Magnetic resonance imaging of placental intralobule structure and function in a preclinical nonhuman primate model†.

Although the central role of adequate blood flow and oxygen delivery is known, the lack of optimized imaging modalities to study placental structure has impeded our understanding of its vascular function. Magnetic resonance imaging is increasingly being applied in this field, but gaps in knowledge remain, and further methodological developments are needed. In particular, the ability to distinguish maternal from fetal placental perfusion and the understanding of how individual placental lobules are functioning are lacking. The potential clinical benefits of developing noninvasive tools for the in vivo assessment of blood flow and oxygenation, two key determinants of placental function, are tremendous. Here, we summarize a number of structural and functional magnetic resonance imaging techniques that have been developed and applied in animal models and studies of human pregnancy over the past decade. We discuss the potential applications and limitations of these approaches. Their combination provides a novel source of contrast to allow analysis of placental structure and function at the level of the lobule. We outline the physiological mechanisms of placental T2 and T2* decay and devise a model of how tissue composition affects the observed relaxation properties. We apply this modeling to longitudinal magnetic resonance imaging data obtained from a preclinical pregnant nonhuman primate model to provide initial proof-of-concept data for this methodology, which quantifies oxygen transfer and placental structure across and between lobules. This method has the potential to improve our understanding and clinical management of placental insufficiency once validation in a larger nonhuman primate cohort is complete.

Uncovering prostate cancer aggressiveness signal in T2-weighted MRI through a three-reference tissues normalization technique.

Quantitative T2-weighted MRI (T2W) interpretation is impeded by the variability of acquisition-related features, such as field strength, coil type, signal amplification, and pulse sequence parameters. The main purpose of this work is to develop an automated method for prostate T2W intensity normalization. The procedure includes the following: (i) a deep learning-based network utilizing MASK R-CNN for automatic segmentation of three reference tissues: gluteus maximus muscle, femur, and bladder; (ii) fitting a spline function between average intensities in these structures and reference values; and (iii) using the function to transform all T2W intensities. The T2W distributions in the prostate cancer regions of interest (ROIs) and normal appearing prostate tissue (NAT) were compared before and after normalization using Student's t-test. The ROIs' T2W associations with the Gleason Score (GS), Decipher genomic score, and a three-tier prostate cancer risk were evaluated with Spearman's correlation coefficient (rS ). T2W differences in indolent and aggressive prostate cancer lesions were also assessed. The MASK R-CNN was trained with manual contours from 32 patients. The normalization procedure was applied to an independent MRI dataset from 83 patients. T2W differences between ROIs and NAT significantly increased after normalization. T2W intensities in 231 biopsy ROIs were significantly negatively correlated with GS (rS = -0.21, p = 0.001), Decipher (rS = -0.193, p = 0.003), and three-tier risk (rS = -0.235, p < 0.001). The average T2W intensities in the aggressive ROIs were significantly lower than in the indolent ROIs after normalization. In conclusion, the automated triple-reference tissue normalization method significantly improved the discrimination between prostate cancer and normal prostate tissue. In addition, the normalized T2W intensities of cancer exhibited a significant association with tumor aggressiveness. By improving the quantitative utilization of the T2W in the assessment of prostate cancer on MRI, the new normalization method represents an important advance over clinical protocols that do not include sequences for the measurement of T2 relaxation times.

Comparison of triple quantum (TQ) TPPI and inversion recovery TQ TPPI pulse sequences at 9.4 and 21.1 T.

PURPOSE: Both sodium T1 triple quantum (TQ) signal and T1 relaxation pathways have a unique sensitivity to the sodium molecular environment. In this study an inversion recovery time proportional phase increment (IRTQTPPI) pulse sequence was investigated for simultaneous and reliable quantification of sodium TQ signal and bi-exponential T1 relaxation times. METHODS: The IRTQTPPI sequence combines inversion recovery TQ filtering and time proportional phase increment. The reliable and reproducible results were achieved by the pulse sequence optimized in three ways: (1) optimization of the nonlinear fit for the determination of both T1-TQ signal and T1 relaxation times; (2) suppression of unwanted signals by assessment of four different phase cycles; (3) nonlinear sampling during evolution time for optimal scan time without any compromises in fit accuracy. The relaxation times T1 and T2 and the TQ signals from IRTQTPPI and TQTPPI were compared between 9.4 and 21.1 T. The motional environment of the sodium nuclei was evaluated by calculation of correlation times and nuclear quadrupole interaction strengths. RESULTS: Reliable measurements of the T1-TQ signals and T1 bi-exponential relaxation times were demonstrated. The fit parameters for all four phase cycles were in good agreement with one another, with a negligible influence of unwanted signals. The agar samples yielded normalized T1-TQ signals from 3% to 16% relative to single quantum (SQ) signals at magnetic fields of both 9.4 and 21.1 T. In comparison, the normalized T2-TQ signal was in the range 15%-35%. The TQ/SQ signal ratio was decreased at 21.1 T as compared with 9.4 T for both T1 and T2 relaxation pathways. The bi-exponential T1 relaxation time separation ranged from 15 to 18 ms at 9.4 T and 15 to 21 ms at 21.1 T. The T2 relaxation time separation was larger, ranging from 28 to 35 ms at 9.4 T and 37 to 40 ms at 21.1 T. CONCLUSION: The IRTQTPPI sequence, while providing a less intensive TQ signal than TQTPPI, allows a simultaneous and reliable quantification of both the T1-TQ signal and T1 relaxation times. The unique sensitivities of the T1 and T2 relaxation pathways to different types of molecular motion provide a deeper understanding of the sodium MR environment.

Quantitative muscle magnetic resonance imaging in limb-girdle muscular dystrophy type R1 (LGMDR1): A prospective longitudinal cohort study.

Limb-girdle muscular dystrophy (LGMD) type R1 (LGMDR1) is the most common subtype of LGMD in Europe. Prospective longitudinal data, including clinical assessments and new biomarkers such as quantitative magnetic resonance imaging (qMRI), are needed to evaluate the natural course of the disease and therapeutic options. We evaluated eight thigh and seven leg muscles of 13 LGMDR1 patients (seven females, mean age 36.7 years, body mass index 23.9 kg/m2) and 13 healthy age- and gender-matched controls in a prospective longitudinal design over 1 year. Clinical assessment included testing for muscle strength with quick motor function measure (QMFM), gait analysis and patient questionnaires (neuromuscular symptom score, activity limitation [ACTIVLIM]). MRI scans were performed on a 3-T MRI scanner, including a Dixon-based sequence, T2 mapping and diffusion tensor imaging. The qMRI values of fat fraction (FF), water T2 relaxation time (T2), fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were analysed. Within the clinical outcome measures, significant deterioration between baseline and follow-up was found for ACTIVLIM (p = 0.029), QMFM (p = 0.012). Analysis of qMRI parameters of the patient group revealed differences between time points for both FF and T2 when analysing all muscles (FF: p < 0.001; T2: p = 0.016). The highest increase of fat replacement was found in muscles with an FF of between 10% and 50% at baseline. T2 in muscles with low-fat replacement increased significantly. No significant differences were found for the diffusion metrics. Significant correlations between qMRI metrics and clinical assessments were found at baseline and follow-up, while only T2 changes in thigh muscles correlated with changes in ACTIVLIM over time (ρ = -0.621, p < 0.05). Clinical assessments can show deterioration of the general condition of LGMDR1 patients. qMRI measures can give additional information about underlying pathophysiology. Further research is needed to establish qMRI outcome measures for clinical trials.

Grading Clear Cell Renal Cell Carcinoma Grade Using Diffusion Relaxation Correlated MR Spectroscopic Imaging.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, and accurate grading is crucial for prognosis and treatment selection. Biopsy is the reference standard for grading, but MRI methods can improve and complement the grading procedure. PURPOSE: Assess the performance of diffusion relaxation correlation spectroscopic imaging (DR-CSI) in grading ccRCC. STUDY TYPE: Prospective. SUBJECTS: 79 patients (age: 58.1 +/- 11.5 years; 55 male) with ccRCC confirmed by histopathology (grade 1, 7; grade 2, 45; grade 3, 18; grade 4, 9) following surgery. FIELD STRENGTH/SEQUENCE: 3.0 T MRI scanner. DR-CSI with a diffusion-weighted echo-planar imaging sequence and T2-mapping with a multi-echo spin echo sequence. ASSESSMENT: DR-CSI results were analyzed for the solid tumor regions of interest using spectrum segmentation with five sub-region volume fraction metrics (VA , VB , VC , VD , and VE ). The regulations for spectrum segmentation were determined based on the D-T2 spectra of distinct macro-components. Tumor size, voxel-wise T2, and apparent diffusion coefficient (ADC) values were obtained. Histopathology assessed tumor grade (G1-G4) for each case. STATISTICAL TESTS: One-way ANOVA or Kruskal-Wallis test, Spearman's correlation (coefficient, rho), multivariable logistic regression analysis, receiver operating characteristic curve analysis, and DeLong's test. Significance criteria: P < 0.05. RESULTS: Significant differences were found in ADC, T2, DR-CSI VB , and VD among the ccRCC grades. Correlations were found for ccRCC grade to tumor size (rho = 0.419), age (rho = 0.253), VB (rho = 0.553) and VD (rho = -0.378). AUC of VB was slightly larger than ADC in distinguishing low-grade (G1-G2) from high-grade (G3-G4) ccRCC (0.801 vs. 0.762, P = 0.406) and G1 from G2 to G4 (0.796 vs. 0.647, P = 0.175), although not significant. Combining VB , VD , and VE had better diagnostic performance than combining ADC and T2 for differentiating G1 from G2-G4 (AUC: 0.814 vs 0.643). DATA CONCLUSION: DR-CSI parameters are correlated with ccRCC grades, and may help to differentiate ccRCC grades. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 2.

Assessment of articular cartilage degradation in response to an impact injury using µMRI.

PURPOSE: Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. MATERIALS AND METHODS: A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. RESULTS: The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2-55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. CONCLUSIONS: This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.

Normative quantitative relaxation atlases for characterization of cortical regions using magnetic resonance fingerprinting.

Quantitative magnetic resonance (MR) has been used to study cyto- and myelo-architecture of the human brain non-invasively. However, analyzing brain cortex using high-resolution quantitative MR acquisition can be challenging to perform using 3T clinical scanners. MR fingerprinting (MRF) is a highly efficient and clinically feasible quantitative MR technique that simultaneously provides T1 and T2 relaxation maps. Using 3D MRF from 40 healthy subjects (mean age = 25.6 ± 4.3 years) scanned on 3T magnetic resonance imaging, we generated whole-brain gyral-based normative MR relaxation atlases and investigated cortical-region-based T1 and T2 variations. Gender and age dependency of T1 and T2 variations were additionally analyzed. The coefficient of variation of T1 and T2 for each cortical-region was 3.5% and 7.3%, respectively, supporting low variability of MRF measurements across subjects. Significant differences in T1 and T2 were identified among 34 brain regions (P < 0.001), lower in the precentral, postcentral, paracentral lobule, transverse temporal, lateral occipital, and cingulate areas, which contain sensorimotor, auditory, visual, and limbic functions. Significant correlations were identified between age and T1 and T2 values. This study established whole-brain MRF T1 and T2 atlases of healthy subjects using a clinical 3T scanner, which can provide a quantitative and region-specific baseline for future brain studies and pathology detection.

Role of T2 relaxometry in localization of mesial temporal sclerosis and the degree of hippocampal atrophy in patients with intractable temporal lobe epilepsy: A cross sectional study.

Mesial temporal lobe epilepsy is one of the most common causes of refractory epilepsy worldwide. A good percentage of patients do not have detectable hippocampal atrophy on magnetic resonance imaging (MRI). The objective of this study is to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable temporal lobe epilepsy (TLE). T2 relaxometry can also be used to correlate the clinical severity of the disease with the relaxometry readings in those who have hippocampal atrophy as well as those who do not. Thirty two patients having clinical and electrophysiological features of TLE were enrolled and a MRI brain with T2 relaxometry was done. Hippocampal T2 relaxometry values were calculated in the head, body, and tail of the hippocampus and average T2 relaxometry values were calculated, and a comparison was done with the controls. For patients with unilateral involvement, the contralateral side was taken as control and in cases of bilateral involvement, controls were identified from normal subjects. T2 relaxometry is found to be superior to MR visual analysis in the early detection of cases of hippocampal sclerosis where there is no atrophy on visual analysis. Nine out of 32 patients (28%) were normal on MR visual analysis; however, showed increased values on T2 relaxometry, correlating with clinical and electrophysiological diagnosis. The rest of the patients with hippocampal atrophy showed a correlation of T2 relaxometry values with the degree of atrophy. The hippocampal T2 measurement is thus more sensitive and specific. The study was clinically significant (p < .0001). There was a mild female predilection of the disease and there was no significant correlation with comorbidities. There was a strong positive correlation with patients having a history of febrile seizures in childhood. T2 relaxometry may accurately lateralize the majority of patients with persistent TLE and offers evidence of hippocampus injury in those patients who do not show evidence of atrophy on MRI and also the T2 relaxometry values correlated with the degree of atrophy. Early identification of hippocampal sclerosis is crucial for prompt management which offers better outcomes.

Vascular space occupancy asymmetric spin echo (VASO-ASE) for non-invasive quantification of cerebral oxygen extraction fraction.

PURPOSE: Asymmetric spin echo (ASE) MRI is a method for measuring regional oxygen extraction fraction (OEF); however, extravascular tissue models have been shown to under-estimate OEF. The hypothesis investigated here is that the addition of a vascular-space-occupancy (VASO) pre-pulse will more fully suppress blood water signal and provide global OEF values more consistent with physiological expectation and 15 O positron emission tomography (PET)-validated T2 -relaxation-under-spin-tagging (TRUST) OEF measures. METHODS: Healthy adults (n = 14; age = 27.7 ± 5.2 y; sex = 7/7 male/female) were scanned at 3.0T. Multi-echo ASE without inter-readout refocusing (ASERF- ), multi-echo ASE with inter-readout refocusing (ASERF+ ), and single-echo VASO-ASE were acquired twice each with common spatial resolution = 3.44 × 3.44 × 3.0 mm and τ = 0-20 ms (interval = 0.5 ms). TRUST was acquired twice sequentially for independent global OEF assessment (τCPMG  = 10 ms; effective TEs = 0, 40, 80, and 160 ms; spatial resolution = 3.4 × 3.4 × 5 mm). OEF intraclass-correlation-coefficients (ICC), summary statistics, and group-wise differences were assessed (Wilcoxon rank-sum; significance: two-sided p < 0.05). RESULTS: ASERF+ (OEF = 36.8 ± 1.9%) and VASO-ASE (OEF = 34.4 ± 2.3%) produced OEF values similar to TRUST (OEF = 36.5 ± 4.6%, human calibration model; OEF = 32.7 ± 4.9%, bovine calibration model); however, ASERF- yielded lower OEF (OEF = 26.1 ± 1.0%; p < 0.01) relative to TRUST. VASO-ASE (ICC = 0.61) yielded lower ICC compared to other ASE variants (ICC >0.89). CONCLUSION: VASO-ASE and TRUST provide similar OEF values; however, VASO-ASE spatial coverage and repeatability improvements are required.

Patellofemoral contact forces and knee gait mechanics 3 months after ACL reconstruction are associated with cartilage degradation 24 months after surgery.

OBJECTIVE: Evaluate patellofemoral cartilage health, as assessed by quantitative magnetic resonance imaging (qMRI) T2 relaxation times, 24-months after ACL reconstruction (ACLR) and determine if they were associated with patellofemoral contact forces and knee mechanics during gait 3 months after surgery. DESIGN: Thirty individuals completed motion analysis during overground walking at a self-selected speed 3 months after ACLR. An EMG-driven neuromusculoskeletal model was used to determine muscle forces, which were then used in a previously described model to estimate patellofemoral contact forces. Biomechanical variables of interest included peak patellofemoral contact force, peak knee flexion angle and moment, and walking speed. These same participants underwent a sagittal bilateral T2 mapping qMRI scan 24-months after surgery. T2 relaxation times were estimated for both patellar and trochlear cartilage. Paired t-tests were used to compare T2 relaxation times between limbs while Pearson correlations and linear regressions were utilized to assess the association between the biomechanical variables of interest and T2 relaxation times. RESULTS: Prolonged involved limb trochlear T2 relaxation times (vs uninvolved) were present 24-months after surgery, indicating worse cartilage health. No differences were detected in patellar cartilage. Significant negative associations were present within the involved limb for all the biomechanical variables of interest 3 months after ACLR and trochlear T2 relaxation times at 24-months. No associations were found in patellar cartilage or within the uninvolved limb. CONCLUSIONS: Altered involved limb trochlear cartilage health is present 24-months after ACLR and may be related to patellofemoral loading and other walking gait mechanics 3 months after surgery.

Multi-echo single-shot spectroscopy combined with simultaneous 2D model fitting for fast and accurate measurement of metabolite-specific concentrations and T2 relaxation times.

The purpose of the current study was to develop a novel single-voxel MR spectroscopy acquisition scheme to simultaneously determine metabolite-specific concentrations and transverse relaxation times within realistic clinical scan times. Partly truncated multi-TE data are acquired as an echo train in a single acquisition (multi-echo single-shot [MESS]). A 2D multiparametric model fitting approach combines truncated, low-resolved short TE data with fully sampled, highly resolved, longer TE data to yield concentration and T2 estimates for major brain metabolites simultaneously. Cramer-Rao lower bounds (CRLB) are used as a measure of performance. The novel scheme was compared with traditional multi-echo multi-shot methods. In silico, in vitro, and in vivo experiments support the findings. MESS schemes, requiring only 2 min 12 s for the acquisition of three echo times, provide valid concentration and relaxation estimates for multiple metabolites and outperform traditional methods for simultaneous determinations of metabolite-specific T2 s and concentrations, with improvements ranging from 5% to 30% for T2 s and from 10% to 50% for concentrations. However, substantial unsuppressed residual water signals may hamper the method's reproducibility, as observed in an initial experiment setup that prioritizes short TEs with severely truncated acquisition for the benefit of signal-to-noise ratio (SNR). Nevertheless, CRLB have been confirmed to be well suited as design criteria, and within-session repeatability approaches CRLB when residual water is removed in postprocessing by exploiting longer and less truncated data recordings. MESS MRS combined with 2D model fitting promises comparable accuracy, increased precision, or inversely shorter experimental times compared with traditional approaches. However, the optimal design must be investigated as a trade-off between SNR, the truncation factor, and TE batch selections, all of which influence the robustness of estimations.

Perfusion and T2 Relaxation Time as Predictors of Severity and Outcome in Sepsis-Associated Acute Kidney Injury: A Preclinical MRI Study.

BACKGROUND: Preventing sepsis-associated acute kidney injury (S-AKI) can be challenging because it develops rapidly and is often asymptomatic. Probability assessment of disease progression for therapeutic follow-up and outcome are important to intervene and prevent further damage. PURPOSE: To establish a noninvasive multiparametric MRI (mpMRI) tool, including T1 , T2 , and perfusion mapping, for probability assessment of the outcome of S-AKI. STUDY TYPE: Preclinical randomized prospective study. ANIMAL MODEL: One hundred and forty adult female SD rats (65 control and 75 sepsis). FIELD STRENGTH/SEQUENCE: 9.4T; T1 and perfusion map (FAIR-EPI) and T2 map (multiecho RARE). ASSESSMENT: Experiment 1: To identify renal injury in relation to sepsis severity, serum creatinine levels were determined (31 control and 35 sepsis). Experiment 2: Animals underwent mpMRI (T1 , T2 , perfusion) 18 hours postsepsis. A subgroup of animals was immediately sacrificed for histology examination (nine control and seven sepsis). Result of mpMRI in follow-up subgroup (25 control and 33 sepsis) was used to predict survival outcomes at 96 hours. STATISTICAL TESTS: Mann-Whitney U test, Spearman/Pearson correlation (r), P < 0.05 was considered statistically significant. RESULTS: Severely ill septic animals exhibited significantly increased serum creatinine levels compared to controls (70 ± 30 vs. 34 ± 9 µmol/L, P < 0.0001). Cortical perfusion (480 ± 80 vs. 330 ± 140 mL/100 g tissue/min, P < 0.005), and cortical and medullary T2 relaxation time constants were significantly reduced compared to controls (41 ± 4 vs. 37 ± 5 msec in cortex, P < 0.05, 52 ± 7 vs. 45 ± 6 msec in medulla, P < 0.05). The combination of cortical T2 relaxation time constants and perfusion results at 18 hours could predict survival outcomes at 96 hours with high sensitivity (80%) and specificity (73%) (area under curve of ROC = 0.8, Jmax = 0.52). DATA CONCLUSION: This preclinical study suggests combined T2 relaxation time and perfusion mapping as first line diagnostic tool for treatment planning. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles.

BACKGROUND: The reference standard for assessing water T2 (T2,H2O ) at high fat fraction (FF) is 1 H MRS. T2,H2O (T2,H2O,MRS ) dependence on FF (FFMRS ) has recently been demonstrated in muscle at high FF (i.e. ≥60%). PURPOSE: To investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI. STUDY TYPE: Retrospective case-control study. POPULATION: A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male). FIELD STRENGTH/SEQUENCE: A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI ), three-point Dixon imaging (for FFMRI and R 2 * mapping). ASSESSMENT: Mono-exponential and bi-exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS . Water resonance full-width-at-half-maximum (FWHM) and B0 spread (∆B0 ) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and R 2 * (mean) values were estimated in the MRS voxel. STATISTICAL TESTS: Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant. RESULTS: Normal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS . The latter subgroup had significantly higher water resonance FWHM, ∆B0 , FFMRI kurtosis, and skewness values but nonsignificantly different R 2 * (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi-exponential analysis. DATA CONCLUSION: The findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0 ), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi-exponential analysis. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Age-Dependent Changes in Knee Cartilage T1 , T2 , and T1p Simultaneously Measured Using MRI Fingerprinting.

BACKGROUND: Magnetic resonance fingerprinting (MRF) techniques have been recently described for simultaneous multiparameter cartilage mapping of the knee although investigation of their ability to detect early cartilage degeneration remains limited. PURPOSE: To investigate age-dependent changes in knee cartilage T1 , T2 , and T1p relaxation times measured using a three-dimensional (3D) MRF sequence in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: The study group consisted of 24 healthy asymptomatic human volunteers (15 males with mean age 34.9 ± 14.4 years and 9 females with mean age 44.5 ± 13.1 years). FIELD STRENGTH/SEQUENCE: A 3.0 T gradient-echo-based 3D-MRF sequence was used to simultaneously create proton density-weighted images and T1 , T2 , and T1p maps of knee cartilage. ASSESSMENT: Mean global cartilage and regional cartilage (lateral femur, lateral tibia, medial femur, medial tibia, and patella) T1 , T2 , and T1ρ relaxation times of the knee were measured. STATISTICAL TESTS: Kruskal-Wallis tests were used to compared cartilage T1 , T2 , and T1ρ relaxation times between different age groups, while Spearman correlation coefficients was used to determine the association between age and cartilage T1 , T2 , and T1ρ relaxation times. The value of P < 0.05 was considered statistically significant. RESULTS: Higher age groups showed higher global and regional cartilage T1 , T2 , and T1ρ . There was a significant difference between age groups in global cartilage T2 and T1ρ but no significant difference (P = 0.13) in global cartilage T1. Significant difference was also present between age groups in cartilage T2 and T1ρ for medial femur cartilage and medial tibia cartilage. There were significant moderate correlations between age and T2 and T1ρ for global cartilage (R2  = 0.63-0.64), medial femur cartilage (R2  = 0.50-0.56), and medial tibia cartilage (R2  = 0.54-0.66). CONCLUSION: Cartilage T2 and T1p relaxation times simultaneously measured using a 3D-MRF sequence in healthy volunteers showed age-dependent changes in knee cartilage, primarily within the medial compartment.

Paramagnetic rim lesions lead to pronounced diffuse periplaque white matter damage in multiple sclerosis.

BACKGROUND: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease. OBJECTIVES: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM). METHODS: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software "SyMRI." RESULTS: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519-2540) vs 1615.8 (1403.3-1953.5) vs 1199.5 (1089.6-1334.6), both p < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5-3040) vs 1869.3 (1491.4-2451.3), p = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927-1093.5) vs 904.3 (793.3-958.5), p = 0.013). CONCLUSION: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS.

Damage and recovery of the intrinsic and extrinsic foot muscles from running a full marathon.

PURPOSE: To investigate the effects of full marathon running on intrinsic and extrinsic foot muscle damage and to determine the relationship with the height change of the longitudinal foot arch following full marathon completion. METHODS: Magnetic resonance imaging-measured transverse relaxation time (T2 ) of the abductor hallucis (ABH), flexor digitorum brevis (FDB) and quadratus plantae (QP), flexor digitorum longus (FDL), tibialis posterior (TP), and flexor hallucis longus (FHL) from 22 collegiate runners were assessed before and 1, 3, and 8 days after full marathon running. The three-dimensional foot posture of 10 of the 22 runners was further obtained using a foot scanner system before and 1, 3, and 8 days after the marathon. RESULTS: Marathon-induced increases in T2 were observed in the QP, FDL, TP, and FHL 1 day after the marathon (+7.5%, +4.7%, +6.7%, and +5.9%, respectively), with the increased T2 of TP persisting until 3 days after the marathon (+4.6%). T2 changes of FDL and FHL from pre-marathon to DAY 1 showed direct correlations with the corresponding change in the arch height ratio (r = 0.823, p = 0.003, and r = 0.658, p = 0.038). CONCLUSION: The damage and recovery response from a full marathon differed among muscles; QP, FDL, TP, and FHL increased T2 after the marathon, whereas ABH and FDB did not. In addition, T2 changes in FDL and FHL and the arch height ratio change were correlated. Our results suggest that the extrinsic foot muscles could be more susceptible to damage than the intrinsic during marathon running.

Placental functional assessment and its relationship to adverse pregnancy outcome: comparison of intravoxel incoherent motion (IVIM) MRI, T2-relaxation time, and umbilical artery Doppler ultrasound.

BACKGROUND: Early identification of placental insufficiency can lead to appropriate treatment selections and can improve neonates' outcomes. Possible contributions of magnetic resonance imaging (MRI) have been suggested. PURPOSE: To evaluate the prognostic capabilities of placental intravoxel incoherent motion (IVIM) parameters and T2-relaxation time, and their correlation with fetal growth and adverse outcomes, comparing umbilical artery (UmA) pulsatility index (PI). MATERIAL AND METHODS: A total of 68 singleton pregnancies at 24-40 weeks of gestation underwent placental MRI and were reviewed retrospectively. UmA-PI was measured using Doppler ultrasound by obstetricians. IVIM parameters (Dfast, Dslow, and f) were calculated with a Bayesian model fitting. First, the associations between gestational age (GA) with placental IVIM parameters, T2-relaxation time, and placental thickness (PT) were evaluated. Second, IVIM parameters, T2 value (Z-score), PT (Z-score), and UmA-PI (Z-score) were compared between ( 1) those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates, ( 2) emergency cesarean section (ECS), and non-ECS, and ( 3) preterm birth and full-term birth. RESULTS: Low birth weight was observed in 15/68 cases (22%). GA was significantly associated only with T2-relaxation time and PT. SGA was significantly associated with T2 value (Z-score), f, and UmA-PI (Z-score). In the ECS groups, T2 value (Z-score), f, and Dfast were significantly lower than those in non-ECS groups. All IVIM parameters and T2 values (Z-score) showed significantly lower scores in the preterm birth group. CONCLUSION: Placental f and T2 value (Z-score) had significant associations with low birth weight and clinical adverse outcomes and could be potential imaging biomarkers of placental insufficiency.

Ultrashort time-to-echo MR morphology of cartilaginous endplate correlates with disc degeneration in the lumbar spine.

PURPOSE: Using ultrashort echo time (UTE) MRI, we determined prevalence of abnormal cartilaginous endplate (CEP), and the relationship between CEP and disc degeneration in human lumbar spines. MATERIALS AND METHODS: Lumbar spines from 71 cadavers (age 14-74 years) were imaged at 3 T using sagittal UTE and spin echo T2 map sequences. On UTE images, CEP morphology was defined as "normal" with linear high signal intensity or "abnormal" with focal signal loss and/or irregularity. On spin echo images, disc grade and T2 values of the nucleus pulposus (NP) and annulus fibrosus (AF) were determined. 547 CEPs and 284 discs were analysed. Effects of age, sex, and level on CEP morphology, disc grade, and T2 values were determined. Effects of CEP abnormality on disc grade, T2 of NP, and T2 of AF were also determined. RESULTS: Overall prevalence of CEP abnormality was 33% and it tended to increase with older ages (p = 0.08) and at lower spinal levels of L5 than L2 or L3 (p = 0.001). Disc grades were higher and T2 values of the NP were lower in older spines (p < 0.001) and at lower disc level of L4-5 (p < 0.05). We found significant association between CEP and disc degeneration; discs adjacent to abnormal CEPs had high grades (p < 0.01) and lower T2 values of the NP (p < 0.05). CONCLUSION: These results suggest that abnormal CEPs are frequently found, and it associates significantly with disc degeneration, suggesting an insight into pathoetiology of disc degeneration.

Determination of the Solid Content of Active Pharmaceutical Ingredient Powders in Suspension-Type Pharmaceutical Oral Jelly Using Time-Domain NMR.

This study determined the content of solid active pharmaceutical ingredient (API) powders dispersed in suspension-type pharmaceutical oral jellies using a low-field time-domain NMR (TD-NMR). The suspended jellies containing a designated API content were prepared and tested. Acetaminophen (APAP), indomethacin (IMC) and L-valine were used as test APIs. First, this study measured the T2 relaxation rate (the reciprocal of T2 relaxation time) by the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence, and then evaluated whether the API content could be determined by the acquired T2 relaxation rate. The T2 relaxation rate negatively correlated with API content to a certain extent, but their correlation was not sufficient for achieving a precise determination. Subsequently, the solid-echo pulse sequence measurement was adopted for this study. We found that NMR signals corresponding to solid components strongly correlated with API content. Thus, this method achieved a precise determination of API contents in suspended jellies. In addition, this study confirmed the effect of API particle size on the T2 relaxation rate by using an L-valine-containing jelly: the T2 relaxation rate became faster when a smaller API size was incorporated into the suspended jelly, while there was no difference in terms of the NMR signals measured by solid-echo pulse sequence. From these findings, TD-NMR could be a powerful tool for evaluating the API dispersion state in suspended oral jellies.

Achilles tendon structure is associated with regular running volume and biomechanics.

Achilles tendinopathy was reported to have the highest incidence proportion of all running-related injuries. The purpose of this study was to analyse the association between the Achilles tendon structure and running activity status. 350 healthy participants (runners and inactive controls, 30-50 years) participated in this research. Each participant completed questionnaires: socioeconomic, psychological, physical activity habits, running status and history and VISA-A. Magnetic resonance imaging, anthropological, running biomechanics and 14 days of physical activity monitoring assessments were performed. There was a higher odd of being in the upper quartile of the Achilles tendon T2* relaxation time with higher maximal knee extension moment independent of age and sex. Compared with runners who ran 21-40 km per week, non-runners and those who ran more than 40 km per week had increased odds of having longest the Achilles tendon T2* relaxation time. Regular running of 21 to 40 km per week is related to the Achilles tendon T2* relaxation time indicating possibly better water content and collagen orientation in these runners with compare to inactive non-runners or highly active individuals. In addition, Achilles tendon T2* relaxation time as indirect indicator of the Achilles tendon structure was positively related to the maximal knee extension moment during running.