AcidoCEST-UTE MRI for the Assessment of Extracellular pH of Joint Tissues at 3 T.

ObjectivesThe goal of this study was to demonstrate feasibility of measuring extracellular pH in cartilage and meniscus using acidoCEST technique with a 3-dimensional ultrashort echo time readout (acidoCEST-UTE) magnetic resonance imaging (MRI).Materials and methodsMagnetization transfer ratio asymmetry, radiofrequency (RF) power mismatch, and relative saturation transfer were evaluated in liquid phantoms for iopromide, iopamidol, and iohexol over a pH range of 6.2 to 7.8, at various agent concentrations, temperatures, and buffer concentrations. Tissue phantoms containing cartilage and meniscus were evaluated with the same considerations for iopamidol and iohexol. Phantoms were imaged with the acidoCEST-UTE MRI sequence at 3 T. Correlation coefficients and coefficients of variations were calculated. Paired Wilcoxon rank-sum tests were used to evaluate for statistically significant differences.ResultsThe RF power mismatch and relative saturation transfer analyses of liquid phantoms showed iopamidol and iohexol to be the most promising agents for this study. Both these agents appeared to be concentration independent and feasible for use with or without buffer and at physiologic temperature over a pH range of 6.2 to 7.8. Ultimately, RF power mismatch fitting of iohexol showed the strongest correlation coefficients between cartilage, meniscus, and fluid. In addition, ratiometric values for iohexol are similar among liquid as well as different tissue types.ConclusionsMeasuring extracellular pH in cartilage and meniscus using acidoCEST-UTE MRI is feasible

Multiplexed capillary electrophoresis system

The use of capillary electrophoresis (CE) has greatly improved DNA sequencing rates compared to conventional slab gel electrophoresis. Part of the improvement in speed, however, has been offset by the loss of the ability (inherent in slab gels) to accommodate multiple lanes in a single run. Highly multiplexed capillary electrophoresis, by making possible hundreds or even thousands of parallel sequencing runs, represents an attractive approach to overcoming the current throughput limitations of existing DNA sequencing instrumentation

Multiplex capillary electrophoresis system

The use of capillary electrophoresis (CE) has greatly improved DNA sequencing rates compared to conventional slab gel electrophoresis. Part of the improvement in speed, however, has been offset by the loss of the ability (inherent in slab gels) to accommodate multiple lanes in a single run. Highly multiplexed capillary electrophoresis, by making possible hundreds or even thousands of parallel sequencing runs, represents an attractive approach to overcoming the current throughput limitations of existing DNA sequencing instrumentation

Towards assessing and improving the reliability of ultrashort echo time quantitative magnetization transfer (UTE-qMT) MRI of cortical bone: In silico and ex vivo study

ObjectiveTo assess and improve the reliability of the ultrashort echo time quantitative magnetization transfer (UTE-qMT) modeling of the cortical bone.Materials and methodsSimulation-based digital phantoms were created that mimic the UTE-qMT properties of cortical bones. A wide range of SNR from 25 to 200 was simulated by adding different levels of noise to the synthesized MT-weighted images to assess the effect of SNR on UTE-qMT fitting results. Tensor-based denoising algorithm was applied to improve the fitting results. These results from digital phantom studies were validated via ex vivo rat leg bone scans.ResultsThe selection of initial points for nonlinear fitting and the number of data points tested for qMT analysis have minimal effect on the fitting result. Magnetization exchange rate measurements are highly dependent on the SNR of raw images, which can be substantially improved with an appropriate denoising algorithm that gives similar fitting results from the raw images with an 8-fold higher SNR.DiscussionThe digital phantom approach enables the assessment of the reliability of bone UTE-qMT fitting by providing the known ground truth. These findings can be utilized for optimizing the data acquisition and analysis pipeline for UTE-qMT imaging of cortical bones

Longitudinal Imaging of Injured Spinal Cord Myelin and White Matter with 3D Ultrashort Echo Time Magnetization Transfer (UTE-MT) and Diffusion MRI

Quantitative MRI techniques could be helpful to noninvasively and longitudinally monitor dynamic changes in spinal cord white matter following injury, but imaging and postprocessing techniques in small animals remain lacking. Unilateral C5 hemisection lesions were created in a rat model, and ultrashort echo time magnetization transfer (UTE-MT) and diffusion-weighted sequences were used for imaging following injury. Magnetization transfer ratio (MTR) measurements and preferential diffusion along the longitudinal axis of the spinal cord were calculated as fractional anisotropy or an apparent diffusion coefficient ratio over transverse directions. The area of myelinated white matter was obtained by thresholding the spinal cord using mean MTR or diffusion ratio values from the contralesional side of the spinal cord. A decrease in white matter areas was observed on the ipsilesional side caudal to the lesions, which is consistent with known myelin and axonal changes following spinal cord injury. The myelinated white matter area obtained through the UTE-MT technique and the white matter area obtained through diffusion imaging techniques showed better performance to distinguish evolution after injury (AUCs > 0.94, p < 0.001) than the mean MTR (AUC = 0.74, p = 0.01) or ADC ratio (AUC = 0.68, p = 0.05) values themselves. Immunostaining for myelin basic protein (MBP) and neurofilament protein NF200 (NF200) showed atrophy and axonal degeneration, confirming the MRI results. These compositional and microstructural MRI techniques may be used to detect demyelination or remyelination in the spinal cord after spinal cord injury

Correction: Lombardi et al. AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis. Int. J. Mol. Sci. 2022, 23, 4466

In the original publication, there was a mistake in Figure 1 as published [...]

Rotator cuff muscle fibrosis can be assessed using ultrashort echo time magnetization transfer MRI with fat suppression

Muscle degeneration following rotator cuff tendon tearing is characterized by fatty infiltration and fibrosis. While tools exist for the characterization of fat, the ability to noninvasively assess muscle fibrosis is limited. The purpose of this study was to evaluate the capability of quantitative ultrashort echo time T1 (UTE-T1) and UTE magnetization transfer (UTE-MT) mapping with and without fat suppression (FS) for the differentiation of injured and control rotator cuff muscles and for the detection of fibrosis. A rat model of chronic massive rotator cuff tearing (n = 12) was used with tenotomy of the right supraspinatus and infraspinatus tendons and silicone implants to prevent healing. Imaging was performed on a 3-T scanner, and UTE-T1 mapping with and without FS and UTE-MT with and without FS for macromolecular fraction (MMF) mapping was performed. At 20 weeks postinjury, T1 and MMF were measured in the supraspinatus and infraspinatus muscles of the injured and contralateral, internal control sides. Histology was performed and connective tissue fraction (CTF) was measured, defined as the area of collagen-rich extracellular matrix divided by the total muscle area. Paired t-tests and correlation analyses were performed. Significant differences between injured and control sides were found for CTF in the supraspinatus (mean ± SD, 14.5% ± 3.9% vs. 11.3% ± 3.7%, p = 0.01) and infraspinatus (17.0% ± 5.4% vs. 12.5% ± 4.6%, p < 0.01) muscles, as well as for MMF using UTE-MT FS in the supraspinatus (9.7% ± 0.3% vs. 9.5% ± 0.2%, p = 0.04) and infraspinatus (10.9% ± 0.8% vs. 10.1% ± 0.5%, p < 0.01) muscles. No significant differences between sides were evident for T1 without or with FS or for MMF using UTE-MT. Only MMF using UTE-MT FS was significantly correlated with CTF for both supraspinatus (r = 0.46, p = 0.03) and infraspinatus (r = 0.51, p = 0.01) muscles. Fibrosis occurs in rotator cuff muscle degeneration, and the UTE-MT FS technique may be helpful to evaluate the fibrosis component, independent from the fatty infiltration process

Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species

Background: Nearly one-quarter of all avian species is either threatened or nearly threatened. Of these, 73 species are currently being rescued from going extinct in wildlife sanctuaries. One of the previously most critically-endangered is the crested ibis, Nipponia nippon. Once widespread across North-East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies. Results: Using high-quality genome sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures of near extinction events in association with environmental and behavioral attributes of species. We confirm that both loss of genetic diversity and enrichment of deleterious mutations of protein-coding genes contribute to the major genetic defects of the endangered species. We further identify that genetic inbreeding and loss-of-function genes in the crested ibis may all constitute genetic susceptibility to other factors including long-term climate change, over-hunting, and agrochemical overuse. We also establish a genome-wide DNA identification platform for molecular breeding and conservation practices, to facilitate sustainable recovery of endangered species. Conclusions: These findings demonstrate common genomic signatures of population decline across avian species and pave a way for further effort in saving endangered species and enhancing conservation genomic efforts.</p

Assessment of White Matter Changes using Quantitative T1ρ Mapping in an Open-Field Low-Intensity Blast Mouse Model of Mild Traumatic Brain Injury (mTBI)

Blast-induced mild traumatic brain injury (mTBI) occurs when shock waves travel through blood vessels and cerebrospinal fluid, leading to cerebral demyelination, which results in cognitive impairments and neuropsychiatric issues that impact quality of life. This study aims to evaluate myelin changes in white matter in mice with mTBI induced by an open-field low-intensity blast (LIB) using a newly implemented 3D adiabatic T1ρ prepared fast spin echo (Adiab-T1ρ-FSE) sequence for quantitative T1ρ MRI mapping. Thirty male C57BL/6 mice, including 15 mTBI and 15 sham controls, were scanned on a 3T Bruker MRI scanner. Luxol fast blue (LFB) staining was performed to assess myelin content differences between the mTBI and sham control groups. A significantly higher T1ρ value in the medial corpus callosum (MCC) was found in mTBI mice compared to controls (126.8 ± 2.5 ms vs. 129.8 ± 2.5 ms; p \u3c 0.001), consistent with the reduced myelin observed in LFB staining (0.80 ± 0.14 vs. 1.02 ± 0.06; p = 0.004). Moreover, a significant negative correlation between T1ρ and histological myelin content measurements was observed (r = −0.57, p = 0.02). Our findings demonstrate that T1ρ is a promising biomarker for detecting mTBI-associated demyelination in the brain