but also between the moderate and severe stages of the disease. (4) Conclusions: The current preclinical study suggests the pulmonary arteriovenous pressure gradient and the time-averaged mean velocity as potential biomarkers to diagnose PAH.

In vivo imaging tools for functional assessment of biomaterials implanted bone regeneration

Since the discovery of X-rays and its first use in imaging of a hand, bone tissue has been the chapter of interest in medical imaging. However, X-ray imaging poses limitations nowadays owing to the augmented complexity of implant scaffolds as well as with the advances in bone engineering. As a result, advanced follow-up imaging techniques are of paramount necessity for effective postoperative characterization. Moreover, it is also needed to search for non-invasive, high-sensitivity, and high-resolution structural, functional, and molecular imaging techniques such as acoustic, optical, magnetic, X-Ray, electron, ultrasound, and nuclear imaging, etc. as an alternative to normally used X-ray computed tomography. Further, enthusiastic preclinical scanners have turned out to be accessible, with sensitivity and resolution even superior to clinical scanners, as a consequence helping a rapid transformation from preclinical to clinical applications. Besides, recently, bone-specific probes and contrast agents are developing for better imaging tools in bone-tissue engineering applications. This review highlights such emerging preclinical imaging tools, each with its individual potencies and flaws, either used only or in combination. In particular, multimodal imaging will significantly add to improve the present understanding in the characterization of bone regenerative processes.

Diffusion-weighted magnetic resonance imaging in rat kidney using two-dimensional navigated, interleaved echo-planar imaging at 7.0T.

The purpose of this study was to investigate the feasibility of two-dimensional (2D) navigated, interleaved multishot echo-planar imaging (EPI) to enhance kidney diffusion-weighted imaging (DWI) in rats at 7.0T. Fully sampled interleaved four-shot EPI with 2D navigators was tailored for kidney DWI (Sprague-Dawley rats, n = 7) on a 7.0-T small bore preclinical scanner. The image quality of four-shot EPI was compared with T2 -weighted rapid acquisition with relaxation enhancement (RARE) (reference) and single-shot EPI (ss-EPI) without and with parallel imaging (PI). The contrast-to-noise ratio (CNR) was examined to assess the image quality for the EPI approaches. The Dice similarity coefficient and the Hausdorff distance were used for evaluation of image distortion. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated for renal cortex and medulla for all DWI approaches. The corticomedullary difference of MD and FA were assessed by Wilcoxon signed-rank test. Four-shot EPI showed the highest CNR among the three EPI variants and lowest geometric distortion versus T2 -weighted RARE (mean Dice: 0.77 for ss-EPI without PI, 0.88 for ss-EPI with twofold undersampling, and 0.92 for four-shot EPI). The FA map derived from four-shot EPI clearly identified a highly anisotropic region corresponding to the inner stripe of the outer medulla. Four-shot EPI successfully discerned differences in both MD and FA between renal cortex and medulla. In conclusion, 2D navigated, interleaved multishot EPI facilitates high-quality rat kidney DWI with clearly depicted intralayer and interlayer structure and substantially reduced image distortion. This approach enables the anatomic integrity of DWI-MRI in small rodents and has the potential to benefit the characterization of renal microstructure in preclinical studies.