Mapping prion pathology in mice using quantitative imaging: an MRI study

Human prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

Evaluation of a single-breath-hold radial turbo-spin-echo sequence for T2 mapping of the liver at 3T

Objectives T2 mapping of the liver is a potential diagnostic tool, but conventional techniques are difficult to perform in clinical practice due to long scan time. We aimed to evaluate the accuracy of a prototype radial turbo-spin-echo (rTSE) sequence, optimized for multi-slice T2 mapping in the abdomen during one breath-hold at 3 T. Methods A multi-sample (fat: 0–35%) agarose phantom doped with MnCl2 and 80 subjects (73 patients undergoing abdomen MR examination and 7 healthy volunteers) were investigated. A radial turbo-spin-echo (rTSE) sequence with and without fat suppression, a Cartesian turbo-spin-echo (Cart-TSE) sequence, and a single-voxel multi-echo STEAM spectroscopy (HISTO) were performed in phantom, and fat-suppressed rTSE and HISTO sequences were performed in in vivo measurements. Two approaches were used to sample T2 values: manually selected circular ROIs and whole liver analysis with Gaussian mixture models (GMM). Results The rTSE-T2s values exhibited a strong correlation with Cart-TSE-T2s (R2 = 0.988) and with HISTO-T2s of water (R2 = 0.972) in phantom with an offset between rTSE and Cart-TSE maps (mean difference = 3.17 ± 1.18 ms). The application of fat suppression decreased T2 values, and the effect was directly proportional to the amount of fat. Measurements in patients yielded a linear relationship between rTSE- and HISTO-T2s (R2 = 0.546 and R2 = 0.580 for ROI and GMM, respectively). Conclusion The fat-suppressed rTSE sequence allows for fast and accurate determination of T2 values of the liver, and appears to be suitable for further large cohort studies. Key Points •Radial turbo-spin-echo T2 mapping performs comparably to Cartesian TSE-T2 mapping, but an offset in values is observed in phantom measurements. •Fat-suppressed radial turbo-spin-echo T2 mapping is consistent with T2 of water as assessed by MRS in phantom measurements. •Fat-suppressed radial turbo-spin-echo sequence allows fast T2 mapping of the liver in a single breath-hold and is correlated with MRS-based T2 of water.

Quantitative magnetic resonance imaging of chronic kidney disease: an experimental in vivo study using rat chronic kidney disease models

Background Recent advances in magnetic resonance imaging (MRI) may allow it to be an alternative emerging tool for the non-invasive evaluation of renal parenchymal disease. Purpose To validate the usefulness of quantitative multiparametric MRI protocols and suggest the suitable quantitative MR sequence protocol to evaluate parenchymal fibrosis using an animal model of chronic kidney disease (CKD) by long-term adenine intake. Material and Methods In this prospective animal study, 16 male Wistar rats were analyzed and categorized into three groups. Rats in the CKD groups underwent 0.25% adenine administration for three or six weeks. Quantitative MRI protocols, including diffusion-weighted imaging (DWI), T1ρ (T1 rho), and T2* mapping were performed using a 9.4-T animal MR scanner. A semi-quantitative histopathologic analysis for renal fibrosis was conducted. Quantitative MR values measured from anatomic regions of kidneys underwent intergroup comparative analyses. Results The apparent diffusion coefficient (ADC) and T1 (T1 rho) values were significantly increased in all CKD groups. Values measured from the cortex and outer medulla showed significant intergroup differences. Total ADC values tended to increase according to periods, and T1ρ values increased in three weeks and decreased in six weeks. Conclusion Quantitative MRI protocols could be a non-invasive assessment modality in the diagnosis and evaluation of CKD. Particularly, T1ρ may be a suitable MR sequence to quantitatively assess renal parenchymal fibrosis.

Cartilage Matrix Degeneration Occurs within the First Year after ACLR and Is Associated with Impaired Clinical Outcome

Objective Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes. Design Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values. Results Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR ( P = .001-.011). T2 value increased ( P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life ( P = .009, ρ = −0.62). Discussion Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.

A Comprehensive Framework to Evaluate the Effects of Anterior Cruciate Ligament Injury and Reconstruction on Graft and Cartilage Status through the Analysis of MRI T2 Relaxation Time and Knee Laxity: A Pilot Study

Background. Anterior cruciate ligament (ACL) tear represents a common orthopedic traumatic issue that often leads to an early development of osteoarthritis. To improve the diagnostic and prognostic techniques involved in the assessment of the joint after the trauma and during the healing process, the present work proposes a multi-parametric approach that aims to investigate the relationship between joint function and soft tissue status before and after ACL reconstruction. Methods. Thirteen consecutive patients who underwent ACL reconstruction were preliminarily enrolled in this study. Joint laxity assessment as well as magnetic resonance imaging with T2 mapping were performed in the pre-operative stage, at four and 18 months after surgery to acquire objective information to correlate knee function and soft tissue condition. Results. Correlations were found between graft and cartilage T2 signal, suggesting an interplay between these tissues within the knee joint. Moreover, graft maturation resulted in being connected to joint laxity, as underlined by the correlation between the graft T2 signal and the temporal evolution of knee function. Conclusions. This preliminary study represents a step forward in assessing the effects of ACL graft maturation on knee biomechanics, and vice versa. The presented integrated framework underlines the possibility to quantitatively assess the impact of ACL reconstruction on trauma recovery and cartilage homeostasis. Moreover, the reported findings—despite the preliminary nature of the clinical impacts—evidence the possibility of monitoring the surgery outcomes using a multi-parametric prognostic investigation tool.

66 Heart and lung tissue characterization of COVID-19 pneumonia by T1 and T2 mapping magnetic resonance imaging

Aims Coronavirus disease 2019 (COVID-19) is a respiratory tract infection which can lead to systemic involvement including myocardial injury, severe respiratory failure and death. Magnetic resonance imaging (MRI) could potentially offer advantages in providing tissue characterization of lung parenchyma and heart muscle in COVID-19. The aim of the present study was to describe data on heart and lung MRI in a cohort of patients hospitalized due to COVID-19 pneumonia. Methods and results n = 11 patients hospitalized with COVID-19 pneumonia underwent a comprehensive MRI examinations including lung and heart tissue mapping, findings were compared to those of an age- and sex-matched cohort of n = 11 individuals. Lung native T1 and T2 mapping assessments were performed by drawing a circular region of interest (ROI) with diameter of 2 cm in the parenchyma visualized from the cardiac four chamber long axis-oriented slice; vessels and areas of pleural effusion were carefully excluded. Myocardial native T1 and T2 mapping were assessed by drawing a ROI within the midventricular left ventricular (LV) septum. No patients had previous history of cardiovascular disease (including known coronary artery disease, heart failure, cardiomyopathy, atrial fibrillation). As compared to controls, patients with COVID-19 had similar cardiac function, higher mid-septum myocardial native T1 (1028 ms vs. 985, P = 0.05) and significantly higher lung native T1 and T2 within affected areas (1375 ms vs. 1201 ms, P = 0.016 and 70 ms vs. 30 ms, P &lt; 0.001 respectively), whereas non-significant differences were observed between remote lung areas of patients and controls (1238 ms vs. 1152 ms, P = 0.088 and 29 ms vs. 33 ms, P = 0.797 respectively). No significant associations were observed between cardiac and lung mapping findings. Conclusions In our cohort of patients with COVID-19, T1 and T2 mapping lung MRI identified pneumonia related abnormalities as compared to healthy controls, likely representing oedema and ongoing inflammation at the lung site. Myocardial native T1 was elevated suggesting the presence of cardiac involvement. A comprehensive MRI examination can be potentially used to assess multiorgan involvement in COVID-19.