Magnetic Resonance Microimaging Research Articles

Abstract 5285: DKK1 blockade inhibits progression of bone metastases via multiple mechanisms and synergize with zoledronate treatment

Abstract Background: Despite the important breakthroughs of immune checkpoint blockade (ICB) therapy in multiple primary cancers, responses of ICB therapy in bone metastases remain extremely poor, largely due to the highly immunosuppressive bone metastasis microenvironment. However, the current understanding of bone metastasis microenvironment is still incomplete, and specific treatment targets for patients with bone metastasis are still lacking. Methods: Transcriptome sequencing data of gastric and breast cancer bone metastasis samples from The TCGA and GEO databases were obtained. The correlation between DKK1 expression and prognosis, intertumoral immune infiltration of bone-metastatic patients was analyzed. Mouse bone metastasis models from gastric, breast and lung cancer were established, and in vivo treatment efficacy of DKK1 and/or zoledronic acid was evaluated by micro-computed tomography (CT), micro-magnetic resonance imaging (MRI) and immunohistochemistry (IHC) staining. The changes of immune components wthin bone-tumor microenvironment were explored via flow cytometry, CyTOF and scRNA-seq analysis. The impact of DKK1 on different immune cell types was analyzed via in vitro co-culture models. Results: Serum detection of gastric cancer patients from our center showed that compared with non-metastatic patients, DKK1 concentration in patients with bone metastasis was the significantly increased (p<0.0001); and compared with other metastatic sites of breast cancer patients, bone metastases had the highest level of DKK1 mRNA expression (p<0.05). Using multiple bone metastasis mouse models, we found that DKK1 blockade significantly controlled the tumor burden of bone metastases. Results of micro-CT and TRAP staining showed that the bone destruction and osteoclast activity within bone lesions were significantly inhibited after DKK1 blockade. In addition, results of flow cytometry and immunofluorescence staining on bone metastasis samples showed that both innate and adaptive anti-immune responses were obviously improved after DKK1 blockade, including increased infiltration of CD8+ T cells, M1 macrophages and decreased infiltration of M2 macrophages. Mechanistically, DKK1 directly induced inhibition of CD8+ T cell activation, M2 polarization of macrophages and maturation of osteoclasts, which all contributes to the immune suppression in the bone metastasis microenvironment. Finally, combined therapy of DKK1 blockade and zoledronic acid had synergistic treatment effects in bone metastases. Conclusion: Our study provides novel insights into the multiple role of DKK1 in the bone metastasis immune microenvironment. DKK1 is a potential immunotherapeutic target for bone metastases, and dual blockade of DKK1 and zoledronic acid is a promising combination immunotherapy strategy for patients with bone metastasis. Citation Format: Tao Shi, Kaijie Liang, Yipeng Zhang, Xiaoyu Zhou, Baorui Liu, Jia Wei. DKK1 blockade inhibits progression of bone metastases via multiple mechanisms and synergize with zoledronate treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5285.

Unraveling Spatially Dependent Hydrophilicity and Reactivity of Confined Carbocation Intermediates during Methanol Conversion over ZSM-5 Zeolite.

Carbocations play a pivotal role as reactive intermediates in zeolite-catalyzed methanol-to-hydrocarbon (MTH) transformations. However, the interaction between carbocations and water vapor and its subsequent effects on catalytic performance remain poorly understood. Using micro-magnetic resonance imaging (μMRI) and solid-state NMR techniques, this work investigates the hydrophilic behavior of cyclopentenyl cations within ZSM-5 pores under vapor conditions. We show that the polar cationic center of cyclopentenyl cations readily initiates water nucleus formation through water molecule capture. This leads to an inhomogeneous water adsorption gradient along the axial positions of zeolite, correlating with the spatial distribution of carbocation concentrations. The adsorbed water promotes deprotonation and aromatization of cyclopentenyl cations, significantly enhancing the aromatic product selectivity in MTH catalysis. These results reveal the important influence of adsorbed water in modulating the carbocation reactivity within confined zeolite pores.

Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis (NASH) has been posited as crucial. The Yanggan Jiangmei Formula (YGJMF) has shown promise in ameliorating hepatic steatosis in NASH patients, yet its pharmacological mechanisms remain largely unexplored. This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings. To simulate NASH both in vivo and in vitro, high-fat-diet (HFD) rats and HepG2 cells stimulated with free fatty acids (FFAs) were utilized. The severity of liver injury and lipid deposition was assessed using serum indicators, histopathological staining, micro-magnetic resonance imaging (MRI), and the liver-to-muscle signal intensity ratio (SIRL/M). Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels. The results from liver pathology, MRI assessments, and biochemical tests in rat models demonstrated YGJMF's significant effectiveness in reducing liver damage and lipid accumulation. Additionally, YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum. Furthermore, YGJMF was found to disrupt NF-κB activation, consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models. The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway, thereby exerting anti-inflammatory effects in NASH.

The High Potential of Micro-Magnetic Resonance Imaging for the Identification of Archaeological Reeds: The Case Study of Tutankhamun

This study explores the potential of micro-magnetic resonance imaging (μ-MRI) for identifying archaeological reeds found in the tomb of Tutankhamun. Reed plants had various historical uses in the past, with ancient Egyptians extensively employing them for crafting a wide range of items. The distinct cross-sectional characteristics of Arundo donax (giant reed) and Phragmites australis (common reed) are observed and described via optical microscopy and μ-MRI in this study. While optical microscopy offers higher resolution, μ-MRI provides advantages for studying archaeobotanical specimens, as it eliminates the need for mechanical sectioning and potentially damaging fragile samples. The application of μ-MRI on a selected archaeological reed allowed us to identify it as Phragmites australis, showing that μ-MRI can yield clear images, maintaining the integrity of the sample. In contrast, diagnostic features appeared greatly deformed on the thin section observed via optical microscopy. Despite the limitations related to the sample size and the need for sample soaking, μ-MRI presents a valuable tool for analyzing archaeological remains in the field of cultural heritage, with the potential for broader applications. Overall, this study contributes to expanding the toolkit available to researchers studying plant remains, providing insights into reed identification and preservation in archaeological contexts.

U-Net based vessel segmentation for murine brains with small micro-magnetic resonance imaging reference datasets.

Identification and quantitative segmentation of individual blood vessels in mice visualized with preclinical imaging techniques is a tedious, manual or semiautomated task that can require weeks of reviewing hundreds of levels of individual data sets. Preclinical imaging, such as micro-magnetic resonance imaging (μMRI) can produce tomographic datasets of murine vasculature across length scales and organs, which is of outmost importance to study tumor progression, angiogenesis, or vascular risk factors for diseases such as Alzheimer's. Training a neural network capable of accurate segmentation results requires a sufficiently large amount of labelled data, which takes a long time to compile. Recently, several reasonably automated approaches have emerged in the preclinical context but still require significant manual input and are less accurate than the deep learning approach presented in this paper-quantified by the Dice score. In this work, the implementation of a shallow, three-dimensional U-Net architecture for the segmentation of vessels in murine brains is presented, which is (1) open-source, (2) can be achieved with a small dataset (in this work only 8 μMRI imaging stacks of mouse brains were available), and (3) requires only a small subset of labelled training data. The presented model is evaluated together with two post-processing methodologies using a cross-validation, which results in an average Dice score of 61.34% in its best setup. The results show, that the methodology is able to detect blood vessels faster and more reliably compared to state-of-the-art vesselness filters with an average Dice score of 43.88% for the used dataset.

Evaluation of the efficacy of micro-Magnetic Resonance Imaging compared with light microscopy to investigate the anatomy of modern and ancient waterlogged wood

Light microscopy is the conventional method used to investigate wood anatomy, identify the wood taxon, and assess its conservation state. It generally requires the mechanical cut of thin sections from a sample to obtain informative images. When dealing with wooden artworks or ancient remains (e.g., archaeological waterlogged wood), it is important to avoid sample destruction. In this work the efficacy of micro-magnetic resonance imaging (μ-MRI) to investigate the anatomy of waterlogged wood is assessed in comparison with light microscopy. Images along the three anatomical directions (transverse, tangential and radial) of six modern wood species and one archaeological specimen of waterlogged wood (from the Neolithic site “La Marmotta”) were obtained both by μ-MRI and light microscopy. μ-MRI images were acquired virtually selecting 2D slices along the three wood anatomical directions. A 3D reconstruction was derived from 2D μ-MRI images. Conventional light microscopy histology was obtained by manually cutting thin sections. To the best of our knowledge, this is the first study in which high-resolution MR images and light microscopy images of the three anatomical directions of seven wood species are compared. The non-destructive μ-MRI approach allows to investigate the 2D and 3D topological organization of the whole waterlogged wood sample up to a resolution of 8 μm. Although the optical microscope attains higher image resolutions and remains superior in the observation of wood diagnostic characters, multi-parametric μ-MRI provides physiological investigation complementary to light microscopy, giving information concerning both a single section and the whole volume of the sample. The presented study may represent a starting point for further improvements of μ-MRI techniques applied to the non-destructive investigation of waterlogged wood samples, especially those of interest for cultural heritage.

Experimental assessment of cardiovascular physiology in the chick embryo.

High resolution assessment of cardiac functional parameters is crucial in translational animal research. The chick embryo is a historically well-used in vivo model for cardiovascular research due to its many practical advantages, and the conserved form and function of the chick and human cardiogenesis programs. This review aims to provide an overview of several different technical approaches for chick embryo cardiac assessment. Doppler echocardiography, optical coherence tomography, micromagnetic resonance imaging, microparticle image velocimetry, real-time pressure monitoring, and associated issues with the techniques will be discussed. Alongside this discussion, we also highlight recent advances in cardiac function measurements in chick embryos.

Label-free atherosclerosis diagnosis through a blood drop of apolipoprotein E knockout mouse model using surface-enhanced Raman spectroscopy validated by machine learning algorithm.

The direct preventative detection of flow-induced atherosclerosis remains a significant challenge, impeding the development of early treatments and prevention measures. This study proposes a method for diagnosing atherosclerosis in the carotid artery using nanometer biomarker measurements through surface-enhanced Raman spectroscopy (SERS) from single-drop blood samples. Atherosclerotic acceleration is induced in apolipoprotein E knockout mice which underwent a partial carotid ligation and were fed a high-fat diet to rapidly induce disturbed flow-induced atherosclerosis in the left common carotid artery while using the unligated, contralateral right carotid artery as control. The progressive atherosclerosis development of the left carotid artery was verified by micro-magnetic resonance imaging (micro-MRI) and histology in comparison to the right carotid artery. Single-drop blood samples are deposited on chips of gold-coated ZnO nanorods grown on silicon wafers that filter the nanometer markers and provide strong SERS signals. A diagnostic classifier was established based on principal component analysis (PCA), which separates the resultant spectra into the atherosclerotic and control groups. Scoring based on the principal components enabled the classification of samples into control, mild, and severe atherosclerotic disease. The PCA-based analysis was validated against an independent test sample and compared against the PCA-PLS-DA machine learning algorithm which is known for applicability to Raman diagnosis. The accuracy of the PCA modification-based diagnostic criteria was 94.5%, and that of the machine learning algorithm 97.5%. Using a mouse model, this study demonstrates that diagnosing and classifying the severity of atherosclerosis is possible using a single blood drop, SERS technology, and machine learning algorithm, indicating the detectability of biomarkers and vascular factors in the blood which correlate with the early stages of atherosclerosis development.

A phantom for the quantitative determination and improvement of the spatial resolution in slice-selective 2D-FT magnetic resonance micro-imaging and -microscopy based on Deep X-ray Lithography (DXRL)

Introduction: The most important assessed quality-control (QC) criteria for improvements in high-resolution imaging are represented by the contrast-to-noise-ratio and spatial resolution. Ultra-High-Field (UHF) Magnetic-Resonance-scanners (B ≥ 7 T) for medical research allowed for the improvement in spatial resolution up to the microimaging and nominal microscopy range [pixel-size: ps < (100 μm)2], even in-vivo on humans just recently. Preclinical MRI- and dedicated MR-microscopy (MRM) scanners already allow for microimaging and MRM (1-256 μm) but lack a sensible spatial resolution phantom for QC and performance improvements in hardware, pulse-sequencing and MRprotocols. In most scientific MRI articles, the spatial resolution is characterized by the ps, though this measurement parameter only limits the actual resolution.Methods: Here the Modulation-Transfer-Function (MTF) is used as evaluation concept for the determination of the spatial resolution in MRM using simple intensity profiles. The resolution limit is defined using a critical modulation-level. In approaching visual impressions on spatial resolution an additional criterion derived from the Modulation-depth-to-Noise-Ratio (MNR) is proposed. A practical method for assessment based on a concrete phantom design and its realization is shown.Results: The phantom design consists of several sets of fine grids, specifically featuring high structural anisotropy for optimum SNR and CNR, with different spatial periods ranging from a1 = 256 μm down to a8 = 2 μm, not only for a quick visual qualitative check, but also for quantification of resolution using the MTF for two different spatial encodings in two orthogonal in-plane directions. The challenging demands on the manufacturing technology especially with regard to the aspect-ratio are approached using Deep-X-Ray-Lithography (DXRL) relying on the high brilliance of Synchroton-radiation. Smallest grid plates with width of 4 μm corresponding to 125 line pairs/mm at a plate depth of 100 μm were achieved.Discussion: MR-microscopic images, originating from a microscopy insert on a human UHF-MR-scanner, were used for demonstration of the evaluation process with two independent resolution-criteria. The developed prototype offers unique possibilities for quantitative resolution QC on UHF human and preclinical MR-scanners. Such a resolution-phantom might be very important for the improvement of MR-pulse-sequences, MR-protocols and even hardware. In principle the phantom can also be used for other microscopic imaging-modalities as for instance μCT and Optical-Coherence-Tomography (OCT).

Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead to muscular atrophy. However, leptin deficiency-induced structural changes in muscles are poorly understood. The zebrafish has emerged as an excellent model organism for studies of vertebrate diseases and hormone response mechanisms. In this study, we explored ex-vivo magnetic resonance microimaging (μMRI) methods to non-invasively assess muscle wasting in leptin-deficient (lepb-/-) zebrafish model. The fat mapping performed by using chemical shift selective imaging shows significant fat infiltration in muscles of lepb-/- zebrafish compared to control zebrafish. T2 relaxation measurements show considerably longer T2 values in the muscle of lepb-/- zebrafish. Multiexponential T2 analysis detected a significantly higher value and magnitude of long T2 component in the muscles of lepb-/- as compared to control zebrafish. For further zooming into the microstructural changes, we applied diffusion-weighted MRI. The results show a significant decrease in the apparent diffusion coefficient indicating increased constraints of molecular movements within the muscle regions of lepb-/- zebrafish. The use of the phasor transformation for the separation of diffusion-weighted decay signals showed a bi-component diffusion system which allows us to estimate each fraction on a voxel-wise basis. A substantial difference was found between the ratio of two components in lepb-/- and control zebrafish muscles, indicating alterations in diffusion behavior associated with the tissue microstructural changes in muscles of lepb-/- zebrafish as compared to control zebrafish. Taken together, our results demonstrate that the muscles of lepb-/- zebrafish undergo significant fat infiltration and microstructural changes leading to muscle wasting. This study also demonstrates that μMRI provides excellent means to non-invasively study the microstructural changes in the muscles of the zebrafish model.

Lossy Image Compression in a Preclinical Multimodal Imaging Study.

The growing use of multimodal high-resolution volumetric data in pre-clinical studies leads to challenges related to the management and handling of the large amount of thesedatasets. Contrarily to the clinical context, currently there are no standard guidelines to regulate the use of image compression in pre-clinical contexts as a potential alleviationof this problem. In this work, the authors study the application of lossy image coding to compress high-resolution volumetric biomedical data. The impact of compression on the metricsand interpretation of volumetric data was quantified for a correlated multimodal imaging study to characterize murine tumor vasculature, using volumetric high-resolution episcopic microscopy (HREM), micro-computed tomography (µCT), and micro-magnetic resonance imaging (µMRI). The effects of compression were assessed by measuring task-specific performances of several biomedical experts who interpreted and labeled multiple data volumes compressed at different degrees. Wedefined trade-offs between data volume reduction and preservation of visual information, which ensured the preservation of relevant vasculature morphology at maximum compression efficiency across scales. Using the Jaccard Index (JI) and the average Hausdorff Distance (HD) after vasculature segmentation, we coulddemonstrate that, in this study, compression that yields toa 256-fold reduction of the data size allowed to keep the error induced by compression below the inter-observer variability, with minimal impact on the assessment of the tumor vasculature across scales.

Monitoring of water sorption and swelling of potato starch-glycerol extruded blend by magnetic resonance imaging and multivariate curve resolution

Magnetic resonance microimaging (MRμI) is an outstanding technique for studying water transfers in millimetric bio-based materials in a non-destructive and non-invasive manner. However, depending on the composition of the material, monitoring and quantification of these transfers can be very complex, and hence reliable image processing and analysis tools are necessary. In this study, a combination of MRμI and multivariate curve resolution-alternating least squares (MCR-ALS) is proposed to monitor the water ingress into a potato starch extruded blend containing 20% glycerol that was shown to have interesting properties for biomedical, textile, and food applications.In this work, the main purpose of MCR is to provide spectral signatures and distribution maps of the components involved in the water uptake process that occurs over time with various kinetics. This approach allowed the description of the system evolution at a global (image) and a local (pixel) level, hence, permitted the resolution of two waterfronts, at two different times into the blend that could not be resolved by any other mathematical processing method usually used in magnetic resonance imaging (MRI). The results were supplemented by scanning electron microscopy (SEM) observations in order to interpret these two waterfronts in a biological and physico-chemical point of view.

Utilization of potato starch suspension for MR-microimaging in exvivo mouse embryos.

Magnetic resonance (MR) microimaging of the mouse embryo is a promising tool to noninvasively investigate the microstructure of the brain of a developing mouse. The proton-free fluid is used for the liquid surrounding the specimen in MR microimaging, but the potential issue of image quality remains due to the air bubbles on the specimen and the retained water proton in the curvature of the embryo. Furthermore, the specimen may move during the scanning, resulting in motion artifact. Here, we developed the new concept of the exvivo microimaging protocol with the robust method using the potato starch-containing biological polymers. Potato starch suspension with PBS significantly reduced T1 and T2 signal intensity of the suspension and strongly suppressed the motion of the embryo. Furthermore, potato starch-PBS suspension is stable for long-time scanning at room temperature. These results indicate the utility of potato starch suspension for MR microimaging in mouse embryos.

Novel micro-MRI approach for subchondral trabecular bone analysis in patients with hip osteoarthritis is comparable to micro-CT approach

To test the agreement between a newly developed micro-magnetic resonance imaging (MRI) analysis of the subchondral bone and the micro-computed tomography (CT) approach. Samples obtained from 10 patients with osteoarthritis undergoing total hip arthroplasty were scanned with a 7.0 T micro-MRI. Proton density-weighted images and proton density-weighted images with fat suppression were obtained. The results were validated with a micro-CT device. Micro-MRI and micro-CT scans of the same sample were aligned, and regions of interest were delineated on equal areas of the sample. Bone volume fraction was calculated by using in-house plugins. The agreement between the methods was tested with Bland-Altman analysis. The agreement between the methods was good, with average difference of 2.167%. The differences between the methods were not significant (P=0.272, t test). The novel micro-MRI approach could be used for subchondral bone analysis. With further optimization for clinical MRI machines, the approach can be also used in the diagnostics of hip osteoarthritis.

Spatial correlation of water distribution and fine structure of arabinoxylans in the developing wheat grain

This study was to investigate the distribution of water and arabinoxylan structures in growing wheat grain using two complementary imaging techniques, magnetic resonance microimaging (μMRI) and mass spectrometry imaging (MSI). μMRI showed an inhomogeneous water distribution, particularly at early stages. This heterogeneity revealed histological differences that corresponded, within the limits of resolution of μMRI, to tissues with specific physiological functions, including the vascular bundles, the cavity and the endosperm periphery. All of these tissues had a higher water content than the central endosperm. MSI revealed distinct xylan structures in these regions with high levels of Araf substitution around the cavity and acetylated xylans concentrated at the endosperm periphery. For the first time, acetylation and Araf substitution of arabinoxylans were found by image processing to spatially correlate with water distribution in planta. Acetylation and Araf substitution of xylans, which alter chain-chain interactions and increase wall porosity, decreased as the grain matured.

Establishment of a visualized mouse orthotopic model of nasopharyngeal carcinoma.

e18048 Background: Nasopharyngeal carcinoma, one of the most common head and neck tumors, is particularly prevalent in Southeast Asia and is characterized by high rates of metastasis and recurrence. Although mouse orthotopic tumor models are commonly employed in studies investigating the mechanisms underlying tumor development and progression, as well as preclinical treatment, currently no such model exists for nasopharyngeal carcinoma. The aim of the current study is to, therefore, establish an orthotopic murine model for nasopharyngeal carcinoma. Methods: To this end, human nasopharyngeal carcinoma C666-1-luc cells, stably expressing the firefly luciferase gene, were injected subcutaneously into the right axilla of BALB/C nude mice. Four weeks later, the resulting subcutaneous tumors were cut into small blocks and grafted into the nasopharynx of immunodeficient BALB/C nude mice to induce tumor formation. Tumor growth was monitored by bioluminescence imaging and small animal magnetic resonance imaging. The histological and immunological antigen expression associated with orthotopic nasopharyngeal carcinoma were analyzed by tissue section analysis and immunohistochemistry (IHC). Results: The tumor formation rate was over 90%. Fluorescence signal detection, micro-magnetic resonance imaging and hematoxylin and eosin staining revealed the successful growth of tumors in the nasopharynx of nude mice. Moreover, IHC analysis detected positive CK, CK5/6, P40 and P63 expression in the mouse orthotopic tumors, which is consistent with the reported antigen expression in the nasopharyngeal tumors of patients. Conclusions: Hence, we successfully established a mouse orthotopic model of nasopharyngeal carcinoma that is highly reproducible, and simple in operation, with low mortality and high tumor formation rates. Moreover, this model facilitates real-time monitoring of tumor growth via in vivo imaging technology, thus, providing a platform for researching nasopharyngeal carcinoma that is more conducive to preclinical research.

Human Obesity Attenuates Cardioprotection Conferred by Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells.

To explore the impact of obesity on reparative potency of adipose tissue-derived mesenchymal stromal/stem cells (A-MSC) in hypertensive cardiomyopathy, A-MSC were harvested from subcutaneous fat of obese and age-matched non-obese human subjects during bariatric or kidney donation surgeries, and then injected into mice 2weeks after inducing renovascular hypertension (RVH) or sham surgery. Two weeks later, left ventricular (LV) function and deformation were estimated in vivo by micro-magnetic resonance imaging and myocardial damage ex vivo. Blood pressure and myocardial wall thickening were elevated in RVH + Vehicle and normalized only by lean-A-MSC. Both A-MSC types reduced LV mass and normalized the reduced LV peak strain radial in RVH, yet obese-A-MSC also impaired LV systolic function. A-MSC alleviated myocardial tissue damage in RVH, but lean-A-MSC decreased oxidative stress more effectively. Obese-A-MSC also showed increased cellular inflammation in vitro. Therefore, obese-A-MSC are less effective than lean-A-MSC in blunting hypertensive cardiomyopathy in mice with RVH.

Nuclear Magnetic Resonance Microimaging for the Qualitative Assessment of Root Canal Treatment: An Ex Vivo Preliminary Study.

Aim: To assess the potential ability of nuclear magnetic resonance micro-imaging (mMRI) to visualize and identify soft tissue debris and unfilled spaces inside radicular canals in endodontic treated extracted teeth, for understanding the causes of treatment failure. Toward this goal, multi-parametric mMRI and cone beam computed tomography (CBCT) were compared. Methodology: A non-recoverable root treated human tooth was extracted due to endodontic failure and excessive mobility. It was examined with both CBCT and mMRI: CBCT was performed with 0.125 mm voxel size (GXCB-500, Kavo-Gendex, Brea, CA, USA) and mMRI was performed with a spectrometer operating at 9.4T magnetic field (Bruker Avance-400, Bruker, Billerica, MA, USA). The mMRI images were obtained with a microimaging probe. Relaxation times (T1 and T2) and diffusion-weighted acquisition sequences were used to obtain multi-parametric maps of the extracted tooth (slice thickness of 200 µm and in plane resolution of 30 × 30 µm2). Results: T1 and T2 maps identified unfilled spaces around and close to Gutta-percha cones instead of CBCT images that were not able to highlight this aspect. T1, T2 and apparent diffusion coefficient (ADC) assumed different values in dentine and in voids, characterized by different dimensions. Moreover, they were able to discriminate between infiltrations of water only and deposits of biological material. Because Gutta-percha cones are constituted of hard, non-porous material, they do not provide a signal and in mMRI images appear as zones of noise. Conclusions: Unlike the CBCT exam, mMRI can detect soft tissue debris and unfilled spaces inside radicular canals. Therefore, this in vitro study showed the potential of mMRI to evaluate the quality of the root canal treatment, suggesting its potential benefit in determining the causes of endodontic failure, without the use of ionizing radiation.

Intervertebral Disc Degeneration Induced by Needle Puncture and Ovariectomy: A Rat Coccygeal Model.

Objectives To establish a novel animal model of intervertebral disc degeneration (IVDD) in rats and to investigate the effect of 17β-estradiol (E2) intervention in this model. Methods This study was divided into two parts: animal model (four groups: Sham, ovariectomy (OVX), Puncture, and OVX+Puncture; three-time points: 4, 8, and 12 weeks; three female rats/group/time point) and drug intervention (Sham, OVX+Puncture+corn oil, and OVX+Puncture+E2; three female rats/group). The rats were analyzed by micromagnetic resonance imaging (MRI), hematoxylin and eosin (HE) staining, and safranin-O staining. Results MRI and histological scores significantly differed among the four groups at the three-time points (all P < 0.05). IVDD progressed with time in the OVX, Puncture, and OVX+Puncture groups (all P < 0.05). The changes were the most obvious in the OVX+Puncture group. In the E2 intervention part, the Veh group had the worst MRI signals and histological scores (P < 0.05). The MRI scores in the E2 group were less obvious compared to the Sham group (P > 0.05). Also, the histological scores were significantly different between the Sham and E2 groups (P < 0.05). Conclusions The combination of ovariectomy and needle puncture can synergically induce IVDD in rat coccygeal discs. Estrogen treatment can effectively ameliorate IVDD progression in the newly established IVDD models.

The Use of Imaging Techniques in Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD)-A Systematic Review.

Although frequently silent, mineral and bone disease (MBD) is one of the most precocious complication of chronic kidney disease (CKD) and is omnipresent in patients with CKD stage 5. Its pathophysiology is complex, but basically, disturbances in vitamin D, phosphate, and calcium metabolism lead to a diverse range of clinical manifestations with secondary hyperparathyroidism usually being the most frequent. With the decline in renal function, CKD-MBD may induce microstructural changes in bone, vascular system and soft tissues, which results in macrostructural lesions, such as low bone mineral density (BMD) resulting in skeletal fractures, vascular and soft tissue calcifications. Moreover, low BMD, fractures, and vascular calcifications are linked with increased risk of cardiovascular mortality and all-cause mortality. Therefore, a better characterization of CKD-MBD patterns, beyond biochemical markers, is helpful to adapt therapies and monitor strategies as used in the general population. An in-depth characterization of bone health is required, which includes an evaluation of cortical and trabecular bone structure and density and the degree of bone remodeling through bone biomarkers. Standard radiological imaging is generally used for the diagnosis of fracture or pseudo-fractures, vascular calcifications and other features of CKD-MBD. However, bone fractures can also be diagnosed using computed tomography (CT) scan, magnetic resonance (MR) imaging and vertebral fracture assessment (VFA). Fracture risk can be predicted by bone densitometry using dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QTC) and peripheral quantitative computed tomography (pQTC), quantitative ultrasound (QUS) and most recently magnetic resonance micro-imaging. Quantitative methods to assess bone consistency and strength complete the study and adjust the clinical management when integrated with clinical factors. The aim of this review is to provide a brief and comprehensive update of imaging techniques available for the diagnosis, prevention, treatment and monitoring of CKD-MBD.